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EDMONTON, Alberta, Jan. 25 (UPI) -- The city of Edmonton, Alberta, is writing off nearly $13 million worth of speeding tickets because the reliability of cameras came into question. Crown Prosecutor Steven Bilodeau said he petitioned the provincial justice ministry to nullify the tickets as people were receiving tickets for impossible infractions, the Edmonton Journal reported. In one case on Jan. 12, a camera snapshot alleged a driver was traveling at 89 mph on a city street, but the video showed all the other vehicles around it moving at the same speed, the Canadian Broadcasting Corp. reported. Bilodeau said all 141,729 tickets issued by the automated system between November 2009 and Jan. 14 will be overturned and refunds will be mailed to those who already paid fines. "It just has to be done," he said. "This is about public confidence." A spokesman for American Traffic Solutions, which supplies the system to the city, said the company was working with the city to rectify the process to ensure the cameras were "properly maintained and calibrated," the Journal said.

Q: Personalization conditions switching doesn`t work in Experience Editor (9.1.0, Initial Release) We personalize one particular rendering on page item. There are some different conditions that have different datasource item for this rendering. Personalization works good on website - datasource is changed according to conditions. But when we try to switch condition in Experience Editor - nothing happens. Datasource does not changed. There are no errors in log files and no errors in browser console. Can anyone help to find what is wrong? Sitecore version is 9.1. A: This is an issue for Sitecore XP 9.1.0 (Initial Release). It is not reproducible in the Sitecore 9.0.x and pre-release version of Sitecore 9.2. If you need a hotfix for Sitecore 9.1, you can request the fix from Sitecore Support. Public reference number is 312777.

viewDecember 2833August Parliament of the Cedar Throne Elections in the Pontesian Dynastic Empire His Imperial Majesty Richard I, by the Grace of God, Emperor of the Pontesian Dynastic Empire, Gran Tadraki, and of his other Realms and Territories, King of Gaduridos, Commander in Chief of the Royal Armed Forces, Defender of the Faith, Jeztriék Atabék. . is a hereditary Head of State and as such does not stand in elections. Elections for the August Parliament of the Cedar Throne Legislative elections have been held for the August Parliament of the Cedar Throne in the Pontesian Dynastic Empire. There were 293,247,237 people with suffrage. A total of 209,918,278 votes have been cast, putting turnout at a satisfying 71.58%. There were 750 seats up for grabs. Elections for the National Directorate Legislative elections have been held for the National Directorate in the Federation of Zardugal. There were 355,236,943 people with suffrage. A total of 112,786,445 votes have been cast, putting turnout at a depressing 31.75%. There were 600 seats up for grabs. Citizens of the Republica Nou Endralon rejoice as their national Tennis idol Theresa Davis has won the International Tennis Championship. Zeiţă Jade Anaïs II has personally congratulated Theresa Davis with the victory. Coach Paul Baker was quoted saying "this is the day where all the hard work finally pays off". viewNovember 2833General Assembly Board Elections in the Republic of Kalopia Elections for the General Assembly Board Legislative elections have been held for the General Assembly Board in the Republic of Kalopia. There were 391,166,871 people with suffrage. A total of 62,358,278 votes have been cast, putting turnout at a miserable 15.94%. There were 500 seats up for grabs. Elections for the Senate Legislative elections have been held for the Senate in the Federal Republic of Solentia. There were 342,059,823 people with suffrage. A total of 56,523,545 votes have been cast, putting turnout at a miserable 16.52%. There were 425 seats up for grabs. Elections for the National Congress Legislative elections have been held for the National Congress in the Republic of Tukarali. There were 366,867,369 people with suffrage. A total of 228,892,364 votes have been cast, putting turnout at a satisfying 62.39%. There were 525 seats up for grabs. Elections for the Enneruol Teid Legislative elections have been held for the Enneruol Teid in the Great State of Lourenne. There were 149,797,430 people with suffrage. A total of 22,449,133 votes have been cast, putting turnout at a miserable 14.99%. There were 75 seats up for grabs. Elections for the Imperium Congress Legislative elections have been held for the Imperium Congress in the Hobrazian Imperium. There were 296,567,048 people with suffrage. A total of 236,974,379 votes have been cast, putting turnout at a satisfying 79.91%. There were 400 seats up for grabs. Elections for the Imperial Satanic Council Legislative elections have been held for the Imperial Satanic Council in the Unholy Davostan Empire. There were 328,238,549 people with suffrage. A total of 50,728,374 votes have been cast, putting turnout at a miserable 15.45%. There were 750 seats up for grabs. The United Workers and Peasants Republic of Mordusia is in an uproar, as a member of the Imperial Diet was implicated in a bribery scheme. The well-known politician Abe Roberts was seen accepting illegal funds from Valentine Miller, head of YRK Inc., in return for favorable conditions for YRK Inc., helping them rise to the top of the Medicine sector. Elections for the Imperial Diet Legislative elections have been held for the Imperial Diet in the Imperial Crownlands of Greater Hulstria. There were 320,661,936 people with suffrage. A total of 223,310,841 votes have been cast, putting turnout at a satisfying 69.64%. There were 725 seats up for grabs. viewSeptember 2833Federal Assembly Elections in the Zogist Empire of Beluzia and Bailon Supreme Emperor of Terra Jesus Codreanu Zog is a hereditary Head of State and as such does not stand in elections. Elections for the Federal Assembly Legislative elections have been held for the Federal Assembly in the Zogist Empire of Beluzia and Bailon. There were 305,601,461 people with suffrage. A total of 231,856,803 votes have been cast, putting turnout at a satisfying 75.87%. There were 100 seats up for grabs. One of the factories of LIB Inc., an important corporation in the heavy materials sector in the Nordiske Republikken av Kazulia, located in the Fylke of Kelvon, has closed the books after several years of losses. Thousands have lost their jobs. viewSeptember 2833Withdrawal of the International Communitarian Reinvestment Treatise Elections for the National Congress Legislative elections have been held for the National Congress in the Republic of Tukarali. There were 366,597,070 people with suffrage. A total of 230,372,715 votes have been cast, putting turnout at a satisfying 62.84%. There were 525 seats up for grabs. Citizens of the Saridani Union rejoice as their national Tennis idol Louise Moore has won the International Tennis Championship. Praetor Napoleon Delman has personally congratulated Louise Moore with the victory. Coach Joachim Gaines was quoted saying "this is the day where all the hard work finally pays off". viewJuly 2833Congress of Councils Elections in the Socialist Republic of Dorvik Elections for the Congress of Councils Legislative elections have been held for the Congress of Councils in the Socialist Republic of Dorvik. There were 277,923,644 people with suffrage. A total of 160,022,058 votes have been cast, putting turnout at a disappointing 57.58%. There were 480 seats up for grabs. This press message was released by the Government of the State of Indrala. Kigami, 21 July 2833 Amidst the rising wave of lawlessness and the threat of a Muslim and maoist insurgency, President Ran Pan declared martial law, by virtue of Proclamation No. 86. This was brought to public in a two hour during INN television appearance of the President in the early evening of 21 July. Ran Pan, ruling by decree, curtailed press freedom and other civil liberties, closed down the National Assembly and media establishments, and ordered the arrest of opposition leaders and militant activists. Listed below are the general orders promulgated by President Ran Pan following the declaration of martial law: General Order No. 1 – The President directed the Secretary of National Defense to arrest or cause the arrest and take into his custody the individuals named in the attached list and to hold them until otherwise so ordered by the President or by his duly designated representative, as well as to arrest or cause the arrest and take into his custody and to hold them otherwise ordered released by him or by his duly authorized representative such persons who may have committed crimes described in the Order. General Order No.2 – The President ordered that all executive departments, bureaus, offices, agencies and instrumentalities of the National Government, government owned or controlled corporations, as well all governments of all the provinces, cities, municipalities and barrios should continue to function under their present officers and employees, until otherwise ordered by the President or by his duly designated representatives. The President further ordered that the Judiciary should continue to function in accordance with its present organization and personnel, and should try to decide in accordance with existing laws all criminal and civil cases, except certain cases enumerated in the Order. General Order No. 3 – The President ordered that a curfew be maintained and enforced throughout Indrala from twelve o’clock midnight until four o’clock in the morning. General Order No. 4 – All rallies, demonstrations and other forms of group actions including strikes and picketing in vital industries such as in companies engaged in manufacture or processing as well as in production or processing of essential commodities or products for exports, and in companies engaged in banking of any kind, as well as in hospitals and in schools and colleges are prohibited. General Order No. 5 – No person shall keep, possess or carry outside of his residence any firearm unless such person is duly authorized to keep, possess or carry any such Indralans except to those who are being sent abroad in the service of the Indralans. Elections for the Legislatura Legislative elections have been held for the Legislatura in the Respublica Tropico de Gaduridos. There were 314,136,200 people with suffrage. A total of 262,416,607 votes have been cast, putting turnout at a magnificent 83.54%. There were 607 seats up for grabs. Elections for the Assemblée Populaire Impériale Legislative elections have been held for the Assemblée Populaire Impériale in the Vice-royauté Impérial d'Alduria. There were 333,589,799 people with suffrage. A total of 245,716,225 votes have been cast, putting turnout at a satisfying 73.66%. There were 505 seats up for grabs. Vacant Office of the President of Cildania Msgr. Richard Ednywain is a hereditary Head of State and as such does not stand in elections. Elections for the House of Parliament Legislative elections have been held for the House of Parliament in the Cildanian Republic. There were 307,936,380 people with suffrage. A total of 240,803,246 votes have been cast, putting turnout at a satisfying 78.20%. There were 101 seats up for grabs. viewApril 2833Parliament of the Jawatankuasa Elections in the Gerajan Protectorates of Malivia The election for the Maharaja Joseph Hunter I, Glorious Arbiter of Justice, Defender of the Protectorates of Vascania, Dovani, and Malivia, Protector of the Gerajan Faith. Maharaja is aided by Governor General The election has been held for the office of Maharaja Joseph Hunter I, Glorious Arbiter of Justice, Defender of the Protectorates of Vascania, Dovani, and Malivia, Protector of the Gerajan Faith. Maharaja is aided by Governor General. Elections for the Parliament of the Jawatankuasa Legislative elections have been held for the Parliament of the Jawatankuasa in the Gerajan Protectorates of Malivia. There were 348,179,305 people with suffrage. A total of 139,673,031 votes have been cast, putting turnout at a disappointing 40.12%. There were 75 seats up for grabs. Tenno Reynard . is a hereditary Head of State and as such does not stand in elections. Elections for the Folkstämma Legislative elections have been held for the Folkstämma in the Great Sekowan People's Federative Socialist Empire. There were 285,224,739 people with suffrage. A total of 163,420,527 votes have been cast, putting turnout at a disappointing 57.30%. There were 600 seats up for grabs. Elections for the États-Généraux Legislative elections have been held for the États-Généraux in the République Populaire Démocratique de Kanjor. There were 272,704,861 people with suffrage. A total of 190,659,551 votes have been cast, putting turnout at a satisfying 69.91%. There were 600 seats up for grabs. viewMarch 2833Council of the Principality Elections in the Principality of Central Macon His Serene Highness the Lusk, Adrian II, Prince of Adelia of Falristan, of Roccato, of Kenai, and of Lagard, First among the Hutors, Lord of Bekenial, Defender of Liberty, Master of Law, &c . is a hereditary Head of State and as such does not stand in elections. Elections for the Council of the Principality Legislative elections have been held for the Council of the Principality in the Principality of Central Macon. There were 334,882,206 people with suffrage. A total of 51,635,507 votes have been cast, putting turnout at a miserable 15.42%. There were 391 seats up for grabs. Elections for the Assemblage van de Republiek Legislative elections have been held for the Assemblage van de Republiek in the Eerste Republiek Vanuku. There were 329,222,100 people with suffrage. A total of 256,505,806 votes have been cast, putting turnout at a satisfying 77.91%. There were 200 seats up for grabs. Elections for the National Assembly Legislative elections have been held for the National Assembly in the State of Indrala. There were 371,859,904 people with suffrage. A total of 291,395,539 votes have been cast, putting turnout at a satisfying 78.36%. There were 750 seats up for grabs. Elections for the Pantian Council Legislative elections have been held for the Pantian Council in the Ex-Baltusian State of Celestia. There were 307,406,134 people with suffrage. A total of 202,501,662 votes have been cast, putting turnout at a satisfying 65.87%. There were 100 seats up for grabs. Elections for the General Assembly Board Legislative elections have been held for the General Assembly Board in the Republic of Kalopia. There were 390,739,952 people with suffrage. A total of 275,223,396 votes have been cast, putting turnout at a satisfying 70.44%. There were 413 seats up for grabs. Elections for the People's Assembly Legislative elections have been held for the People's Assembly in the Free and United Country of Kalistan. There were 287,735,696 people with suffrage. A total of 236,332,772 votes have been cast, putting turnout at a magnificent 82.14%. There were 750 seats up for grabs. viewJanuary 2833Announcement from the Government of the State of Indrala This press message was released by the Government of the State of Indrala. COUP D'ETAT IN INDRALA Kigami, 4 January 2833 - Striking when Karuso returned to the Presidential Palace after meeting the National Assembly, army commander Gen. Bhumipol Ran Pan sent tanks and troops into the drizzly, nighttime streets of Kigami. The military ringed the Presidential Palace and Karuso's office, seized control of television stations and declared a provisional authority loyal to the army. President Karuso was put under house arrest later that night. The coup leaders declared martial law, revoked the constitution and ordered all troops not to leave duty stations without permission from their commanders. The stock exchange was to be closed Wednesday, along with schools, banks and government offices. General Ran Pan will serve as acting President, army spokesman Col. Akarat Sitkah said. Ironical is that Ran Pan, well-regarded within the military, is also a well-known member of the Nationalista Party, the party of the deposed President Karuso. Recently, Ran Pan urged a hard-fisted approach with the separatists in contrast to Karuso's weak policy of negotiations. Many analysts have said that with Karuso in power, peace in the central regions was unlikely. Ran Pan will be interim-president until there will be new elections. When these elections will occure, is not yet decided. Signed, the Government of the State of Indrala viewJanuary 2833Federal Council Elections in the Federal Republic of Darnussia Elections for the Federal Council Legislative elections have been held for the Federal Council in the Federal Republic of Darnussia. There were 326,512,087 people with suffrage. A total of 268,049,518 votes have been cast, putting turnout at a magnificent 82.09%. There were 200 seats up for grabs. One of the factories of JDE Inc., an important corporation in the logistics sector in the Republica Nou Endralon, located in the Provincie of Tiania, has closed the books after several years of losses. Thousands have lost their jobs. People celebrate new year's day across the world. They have high hopes that the year 2833 will bring joy and happiness for all. The first day of January marks the end of a period of remembrance of the passing year. Television and radio shows all over the world have recalled the good times and the bad times of the year that has gone by. Everyone wonders: will the new year bring peace and prosperity, or will it bring war and poverty? Random fact: It is not allowed to call more than 5 elections in 5 game years in a nation. The default sanction for a player persisting in the early election tactic will be a seat reset.

// Copyright 2013 Chris McGee <sirnewton_01@yahoo.ca>. All rights reserved. // Use of this source code is governed by a BSD-style // license that can be found in the LICENSE file. package main import ( "encoding/json" "errors" "go/build" "io" "net/http" "os" "path/filepath" "strconv" "strings" ) type Project struct { Id string Location string ContentLocation string } type Workspace struct { Id string Directory bool ChildrenLocation string Location string LastModified int64 Name string Projects []Project Children []FileDetails } type WorkspacesList struct { UserName string Name string Id string Workspaces []Workspace } func getWsProjects() ([]Project, []FileDetails) { projects := make([]Project, 0, 0) children := make([]FileDetails, 0, 0) nameMap := make(map[string]string) logger.Printf("Retrieving workspace projects from source directories\n") for _, srcDir := range srcDirs { logger.Printf("Walking %v to get projects.\n", srcDir) if strings.HasPrefix(srcDir, goroot) { continue } filesDir := srcDir _, err := os.Stat(filesDir) if err != nil { logger.Printf("src directory doesn't exist in gopath at %v", filesDir) return []Project{}, []FileDetails{} } dir, err := os.Open(filesDir) if err != nil { logger.Printf("Unable to open src directory in gopath at %v", filesDir) return []Project{}, []FileDetails{} } names, err := dir.Readdirnames(-1) dir.Close() for _, name := range names { logger.Printf("Found project %v\n", name) if strings.HasPrefix(name, ".") { continue } if nameMap[name] == "1" { continue } nameMap[name] = "1" fileinfo, err := os.Stat(filesDir + "/" + name) if err != nil { logger.Printf("Error: %v\n", err.Error()) return []Project{}, []FileDetails{} } projectInfo := Project{Id: name, Location: "/workspace/project/" + name, ContentLocation: "/file/" + name} projects = append(projects, projectInfo) info := FileDetails{} info.Name = fileinfo.Name() info.Id = fileinfo.Name() info.Location = "/file/" + name info.Directory = fileinfo.IsDir() // Provide a location to import into a directory if info.Directory { info.ImportLocation = "/xfer" + info.Location } info.LocalTimeStamp = fileinfo.ModTime().Unix() * 1000 info.ETag = strconv.FormatInt(fileinfo.ModTime().Unix(), 16) info.Parents = []FileDetails{} // TODO Calculate parent and put the object in here info.Attributes = make(map[string]bool) info.Attributes["ReadOnly"] = false executable := false mode := fileinfo.Mode() if (mode&os.ModePerm)&0111 != 0 { executable = true } info.Attributes["Executable"] = executable info.ChildrenLocation = "/file/" + name + "?depth=1" children = append(children, info) } } // Create a virtual project that represent the source code present at the GOROOT gorootPkgPath := filepath.Join(goroot, "/src/pkg") gorootInfo, err := os.Stat(gorootPkgPath) if err == nil { projectInfo := Project{Id: "GOROOT", Location: "/workspace/project/GOROOT", ContentLocation: "/file/GOROOT"} projects = append(projects, projectInfo) info := FileDetails{} info.Name = "GOROOT" info.Id = "GOROOT" info.Location = "/file/GOROOT" info.Directory = true info.LocalTimeStamp = gorootInfo.ModTime().Unix() * 1000 info.ETag = strconv.FormatInt(gorootInfo.ModTime().Unix(), 16) info.Parents = []FileDetails{} // TODO info.Attributes = make(map[string]bool) info.Attributes["ReadOnly"] = true executable := false mode := gorootInfo.Mode() if (mode&os.ModePerm)&0111 != 0 { executable = true } info.Attributes["Executable"] = executable info.ChildrenLocation = "/file/GOROOT?depth=1" children = append(children, info) } return projects, children } func workspaceHandler(writer http.ResponseWriter, req *http.Request, path string, pathSegs []string) bool { numPathSegs := len(pathSegs) switch { case req.Method == "POST" && numPathSegs == 2: if !strings.HasPrefix(req.Header.Get("Content-Type"), "application/json") { ShowError(writer, 400, "No project name provided", nil) return true } var data map[string]string dec := json.NewDecoder(req.Body) err := dec.Decode(&data) if err != nil { ShowError(writer, 400, "Invalid request body", nil) return true } projectName, ok := data["Name"] if !ok { ShowError(writer, 400, "No project name provided in JSON object", nil) return true } //workspaceId := pathSegs[1] // New top-level folders (ie projects) go at the end of the GOPATH gopaths := filepath.SplitList(build.Default.GOPATH) filesDir := gopaths[len(gopaths)-1] + "/src" createOptions := req.Header.Get("X-Create-Options") // This is a move if strings.Contains(createOptions, "move") { origLocation := data["Location"] origSegments := strings.Split(origLocation, "/") origProject := origSegments[len(origSegments)-1] origPath := "" for _, srcDir := range srcDirs { p := filepath.Join(srcDir, origProject) _, err := os.Stat(p) if err == nil { origPath = p break } } if origPath == "" { ShowError(writer, 400, "Original project not found", nil) return true } // Delete the destination if !strings.Contains(createOptions, "no-overwrite") { err := os.RemoveAll(filesDir + "/" + projectName) if err != nil { ShowError(writer, 500, "Destination already exists and couldn't be deleted", nil) return true } } err = os.Rename(origPath, filesDir+"/"+projectName) if err != nil { ShowError(writer, 500, "Could not move project", err) return true } } else if strings.Contains(createOptions, "copy") { origLocation := data["Location"] origSegments := strings.Split(origLocation, "/") origProject := origSegments[len(origSegments)-1] origPath := "" for _, srcDir := range srcDirs { p := filepath.Join(srcDir, origProject) _, err := os.Stat(p) if err == nil { origPath = p break } } if origPath == "" { ShowError(writer, 400, "Original project not found", nil) return true } overwrite := !strings.Contains(createOptions, "no-overwrite") err = filepath.Walk(origPath, func(path string, info os.FileInfo, err error) error { if err != nil { return err } destRelPath, _ := filepath.Rel(origPath, path) destPath := filepath.Join(filesDir, destRelPath) if !overwrite { _, statErr := os.Stat(destPath) if statErr == nil { // Already exists, return error return errors.New("File exists, can't overwrite") } } if info.IsDir() { err = os.Mkdir(destPath, info.Mode()) if err != nil && overwrite { err = nil } } else { sourceFile, err := os.Open(path) if err != nil { return err } defer sourceFile.Close() destFile, err := os.Create(destPath) if err != nil { return err } defer destFile.Close() _, err = io.Copy(destFile, sourceFile) } return err }) if err != nil { ShowError(writer, 500, "Error copying project", err) return true } writer.WriteHeader(201) return true } else { projectPath := filesDir + "/" + projectName os.Mkdir(filesDir, 0700) err = os.Mkdir(projectPath, 0700) if err != nil { ShowError(writer, 500, "Unable to create project directory", err) return true } } contentLocation := "/file/" + projectName location := "/workspace/project/" + projectName newProject := Project{Id: projectName, ContentLocation: contentLocation, Location: location} writer.Header().Set("Location", location) ShowJson(writer, 201, newProject) return true case req.Method == "GET" && numPathSegs < 3: workspaceList := WorkspacesList{Id: "anonymous", UserName: "anonymous", Name: "anonymous"} workspace := Workspace{Id: "1", Directory: true, ChildrenLocation: "/workspace/1", Location: "/workspace/1", LastModified: 1, Name: "Go Development"} workspace.Projects, workspace.Children = getWsProjects() workspaceList.Workspaces = []Workspace{workspace} etag := "1" writer.Header().Add("ETag", etag) if numPathSegs == 1 { // TODO Figure out if outputting all of the details (project, children) is too much for the plain workspace GET call ShowJson(writer, 200, workspaceList) } else { //workspaceId := pathSegs[1] ShowJson(writer, 200, workspace) } return true case req.Method == "POST" && numPathSegs == 1: ShowError(writer, 400, "Workspace POST not supported.", nil) return true case req.Method == "PUT" && numPathSegs == 2: ShowError(writer, 400, "Workspace PUT not supported.", nil) return true case req.Method == "DELETE" && numPathSegs == 3 && pathSegs[1] == "project": for _, srcDir := range srcDirs { projectPath := filepath.Join(srcDir, pathSegs[2]) _, err := os.Stat(projectPath) if err == nil { err = os.RemoveAll(projectPath) if err != nil { ShowError(writer, 400, "Project could not be removed", err) return true } ShowJson(writer, 200, "") return true } } ShowError(writer, 200, "Project could not be found. It was not removed.", nil) return true case req.Method == "DELETE" && numPathSegs == 2: ShowError(writer, 400, "Workspace deletion is not supported.", nil) return true } return false }

found: New York times (online), viewed Apr. 13, 2015(in obituary published Apr. 10: Judith Malina; b. June 4, 1926, Kiel, Germany; m. Julian Beck (d. 1985); d. Friday [Apr. 10, 2015], Englewood, N.J., aged 88; actor and director who with her husband founded the Living Theater [i.e. Theatre], a troupe of activists and provocateurs who advanced the idea of political theater in America, catalyzed fierce debate over their methods and intentions, and in the name of art ran afoul of civic authorities on three continents)

This invention relates generally to the field of floor coverings and more specifically to a Method and Apparatus For Optimization of Floor Covering And System For User Configuration and Real Time Pricing Information.

using Uno; using Uno.UX; using Uno.Platform.EventSources; using Fuse.Controls.FallbackTextRenderer; using Fuse.Controls.Graphics; using Fuse.Drawing; using Fuse.Elements; using Fuse.Input; using Fuse.Internal; using Fuse.Triggers; using Fuse.Controls.Native; using Fuse.Controls.FallbackTextEdit; namespace Fuse.Controls { extern (!Mobile) class DesktopTextEdit : TextEdit, INotifyFocus { public DesktopTextEdit(bool isMultiline): base(isMultiline) { _lineCache = new LineCache(OnTextEdited, InvalidateLineCacheLayout, isMultiline); _textWindow = new TextWindow(this, _lineCache); Children.Add(_textWindow); TextService.TextEntered.AddHandler(this, OnTextEntered); Pointer.Pressed.AddHandler(this, OnPointerPressed); Pointer.Moved.AddHandler(this, OnPointerMoved); Pointer.Released.AddHandler(this, OnPointerReleased); Keyboard.KeyPressed.AddHandler(this, OnKeyPressed); } bool UseGraphicsPlaceholder { get { return string.IsNullOrEmpty(Value); } } void INotifyFocus.OnFocusGained() { TextSource.BeginTextInput(0); //TODO: Remove this argument _selection = null; InvalidateLayout(); InvalidateVisual(); } void INotifyFocus.OnFocusLost() { TextSource.EndTextInput(); _selection = null; if (_textWindow != null) _textWindow.InvalidateVisual(); ResetWindowPosition(); InvalidateLayout(); InvalidateVisual(); } protected override void OnPlaceholderTextChanged() { base.OnPlaceholderTextChanged(); InvalidateVisual(); InvalidateLayout(); } protected override void OnPlaceholderColorChanged() { base.OnPlaceholderColorChanged(); InvalidateVisual(); InvalidateLayout(); } internal override string RenderValue { get { // Only use the built-in text rendering mechanism to render // the placeholder text return UseGraphicsPlaceholder ? PlaceholderText : null; } } internal override float4 RenderColor { get { return UseGraphicsPlaceholder ? PlaceholderColor : Color; } } protected override void OnRooted() { base.OnRooted(); if defined(!Mobile) { _caretBrush.Pin(); UpdateManager.AddAction(Update); } } protected override void OnUnrooted() { base.OnUnrooted(); if defined(!Mobile) { _caretBrush.Unpin(); UpdateManager.RemoveAction(Update); } } protected override void OnIsPasswordChanged() { base.OnIsPasswordChanged(); if (_lineCache == null) return; if (IsPassword) { _lineCache.Transform = new LineCachePasswordTransform(); } else { _lineCache.Transform = null; } } protected override void OnValueChanged(IPropertyListener origin) { base.OnValueChanged(origin); UpdateValue(Value); } void UpdateValue(string value) { if (_lineCache == null) return; _lineCache.Text = value; _textWindow.InvalidateVisual(); _caretPosition = Focus.IsWithin(this) ? _lineCache.GetLastTextPos() : new TextPosition(0, 0); _selection = null; InvalidateLayout(); InvalidateVisual(); } public string SelectedText { get { return _selection != null ? _lineCache.GetString(_selection) : ""; } } void Update() { if (Focus.IsWithin(this)) { InvalidateVisual(); } else { var pt = _lineCache.Transform as LineCachePasswordTransform; if (pt != null) { if (Time.FrameTime > _revealEnd) { if( pt.SetReveal( -1 ) ) _lineCache.InvalidateVisual(); } } } } void InvalidateLineCacheLayout() { InvalidateLayout(); } void OnTextEdited() { SetValueInternal(_lineCache.Text); } //for password temporary character veal double RevealTime = 2.0; double _revealEnd; bool IsWordWrapEnabled { get { return TextWrapping == Fuse.Controls.TextWrapping.Wrap; } } public void SelectAll() { _selection = _lineCache.GetFullTextSpan(); _caretPosition = _lineCache.GetLastTextPos(); InvalidateVisual(); } WordWrapInfo _wrapInfo; protected override float2 GetContentSize(LayoutParams lp) { if defined (Mobile) return base.GetContentSize(lp); else { if (Font == null) return float2(0f); if (UseGraphicsPlaceholder) return Math.Ceil(base.GetContentSize(lp)) + 1; _wrapInfo = CreateWrapInfo(lp.X, lp.HasX); var r = Math.Ceil(GetTextBoundsSize(_wrapInfo)) + 1; if (lp.HasX) r.X = Math.Min(r.X, lp.X); return r; } } WordWrapInfo CreateWrapInfo(float wrapWidth, bool haveWidth) { var renderer = TextRenderer.GetTextRenderer(Font); return new WordWrapInfo(renderer, haveWidth && IsWordWrapEnabled, wrapWidth, FontSize, renderer.GetLineHeight(FontSize), LineSpacing, AbsoluteZoom); } protected override float2 OnArrangeMarginBox(float2 position, LayoutParams lp) { if defined (Mobile) return base.OnArrangeMarginBox(position, lp); else { var sz = base.OnArrangeMarginBox(position, lp); _textWindow.ArrangeMarginBox(float2(0), LayoutParams.Create(sz)); return sz; } } public override void Draw(DrawContext dc) { if defined(!Mobile) FallbackDraw(dc); else base.Draw(dc); } void FallbackDraw(DrawContext dc) { base.DrawVisual(dc); if (_wrapInfo == null) _wrapInfo = CreateWrapInfo(ActualSize.X,true); var textBoundsSize = GetClampedTextBoundsSize(_wrapInfo); var textBoundsWidth = textBoundsSize.X; BringCaretIntoView(_wrapInfo, textBoundsWidth); DrawBackground(dc, Opacity); if (!string.IsNullOrEmpty(Value)) _textWindow.Draw(_wrapInfo, _selection, Color, SelectionColor, Value.Length, TextAlignment, textBoundsSize, -_windowPos, dc); if (Focus.IsWithin(this) && CaretColor.W > 0) { DrawCaret(_wrapInfo, textBoundsWidth, dc); UpdateManager.PerformNextFrame(InvalidateVisual); } } SolidColor _caretBrush = new SolidColor(); void DrawCaret(WordWrapInfo wrapInfo, float textBoundsWidth, DrawContext dc) { var caretRect = GetCaretRect(wrapInfo, textBoundsWidth); var pos = TextBoundsToControl(caretRect.Position); float blink = Math.Cos((float)(Time.FrameTime - _caretBlinkTime) * 2.0f * Math.PIf) * .5f + .5f; blink = 1.0f - Math.Pow(1.0f - blink, 4.3f); var caretSize = float2(1.0f, caretRect.Size.Y); _caretBrush.Color = float4(CaretColor.XYZ, CaretColor.W * blink); _caretBrush.Prepare(dc, caretSize); Fuse.Drawing.Primitives.Rectangle.Singleton.Fill(dc,this, caretSize, float4(0), _caretBrush, pos ); } // Line cache LineCache _lineCache; Rect GetClampedTextBoundsRect(WordWrapInfo wrapInfo) { return new Rect(float2(0), GetClampedTextBoundsSize(wrapInfo)); } float2 GetClampedTextBoundsSize(WordWrapInfo wrapInfo) { return Math.Max(GetTextBoundsSize(wrapInfo), ActualSize); } float2 GetTextBoundsSize(WordWrapInfo wrapInfo) { return _lineCache.GetBoundsSize(wrapInfo); } // Window TextWindow _textWindow; float2 _windowPos; void SetWindowPos(float2 p) { if (p != _windowPos) _textWindow.InvalidateVisual(); _windowPos = p; } void ResetWindowPosition() { SetWindowPos(float2(0)); } // Caret/Selection TextPosition _caretPosition = TextPosition.Default; TextPosition _interactionSelectionStartPos; TextSpan _selection; double _caretBlinkTime; void ResetCaretBlink() { _caretBlinkTime = Time.FrameTime; } void SetCaretPos(float2 p) { var wrapWidth = ActualSize.X; var wrapInfo = CreateWrapInfo(wrapWidth,true); var textBoundsWidth = GetClampedTextBoundsSize(wrapInfo).X; _caretPosition = _lineCache.BoundsToTextPos(wrapInfo, TextAlignment, textBoundsWidth, ControlToTextBounds(p)); BringCaretIntoView(wrapInfo, textBoundsWidth); ResetCaretBlink(); } void BringCaretIntoView(WordWrapInfo wrapInfo, float textBoundsWidth) { var windowRect = new Rect(_windowPos, ActualSize); var caretRect = GetCaretRect(wrapInfo, textBoundsWidth); var textRect = GetClampedTextBoundsRect(wrapInfo); var caretVisibleRect = windowRect.MoveRectToContainRect(caretRect); var clampedRect = caretVisibleRect.MoveRectInsideRect(textRect); SetWindowPos(clampedRect.Position); } Rect GetCaretRect(WordWrapInfo wrapInfo, float textBoundsWidth) { var pos = _lineCache.TextPosToBounds(wrapInfo, TextAlignment, textBoundsWidth, _caretPosition); var width = 2.0f; return new Rect(pos, float2(width, wrapInfo.LineHeight)); } void DeleteSelection() { if (_selection == null) return; _caretPosition = _lineCache.DeleteSpan(_selection); _selection = null; _interactionSelectionStartPos = null; } // Transformations float2 ControlToWindow(float2 p) { return p; } float2 WindowToControl(float2 p) { return p; } float2 WindowToTextBounds(float2 p) { return p + _windowPos; } float2 TextBoundsToWindow(float2 p) { return p - _windowPos; } float2 ControlToTextBounds(float2 p) { return WindowToTextBounds(ControlToWindow(p)); } float2 TextBoundsToControl(float2 p) { return WindowToControl(TextBoundsToWindow(p)); } static SwipeGestureHelper _horizontalGesture = new SwipeGestureHelper(15.0f, new DegreeSpan(45.0f, 135.0f), // Right new DegreeSpan(-45.0f, -135.0f)); // Left static SwipeGestureHelper _verticalGesture = new SwipeGestureHelper(15.0f, new DegreeSpan( -45.0f, 45.0f), new DegreeSpan(-135.0f, -180.0f), new DegreeSpan( 135.0f, 180.0f)); void OnLostCapture() { Focus.ReleaseFrom(this); _selection = null; _down = -1; } float2 _startCoord = float2(0f); int _down = -1; void OnPointerPressed(object sender, PointerPressedArgs c) { if (_down == -1) { _startCoord = c.WindowPoint; _down = c.PointIndex; if (Focus.IsWithin(this)) { c.TryHardCapture(this, OnLostCapture); } else { c.TrySoftCapture(this, OnLostCapture); } StartSelection(c.WindowPoint); } } void OnPointerMoved(object sender, PointerMovedArgs c) { if (_down != c.PointIndex) return; MoveSelection(c.WindowPoint); if (c.IsHardCapturedTo(this)) { c.IsHandled = true; } else if (c.IsSoftCapturedTo(this)) { var diff = c.WindowPoint - _startCoord; var withinBounds = _horizontalGesture.IsWithinBounds(diff); /*if (!withinBounds && _lineCache.Lines.Count > 1) { withinBounds = _verticalGesture.IsWithinBounds(diff); }*/ if (withinBounds) { c.TryHardCapture(this, OnLostCapture); Focus.GiveTo(this); } } } void OnPointerReleased(object sender, PointerReleasedArgs c) { if (_down != c.PointIndex) return; if (c.IsHardCapturedTo(this)) { c.ReleaseCapture(this); c.IsHandled = true; } if (c.IsSoftCapturedTo(this)) { c.ReleaseCapture(this); } _down = -1; } void StartSelection(float2 windowPoint) { SetCaretPos(WindowToLocal(windowPoint)); ResetCaretBlink(); _selection = null; _interactionSelectionStartPos = _caretPosition; ClearPasswordReveal(); } void MoveSelection(float2 windowPoint) { SetCaretPos(WindowToLocal(windowPoint)); if (_interactionSelectionStartPos == null) _interactionSelectionStartPos = _caretPosition; _selection = _interactionSelectionStartPos != _caretPosition ? new TextSpan(_interactionSelectionStartPos, _caretPosition) : null; } string _placeholderFallback; void SetPlaceholderTextFallback() { } LineCachePasswordTransform PasswordTransform { get { if (_lineCache == null) return null; return _lineCache.Transform as LineCachePasswordTransform; } } void OnTextEntered(object sender, TextEnteredArgs args) { DeleteSelection(); args.IsHandled = true; if (MaxLength != 0 && Value.Length >= MaxLength) return; foreach (var character in args.Text) { if (character == '\n' || character == '\r' || (int)character < 32) continue; _caretPosition = _lineCache.InsertChar(_caretPosition, character); if( PasswordTransform != null ) { PasswordTransform.SetReveal( _caretPosition.Char - 1 ); _revealEnd = Time.FrameTime + RevealTime; } var wrapWidth = ActualSize.X; var wrapInfo = CreateWrapInfo(wrapWidth,true); var textBoundsWidth = GetClampedTextBoundsSize(wrapInfo).X; BringCaretIntoView(wrapInfo, textBoundsWidth); ResetCaretBlink(); } } void ClearPasswordReveal() { if( PasswordTransform != null ) if( PasswordTransform.SetReveal( -1 ) ) _lineCache.InvalidateVisual(); } void OnKeyPressed(object sender, KeyPressedArgs args) { bool recognizedKey = false; var wrapWidth = ActualSize.X; var wrapInfo = CreateWrapInfo(wrapWidth,true); var textBoundsWidth = GetClampedTextBoundsSize(wrapInfo).X; ClearPasswordReveal(); if (!IsReadOnly) { switch (args.Key) { case Uno.Platform.Key.Enter: if (IsMultiline) { DeleteSelection(); _caretPosition = _lineCache.InsertNewline(_caretPosition); } else if(TextSource.IsTextInputActive) OnAction(TextInputActionType.Primary); recognizedKey = true; break; case Uno.Platform.Key.Delete: if (_selection == null) { _caretPosition = _lineCache.TryDelete(_caretPosition); } else { DeleteSelection(); } recognizedKey = true; break; case Uno.Platform.Key.Backspace: if (_selection == null) { _caretPosition = _lineCache.TryBackspace(_caretPosition); } else { DeleteSelection(); } recognizedKey = true; break; default: break; } } switch (args.Key) { case Uno.Platform.Key.A: if(!args.IsMetaKeyPressed) break; SelectAll(); recognizedKey = true; break; case Uno.Platform.Key.Left: HandleLeftArrow(args); recognizedKey = true; break; case Uno.Platform.Key.Right: HandleRightArrow(args); recognizedKey = true; break; case Uno.Platform.Key.Up: var oldCaretPos = _caretPosition; _caretPosition = _lineCache.TryMoveUp(wrapInfo, TextAlignment, textBoundsWidth, _caretPosition); if(args.IsShiftKeyPressed && _caretPosition.Line == oldCaretPos.Line) { _caretPosition = _lineCache.Home(wrapInfo, oldCaretPos); } Select(oldCaretPos, _caretPosition, args.IsShiftKeyPressed); recognizedKey = true; break; case Uno.Platform.Key.Down: var oldCaretPos = _caretPosition; _caretPosition = _lineCache.TryMoveDown(wrapInfo, TextAlignment, textBoundsWidth, _caretPosition); if(args.IsShiftKeyPressed && _caretPosition.Line == oldCaretPos.Line) { _caretPosition = _lineCache.End(wrapInfo, oldCaretPos); } Select(oldCaretPos, _caretPosition, args.IsShiftKeyPressed); recognizedKey = true; break; case Uno.Platform.Key.Home: var oldCaretPos = _caretPosition; _caretPosition = _lineCache.Home(wrapInfo, _caretPosition); Select(oldCaretPos, _caretPosition, args.IsShiftKeyPressed); recognizedKey = true; break; case Uno.Platform.Key.End: var oldCaretPos = _caretPosition; _caretPosition = _lineCache.End(wrapInfo, _caretPosition); Select(oldCaretPos, _caretPosition, args.IsShiftKeyPressed); recognizedKey = true; break; default: break; } if (recognizedKey) { ResetCaretBlink(); args.IsHandled = true; } } void HandleLeftArrow(KeyPressedArgs args) { if(args.IsMetaKeyPressed) { var oldCaretPosition = _caretPosition; _caretPosition = _lineCache.TryMoveOneWordLeft(_caretPosition); Select(oldCaretPosition, _caretPosition, args.IsShiftKeyPressed); } else { if(args.IsShiftKeyPressed) { var oldCaretPosition = _caretPosition; _caretPosition = _lineCache.TryMoveLeft(_caretPosition); SelectFunc(oldCaretPosition, _caretPosition); } else { if(_selection != null) { _caretPosition = _selection.Start; _selection = null; } else { _selection = null; _caretPosition = _lineCache.TryMoveLeft(_caretPosition); } } } } void HandleRightArrow(KeyPressedArgs args) { if(args.IsMetaKeyPressed) { var oldCaretPosition = _caretPosition; _caretPosition = _lineCache.TryMoveOneWordRight(_caretPosition); Select(oldCaretPosition, _caretPosition, args.IsShiftKeyPressed); } else { if(args.IsShiftKeyPressed) { var oldCaretPosition = _caretPosition; _caretPosition = _lineCache.TryMoveRight(_caretPosition); SelectFunc(oldCaretPosition, _caretPosition); } else { if(_selection != null) { _caretPosition = _selection.End; _selection = null; } else { _selection = null; _caretPosition = _lineCache.TryMoveRight(_caretPosition); } } } } void Select(TextPosition oldCaretPos, TextPosition newCaretPos, bool shouldSelect) { if(shouldSelect) { SelectFunc(oldCaretPos, newCaretPos); } else { _selection = null; } } void SelectFunc(TextPosition oldCaretPos, TextPosition newCaretPos) { bool movesLeft = oldCaretPos > newCaretPos; if(_selection == null) { if(movesLeft) { _selection = new TextSpan(newCaretPos, oldCaretPos); } else { _selection = new TextSpan(oldCaretPos, newCaretPos); } } else if(_selection.End > oldCaretPos) { if(movesLeft) { _selection = new TextSpan(newCaretPos, _selection.End); } else { _selection = new TextSpan(_selection.End, newCaretPos); } } else if(_selection.Start <= oldCaretPos) { if(movesLeft) { _selection = new TextSpan(newCaretPos, _selection.Start); } else { _selection = new TextSpan(_selection.Start, newCaretPos); } } } } }

Hey folks, Harry here with a great update on X-MEN: FIRST CLASS that just came from Producer: Bryan Singer - who tells me he's been working on X-MEN: FIRST CLASS for over a year now and with the looming August 31st, filming date approaching - he wanted to clarify some of what it is they're doing. First off - the film takes place in the 1960's. John F Kennedy is the President of the United States. Martin Luther King and Malcolm X are on TV doing marches. There is a spirit of a hopeful future that was prevalent in that time. We will see how Xavier and Erik Lehnsherr met - and how they dreamt of a future with Mutant & Human kind. They're going to be in their late twenties. Xavier - as played by James McAvoy will not be in his wheelchair to begin the film - but we will see how he wound up in a wheelchair. I asked if McAvoy would have a nice shiny chrome dome - and folks. We're going to see Professor X when he still had hair. We'll see McAvoy and Fassbender's Magneto formulate what it is they are attempting by creating the X-MEN. Now Bryan wanted us to know this is not the conventional FIRST CLASS comic - but rather a new beginning for X-MEN. Set in the 60s - Vaughn is technologically inspired by JAMES BOND's tech of the time. The costumes will be far more comic bookish than we've seen before - and while Scott and Jean aren't here - Cyclops' brother Alex Summers aka Havoc will be, as played by Lucas Till. With January Jones and Kevin Bacon playing Emma Frost and Sebastian Shaw - we will be getting the HELLFIRE CLUB. I commented that the HELLFIRE CLUB has always felt like something that it would be wrong to modernize, as it felt as though it were something specific to the swinging Hefner era of the 60s... and Bryan said that's exactly why they're making use of the HELLFIRE CLUB... the dress and the costumes associated with that glorious period of the X-MEN... belong in the 60s. I asked if Kevin Bacon would be sporting that little ponytail with the ribbon - Bryan laughed and said, "We'll see". In regards to the cast, Bryan was especially excited to land Nicholas Hoult as Hank McCoy/Beast. Nicholas was set for FURY ROAD, but their start date shifted which opened up his availability for FIRST CLASS. Also - Rose Byrne is playing Moira MacTaggert, I liked her in KNOWING. And I think she's fairly perfect for Moira. The cast list over on IMDB is correct (with the exception of the Rosamund Pike rumor). Looks like filming will begin with Xavier at Oxford University in the 60s. And Bryan is excited that the film is going to have a much more international feel than the prior X-MEN movies. They'll be shooting in England & the United States - and they'll be representing other locales around the globe as well, but would only tell me that Russia (aka The Soviet Union... CCCP) will be amongst them. He doesn't want to show all the cards just yet. But the International flavor will give the film a more James Bond vibe... I get the idea that this is going to be something quite special. How can I say that based on a quick conversation with Bryan? Well... folks, this is the first time that we're going to get a silver age MARVEL story. That's incredibly exciting to me. Hearing Bryan actually saying that the costumes will be far more reflective of what we saw in the comics - well that is exciting. But more than that... I just can't wait to see young vital versions of Xavier and Magneto played by excellent actors in their prime. But more so... This is the time for Matthew Vaughn to shine. I loved KICK ASS, but it didn't have the namebrand of X-MEN or the scope that those stories have. Here, everything that Vaughn has can be put on display. Having Vaughn work in a James Bond-esque period - that was the period that the X-MEN first came to life. There's potential for something amazing. There are characters that we're not being told about though. Bryan said so. And we can all speculate as to who they are. We know we're going to have Darwin, Young Raven Darkholme, Banshee, Havok, lil Mystique, Azazel, Emma Frost, Beast, Xavier, Magneto and a female Angel. So... who's missing? Well - I'm kinda hoping for Donald Pierce and Harry Leland - myself. How about you? Project862006 08-20-2010 08:03 PM Re: HOT!!! New Interview w/ Bryan Singer! (August 20th) sounds good i guess Havoc will be the older brother then lol MultiPurposePon 08-20-2010 08:10 PM Re: HOT!!! New Interview w/ Bryan Singer! (August 20th) Aaaaaaaaaaaaand Cyclops gets the shaft yet again! I strongly believe that Singer hates the character. Either way, I'm done with caring about this film. Project862006 08-20-2010 08:12 PM Re: HOT!!! New Interview w/ Bryan Singer! (August 20th) scott cant be in the 60's lol havoc is fair game since he was in no film Lightning Strykez! 08-20-2010 08:22 PM Re: HOT!!! New Interview w/ Bryan Singer! (August 20th) Well, placing this film in the 60s I think is a brilliant idea...very retro. The question is: Does the entire film take place in that time period? If so, it does far-outpace the timeline of what we saw in X1. Jean, Scott and Storm had to have been born in the very late 60s'/early 70's to fit the roles played by Famke, James and Halle. Which means...no Jean, Scott or Storm in "First Class." I find it strange though that Beast is in this...how old is he by X3? Was he literally Kelsey Grammar's age? LOL Blackman 08-20-2010 08:28 PM Re: HOT!!! New Interview w/ Bryan Singer! (August 20th) It's really risky that their releasing an X-Men film with none of the most known characters in the jam packed 2011 Doctor Jones 08-20-2010 08:32 PM Re: HOT!!! New Interview w/ Bryan Singer! (August 20th) Love all these ideas. I love the fact it's in the 60's and has an international James Bond feel to it. This is the first comic book film to do that and that's awesome. I can do without Scott and Jean I guess. Let's just hope for sequels. The Wizard 08-20-2010 08:34 PM Re: HOT!!! New Interview w/ Bryan Singer! (August 20th) Sounds great. So Bacon is indeed playing Shaw. Looking forward to First Class more than ever. Project862006 08-20-2010 08:35 PM Re: HOT!!! New Interview w/ Bryan Singer! (August 20th) well Kelsey was 51 when X3 came out i guess you could always round it up to like mid 50's Doctor Jones 08-20-2010 08:39 PM Re: HOT!!! New Interview w/ Bryan Singer! (August 20th) Yeah, I don't think they or we should be pinpointing the exact ages of these characters. Just rounded. Plus you know, Beast has blue fur so who's gonna notice? So Emma WASN'T 20-something years old in Wolverine afterall? It's cool that they're trying to pave the way for their own dream movie, but borrowing characters from other films makes things messy. I know they were only cameos, but Banshee and Emma were both in XO. My head's just buzzing now.. no bald crippled Xavier? Wah? The Original Bamfer 08-20-2010 08:56 PM Re: HOT!!! New Interview w/ Bryan Singer! (August 20th) I'm disappointed that we probably won't see Jean and Scott, but deep down I'm thinking they made the right decision. As hard as it is to admit it. :csad: Electrix 08-20-2010 08:58 PM Re: HOT!!! New Interview w/ Bryan Singer! (August 20th) They're obviously leaving Jean, Cyclops and Storm for a sequel. Fox want a trilogy so they won't be putting all the characters in at once. MultiPurposePon 08-20-2010 09:00 PM Re: HOT!!! New Interview w/ Bryan Singer! (August 20th) Quote: Originally Posted by The Original Bamfer (Post 18783548) I'm disappointed that we probably won't see Jean and Scott, but deep down I'm thinking they made the right decision. As hard as it is to admit it. :csad: That's the equivalent as telling your girlfriend: I promise I won't c** inside You know it's a lie, she knows it a lie, but you still say it anyway! Charles Xavier with hair? He lost it in high school due to his mutation. Fail Havok is Scott's younger brother. Fail Emma Frost is 20-something in Wolverine (which takes place in the 70s) and 30-something in the 60s. Fail They can't even create a movie that makes sense withing their own continuity.. forget about the comics one. TheComicbookKid 08-20-2010 09:01 PM Re: HOT!!! New Interview w/ Bryan Singer! (August 20th) I said to my brothers that I think X:FC will be the best movie quality wise but not make the most money. All this kind of confirms that for me. I'm excited and scared to see this now. TheComicbookKid 08-20-2010 09:02 PM Re: HOT!!! New Interview w/ Bryan Singer! (August 20th) Quote: Originally Posted by Squidboy (Post 18783546) So Emma WASN'T 20-something years old in Wolverine afterall? It's cool that they're trying to pave the way for their own dream movie, but borrowing characters from other films makes things messy. I know they were only cameos, but Banshee and Emma were both in XO. My head's just buzzing now.. no bald crippled Xavier? Wah? If Singer didn't make it(Wolverine and X3), don't worry about. TheWatcher 08-20-2010 09:04 PM Re: HOT!!! New Interview w/ Bryan Singer! (August 20th) You get em Poni. I hoping for Time Travel now. DarkSovereignty 08-20-2010 09:17 PM Re: HOT!!! New Interview w/ Bryan Singer! (August 20th) sounds awesome, i've been waiting for a superhero period piece (besides watchmen). JP 08-20-2010 09:23 PM Re: HOT!!! New Interview w/ Bryan Singer! (August 20th) Holy crap! K, my excitement went from a 9 to a 6 to an 11 This may be the best X-Men film yet. TheComicbookKid 08-20-2010 09:23 PM Re: HOT!!! New Interview w/ Bryan Singer! (August 20th) Only downside is that the second class of Scott and Jean will be in the 80s. Scott in a Members Only jacket? Ew JackMercy 08-20-2010 09:26 PM Re: HOT!!! New Interview w/ Bryan Singer! (August 20th) Again, semantics, but...my understanding was that the character thought to be a version of Emma Frost in Wolverine wasn't actually formally named in the credits -- am I correct? (I don't have a copy to reference.) Though they did kind of blow it by naming/using Scott Summers within the film... Either way, I sense that Singer and Vaughn here are playing more freely with X-Men film contunity...and kindly choosing not to incorporate certain elements of the rather undesirable third film or Wolverine. Also -- and this is important -- Fox is apparently allowing them to do so. Munch on that for a bit. Also, read Harry's words via Singer: he describes the film as a "new beginning" to the universe -- i.e. if the movie works, they can and should be able to move freely creatively from here on forward. As I've said already, I'm rather intrigued by what Singer and Vaughn seem to be cooking up... :word: TheWatcher 08-20-2010 09:28 PM Re: HOT!!! New Interview w/ Bryan Singer! (August 20th) I am intrigued. TheWatcher 08-20-2010 09:33 PM Re: HOT!!! New Interview w/ Bryan Singer! (August 20th) "The costumes will be far more comic bookish than we've seen before"= :awesome::awesome::awesome::awesome:

Q: Regex to get string between two characters I want to get everything between [ and ] like: [hello] hi should give: hello I tried \[(.*)\] but when i use: [hello] hi [yo] it gives: hello] hi [yo How can i make it so that it returns only the first one, then the second one like hello and yo A: \[(.*)\] is greedy meaning the * matches until the last occurance. Use a ? and it will stop at the first. \[(.*?)\] Demo: https://regex101.com/r/cM6aD7/1 PreDemo: https://regex101.com/r/cM6aD7/2

UNPUBLISHED UNITED STATES COURT OF APPEALS FOR THE FOURTH CIRCUIT No. 99-7549 JIMMY G. BLAKELY, Plaintiff - Appellant, versus COUNTY OF GREENVILLE; GREENVILLE COUNTY DETEN- TION CENTER; GERALD SEALS; JIM DORRIETY, Defendants - Appellees. Appeal from the United States District Court for the District of South Carolina, at Rock Hill. Margaret B. Seymour, District Judge. (CA-98-2468-0-24) Submitted: February 24, 2000 Decided: March 3, 2000 Before MOTZ and KING, Circuit Judges, and BUTZNER, Senior Circuit Judge. Affirmed by unpublished per curiam opinion. Jimmy G. Blakely, Appellant Pro Se. Russell W. Harter, Jr., CHAPMAN, HARTER & GROVES, P.A., Greenville, South Carolina, for Appellees. Unpublished opinions are not binding precedent in this circuit. See Local Rule 36(c). PER CURIAM: Jimmy G. Blakely appeals the district court’s order denying relief on his 42 U.S.C.A. § 1983 (West Supp. 1999) complaint. We have reviewed the record and the district court’s opinion accepting the magistrate judge’s recommendation and find no reversible error. Accordingly, we affirm on the reasoning of the district court. See Blakely v. County of Greenville, No. CA-98-2468-0-24 (D.S.C. Oct. 29, 1999). We dispense with oral argument because the facts and legal contentions are adequately presented in the materials before the court and argument would not aid the decisional process. AFFIRMED 2

"Filed out from Dolphin Smalltalk 7"! ENHMETARECORD subclass: #EMRPLGBLT instanceVariableNames: '' classVariableNames: '_OffsetOf_aptlDest _OffsetOf_cbBitsMask _OffsetOf_cbBitsSrc _OffsetOf_cbBmiMask _OffsetOf_cbBmiSrc _OffsetOf_crBkColorSrc _OffsetOf_cxSrc _OffsetOf_cySrc _OffsetOf_iUsageMask _OffsetOf_iUsageSrc _OffsetOf_offBitsMask _OffsetOf_offBitsSrc _OffsetOf_offBmiMask _OffsetOf_offBmiSrc _OffsetOf_rclBounds _OffsetOf_xformSrc _OffsetOf_xMask _OffsetOf_xSrc _OffsetOf_yMask _OffsetOf_ySrc' poolDictionaries: '' classInstanceVariableNames: ''! EMRPLGBLT guid: (GUID fromString: '{cdae1f25-39c4-4555-985b-3b2cd197d3e0}')! EMRPLGBLT addClassConstant: '_OffsetOf_aptlDest' value: 16r18! EMRPLGBLT addClassConstant: '_OffsetOf_cbBitsMask' value: 16r88! EMRPLGBLT addClassConstant: '_OffsetOf_cbBitsSrc' value: 16r6C! EMRPLGBLT addClassConstant: '_OffsetOf_cbBmiMask' value: 16r80! EMRPLGBLT addClassConstant: '_OffsetOf_cbBmiSrc' value: 16r64! EMRPLGBLT addClassConstant: '_OffsetOf_crBkColorSrc' value: 16r58! EMRPLGBLT addClassConstant: '_OffsetOf_cxSrc' value: 16r38! EMRPLGBLT addClassConstant: '_OffsetOf_cySrc' value: 16r3C! EMRPLGBLT addClassConstant: '_OffsetOf_iUsageMask' value: 16r78! EMRPLGBLT addClassConstant: '_OffsetOf_iUsageSrc' value: 16r5C! EMRPLGBLT addClassConstant: '_OffsetOf_offBitsMask' value: 16r84! EMRPLGBLT addClassConstant: '_OffsetOf_offBitsSrc' value: 16r68! EMRPLGBLT addClassConstant: '_OffsetOf_offBmiMask' value: 16r7C! EMRPLGBLT addClassConstant: '_OffsetOf_offBmiSrc' value: 16r60! EMRPLGBLT addClassConstant: '_OffsetOf_rclBounds' value: 16r8! EMRPLGBLT addClassConstant: '_OffsetOf_xformSrc' value: 16r40! EMRPLGBLT addClassConstant: '_OffsetOf_xMask' value: 16r70! EMRPLGBLT addClassConstant: '_OffsetOf_xSrc' value: 16r30! EMRPLGBLT addClassConstant: '_OffsetOf_yMask' value: 16r74! EMRPLGBLT addClassConstant: '_OffsetOf_ySrc' value: 16r34! EMRPLGBLT comment: '<EMRPLGBLT> is an <ExternalStructure> class to wrap the struct ''Win32.EMRPLGBLT'' from type information in the ''Win32 API (ANSI). Derived from Bruce McKinney´s Hardcore Visual Basic Type Library'' library. The type library contains no documentation for this struct Warning: This comment was automatically generated from the struct''s type information, but any changes made here will not be overwritten if the wrapper class is regenerated. IDL definition follows: typedef [uuid(CDAE1F25-39C4-4555-985B-3B2CD197D3E0)] struct tagEMRPLGBLT { EMR EMR; [helpstring("Inclusive-inclusive bounds in device units")] RECTL rclBounds; POINTL aptlDest[3]; long xSrc; long ySrc; long cxSrc; long cySrc; [helpstring("Source DC transform")] XFORM xformSrc; [helpstring("Source DC BkColor in RGB")] COLORREF crBkColorSrc; [helpstring("Source bitmap info color table usage")] DWORD iUsageSrc; [helpstring("Offset to the source BITMAPINFO structure")] DWORD offBmiSrc; [helpstring("Size of the source BITMAPINFO structure")] DWORD cbBmiSrc; [helpstring("Offset to the source bitmap bits")] DWORD offBitsSrc; [helpstring("Size of the source bitmap bits")] DWORD cbBitsSrc; long xMask; long yMask; [helpstring("Mask bitmap info color table usage")] DWORD iUsageMask; [helpstring("Offset to the mask BITMAPINFO structure if any")] DWORD offBmiMask; [helpstring("Size of the mask BITMAPINFO structure if any")] DWORD cbBmiMask; [helpstring("Offset to the mask bitmap bits if any")] DWORD offBitsMask; [helpstring("Size of the mask bitmap bits if any")] DWORD cbBitsMask; } EMRPLGBLT; '! !EMRPLGBLT categoriesForClass!Win32-Structs! ! !EMRPLGBLT methodsFor! aptlDest "Answer the <StructureArray> value of the receiver's 'aptlDest' field." ^StructureArray fromAddress: bytes yourAddress + _OffsetOf_aptlDest length: 3 elementClass: POINTL! aptlDest: aStructureArrayOfPOINTL "Set the receiver's 'aptlDest' field to the value of the argument, aStructureArrayOfPOINTL" | size | size := aStructureArrayOfPOINTL byteSize min: ##(3 * POINTL basicByteSize). aStructureArrayOfPOINTL replaceBytesOf: bytes from: ##(_OffsetOf_aptlDest + 1) to: _OffsetOf_aptlDest + size startingAt: 1! cbBitsMask "Answer the <Integer> value of the receiver's 'cbBitsMask' field." ^bytes dwordAtOffset: _OffsetOf_cbBitsMask! cbBitsMask: anInteger "Set the receiver's 'cbBitsMask' field to the value of the argument, anInteger" bytes dwordAtOffset: _OffsetOf_cbBitsMask put: anInteger! cbBitsSrc "Answer the <Integer> value of the receiver's 'cbBitsSrc' field." ^bytes dwordAtOffset: _OffsetOf_cbBitsSrc! cbBitsSrc: anInteger "Set the receiver's 'cbBitsSrc' field to the value of the argument, anInteger" bytes dwordAtOffset: _OffsetOf_cbBitsSrc put: anInteger! cbBmiMask "Answer the <Integer> value of the receiver's 'cbBmiMask' field." ^bytes dwordAtOffset: _OffsetOf_cbBmiMask! cbBmiMask: anInteger "Set the receiver's 'cbBmiMask' field to the value of the argument, anInteger" bytes dwordAtOffset: _OffsetOf_cbBmiMask put: anInteger! cbBmiSrc "Answer the <Integer> value of the receiver's 'cbBmiSrc' field." ^bytes dwordAtOffset: _OffsetOf_cbBmiSrc! cbBmiSrc: anInteger "Set the receiver's 'cbBmiSrc' field to the value of the argument, anInteger" bytes dwordAtOffset: _OffsetOf_cbBmiSrc put: anInteger! crBkColorSrc "Answer the <Integer> value of the receiver's 'crBkColorSrc' field." ^bytes dwordAtOffset: _OffsetOf_crBkColorSrc! crBkColorSrc: anInteger "Set the receiver's 'crBkColorSrc' field to the value of the argument, anInteger" bytes dwordAtOffset: _OffsetOf_crBkColorSrc put: anInteger! cxSrc "Answer the <Integer> value of the receiver's 'cxSrc' field." ^bytes sdwordAtOffset: _OffsetOf_cxSrc! cxSrc: anInteger "Set the receiver's 'cxSrc' field to the value of the argument, anInteger" bytes sdwordAtOffset: _OffsetOf_cxSrc put: anInteger! cySrc "Answer the <Integer> value of the receiver's 'cySrc' field." ^bytes sdwordAtOffset: _OffsetOf_cySrc! cySrc: anInteger "Set the receiver's 'cySrc' field to the value of the argument, anInteger" bytes sdwordAtOffset: _OffsetOf_cySrc put: anInteger! iUsageMask "Answer the <Integer> value of the receiver's 'iUsageMask' field." ^bytes dwordAtOffset: _OffsetOf_iUsageMask! iUsageMask: anInteger "Set the receiver's 'iUsageMask' field to the value of the argument, anInteger" bytes dwordAtOffset: _OffsetOf_iUsageMask put: anInteger! iUsageSrc "Answer the <Integer> value of the receiver's 'iUsageSrc' field." ^bytes dwordAtOffset: _OffsetOf_iUsageSrc! iUsageSrc: anInteger "Set the receiver's 'iUsageSrc' field to the value of the argument, anInteger" bytes dwordAtOffset: _OffsetOf_iUsageSrc put: anInteger! offBitsMask "Answer the <Integer> value of the receiver's 'offBitsMask' field." ^bytes dwordAtOffset: _OffsetOf_offBitsMask! offBitsMask: anInteger "Set the receiver's 'offBitsMask' field to the value of the argument, anInteger" bytes dwordAtOffset: _OffsetOf_offBitsMask put: anInteger! offBitsSrc "Answer the <Integer> value of the receiver's 'offBitsSrc' field." ^bytes dwordAtOffset: _OffsetOf_offBitsSrc! offBitsSrc: anInteger "Set the receiver's 'offBitsSrc' field to the value of the argument, anInteger" bytes dwordAtOffset: _OffsetOf_offBitsSrc put: anInteger! offBmiMask "Answer the <Integer> value of the receiver's 'offBmiMask' field." ^bytes dwordAtOffset: _OffsetOf_offBmiMask! offBmiMask: anInteger "Set the receiver's 'offBmiMask' field to the value of the argument, anInteger" bytes dwordAtOffset: _OffsetOf_offBmiMask put: anInteger! offBmiSrc "Answer the <Integer> value of the receiver's 'offBmiSrc' field." ^bytes dwordAtOffset: _OffsetOf_offBmiSrc! offBmiSrc: anInteger "Set the receiver's 'offBmiSrc' field to the value of the argument, anInteger" bytes dwordAtOffset: _OffsetOf_offBmiSrc put: anInteger! rclBounds "Answer the <RECT> value of the receiver's 'rclBounds' field." ^RECT fromAddress: bytes yourAddress + _OffsetOf_rclBounds! rclBounds: aRECT "Set the receiver's 'rclBounds' field to the value of the argument, aRECT" aRECT replaceBytesOf: bytes from: ##(_OffsetOf_rclBounds + 1) to: ##(_OffsetOf_rclBounds + RECT basicByteSize) startingAt: 1! xformSrc "Answer the <XFORM> value of the receiver's 'xformSrc' field." ^XFORM fromAddress: bytes yourAddress + _OffsetOf_xformSrc! xformSrc: aXFORM "Set the receiver's 'xformSrc' field to the value of the argument, aXFORM" aXFORM replaceBytesOf: bytes from: ##(_OffsetOf_xformSrc + 1) to: ##(_OffsetOf_xformSrc + XFORM basicByteSize) startingAt: 1! xMask "Answer the <Integer> value of the receiver's 'xMask' field." ^bytes sdwordAtOffset: _OffsetOf_xMask! xMask: anInteger "Set the receiver's 'xMask' field to the value of the argument, anInteger" bytes sdwordAtOffset: _OffsetOf_xMask put: anInteger! xSrc "Answer the <Integer> value of the receiver's 'xSrc' field." ^bytes sdwordAtOffset: _OffsetOf_xSrc! xSrc: anInteger "Set the receiver's 'xSrc' field to the value of the argument, anInteger" bytes sdwordAtOffset: _OffsetOf_xSrc put: anInteger! yMask "Answer the <Integer> value of the receiver's 'yMask' field." ^bytes sdwordAtOffset: _OffsetOf_yMask! yMask: anInteger "Set the receiver's 'yMask' field to the value of the argument, anInteger" bytes sdwordAtOffset: _OffsetOf_yMask put: anInteger! ySrc "Answer the <Integer> value of the receiver's 'ySrc' field." ^bytes sdwordAtOffset: _OffsetOf_ySrc! ySrc: anInteger "Set the receiver's 'ySrc' field to the value of the argument, anInteger" bytes sdwordAtOffset: _OffsetOf_ySrc put: anInteger! ! !EMRPLGBLT categoriesFor: #aptlDest!**compiled accessors**!public! ! !EMRPLGBLT categoriesFor: #aptlDest:!**compiled accessors**!public! ! !EMRPLGBLT categoriesFor: #cbBitsMask!**compiled accessors**!public! ! !EMRPLGBLT categoriesFor: #cbBitsMask:!**compiled accessors**!public! ! !EMRPLGBLT categoriesFor: #cbBitsSrc!**compiled accessors**!public! ! !EMRPLGBLT categoriesFor: #cbBitsSrc:!**compiled accessors**!public! ! !EMRPLGBLT categoriesFor: #cbBmiMask!**compiled accessors**!public! ! !EMRPLGBLT categoriesFor: #cbBmiMask:!**compiled accessors**!public! ! !EMRPLGBLT categoriesFor: #cbBmiSrc!**compiled accessors**!public! ! !EMRPLGBLT categoriesFor: #cbBmiSrc:!**compiled accessors**!public! ! !EMRPLGBLT categoriesFor: #crBkColorSrc!**compiled accessors**!public! ! !EMRPLGBLT categoriesFor: #crBkColorSrc:!**compiled accessors**!public! ! !EMRPLGBLT categoriesFor: #cxSrc!**compiled accessors**!public! ! !EMRPLGBLT categoriesFor: #cxSrc:!**compiled accessors**!public! ! !EMRPLGBLT categoriesFor: #cySrc!**compiled accessors**!public! ! !EMRPLGBLT categoriesFor: #cySrc:!**compiled accessors**!public! ! !EMRPLGBLT categoriesFor: #iUsageMask!**compiled accessors**!public! ! !EMRPLGBLT categoriesFor: #iUsageMask:!**compiled accessors**!public! ! !EMRPLGBLT categoriesFor: #iUsageSrc!**compiled accessors**!public! ! !EMRPLGBLT categoriesFor: #iUsageSrc:!**compiled accessors**!public! ! !EMRPLGBLT categoriesFor: #offBitsMask!**compiled accessors**!public! ! !EMRPLGBLT categoriesFor: #offBitsMask:!**compiled accessors**!public! ! !EMRPLGBLT categoriesFor: #offBitsSrc!**compiled accessors**!public! ! !EMRPLGBLT categoriesFor: #offBitsSrc:!**compiled accessors**!public! ! !EMRPLGBLT categoriesFor: #offBmiMask!**compiled accessors**!public! ! !EMRPLGBLT categoriesFor: #offBmiMask:!**compiled accessors**!public! ! !EMRPLGBLT categoriesFor: #offBmiSrc!**compiled accessors**!public! ! !EMRPLGBLT categoriesFor: #offBmiSrc:!**compiled accessors**!public! ! !EMRPLGBLT categoriesFor: #rclBounds!**compiled accessors**!public! ! !EMRPLGBLT categoriesFor: #rclBounds:!**compiled accessors**!public! ! !EMRPLGBLT categoriesFor: #xformSrc!**compiled accessors**!public! ! !EMRPLGBLT categoriesFor: #xformSrc:!**compiled accessors**!public! ! !EMRPLGBLT categoriesFor: #xMask!**compiled accessors**!public! ! !EMRPLGBLT categoriesFor: #xMask:!**compiled accessors**!public! ! !EMRPLGBLT categoriesFor: #xSrc!**compiled accessors**!public! ! !EMRPLGBLT categoriesFor: #xSrc:!**compiled accessors**!public! ! !EMRPLGBLT categoriesFor: #yMask!**compiled accessors**!public! ! !EMRPLGBLT categoriesFor: #yMask:!**compiled accessors**!public! ! !EMRPLGBLT categoriesFor: #ySrc!**compiled accessors**!public! ! !EMRPLGBLT categoriesFor: #ySrc:!**compiled accessors**!public! ! !EMRPLGBLT class methodsFor! defineFields "Define the fields of the EMRPLGBLT structure. EMRPLGBLT compileDefinition typedef [uuid(CDAE1F25-39C4-4555-985B-3B2CD197D3E0)] struct tagEMRPLGBLT { EMR EMR; [helpstring('Inclusive-inclusive bounds in device units')] RECTL rclBounds; POINTL aptlDest[3]; long xSrc; long ySrc; long cxSrc; long cySrc; [helpstring('Source DC transform')] XFORM xformSrc; [helpstring('Source DC BkColor in RGB')] COLORREF crBkColorSrc; [helpstring('Source bitmap info color table usage')] DWORD iUsageSrc; [helpstring('Offset to the source BITMAPINFO structure')] DWORD offBmiSrc; [helpstring('Size of the source BITMAPINFO structure')] DWORD cbBmiSrc; [helpstring('Offset to the source bitmap bits')] DWORD offBitsSrc; [helpstring('Size of the source bitmap bits')] DWORD cbBitsSrc; long xMask; long yMask; [helpstring('Mask bitmap info color table usage')] DWORD iUsageMask; [helpstring('Offset to the mask BITMAPINFO structure if any')] DWORD offBmiMask; [helpstring('Size of the mask BITMAPINFO structure if any')] DWORD cbBmiMask; [helpstring('Offset to the mask bitmap bits if any')] DWORD offBitsMask; [helpstring('Size of the mask bitmap bits if any')] DWORD cbBitsMask; } EMRPLGBLT; " super defineFields. self defineField: #rclBounds type: (StructureField type: RECT) offset: 8; defineField: #aptlDest type: (StructureArrayField type: POINTL length: 3) offset: 24; defineField: #xSrc type: SDWORDField new offset: 48; defineField: #ySrc type: SDWORDField new offset: 52; defineField: #cxSrc type: SDWORDField new offset: 56; defineField: #cySrc type: SDWORDField new offset: 60; defineField: #xformSrc type: (StructureField type: XFORM) offset: 64; defineField: #crBkColorSrc type: DWORDField new offset: 88; defineField: #iUsageSrc type: DWORDField new offset: 92; defineField: #offBmiSrc type: DWORDField new offset: 96; defineField: #cbBmiSrc type: DWORDField new offset: 100; defineField: #offBitsSrc type: DWORDField new offset: 104; defineField: #cbBitsSrc type: DWORDField new offset: 108; defineField: #xMask type: SDWORDField new offset: 112; defineField: #yMask type: SDWORDField new offset: 116; defineField: #iUsageMask type: DWORDField new offset: 120; defineField: #offBmiMask type: DWORDField new offset: 124; defineField: #cbBmiMask type: DWORDField new offset: 128; defineField: #offBitsMask type: DWORDField new offset: 132; defineField: #cbBitsMask type: DWORDField new offset: 136. self byteSize: 140! getFieldNames ^#(#iType #nSize #rclBounds #aptlDest #xSrc #ySrc #cxSrc #cySrc #xformSrc #crBkColorSrc #iUsageSrc #offBmiSrc #cbBmiSrc #offBitsSrc #cbBitsSrc #xMask #yMask #iUsageMask #offBmiMask #cbBmiMask #offBitsMask #cbBitsMask)! iTypes "Answer the integer enhanced metafile record type id for this record class." ^Array with: EMR_PLGBLT! ! !EMRPLGBLT class categoriesFor: #defineFields!**auto generated**!public!template definition! ! !EMRPLGBLT class categoriesFor: #getFieldNames!**compiled accessors**!constants!private! ! !EMRPLGBLT class categoriesFor: #iTypes!constants!public! !

Researchers have developed a new way to improve lithium ion battery efficiency. Through the growth of a cubic crystal layer, the scientists have created a thin and dense connecting layer between the electrodes of the battery. Professor Nobuyuki Zettsu from the Center for Energy and Environmental Science in the Department of Materials Chemistry of Shinshu University in Japan and the director of the center, Professor Katsuya Teshima, led the research. The authors published their results online in January this year in Scientific Reports. "Owing to some intrinsic characteristics of liquid electrolytes, such as low lithium transport number, complex reaction at the solid/liquid interface, and thermal instability, it has not been possible to simultaneously achieve high energy and power in any of the current electrochemical devices," said Nobuyuki Zettsu, as first author on the paper. Lithium ion batteries are rechargeable and power such devices as cell phones, laptops, power tools, and even store power for the electrical grid. They're particularly sensitive to temperature fluxes, and have been known to cause fires or even explosions. In response to the problems with liquid electrolytes, scientists are working toward developing a better all-solid-state battery without liquid. "Despite the expected advantages of all-solid-state batteries, their power characteristic and energy densities must be improved to allow their application in such technologies as long-range electric vehicles," Zettsu said. "The low rate capabilities and low energy densities of the all-solid-state batteries are partly due to a lack of suitable solid-solid heterogeneous interface formation technologies that exhibit high iconic conductivity comparable to liquid electrolyte systems." Zettsu and his team grew garnet-type oxide solid electrolyte crystals in molten LiOH used as a solvent (flux) on a substrate that bonded the electrode into a solid state as they grew. A specific crystal compound known to grow cubically allowed the researchers to control the thickness and connection area within the layer, which acts as a ceramic separator. advertisement "Electron microscopy observations revealed that the surface is densely covered with well-defined polyhedral crystals. Each crystal is connected to neighboring ones," wrote Zettsu. Zettsu also said that the newly grown crystal layer could be the ideal ceramic separator when stacking the electrolyte layer on the electrode layer. "We believe that our approach having robustness against side reactions at the interface could possibly lead to the production of ideal ceramic separators with a thin and dense interface," wrote Zettsu, noting that the ceramics used in this particular experiment were too thick to be used in solid batteries. "However, as long as the electrode layer can be made as thin as 100 microns, the stacking layer will operate as a solid battery." One hundred microns is about the width of a human hair, and slightly less than twice the thickness of a standard electrode layer in contemporary lithium-ion batteries. "All-solid-state batteries are promising candidates for energy storage devices," Zettsu said, noting that several collaborations between researchers and private companies are already underway with the ultimate goal of displaying all-solid-state battery samples at the 2020 Olympic games in Tokyo. Zettsu and other researchers plan to fabricate prototype cells for electric vehicle use and for wearable devices by 2022. Other collaborators on this project include researchers from the Institute for Materials Research at Tohoku University, Frontier Research Institute for Materials Science at Nagoya Institute of Technology, and the National Institute for Materials Science.

Saturday, July 31, 2010 Lois Christensen I have been playing with some family pictures and having fun layering them. This is a picture of my husband's mother, when she graduated from college. She attended John Fletcher College and graduated from Iowa State Teachers College in 1929. The couple in the lower left background are her parents Charles and Alice Collins.

Erin Pizzey took to internet community Reddit this past weekend to answer questions from users. She is known for her integral hand and tireless efforts in exposing domestic violence to the public consciousness throughout the 1970s by setting up one of the first battered women’s shelters and writing the groundbreaking book on the subject of domestic assault: Scream Quietly or the Neighbours Will Hear. In more recent years she has taken on neglect and abuse of men and boys as her cause and this is where the majority of her questions and answers focused. andreipmbcn: Looking at it from a perspective of abuse and neglect, would you say that there is a general attitude of neglect towards men today? erinpizzey: […] My problem is that it’s men who’ve been victims of domestic violence, which is largely ignored by society… and not only ignored, but ridiculed. Billions are spent – billions I say – across the world for women’s refuges and virtually nothing for men. And the one men’s refuge in Canada was so denigrated and despised by the Canadian government, as you will see from our introduction, Earl committed suicide after he was forced to sell his home and he lost everything. The Earl she is referring to is Earl Silverman, a Canadian man who spent 20 years of his life crusading for better access to victim and emergency services for men and boys who are victims of abuse. Earl was a victim of abuse at the hands of a former spouse and dedicated his time, energy, and money towards creating a shelter specifically for male victims fleeing abusive situations. For three years Silverman ran the Men’s Alternative Safe House out of his own home, taking in about 20 men and children over that period. Earl spent the entirety of his own savings to keep MASH running while trying, unsuccessfully, to convince the government to allocate funds for his and other projects directed at male victims. MASH was the only refuge of its kind in Canada. After years of being unable to keep the shelter through his own funds and meagre private donations he was driven to financial ruin and forced to sell his home and, by association, give up his hopes for helping other victims. After selling his house he committed suicide on Friday, April 26, by hanging himself in the garage. Silverman’s death appears to be caused entirely by what he and Prizzy have been fighting. He was a victim of abuse whose inability to find services eventually killed him. Suicide is a predominantly male problem with rates in Canada making it the seventh highest cause of death for men here. In Canada just under one in every 5,000 men will kill themselves. In Yukon, Quebec, and Northwest Territories it is one in every 4,000 men. In Nunavut one in every 1,000 men will commit suicide. There are many who would argue that men are incapable of experiencing abuse, physical or otherwise. Police statistics, for example, seem to tell a different story where only 20 percent of victims from domestic calls are male. In fact, according to Statistics Canada, men are almost exactly as likely as women to be victims of domestic abuse: “A similar proportion of men and women reported experiencing spousal violence during the five years prior to the survey. Among men, 6.0% or about 585,000, encountered spousal violence during this period, compared with 6.4% or 601,000 women.” Perhaps the low rate of police calls for men in distress is not indicative of low rates of abused males but rather indicative of men being afraid to coming forward to police or attempt to escape their situation. Male victims are being told from all sides that they are not victims; that statistics are so low they don’t matter; that if they were a real man they would just suck it up and take it; that women aren’t capable of delivering the same kinds of abuse that men can; that what they are experiencing is normal. After hearing enough of that, it is no surprise that men would be afraid to step forward. Even if they did manage to overcome everything they’ve ever been told, now that Canada’s only shelter for men is gone, where would they even go? Ed Note: This story has been updated to include more reliable figures on suicide in Canada.

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--- author: - - bibliography: - 'references.bib' title: | An Operational Semantic Basis\ for OpenMP Race Analysis --- OpenMP; operational semantics; concurrency; formal definition; data race; data race detection tool; structured parallelism

cnxps.cmd.push(function () { cnxps({ playerId: '36af7c51-0caf-4741-9824-2c941fc6c17b' }).render('4c4d856e0e6f4e3d808bbc1715e132f6'); }); Israeli researchers are at the forefront of medical innovation to offer new solutions in the fight against the novel coronavirus outbreak.British company diagnostics.ai, whose research and development is entirely based in Herzliya, is already providing labs in the UK and US with their advanced diagnostic technique, employing artificial intelligence for faster and more accurate results, Brian Glenville, chairman of diagnostics.ai and former head of heart surgery at Hadassah-University Medical Center, told The Jerusalem Post.“In the old days, if you went to the doctor with a chest infection, they would ask you to cough into a pot and send the specimen to a laboratory, which would put it on a plate to grow,” he said. “After 48 hours they would put some antibiotic discs next to it, and another 48 hours later they would tell you which one worked for that bug.”“Several years [later], tests called Real Time PCR or Q-PCR came in,” he added. “They look at the nuclear content, the DNA or RNA, in the bacteria or the virus.”To perform the test, a biological specimen of the patients, for example, saliva or blood, is put into a machine called thermal cycler, which heats and cools the material 30 or 40 times until the DNA or RNA fragments in the specimen have split. The fragments then join to a molecule of fluorescent light.“That’s how you find out what is the content of your biological solutions are,” Glenville said. “The problem is that the answer comes out as a curve on a graph, which means it requires an analysis by a skilled medical technician.”The requirement for an expert to analyze the results of the test might not be particularly challenging if the number of tests performed remains low. But when hundreds, if not thousands, of tests are needed – as in the case of the current emergency – tiredness and other human factors, including the risk for the technicians to get infected themselves, represents an obstacle.As an alternative, there are kits made by manufactures that include whatever is necessary to execute the tests and give the answer. But they are expensive and inflexible, which means that if the virus mutates, their technology won’t be suitable.“They are also not as automatic and not as accurate as they could be,” Glenville said.What diagnostics.ai has developed is truly automatic and can analyze any virus or bacteria.Once the biological specimen is analyzed, which takes 40 minutes to an hour, the results are almost instantaneous, and they are fed to the hospital information system right away.The technology was studied by one of the largest virology units in Europe, the West of Scotland Specialist Virology Centre, comparing the results of diagnostics.ai with those by their best technicians.As explained in an article published in the Journal of Clinical Virology, they were found superior in terms of accuracy.The company’s technology is generic, which means it does not work only for a specific virus but for any virus or bacteria. It is currently used for infections. But diagnostics.ai is planning to employ it for cancer and genetic expressions and any other form of testing to analyze material containing DNA or RNA.“One of the laboratories in a large London hospital just asked us to increase their volumes tenfold, and I think it is only the beginning,” Glenville said.A new and more efficient method to diagnose the coronavirus was successfully tested by Israeli researchers at the Technion-Israel Institute of Technology and Rambam Health Care Campus. The new testing method will dramatically increase the rate at which tests can be done for the deadly virus, it was announced on Thursday.The current testing method in Israel and most of the world has been to only focus on people with specific symptoms. This new testing method enables the testing of people with no symptoms and for dozens of tests to be carried out at once, ultimately accelerating efforts in curbing the virus.“This experiment conducted by Technion and Rambam researchers is complex and under normal circumstances would take months,” Technion president Prof. Uri Sivan said. “This is a remarkable example of the mobilization of an outstanding team in a time of crisis. The initial experiment was completed in less than four days.”The current rate of testing in Israel, done by the common PCR method (polymerase chain reaction), is about 1,200 a day. And each one must be examined individually, which takes several hours, causing bottlenecks in testing and slowing efforts to curb the virus.The Rambam Clinical Microbiology Laboratory is only able to test 200 COVID-19 samples a day.Now, molecular testing for the virus, using the new pooling method, can be done by combining samples taken from 32 or 64 patients, enabling simultaneous testing of dozens of samples. In rare cases where a positive case is found in a joint sample, only then will each of the specific samples be tested individually.“Even when we conducted a joint examination of 64 samples in which only one was a positive carrier, the system identified that there was a positive sample,” said Prof. Roy Kishony, head of the research group at the Technion’s the Faculty of Biology.“This is not a breakthrough but a demonstration of the effectiveness of using the existing method and even the existing equipment to significantly increase the volume of samples tested per day,” he said.

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Using genetic variation to study immunomodulation. The generation of a draft sequence of a human genome has led to the identification of millions of common variants, known as single nucleotide polymorphisms, which constitute a resource for studying complex diseases. Currently, high-density maps of variants in candidate genes, chromosomal regions or the entire genome should encourage investigation of determinants of human immune response, using quantitative analysis. Ultimately, this approach should identify novel targets for therapeutic intervention.

Help Us Write a Sonnet: Line Six By David Lehman June 10, 2014 Click here to read previous lines from our crowd-sourced sonnet, and here for David Lehman’s description of the history and requirements of the form. How like a prison is my cubicle, And yet how far my mind can freely roam From gaol to Jerusalem, Hell to home. Freedom ends or starts with a funeral. Say what must die inside that I may not Cast down this die and cross the Rubicon Line six, Anna E. Moss’s “Cast down this die and cross the Rubicon,” won me over with its repetition of the previous line’s “die” but in a completely different sense: not the verb of mortality but a noun, the singular of dice. The line makes a cunning allusion to Julius Caesar, who said “alea lacta est”—“the die is cast”—when he and his armies successfully crossed the Rubicon River south of Ravenna in 49 B.C. For the second straight week, Joe Lawlor is top runner-up. He proposed a period after line five and then “Say what must not that I may bear to live.” Third place goes to Lewis Saul for sheer creativity: “Croak in Benghazi. Wasn’t that your wish?” I was also taken with several smart candidates suggested by Hazel Nolan, including “Betray the grass-stained girl I used to be” and “Betray the barefoot boy, who once ran free,” though I wondered whether these gender-specific constructions might prove a burden to contestants of the opposite sex. For line seven, we have the opportunity to revitalize a trite expression (“cross the Rubicon” meaning something like “no turning back”) by grounding it in fact or conjecture. What happened there in 49 B.C? What does the river look like? I can imagine a continuation of the ironic comparison of the speaker with world-conqueror Julius Caesar. But it is not my poem—it is ours, and I depend on your ingenuity, ladies and gentlemen. Oh, and we need to rhyme the next line, if only loosely, with “Rubicon.” A tall order? No taller than “cubicle,” with which it shares the same foundational consonants. “Leprechaun,” “marathon,” and “novocaine” would be equally eligible, to give some examples that come to mind. WINNER’S CIRCLE: How like a prison is my cubicle, (DL) And yet how far my mind can freely roam (Leo Braudy) From gaol to Jerusalem, Hell to home. (Brian Anderson and his 12th grade composition class) Freedom ends or starts with a funeral. (Frank Bidart) Say what must die inside that I may not (MQ) Cast down this die and cross the Rubicon (Anna E. Moss) Please leave your suggestion for the next line in a comment below. David Lehman is the series editor for The Best American Poetry annual anthology. He has published eight books of poetry, the most recent of which is New and Selected Poems.

Q: Why is Logic Apps' if() expression executing both code paths simultaneously? I am getting failures on a Logic App because the if() expression is executing both the true and false paths. The false path is going to fail if it executes which is why I put it in an if() in the first place. The expression is: if(empty(triggerBody()?['data']?['eta']), null, formatDateTime(triggerBody()?['data']?['eta'], 'yyyy-MM-dd')) I've also tried: if(equals(triggerBody()?['data']?['eta'], null), null, formatDateTime(triggerBody()?['data']?['eta'], 'yyyy-MM-dd')) The data is null: ... "data": { "eta": null, ... I've tested this by swapping out formatDateTime() with a string like 'is not null'. When I do this I get the expected output (null) and no failure. Update: Someone from the Logic Apps team suggested the following as an alternative: @if(empty(triggerBody()?['data']?['eta']), null, formatDateTime(coalesce(triggerBody()?['data']?['eta'], '1999-01-01'), 'yyyy-MM-dd')) The usage of coalesce() is suggested here because it returns the first non-null result. So in this way I can at least be assured of providing a value to formatDateTime(). A: Why? Because that's the way it's written. ;) What you are seeing is the expected behavior of if() execution in a LogicApp. Someone from the LogicApp team mentioned this (Channel 9?, sorry don't recall) and don't expect it to change any time soon. If either case might cause a runtime error, you'll need to do it in two steps.

Friday Code Monkey Song - TheOrange http://blog.crowdstorm.com/?p=154 ====== danielha Coulton's stuff is great. And although this is one of my favorites, it's important to remember that you don't HAVE to be a code monkey if you're a software engineer. I think a lot of students are getting discouraged from the computer science field because they don't want to be pre-Matrix Neo or stuck in the daily grind from Office Space. You definitely can end up in that situation but if you're smart and passionate, you won't. Being a developer in a startup is an example of that. If you love what you're working on and you're contributing to its potential, you're not going to be that monkey. Or if there's nothing already out there where you can apply this passion, take the entrepreneurial route. That's likely why we're all here on this site to begin with. :) ------ TheOrange This is really funny - think of all you are missing by not being a coder for a faceless corporation. ~~~ danw Jonathan Coulton rocks. Check out his other stuff and buy his music at http://www.jonathancoulton.com/

54 F.3d 767 In re Jathor Eliaeh Easley, III, a/k/a, d/b/a Jay'sPhotography; Jathor Eliaeh Easley, IIIv.Superior Court of New Jersey, Middlesex County Probation Dept. NO. 94-5782 United States Court of Appeals,Third Circuit. Apr 19, 1995 Appeal From: D.N.J., No. 94-cv-03363, Brown, J. 1 AFFIRMED.

#include <iostream> #include "BenchUtil.h" #include "basicbenchmark.h" int main(int argc, char *argv[]) { DISABLE_SSE_EXCEPTIONS(); // this is the list of matrix type and size we want to bench: // ((suffix) (matrix size) (number of iterations)) #define MODES ((3d)(3)(4000000)) ((4d)(4)(1000000)) ((Xd)(4)(1000000)) ((Xd)(20)(10000)) // #define MODES ((Xd)(20)(10000)) #define _GENERATE_HEADER(R,ARG,EL) << BOOST_PP_STRINGIZE(BOOST_PP_SEQ_HEAD(EL)) << "-" \ << BOOST_PP_STRINGIZE(BOOST_PP_SEQ_ELEM(1,EL)) << "x" \ << BOOST_PP_STRINGIZE(BOOST_PP_SEQ_ELEM(1,EL)) << " / " std::cout BOOST_PP_SEQ_FOR_EACH(_GENERATE_HEADER, ~, MODES ) << endl; const int tries = 10; #define _RUN_BENCH(R,ARG,EL) \ std::cout << ARG( \ BOOST_PP_CAT(Matrix, BOOST_PP_SEQ_HEAD(EL)) (\ BOOST_PP_SEQ_ELEM(1,EL),BOOST_PP_SEQ_ELEM(1,EL)), BOOST_PP_SEQ_ELEM(2,EL), tries) \ << " "; BOOST_PP_SEQ_FOR_EACH(_RUN_BENCH, benchBasic<LazyEval>, MODES ); std::cout << endl; BOOST_PP_SEQ_FOR_EACH(_RUN_BENCH, benchBasic<EarlyEval>, MODES ); std::cout << endl; return 0; }

Introduction {#Sec1} ============ Apatite-iron oxide ore is by far the biggest source of iron in Europe and one of the main iron sources worldwide^[@CR1]^. In Europe, these magnetite-dominated ores have traditionally been sourced from two principal regions, the Bergslagen ore province in south central Sweden and the Kiruna-Malmberget region in northern Sweden (Fig. [1](#Fig1){ref-type="fig"})^[@CR2]^. The apatite-iron oxide ores from these localities are internationally renowned and similar ores elsewhere are usually referred to as being of Kiruna-type^[@CR3]--[@CR5]^. While the Grängesberg and Kiruna deposits are Palaeoproterozoic in age^[@CR6]^, similar apatite-iron oxide deposits along the American Cordilleras are much younger and range in age from Jurassic to Neogene, like the Pliocene El Laco deposit in Chile^[@CR7]--[@CR9]^. Together with the occurrences of Paleozoic apatite-iron oxide ores in Turkey, Iran, and China, and Triassic examples from Korea^[@CR10]--[@CR13]^, apatite-iron oxide ores have repeatedly formed across the globe and throughout geological time.Fig. 1Sample overview map. **a** Global map showing the different locations of origin for apatite-iron-oxide ore and reference samples. **b** A close-up view of the main part of the Fennoscandian Shield showing the sample locations for magnetites from Sweden The origin of the Kiruna-type apatite-iron-oxide ores remains ambiguous, however, despite a long history of study and a concurrently intense scientific debate. Several fundamentally different modes of formation have been proposed. Today two broad schools of thought prevail, represented by either direct magmatic formation processes, such as segregation or crystallization, or by hydrothermal replacement processes, including hydrothermal precipitation in the sense of iron-oxide-copper-gold (IOCG) deposits^[@CR3],[@CR4],[@CR14]--[@CR31]^. Specifically, the discussion revolves around a direct magmatic origin (ortho-magmatic) from volatile- and Fe--P-rich magmas or high-temperature magmatic fluids^[@CR1],[@CR5],[@CR18],[@CR31]^, versus a purely hydrothermal one, where circulating, metal-rich fluids replace original host rock mineralogy with apatite-iron-oxide mineralizations at medium to low temperature^[@CR4],[@CR19],[@CR28]--[@CR30],[@CR32]^. An ortho-magmatic origin is generally understood to be either formation by direct crystallization from a magma or from high-temperature magmatic fluids (e.g. ≥800 °C), or via high-temperature liquid immiscibility and physical separation of an iron oxide-dominated melt from a silicate-dominated magma, where the former may subsequently crystallize as a separate body^[@CR17],[@CR18],[@CR33]--[@CR38]^. Hydrothermal processes, in turn, encompass transport and precipitation, including replacement-type reactions, by means of aqueous fluids at more moderate to low temperatures (typically ≤400 °C)^[@CR27],[@CR29],[@CR30],[@CR32]^. Both the magmatic and the hydrothermal hypotheses are supported in part by field observations, textural relationships, and mineral chemistry, however, petrological field evidence and chemical trends of major and trace elements have frequently been interpreted in different ways^[@CR5],[@CR14],[@CR16]--[@CR22],[@CR28]--[@CR32]^. Moreover, many of previous investigations have focused on one case study only and frequently present a range of various data, with individual data sets often being relatively restricted in respect to data volume. What has so far been missing is a broad and decisive geochemical approach to distinguish between these two rival formation hypotheses on an across-deposit scale. To date no systematic stable isotope study employing several distinct Kiruna--type apatite iron oxide ore deposits is available and, importantly, no systematic comparison with accepted magmatic and hydrothermal rock and ore suites has previously been presented in the literature. Results {#Sec2} ======= Scientific rationale and sample selection {#Sec3} ----------------------------------------- Here we use the isotopes of iron and oxygen, the two essential elements in magnetite (Fe~3~O~4~), on magnetite samples from four major Kiruna-type ore provinces. Magnetite is the main iron-bearing component in Kiruna-type deposits and our approach therefore utilizes highly reliable major elements as petrogenetic tracers, as opposed to, e.g., traditional minor element approaches that rely on low-concentration constituents in these ores and their host rocks. We present an extensive set of new Fe and O isotope data of magnetite from a suite of world-class Kiruna-type ores from three continents, represented by Sweden, Chile, and Iran, and complement these data by a large suite of new comparative data on accepted magmatic and hydrothermal reference samples (54 new Fe--O coupled isotope ratios and another 12 individual ratios, totaling 120 new individual isotope ratios). In addition, the four different regions of Kiruna-type deposits investigated are separated in space and time, as are the extensive suite of volcanic, plutonic, and low-temperature reference materials that we employ to define the endmember processes reflected in our ore deposit data (see Fig. [1](#Fig1){ref-type="fig"} and Supplementary Table [1](#MOESM1){ref-type="media"}). We use these data to address whether Kiruna-type apatite-iron oxide ores form primarily through direct magmatic processes (magma and magmatic fluids) at high temperatures (≥800 °C), or alternatively, through precipitation from hydrothermal fluids at considerably lower temperatures (≤400 °C). The comparative aspect of our work is a particular strength and to the best of our knowledge, no other systematic study with such global coverage has been performed to date. In addition, we offer the first substantial data sets for coupled Fe and O isotopes for the world famous Kiruna, Grängesberg, and Bafq deposits, plus new comparative data for El Laco that are consistent with published data for this deposit^[@CR5],[@CR14],[@CR17],[@CR18],[@CR32]^. The study's global extent, its systematic approach, its large data volume, and most crucially, the global Fe--O isotope correlation permits a decisive conclusion, which allows us to advance our understanding of the relationship between magmatic and hydrothermal processes in the genesis of Kiruna-type iron-oxide ore deposits. The use of a broad set of Fe--O isotope data is especially useful as it establishes not only genetic similarities between different deposits, but also provides constrains on the formation temperatures^[@CR1],[@CR5],[@CR39]^ and allows us to identify a high-temperature versus a low-temperature origin of individual ore deposits. To facilitate a widely applicable comparison of apatite-iron-oxide ores, analyses of iron and oxygen isotope ratios of magnetite from massive apatite-iron-oxide ores from the Kiruna Mining District in northern Sweden (*n* = 14), the Grängesberg Mining District and the nearby Blötberget ore body in central Sweden (*n* = 16), the El Laco district in Chile (*n* = 6), and the Bafq Mining District in central Iran (*n* = 6; Figs. [1](#Fig1){ref-type="fig"} and [2](#Fig2){ref-type="fig"}) were performed. These ore provinces and regions are briefly introduced below, and full details are given in Supplementary Note [1](#MOESM1){ref-type="media"}.Fig. 2Images of apatite-iron oxide ores in this study. False-color BSE images of massive magnetite ore samples from **a**, **b** Kiruna; **c**, **d** Grängesberg; **e**, **f** Bafq; and **g**, **h** El Laco. Kiruna, Grängesberg, and Bafq magnetite samples are homogeneous and commonly lack zonation or signs of alteration. El Laco (**g**, **h**), is exceptional in this respect as for some samples intra-crystal zonation is observed. As a supplement, regular greyscale BSE images for these samples are provided in Supplementary Fig. [1](#MOESM1){ref-type="media"} The study of apatite-iron-oxide mineralizations began at the iconic deposits of the Kiruna Mining District^[@CR3]^. The present Kiruna mine at Kiirunavaara is the largest deposit of its type, and is the main supplier of iron ore in Europe. This deposit alone represents a pre-mining reserve of ≥2 billion tons of high grade ore. The ores in Kiruna and similar Palaeoproterozoic deposits in the district (Supplementary Table [1](#MOESM1){ref-type="media"}) are dominated by magnetite and contain between 50 and 70% Fe with a P content of, commonly, up to 2 wt.% that is mainly hosted by fluorapatite and subordinate monazite-(Ce)^[@CR25]^. Additional gangue minerals that can occur in small proportions are Mg-rich actinolite, phlogopite, chlorite, titanite, talc, feldspar, quartz, carbonates, sulfides, sulfates, and clays^[@CR3],[@CR5],[@CR25]^. The apatite-iron-oxide ores of the Grängesberg and the nearby Blötberget deposits represent the largest iron-ore accumulation in the Bergslagen ore province, a classic mining region in central Sweden considered to represent a Palaeoproterozoic continental rift or back arc basin^[@CR40]^. A historic production of 156 Mt of ore, averaging 60% Fe and 0.81% P, is documented from Grängesberg. In addition to iron oxides (dominantly magnetite), the presence of phosphates such as fluorapatite, monazite-(Ce), and xenotime-(Y), together with REE-silicates constitute a potentially significant P and REE resource^[@CR1],[@CR41]^. The El Laco apatite-iron-oxide ore deposit at the Pico Laco volcanic complex in northern Chile consists of seven individual ore bodies which together comprise \~500 Mt of mainly magnetite-dominated ore with an average grade of 60% Fe^[@CR5],[@CR18],[@CR26],[@CR30]^. The Plio- to Pleistocene El Laco deposit is part of the young apatite-iron-oxide mineralizations that characterize the eastern high Andes and is separate from the Cretaceous apatite-iron-oxide ores of the so-called Chilean Iron Belt^[@CR7],[@CR14],[@CR17],[@CR18]^. The Bafq Mining District in Central Iran comprises 34 documented iron ore mineralizations with a total reserve of \~2 billion tons of iron ore with grades between 53 and 65%^[@CR11],[@CR42]^. The apatite-iron oxide ores of the Bafq region are coeval with their early Cambrian andesitic and rhyolitic host rocks that formed in a volcanic arc setting^[@CR43]^. Samples from the Bafq Mining District were collected from the Sechahun, Lakkeh Siah, Chadormalu, and Esfordi deposits^[@CR42]^. Analyzed plutonic reference samples (Fig. [1](#Fig1){ref-type="fig"}) include magnetite from the layered igneous intrusion of Panzhihua in China (*n* = 2), the Bushveld igneous complex in South Africa (*n* = 1), and the layered intrusions of Taberg (*n* = 1), Ulvön (*n* = 1), and Ruoutevare (*n* = 1) in Sweden and an iron-rich gabbro nodule from Iceland (*n* = 1). Samples representative of magmatic magnetites of volcanic derivation were chosen from basalts and dolerite from the Canary Islands (*n* = 3), recent basaltic andesites from Indonesia (*n* = 6), dacites from New Zealand (*n* = 2) and a hypabyssal dolerite from Cyprus (*n* = 1; Supplementary Table [1](#MOESM1){ref-type="media"}). Reference samples for low-temperature or hydrothermal iron ore deposits include magnetite from the polymetallic magnetite-skarn deposit at Dannemora (*n* = 4), the banded iron formation at Striberg (*n* = 1), and the marble-hosted iron oxide deposit at Björnberget (*n* = 1), all situated in Bergslagen, Central Sweden (Supplementary Table [1](#MOESM1){ref-type="media"}, Supplementary Note [1](#MOESM1){ref-type="media"}). Our interpretations are based on the combination of new iron (*n* = 63) and oxygen (*n* = 57) isotope ratios combined with literature data for magnetite from apatite-iron-oxide ores and available volcanic, plutonic and the low-temperature or hydrothermal reference materials^[@CR1],[@CR5],[@CR14],[@CR31],[@CR32],[@CR44]--[@CR48]^. Notably, the literature data for low-temperature or hydrothermal magnetite include a sample from the north-American Mineville apatite-iron-oxide deposit, which has been extensively overprinted by later hydrothermal processes^[@CR14],[@CR49]^. Iron and oxygen isotope results {#Sec4} ------------------------------- Magnetite from massive apatite-iron-oxide ores from Kiruna have a relatively restricted δ^56^Fe range of +0.12 to +0.41‰ (*n* = 11) (Supplementary Table [1](#MOESM1){ref-type="media"}, Fig. [3](#Fig3){ref-type="fig"}). The Grängesberg and Blötberget magnetite samples show δ^56^Fe-values mainly between +0.11 and +0.40‰ (*n* = 16). However, one sample from Grängesberg shows an exceptionally high value of +1.0‰. Apatite-iron-oxide ores from El Laco yield δ^56^Fe-values between +0.24 and +0.36‰ (*n* = 6). Magnetite from Bafq have a range in the +0.20 to +0.32‰ interval (*n* = 6).Fig. 3Iron isotope results. Shown is **a** the distribution of iron isotopes in magnetites from the Kiruna and Grängesberg districts, El Laco, and the Bafq district from this study, and **b** our data together with available literature data^[@CR14],[@CR45],[@CR47],[@CR48]^. Reference fields for common hydrothermal and magmatic magnetites are shown for comparison^[@CR39],[@CR45]--[@CR47],[@CR51],[@CR69],[@CR70]^. Magnetites from apatite-iron oxide ores show a clear distinction from low-temperature or hydrothermal magnetites and overlap with the layered intrusions and volcanic reference magnetites (i.e. in the magmatic reference field). Data from Wang et al.^[@CR45]^ show the effects of a progressive transgression from ortho-magmatic processes to hydrothermal fluid evolution from originally higher to lower δ^56^Fe values and an originally magmatic fluid may thus evolve into a hydrothermal fluid. One hydrothermal sample from the highly altered, remobilized, and recrystallized Mineville deposit in the USA (δ^56^Fe = −0.92‰, δ^18^O = −0.79)^[@CR14]^ is not shown for simplification. Ve-Di samples represent vein and disseminated magnetites Magnetite samples from the plutonic and volcanic reference suites show δ^56^Fe-values from +0.11 to +0.61‰ (*n* = 5) and from +0.06 to +0.46‰ (*n* = 13), respectively, consistent with iron isotope values for magmatic rock suites elsewhere (e.g. Figure [3](#Fig3){ref-type="fig"})^[@CR39],[@CR46]^. The low-temperature deposit group, i.e., the Dannemora iron oxide skarn samples and the Björnberget and the Striberg samples, on the other side, show relatively low δ^56^Fe-values that range from −0.57 to +0.01‰. The magnetite compositions in the low-temperature group form a separate group (Fig. [3](#Fig3){ref-type="fig"}) that does not overlap with the reported range of igneous magnetites (+0.06 to +0.49‰)^[@CR39],[@CR46]^, but with low-temperature hydrothermal samples from elsewhere (e.g., Mineville, USA and Xinqiao, China)^[@CR14],[@CR45],[@CR49]^. Magnetite separates from the Kiruna Mining District range in δ^18^O value from −1.0‰ to +4.1‰ (*n* = 14), and those from Grängesberg and Blötberget are between −1.1 and +2.8‰ (*n* = 16). (Supplementary Table [1](#MOESM1){ref-type="media"}, Fig. [4](#Fig4){ref-type="fig"}). Magnetite from El Laco shows a large range in δ^18^O values from −4.3 to +4.4‰ (*n* = 6), whereas magnetite samples from Bafq give a smaller range of +0.6 to +3.4‰ (*n* = 6).Fig. 4Oxygen isotope results. **a** Oxygen isotopes of magnetite samples from Kiruna, Grängesberg, El Laco, and the Bafq district from this study are compared to reference samples from layered igneous intrusions, recent volcanic magnetites, and low-temperature or hydrothermal ore deposits as well as **b** data from the Chilean Iron Belt^[@CR14]^, the Pea Ridge and Pilot Knob deposits^[@CR48]^. The range of typical igneous magnetite is outlined in the reference box^[@CR50]^. The majority of magnetite samples from apatite-iron oxide ores plot within the reference field for common magmatic δ^18^O-values and overlap with magnetite values from recent volcanic rocks and layered intrusions. The low-temperature or hydrothermal reference suite, together with low-temperature magnetite literature data^[@CR14],[@CR44]^, plot dominantly to the left of the magmatic magnetite field, with only one exception, a magnetite from the Fe-skarn deposit at Dannemora. This particular outlier comes from a part of the deposit (Konstäng) which itself represents a geochemical anomaly within the Dannemora deposit. Our values for El Laco overlap with results from previous studies^[@CR5],[@CR14],[@CR17],[@CR18],[@CR32]^ Magnetites from the plutonic reference samples (Panzhihua, Bushveld, Taberg, Ulvön, Ruoutevare, and Iceland gabbro bomb; *n* = 7), and from recent volcanic provinces (New Zealand, Indonesia and Tenerife, *n* = 3) show exclusively positive δ^18^O-values between +1.8 and +4.8‰, and +3.7 to +3.9‰ respectively, which is within or near the commonly accepted range of igneous magnetites (δ^18^O = +1.0 to +4.0‰)^[@CR50]^. The low-temperature and hydrothermal reference ore samples (e.g. Dannemora, Björnberget, and Striberg), have low δ^18^O values (−1.2 to −0.4‰; *n* = 5) with one exception; a skarn sample from Dannemora that has a δ^18^O-value of +2.1‰ (Supplementary Table [1](#MOESM1){ref-type="media"}). This particular sample, however, comes from a part of the deposit (Konstäng) which itself is reported to be geochemically anomalous with respect to the deposit as a whole (see Supplementary Note [1](#MOESM1){ref-type="media"}). Comparing the oxygen and iron isotope data of magnetite samples from Kiruna, Grängesberg, El Laco, and Bafq, we find that they overlap with the magnetite data from the plutonic and recent volcanic reference samples. Recognized low-temperature or hydrothermal deposits, such as Striberg, Björnberget, and Dannemora record magnetite isotope values that, in turn, differ distinctly in their Fe and O isotope signatures from magmatic values (Figs. [3](#Fig3){ref-type="fig"} and [4](#Fig4){ref-type="fig"}). We note that the oxygen isotope data from two vein and disseminated (Ve-Di) magnetite samples from Grängesberg, three samples from Kiruna, as well as magnetite from two samples from El Laco overlap with the low-temperature and hydrothermal reference group. However, these samples still show Fe isotope signatures that are similar to our magmatic reference suite and are hence assumed to reflect originally igneous sources. The compositional overlap between Kiruna-type magnetite and the plutonic and volcanic reference suite for Fe and O isotopes is consistent with an ortho-magmatic (magma or highest-temperature magmatic-fluids) origin for the Kiruna-type apatite-iron-oxide samples in this study. Low-temperature processes are reflected in a small number of the Kiruna-type ore samples (*n* = 7) represented by vein- and disseminated-type magnetite samples. The exceptionally high Fe-value for one Grängesberg sample, in turn, is in agreement with the "ultra-magmatic" Fe isotope composition recorded in magnetite from the Bushveld complex (Fig. [3](#Fig3){ref-type="fig"})^[@CR51]^. In contrast, the lower δ^56^Fe- and δ^18^O-values in Figs. [3](#Fig3){ref-type="fig"} and [4](#Fig4){ref-type="fig"} then either reflect the lower end of the magmatic temperature range, or secondary effects, such as alteration, as well as leaching and subsequent re-precipitation at temperatures below 400 °C, which postdates an initial high-temperature (magmatic) stage of formation (Fig. [5](#Fig5){ref-type="fig"}). Therefore, the oxygen and iron isotope data for the massive apatite-iron oxide magnetites indicate an originally high-temperature magmatic signature that, most clearly for oxygen isotopes, transitions to lower temperature values indicating a gradual cooling trend. One critical issue, especially for the Palaeoproterozoic Swedish deposits, which have gone through variable grades of metamorphism, is that post-depositional processes (e.g., fluid overprint, re-heating) might have affected the primary isotope composition of the ore and cannot be entirely excluded. Yet, since the same trends in isotope signatures are observed for both the older and younger, less geologically overprinted deposits, we argue that post-depositional changes in isotope composition was negligible in respect to the Fe--O isotope chemistry of our magnetite samples. This is particularly the case for the massive magnetite ores, where this overall chemically inert and refractory mineral would provide local buffering with regards to post-depositional re-equilibration^[@CR1]^.Fig. 5Distribution of Fe and O isotope values of magnetite samples used in this study. **a** The various magnetite samples can be divided into three groups according to their Fe--O isotope composition; (i) high-temperature magmatic magnetites, (ii) hydrothermal magnetite samples, and (iii) low-temperature magnetite samples. **b** Most of the magnetite compositions of the apatite-iron-oxide ores in this study lie within, or near, the reference field for igneous magnetite, and overlap with the plutonic and volcanic magnetite samples analysed as reference suite. See also Supplementary Note [1](#MOESM1){ref-type="media"} and Supplementary Fig. [2](#MOESM1){ref-type="media"} for a detailed assessment of temperature-dependent equilibrium compositions. Reference field for common igneous and hydrothermal magnetites are based on literature data^[@CR14],[@CR39],[@CR44],[@CR46],[@CR47],[@CR50],[@CR51]^ Discussion {#Sec5} ========== Based on fluid and melt inclusion studies and isotope compositions of mineral pairs, high temperatures of ore formation have been proposed for various apatite-iron oxide ores. For instance, temperature determinations for equilibrium magnetite--quartz pairs and magnetite--pyroxene pairs from Kiruna, El Laco, and Grängesberg yield temperatures that consistently exceed 600 °C^[@CR1],[@CR5]^. Such crystallization temperatures are further supported by, e.g., the occurrence of high-temperature actinolite in, e.g., the Los Colorados and Kiruna deposits^[@CR14],[@CR34],[@CR52]^ by Ti exsolution textures in magnetite from Kiruna^[@CR52]^, and by Zr in titanite studies at Kiruna that suggest 750--800 °C^[@CR53]^. These temperature determinations provide independent support for a high-temperature (ortho-magmatic) origin of these ore assemblages. Using these temperatures as a reference point and employing appropriate equilibrium fractionation factors, we modeled the isotope compositions of respective equilibrium sources to test the mineralization conditions of our sample suite (Supplementary Table [2](#MOESM1){ref-type="media"} and Supplementary Fig. [2](#MOESM1){ref-type="media"}). We applied available fractionation factors between magnetite and andesite/dacite magma (T\~1000 °C) as well as between an equilibrium aqueous magmatic fluid phase at temperatures between 600 and 800 °C for both iron and oxygen isotopes (see Supplementary Tables [2](#MOESM1){ref-type="media"}, [3](#MOESM1){ref-type="media"}, [4](#MOESM1){ref-type="media"}, [5](#MOESM1){ref-type="media"}). For oxygen isotopes, the calculations indicate that magnetite samples from apatite-iron oxide ores with δ^18^O ≥ 0, corresponding to over 80% of our sample set, reflect equilibrium with either an intermediate magma (δ^18^O of +5.7 to +8.7‰) or a high-temperature magmatic fluid (δ^18^O of +5.2 to +9.6‰; Supplementary Tables [2](#MOESM1){ref-type="media"}, [3](#MOESM1){ref-type="media"}, [4](#MOESM1){ref-type="media"}, and [5](#MOESM1){ref-type="media"}, Supplementary Fig. [2](#MOESM1){ref-type="media"}). Although equilibrium with ortho-magmatic, high-temperature sources are found for most of our samples, it naturally remains difficult to distinguish between a magma or a very high-temperature, magmatically derived aqueous fluid as the initial magnetite source. This realization is highlighted by the fact that our oxygen isotope values from Kiruna-type magnetite samples overlap with oxygen isotopes from the Granisle porphyry copper deposit presented in Bilenker et al.^[@CR14]^, which is proposed to have formed entirely from expelled ortho-magmatic fluids. For the same samples, iron isotope equilibrium source calculations yield values that correspond to magmas and modeled magmatic fluids with δ^56^Fe values from +0.08 to +0.38‰, and −0.13 to +0.17‰, respectively, which plot partly above the reported array of intermediate magmas and magmatic waters (Supplementary Fig. [2](#MOESM1){ref-type="media"})^[@CR39],[@CR54]^. This suggests that the metal sources of the samples that exceed the range were likely enriched in the heavy iron isotope (^56^Fe) already at the time of magnetite formation^[@CR39],[@CR46]^, which we refer to as ultra-magmatic. Such ^56^Fe enrichment may be caused by magmatic degassing, which is common in many volcanic systems^[@CR39]^, or more likely represents the result of iron oxide-enriched melts acting as an iron sink^[@CR55]^. Notably, this enrichment is also seen in some samples of our magmatic (plutonic and volcanic) reference suite (Supplementary Table [4](#MOESM1){ref-type="media"}, Supplementary Fig. [2](#MOESM1){ref-type="media"}), as well as in several Kiruna-type apatite-iron-oxide derived magnetite samples in other studies (Supplementary Table [5](#MOESM1){ref-type="media"}, Supplementary Fig. [2](#MOESM1){ref-type="media"})^[@CR14],[@CR48]^. Magma degassing may preferentially remove the lighter Fe isotopes^[@CR39]^, increasing the δ^56^Fe in the melt. Alternatively, the iron-sink scenario is possibly caused by the tendency for magnetite to incorporate the heavy Fe isotopes over the lighter ones either during crystallization or during silicate-metal immiscibility. This could lead to ultra-magmatic signals following prolonged crystallization of silicate phases from a basaltic magma. Specifically, the heavier iron isotope that partitions into the melt due to removal of early Fe-fractionating minerals, such as olivine and pyroxene, will deplete the melt in the isotopically lighter Fe^2+^ and will leave Fe^3+^ preferentially in the residual magma^[@CR46]^. When magnetite becomes the dominant iron-bearing phase later in the crystallization sequence it will consequently reflect the isotopically heavy melt signature^[@CR46]^. Finally, the high Fe^3+^/Fe~tot~ and the strong bonding in the tetrahedral site for Fe^3+^ in magnetite make it a highly suitable host for the heavier iron isotope^[@CR46]^. The combined effects of magma degassing, prolonged fractional crystallization leading to more andesitic to dacitic melts, and the preference of magnetite for the heavy iron isotope are the likely reasons for the ultra-magmatic signature in several magnetite samples from the plutonic-volcanic reference suite as well as from some apatite-iron-oxide ore samples. The key concepts proposed by the magmatic school of thought are formation of Kiruna-type ores by either liquid immiscibility or separation of magnetite cumulates (by sinking or flotation/frothing) from a silicate melt^[@CR5],[@CR17],[@CR18],[@CR31],[@CR38],[@CR48]^. To evaluate which magmatic process is dominantly responsible for the formation of the massive magnetite bodies has proven difficult and while some petrological and experimental studies favor the concept of liquid immiscibility^[@CR18],[@CR38]^, other workers suggest cumulate-type processes^[@CR14],[@CR31]^. Unfortunately, the currently available experiments that support liquid immiscibility are not truly representative of nature (e.g. 40 wt.% P~2~O~5~ in a starting melt)^[@CR36],[@CR38]^. Such a composition contrasts with the host rocks to actual Kiruna-type deposits at Bafq, El Laco, Grängesberg, and Kiruna. Using our new data to assess formation mechanisms, we can employ the isotope fractionation between immiscible Fe-rich melts and their silicate counterparts^[@CR35],[@CR56]^. Assuming a hydrous system, the maximum fractionation for oxygen isotopes between an iron-rich melt and a silicate melt is 0.8‰^[@CR35]^. Testing if our massive magnetite samples are representative of an Fe-rich melt that formed from immiscibility would require associated equilibrium silicate melts with δ^18^O between −3.5 and +5.2‰. These values are out of the range of common intermediate igneous rocks^[@CR57],[@CR58]^. Testing the same approach for the plutonic reference material (*n* = 7) produces two equilibrium melts (δ^18^O = +5.4 and +5.6‰) that both match a basaltic igneous composition (MORB = +5.7 ± 0.4‰). The formation of Kiruna-type ores by liquid immiscibility is therefore not fully aligned with our data. Although this would, at first glance, favor cumulate processes over liquid immiscibility, there is probably uncertainty as to the natural fractionation of δ^18^O during liquid immiscibility and, to date, little information is available for Fe--isotopes in such situations. This leads us to encourage further tests in order to verify which of these two magmatic processes is more dominant in the formation of apatite-iron oxide systems. Future developments in the field of in-situ analysis of Fe--O isotope composition may hopefully help resolve small features such as thin, Ti-poor outer alteration rims as reported by e.g., Knipping et al.^[@CR31]^ on magnetite samples from the Los Colorados apatite-iron-oxide deposit that these authors interpret to have bearing on the ore formation process. However, such textures cannot yet be analyzed for Fe and O isotopes in situ^[@CR59]^, and in respect to our whole-grain results, such volumetrically small features would have a minimal effect on the bulk isotope signature of our samples. In contrast to the massive ore samples, the vein and disseminated magnetites associated with apatite-iron oxide ores and low-δ^18^O massive magnetite ores from Kiruna, Grängesberg, and El Laco (i.e. δ^18^O~mgt ~\< 0‰, *n* = 7) are not in equilibrium with recognized magmatic sources at the previously established temperatures. For these samples equilibrium with magmatic sources would only be obtained at temperatures below 400 °C (Supplementary Table [6](#MOESM1){ref-type="media"}). Notably, Fe--P-rich magmas can only be liquid down to \~600 °C^[@CR34]^ implying that these magnetite samples cannot have formed directly from a magma. Moreover, the O isotope signatures in these magnetites overlap with those of our low-temperature and hydrothermal reference group and they can either be explained by a cooling magmatic fluid, or by a low-temperature hydrothermal system with external fluid influx. For El Laco, disequilibrium between high-temperature magmatic sources and a sub-set of low-δ^18^O samples has previously been discussed and is attributed to late-stage or secondary processes^[@CR5],[@CR32]^. The low-δ^18^O magnetite samples from El Laco are also associated with considerable amounts of hematite that probably formed as a result of oxidation of magnetite by low-δ^18^O, possibly meteoric-dominated, hydrothermal fluids at temperatures of ≤150 °C^[@CR5],[@CR32]^. Meteoric fluids, particularly from higher altitudes such as the Andes, could cause such a negative shift in oxygen isotopes. However, these fluids would be Fe poor and may thus have only limited effect on iron isotope composition. For the isotope analysis great care was taken to avoid any direct hematite contamination of the samples, yet minor hematite formation along fractures in discrete magnetite grains is seen in some El Laco samples and may in part explain the larger spread in oxygen isotope data^[@CR5],[@CR14],[@CR17],[@CR18],[@CR32]^. Our iron isotope data, on the other hand, confirm a magmatic isotope signal throughout, i.e., even in the low-δ^18^O samples. The low-δ^18^O but magmatic δ^56^Fe magnetite compositions at El Laco are thus likely to represent overprint, remobilization, and reprecipitation of an originally magmatic iron and oxygen signal by hydrothermal fluids that strongly affected oxygen isotopes in the magnetite, but had little effect on the iron isotopes^[@CR14],[@CR31]^. The fluids affecting the ores may either have been derived from the cooling magmatic system or from an external fluid contribution during the evolution of the mineralization. Remarkably, hydrothermal overprint in the Kiruna Mining District in Sweden, for instance, has now been suggested to post-date ore formation with up to 250 My^[@CR52]^. If this is correct, it implies that some non-magmatic (i.e. hydrothermal) isotope signals in apatite-iron-oxide ores may be entirely unrelated to the original mode of formation. The Fe--O isotope data obtained on magnetite samples from apatite-iron oxide ores from Sweden, Chile, and Iran are thus broadly consistent with the few available Fe--O isotope values from (a) the literature (apatite-iron-oxide ores from USA and the Chilean iron belt), and (b) the volcanic and plutonic reference data in this study from various layered igneous intrusions (from China, South Africa and Sweden) and from recent volcanic provinces (Indonesia, Canary Islands, New Zealand, and Iceland). Moreover, the iron and oxygen isotopes of magnetite samples from apatite-iron oxide ores differ, for most samples, from magnetites produced by low temperature or hydrothermal processes (≤400 °C). The iron and oxygen isotope data together with the calculated equilibrium sources are therefore in agreement with a predominantly (ortho-)magmatic origin (magma and high temperature magmatic fluids) for the investigated Kiruna-type deposits, rather than of a low-temperature hydrothermal one. While our data are very well suited to distinguish these broad formation conditions, they are not ideally suited to resolve the precise formation process and agent, i.e, we cannot distinguish magma versus high-temperature fluid or liquid immiscibility processes versus magnetite accumulation (Supplementary Fig. [2](#MOESM1){ref-type="media"}). Accepting an essentially magmatic nature of these deposits, a local hydrothermal overprint and replacement within a volcanic to sub-volcanic system would naturally be expected (Fig. [6](#Fig6){ref-type="fig"}), and will involve localized late-stage or secondary hydrothermal alteration and overprint^[@CR1],[@CR18],[@CR32],[@CR41]^. Hydrothermal alteration might locally be pronounced and may seem pervasive in places, as is known from many volcanic provinces^[@CR60],[@CR61]^. This by-product of otherwise ortho-magmatic formation processes must, however, not be confused with the main source signal of most Kiruna-type magnetite samples revealed in our study (Figs. [5](#Fig5){ref-type="fig"} and [6](#Fig6){ref-type="fig"}).Fig. 6Schematic representation of magmatic stages for Kiruna-type apatite-iron-oxide ores from this and other studies, and from the analyzed reference materials. Stages II and III comprise ortho-magmatic ore formation: with decreasing temperature and on-going crystallization in the melt, the volatile/fluid pressure will increase and magmatic fluids are being expelled into the surrounding rocks. Below \~600 °C (towards the end of stage III), the magmatic-derived volatile pressure may begin to decrease, allowing progressively more of available external fluids into the system that initiate hydrothermal activity (\<400 °C). Massive apatite-iron oxide ores appear to commence crystallization in the ortho-magmatic stages (Stages II and III), whereas vein and disseminated magnetites formed mainly during Stage IV (hydrothermal precipitation and replacement). This implies that the commonly observed hydrothermal signals in apatite-iron oxide ores are late-stage products that are results of syn- to post-magmatic hydrothermal processes active during the cooling of the volcanic system, or in some cases possibly reprecipitation during later overprints Hydrothermally formed magnetite is isotopically distinct and appears subordinate in our sample suite. The bulk of the Kiruna-type ore investigated thus formed in sub-volcanic environments under essentially high-temperature magmatic conditions, in line with the magmatic school of thought^[@CR3],[@CR5],[@CR14],[@CR17],[@CR18],[@CR31],[@CR62]^. Precipitation of magnetite was either from iron-oxide-saturated intermediate magmas or from immiscible Fe-rich melts that separated from broadly andesitic to dacitic parent magmas and subsequent physical (either gravity or gas-driven) magnetite segregation to form massive magnetite melts and mushes^[@CR18],[@CR24],[@CR31],[@CR35],[@CR63]^. Kiruna-type apatite-iron-oxide ores are hence dominantly a magmatic phenomenon and they presumably continue to form in active arc- and back-arc type sub-volcanic environments up to the present day. Our combined isotope data and calculations represent a significant advance in the understanding of Kiruna-type ore deposits and over-rules most arguments for a completely hydrothermal mode of formation. Moreover, we provide a reference system for Fe--O isotopes in Kiruna-type ores against which future research can test genetic concepts for low- versus high-temperature origin of as yet underexplored Kiruna-type deposits. Methods {#Sec6} ======= Sampling {#Sec7} -------- Samples from the Kiruna Mining District (*n* = 11) come from the type locality for Kiruna-type apatite-iron-oxide ores at Kiirunavaara, Sweden, as well as from other apatite-iron-oxide deposits in the district, including magnetite dykes in the footwall of the smaller deposit at Luossavaara, as well as massive ore from the Mertainen and Rektorn deposits. Mineralized samples from the Grängesberg Mining District (GMD) were collected from three drillcores (DC), DC 690 (*n* = 7), DC 717 (*n* = 3), and DC 575 (*n* = 3) that transect the deposit with a shallow plunge (\<20 °) and were drilled at 650 m (*n* = 2) and 570 m below the surface respectively. In addition to massive apatite-iron-oxide samples, two Grängesberg samples were selected from magnetite veins and disseminations in the host rocks. One sample was collected from the smaller Blötberget apatite-iron-oxide deposit within the greater Grängesberg area and another from the nearby but contrasting marble-hosted hydrothermal/low-temperature iron oxide deposit at Björnberget (*n* = 1). Samples from El Laco (*n* = 6) were sampled at the surface and come from Laco Sur, the southern deposit in the area. To obtain a meaningful and widely applicable comparison of the apatite-iron-oxide ores with hydrothermal and magmatic reference samples, oxygen, and iron isotope values were also determined on magnetite from massive ore from the iron oxide-polymetallic skarn deposit at Dannemora in Sweden (*n* = 4), the banded iron formation at Striberg in Sweden (*n* = 1), the layered igneous intrusion of Panzhihua in China (*n* = 2), the Bushveld igneous complex in South Africa (*n* = 1), the Swedish layered igneous intrusions of Taberg (*n* = 1), Ulvön (*n* = 1), and Ruoutevare (*n* = 1), and from a gabbro bomb from Skjaldbreiður in Iceland (*n* = 1). Samples representative of recent igneous magnetites were chosen from basaltic andesites from Indonesia (*n* = 6), basalts, and dolerite from the Canary Islands (*n* = 3), dacites from New Zealand (*n* = 2), and a dolerite from Troodos massif in Cyprus (*n* = 1). An overview of the samples used in this study and details on their mineral assemblage and provenance is given in Supplementary Table [1](#MOESM1){ref-type="media"}. An outline of the geological setting of our sample suite is given in the Supplementary Information. Iron isotope analysis {#Sec8} --------------------- Analysis of the individual magnetite samples for Fe isotopes was dominantly carried out at the Victoria University in Wellington, New Zealand (*n* = 47). The crystals were digested and chemically purified with concentrated HF and HNO~3~ acid and the analysis was then done using a ^57^Fe-- ^58^Fe double spike and a Nu Plasma MC-ICP-MS (Multicollector-Inductively Coupled Plasma Mass Spectrometer). As a standard the international IRMM-014 CRM material was used. Full details on the Fe isotope analysis are given in Millet et al.^[@CR64]^. All iron isotope data were recorded as δ^56^Fe, which is the deviation of ^56^Fe/^54^Fe relative to the IRMM-014 CRM standard material. The average 2*σ* error during iron isotope analysis was 0.03‰. A set of magnetite samples (*n* = 11) was analysed for iron-isotopes by ALS Scandinavia Ltd. in Luleå, Sweden. The magnetite samples were prepared for analysis by microwave-assisted digestion in a HNO~3~ + HCl + HF mixture according to the method described in Ingri et al.^[@CR65]^. The isotope analysis was then carried out with a Thermo Scientific Neptune MC-ICP mass spectrometer. The δ^56^Fe-values were calculated with relation to the IRMM-014 CRM standard. The 2*σ* error was calculated from two independent consecutive measurements and was on average also about 0.03‰. Six further magnetite samples were analyzed at the Vegacenter at the Swedish Museum of Natural History in Stockholm. The crystals were digested and chemically purified using concentrated HF and HNO~3~ and 10 M HCl acid following the procedures of Borrok et al.^[@CR66]^ and Millet et al.^[@CR64]^. The samples were diluted with 0.3 M HNO~3~ to a concentration of 2--3 ppm before measurement. The Fe isotope analyses were performed on a Nu Plasma II HR-MC-ICP-MS in pseudo-high-resolution mode to resolve interfering species. The samples were corrected for mass bias using the standard-sample bracketing technique, normalizing to the IRMM-014 standard. The average 2*σ* external reproducibility for the samples was 0.06‰ for δ^56^Fe. Oxygen isotope analysis {#Sec9} ----------------------- The analysis for oxygen isotopes was carried out at the University of Cape Town (South Africa) using a Finnigan DeltaXP dual inlet gas source mass spectrometer (*n* = 59). For the oxygen analysis the magnetite samples were prepared by laser fluorination^[@CR67]^, whereby they were reacted with 10 kPa of BrF~5~, and the purified O~2~ was collected onto a 5 Å molecular sieve in a glass storage bottle. As a reference and calibration standard Monastery garnet was used^[@CR68]^. All oxygen data were recorded in the usual δ^18^O notation relative to SMOW where δ^18^O = (*R*~sample~/*R*~standard ~− 1)×1000, and *R *= the measured ratio ^18^O/^16^O. All oxygen isotope data were obtained with a 2*σ* error of ≤0.2‰. Supplementary information ========================= {#Sec10} Supplementary Information Source Data **Journal peer review information:** *Nature Communications* thanks the anonymous reviewers for their contribution to the peer review of this work. **Publisher's note:** Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Supplementary information ========================= **Supplementary Information** accompanies this paper at 10.1038/s41467-019-09244-4. We thank Prof. N. Arndt (Université Joseph Fourier, Grenoble), Prof. J. Gamble (Victoria University, Wellington), Dr. J. O. Nyström (Swedish Museum of Natural History, Stockholm), Gunnar Rauséus (Dannemora Mineral AB), and Prof. C. J. Stillman (Trinity College Dublin) for donating samples for this study. We further thank Dr. J. Omrani, Dr. A. Houshmandzadeh, Dr. M. Kargarrazi, and the Geological Survey of Iran for their help and support during field work and data interpretation, as well as the staff at the Geological Survey of Sweden (SGU) Mineral Office in Malå, for helpful assistance during drill core sampling. We thank Joel Baker for his help during isotope analyses at the Victoria University in Wellington and Harri Geiger, and Weian Sun for help during the microprobe sessions. Generous funding from the SGU, the Swedish Research Council (VR) and Uppsala University (UU) is gratefully acknowledged. This is Vegacenter contribution \#012. V.R.T., E.J., and K.H. conceived the study. Field work was carried out by E.J., K.H., K.P.N., S.A.M., U.B.A., and V.R.T. Sample preparation was carried out by F.W. and S.S. Isotope analyses were performed by C.H., E.K., F.W., and M.A.M. Modeling was performed by F.W., V.R.T., and C.H., and illustrations were prepared by F.W. and V.R.T. The manuscript was written by V.R.T. and F.W. with contributions from all co-authors. The authors declare that all relevant data are available within the article and its supplementary information files. Competing interests {#FPar1} =================== The authors declare no competing interests.

Q: Can one get the type that a specific attribute is decorating Say I have a situation like so: [MyAttribute] public class MyClass { } [AttributeUssage(AttributeTargets.Class)] public class MyAttribute { public MyAttribute(String a_strName) { } } Is there anyway that within constructor of MyAttribute I can know that the attribute is attached to MyClass? A: No, I'm afraid not - attributes don't "know" what they're applied to.

Nintendo NX rumours suggest better software output and more games than Wii U New rumours have revealed details of what to expect from the new Nintendo NX. [Representational Image] Nintendo NX rumoured to have bigger games library than Wii U. In Picture: New Nintendo 3DS released in the U.S.Nintendo website Numerous rumours have been doing the rounds on Nintendo's upcoming console the Nintendo NX since last year. But now, Nintendo insider Emily Rogers, who is known for accurate leaks, has said in her blog that the software output for NX will "blow away" the current ones that exist for Wii U. She further added that Nintendo intends to build a bigger library of games, exceeding games released for Wii U games over three to four years. Rogers said the information was based on her sources close to Nintendo, and shared the following points: The big fundamental focal point behind NX is to vastly increase the software output from Nintendo's first party teams and studios. To accomplish this, the entire process of how Nintendo develops and produces software has gone through radical changes. There is a new strategy that was put in place to create and release first party software at a faster rate. Multiple unannounced Wii U projects were moved over to NX. The NX could potentially see the highest output of first party software in the company's history. Nevertheless, she warns of possible "software delay" as there is nothing like a "perfect strategy." She also revealed that Nintendo might not reveal everything (in terms of video games) at E3 2016 and might save some announcements for a later date.

The protective efficacy of basic fibroblast growth factor in radiation-induced salivary gland dysfunction in mice. Radiotherapy is one of the most effective treatments for head and neck cancer. However, in addition to the target tumor, normal salivary glands are also included in the irradiation field. This unavoidably results in dry mouth syndrome as a side effect. In this study, the protective efficacy of basic fibroblast growth factor (bFGF) was investigated in radiation-damaged salivary glands. Prospective animal experiment with control. Nine-week-old female C57BL/6 mice were divided into three groups. All mice in two of the three groups were irradiated (10 Gy) at the same time. In the bFGF-treated group, bFGF was administered to the submandibular glands for 3 consecutive days after neck irradiation. Mice in the untreated control group were administered distilled water. Mice in the third group were not irradiated and did not receive any additional treatments. Saliva flow rate and submandibular gland morphology were assessed, and the apoptotic response of irradiated submandibular glands was also evaluated. Administration of bFGF improved hyposalivation 8 weeks after irradiation, and histologic analysis revealed that bFGF-treated glands contained more acinar cells compared to untreated glands. The apoptotic response to irradiation, examined 1 and 2 days after irradiation, was reduced, and quantitative real-time polymerase chain reaction revealed a paracrine effect for bFGF in the glands that received bFGF treatment. Our study indicates that bFGF prevents salivary gland dysfunction after irradiation. The protective benefits of bFGF may be attributed to the inhibition of radiation-induced apoptosis as well as the paracrine effect it has in these tissues.

Michael McNamara (politician) Michael McNamara (born 1 March 1974) is an Irish Independent politician who has been a Teachta Dála (TD) for the Clare constituency since the 2020 general election, and previously from 2011 to 2016 when he was elected as a Labour Party TD. He was a member of the Oireachtas Committee on Agriculture, Food and the Marine, and a member of the Parliamentary Assembly of the Council of Europe from 2011 to 2016. McNamara is a barrister and has worked at the OSCE and on human rights and democracy projects of the European Union and United Nations. He was an unsuccessful independent candidate at the 2009 European Parliament election for the North-West constituency. In May 2015, he was expelled from the parliamentary Labour Party for voting against the government in the sale of Aer Lingus shares, the third time he voted against the government. He rejoined the parliamentary Labour Party in September 2015. He lost his seat at the 2016 general election. He was elected as an independent candidate for the Clare constituency at the 2020 general election. References External links Michael McNamara's page on the Labour Party website Category:1974 births Category:Living people Category:Alumni of University College Cork Category:Independent TDs Category:Irish barristers Category:Labour Party (Ireland) TDs Category:Members of the 31st Dáil Category:Members of the 33rd Dáil Category:Politicians from County Clare

Autism spectrum disorder (ASD) is a developmental condition characterized by deficits in social communication and restricted, repetitive behaviours or interests[@b1] that is estimated to affect 1 in 68 children in the United States[@b2]. Genetic variation contributes strongly to ASD risk, as evidenced by high familial recurrence[@b3][@b4][@b5], overlap with monogenic syndromes such as Fragile X (*FMR1*) or Smith--Lemli--Opitz syndrome (*DHCR7*)[@b6], and higher rates of gene-disrupting genetic variants in ASD cases compared with their siblings or controls[@b7][@b8][@b9]. The set of genes that can be definitively implicated as ASD risk genes has been growing rapidly, and predictive models from studies of single nucleotide variants in sporadic cases estimate that there are likely to be hundreds of genes involved in ASD risk[@b8][@b10]. Given the scope of this genetic heterogeneity, understanding the biological aetiologies of ASD and designing broadly applicable treatments has proven challenging. One robust risk factor for ASD is sex: for every female with ASD in the United States, there are 4.5 affected males[@b2], and a male bias in prevalence is consistent across countries and across diagnostic criteria[@b11]. A multiple threshold liability model has been applied to conceptualize this difference in vulnerability, which posits that a higher minimum liability is required for females to manifest the ASD phenotype as compared with males[@b12][@b13][@b14]; this is also referred to as the female protective model. There is now evidence from population-wide data, family-level data[@b14] and at the genetic level[@b7][@b9][@b15] to support the hypothesis from this model that autistic females with ASD carry greater genetic liability. However, we note that a female protective model is not incompatible with the existence of male-specific risk factors, and the molecular mechanisms responsible for either protecting females or potentiating males\' vulnerability remain unknown. Several theories have been proposed regarding sex-differential risk and protective mechanisms, though the evidence supporting each is varied[@b12]. For example, ASD has been conceptualized as an X-linked disorder[@b16][@b17], and although several X-chromosome genes have been implicated, numerous autosomal genes contribute to risk as well[@b7][@b8]; X-chromosome genes alone do not explain the overall male bias[@b9][@b18][@b19]. Imprinted, paternally expressed X-chromosome genes have also been proposed to exert protective effects on females[@b20], though such genes have yet to be identified. Beyond genetics, the extreme male brain theory of autism posits that elevated prenatal testosterone exposure increases risk[@b21]. While recent evidence has linked increased fetal testosterone levels to later ASD diagnoses in a population sample[@b22], the molecular and cellular mechanisms that act to link an early hormone exposure to a later ASD phenotype are unknown. It is also plausible that multiple mechanisms, acting independently or interacting with one another, collectively account for the sex bias in ASD risk. We reasoned that since sex-differential gene expression patterns contribute to the development and function of a sexually dimorphic brain, evaluating genome-wide sex-differential gene expression in neural tissue could elucidate points of overlap with ASD risk genes and related pathways. Here we test two basic hypotheses about the relationship between sexually dimorphic expression and ASD risk genes: (1) ASD risk genes are expressed at different levels in males and females. With differing baseline expression levels, the magnitude of the impact of a disruptive mutation in a risk gene is likely to differ by sex. Accordingly, we expect to observe enrichment of sex-differentially expressed (sex-DE) genes among known ASD risk genes. (2) ASD risk genes are expressed at the same level in males and females, but genes in interacting molecular pathways and/or cellular processes are differentially expressed by sex. In this case, the downstream impact of sex-neutrally expressed ASD risk genes is likely modulated by their interactions with sexually dimorphic processes. If this were the case, we would expect to observe enrichment of sex-DE genes among gene sets representing processes associated with ASD pathophysiology, but not among ASD risk genes themselves. To evaluate these hypotheses, we identify sexually dimorphic gene expression patterns in adult and prenatal human cerebral cortex tissue and test ASD-associated gene sets for enrichment of sex-differential expression. We observe significantly male-biased expression patterns for microglial-function-enriched, ASD-upregulated, co-expression modules from post-mortem ASD brain[@b23][@b24] and microglia and astrocyte marker genes[@b25][@b26][@b27], but no enrichment of sex-differential expression for ASD risk genes. These patterns are most consistent with our second hypothesis, and suggest that sex differences in biological processes captured by specific ASD-dysregulated co-expression modules, or sexual dimorphisms in cortical microglia and/or astrocytes, may play critical roles in setting males\' greater risk for ASD. Results ======= To identify sex-differential gene expression patterns in the human brain, we analysed RNA-sequencing (RNA-seq) gene expression data from human cerebral cortex tissue from the BrainSpan project[@b28] and from an independent, in-house data set, as well as published array data from prenatal samples[@b29]. We focused on cerebral cortex, since ASD risk genes are highly expressed in this region in neurotypical brain[@b30][@b31], and examination of post-mortem autistic brain has demonstrated consistent gene expression changes in the cerebral cortex as well[@b23][@b24]. To characterize stable sex differences in gene expression, we evaluated samples from adult subjects, and to assess sex-differential expression during early development, when many ASD risk genes are highly expressed, we evaluated samples from prenatal subjects. We then tested multiple ASD risk gene sets, ASD-associated gene sets and cell type markers for enrichment of sex-differential expression[@b8][@b23][@b24][@b25][@b26][@b27][@b32][@b33][@b34], to determine whether sexually dimorphic utilization of ASD risk genes, or genes in interacting processes, may contribute to the sex bias in ASD prevalence. Sex-differential expression in adult human cortex ------------------------------------------------- We first analysed RNA-seq data from 58 post-mortem cortex samples from the BrainSpan project[@b28] for sex-differential gene expression using a linear mixed model. This set of samples was collected from 10 teenage and adult subjects matched for sex, age and brain region (13--40 years; 5 females), and filtered for outliers ([Supplementary Table 1](#S1){ref-type="supplementary-material"}). Sex-differential expression patterns in adult cortex show expected, robust differential expression of Y-chromosome genes and *XIST*, an X-chromosome transcript that initiates X-chromosome inactivation and is only expressed in females ([Fig. 1a](#f1){ref-type="fig"}). We note that all Y-chromosomal transcripts that fail to show male-biased expression are pseudogenes with high sequence similarity to their corresponding genes on other chromosomes. Previous studies of sex-differential expression in human brain have preferentially reported sex-DE genes with pronounced fold differences (FDs), such as those on the X and Y chromosomes[@b29][@b35][@b36]. Beyond these differences driven by sex chromosome copy number, sex-differential expression of autosomal and non-*XIST* X-chromosome transcripts are generally subtle in magnitude[@b37], and may reflect sex-specific tuning of molecular pathways. Using a minimum FD magnitude of 1.2, a standard threshold, we identify 186 genes at *P*\<0.005, 311 genes at *P*\<0.01 and 866 genes at *P*\<0.05 ([Fig. 1b](#f1){ref-type="fig"} and [Supplementary Data 1](#S1){ref-type="supplementary-material"}); just 58 genes are sex-DE at a Benjamini--Hochberg adjusted *P* value of 0.05, 21 of which are on the sex chromosomes. The 37 autosomal sex-DE genes, then, are not sexually dimorphic due to copy number differences between males and females. Instead, they may be the regulatory targets of sex steroid hormone receptors or transcription factors from the X or Y chromosomes, or they may be preferentially expressed in a certain cell type that is differentially represented in male and female cortex. Over-representation analysis for gene sets of interest ------------------------------------------------------ To determine whether genes associated with ASD risk show sex-differential expression in the human adult cortex, we examined sets of known risk genes from several sources: (a) candidate genes from a manually curated database[@b32]; (b) genes with rare, *de novo*, protein-disrupting or missense single nucleotide variants in sporadic ASD cases from the Simons Simplex Collection[@b8]; and (c) FMRP (Fragile X mental retardation protein) binding targets[@b33] ([Supplementary Data 2](#S1){ref-type="supplementary-material"}). Together, these gene sets capture a broad scope of ASD risk genes, including heavily studied candidates, genes with evidence of *de novo* risk variants, and genes from a strongly ASD-associated regulatory network[@b33]. For each gene set, we first applied a Fisher\'s exact test to assess its overlap with sex-DE genes defined by specific thresholds (FD≥1.2 and *P*≤0.05, [Fig. 1c](#f1){ref-type="fig"}, [Supplementary Data 3](#S1){ref-type="supplementary-material"}; FD≥1.2 and *P*≤0.01 or *P*≤0.005, [Supplementary Data 3](#S1){ref-type="supplementary-material"}). To corroborate these results and assess sexually dimorphic shifts in gene expression across the transcriptome without applying arbitrary thresholds, we also used a binomial test to assess each gene set\'s distribution into two possible outcomes: higher expression in males (FD\>1, any *P* value), or higher expression in females (FD\<1, any *P* value). We found no evidence from either test for significant sex-differential expression of any of these diverse sets of ASD risk genes in the adult cerebral cortex, providing no evidence supporting hypothesis 1 ([Fig. 1d](#f1){ref-type="fig"} and [Supplementary Data 3](#S1){ref-type="supplementary-material"}). Next, we tested gene sets with evidence of ASD-associated expression patterns in adult human cortex[@b23][@b24] ([Supplementary Data 2](#S1){ref-type="supplementary-material"}), neural cell type marker gene sets[@b25][@b26][@b27] ([Supplementary Data 4](#S1){ref-type="supplementary-material"}) and genes marking cell types of the adaptive immune system[@b34] ([Supplementary Data 5](#S1){ref-type="supplementary-material"}) for sex-differential expression. We include immune cell markers in this analysis, since recent work has suggested complementary roles for T cells and microglia in mediating behaviour, specifically pain responses, in female versus male animals[@b38]. The ASD-associated gene sets include genes differentially expressed in post-mortem cortex from subjects diagnosed with ASD[@b24], and two ASD-associated co-expression modules from this same study (asdM12~V~, downregulated in ASD and enriched for genes with neuronal and synaptic functions; and asdM16~V~, upregulated in ASD and enriched for genes involved in immune and inflammatory responses)[@b24]. We also tested three ASD-associated co-expression modules from a subsequent RNA-seq study by Gupta *et al.*[@b23], which used a larger, but overlapping set of individuals (asdM1~G~, downregulated in ASD, and asdM6~G~, upregulated in ASD, both modules are enriched for neuronal markers and synaptic genes and overlap with the asdM12~V~ module[@b24]; asdM5~G~, which is upregulated in ASD, enriched for M2-state microglial genes, and overlaps with the asdM16~V~ module[@b24]). These DE genes and co-expression modules comprise large gene sets that were coherently altered in samples of ASD cases harbouring different genetic aetiologies. Therefore, these sets are likely to represent the downstream consequences of deleterious variants in risk genes, an upstream or ongoing background of molecular risk for ASD, or a secondary response to alterations in brain function that accompany ASD, any of which might be sexually dimorphic. In contrast to the ASD risk genes, we observe significant enrichment and depletion for neural cell type markers and gene sets dysregulated in post-mortem brain from autistic subjects[@b24]. Among genes expressed at significantly higher levels (FD≥1.2, *P*\<0.05) in males than in females (male-DE), we find a sevenfold enrichment of ASD-upregulated genes (7.0-fold, Fisher-adjusted *P* (*P*~Fisher_adj~)=1.5e-04; [Fig. 1c](#f1){ref-type="fig"} and [Supplementary Data 3](#S1){ref-type="supplementary-material"}). Among genes upregulated in ASD post-mortem cortex (ASD-up)[@b24], 67% show higher expression in males than in females (male-higher, 21% shift from background expectation, binomial test-adjusted *P* (*P*~Binom_adj~)=6.9e-03, [Fig. 1d](#f1){ref-type="fig"}). Genes belonging to the ASD-upregulated module asdM16~V~ also show enrichment for significantly male-DE genes (5.2-fold, *P*~Fisher_adj~=1.8e-10, [Fig. 1c](#f1){ref-type="fig"}) and a significant shift towards male-biased expression overall (73% male-higher, 28% shift, *P*~Binom_adj~=4.9e-21, [Fig. 1d](#f1){ref-type="fig"}). The related co-expression module asdM5~G~ from Gupta *et al.*[@b23] also shows this male-biased shift in expression (57% male-higher, 11% shift, *P*~Binom_adj~=9.2e-08, [Fig. 1d](#f1){ref-type="fig"}). It is critical to note that this apparent concordance between sex and ASD status is not the result of a male skew or lack of sex balance in the cases and controls used by either post-mortem ASD study[@b23][@b24], as all samples consisted predominantly of males (Voineagu *et al.*[@b24]: 4/16 female ASD cases and 1/16 female controls; Gupta *et al.*[@b23]: 8/32 female ASD cases and 9/41 female controls). Both of these published studies use multiple approaches to show that sex confounds do not drive the observed ASD-associated gene expression changes in brain[@b23][@b24]. The ASD-upregulated gene list asdM16~V~, and asdM5~G~ are associated with astrocyte and microglial function; asdM16~V~ overlaps significantly with human microglial and astrocyte co-expression modules identified in neurotypical cerebral cortex[@b24][@b39] and asdM5~G~ is enriched for gene expression signatures from M2 microglia[@b23]. Consistent with this, we also observe significant enrichments among male-DE genes for two independently generated sets of microglia markers (Albright *et al.*[@b25]: 2.1-fold, *P*~Fisher_adj~=0.029; Zeisel *et al.*[@b27]: 6.4-fold, *P*~Fisher_adj~=1.8e-12, [Fig. 1e](#f1){ref-type="fig"}, [Supplementary Data 3](#S1){ref-type="supplementary-material"}) and for two independently generated sets of astrocyte markers (Cahoy *et al.*[@b26]: 2.4-fold, *P*~Fisher_adj~=1.4e-08; Zeisel *et al.*[@b27]: 4.2-fold, *P*~Fisher_adj~=1.0e-04, [Fig. 1e](#f1){ref-type="fig"}); this is corroborated by significant shifts towards male-biased expression for both astrocyte gene sets and the microglial markers generated by single-cell RNA-seq[@b27] (Cahoy *et al.*[@b26], astrocytes: 60% male-higher, 15% shift, *P*~Binom_adj~=8.5e-37; Zeisel *et al.*[@b27], astrocytes: 69% male-higher, 23% shift, *P*~Binom_adj~=4.2e-09; microglia: 64% male-higher, 19% shift, *P*~Binom_adj~=1.7e-07, [Fig. 1f](#f1){ref-type="fig"}). In contrast, the forebrain neuronal marker gene set[@b26] is significantly enriched for genes expressed at significantly higher levels in females than in males (FD≥1.2, *P*\<0.05; female-DE; 1.8-fold, *P*~Fisher_adj~=0.019, [Fig. 1e](#f1){ref-type="fig"}) and shifted towards female-biased expression overall (64% with higher expression in females (female-higher), 9% shift, *P*~Binom_adj~=3.3e-11, [Fig. 1f](#f1){ref-type="fig"}). Similarly, genes in the ASD-downregulated, neuronal and synaptic module asdM12~V~ show enrichment for female-DE genes (2.7-fold, *P*~Fisher_adj~=5.8e-03, [Fig. 1c](#f1){ref-type="fig"}), while the ASD-downregulated module asdM1~G~ shows depletion of male-DE genes (0.37-fold, *P*~Fisher_adj~=8.1e-04, [Fig. 1c](#f1){ref-type="fig"}); both show a significant shift towards female-biased expression overall (asdM12~V~: 70% female-higher, 16% shift, *P*~Binom_adj~=1.0e-07; asdM1~G~: 64% female-higher, 10% shift, *P*~Binom_adj~=8.2e-14, [Fig. 1d](#f1){ref-type="fig"}). No T- or B-cell modules showed any significant enrichment with sex-DE genes or any significant shift towards male- or female-biased expression ([Supplementary Fig. 1a](#S1){ref-type="supplementary-material"}). Comparison of sex- and ASD-differential expression patterns ----------------------------------------------------------- We were particularly interested in the sex-DE enrichment in the ASD-associated co-expression modules from post-mortem brain, asdM16~V~ and asdM12~V~ (ref. [@b24]). Previous studies have demonstrated that co-expression modules frequently correspond to neural cell types and coherent biological functions[@b39][@b40]; thus, sex-DE enrichments in these modules may most directly implicate pathways involved in sex-biased ASD risk. Strikingly, we observe that all 36 sex-DE genes that are also members of asdM16~V~ are expressed at higher levels in ASD than in control cortex[@b24], 29 of which are also expressed at higher levels in neurotypical male than in female cortex ([Fig. 2a](#f2){ref-type="fig"}). We also observe that all of the 22 sex-DE genes in asdM12~V~ are expressed at lower levels in ASD than in control cortex, and 20 of these are also expressed at higher levels in females compared with males ([Fig. 2b](#f2){ref-type="fig"}). In short, we find concordant directionality of differential expression by sex and ASD status, with asdM16~V~ sex-DE genes expressed at higher levels in ASD and typical males and asdM12~V~ sex-DE genes expressed at higher levels in controls and typical females. To assess the extent of these parallel expression patterns across the transcriptome, we compared the FDs from sex-DE genes with FDs observed in the differential expression analysis of ASD cortex[@b24]. For the 374 sex-DE genes (FD≥1.2, *P*≤0.05) that were also tested in the ASD-DE analysis, we observe a highly significant positive correlation between the sex-differential and ASD-differential FDs (*r*=0.30, *P*=5.7e-09, [Fig. 2c](#f2){ref-type="fig"}), as well as for the subset of genes differentially expressed at FD≥1.2 and *P*≤0.05 in both comparisons (*r*=0.29, *P*=5.7e-04, *N*=90 genes). We note that among the 47 genes expressed at significantly higher levels in both males and in ASD, 22 are asdM16~V~ members[@b24] and 19 are astrocyte markers[@b26] (16 belong to both sets). Among the 25 genes expressed at significantly higher levels in both females and in unaffected controls, 11 are asdM12~V~ members[@b41] and 12 are neuron markers[@b14] (5 belong to both sets). These results suggest that the parallels in sex-differential and ASD-differential expression direction extend beyond asdM16~V~ and asdM12~V~, and that this pattern may be more broadly indicative of sexually dimorphic transcriptomes originating from specific neural cell types. Independent replication of adult sex-differential expression ------------------------------------------------------------ To validate these observations, we next analysed RNA-seq data from an independent sample of adult cortex tissue (16--56 years, [Supplementary Table 1](#S1){ref-type="supplementary-material"}) for sex-differential expression patterns. Using this smaller data set, we identify 65 genes at *P*\<0.005, 98 genes at *P*\<0.01 and 519 genes at *P*\<0.05 ([Supplementary Fig. 2a,b](#S1){ref-type="supplementary-material"} and [Supplementary Data 1](#S1){ref-type="supplementary-material"}). Overall, sex-DE genes from the BrainSpan data were expressed at comparable levels and with positively correlated fold differences in this independent sample (expression levels: *r*=0.78, *P*=2.9e-150; log~2~(FD)s, *r*=0.57, *P*=3.6e-65; [Fig. 3a](#f3){ref-type="fig"}). We observed no over-representations of ASD risk genes among significantly sex-DE genes (FD≥1.2, *P*\<0.05) from these data ([Supplementary Fig. 2d](#S1){ref-type="supplementary-material"} and [Supplementary Data 6](#S1){ref-type="supplementary-material"}); however, FMRP targets were more likely to show higher expression in females than in males (62% female-higher, 13% shift, *P*~Binom_adj~=2.9e-10, [Supplementary Fig. 2d](#S1){ref-type="supplementary-material"}). Oligodendrocyte markers and endothelial cell markers also showed shifts towards female-biased expression (Cahoy *et al.*[@b26] oligodendrocytes: 56% female-higher, 9% shift, *P*~Binom_adj~=1.5e-11; Zeisel *et al.*[@b27] oligodendrocytes: 59% female-higher, 15% shift, *P*~Binom_adj~=5.8e-07; endothelial cells[@b27]: 55% female-higher, 11% shift, *P*~Binom_adj~=5.7e-03, [Supplementary Fig. 2f](#S1){ref-type="supplementary-material"}). We also found depletion of male-DE genes in asdM1~G~ (0.26-fold, *P*~Fisher_adj~=0.027, [Supplementary Fig. 2c](#S1){ref-type="supplementary-material"}), but enrichments for asdM16~V~ genes (4.7-fold, *P*~Fisher_adj~=2.8e-03; 64% male-higher, 11% shift, *P*~Binom_adj~=5.2e-03, [Supplementary Fig. 2c,d](#S1){ref-type="supplementary-material"}), asdM6~G~ genes (58% male-higher, 7% shift, *P*~Binom_adj~=0.014, [Supplementary Fig. 2d](#S1){ref-type="supplementary-material"}), astrocyte marker genes (Cahoy *et al.*[@b26]: 61% male-higher, 10% shift, *P*~Binom_adj~=1.7e-16; Zeisel *et al.*[@b27]: 69% male-higher, 18% shift, *P*~Binom_adj~=6.6e-06, [Supplementary Fig. 2f](#S1){ref-type="supplementary-material"}) and ependymal cell markers (60% male-higher, 9% shift, *P*~Binom_adj~=0.027, [Supplementary Fig. 2f](#S1){ref-type="supplementary-material"}). Again, we find no sex-differential expression signal in T- and B-cell modules ([Supplementary Fig. 1b](#S1){ref-type="supplementary-material"} and [Supplementary Data 6](#S1){ref-type="supplementary-material"}). Of the 164 genes expressed more highly in males with a FD≥1.2 in both adult data sets, 24 are asdM16~V~ members (8.8-fold enrichment, *P*=5.5e-14) and 70 are astrocyte markers (10.3-fold enrichment, *P*=3.3e-35; 14 of these genes are belong to both sets), further supporting the characterization of astrocytic genes and ASD-upregulated, microglial-function-enriched asdM16~V~ genes, as displaying male-biased expression in the adult human cortex ([Fig. 3b](#f3){ref-type="fig"}). Sex-differential expression in prenatal human cortex ---------------------------------------------------- One possible explanation for the lack of enrichment of ASD risk genes among sex-DE genes from adult brain is that ASD risk genes may be acting primarily during fetal brain development[@b30][@b31]. To address this, we next analysed array expression data from 86 neocortex samples from 8 subjects (4 females) between 16--22 post-conception weeks[@b29] ([Supplementary Table 1](#S1){ref-type="supplementary-material"}). This prenatal epoch follows the mid-gestation peak in testosterone secretion from males\' differentiated testes[@b42][@b43] and thus captures a stage during which steroid hormones are likely to be exerting organizational effects. We find 306 sex-DE genes at *P*\<0.005, 440 sex-DE genes at *P*\<0.01 and 1,037 sex-DE genes at *P*\<0.05, with 96 genes sex-DE at an adjusted *P*\<0.05 ([Fig. 4a,b](#f4){ref-type="fig"} and [Supplementary Data 1](#S1){ref-type="supplementary-material"}). Results from over-representation analysis for the gene sets of interest within these prenatally sex-DE genes mirror those in the adult data: there are no significant enrichments for ASD risk gene sets, and FMRP interactors are significantly depleted within male-DE genes (0.33-fold, *P*~Fisher_adj~=8.0e-04, [Fig. 4c](#f4){ref-type="fig"}, [Supplementary Data 7](#S1){ref-type="supplementary-material"}). As in adult brain, genes expressed more highly in prenatal male cortex show robust enrichments for post-mortem cortex ASD-upregulated genes (4.6-fold, *P*~Fisher_adj~=3.3e-03, [Fig. 4c](#f4){ref-type="fig"}), asdM16~V~ genes (4.0-fold, *P*~Fisher_adj~=2.6e-09; 67% male-higher, 16% shift, *P*~Binom_adj~=6.2e-05, [Fig. 4c](#f4){ref-type="fig"}), asdM5~G~ genes (2.9-fold, *P*~Fisher_adj~=5.1e-09; 61% male-higher, 13% shift, *P*~Binom_adj~=4.2e-07, [Fig. 4c,d](#f4){ref-type="fig"}), microglia markers (Albright *et al.*[@b25]: 2.1-fold, *P*~Fisher_adj~=2.8e-03; 60% male-higher, 11.4% shift, *P*~Binom_adj~=1.2e-04; Zeisel *et al.*[@b27]: 2.9-fold, *P*~Fisher_adj~=0.027, [Fig. 4e,f](#f4){ref-type="fig"}), endothelial markers (3.7-fold, *P*~Fisher_adj~=3.2e-06, [Fig. 4e](#f4){ref-type="fig"}) and a significant depletion of forebrain neuron marker genes (0.41-fold, *P*~Fisher_adj~=2.3e-05; 58% female-higher, 7% shift, *P*~Binom_adj~=1.3e-04, [Fig. 4e,f](#f4){ref-type="fig"}). As in adult, T- and B-cell modules show no enrichments or depletions of sex-DE genes, nor any sex-skewed expression shifts ([Supplementary Fig. 1c](#S1){ref-type="supplementary-material"} and [Supplementary Data 7](#S1){ref-type="supplementary-material"}). Taken together, these findings fail to support the hypothesis that ASD risk genes are differentially expressed by sex in the human cerebral cortex. Rather, we observe that sex-DE genes are enriched among specific classes of changes observed in post-mortem cortex from ASD patients, which is indicative of shared biology between ASD and typical sexual dimorphisms. These patterns of sex-DE enrichment follow what is observed in ASD cortex, with higher expression of microglial and astrocyte genes (exemplified by asdM16~V~ and asdM5~G~) in the more susceptible male population, and higher expression of a cohort of synaptic genes (exemplified by asdM12~V~), in the more protected, female population. Discussion ========== Autism risk is sexually dimorphic, and genetic studies are most consistent with a female protective effect. To begin to explore potential mechanisms mediating sex-differential genetic risk, we tested the hypothesis that ASD risk genes would show sexually dimorphic expression in the cerebral cortex, a region that plays a major role in complex human cognitive phenotypes, including social behaviour, and where many ASD genes are expressed[@b30][@b31]. We observe both in adult and fetal brain that while some ASD risk genes do show sex-differential expression, overall this is not beyond what would be expected by chance. Furthermore, these sex-neutral expression patterns are evident in the mid-fetal cortex, a spatiotemporal point of convergence for ASD risk genes\' expression[@b30][@b31]. Instead, we find support for a second hypothesis: that genes whose expression patterns are altered in post-mortem autistic brain, which highlight downstream or interacting pathways, but not ASD risk genes themselves, are differentially expressed by sex. The convergence of male-DE genes with these downstream pathways, but not with risk genes or neuronal markers, is consistent with the evidence presented by Voineagu *et al.*[@b24]: asdM16~V~ is upregulated in ASD brain and enriched for immune system function and inflammatory response genes, but not for common ASD susceptibility variants. The asdM16~V~ module is therefore interpreted as representing a secondary, likely downstream effect of genetically causal perturbations. Whether a secondary effect of genetic variants or a result of independent mechanisms, it may be that expression of this gene set beyond a certain threshold is detrimental to neural development and function. Our findings show that typical males land closer to this putative threshold than females do, potentially implicating these genes expressed at higher levels in the male and ASD cortex in mechanisms driving male-biased ASD risk. Furthermore, to the extent that asdM16~V~ upregulation contributes to ASD pathophysiology, this module may serve as a useful target for pharmacological treatments that could modulate the effects of heterogeneous risk variants acting upstream. Alternatively or concordantly, it may also be the case that ASD-protective genes are expressed at a higher level in females. Genes in the neuronal- and synapse function-enriched asdM12~V~ module may represent such a protective gene set, as these genes are downregulated in ASD post-mortem cortex[@b24]. Genes belonging to asdM12~V~ do show higher expression in adult female cortex from the BrainSpan sample ([Fig. 1c,d](#f1){ref-type="fig"}), though neither the replication adult sample nor the prenatal sample show this same female skew. Alternatively, the relatively sex-neutral expression of asdM12~V~ genes in contrast to asdM16~V~ may simply reflect the absence of a particular ASD pathophysiological process in neurotypical samples. We also observed a correlation in the relative FDs of sex-DE genes and ASD-DE genes that extends beyond the asdM16~V~ module, such that genes expressed more highly in typical male cortex also tend to be more highly expressed in ASD cortex, while genes more highly expressed in typical female cortex also tend to be expressed at lower levels in ASD cortex[@b24]. Again, we emphasize this agreement in fold change direction between sex and ASD status is not likely the result of a male-confounded analysis by Voineagu *et al.*[@b24] or Gupta *et al.*[@b23], as cases and controls were sex balanced, and any potential sex effects were also regressed out in those studies. Interestingly, the gene expression patterns we observe fit squarely with hypotheses derived from both the extreme male brain theory and from the concept of female protective factors in ASD: male-DE (ASD-upregulated) genes could act to increase risk, while female-DE (ASD-downregulated) genes could have protective functions. However, we caution that FDs do not indicate the underlying mechanism of gene regulation (that is, active upregulation in males can return the same result as repression in females). We cannot yet conclude that parallel expression differences between the sexes and in ASD are derived from the same regulatory mechanisms, but this work provides a starting point for their study. Additional experiments that include sufficient numbers of cases and controls of both sexes will be necessary to tease apart how sex and ASD status interact to affect gene expression, for example, to determine whether male-DE genes are expressed at even higher levels in ASD cases. Astrocyte and microglial markers are also reliably enriched among male-DE genes in both adult and prenatal cortex. We recognize two possible explanations for this: (1) a greater proportion of astrocytes and microglia to neurons in male cortex results in higher measured gene expression in males; or (2) males\' cortical astrocytes and microglia are more transcriptionally active than females\'. Aside from early, tenuous observations of greater cortical neuron density in males[@b44], sex differences in the cellular composition of human cortex have not been sufficiently characterized to determine if there is a greater number of certain glial subtypes in male cortex. In contrast, there is clear evidence for sexually dimorphic astrocyte morphology in animals, particularly in hypothalamic nuclei, with male astrocytes showing a greater number of longer and more branched processes[@b45][@b46][@b47]. In addition, sex steroid hormones may play a role in astrocyte differentiation and regulation, as oestrogen receptors are expressed in hypothalamic and hippocampal astrocytes[@b48][@b49], and female animals exposed to testosterone neonatally show male-typical astrocyte morphology[@b46]. Given the participation of astrocytes in the modulation of neurotransmission[@b50][@b51] and of microglia and astrocytes in synapse formation and function[@b52][@b53][@b54][@b55], it is plausible that sexual dimorphisms in astrocyte and/or microglia number or function would lead to sex-differential effects on neuronal connectivity[@b56]. It is also interesting to consider that numerous ASD risk genes function at the synapse[@b7][@b9][@b57][@b58][@b59], and that as a third synaptic component along with pre- and postsynaptic neurons, sexually dimorphic astrocytes and/or microglia are well positioned to broadly influence the effects of upstream, heterogeneous risk variants. We also acknowledge several limitations of our study. First, our analyses utilize gene expression data from the human cerebral cortex, a region that other studies have indicated is a convergent area where many ASD risk genes likely exert their action[@b30][@b31]. However, other brain regions not sampled in our data sets, such as the hypothalamic nuclei, are known to be robustly sexually dimorphic[@b60]. It may be that ASD risk genes are differentially expressed by sex in these sexually dimorphic regions, or that it is the connections between these regions and other parts of the brain where the sex-differential risk-modulatory mechanisms act (as opposed to purely within-cortex interaction at the level of molecular pathways and local cell--cell connections). Assessment of additional brain regions, including hypothalamic nuclei and other subcortical structures, in sufficiently powered test and replication sets will be useful for addressing this important question, once such data are available. The mechanism(s) of the sex-biased expression observed here are not known, but present significant opportunities for understanding ASD\'s sex-biased pathogenesis. For example, transcription of sex-DE genes identified here may be regulated by sex-differential factors, such as transcription factors from the sex chromosomes, or by sex steroid receptor binding to hormone response elements upstream from transcription start sites. Chromatin immunoprecipitation experiments in human neural tissue coupled with functional assays in model systems will be needed to thoroughly characterize binding sites for these regulatory elements throughout the genome. Alternatively, the sex differences we have observed may not result from differential transcription regulation, but instead from sex differences in the proportions of different neural cell types within male and female tissue. The overlap between male-DE genes and astrocyte and microglial marker genes is consistent with this possibility, although the processes that lead to sex differences in cell type proliferation or differentiation are unclear. Quantitative histological studies of male and female human brain will be critical to characterize the extent to which cell type composition differs between the sexes, and neurodevelopmental follow-up will be required to demonstrate how these differences arise. The extent to which the convergent transcriptional changes previously observed in ASD cortex[@b23][@b24] represent causal aetiologies versus consequences of brain dysfunction also remains to be delineated[@b61]. In the case of ASD-associated co-expression modules enriched for risk variants, such as asdM12~V~, enrichment of genes carrying ASD risk variants provides evidence for a causal, primary role in ASD aetiology. However, ASD-associated co-expression modules that lack enrichment for genetic risk variants, such as asdM16~V~, may be linked to ASD in one of several ways: (1) They reflect direct downstream consequences of variants in, or dysregulation of, primary, 'causal\' genes (for example, asdM12~V~) that actively participate in the pathophysiological processes that shape and maintain an autistic-functioning brain; (2) they represent risk pathways that are independent of primary risk genes, for example, consequences of an environmental exposure, that also actively participate in ASD\'s aetiology; or (3) they exemplify consequences of living with ASD to the brain, which may modify the presentation of ASD or its comorbidities, but that do not have a role in ASD\'s aetiology. For example, the gene expression signature captured by non-variant-enriched, co-expression module asdM16~V~, which is upregulated in post-mortem adult autistic cortex, may reflect the impact of chronic social stress experienced across the lifespan. If male and female brains respond differently to stress[@b62], then the concordance we observe between these gene expression signatures may be tangential to ASD\'s primary pathophysiology. Though, one would expect that such stress would be cumulative over the lifespan, so that a stress-driven gene expression profile would increase with experience and age. Neither of the ASD-associated co-expression modules is significantly correlated with age[@b23][@b24], making this explanation less likely. Nevertheless, extensive characterization of animal models of ASD genetic risk variants, including gene expression patterns, may help to determine whether expression signatures like these are purely consequential, or if they are evident during early development and play a role in ASD aetiology. In any case, the sex-DE patterns that we observe in multiple, independent samples demonstrate that currently identified ASD risk genes are not innately sex-differentially expressed in the developing or adult human cerebral cortex. Instead, it is the molecular, cellular or circuit-level context in which ASD risk genes operate that is likely responsible for modulating ASD liability in a sex-differential manner. This notion fits with the remarkable consistency of the male bias in ASD prevalence, despite ongoing evidence of considerable genetic heterogeneity in ASD. Study of astrocyte--neuronal and microglia--neuronal synapse interactions, and study of the causes and functional consequences of higher expression of astrocyte and microglial genes in male brain and synaptic genes in female brain, are needed to determine how sex-differential functioning of these pathways impact sexually dimorphic risk for a variety of neurodevelopmental disorders, including ASD. Methods ======= Adult BrainSpan data set ------------------------ Developmental RNA-seq data from the BrainSpan project[@b28] summarized to Gencode 10 (ref. [@b41]) gene-level reads per kilobase million mapped reads (RPKM) were used. Data were normalized for GC content, using conditional quantile normalization[@b63], batch-corrected for processing site using ComBat[@b64] and log~2~-transformed (log~2~(RPKM+1)). Samples from regions of the frontal, temporal and parietal cortex from subjects aged 13--40 years, with RNA integrity number (RIN) of at least 8.0, were retained for this analysis. Non-expressed genes defined as having a log~2~-transformed RPKM expression level of \<1 in more than 50% of all male or female samples were removed. Outlier samples were identified by evaluating inter-sample correlations and hierarchical clustering, first within each sex, and then on the full data set (samples of both sexes considered together); samples with inter-sample correlations \>2.5 s.d.\'s from the mean were removed. The data were then quantile normalized to mitigate the effects of systematic differences in the distribution of expression levels across samples on the differential expression analysis results. After gene filtering and outlier removal, 72 samples (29 from males and 43 from females) and 16,843 expressed genes remained. To balance the male and female sample sets, we then matched a subset of the female samples to the male samples by age and brain region, and again filtered for expressed genes. The final data set consisted of 58 samples from 10 subjects (29 samples from 5 subjects of each sex; [Supplementary Table 1](#S1){ref-type="supplementary-material"}) and 16,392 genes ([Supplementary Data 1](#S1){ref-type="supplementary-material"}). Adult replication data set -------------------------- The adult replication sample comprised seven frontal and temporal cortex samples from five male individuals matched to seven cortical samples from five female individuals with no history of neuropsychiatric or neurological diagnoses. Male and female samples were matched for age, post-mortem interval (PMI) and brain region. These samples were a subset of a larger set acquired from the Harvard Brain and Tissue Bank and the Eunice Kennedy Shriver National Institute for Child Health and Human Development Brain and Tissue Bank for Developmental Disorders following the tissue acquisition policies of the respective brain banks. Approximately 100 mg of tissue from each sample was dissected on dry ice; RNA isolations were performed using the miRNeasy kit (Qiagen), RNA quality was quantified using the RIN[@b65] and ribosomal RNA was depleted using the Ribo-Zero Gold kit (Epicentre). Remaining RNA was then size selected with AMPure XP beads (Beckman Coulter) and re-suspended, and sequencing libraries with indexed adaptors were prepared according to the Illumina TruSeq protocol. Fifty base-pair, paired-end reads were generated on a HiSeq 2000/2500, with 24 samples pooled per lane. Reads were mapped to the human reference genome (hg19) using Gencode v18 annotations with TopHat2, allowing for up to 10 multiple mappings per read[@b41][@b66]. Output BAM files were filtered to ensure that every read had a valid pair, resulting in only paired-end reads (fragments) being used for downstream analyses. Transcript levels were quantified using Gencode v18 gene models at the union gene model level using HT-seq Counts[@b67]. We normalized these data for GC content biases using the cqn package in R (ref. [@b63]), which resulted in log~2~(normalized FPKM) values, and ensured that there were no sample outliers with a summed sample correlation *Z*-score\>2 (ref. [@b68]). Genes not expressed in the subset of neurotypical samples selected for these analyses were identified (log~2~-transformed FPKM expression level \<1 in more than 50% of all male or female samples) and removed. Outlier samples with inter-sample correlations \>2.5 s.d.\'s from the mean, either within each sex or within the complete sample set, were removed. The expression data for the remaining samples were then quantile normalized. The final filtered data set consisted of 13 samples from 10 subjects ([Supplementary Table 1](#S1){ref-type="supplementary-material"}), and 19,354 genes ([Supplementary Data 1](#S1){ref-type="supplementary-material"}). Prenatal data set ----------------- Exon array data analysed by Kang *et al.*[@b29] and downloaded from the Gene Expression Omnibus (GSE25219) were used for the assessment of prenatal gene expression. Only samples from subjects between 16 and 22 post-conception weeks from the frontal, temporal and parietal cortex, and with RIN of 8.0 or greater were used in this stage of analysis. Probe set IDs from the downloaded data were matched to Ensembl Gene IDs from Gencode 10 using the biomaRt function in R. Non-expressed genes were defined as those genes with a log~2~-transformed median probe set intensity of \<6 in \>80% of male or female samples within the selected sample set, and were removed. Outlier samples were detected by evaluating inter-sample correlations and hierarchical clustering within each sex and within the complete data set, and samples with inter-sample correlation \>2.5 s.d.\'s from the mean were removed. Expression data for the remaining samples were quantile normalized. After these processing steps, 142 samples (43 from males and 99 from females) and 9,985 expressed genes remained. To balance the number of male and female samples for analysis, we then matched a subset of the female samples to the male samples on age and brain region, and again filtered for expressed genes. The final data set consisted of 86 samples from 8 subjects (43 samples from 4 subjects of each sex; [Supplementary Table 1](#S1){ref-type="supplementary-material"}), and 9,889 genes ([Supplementary Data 1](#S1){ref-type="supplementary-material"}). Differential expression analysis -------------------------------- Differential expression analyses for all data sets were performed using a linear mixed model and Bayesian *t*-tests as implemented in LIMMA[@b69], a robust method for analysing small samples. For all analyses, the main contrast in the regression model was sex, and subject was included as a random effect to account for the non-independence of samples from the same individual brain (that is, different brain regions). Covariates were included, where available, in the model as fixed effects: RIN, age, PMI, cortical lobe and pH for the adult BrainSpan data; RIN, age, PMI and cortical lobe for the replication data; and RIN, age, PMI, cortical lobe and pH for the prenatal data. Per-subject average values were substituted for missing PMI and pH information. Genes with a FD magnitude of 1.2 or greater and an unadjusted *P* value of 0.005, 0.01 or 0.05 were called as differentially expressed by sex (sex-DE; [Supplementary Data 1](#S1){ref-type="supplementary-material"}). Annotation gene sets -------------------- ASD candidate genes were selected from the SFARI Gene Autism Database[@b32] and filtered to those genes classified as syndromic (category S) or with evidence levels between 1--4 for a set of 153 genes. To also investigate a risk gene set based on evidence from an unbiased, experimental screen, we used the set of genes with rare *de novo* variants (RDNVs) in sporadic ASD cases from exome sequencing of families from the Simons Simplex Collection[@b8]. All genes with RDNVs in autistic probands were compiled and classified as protein-disrupting (nonsense, splice site or frameshift mutations), missense or silent variants. Here we use the gene set with protein-disrupting variants (353 genes) and the expanded gene set with either protein-disrupting or missense variants (1,771 genes). We also evaluated the set of transcripts that are binding targets of FMRP, a functionally defined gene set that is enriched for ASD risk genes[@b70]. Here we tested the 725 human orthologues of FMRP target genes as characterized in mouse brain[@b33] ([Supplementary Data 2](#S1){ref-type="supplementary-material"}). Seven gene sets with ASD-associated expression patterns in adult human cortex were also tested. From a 2011 study by Voineagu *et al.*[@b24], we tested genes expressed at significantly (1) higher (FD≥1.2, *q*-value\<0.1, 88 genes) or (2) lower levels in ASD than in control cortex (125 genes); (3) ASD-associated, unsigned co-expression modules from weighted gene co-expression network analysis, asdM12~V~ (downregulated in ASD, 414 genes); and (4) asdM16~V~ (upregulated in ASD, 361 genes). From a 2014 study by Gupta and colleagues[@b23] that used a larger, but overlapping, sample of individuals as Voineagu *et al.*[@b24], but which analysed BA19, a different cortical region, we tested several ASD-associated weighted gene co-expression network analysis modules, including (5) asdM1~G~ (downregulated in ASD, 1,643 genes), (6) asdM6~G~ (upregulated in ASD, 667 genes) and (7) asdM5~G~ (upregulated in ASD, 759 genes) ([Supplementary Data 2](#S1){ref-type="supplementary-material"}). Since gene expression patterns in the brain often reflect the transcriptional activity of distinct neural cell types[@b39][@b40], we also culled gene sets marking different cell types from several studies in the literature. From a microarray study of sorted cell types in mouse forebrain[@b26], we tested markers for neurons (1,489 genes), oligodendrocytes (1,626 genes) and astrocytes (1,968 genes). From a microarray study of human microglial cells in culture[@b25], we tested genes with at least a twofold upregulation in activated, microglia-enriched, mixed glial cultures (∼60% microglia) (773 genes). From a single-cell RNA-seq study of mouse somatosensory cortex and hippocampus[@b27], we tested markers for CA1 pyramidal neurons (355 genes), S1 pyramidal neurons (235 genes), interneurons (319 genes), oligodendrocytes (397 genes), astrocytes (216 genes), microglia (368 genes), endothelial cells (312 genes), ependymal cells (402 genes) and mural cells (pericytes and vascular smooth muscle cells, 137 genes) ([Supplementary Data 4](#S1){ref-type="supplementary-material"}). Recent evidence has also suggested complementary roles for microglia and immune cells in mediating behaviour in male versus female animals[@b38]. To evaluate whether adaptive immune cells contribute to the sex-differential gene expression that we observe in the brain, we tested co-expression modules generated by the Immunological Genome Project from mouse haematopoietic cells that are associated with T- and B-cell lineage regulator genes[@b34]: T-cell module 18 (106 genes); gamma delta T-cell module 65 (30 genes); gamma delta, natural killer T and T4 module 56 (58 genes); alpha beta T-cell module 57 (52 genes); B-cell module 33 (125 genes); B-cell module 61 (38 genes); and B-cell module 76 (15 genes; [Supplementary Data 5](#S1){ref-type="supplementary-material"}). For the enrichment analyses, we used the following gene sets as background: for SFARI candidate genes, genes with RDNVs in ASD cases and activated microglial markers, we used expressed genes with a Gencode biotype annotation of 'protein coding\'; for gene sets with ASD-associated expression patterns and for immune cell markers, we used expressed genes also tested in the corresponding source publication[@b23][@b24][@b34]; and for FMRP target genes[@b33] and cell type markers from Cahoy *et al.*[@b26] and Zeisel *et al.*^27^, we used the genome-wide set of one-to-one human--mouse orthologues as background ([Supplementary Data 8](#S1){ref-type="supplementary-material"}). For all background and gene sets of interest, gene identifiers were converted to Ensembl Gene IDs in Gencode using the biomaRt package in R to allow for unambiguous comparisons between genes from different data sources. Gene set membership, background set membership and sex-DE categorization for all expressed genes tested for differential expression in the three data sets are recorded in [Supplementary Data 9](#S1){ref-type="supplementary-material"}. Over-representation analysis ---------------------------- To evaluate the enrichment of gene sets of interest among sex-DE genes, we applied a two-sided Fisher\'s exact test separately to sex-DE gene sets expressed more highly in males (male-DE) and in females (female-DE) at three *P* value thresholds (unadjusted *P*\<0.005, 0.01 and 0.05, [Supplementary Data 3, 6 and 7](#S1){ref-type="supplementary-material"}) in R. *P* values from the Fisher\'s exact tests run within each data set were adjusted for 62 tests performed against the 31 gene sets of interest (4 ASD risk gene sets, 7 ASD expression gene sets, 13 neural cell type marker sets and 7 adaptive immune cell marker sets) at each of the three significance levels for the sex-DE input genes. To further investigate patterns of sexually dimorphic expression within each gene set of interest without applying arbitrary thresholds to define sex-DE genes, we also assessed the distribution of the genes in each set into two mutually exclusive categories: higher expression in males (positive log~2~(fold difference), at any *P* value); or higher expression in females (negative log~2~(fold difference), at any *P* value). We then applied a two-sided binomial test against the distribution of male-higher and female-higher genes in the corresponding background gene set ([Supplementary Data 3, 6 and 7](#S1){ref-type="supplementary-material"}). *P* values from all binomial tests within each data set were Bonferroni-corrected for the 31 gene sets tested. Additional information ====================== **Accession codes:** Gene expression data analysed in this study come from publicly available resources (adult BrainSpan RNA-seq data, [www.brainspan.org](http://www.brainspan.org); prenatal array data, GEO accession [GSE25219](GSE25219); and adult replication RNA-seq data, GEO accession [GSE76852](GSE76852)). Computer code used in this study is available on request. **How to cite this article:** Werling, D. M. *et al.* Gene expression in human brain implicates sexually dimorphic pathways in autism spectrum disorders. *Nat. Commun.* 7:10717 doi: 10.1038/ncomms10717 (2016). Supplementary Material {#S1} ====================== ###### Supplementary Information Supplementary Figures 1-2 and Supplementary Table 1 ###### Supplementary Data 1 Sex-differential expression results from all three data sets: adult BrainSpan RNA-seq, adult replication set RNA-seq, prenatal exon array. ###### Supplementary Data 2 Tables for all ASD-risk and ASD-associated gene sets tested for enrichment of sex-differential expression. ###### Supplementary Data 3 Over-representation analysis results for adult BrainSpan RNA-seq data set. ###### Supplementary Data 4 Tables for all neural cell type marker gene sets tested for enrichment of sex-differential expression. ###### Supplementary Data 5 Tables for all adaptive immune system cell type marker gene sets tested for enrichment of sex-differential expression. ###### Supplementary Data 6 Over-representation analysis results for adult replication RNA-seq data set. ###### Supplementary Data 7 Over-representation analysis results for prenatal exon array data set. ###### Supplementary Data 8 Tables for all gene sets used as background in over-representation analyses. ###### Supplementary Data 9 Membership in gene sets of interest, background gene sets, and sex-differentially expressed gene sets for all expressed genes from each of the three data sets analyzed. We acknowledge data resources from the BrainSpan consortium (<http://brainspan.org>; 5RC2MH089921 to Ed Lein). This work was supported by the US National Institute of Mental Health grants (5R37MH060233 and 5R01MH094714, D.H.G.), an Autism Center for Excellence network grant (9R01MH100027) and NRSA and NIMH training fellowships (F31MH093086, D.M.W.; F30MH099886 and T32MH073526, N.N.P.). We also thank members of the Geschwind laboratory as well as Dr Stephan Sanders for helpful discussions and suggestions. D.H.G. serves on the scientific advisory board for SynapDx. The remaining authors declare no competing financial interests. **Author contributions** D.M.W. and D.H.G. designed the study and interpreted the results; D.M.W. performed data processing and all differential expression and over-representation analyses; N.N.P. ran the preprocessing for the adult replication data set and contributed code for over-representation analyses; D.M.W. drafted the manuscript with assistance from D.H.G. and input from N.N.P. {#f1} ![Sex-differential expression parallels gene expression patterns in ASD brain.\ Bar plots show FDs by sex and ASD status of sex-DE genes (FD≥1.2 and *P*\<0.05) that also belong to ASD-associated co-expression modules[@b24]. (**a**) Module asdM16~V~, which is significantly upregulated in ASD and enriched for genes involved in the inflammatory response and immune system functions, and (**b**) module asdM12~V~, which is significantly downregulated in ASD and enriched for genes with neuronal and synaptic functions. (**c**) FDs of sex-DE genes (FD≥1.2, *P*\<0.05, 374 genes) by sex and status. Best-fit line and its 95% confidence interval are shown. CTL, control from ASD expression study; F, female; M, male.](ncomms10717-f2){#f2} {#f3} {#f4}

Coleophora vicinella Coleophora vicinella is a moth of the family Coleophoridae. It is found from France to Ukraine and then further south. The wingspan is 16–17 mm. The larvae feed on Astragalus, Coronilla, Dorycnium, Galega and Medicago sativa. They create an ochreous pistol case with many sharp ridges and a sharp ventral keel. The pallium (cloak) covers about three quarters of the case and has a pair of wing like extensions at the rear. It is strongly inflated and has a scalloped surface structure. The colour is yellowish white at first, but brown or even black later. The mouth angle is 45°. Older larvae no longer feed within fleck mines, but feed on all leaf tissue except the stronger veins. Larvae can be found from autumn to May of the following year. References vicinella Category:Moths of Europe

To limit the description of De'Ann Clark to the positions of CEO and President of TREO International, Inc. (TREO) is too confining. As the head of TREO, she guided the company successfully through several economic boom-and-bust cycles over two decades. She positioned TREO as a credible player in the Default and Real Estate industries (performing Valuations, Loss Mitigation, Nationwide Asset & Property Management services, and Residential & Commercial Real Estate Investment Brokerage). However, this does not fully define her. Ms. Clark is also an entrepreneur, owning and operating several companies, and a Court-Appointed Receiver, who works hands-on to restructure the debt of defaulted commercial assets to maximize recovery. Because of her wide recognition as an Industry leader, she is a frequent speaker for default management conferences and summits.

Greg Toppo USATODAY WASHINGTON — Two weeks after Republican Donald Trump defeated Democrat Hillary Clinton in the Nov. 8 presidential election, the USA’s teachers unions are wondering what happened to their chosen candidate — and how so many of their members could have voted for her opponent. Despite early and eager endorsements of Clinton by both unions, the nation’s school teachers and other school workers contributed substantially to Trump’s Nov. 8 win. How substantially? About one in five American Federation of Teachers (AFT) members who cast a ballot voted for Trump, the union’s leader estimated. Among the larger National Education Association (NEA), which comprises more than 3 million members, more than one in three who voted did so for the billionaire developer, early data show. AFT President Randi Weingarten, whose union represents about 1.6 million teachers and other workers, said some of the reason for Clinton's defeat was timing — and perhaps sexism. “Frankly I was always concerned about whether the country was ready to have a female president,” she said. “There was an intensity of hatred that male political figures never get. So I think we’re never really going to understand it.” Most of the USA’s largest labor unions endorsed Clinton as early as 2015, including NEA, AFT, the Service Employees International Union (SEIU), the International Brotherhood of Teamsters and the American Federation of State, County and Municipal Employees (AFSCME). Despite the support, Clinton won union households nationwide by just eight percentage points, exit polls show: 51% to Trump’s 43%. Clinton carried white, college-educated women, but just barely: 51% to 45%. Among white women without a college degree, Trump won resoundingly: 63% to Clinton’s 34%. In that sense, teachers, who at last count were about 82% white and 76% female, actually outperformed other groups when it came to their support for Clinton. Weingarten last week said internal figures show that Clinton earned about 80% of her members' votes, in spite of a “very effective” effort to disparage the former secretary of state’s character. At NEA, an aggressive member-to-member campaign and strategic political effort actually did get out the vote for Clinton, officials said: As late as last September, nearly 60% of its members identified as “Republicans or independents.” At the time, Clinton’s NEA support stood at just 58%. By Election Day, it rose to 65%. NEA President Lily Eskelsen García, a former Utah teacher, said that despite Clinton’s loss, the union engaged members in “record levels of activism," supporting down-ballot candidates and initiatives "important to students and working families.” Among other efforts, unions defeated a well-funded charter school expansion effort in Massachusetts and helped ensure the continuation of a tax hike to fund education in California. NEA's state and national political directors met in Nashville last weekend to figure out what comes next, and educators nationwide are waiting to find out who President-elect Trump names as education secretary. On Wednesday, school voucher advocate Betsy DeVos said in a tweet that she would work with Trump to "make American education great again." In a statement, García said NEA will “listen closely” as Trump lays out his education vision. “We haven’t heard any specifics from the incoming administration about education policies, so we can’t speculate further,” she said. In an interview, Weingarten said she had “no regrets — absolutely no regrets” about the union’s endorsement of Clinton, adding that Democratic runner-up Sen. Bernie Sanders “was never tested or vetted by anyone, and frankly we have no idea whether he would have actually been able to get through this crucible … either.” She added that Clinton “has spent her life fighting for families and children — and that’s what we spend our life fighting for. Were there mistakes she made? Of course. Were there mistakes we made? Of course. But she is someone who for 30 years has been in the service of the public and incredibly qualified.” Follow Greg Toppo on Twitter: @gtoppo

Q: Explicitly specify defaulted template parameter located after template parameter pack Why can't I explicitly specify d in following case? #include <iostream> template< typename a, typename b = int, typename ...c, typename d = int > int f(a, b, c..., d) { return sizeof...(c); } int main() { std::cout << f< int, int, int, int/*, char*/ >(1, 2, 3, 4, 'd') << std::endl; return 0; } If I uncomment last template argument, then I expect output 2, but instead I get a hard error: main.cpp:14:18: error: no matching function for call to 'f' std::cout << f< int, int, int, int, char >(1, 2, 3, 4, 'd') << std::endl; ^~~~~~~~~~~~~~~~~~~~~~~~~~~~~ main.cpp:6:1: note: candidate function not viable: requires 6 arguments, but 5 were provided f(a, b, c..., d) ^ 1 error generated. What is the rule to deny it in this case? A: Because packs are greedy. So char is actually part of c and you're expected to supply the argument associated with d, which is of type int due to the default.

José Paulo José Paulo Rubim (born 26 July 1946) is a Brazilian football manager. In 2010 he was named head coach of Benin. He left this position later the same year. Managerial statistics References Category:1946 births Category:Living people Category:Expatriate football managers in Liberia Category:Brazilian expatriate sportspeople in China Category:Expatriate football managers in China Category:Brazilian expatriate sportspeople in Portugal Category:Expatriate football managers in Portugal Category:Brazilian expatriate sportspeople in Tunisia Category:Expatriate football managers in Tunisia Category:Brazilian expatriate sportspeople in Saudi Arabia Category:Expatriate football managers in Saudi Arabia Category:Brazilian expatriate sportspeople in the United Arab Emirates Category:Expatriate football managers in the United Arab Emirates Category:Brazilian expatriate sportspeople in Qatar Category:Expatriate football managers in Qatar Category:Brazilian expatriate sportspeople in Algeria Category:Expatriate football managers in Algeria Category:Expatriate football managers in Benin Category:Brazilian football managers

A Glove for my Companion A very well crafted holster and a perfect match for my PX4. It is probably the classiest holster I have ever seen and the quality and suppleness of the leather is superior indeed. In fact, I am complimented on my holster when I proudly show my PX4 to other enthusiasts. Any more bulk and it would be difficult to conceal. A problem I have with other holsters. FITS PX4 .45 cal Fits .45 cal. nicely...and very well made and looks good....try finding a holster for this pistol on alternative websites...almost impossible...a little tight at first, but its leather, leather stretches! new holster Just got my new holster and it fits my px4 storm 40 cal. like a glove. The only complaint i have is that the fastener on the back side for the strap is a little to high....basically ( i need to lose weight lol) all in all it is an awesome holster.

“Cloud computing” services provide shared resources, applications, and information to computers and other devices upon request. In cloud computing environments, services can be provided by one or more servers accessible over the Internet rather than installing software locally on in-house computer systems. As such, users having a variety of roles can interact with cloud computing services.

Use of Antibiotic Plates and Spacers for Fracture in the Setting of Periprosthetic Infection. Prosthetic joint infection is a common cause of hip revision surgery, typically managed with a staged protocol and an antibiotic cement spacer. Patients being treated for prosthetic joint infection are at risk of fracture below the level of the spacer. Fracture in the setting of periprosthetic infection is a complex problem that requires the treating surgeon to use multiple techniques to achieve a successful outcome. The purpose of this case report is to highlight surgical strategies to successfully manage periprosthetic fractures complicated by infection.

Introduction {#s1} ============ Drug repositioning is known as the 'old drug, new disease' paradigm. It aims to find new diseases to cure for existing drugs and thus offers the possibility for faster, safer, and cheaper drug development. Given the huge search space and the rapid accumulation of drug related data at molecular level, computational approaches are highly desired to narrow down the gap between medical indications and elucidation of drug effects [@pone.0078518-DiMasi1]. In addition to their low cost and time-efficiency predictions, computational methods have the advantage in understanding the mechanisms of drug actions. Drug takes effect via its protein targets in cell to cure disease. Thus, many previous studies in computational drug repositioning focused on the drugs with known downstream target proteins in disease-specific molecular networks [@pone.0078518-Kinnings1]--[@pone.0078518-Kotelnikova1]. However, low-throughput data limits the applications in small scale. Recent accumulated high-throughput data for both drugs and diseases provide possibilities to uncover novel statistical associations between drugs and diseases in a large-scale manner. Many methods have been developed in this direction, including: (i) matching drug indications by their disease-specific response profiles based on the Connectivity Map (CMap) dataset [@pone.0078518-Hu1] and (ii) predicting novel associations among drugs and diseases by the 'Guilt and Association' (GBA) approaches [@pone.0078518-Chiang1]. Every method has its pros and cons. CMap approach relies on the dynamic gene expression datasets generated under different conditions and suffers from low precision [@pone.0078518-Hu1]. GBA [@pone.0078518-Chiang1] approach takes advantage of disease associations with the same drug, but it is only applicable in the case that some indications for the drug in question are already known and complete. Integrative analysis is one way out [@pone.0078518-Wu1]. Recently, a novel integrative method was proposed for drug-disease association prediction [@pone.0078518-Gottlieb1]. This method heuristically summarized multiple drug-drug and disease-disease similarity measures from various aspects and repositioning was done based on the observation that similar drugs tend to treat similar diseases. The authors reported high specificity and sensitivity (AUC = 0.9). This approach applied logistic regression to integrate multiple drug-drug and disease-disease similarity metrics to collect the evidence for a strong association. This scheme provides a machine learning framework, and there is still much room to improve both from more general data collecting and accurate predicting. In this paper, we construct a universal Predictor for Drug Repositioning (PreDR) to dissect drug-disease associations in a large-scale manner. We notice the rapid development of high-throughput technologies and ever-increasing accumulation of genome-wide datasets. On one hand, high-quality drug-disease networks have been constructed as the gold-standard to learn. On the other hand, drug's functional roles in cell can be depicted from different aspects. For example, drug's chemical structure provides information by the 'structure determines function' paradigm. Target protein provides the direct effect at molecular level, and side effect hints the unwanted effect at phenotype level. One straightforward idea is to learn understandable rules from these existing data and to predict novel drug-disease relationships. We demonstrate that drugs with similar chemical structures, target proteins, or side-effects will indicate similar diseases. Then we integrate heterogeneous chemical structures, target proteins, and side-effects information sources. Specifically, drug and disease are characterized by their similarity-based profiles, and kernel function is then defined to correlate drug with disease. Finally the potential drug-disease interactions are inferred by a machine learning model, i.e., support vector machine (SVM), which is motivated by statistical learning theory [@pone.0078518-Vapnik1], [@pone.0078518-Vapnik2] and has been proven successful on many different classification problems in bioinformatics [@pone.0078518-Schlkopf1]. PreDR provides an efficient way to overcome the main difficulty that these data sources are from three different levels and are extremely heterogenous. PreDR is validated on a well-established drug-disease network with 1,933 interactions between 593 drugs and 313 diseases. By cross-validation, we find that all chemical structures, drug targets, and side-effects are predictive in different power. Combining these heterogenous properties predicts more drug-disease associations supported by literature and disease pathway database. Moreover, some novel predictions are supported by clinical trials database. Materials and Methods {#s2} ===================== We design a novel algorithm, named PreDR, to predict drug repositioning by associating known drugs with potential disease labels based on kernel fusion of heterogenous data sources. The schematic illustration of PreDR is shown in [Figure 1A](#pone-0078518-g001){ref-type="fig"}. The functional role of drug is characterized by its molecular structure, molecular activity, and phenotype data. PreDR aims to optimally integrate these three data sources and to connect drug with disease more accurately. {#pone-0078518-g001} We treat drug-disease interaction prediction as a binary classification problem, i.e., determining whether a give pair of drug and disease is associated or not. We introduce SVM-based algorithm to cope with this task. The algorithm works in three phases ([Figure 1](#pone-0078518-g001){ref-type="fig"}): (Phase I) Collecting known drug-disease interactions as gold-standard positives in a bipartite graph. (Phase II) Modeling drug-drug and disease-disease similarity metrics. Drug similarity is derived from chemical structure, target protein, and side-effects. Disease similarity is based on semantic similarity of disease phenotypes [@pone.0078518-vanDriel1]. (Phase III) Fusing the similarity among drugs and similarity among diseases by kernel methods, and applying SVM algorithm to predict the unknown relationships between drugs and diseases. Given two drug-disease pairs, we consider to construct a kernel function which potentially correlates with their similarity. Since the kernel function represents the similarities among the training samples in some sense [@pone.0078518-Hofmann1], we focus on the similarities among drugs and similarities among diseases. Therefore, we try to construct the similarity profile to represent drug and disease, respectively, in the following subsections. Collecting Structure, Activity, and Phenotype Data for Drugs {#s2a} ------------------------------------------------------------ ### Chemical structure data {#s2a1} It is generally believed that drugs with similar chemical structure would carry out common therapeutic function, thus likely treat common diseases. So here, drugs are firstly represented by its chemical structure similarity profile. PubChem database (<http://pubchem.ncbi.nlm.nih.gov/>) has defined 881 chemical substructures based on fingerprint search. Then a given drug can be represented by an 881 dimensional binary vector *x*. Each element of *x* is encoded as 1 or 0, which means the presence or absence of corresponding PubChem substructure. The description of these 881 chemical substructures is available at PubChem's website. There are 107,292 associations between drugs and chemical substructures in the dataset, and each drug has 120.8 substructures on average [@pone.0078518-Pauwels1]. The similarity between two drugs *d* and is evaluated by the weighted cosine correlation coefficient [@pone.0078518-Yamanishi1] as followswhere is the weight function for the k-th substructure, and defined aswhere is the frequency of the k-th substructure, and is the total number of substructures, is the standard derivation of , and is a parameter and set to 10 in this study. The weight function puts more emphasis on rare substructures rather than frequent ones across different drugs, because rare substructures are more informative than common ones for specific function. Suppose that we have drugs in total, a matrix is then constructed to represent the chemical structure similarity matrix. Each row (or column) of this matrix is the chemical structure similarity profile for a single drug. ### Drug-target interaction data {#s2a2} Drugs sharing common targets often possess similar therapeutic function. So there are many drug-target prediction studies for drug function. In our case, drugs interacting with the same targets are assumed to treat common diseases. In this subsection, we represent drug-drug similarity by their target protein similarity. The high-quality drug-target interactions can be manually constructed from the KEGG BRITE [@pone.0078518-Kanehisa1], BRENDA [@pone.0078518-Schomburg1], SuperTarget [@pone.0078518-Gnther1], and DrugBank [@pone.0078518-Wishart1]. In addition, the drug target interactions are well-studied for some specific protein families in previous studies [@pone.0078518-Yamanishi1], [@pone.0078518-Yamanishi2]--[@pone.0078518-Wang2]. Here, we mainly collected drug-targets data from DrugBank [@pone.0078518-Wishart1], and defined drug similarity by target proteins' sequence similarity. That is, given two drugs and , the similarity among them can be calculated as followswhere and are the sets of target proteins, is sequence similarity among protein and , which is calculated by a normalized version of Smith-Waterman scores [@pone.0078518-Yamanishi2], [@pone.0078518-Smith1]. The matrix is then constructed to represent the compound target similarity matrix. Each row (or column) of this matrix is the target protein similarity profile for a single drug. Unlike chemical structure similarity matrix , target protein similarity matrix may not be a positive semidefinite matrix and needs the following normalization stepwhere is diagonal matrix. The k-th diagonal element of is . ### Side-effect data {#s2a3} Drug side-effects, or adverse drug reactions, is one of the main causes of drug development failure and drug withdrawal from the market [@pone.0078518-Pauwels1]. This high level phenotype data for drugs indicates the malfunction by off-targets. Thus side-effects data is useful to infer whether two drugs share similar target proteins [@pone.0078518-Campillos1]. In this study, drug side-effects are utilized to drug repositioning as some previous studies did [@pone.0078518-Yang1], [@pone.0078518-DuranFrigola1]. Similar to structure and target data, drug side-effects information is also applied to construct the drug similarity profile. There are a total of 1,450 side-effect annotations in the SIDER database (<http://sideeffects.embl.de/>) for 888 approved drugs. Then each drug can be represented as an 1,450 dimensional binary vector . Each element of is encoded as 1 or 0 to indicate the presence or absence of corresponding side-effect. Drugs similarity under their side-effects metric is assessed by the weighted cosine correlation coefficient between and as followswhere is the weight function for the k-th side-effectwhere is the frequency of the k-th side-effect in the data, and is the total number of side-effect, is the standard derivation of , and is a parameter (set to be 10 in this study). The matrix then represents the drug similarity matrix by their side-effects similarity. Each row (or column) of this matrix is the side-effect similarity profile for a single drug. Characterizing Disease Similarity by Phenotype Data {#s2b} --------------------------------------------------- Similar to drug similarity profile, we used the disease similarity profiles to represent diseases. The disease-disease similarities were measured by their semantic similarity of disease phenotypes [@pone.0078518-vanDriel1]. Text mining techniques were utilized to classify over 5,000 human phenotypes contained in the Online Mendelian Inheritance in Man (OMIM) database [@pone.0078518-vanDriel1]. The phenotype similarity data are accessible through website at <http://www.cmbi.ru.nl/MimMiner/>. As a result, the similarity between two diseases and can be calculated as followswhere is semantic similarity of disease phenotype and , which is calculated by text mining approach in [@pone.0078518-vanDriel1]. The matrix represents the similarities for all pairwise diseases. Each row (or column) is the phenotype similarity profile for a single disease. Kernel Fusion {#s2c} ------------- With the representation of drugs and diseases by their similarity profiles, the similarity between two drug-disease pairs and can be calculated as Kronecker product kernel [@pone.0078518-Basilico1]--[@pone.0078518-Hue1] as followswhere can be any one of , , and or their combination. In this paper, "Chem" denotes the case when , "Inter" denotes the case when , "Side-effect" denotes the case when , and "Comb" denotes the case when , which means drug similarity supported by one or more than one metrics. Taken together, the rationale behind our kernel function construction scheme for drug-disease pairs is that two drug-disease pairs are similar only when the corresponding diseases and drugs are simultaneously similar supported by heterogeneous data sources. SVM Prediction with the Defined Kernel Function {#s2d} ----------------------------------------------- With the above kernel function construction scheme, the drug-disease interactions prediction task is formalized as a binary classification problem. We treat the known drug-disease pairs as the gold-standard positives and the others as the gold-standard negatives. We note that this may cause the training data imbalance problem. Because there are more negatives and only a relatively small number of positives. This situation makes the SVM ineffective in determining the class boundary [@pone.0078518-Wu2]. To maintain a balance, we randomly select a set of training negatives from the unlabelled data to have the same size with the training positives. Feeding the kernel function in [Equation (8](#pone.0078518.e049){ref-type="disp-formula"}) and training dataset to SVM, the classifier can be calculated by SVM algorithm. Benchmark Datasets and Algorithm Implementation {#s2e} ----------------------------------------------- The benchmark dataset, which is used to test the performance of PreDR as a community standard, was summarized in [@pone.0078518-Gottlieb1]. It spans 1,933 associations between 593 drugs taken from DrugBank [@pone.0078518-Wishart1] and 313 diseases in OMIM database [@pone.0078518-Hamosh1]. The drug chemical structure representation matrix was from [@pone.0078518-Pauwels1] (<http://cbio.ensmp.fr/yyamanishi/side-effect/>), which contains 888 approved drugs represented by 881 substructures derived from PubChem [@pone.0078518-Chen1]. Drug targets and targets sequences are from DrugBank [@pone.0078518-Wishart1]. The Smith-Waterman scores among protein sequences were calculated by MATLAB's Bioinformatics Toolbox. Drug side-effects are from SIDER [@pone.0078518-Kuhn1]. The disease phenotype similarity data was obtained at <http://www.cmbi.ru.nl/MimMiner/>. We trained the SVM-based predictor by using [@pone.0078518-Chang1]. In our implementation, the penalty parameter was optimized by a grid search approach with 3-fold cross-validation, and the optimal value of is . To evaluate the performance of our methods, 10-fold cross-validation was utilized. The performance of PreDR is shown by receiver operating characteristic (ROC) curve [@pone.0078518-Gribskov1], which shows the trade-off between the true positive (correctly predicted interactions) rate (TPR) with respect to the false positive (wrongly predicted interactions) rate (FPR). Furthermore, the evaluation criteria shown in [Table S1](#pone.0078518.s004){ref-type="supplementary-material"} are also applied to assess the performance rigorously. Results {#s3} ======= Chemical Structure, Drug-target Interactions, and Side-effects are all Predictive {#s3a} --------------------------------------------------------------------------------- We collect three data sources from structure, activity, and phenotype levels to characterize drugs: chemical structures, target proteins, and side-effects. First we test the fact that drugs with similar structures (target proteins or side-effects) will treat similar diseases. To show this, we correlate drug's profile by chemical structure, target protein, side-effect similarity, and their curing disease profile. The drug similarity by disease profiling is defined as followswhere and are the sets of diseases associated with drug and in gold standard positives, and is the disease phenotype similarity calculated by text mining approach [@pone.0078518-vanDriel1]. [Figure 2A](#pone-0078518-g002){ref-type="fig"} plots the weak correlations between drug similarity by their structures, protein targets, side-effects with drug similarity by its disease profile. It shows that drug's disease profile similarity is more correlated with its side-effect similarity comparing with chemical structure and protein targets similarity. The Pearson's correlation coefficients (PCCs) between drug' disease profile similarity and the similarity from chemical structures, target proteins, and side-effects data are shown in [Figure 2B](#pone-0078518-g002){ref-type="fig"}. It shows that the correlation coefficients tend to be larger when two drugs are more similar. For example, the correlation coefficients are all larger than 0.2 with high confidence when drugs are similar than 0.8 for all three kind of data sources. Correlation coefficient between side-effects profile based similarity and disease profile based similarity is larger than 0.3 ([Figure 2B](#pone-0078518-g002){ref-type="fig"}). Taken together, chemical structure, target protein, and side-effect similarity correlate with drug's disease profile similarity, i.e., drugs similar in either structure, target, or side-effects tend to cure similar diseases. {#pone-0078518-g002} In addition to global similarity by disease profile, we also correlate the similarity obtained from three kinds of data sources with the drugs' distance in the known drug-disease interaction network. We define the distance of two drugs in the network as the length of the shortest path between them in the network. We plot the distributions of chemical structure, target protein, and side-effects similarity scores with respect to network distance in [Figure S1](#pone.0078518.s001){ref-type="supplementary-material"}. It shows that all three kinds of similarities are larger than 0.6 for 75% drug pairs sharing common diseases. That is, two drugs with larger similarity scores in the three data sources tend to share common diseases. All the facts suggest predictability of different data sources for drug-disease associations. This analysis provides support for our follow-up integrative analysis. Drug Repositioning by Single Data Source {#s3b} ---------------------------------------- In this subsection, we assess the effects of chemical structures, target proteins, and side-effects in drug repositioning prediction. Their performances are evaluated and visualized by ROC curves [@pone.0078518-Gribskov1]. Firstly, we replace the drug similarity matrix in kernel function (8) (see Materials and Methods) with , , and to test the effect of chemical structure, target protein, and side-effects similarity in uncovering the experimentally observed drug-disease interactions. The ROCs for each data source are displayed in [Figure 3A](#pone-0078518-g003){ref-type="fig"}. It shows that all the ROC curves are beyond the diagonal (random classification) and closer to the 0--1 baseline. The corresponding evaluation criteria when the corresponding F-measure reaches its maximum are listed in [Table 1](#pone-0078518-t001){ref-type="table"}. We can see that "Chem" obtains AUC 0.83 and Sn 0.83. That is, chemical structure is useful in drug-disease interaction prediction. Target proteins and side-effects play their important roles in predicting drug-disease interactions too. The Accs, Sns, Pres and F-measures are all larger than 0.8 for "Inter" and "Side-effect", and AUCs reach 0.88. It indicates that target proteins and side-effects can address the activity and effect of drug in cell thus uncover more experimentally observed drug-disease interactions. {#pone-0078518-g003} 10.1371/journal.pone.0078518.t001 ###### The performance comparison for different data sources. {#pone-0078518-t001-1} Data source AUC Acc Sn Sp Pre F-measure ------------- ----------- ----------- ----------- ----------- ----------- ----------- Chem 0.834 0.763 0.737 0.792 0.781 0.763 Inter 0.889 0.812 0.824 0.799 0.804 0.811 Side-effect 0.894 0.813 0.826 0.799 0.804 0.812 **Comb** **0.902** **0.823** **0.847** **0.799** **0.808** **0.822** The best predictions are highlighted in bold. Since we are more interested in the performance of these methods when FPR is rather small, we also draw ROC curves when FPR is less than 0.05 in [Figure 3B](#pone-0078518-g003){ref-type="fig"}. It shows that, "Chem" obtains the highest TPR when FPR is very small, and with the number of known interactions increasing, "Side-effect" reveals more experimentally observed drug-disease interactions. All these results suggest that, each data source will do one's bit in prediction. Therefore, combination of these three data sources produces a much more sophisticated picture of the interactions among drugs and diseases. Data Fusion Improves Drug Repositioning {#s3c} --------------------------------------- The usefulness of each data source is validated in uncovering the experimentally observed indications for drugs. In the following, we validate the effect of combination of three data sources. The performances of combination method: "Comb" is also evaluated and visualized by ROC curve in [Figure 3](#pone-0078518-g003){ref-type="fig"} and various evaluation criteria in [Table 1](#pone-0078518-t001){ref-type="table"}. [Figure 3](#pone-0078518-g003){ref-type="fig"} shows that, "Comb" not only obtains the best area under ROC curve, but also achieves the highest TPR when FPR less than 0.05. This specifically demonstrates that "Comb" improves performance when predicting a small fraction of known drug-disease interactions as positives. [Table 1](#pone-0078518-t001){ref-type="table"} shows that, "Comb" performs better than using single data source. For example, "Inter" and "Side-effect" reach the AUC 0.889 and 0.894, respectively, while "Comb" obtains an AUC 0.902. "Inter" and "Side-effect" obtain F-measures 0.811 and 0.812, respectively. "Comb" obtains a F-measure 0.822 and improves by one percent. These facts demonstrate that the significant improvement is obtained by data integration. For drug-disease interaction prediction task, the gold standard positives are relatively not abundant. The area under precision-recall curve [@pone.0078518-Raghavan1] (AUPR) is a more significant quality measure than the AUC, as it punishes much more the existence of false positive examples found among the best ranked prediction scores [@pone.0078518-Davis1]. So we use the AUPRs ([Figure S2](#pone.0078518.s002){ref-type="supplementary-material"}) and precision-recall curves ([Figure S3](#pone.0078518.s003){ref-type="supplementary-material"}) to validate our results. All results shown in [Figure S2](#pone.0078518.s002){ref-type="supplementary-material"} and [Figure S3](#pone.0078518.s003){ref-type="supplementary-material"} suggest that each data source is predictive and data integration brings the improvement. Leave One Drug Out Cross-validation {#s3d} ----------------------------------- Given a new drug, people are interested in which disease it will cure, i.e., whether this novel drug is related with known diseases. To this end, we test the performance of our method by doing leave one drug out cross-validation. That is, we exclude each drug and its interactions from gold standard positives (known drug-disease interaction network). This drug and its interactions are taken in turn as a test dataset to validate the model trained on the remaining drug-disease interaction network. The procedure is illustrated in [Figure 4A](#pone-0078518-g004){ref-type="fig"}. The AUCs for leave one drug out cross-validation are shown as barplot in [Figure 4B](#pone-0078518-g004){ref-type="fig"}. The results are similar to 10 fold cross-validation results. "Chem" achieves the worst AUC, "Inter" obtains a better one, and "Side-effect" performs the best. Furthermore, all three data sources have larger AUCs than 0.78. "Inter" and "Side-effect" make AUC 0.80 and 0.84, respectively. "Comb" receives an AUC 0.85. These results demonstrate the data source complementarily and utility of heterogeneous data integration. {#pone-0078518-g004} Comparing with Previous Work {#s3e} ---------------------------- We compared PreDR with previous work in [@pone.0078518-Gottlieb1] since the gold-standard positives used in our study is the same. The authors in [@pone.0078518-Gottlieb1] measured the similarity of the pertaining drug and disease only for the nearest known associated drug-disease pair. Specifically, a simple geometric mean based score is calculated to combine the drug-drug similarity with disease-disease similarity, and the maximal score with the known associated drug-disease pair is extracted as classification feature [@pone.0078518-Gottlieb1]. Differently, we measured similarities among all the drugs and among all the diseases to represent drug and disease, respectively. And then we use kernel function and SVM classifier to train the model. That is, we utilize the global information extracted from drug-disease data in PreDR. To show this advantage, we illustrated one example in [Figure 5A](#pone-0078518-g005){ref-type="fig"}. Here the candidate association between drug and disease (shown as black dash line in [Figure 5A](#pone-0078518-g005){ref-type="fig"}) cannot be inferred directly by the most similar known association (shown as black solid line in [Figure 5A](#pone-0078518-g005){ref-type="fig"}). Because drug 'Eletriptan' is not very similar to drug 'Orphenadrine' (similarity score is 0.367). However our method can utilize the drug 'Benztropine' as a bridge to connect drug 'Eletriptan' and drug 'Orphenadrine'. In this way we can have more confidence to associate candidate drug-disease pair. Because this prediction is achieved by the indirect drug similarity and we call it as 'indirect drug-disease association'. Indeed, more drug-disease associations can be uncovered by PreDR ([Figure 5B](#pone-0078518-g005){ref-type="fig"}). {#pone-0078518-g005} On cross-validation accuracy, the authors in [@pone.0078518-Gottlieb1] had obtained an AUC 0.9 in predicting drug indications. In our study, "Comb" achieves an AUC 0.91, which is nearly the same as the authors obtained in [@pone.0078518-Gottlieb1]. The authors in [@pone.0078518-Gottlieb1] used more data sources to measure the drugs and diseases associations, including GO annotations for target proteins, the genetic based disease similarity from gene expression experiments and so on. Given the fact that we use less data sources, PreDR works well to achieve comparable performance. We note that these data sources can be easily integrated into PreDR. Since our aim here is to demonstrate a useful data integrative analysis framework instead of the most comprehensive and accurate predictions. We only pick one representative data source from the structure, activity, and phenotype levels. Thus we have the sufficient reason to believe that the improvement can be expected by introducing more data for each level. Novel Predictions {#s3f} ----------------- In this subsection, we test whether PreDR can produce biologically useful predictions. To this end, we focus on the unknown (non-interacting) drug-disease pairs. We used kernel "Comb" on the gold standard positives and randomly selected gold standard negatives from the unlabelled pairs, and tested it on the remaining drug-disease pairs. Our expectation is that "Comb" can discover many missing associations. We drew the predicted drug-disease network in [Figure 6](#pone-0078518-g006){ref-type="fig"} (only top 100 newly predicted interactions are shown for conciseness). Take drug 'Hydroxyurea' as an example, disease 'Colorectal Cancer; Crc' is revealed because that the similar drug 'Capecitabine' which shares the same side-effect 'erythema', treats disease 'Colorectal Cancer; Crc' (illustrated in [Figure 7](#pone-0078518-g007){ref-type="fig"}). The top five novel predictions are listed in [Table S2](#pone.0078518.s005){ref-type="supplementary-material"}. For each novel prediction, we checked the drug target proteins form DrugBank [@pone.0078518-Wishart1], the disease genes from OMIM [@pone.0078518-Hamosh1], and the corresponding pathway information from KEGG BRITE [@pone.0078518-Kanehisa1]. Finally, we checked whether novel predictions appear in current clinical trials database (<http://clinicaltrials.gov/>). Take the most confident prediction as an example, target protein 'Endothelin-1 receptor' (EDNRA) for 'Bosentan', and the disease gene 'KCNMB1' (Kca) for 'Hypertension, Diastolic, Resistance To' belong to the same pathway 'Arachidonic Acid metabolism' ([Figure 8](#pone-0078518-g008){ref-type="fig"}). Furthermore, we find that this drug-disease pair appears in current clinical trials, the 'ClinicalTrials.gov Identifier' is NCT00820352. That is, this novel drug-disease association may be true with high probability. {#pone-0078518-g006} {#pone-0078518-g007} {#pone-0078518-g008} The target of 'Hydroxyurea' is 'Ribonucleoside-diphosphate reductase large subunit' (RRM2: p53R2), the disease gene of 'Colorectal Cancer; Crc' is 'TP53' (p53). In addition EDNRA and Kca belong to the same pathway hsa04115 (shown in [Figure 8](#pone-0078518-g008){ref-type="fig"}). Unfortunately, we do not find the evidence of this pair in current clinical trials database. However, the lower pathway distance between disease gene and target already shows the high probability for their association. The target of 'Dasatinib' is 'Tyrosine-protein kinase ABL1' (ABL1: BCRABL), the disease gene of 'Leukemia, Acute Myeloid; Aml' is 'Mast/stem cell growth factor receptor Kit' (KIT). In addition ABL1 and KIT belong to the same pathway hsa05200. Furthermore. this drug disease pair is found the current clinical trials database, the 'ClinicalTrials.gov Identifier' are NCT01392703 and NCT00850382. It means that this novel pair may interact in vivo with high probability. The target of 'Nabumetone' is 'Prostaglandin G/H synthase 2' (PTGS2), the disease gene of 'Sensory Ataxic Neuropathy, Dysarthria, And Ophthalmoparesis; Sando' is 'DNA polymerase subunit gamma-1' (POLG). In addition ABL1 and KIT belong to a same pathway hsa01100. No evidence is found for this pair in clinical trials database. The target of 'Acebutolol' is 'Beta-1 adrenergic receptor' (ADRB1: ADR), the disease gene of 'Alcohol Dependence' is 'Gammaaminobutyric acid receptor subunit alpha-2' (GABRA2: GABR). In addition ABL1 and KIT belong to a same pathway hsa04080 No evidence is found for this pair in current clinical trials database. The lower pathway distance between disease gene and target shows the high probability for their association. Among our top five predictions, two of them are supported by current clinical trials. All these results suggest that, PreDR can uncover potential repositioning of drugs, and can provide candidates for further high-resolution validation. Discussion {#s4} ========== In this paper, we propose a new computational method, PreDR, to predict drug repositioning. PreDR allows us to infer novel associations among drugs and diseases by integrating heterogeneous data sources. Our main contributions here are both in integrating the heterogeneous drug and disease similarity profiles by kernel function and construction of a predictive model. Specifically, we characterize the drug similarity profiles form three levels. Chemical structures, target proteins, and side-effects data are collected to represent structure, activity, and phenotype for drugs. Treating the task as a binary classification problem, we train a SVM-based predictor to uncover unknown interactions between drugs and diseases. The improvement in various evaluation criteria is obtained on a well-established dataset with 1,933 interactions among 593 drugs and 313 diseases. Leave one drug out cross-validations, database search, literature survey, and functional annotation analysis reveal that PreDR provides high quality predictions. For example, among the top five novel predictions, two of them are supported by current clinical trials database. Taken together, PreDR can serve as a useful tool for drug repositioning and promote the further drug discovery. One possible concern is that PreDR works well by those 'trivial' predictions. For example, those drugs sharing common target are easily to be predicted to cure the same diseases. To address this issue, we test our PreDR by filtering out the potential "trivial' predictions. Take target protein as an example, we filter the target proteins with high sequence similarity (0.8). That is, the drugs with high sequence similarity targets (0.8) are excluded from gold standard positives. On this filtered dataset, we validate PreDR's prediction performance. We achieve the AUC 0.754 for "Inter", which is lower than 0.889 obtained by "Inter" on the full gold standard positive dataset, but much higher than 0.5 (random classification). This experiment suggests that PreDR can reveal 'non-trivial' predictions, by fully considering the global and remote similarity in kernel function. In this article, we attempt to improve the performance by integrating target proteins information. The experimental results show that, comparing with chemical structures, the performance is indeed improved by characterizing drugs in target sequence-based similarity. In fact, there are other ways to define the drug similarity based on their targets. For example, target closeness in protein-protein interaction (PPI) network can be used [@pone.0078518-Gottlieb1]. Therefore we take the targets closeness in a human PPI network derived from HPRD (Release 9) to incorporate into PreDR. Unfortunately, the prediction accuracy is worse than sequence-based similarity. This may be due to the high false positive rate and relative low precision of single PPI network. In the future, we will define the targets closeness based on an integrated human PPI networks collected from multiple curated databases, including HPRD [@pone.0078518-KeshavaPrasad1], OPHID [@pone.0078518-Brown1], and BIND [@pone.0078518-Bader1] databases. For disease, we only apply the phenotypic similarity in current study. Studies have shown that phenotypically similar diseases are often caused by functionally related genes [@pone.0078518-Wu3]. In addition, many large-scale studies support the idea that genes sharing similar diseases are tightly linked in the network [@pone.0078518-Fraser1], [@pone.0078518-McGary1]. Therefore, disease genes closeness in a PPI network is useful to correlate disease with candidate genes [@pone.0078518-Wu3]. Apart from gene closeness, genes with similar sequences may be functionally related [@pone.0078518-Whisstock1], [@pone.0078518-Dobson1]. It is promising to use disease gene sequence similarity and closeness in a PPI network to characterize disease. So we applied disease gene sequence similarity and closeness in a human PPI networks to measure the disease similarity, and then extend PreDR. Unfortunately, neither sequence similarity nor closeness in a human PPI networks can achieve better results than phenotype-based similarity (see [Table S3](#pone.0078518.s006){ref-type="supplementary-material"}). The inefficient performance may be due to the fact that the gap between phenotype (disease) and genotype (gene) is too large and the associations are not so accurate. One possible way out is to validate the disease gene based similarity by GO annotation terms, which may closely correlate with the disease similarity. Supporting Information {#s5} ====================== ###### **The distribution of drug similarity scores among the drugs sharing common diseases (Distance is 2 for Drug1 and Drug 2), mediate (Distance is 4 for Drug1 and Drug 2) or unrelated (Distance is 6 for Drug1 and Drug 2), respectively.** [Figure S1](#pone.0078518.s001){ref-type="supplementary-material"} shows that the drugs sharing common disease tend to have higher side-effect similarity comparing with the structure and target protein similarity. (TIF) ###### Click here for additional data file. ###### **The AUPRs derived from different similarity measurements (Chem: chemical structure, Inter: drug target interaction, Side-effect: side-effect based similarity and Comb: integration of Chem, Inter, and Side-effect).** [Figure S2](#pone.0078518.s002){ref-type="supplementary-material"} shows that all chemical structures, target proteins, and side-effects are predictive in drug repositioning prediction, and improved performance can be achieved by integration of them. (TIF) ###### Click here for additional data file. ###### **The precision-recall curves derived from different similarity measurements (chem: chemical structure, inter: drug target interaction, side-effect: side-effect based similarity, and comb: Integration of chem, inter, and side-effect).** [Figure S3](#pone.0078518.s003){ref-type="supplementary-material"} presents, all methods make precision higher than 0.7 when recall value is larger than 0.8, and comb achieves the highest precision with higher recall values. All these results suggest that each data source is predictive and by combination further performance improvement can be obtained. (TIF) ###### Click here for additional data file. ###### **The definitions of evaluation criteria.** [Table S1](#pone.0078518.s004){ref-type="supplementary-material"} lists the evaluation criteria used in this article. Here TP is the number of drug-disease pairs correctly predicted to interact, FP is the number of drug-disease pairs predicted to interact but actually not. And TN is the number of drug-disease pairs do not interact and predicted correctly, FN is the number of drug-disease pairs predicted not to interact but actually interact. (PDF) ###### Click here for additional data file. ###### **The top five drug repositioning predictions by our method.** [Table S2](#pone.0078518.s005){ref-type="supplementary-material"} presents the top five novel predicted drug-disease interactions. (PDF) ###### Click here for additional data file. ###### **The performance comparison of disease gene closeness in a human PPI network under different drug similarity measurements to predict drug repositioning. The best predictions obtained are highlighted in bold.** [Table S3](#pone.0078518.s006){ref-type="supplementary-material"} just lists the performance of disease gene closeness in PPI network due to the fact that disease gene sequence similarity performs worse than its closeness in PPI network. (PDF) ###### Click here for additional data file. The authors would like to thank the editor and reviewers for their thoughtful comments, which greatly improved the clarity of our paper. [^1]: **Competing Interests:**The authors have declared that no competing interests exist. [^2]: Conceived and designed the experiments: YCW YW. Performed the experiments: YCW. Analyzed the data: YCW YW. Contributed reagents/materials/analysis tools: YCW YW SLC NYD. Wrote the paper: YCW YW. Contribution type: SLC NYD.

Child care vouchers - if you have children attending a nursery or looked after by a professional childminder, your employer can join a Childcare voucher scheme. This allows for £55 of the weekly cost to be deducted free of tax and NI if you are a basic tax rate payer, or £28 if you are a higher rate tax payer. Pensions – if you pay into a work pension scheme, 20% tax is automatically deducted. For high rate tax payers, you can claim additional relief either by declaring it on your Self-Assessment or calling the taxman. Company cars – are a pain and the tax is huge BUT if you have a company van, the benefit in kind is capped at £3,000 so for a basic rate tax payer the cost of driving is only £600 or £1,200 for a higher rate payer. Professional membership fees - your membership to a recognised trade or professional body it is a deductible expense, but not for your hobbies. Share incentive schemes - there are loads of schemes that allow either NI or Capital Gains Tax to be saved, you don’t have work for a listed company either. Giving your work colleagues a lift to work - if your employer encourages car pooling you can claim 5p a mile for the passenger without incurring any additional tax charge. Cycle to work - get your employer to provides a bike both for travel to work and play, it’s not considered as a benefit in kind. Then after a time you can buy it off them at market value. Season ticket loans - your company can advance the cost of an annual season ticket up to £5,000, much cheaper than buying a ticket weekly. From April 2014 this increases to £10,000 (not really sure if that’s a blessing?) Electric Cars – from April 2015 there’s no benefit in kind. Working from home – it is becoming increasingly more common for staff to work from home. You can claim £4 a week allowance without having to produce receipts.

Structure and optical properties of silica-supported Ag-Au nanoparticles. Bimetallic Ag-Au nanoparticles are synthesized by sequential deposition of Au and Ag on amorphous silica by Radio Frequency (RF)-sputtering under mild conditions. Specimens are thoroughly characterized by a multi-technique approach, aimed at investigating the system properties as a function of the Ag/Au content, as well as the evolution induced by ex-situ annealing under inert (N2) or reducing (4% H2/N2) atmospheres. The obtained results demonstrate the possibility to obtain Ag-Au alloyed nanoparticles with controllable size, shape, structure, and dispersion under mild conditions, so that the optical properties can be finely tuned as a function of the synthesis and thermal treatment conditions.

What kind of Little are you? Being a Daddy's Little Girl is a precious thing, but not every little girl is the same. Really little girls are like snowflakes, every one is different and that's what makes them so special. :) I couldn't possibly list every type of little girl out there, but here are some of the basic types. The question is, which kind of little girl are you? Created by: Hailey of Tribe (your link here more info)

Telcos See Net Loss in Broadband Users For First Time Say Hello to Your New Cable Broadband Overlords Peter Svensson at the Associated Press notes that phone companies collectively lost broadband subscribers last quarter for the first time ever. According to the AP, the top eight largest phone companies lost a collective 70,000 broadband subscribers on the quarter, while the top four cable operators saw a net gain of 290,000 subscribers. As we've been discussing, AT&T and Verizon no longer much care about residential broadband. They consider these networks too expensive to upgrade and would rather focus on wireless services. That leaves huge chunks of the country on slower DSL services, and even in places where some carriers have upgraded, they've cut corners with fiber-to-the-node services that still leave them in a poor competitive position against cable. The poster children of telco network upgrades, Verizon FiOS and AT&T U-Verse, have also seen frozen expansion and increasingly less emphasis on competing on price. That's great for cable but the result, as Susan Crawford informs the AP, is going to be a cable monopoly in a larger chunk of the country than ever before: quote: Susan Crawford, a professor at Cardozo Law School in New York and a former assistant to President Obama on telecommunications, has argued that a looming cable monopoly in three-quarters of the country is "the central crisis of our communications era." She suggests that the U.S. follow the example of countries that have forced cable providers to allow other companies provide Internet service over their cables. The service-providers would compete with each other and provide some choice to the consumer, she says. There are of course a smattering of smaller, more rural-focused telcos (Windstream, Frontier, Fairpoint, CenturyLink), but like their larger incumbent brothers, investor pressure has them treating network upgrades as some kind of disease, leaving them incapable of adequately competing with cable services and speeds. Fortunately for them, most of them operate in uncompetitive markets where they can jack up costs and skimp on improvements as they see fit. Unfortunately for you, a stronger cable monopoly means an even less competitive market than we've had. A less competitive market means even higher prices and lower-quality service -- a major problem given that by nearly every objective metric (speed, price, penetration) the United States was already There are of course a smattering of smaller, more rural-focused telcos (Windstream, Frontier, Fairpoint, CenturyLink), but like their larger incumbent brothers, investor pressure has them treating network upgrades as some kind of disease, leaving them incapable of adequately competing with cable services and speeds. Fortunately for them, most of them operate in uncompetitive markets where they can jack up costs and skimp on improvements as they see fit. Unfortunately for you, a stronger cable monopoly means an even less competitive market than we've had. A less competitive market means even higher prices and lower-quality service -- a major problem given that by nearly every objective metric (speed, price, penetration) the United States was already thoroughly average to begin with. News Jump Stark New Reality In The Telco Business: Dumb Pipes No Longer Cut It; AT&T Unveils Mix and Match Plans; + more news AT&T Extends Overage Charge Waiver; Verizon And T-Mobile Each Insist Their 5G Strategy Is The Right One; + more news War Of Words Heats Up: T-Mobile Fires Back At Verizon, AT&T; Amazon Intros Gaming Service To Take On Stadia; + more news Starlink's Network Faces Huge Limitations; AT&T Whines T-Mobile Merger Put Too Much Spectrum In One Place; + more news WISPs Get CBRS Range As Great As Six Miles At 100 Mbps Speeds; Windstream Officially Exits Bankruptcy; + more news Charter Relaunches Free 60-day Internet And Wi-Fi Offer; NCTA: FCC Should Stick With 25/3 Speed Threshold; + more news Comcast Shuts Off Internet for Subs Who Were Sold Service Illegally; AT&T, Verizon Team To Stop T-Mobile 5G; + more news California Defends Its Net Neutrality Law; AT&T's Traffic Up 20% Despite Data Traffic Actually Being Down; + more news Are The Comcast-Charter X1 Talks Dead In The Water?; AT&T May Offer Phone Plans With Ads For Discounts; + more news Europe's Top Court: Net Neutrality Rules Bar Zero Rating; ViacomCBS To Rebrand CBS All Access As Paramount+; + more news ---------------------- this week last week most discussed view: topics flat nest IowaCowboy Supermarket Hero Premium Member join:2010-10-16 Springfield, MA ARRIS SB6183 Netgear R8000 1 recommendation IowaCowboy Premium Member Cable is the only viable option Where I live (Springfield, MA), Comcast is the only viable option as the only other options are DSL (becoming the new dial-up), Verizon LTE HomeFusion (expensive with low caps) and the satellite providers (high latency with plenty of throttling and expensive). Comcast Internet is decent except when there is a problem as getting them to fix anything is just like pulling teeth. antdude ANTh Vader Premium Member join:2001-03-25 US antdude Premium Member Re: Cable is the only viable option Same for me in two cities. Both are Verizon and have no DSL and FIOS even though they exist, just not in those neighborhoods. baineschile 2600 ways to live Premium Member join:2008-05-10 Sterling Heights, MI 1 recommendation baineschile Premium Member Clarify ATT and VZ do care about residential broadband, but only with their UVerse and FIOS products. That being said, i feel like the cable guys have double the speeds every 2 years for the last decade, and that trend seems to be continuing. Dominokat "Hi" Premium Member join:2002-08-06 Boothbay, ME Dominokat Premium Member Re: Clarify said by baineschile: ...i feel like the cable guys have double the speeds every 2 years for the last decade, and that trend seems to be continuing. I am able to get 15/1 from DSL. For the same price as 20/2 from Time Warner. And the price. Not literally "double" but they keep raising the price, even though the cost for byte (to them) keep falling.I am able to get 15/1 from DSL. For the same price as 20/2 from Time Warner. Os join:2011-01-26 US Os to baineschile Member to baineschile How many places does Verizon want to lay FiOS? That's the problem. This is why we have caps and overages, not because of network congestion, but because there's nothing stopping the cable companies from just gouging their customers. Where will they go? The internet is basically crippled on DSL. Crookshanks join:2008-02-04 Binghamton, NY Crookshanks Member Re: Clarify said by Os: Where will they go? The internet is basically crippled on DSL. Yeah, the sheer horror, browsing the internet at a lousy 1.5mbit/s to 3.0mbit/s! JasonOD @comcast.net JasonOD Anon Predictable So what did you expect the telco's do? They can't magically rewire everyone to something more robust than copper, and can't suspend the laws of DSL delivered physics. In short, they're stuck with an obsolete technology that can't compete with cable. And face it, fibre, or FIOS is just too expensive right now. Despite google's tiny subsidized 'experiment', FTTH is not a viable option in the US. Putting their eggs in wireless is the only smart choice they have. tanzam75 join:2012-07-19 tanzam75 Member Re: Predictable The telcos simply fell victim to digital communications, which allowed Triple Play services to be offered over the same line. A historical accident left them with a lower-capacity network than their competitor. So they found themselves in an overbuild situation to remain competitive. But in this overbuild situation, the cable companies were the incumbent, and the telcos were the challenger. That's not a good position to be in. If your competitor gets to use their existing plant, and you have to build a brand-new one from scratch, then you'll be at a severe cost disadvantage. The only way this situation could turn around is if bandwidth demands exceeded the carrying capacity of coax, such that fiber-to-the-premises became a necessity. Then the odds would be evened, and neither party would have an advantage. (Well, not the only way. There could be government intervention. China Telecom and China Unicom are in the middle of a project to replace their entire copper networks with fiber. Their current target is one HUNDRED million homes passed, each, by the end of the current Five-Year Plan: 2011-2015. But, well, that's socialism, and we can't have that.) buzz_4_20 join:2003-09-20 Biddeford, ME (Software) Sophos UTM Home Edition Ruckus R310 buzz_4_20 Member Network Design. DSL can't compete on Speed or availability, and Telco's don't seem to be doing much to expand offerings. I Love my DSL but Time Warner offers 50/5 in my area now. Sooner or later I'll end up switching just to have the higher speed. Wireless may be the future of profits, but Fiber is an investment that should be made at least NEAR peoples homes. With fiber at their disposal the Telco would never have to worry about cable being faster. YukonHawk join:2001-01-07 Patterson, NY YukonHawk Member FIOS is DEAD! Verizon and AT&T have shot themselves in the foot!!!! They were stupid for not expanding further! Corporate Bean counter idiots! N3OGH Yo Soy Col. "Bat" Guano Premium Member join:2003-11-11 Philly burbs N3OGH Premium Member Re: FIOS is DEAD! Perhaps Fios EXPANSION is dead. Fios is alive & well and bringing me the intertubes on a daily basis. Verizon & AT&T built their next generation plants out to the areas they chose to serve probably based mostly on economics & market research. They have no desire to expand. Verizon would rather focus on their more profitable non union wireless division than deal with their rickety old copper plant decifal join:2007-03-10 Bon Aqua, TN decifal Member Re: FIOS is DEAD! That maybe so, but your not going to expand subscribers by simply not upgrading more areas that are under your footprint.. sure you can have the best service around, but if people with "no" service options cannot subscribe then your losing potential income.. If the current landline division isn't profitable, figure out how to make it so.. Either by selling it, or leasing it, or redoing it all together.. Just letting a huge chunk of people go unserviced is irresponsible.. And no, i'm not talking about the areas where you drive 15 miles and see only one house.. There are many many many places undeserved where the potential for adding subscribers is very high as they would be the only provider in the area... I don't get comcast/att's math.. I've heard comcast wants 12 house's per mile before building out.. Yet we now have over 125 homes right on the road for 3.8 miles.. Do we have services? No.. Neither att or comcast have yet to bother.. Keep in mind these are homes right on the main stretch here, there are many branch off roads with many many more house's.. Yet this area is just a black hole for broadband for some reason.. I've seen VRADS and cable ran out to practically the middle of nowhere just to service one house.. There was absolutely nothing else in the whole area..... It just doesn't make sense... WhatNow Premium Member join:2009-05-06 Charlotte, NC WhatNow Premium Member Re: FIOS is DEAD! AT&T placed vrads where there was a fiber feed first. in some cases the neighborhoods the local elected officials live in were a prime choice. From what I have seen income was not the driving factor. PastTense join:2011-07-06 united state PastTense Member Predictions for the Future? So how does everyone see the situation in 5, 10, 20 years? Will it just be wireless and cable--with the landlines dead? Or will fiber take off (and who will provide this fiber: the Telcos or Google or ....? Os join:2011-01-26 US Os Member Re: Predictions for the Future? I don't see anyone laying fiber without government intervention. Punitive caps and high costs on both cable and wireless will all but stifle technological development, and the world will laugh as they leave us in the dust and take our tech jobs. elray join:2000-12-16 Santa Monica, CA elray Member Re: Predictions for the Future? said by Os: I don't see anyone laying fiber without government intervention. Punitive caps and high costs on both cable and wireless will all but stifle technological development, and the world will laugh as they leave us in the dust and take our tech jobs. Caps are rarely "punitive", and cable broadband is not expensive. Neither will "stifle" development of any kind. Utter nonsense.Caps are rarely "punitive", and cable broadband is not expensive.Neither will "stifle" development of any kind. Os join:2011-01-26 US Os Member Re: Predictions for the Future? $30 for unlimited data to $50 for 1GB is not punitive? What incentive does cable not have to rip people off when they're the only game in town? That is what is coming. You can't have a natural monopoly without regulation, the end result without that is massive inefficiency and terrible service at high prices. elray join:2000-12-16 Santa Monica, CA elray Member Re: Predictions for the Future? $30 for unlimited wireless broadband - was never unlimited, as we witnessed time and again with the rush to saturation. Where are you forced to pay $50 for 1GB? Please, dispense with the hyperbole. Given the right circumstances, you're correct, any last-mile entity could find itself able to set pricing if they truly fear no competition, i.e. Frontier. But those situations are the rare exception, not the rule, and the margins are that fat, they will invite a competitor. In our case, we have but one wired broadband option, but the de facto monopoly provider isn't sophisticated enough to know they have us, so their rates reflect the potential of nearby competitors. I've always agreed with your assertion - the last mile is a natural monopoly, and therefore would be best served by a regulated entity. But that isn't on the table; instead, we have the socialists rallying for yet another expansion of government, which would yield the highest rates of all. A newly re-regulated monopoly would assure that wired "universal service" could be delivered to 95% of the country, and for the 5% beyond reasonable reach of cabling, we could have a reasonable fixed-LTE tariff - not unlimited, but generous enough to retire satellite service. sparc join:2006-05-06 sparc Member Why is uverse so expensive to implement? There are plenty of large sized urban AT&T communities without uverse. I just don't get why the costs are that outrageous. It's not like they have to dig up people's yards to get fiber to the home. Despite what you may feel about fiber to the node, it is at least better than the current reality with AT&T dsl. This whole system is just so broken. The government is nowhere to be seen and is about to rubber stamp yet another uncompetitive deal with Verizon and the cable companies. I'm at the point where I think AT&T and Verizon should be forced to spin off their entire landline business. It really just puts everything into perspective that these Telcos are letting everything else die in favor of AT&T Wireless and Verizon Wireless. knighttoday @pdx.net knighttoday Anon leaving DSL I left my DSl service for Comcast a year ago and I did not want to make that move. Sure DSL is slower but it worked for me. I left because of the absolutely crappy service Qwest/Century Link offered. Sure Comcast is just as bad but at least I am getting higher bandwidth for the same cost. Too bad these large companies simply miss Customer Service as something to sell besides high speeds. I'd gladly take slower bandwidth for high end customer service. majortom1029 join:2006-10-19 Medford, NY 1 recommendation majortom1029 Member hmm They have only have themselves to blame. I live on long island and Verizon will not finish their fios rollout. It has nothing to do with money since most of long island is middle class. I cannot get dsl or satellite and I can only get cablevision tv and internet. Chubbysumo join:2009-12-01 Duluth, MN Chubbysumo Member there is only so many houses to hook up so, at one point, it will be nothing but churn, as people jump from 1 uncompetitive ISP to the next. Lets just hope by then, that there has been some regulation to improve competing based on prices. nonamesleft join:2011-11-07 Manitowoc, WI nonamesleft Member They purposely left the lines degrade. Letting the lines degrade on purpose, then whining that they are losing customers. I have had Dsl 4 different times, most of the time the problem was the signal fluctuated constantly. Fix the damn line problems and they will come back! When dsl works it was perfectly fine, lowest latency I have ever seen when it stays synced up. a333 A hot cup of integrals please join:2007-06-12 Rego Park, NY a333 Member Re: They purposely left the lines degrade. Gotta say I agree with that... only on a 1 Mbps DSL plan here, but FastPath + short loop length + underground utilities means I have NEVER had a single case of dropped sync, and latency (almost always 8-10 ms to the DSLAM) and jitter (pretty close to 0) make the connection "feel" so much better than even my phone on T-mobile despite it having something like 3 - 5 times the bandwidth most of the time. tmc8080 join:2004-04-24 Brooklyn, NY tmc8080 Member looped recording.. add to that the lust for profits similar to oil companies in wireless and you have the makings of an abandonment of even the competitive chunk of wireline too! AT&T made out like a bandit acquiring Bell South and then stopped u-verse dead in it's tracks... WTF?!? Wasn't that a condition of the merger? That major cities in the southern USA would be upgraded to u-verse, with is a piss-poor dsl technology? It would be nice if they saw the wisdom of changing over to FTTP, but they actually plan on doing NOTHING with wireline and will pursue wireless at ALL costs.. The public interest is being neglected for years, so the question is how long will the federal government let this go on for? How many lines will AT&T, Comcast and Verizon have to cross before more federal action takes place in telecom? remember how broken records loop a few seconds of recorded audio/music.. well, that's basicaly what you have for telecom competition in much of the country..add to that the lust for profits similar to oil companies in wireless and you have the makings of an abandonment of even the competitive chunk of wireline too!AT&T made out like a bandit acquiring Bell South and then stopped u-verse dead in it's tracks... WTF?!? Wasn't that a condition of the merger? That major cities in the southern USA would be upgraded to u-verse, with is a piss-poor dsl technology? It would be nice if they saw the wisdom of changing over to FTTP, but they actually plan on doing NOTHING with wireline and will pursue wireless at ALL costs..The public interest is being neglected for years, so the question is how long will the federal government let this go on for?How many lines will AT&T, Comcast and Verizon have to cross before more federal action takes place in telecom? »www.youtube.com/watch?v= ··· As71knV8 tanzam75 join:2012-07-19 tanzam75 Member Re: looped recording.. said by tmc8080: AT&T made out like a bandit acquiring Bell South and then stopped u-verse dead in it's tracks... WTF?!? Wasn't that a condition of the merger? BellSouth was acquired in 2006. U-verse deployment did not begin until 2008. Was it?BellSouth was acquired in 2006. U-verse deployment did not begin until 2008. tmc8080 join:2004-04-24 Brooklyn, NY tmc8080 Member Re: looped recording.. said by tanzam75: said by tmc8080: AT&T made out like a bandit acquiring Bell South and then stopped u-verse dead in it's tracks... WTF?!? Wasn't that a condition of the merger? BellSouth was acquired in 2006. U-verse deployment did not begin until 2008. Was it?BellSouth was acquired in 2006. U-verse deployment did not begin until 2008. Deployment was in the works in Bell South pre-merger to deploy a combination of FTTP and DSL where market demand met each ROI goal (ie numbers of customer interest). AT&T had very little interest in FTTP for residential use from the very beginning, but it looked good in the press release. So-called greenfield builds are a vaporware way of promising the moon and delivering a paper moon. Docsis 2.0 was freshly minted capable of 30 (spec'd for 42 down) megabits.. paltry 8 megabit DSL was no longer adequate. ARGONAUT Have a nice day. Premium Member join:2006-01-24 New Albany, IN ARGONAUT Premium Member > Cable companies know they have you. fiber_man Things Happen For A Reason Premium Member join:2001-01-27 Port Saint Lucie, FL fiber_man Premium Member regulation thank Judge Greene for this mess he started in 1984. things were a lot better when the government had oversight of these companies. tanzam75 join:2012-07-19 tanzam75 Member Re: regulation said by fiber_man: thank Judge Greene for this mess he started in 1984. things were a lot better when the government had oversight of these companies. The Bell System myth of uniform excellence in service is exactly that -- a myth. Some Bell operating companies were better than others, and some areas were better-served than others. In 1984, you could find areas with electronic switching and private lines to every household. You could also find areas -- in Bell territory, not at some tiny independent rural telecom -- that had party lines and crossbar switching systems. For example, Pacific Bell was one of the more neglected companies in the Bell System. The California public-utilities commission had a highly adversarial relationship with Pacific Bell, so Ma Bell preferred to direct its money towards friendlier locales. California became the neglected stepchild of the Bell System, where they did the minimum that they could get away with. In other words, the golden days of the regulated past are hardly the panancea that they're made out to be. A public utilities commission had limited ability to force upgrades. They can force maintenance, but they cannot force upgrades. This would solve the problem of "Our phones have crosstalk, and our DSL keeps losing sync -- why won't they fix the rotting copper?" It would not solve the problem of "We have no cable, the DSL maxes out at 1 Mbps, and nobody is willing to build fiber-to-the-premises." It's easy to look back with rose-colored glasses, and remember only the good stuff.The Bell System myth of uniform excellence in service is exactly that -- a myth. Some Bell operating companies were better than others, and some areas were better-served than others. In 1984, you could find areas with electronic switching and private lines to every household. You could also find areas -- in Bell territory, not at some tiny independent rural telecom -- that had party lines and crossbar switching systems.For example, Pacific Bell was one of the more neglected companies in the Bell System. The California public-utilities commission had a highly adversarial relationship with Pacific Bell, so Ma Bell preferred to direct its money towards friendlier locales. California became the neglected stepchild of the Bell System, where they did the minimum that they could get away with.In other words, the golden days of the regulated past are hardly the panancea that they're made out to be. A public utilities commission had limited ability to force upgrades. They can force maintenance, but they cannot force upgrades.This would solve the problem of "Our phones have crosstalk, and our DSL keeps losing sync -- why won't they fix the rotting copper?" It would not solve the problem of "We have no cable, the DSL maxes out at 1 Mbps, and nobody is willing to build fiber-to-the-premises." BewareofDoug join:2001-08-07 Englewood, CO BewareofDoug Member I'm one of those who just went the other way I just switch from Comcast to CenturyLink/Qwest, and got an upgraded internet connection. I had 25/5(?) with Comcast, now have VDSL2 at 40/20. When I had Qwest in the past, virtually all of my problems were related to house wiring as the source. Does the average person need more than 40/20 at this point? Not in my view, but I suppose in a large household with lots of gaming and video streaming. But with myself and 3 boys mid-teens to early 20s, it's plenty. But I understand 40/20 is the exception for Telcos. Up until the last month or so, 7M DSL was the limit for my house. your comment..

module App.Section.Demo exposing ( Model , Msg , init , update , view , subscriptions , routeChanged ) {-| The main demo component. Handles the demo section routing. -} import Html exposing (Html, section, h1, p, text) import App.Section.Demo.Route exposing (Route(..)) type Model = Model { routeModel : Route } type Msg = RouteChanged Route routeChanged : Route -> Msg routeChanged route = RouteChanged route init : Route -> ( Model, Cmd Msg ) init route = ( Model { routeModel = route } , Cmd.none ) update : Msg -> Model -> ( Model, Cmd Msg ) update msg (Model model) = case msg of RouteChanged route -> ( Model { model | routeModel = route } , Cmd.none ) view : Model -> Html Msg view (Model model) = case model.routeModel of DemoRoute -> section [] [ h1 [] [ text "Demo Overview" ] , p [] [ text "An overview of all demo pages will go here." ] ] AccordionDemoRoute -> section [] [ h1 [] [ text "Accordion Demo" ] , p [] [ text "An accordion component demo will go here." ] ] CheckboxDemoRoute -> section [] [ h1 [] [ text "Checkbox Demo" ] , p [] [ text "A checkbox demo will go here." ] ] OtherDemoRoute -> section [] [ h1 [] [ text "Other Demo" ] , p [] [ text "Some other demo will go here." ] ] subscriptions : Model -> Sub Msg subscriptions (Model model) = Sub.none

45th United States Congress The Forty-fifth United States Congress was a meeting of the legislative branch of the United States federal government, consisting of the United States Senate and the United States House of Representatives. It met in Washington, D.C. from March 4, 1877, to March 4, 1879, during the first two years of Rutherford Hayes's presidency. The apportionment of seats in the House of Representatives was based on the Ninth Census of the United States in 1870. The Senate had a Republican majority, and the House had a Democratic majority. The 45th Congress remained politically divided between a Democratic House and Republican Senate. President Hayes vetoed an Army appropriations bill from the House which would have ended Reconstruction and prohibited the use of federal troops to protect polling stations in the former Confederacy. Striking back, Congress overrode another of Hayes’s vetoes and enacted the Bland-Allison Act that required the purchase and coining of silver. Congress also approved a generous increase in pension eligibility for Northern Civil War veterans. Major events March 4, 1877: Rutherford B. Hayes became President of the United States Major legislation February 28, 1878: Bland–Allison Act (Coinage Act (Silver Dollar)), Sess. 2, ch. 20, April 29, 1878: National Quarantine Act, Sess. 2, ch. 66, June 3, 1878: Timber and Stone Act, Sess. 2, ch. 151, June 18, 1878: Posse Comitatus Act, Sess. 2, ch. 263, §15, Party summary The count below identifies party affiliations at the beginning of the first session of this Congress, and includes members from vacancies and newly admitted states, when they were first seated. Changes resulting from subsequent replacements are shown below in the "Changes in membership" section. During this Congress, two Senate seats and one House seat were added for the new state, Colorado. Senate House of Representatives Leadership Senate President: William A. Wheeler (R) President pro tempore: Thomas W. Ferry (R) Republican Conference Chairman: Henry B. Anthony Democratic Caucus Chairman: William A. Wallace House of Representatives Speaker: Samuel J. Randall (D) Democratic Caucus Chairman: Hiester Clymer Republican Conference Chair: Eugene Hale Democratic Campaign Committee Chairman: Joseph Clay Stiles Blackburn Members This list is arranged by chamber, then by state. Senators are listed in order of seniority, and Representatives are listed by district. Senate Senators were elected by the state legislatures every two years, with one-third beginning new six-year terms with each Congress. Preceding the names in the list below are Senate class numbers, which indicate the cycle of their election. In this Congress, Class 1 meant their term began in the last Congress, requiring reelection in 1880; Class 2 meant their term began in this Congress, requiring reelection in 1882; and Class 3 meant their term ended in this Congress, requiring reelection in 1878. Skip to House of Representatives, below Alabama 3. George E. Spencer (R) 2. John T. Morgan (D) Arkansas 3. Stephen W. Dorsey (R) 2. Augustus H. Garland (D) California 3. Aaron A. Sargent (R) 1. Newton Booth (AM) Colorado 3. Jerome B. Chaffee (R) 2. Henry M. Teller (R) Connecticut 1. William W. Eaton (D) 3. William H. Barnum (D) Delaware 1. Thomas F. Bayard, Sr. (D) 2. Eli M. Saulsbury (D) Florida 3. Simon B. Conover (R) 1. Charles W. Jones (D) Georgia 3. John B. Gordon (D) 2. Benjamin H. Hill (D) Illinois 3. Richard J. Oglesby (R) 2. David Davis (I) Indiana 3. Oliver H. P. T. Morton (R), until November 1, 1877 Daniel W. Voorhees (D), from November 6, 1877 1. Joseph E. McDonald (D) Iowa 3. William B. Allison (R) 2. Samuel J. Kirkwood (R) Kansas 3. John J. Ingalls (R) 2. Preston B. Plumb (R) Kentucky 3. Thomas C. McCreery (D) 2. James B. Beck (D) Louisiana 3. James B. Eustis (D) 2. William Pitt Kellogg (R) Maine 1. Hannibal Hamlin (R) 2. James G. Blaine (R) Maryland 3. George R. Dennis (D) 1. William Pinkney Whyte (D) Massachusetts 1. Henry L. Dawes (R) 2. George F. Hoar (R) Michigan 2. Thomas W. Ferry (R) 1. Isaac P. Christiancy (R), until February 10, 1879 Zachariah Chandler (R), from February 22, 1879 Minnesota 2. William Windom (R) 1. Samuel J. R. McMillan (R) Mississippi 1. Blanche Bruce (R) 2. Lucius Q. C. Lamar (D) Missouri 3. Lewis V. Bogy (D), until September 20, 1877 David H. Armstrong (D), September 29, 1877 - January 26, 1879 James Shields (D), from January 27, 1879 1. Francis Cockrell (D) Nebraska 1. Algernon Paddock (R) 2. Alvin Saunders (R) Nevada 3. John P. Jones (R) 1. William Sharon (R) New Hampshire 3. Bainbridge Wadleigh (R) 2. Edward H. Rollins (R) New Jersey 1. Theodore F. Randolph (D) 2. John R. McPherson (D) New York 3. Roscoe Conkling (R) 1. Francis Kernan (D) North Carolina 2. Matt W. Ransom (D) 3. Augustus S. Merrimon (D) Ohio 3. John Sherman (R), until March 8, 1877 Stanley Matthews (R), from March 21, 1877 1. Allen G. Thurman (D) Oregon 3. John H. Mitchell (R) 2. La Fayette Grover (D) Pennsylvania 3. Simon Cameron (R), until March 12, 1877 J. Donald Cameron (R), from March 20, 1877 1. William A. Wallace (D) Rhode Island 2. Henry B. Anthony (R) 1. Ambrose Burnside (R) South Carolina 3. John J. Patterson (R) 2. Matthew Butler (D) Tennessee 1. James E. Bailey (D) 2. Isham G. Harris (D) Texas 1. Samuel B. Maxey (D) 2. Richard Coke (D) Vermont 1. George F. Edmunds (R) 3. Justin S. Morrill (R) Virginia 2. John W. Johnston (D) 1. Robert E. Withers (D) West Virginia 2. Henry G. Davis (D) 1. Frank Hereford (D) Wisconsin 3. Timothy O. Howe (R) 1. Angus Cameron (R) House of Representatives The names of members of the House of Representatives are preceded by their district numbers. Alabama (8 Democrats) . James T. Jones (D) . Hilary A. Herbert (D) . Jeremiah N. Williams (D) . Charles M. Shelley (D) . Robert F. Ligon (D) . Goldsmith W. Hewitt (D) . William H. Forney (D) . William W. Garth (D) Arkansas (4 Democrats) . Lucien C. Gause (D) . William F. Slemons (D) . Jordan E. Cravens (ID) . Thomas M. Gunter (D) California (3-1 Republican) . Horace Davis (R) . Horace F. Page (R) . John K. Luttrell (D) . Romualdo Pacheco (R), until February 7, 1878 Peter D. Wigginton (D), from February 7, 1878 Colorado (1 Republican) . James B. Belford (R), until December 13, 1877 Thomas M. Patterson (D), from December 13, 1877 Connecticut (3-1 Democratic) . George M. Landers (D) . James Phelps (D) . John T. Wait (R) . Levi Warner (D) Delaware (1 Democrat) . James Williams (D) Florida (1-1 split) . Robert H. M. Davidson (D) . Horatio Bisbee, Jr. (R), until February 20, 1879 Jesse J. Finley (D), from February 20, 1879 Georgia (9 Democrats) . Julian Hartridge (D), until January 8, 1879 William B. Fleming (D), from February 10, 1879 . William E. Smith (D) . Philip Cook (D) . Henry R. Harris (D) . Milton A. Candler (D) . James H. Blount (D) . William H. Felton (ID) . Alexander Stephens (D) . Hiram P. Bell (D), from March 13, 1877 Illinois (11-8 Republican) . William Aldrich (R) . Carter H. Harrison (D) . Lorenzo Brentano (R) . William Lathrop (R) . Horatio C. Burchard (R) . Thomas J. Henderson (R) . Philip C. Hayes (R) . Greenbury L. Fort (R) . Thomas A. Boyd (R) . Benjamin F. Marsh (R) . Robert M. Knapp (D) . William M. Springer (D) . Thomas F. Tipton (R) . Joseph G. Cannon (R) . John R. Eden (D) . William A. J. Sparks (D) . William R. Morrison (D) . William Hartzell (D) . Richard W. Townshend (D) Indiana (9-4 Republican) . Benoni S. Fuller (D) . Thomas R. Cobb (D) . George A. Bicknell (D) . Leonidas Sexton (R) . Thomas M. Browne (R) . Milton S. Robinson (R) . John Hanna (R) . Morton C. Hunter (R) . Michael D. White (R) . William H. Calkins (R) . James L. Evans (R) . Andrew H. Hamilton (D) . John H. Baker (R) Iowa (9 Republicans) . Joseph C. Stone (R) . Hiram Price (R) . Theodore W. Burdick (R) . Nathaniel C. Deering (R) . Rush Clark (R) . Ezekiel S. Sampson (R) . Henry J. B. Cummings (R) . William F. Sapp (R) . S. Addison Oliver (R) Kansas (3 Republicans) . William A. Phillips (R) . Dudley C. Haskell (R) . Thomas Ryan (R) Kentucky (10 Democrats) . Andrew Boone (D) . James A. McKenzie (D) . John William Caldwell (D) . J. Proctor Knott (D) . Albert S. Willis (D) . John G. Carlisle (D) . Joseph C. S. Blackburn (D) . Milton J. Durham (D) . Thomas Turner (D) . John B. Clarke (D) Louisiana (4-2 Democratic) . Randall L. Gibson (D) . E. John Ellis (D) . Chester B. Darrall (R), until February 20, 1878 Joseph H. Acklen (D), from February 20, 1878 . Joseph B. Elam (D) . John E. Leonard (R), until March 15, 1878 John S. Young (D), from November 5, 1878 . Edward W. Robertson (D) Maine (5 Republicans) . Thomas B. Reed (R) . William P. Frye (R) . Stephen D. Lindsey (R) . Llewellyn Powers (R) . Eugene Hale (R) Maryland (6 Democrats) . Daniel M. Henry (D) . Charles B. Roberts (D) . William Kimmel (D) . Thomas Swann (D) . Eli J. Henkle (D) . William Walsh (D) Massachusetts (10-1 Republican) . William W. Crapo (R) . Benjamin W. Harris (R) . Walbridge A. Field (R), until March 28, 1878 Benjamin Dean (D), from March 28, 1878 . Leopold Morse (D) . Nathaniel P. Banks (R) . George B. Loring (R) . Benjamin F. Butler (R) . William Claflin (R) . William W. Rice (R) . Amasa Norcross (R) . George D. Robinson (R) Michigan (8-1 Republican) . Alpheus S. Williams (D), until December 21, 1878 . Edwin Willits (R) . Jonas H. McGowan (R) . Edwin W. Keightley (R) . John W. Stone (R) . Mark S. Brewer (R) . Omar D. Conger (R) . Charles C. Ellsworth (R) . Jay A. Hubbell (R) Minnesota (3 Republicans) . Mark H. Dunnell (R) . Horace B. Strait (R) . Jacob H. Stewart (R) Mississippi (6 Democrats) . Henry L. Muldrow (D) . Vannoy H. Manning (D) . Hernando Money (D) . Otho R. Singleton (D) . Charles E. Hooker (D) . James R. Chalmers (D) Missouri (9-4 Democratic) . Anthony F. Ittner (R) . Nathan Cole (R) . Lyne S. Metcalfe (R) . Robert A. Hatcher (D) . Richard P. Bland (D) . Charles H. Morgan (D) . Thomas T. Crittenden (D) . Benjamin J. Franklin (D) . David Rea (D) . Henry M. Pollard (R) . John B. Clark, Jr. (D) . John M. Glover (D) . Aylett H. Buckner (D) Nebraska (2 Republicans) . Frank Welch (R), until September 4, 1878 Thomas J. Majors (R), from November 5, 1878 Nevada (1 Republican) . Thomas Wren (R) New Hampshire (2-1 Republican) . Frank Jones (D) . James F. Briggs (R) . Henry W. Blair (R) New Jersey (4-3 Democrat) . Clement H. Sinnickson (R) . John H. Pugh (R) . Miles Ross (D) . Alvah A. Clark (D) . Augustus W. Cutler (D) . Thomas B. Peddie (R) . Augustus A. Hardenbergh (D) New York (17-16 Republican) . James W. Covert (D) . William D. Veeder (D) . Simeon B. Chittenden (R) . Archibald M. Bliss (D) . Nicholas Muller (D) . Samuel S. Cox (D) . Anthony Eickhoff (D) . Anson G. McCook (R) . Fernando Wood (D) . Abram S. Hewitt (D) . Benjamin A. Willis (D) . Clarkson N. Potter (D) . John H. Ketcham (R) . George M. Beebe (D) . Stephen L. Mayham (D) . Terence J. Quinn (D), until June 18, 1878 John M. Bailey (R), from November 5, 1878 . Martin I. Townsend (R) . Andrew Williams (R) . Amaziah B. James (R) . John H. Starin (R) . Solomon Bundy (R) . George A. Bagley (R) . William J. Bacon (R) . William H. Baker (R) . Frank Hiscock (R) . John H. Camp (R) . Elbridge G. Lapham (R) . Jeremiah W. Dwight (R) . John N. Hungerford (R) . E. Kirke Hart (D) . Charles B. Benedict (D) . Daniel N. Lockwood (D) . George W. Patterson (R) North Carolina (7-1 Democratic) . Jesse J. Yeates (D) . Curtis H. Brogden (R) . Alfred M. Waddell (D) . Joseph J. Davis (D) . Alfred M. Scales (D) . Walter L. Steele (D) . William M. Robbins (D) . Robert B. Vance (D) Ohio (12-8 Republican) . Milton Sayler (D) . Henry B. Banning (D) . Mills Gardner (R) . John A. McMahon (D) . Americus V. Rice (D) . Jacob D. Cox (R) . Henry L. Dickey (D) . J. Warren Keifer (R) . John S. Jones (R) . Charles Foster (R) . Henry S. Neal (R) . Thomas Ewing, Jr. (D) . Milton I. Southard (D) . Ebenezer B. Finley (D) . Nelson H. Van Vorhes (R) . Lorenzo Danford (R) . William McKinley, Jr. (R) . James Monroe (R) . James A. Garfield (R) . Amos Townsend (R) Oregon (1 Republican) . Richard Williams (R) Pennsylvania (17-10 Republican) . Chapman Freeman (R) . Charles O'Neill (R) . Samuel J. Randall (D) . William D. Kelley (R) . Alfred C. Harmer (R) . William Ward (R) . I. Newton Evans (R) . Hiester Clymer (D) . A. Herr Smith (R) . Samuel A. Bridges (D) . Francis D. Collins (D) . Hendrick B. Wright (D) . James B. Reilly (D) . John W. Killinger (R) . Edward Overton, Jr. (R) . John I. Mitchell (R) . Jacob M. Campbell (R) . William Stenger (D) . Levi Maish (D) . Levi A. Mackey (D) . Jacob Turney (D) . Russell Errett (R) . Thomas M. Bayne (R) . William S. Shallenberger (R) . Harry White (R) . John M. Thompson (R) . Lewis F. Watson (R) Rhode Island (2 Republicans) . Benjamin T. Eames (R) . Latimer W. Ballou (R) South Carolina (3-2 Republican) . Joseph Rainey (R) . Richard H. Cain (R) . D. Wyatt Aiken (D) . John H. Evins (D) . Robert Smalls (R) Tennessee (8-2 Democratic) . James H. Randolph (R) . Jacob M. Thornburgh (R) . George G. Dibrell (D) . Haywood Y. Riddle (D) . John M. Bright (D) . John F. House (D) . Washington C. Whitthorne (D) . John D. C. Atkins (D) . William P. Caldwell (D) . H. Casey Young (D) Texas (6 Democrats) . John H. Reagan (D) . David B. Culberson (D) . James W. Throckmorton (D) . Roger Q. Mills (D) . De Witt C. Giddings (D) . Gustave Schleicher (D), until January 10, 1879 Vermont (3 Republicans) . Charles H. Joyce (R) . Dudley C. Denison (R) . George W. Hendee (R) Virginia (8-1 Democratic) . Beverly B. Douglas (D), until December 22, 1878 Richard Lee T. Beale (D), from January 23, 1879 . John Goode, Jr. (D) . Gilbert C. Walker (D) . Joseph Jorgensen (R) . George Cabell (D) . John R. Tucker (D) . John T. Harris (D) . Eppa Hutton, II (D) . Auburn Pridemore (D) West Virginia (3 Democrats) . Benjamin Wilson (D) . Benjamin F. Martin (D) . John E. Kenna (D) Wisconsin (4-3 Republican) . Charles G. Williams (R) . Lucien B. Caswell (R) . George C. Hazelton (R) . William P. Lynde (D) . Edward S. Bragg (D) . Gabriel Bouck (D) . Herman L. Humphrey (R) . Thaddeus C. Pound (R) Non-voting members (5-3 Republican) . Hiram S. Stevens (D) . Jefferson P. Kidder (R) . Stephen S. Fenn (D) . Martin Maginnis (D) . Trinidad Romero (R) . George Q. Cannon (R) . Orange Jacobs (R) . William W. Corlett (R) Changes in membership The count below reflects changes from the beginning of the first session of this Congress. Senate replacements: 5 Democratic: 1 seat net gain Republican: 1 seat net loss deaths: 2 resignations: 3 interim appointments: 1 contested elections: 0 Total seats with changes: 5 |- | Ohio (3) | nowrap | John Sherman (R) | Resigned March 8, 1877 to become U.S. Secretary of the Treasury.Successor elected March 21, 1877. | nowrap | Stanley Matthews (R) | March 21, 1877 |- | Pennsylvania (3) | nowrap | Simon Cameron (R) | Resigned March 12, 1877.Successor elected March 20, 1877. | nowrap | J. Donald Cameron (R) | March 20, 1877 |- | Missouri (3) | nowrap | Lewis V. Bogy (D) | Died September 20, 1877.Successor was appointed September 29, 1877, to continue the term. | nowrap | David H. Armstrong (D) | September 29, 1877 |- | Indiana (3) | nowrap | Oliver P. Morton (R) | Died November 1, 1877.Successor elected January 31, 1879. | nowrap | Daniel W. Voorhees (D) | November 6, 1877 |- | Missouri (3) | nowrap | David H. Armstrong (D) | Interim appointee retired.Successor elected January 26, 1879. | nowrap | James Shields (D) | January 27, 1879 |- | Michigan (1) | nowrap | Isaac P. Christiancy (R) | Resigned February 10, 1879 due to ill health.Successor elected February 22, 1879. | nowrap | Zachariah Chandler (R) | February 22, 1879 |} House of Representatives replacements: 10 Democratic: 5 seat net gain Republican: 5 seat net loss deaths: 7 resignations: 1 contested election: 5 Total seats with changes: 13 |- | | Vacant | style="font-size:80%" | Rep Benjamin Harvey Hill resigned in previous congress | nowrap | Hiram P. Bell (D) | March 13, 1877 |- | | nowrap | James B. Belford (R) | style="font-size:80%" | Lost contested election December 13, 1877 | nowrap | Thomas M. Patterson (D) | December 13, 1877 |- | | nowrap | Romualdo Pacheco (R) | style="font-size:80%" | Lost contested election February 7, 1878 | nowrap | Peter D. Wigginton (D) | February 7, 1878 |- | | nowrap | Chester B. Darrall (R) | style="font-size:80%" | Lost contested election February 20, 1878 | nowrap | Joseph H. Acklen (D) | February 20, 1878 |- | | nowrap | John E. Leonard (R) | style="font-size:80%" | Died March 15, 1878 | nowrap | J. Smith Young (D) | November 5, 1878 |- | | nowrap | Walbridge A. Field (R) | style="font-size:80%" | Lost contested election March 28, 1878 | nowrap | Benjamin Dean (D) | March 28, 1878 |- | | nowrap | Terence J. Quinn (D) | style="font-size:80%" | Died June 18, 1878 | nowrap | John M. Bailey (R) | November 5, 1878 |- | | nowrap | Frank Welch (R) | style="font-size:80%" |Died September 4, 1878 | nowrap | Thomas J. Majors (R) | November 5, 1878 |- | | nowrap | Alpheus S. Williams (D) | style="font-size:80%" | Died December 21, 1878 | Vacant | Not filled this term |- | | nowrap | Beverly B. Douglas (D) | style="font-size:80%" | Died December 22, 1878 | nowrap | Richard L. T. Beale (D) | January 23, 1879 |- | | nowrap | Julian Hartridge (D) | style="font-size:80%" | Died January 8, 1879 | nowrap | William B. Fleming (D) | February 10, 1879 |- | | nowrap | Gustav Schleicher (D) | style="font-size:80%" | Died January 10, 1879 | Vacant | Not filled this term |- | | nowrap | Horatio Bisbee, Jr. (R) | style="font-size:80%" | Lost contested election February 20, 1879 | nowrap | Jesse J. Finley (D) | February 20, 1879 |} Committees Lists of committees and their party leaders, for members (House and Senate) of the committees and their assignments, go into the Official Congressional Directory at the bottom of the article and click or tap on the link (5 links), in the directory after the pages of terms of service, you will see the committees of the Senate, House (Standing with Subcommittees, Select and Special) and Joint and after the committee pages, you will see the House/Senate committee assignments in the directory, on the committees section of the House and Senate in the Official Congressional Directory, the committee's members on the first row on the left side shows the chairman of the committee and on the right side shows the ranking member of the committee. Senate Agriculture Appropriations Audit and Control the Contingent Expenses of the Senate Civil Service and Retrenchment Claims Commerce Distributing Public Revenue Among the States (Select) District of Columbia Education and Labor Elections of 1878 (Select) Engrossed Bills Epidemic Diseases (Select) Examine the Several Branches in the Civil Service (Select) Finance Foreign Relations Hot Springs (Arkansas) Commission (Special) Indian Affairs Judiciary Late Presidential Election Louisiana Manufactures Mexican Relations (Select) Military Affairs Mines and Mining Mississippi River Levee System (Select) Naval Affairs Ordnance and War Ships (Select) Patents Pensions Post Office and Post Roads Private Land Claims Privileges and Elections Public Lands Railroads Revision of the Laws Revolutionary Claims Rules Tariff Regulation (Select) Tenth Census (Select) Territories Transportation Routes to the Seaboard (Select) Treasury Department Account Discrepancies (Select) Whole House of Representatives Accounts Agriculture Appropriations Banking and Currency Claims Coinage, Weights and Measures Commerce District of Columbia Education and Labor Elections Enrolled Bills Expenditures in the Interior Department Expenditures in the Justice Department Expenditures in the Navy Department Expenditures in the Post Office Department Expenditures in the State Department Expenditures in the Treasury Department Expenditures in the War Department Expenditures on Public Buildings Foreign Affairs Indian Affairs Invalid Pensions Levees and Improvements of the Mississippi River Manufactures Mileage Military Affairs Militia Mines and Mining Mississippi Levees Naval Affairs Pacific Railroads Patents Post Office and Post Roads Public Buildings and Grounds Public Expenditures Public Lands Railways and Canals Revision of Laws Rules (Select) Standards of Official Conduct Territories War Claims Ways and Means Whole Joint committees Conditions of Indian Tribes (Special) Reorganization of the Army Transfer of the Indian Bureau Caucuses Democratic (House) Democratic (Senate) Employees Architect of the Capitol: Edward Clark Librarian of Congress: Ainsworth Rand Spofford Public Printer of the United States: John D. Defrees Senate Chaplain: Byron Sunderland (Presbyterian) Secretary: George C. Gorham Sergeant at Arms: John R. French House of Representatives Chaplain: John Poise (Methodist) W. P. Harrison (Methodist), elected December 3, 1877 Clerk: George M. Adams Clerk at the Speaker’s Table: William H. Scudder J. Randolph Tucker, Jr. Doorkeeper: John W. Polk Postmaster: James M. Steuart Reading Clerks: Sergeant at Arms: John G. Thompson See also United States elections, 1876 (elections leading to this Congress) 1876 United States presidential election United States Senate elections, 1876 United States House of Representatives elections, 1876 United States elections, 1878 (elections during this Congress, leading to the next Congress) United States Senate elections, 1878 and 1879 United States House of Representatives elections, 1878 Notes References External links Biographical Directory of the U.S. Congress U.S. House of Representatives: House History U.S. Senate: Statistics and Lists

Q: Converting Oracle's join syntax using the plus sign (+) to standard join syntax I am trying to understand Oracle join syntax of using (+) to join two tables. Could someon show me how would this query would look if it was converted to use the standard join syntax? select p1.product_id, p1.product_name, p2.product_code, (decode(p3.product_type, null, 'N/A',p3.product_type) as product_type from products p1, product_descriptions p2, product_descriptions p3 where p1.product_id=p2.product_id and p2.product_age=p3.product_age(+) and p2.product_type=p3.product_type(+) and p3.status(+)='VALID' A: Something like this: select p1.product_id, p1.product_name, p2.product_code, (decode(p3.product_type, null, 'N/A', p3.product_type) as product_type from products p1 join product_descriptions p2 on p1.product_id = p2.product_id left join product_descriptions p3 on p3.product_age = p2.product_age and p3.product_type = p2.product_type and p3.status = 'VALID'; The where p1.product_id=p2.product_id is a normal inner join between p1 and p2. The others are outer joins; the way it's written looks like a mix of left and right outer joins, but since and p2.product_age=p3.product_age(+) is the same as and p3.product_age(+)=p2.product_age then it isn't really; it's a fairly straightforward left outer join between the product of the p1/p2 join and p3. As an aside, I'm not a fan of aliases like p1, p2 and p3 as they are not descriptive, and it's easy to get lost when you do this in more complicated queries. I'm not alone. I'm not sure you even need the outer join, but it rather depends on the data. If product_age and product_type is unique then you could case the p2.status; if it isn't then you're probably assuming that only one product_age/product_type row can be VALID, otherwise you'd get duplicates. Just musing about what you're trying to do...

Now playing: Watch this: Asus adds a variety of new designs with the ZenWatch... Seamus Byrne/CNET TAIPEI -- Asus chairman Jonney Shih -- an engaging speaker here ahead of the Computex trade show -- has ambitious plans in the smartphone business, despite being "a little bit late" to the market. Its latest effort is a phone designed for taking selfies, called the ZenFone Selfie , announced alongside a range of 8-inch ZenPad tablets, a beautiful new all-in-one PC and a new version of its smartwatch, the ZenWatch 2 . We aim to achieve 25 million phone shipments this year. Jonney Shih, Asus chairman. "This year our goal is to try to get into the worldwide top 10," Shih said in an interview. "Our internal goal is a lot more aggressive, but for the public figures, we aim to achieve 25 million phone shipments. Last year, we hit 8 million." Those figures are a tiny fraction of the numbers shipped by giants such as Samsung, with 318 million phones in 2014, and Apple, which shipped 193 million, according to analyst firm International Data Corporation (IDC). Nevertheless, there's a significant drop off after those two companies, with number five LG shipping fewer than 60 million devices. And Shih believes his company has cracked the code to enter that exclusive club. "We have been driving the performance milestone, but we have also been internalising the practice of design thinking for around eight years, and that started from the Eee PC. It's not just talking about the gigahertz of the CPU, the RAM and what sort of bandwidth, but more about the desirability of a product first," he said. Latching onto trends is also something Shih believes will help Asus sell truckloads of phones. The Asus chairman pointed out the current trend of unlocked phones being a key driver in phone sales in more established markets such as the US and Japan, and claims the company's ZenFone 2 is one of the top five unlocked phones sold on Amazon. Asus was originally known for its hardware PC components and laptops, but after the success of the Eee PC -- the original netbook which made its debut in 2007 at Computex -- the company made the decision to venture into the mobile smartphone market in 2009 with a partnership with Garmin. The partnership didn't last long. In 2011, Asus started production of its own handsets powered by Google's Android software. Under the leadership of Shih and Asus CEO Jerry Shen, who keeps a lower media profile, the company hasn't shied away from more esoteric designs. The PadFone stands out -- a phone that could convert into a tablet when it was slotted into a larger screen. A few sequels appeared, but Asus has declined to update it this year. "For the PadFone, we launched it when we weren't in the mainstream competition, so we tried to cut in with the innovation aspect," Shih said. "But with mobile phones becoming more mainstream, we don't have enough time to just do something like the PadFone for innovation, we need to become mainstream and aim for big volume, and that's why, starting in 2014, that was a different journey for Asus." But there's a reason for this and while you may not see any new PadFones for now, Shih says it may return in the future, though when it does appear, it's likely to be a higher-end offering. "One of Asus' biggest strengths is its design chops. But I can't help but think of similarities with Samsung and wonder if hardware alone is enough," said Bryan Ma, IDC's vice president for the Asia Pacific client devices research group. "There's no doubt that Asus have very impressive engineering skills, and have proven time and again how they can think outside the box," Ma added. "The company is also one of the more progressive OEMs when it comes to hardware design, but the question is whether that will be enough?" The company is also one of the more progressive OEMs when it comes to hardware design, but the question is whether that will be enough. Bryan Ma, IDC analyst Instead of looking at the mostly plastic hardware of its phones -- Shih believes it's better than metal for smartphones -- Asus has turned to its software to make its case to potential customers. Each smartphone and tablet comes with a custom interface called Zen UI, on top of Android, which loads all sorts of features, many of them of dubious usefulness. If anything, the number of features can be overwhelming -- making the experience anything but zen-like. Data provided by IDC shows Asus is currently in 18th place in the global smartphone shipments market, but if the company can execute its strategy properly, it seems likely to break into the coveted top 10. The company is looking at Asian markets such as India, Indonesia and China as key battlegrounds this year, though it will need to make a truly global impact if it's going to take the next step and break into the top five.

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Introduction {#S1} ============ Allogeneic bone marrow transplantation \[BMT; allogeneic hematopoietic stem-cell transplantation (allo-HCT)\] is a curative option to treat hematological malignancies. However, graft-versus-host disease (GVHD) limits the success of allo-HCT ([@B1]). GVHD pathogenesis is characterized by a robust immunological attack by donor T cells against normal tissues of transplanted recipients ([@B2]). As donor T cells are the driving force in GVHD, suppressing T-cell responses is a standard therapeutic approach for the treatment of GVHD. However, these broadly immunosuppressive drugs, including corticosteroids and inhibitors of calcineurin or mammalian target of rapamycin (mTOR), leave patients highly susceptible to infections and induce remission in \<50% of patients. The mortality rate of patients with steroid-refractory aGVHD is close to 90% ([@B3]). Hence, understanding T-cell pathobiology is critical to the development of effective therapies to prevent GVHD. Cell metabolism impacts the fate and function of T cells ([@B4]). Targeting T-cell metabolism is a viable therapeutic strategy in other immunological disorders, including systemic lupus erythematosus, rheumatoid arthritis, and experimental autoimmune encephalomyelitis ([@B5]--[@B7]). A growing body of evidence from multiple studies suggests T-cell metabolism is a promising target for controlling GVHD. Recently, our group and others attempted to characterize the metabolic profile of donor T cells following allo-HCT, yet a consensus on the data has not been reached ([@B2], [@B8], [@B9]). In this review, we will detail the recent findings in the evolving field of immuno-metabolism with a focus on T-cell metabolism in the context of allo-HCT and discuss how this knowledge can help us reevaluate our current understanding of immune activation and suppression after allo-HCT, and promising immunotherapeutic strategies to archive long-term transplantation tolerance in transplanted recipients aiming to prevent allograft rejection and GVHD. Overview of T-Cell Metabolism {#S2} ============================= Glycolysis and oxidative phosphorylation (OXPHOS) are fundamental cellular processes in generating energy, or adenosine triphosphate (ATP) ([@B10], [@B11]). Naïve T cells rely primarily on OXPHOS to meet their energy demands ([@B12]). Upon antigen recognition, naïve T cells clonally expand into T effector cells (Teffs). Upon antigen clearance, most of these effector T cells die, but a subset of long-lived memory T cells (Tm) persist with an enhanced mitochondrial capacity relying on fatty acid oxidation (FAO) to fuel OXPHOS ([@B13]). OXPHOS can generate up to 36 molecules of ATP. The transition from resting naïve T-cells into activated Teffs requires substantial metabolic reprogramming ([@B12], [@B13]). A Teff's metabolic profile is characterized by a shift to aerobic glycolysis as a main energy source ([@B12], [@B14]). Aerobic glycolysis involves the mitochondrion-independent metabolism of glucose into pyruvate and provides only two molecules of ATP per glucose ([@B15]). While glycolysis is less efficient than OXPHOS at yielding an abundance of ATP per molecule of glucose, aerobic glycolysis supplies metabolic intermediates for cell growth and proliferation as well as induces the pentose phosphate pathway (PPP), which produces nucleotides and amino acids that subsequently generate reducing power in the form of NADH to maintain cellular redox balance (NAD^+^/NADH) ([@B15]). Teffs also use glutamine as a carbon source to fuel the tricarboxylic acid (TCA) cycle *via* α-ketoglutarate (α-KG) through the process of glutaminolysis ([@B16], [@B17]). Metabolism and CD4^+^T Cell Differentiation {#S3} =========================================== Depending on the nature of antigen and cytokine signal, CD4^+^ T cells differentiate into Th1, Th2, Th9, Th17, T follicular helper cells (Tfh), Tr-1, or Treg. While Th1, Th2, and Th17 are pathogenic, Tr-1 and Treg are suppressive in acute GVHD ([@B18]--[@B20]). Metabolism plays a critical role in CD4^+^ T-cell differentiation ([@B12]). While Th1, Th2, and Th17 lineages preferentially use glycolysis to meet energetic demand though activation of PI3K/Akt/mTOR pathway, CD4^+^ Tregs use mitochondrial-dependent FAO ([@B4]). Therefore, enhanced FAO *via* inhibiting mTOR leads to increased Treg generation ([@B21]). Hypoxia-inducible factor 1 is the key regulator of anabolic metabolism in Th17 cells ([@B22]). Meanwhile, Tfh, a pathogenic T-cell subset in chronic GVHD, depend on glycolysis and lipogenesis to meet energy demands required for differentiation ([@B23]). The metabolic profiles of Th9 and Tr1 remain unclear. Metabolism of Allogeneic T Cells {#S4} ================================ Glucose Metabolism {#S4-1} ------------------ Using MHC-mismatched or haploidentical murine models of BMT, we uncovered that upon alloantigen activation, donor T cells increase both glycolysis and OXPHOS to obtain energetic materials necessary for activation and proliferation ([@B2], [@B9]). Albeit, they preferentially rely on glycolysis to maintain their capacity to induce GVHD ([@B2], [@B9], [@B24]). While OXPHOS of donor T cells isolated from syngeneic (no GVHD) and allogeneic (GVHD) recipients were similar, the glycolytic activity of donor T cells was significantly higher in allogeneic than syngeneic recipients, indicating an escalation of T-cell glucose metabolism correlated with GVHD development ([@B2]) (Figure [1](#F1){ref-type="fig"}). Furthermore, T cells isolated from livers of allogeneic recipients exhibited higher glycolytic activity compared to those of syngeneic recipients 14 days after allo-HCT, implying an enduring glycolytic response by allogeneic T cells in GVHD target organs. While *in vitro* activated T cells upregulate and maintain expression of Glut1 for sufficient glucose uptake ([@B17]), allo-activated T cells also increase Glut 3 to fulfill their extremely high demand for glucose ([@B2]). In addition, alloantigen-activated T cells upregulate both hexokinase 1 (HK1) and HK2 to facilitate induction of glycolysis ([@B2]). To maintain sufficient glycolytic activity, allogeneic CD4^+^ T cells activate mTOR and increase differentiation into Th1 and Th17 ([@B2], [@B25]) while decreasing Treg generation ([@B24]). Inhibition of glycolysis by genetic depletion or pharmacological blockade of mTORC1 ([@B2], [@B26]) or glycolytic checkpoints, including glut-1 ([@B24]), HK-2, PFKB3 ([@B2]), or PKM2 (unpublished study), reduces alloreactive T-cell generation and subsequently ameliorates GVHD severity. Alternatively, enhancing FAO to inhibit mTOR using PI3K/AKT or AMPK inhibitors ([@B27], [@B28]) effectively prevents GVHD development. ![**(A)** Naïve/resting T cells are dependent on oxidative phosphorylation with fatty acid oxidation (FAO) as a major material resource. Upon activation by self-antigens under homeostatic state, naïve/resting T cells reprogram their metabolic phenotype to become partially activated T cells ([@B29]), which possess glycolytic metabolic phenotype. Due to lack of specific TCR stimulation, a large proportion of non-alloreactive T cells gradually die. However, specific self-epitopes of T cells can become memory T cells (Tm) which depend upon FAO for their metabolism. **(B)** Upon activation by alloantigen in transplant recipients, naïve/resting T cells proliferate and their memory differentiate to activate T cells both alloreactive and non-alloreactive. Alloreactive T cells and their differentiated memory cells are capable of causing target organ damage. Alloreactive T cells have much higher glycolytic activity compared to non-alloreactive counterpart. Both alloreactive and non-alloreactive T cells can die or differentiate into Tms accordingly. Glucose retention and glycolytic activity decide survival and alloreactivity of alloreactive T cells to induce graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation.](fimmu-09-00176-g001){#F1} OXPHOS and Oxidative Stress in Allogeneic T Cells {#S4-2} ------------------------------------------------- Allogeneic T cells in lymphoid or target organs of recipients significantly increase OXPHOS compared to resting T cells after allo-HCT ([@B2], [@B9]). Since OXPHOS activity was comparable in allogeneic and syngeneic T cells ([@B2]), increased OXPHOS may not be a direct mechanism by which pathogenic T cells are generated. However, due to increased non-mitochondrial oxygen consumption rate (OCR), allogeneic T cells had higher levels of oxidative stress yet lower levels of antioxidants ([@B2], [@B9]). As reactive oxygen species (ROS) are required for T-cell activation ([@B30]), this indicates chronic allo-activation of donor T cells after transplant. Increased ROS generation in allogeneic T cells may be the result of a hyperpolarized mitochondrial membrane potential (ΔΨm), subsequently making alloreactive CD4^+^ and CD8^+^T cells highly susceptible to small-molecule inhibitors of mitochondrial F1F0 adenosine triphosphate synthase in haploidentical BMT model ([@B9], [@B31]). The Pentose Phosphate Pathway {#S4-3} ----------------------------- In murine models of GVHD, alloantigen-activated T cells have increased PPP activity ([@B2], [@B31]). Intracellular glucose metabolized by HK forms glucose 6-phospate (G-6P), which then enters the PPP to generate ribose-5 phosphate (R-5P); the carbon donor during nucleotide biogenesis ([@B32]). The conversion of G-6P to R-5P is regulated by glucose-6-phosphate dehydrogenase in the oxidative arm of the PPP ([@B33]), which is significantly increased in allogeneic T cells ([@B2], [@B31]). The oxidative arm of the PPP is crucial for the formation of NADPH, which plays a critical role in reductive biosynthesis of antioxidant molecules, such as GSH ([@B34]). GSH promotes T-cell expansion by driving glycolysis and glutaminolysis, and supporting mTORC1 and c-Myc signaling in inflammation ([@B35]). Due to chronic stimulation by alloantigens, nucleotide biosynthesis is sustained to support anabolic growth of T cells during allogeneic responses; leading to a deficit in purine and pyrimidine catabolism ([@B2]) and exhaustion of GS and GSH ([@B9]). Glutamine Metabolism {#S4-4} -------------------- Glutamine uptake and metabolism are crucial for normal T-cell function ([@B36]). Donor T cells require the rapid synthesis of macromolecules for their growth, proliferation, and for energy after allo-HCT ([@B11]). Glutamine converted to glutamate can support the progression of the TCA cycle, ultimately leading to production of α-KG, a citrate precursor. To generate new lipids, citrate is secreted into the cytosol and metabolized to form acetyl-CoA, the backbone for lipid synthesis ([@B34]). In addition to the PPP, glutaminolysis can provide NADPH to support lipid and nucleotide biosynthesis as well as maintenance of GSH ([@B37]). *In vitro*-activated T cells utilize the transcription factor Myc to incorporate glutamine into metabolic pathways ([@B17]). Allogeneic T cells increase glutamine uptake by upregulating glutamine transport channels, such as glutamine-fructose-6-phosphate transaminase, phosphoribosyl pyrophosphate amidotransferase, and glutaminase 2 post allo-HCT ([@B2]). While the level of glutamine was increased in allogeneic T cells, the level of glutamate was lower. Moreover, the levels of aspartate and ornithine, products of glutamate conversion to α-KG by ornithine aminotransferase and glutamate oxaloacetate transaminase, respectively, were increased in allogenic T cells after allo-HCT ([@B2], [@B31]). These data suggest that alloantigen-activated T cells further increase glutaminolysis to replenish intermediate metabolites of the TCA cycle that are depleted in proliferating T cells after allo-HCT. Studies using radioactive tracers indicate that alloreactive CD4^+^ and CD8^+^ T cells preferentially use glutamine to provide substrates for ribose synthesis ([@B31]). Fatty Acid Metabolism {#S4-5} --------------------- Alloantigen-activated T cells accumulate various types of FAs and lysophospholipids after allo-HCT ([@B2]). In addition to glucose and glutamine, lipids are an effective energy source as well as biosynthetic intermediates ([@B38]). FAs can be generated through three different pathways: environmental uptake, synthesis, or hydrolysis of membrane or lipid droplets ([@B39]). FAs are classified according to (a) to their backbone lengths (short-, medium-, long-, and very long-chain), (b) saturation, i.e., the number of double bonds (unsaturated, mono-, poly-unsaturated), and (c) position of the double bonds ([@B37]). During activation, *in vitro* activated T cells augment fatty acid synthase (FAS) while decreasing FAO, thus enhancing the accumulation of FA metabolites needed for the membrane ([@B17]). The effect of lipids on T-cell function seems to be mediated by a complex network dependent on the type of lipids ([@B40]). Fatty Acid Synthesis {#S4-6} -------------------- FAs have an important role in Teff function and differentiation. Acetyl-CoA carboxylases 1 (ACC1), ACC2, and FAS are recognized as key rate-limiting enzymes in this process ([@B41]). Inhibition of FAS limits development of Th1, Th2, and Th17 subsets ([@B42], [@B43]). Blockade of the enzyme ACC1 enhances the formation of Tregs during Th17 differentiation ([@B43]). *In vitro*, induction of FAS after TCR stimulation is regulated *via* the mTORC1--SREBP pathway ([@B14], [@B44]). Moreover, Myc is essential for activation of glucose-metabolizing genes and also for FA synthesis, linking glycolysis to *de novo* FAS ([@B45]). Recent studies showed that FAS is required for maintaining glycolytic activity in allogeneic T cells ([@B46]). Disruption of FAS at ACC1 effectively ameliorates GVHD development ([@B46], [@B47]). This study emphasizes the relationship between glycolysis and FAS in allogeneic T cells. Fatty Acid Oxidation {#S4-7} -------------------- Fatty acid oxidation is a multistep energetic process by which FAs are broken down in the mitochondria *via* sequential removal of 2-carbon units at the β-carbon position of a fatty acyl-CoA molecule ([@B39], [@B48]). A given long-chain acyl-CoA that enters the FAO yields one molecule of acetyl-CoA from each cycle of FAO. This acetyl-CoA can be directly shuttled into TCA cycle. The NADH and FADH~2~ produced during FAO and the TCA cycle are then available to be used. While saturated short long-chain FA (SCFAs) and medium chain FA are almost exclusively oxidized in the mitochondria, long-chain FA and very long-chain fatty acids (\>14 carbons) can also be oxidized in peroxisomes ([@B49]). Previous studies have indicated that alloreactive T cells increase FAO, and that targeting FAO could arrest GVHD in haploidentical allo-HCT ([@B8], [@B9]). Although they reported substantial increases in FA transport and intracellular acylcarnitines, suggesting changes in FA metabolism, it was not determined if FAO was directly responsible for the increase in OXPHOS ([@B31], [@B34]). Also, no improvement in survival of recipients treated with FAO inhibitors was shown. By contrast, our recent study showed intracellular carnitine-derived metabolites were diminished in alloantigen-activated T cells after MHC-mismatched or haploidentical allo-HCT ([@B2]). Allogeneic T cells dramatically decreased mitochondrial-dependent FAO and pyruvate oxidation through the TCA cycle. Therefore, it is possible that FAO is downregulated in allogeneic T cells after allo-HCT. These inconsistent observations likely result from the different controls used in these two studies. While studies from Ferrara's group compared bioenergetic parameters of allogeneic T cells to naïve/resting T cells ([@B9]), we used those isolated from syngeneic recipients as controls ([@B2]); intended to account for homeostatic proliferation of T cells under an inflammatory environment ([@B29]). In addition, we observed both Glut1 and Glut3 expression could serve as indicators of glycolytic activity ([@B9]), as alloreactive T cells increase Glut3 to an even larger extent than Glut1 in allogeneic recipients ([@B2]). Taken together, with study from by Rathmell's group ([@B24]), we speculate that FAO might not be the major material resource fueling the TCA cycle and OXPHOS in alloreactive T cells. Sphingolipids (SLs) in Allogeneic T-Cell Metabolism {#S4-8} --------------------------------------------------- Sphingolipids represent a major class of lipids important for cell membrane formation ([@B50]). S1P is emerging as a key regulator of proliferation, inflammation, vasculogenesis, and resistance to apoptotic cell death ([@B51]). Recently, a report demonstrated that S1P1 regulates T cell metabolism through activation of mTOR-Akt, which suppressed Treg function ([@B52]). Blockade of the S-1P receptor effectively prevents GVHD by modulating the migration of allogeneic T cells. Ceramide plays a central role in the metabolism of SL ([@B53], [@B54]). Ceramide can be generated *via de novo* synthesis or by degradation of complex SLs, especially sphingomyelin ([@B51]). The key rate-limiting step in the biosynthesis of ceramide is the attachment of various acyl-CoA side chains to a sphingoid base by ceramide synthases (CerS) ([@B55]). The CerS show substrate preferences for specific chain lengths of fatty acyl CoAs. Briefly, CerS1 shows significant preference for C18-FA CoA, CerS4 for C18-/C20-FA CoA, CerS5 and CerS6 for C16- FA CoA, CerS2 for C22/C24- FA CoA, and CerS3 for ultra-long-chain FA CoA ([@B51], [@B56]). Recent work from our lab showed that CerS6 regulates SL metabolism in alloantigen-activated CD4^+^ and CD8^+^ T cells and required for alloreactive T cells to induce GVHD ([@B57]). The Role of PD-1 and Check Point Blockade on Allogeneic T Cell Metabolism {#S5} ========================================================================= The coinhibitory receptor programmed death 1 (PD-1; CD279) has key roles in modulating T-cell responses in both normal and antitumor immunity ([@B58]). PD-1 binds to PD-L1 (B7-H1; CD274), which is expressed by macrophages, DCs and non-hematopoietic cells, and PD-L2 (B7-DC; CD273), which is primarily expressed by monocytes and inflammatory macrophages in GVHD target organs ([@B59], [@B60]). Donor T cells significantly upregulate PD-1 expression, which can increase in response to FAO, superoxide, hyperpolarized mitochondrial membrane potential, and ROS formation which subsequently induces T-cell death following allo-HCT. In the absence of PD-1/PD-L1 ligation, donor T cells displayed higher glycolytic activity and OCR. Hence, PD-L1/PD-1 ligation, versus that of PD-L2/PD-1, plays a predominant role in downregulating GVHD ([@B59]). Microbiota Regulates T Cell Metabolism {#S6} ====================================== The composition, or diversity, of intestinal microbiota shapes the innate and adaptive immune responses ([@B61]). The onset of GVHD is associated with a progressive reduction in microbiota diversity, with an increase in Lactobacillales and Blautia and a decrease in Clostridiales species ([@B62]--[@B64]). The microbiota metabolome, which consists of products generated by host metabolism, microbial metabolism, and mammalian--microbial co-metabolism in the intestines, influences the development of GVHD ([@B65], [@B66]). SCFA-bacterial metabolites, derived from carbohydrate fermentation and include acetate, propionate, isobutyrate, and butyrate, increase histone H3 acetylation in the locus of Foxp3; thereby increasing the numbers of Tregs directly, yet also indirectly through increasing the production of TGFβ in the intestinal epithelium ([@B67]). The effect of SCFAs on T cells is also related to mTOR activation ([@B68]). SCFAs induce the expression of receptor GPR15, which is responsible for the recruitment of Tregs to the large intestine ([@B69]--[@B71]). Restoration of butyrate, which is diminished in intestinal epithelial cells (IECs) after allo-HCT, improved IEC junctional integrity, decreased apoptosis, and mitigated GVHD ([@B66]). Aryl hydrocarbon receptor (AhR) is a cellular metabolic sensor ([@B72]). AhR ligands are derived from intestinal microbiota metabolism. AhR ligand, indole-3-aldehyde, produced by Lactobacilli through tryptophan breakdown ([@B73]), modulates the development of GVHD through inducing Tregs and Tr1 cells ([@B74]). Targeting T-Cell Metabolism to Separate GVHD and the Graft-Versus-Tumor Effect {#S7} ============================================================================== Given that tumors and alloreactive T cells share a glycolytic phenotype, pharmacological glycolysis inhibition could prevent both GVHD and tumor relapse, a primary complication after allo-HCT. Inhibition of glucose-metabolizing enzymes could reduce allogeneic T activation and function ([@B2], [@B17]) and, further, lower levels of glycolysis would support the generation of long-lived CD8 Tm ([@B3]) which are required for maintaining the graft-versus-tumor (GVT) effect. Moreover, *in vivo* activated CD4^+^T cells are more dependent on glycolysis than CD8^+^T cells ([@B75]), which are critically important for maintaining GVT activity in allo-HCT. Increasing evidence indicates that CD8^+^ T cells with lower rates of glycolytic activity have better antitumor efficacy in eradicating established tumor in adoptive T cell transfer (ACT) models ([@B76]). Blocking glucose metabolism at HK2 by 2-deoxyglucose improves antitumor efficacy of ACT therapy ([@B40]). The aforementioned evidence suggests a valid possibility of targeting glycolysis to treat GVHD while preserving the GVT effect after allo-HCT. Impact of Current Immunosuppressive Drugs on T-Cell Metabolism in Allo-HCT {#S8} ========================================================================== Corticosteroids inhibit glycolysis and endogenous respiration in donor lymphocytes and impair GVL activity ([@B77]). Inhibiting mTOR with rapamycin decreases glycolysis and enhances FAO in donor T cells; this is expected to reduce alloreactive T cells and enhance Treg function ([@B27]). However, attempts to conceptually translate this into patients have proven difficult. This challenge may be because rapamycin can promote CD8 memory T-cell responses by enhancing FAO and hence be detrimental in establishing tolerance ([@B78]). Alternatively, inhibition of calcineurin with cyclosporine diminishes glycolytic activity of donor T cells by decreasing glycolytic enzymes and the expression of glut1/3 ([@B79]); which support Treg expansion and GVHD attenuation ([@B80]). Concluding Remarks {#S9} ================== Current immunosuppressive regimens, including steroids and calcineurin inhibitors, help to prevent allograft rejection and GVHD. Consequently, patients are vulnerable to complications, such as opportunistic infections and tumor relapse. Therefore, bioenergetic signatures of immune cells at different stages of tolerance induction after transplant could serve as a promising clinical therapeutic strategy. Metabolism inhibitors, in concert with cancer immunotherapies, highlight an avenue by which to achieve better antitumor efficacy and functional tolerance to allografts. Hence, distinguishing metabolic signatures between allogeneic T cells and tumor cells is critical to truly fulfilling this goal. Author Contributions {#S10} ==================== HN and XZ-Y wrote manuscript and HN, SK, DB, and XZ-Y revised manuscript. Conflict of Interest Statement {#S11} ============================== The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. **Funding.** This work is partially supported by NIH grants R01 AI118305, CA118116, CA169116, and R21 CA192202 (to XZ-Y). [^1]: Edited by: Claudio Mauro, Queen Mary University of London, United Kingdom [^2]: Reviewed by: Lianjun Zhang, University of Lausanne, Switzerland; Harley Y. Tse, Wayne State University, United States [^3]: Specialty section: This article was submitted to Immunological Tolerance and Regulation, a section of the journal Frontiers in Immunology

A Kansas City, Missouri, man who told an off-duty police officer that something had happened and someone was dead has been charged in the kill…

Introduce your family to A&W Root Beer and make frosty mug memories. Not a significant source of nutrients. *Percent Daily Values based on a 2,000 calorie diet. Not a significant source of nutrients. *Percent Daily Values based on a 2,000 calorie diet. Not a significant source of nutrients. *Percent Daily Values based on a 2,000 calorie diet. Not a significant source of nutrients. *Percent Daily Values based on a 2,000 calorie diet. Click here for nutrition facts Fill to top with A&W® Root Beer. Top with caramel sauce and pinch of sea salt. Fill to top with A&W® Root Beer. Top with whipped cream, chocolate sauce, chopped nuts, maraschino cherry, sprinkles, and remaining brownie bits. Fill to top with A&W® Root Beer. Put some brownie bits in the mug. Top with a toasted marshmallow, mini chocolate chips, and graham cracker crumbs. Fill to top with A&W® Root Beer. Fill to top with A&W® Root Beer. Top with caramel sauce and pinch of sea salt. Fill to top with A&W® Root Beer. Top with whipped cream, chocolate sauce, chopped nuts, maraschino cherry, sprinkles, and remaining brownie bits. Fill to top with A&W® Root Beer. Put some brownie bits in the mug. Top with a toasted marshmallow, mini chocolate chips, and graham cracker crumbs. Fill to top with A&W® Root Beer. A&W is a registered trademark of A&W Concentrate Company. © Dr Pepper/Seven Up, Inc.

Experts from the National Museum of Ireland plan to radiocarbon date an ancient bog body found at a Midlands bog today. It is the second one to be found at the midlands bog in two years. The partial remains, comprising of adult leg and foot bones and flesh, were discovered by Bord Na Móna workers at Rossan Bog close to the Westmeath border in Co Meath on Saturday. Once the find was made, a Bord Na Móna worker initiated company protocol and called gardai to examine the scene. Work was stopped and the National Museum of Ireland was notified. The find was made close to the discovery of a Bronze Age bog body in December 2012, later named Moydrum Man, which was radiocarbon dated to between 700 and 400BC. A team of archaeologists and conservators from the National Museum of Ireland spent last weekend examining the find at the bog before removing the remains on Monday. They have yet to determine the gender or age of the body, but are convinced the remains are those of an adult. Further analysis of the bog body will now take place in the National Museum of Ireland’s conservation laboratory at Collins Barracks, Dublin. Maeve Sikora of the museum’s Irish antiquities division, who led the museum’s fieldwork team, thanked Bord na Móna staff for promptly reporting the find and providing assistance at the site. National Museum of Ireland Director Raghnall Ó Floinn welcomed the new discovery and said, “every new find helps to bring us closer to understanding the lives and belief systems of our ancestors.” Oxygen-free conditions in bogs assist in the preservation of organic material such as human tissue. The survival of such remains allows for more detailed research into past lives than if only the bone was to survive. Bog bodies have been found across northern Europe from Ireland to Scandinavia. Many show evidence for violent death and are believed to be sacrificial offerings connected to kingship and sovereignty. The National Museum of Ireland holds the finest collection of bog bodies in the world. The best preserved examples along with related bog finds can be seen in the exhibition Kingship and Sacrifice at the National Museum of Ireland in Dublin. museum.ie/en/exhibition/kingship-and-sacrifice.aspx

Inagawa Dam is a dam in Ōkuwa, Nagano Prefecture, Japan, completed in 1977. See also List of dams and reservoirs in Japan References Category:Dams in Nagano Prefecture Category:Dams completed in 1977 Category:1977 establishments in Japan Category:Gravity dams

Bank of Japan extends funding steps, with eye on exit By Hideyuki Sano TOKYO, July 15 (Reuters) – The Bank of Japan voted to extend its corporate finance-support measures by three months, after which they could be scaled backed or scrapped if financial conditions keep improving, the head of the central bank said on Wednesday. The BOJ board voted unanimously to keep buying commercial paper and corporate bonds from banks and keep providing long-term loans to banks at 0.1 percent interest, extending the measures it introduced to deal with a crunch in credit markets. But the three-month extension was shorter than the six months some had expected. “We extended them by three months instead of six because we thought current improvements in financial conditions would continue for some time, and that it would be appropriate to examine economic and financial conditions again three months later,” Governor Masaaki Shirakawa told a news conference. The bank kept interest rates at 0.10 percent and stuck to the main scenario it outlined in April of a slow return to moderate economic growth towards the end of the year “The BOJ can’t really get complacent and withdraw liquidity because it’s too soon, but if it continues supplying liquidity it’s operating on diminishing returns — it’s basically sending the wrong message because the economy has bottomed,” said Naomi Fink, Japan strategist at Bank of Tokyo-Mitsubishi UFJ. Financial markets had expected the BOJ to keep its special measures in place. After the BOJ’s announcement, the yen was steady around 93.54 yen per dollar, while JGB futures were little changed. ECONOMY STOPPED WORSENING The BOJ also said the economy had stopped worsening in its policy statement, giving a less bleak assessment than last month when it said it was beginning to stop worsening. But it added that economic uncertainties remained high and its policy would continue to focus on downside economic risks for now. Funding conditions for big companies have improved for the first time in eight quarters, but small firms are struggling to gain access to credit, the bank’s tankan corporate survey showed earlier this month. “The BOJ felt it was necessary to provide some assurance about its corporate support measures, recognising that the economy is still quite fragile, as reflected in the tankan survey,” said David Cohen, director of asian economic forecasting at Action Economics in Singapore. In addition, the economy is saddled with excess production capacity and labour after four straight quarters of contraction. Still, the BOJ is worried that its heavy intervention in credit markets could distort the normal workings of the economy, which it says should be guided by market forces. Its buying of commercial paper has pushed interest rates on such debt so low that some issuers have been able to borrow funds even more cheaply than the government. The central bank’s recent offers to buy CP have attracted few bids, in another sign markets no longer need this support. The BOJ has already achieved most of what it wanted from these steps, increasing the availability of funds and bringing down “term interest rates” such as three-month rates. Issuance of corporate bonds surged to a record 2.29 trillion yen in June, according to Reuters data, after freezing up late last year in the wake of the collapse of Lehman Brothers. Corporate bond issuance averaged less than 500 billion yen per month during 2002-2007, when the economy was expanding. The three-month TIBOR rate has dropped more than 30 basis points to about 0.55 percent from 0.90 percent late last year. The yield on three-month government treasury bills has dropped to around 0.15 percent from about 0.30 percent earlier this year. MORE VOLATILE Shirakawa said keeping extraordinary steps in place even after conditions have improved could only make the economy more volatile. BOJ officials believe cheap funding, if left unchecked, could lead to too much corporate borrowing, which is now seen as a cause of the global financial crisis. Many economists predict the economy will grow in April-June thanks to a rebound in output and exports from the first quarter. So far the economy seems to be tracking the BOJ’s projection in April of a slow return to moderate growth as the world economy picks up. Still, its recovery will remain feeble after Japan’s economy contracted a total of 8.8 percent in the last four quarters. A rebound also depends on a recovery in the global economy as domestic demand is expected to remain weak while companies shed jobs to deal with much weaker global demand. “I feel maybe it’s quite some time away before the central bank will consider an exit strategy as the funding environment has not improved particularly for medium- and small-sized businesses,” said Junko Nishioka, chief Japan economist at RBS. The BOJ said the economy will contract 3.4 percent in the year to March and grew 1.0 percent in the following year, slightly lowering estimates from its forecast in April. That would be one the weakest growth outlook in Asia. (Reporting by Hideyuki Sano; Editing by Hugh Lawson) Please click here for a graphic on financial conditions and Japan’s economic growth, and here for a graphic on the BOJ’s CP buying and CP rates.

A 3-dimensional view of access to licensed and subsidized medicines under single-payer systems in the US, the UK, Australia and New Zealand. Patients' access to medicines can be profoundly affected by the decisions made by medicine licensing bodies and public reimbursement agencies. The present study compares access to licensed and subsidized medicines under a single-payer system in each of the US, the UK, Australia and New Zealand (NZ). These systems are the US Department of Veterans Affairs National Formulary (VANF), the UK NHS for England and Wales, Australian Pharmaceutical Benefits Scheme (PBS) and NZ's Pharmaceutical Management Agency (PHARMAC). The VANF, PBS and PHARMAC all use positive lists of medicines that are subsidized, along with pharmacoeconomic analysis and price negotiations with suppliers. The NHS uses a negative list of medicines that are not to be subsidized, along with pharmacoeconomic analysis of a small number of medicines and caps on manufacturers' profits. Our objective was to compare licensed and subsidized medicines in terms of the following: (i) total numbers of entities (unique Anatomical Therapeutic Chemical [ATC] codes); (ii) times since first registration (age) of the entities; and (iii) numbers of innovative entities. This was an observational study in order to test pre-defined hypotheses. All products listed in a major prescribing reference in each country were included in the study. All products were classified by ATC code and their registration dates recorded. Products were collapsed by ATC code to determine 'best-case' licensing and subsidy for each entity, along with the date of first registration. Innovative entities selected for 'fast-track' approval by the US FDA or as a 'breakthrough or substantial improvement' by the Canadian Patented Medicines Prices Review Board were identified. Results were verified by a sensitivity analysis that excluded entities only available in injectable formulations (as these may not always be listed in general prescribing references), and by a parallel analysis done by active agent rather than ATC code. Of the 918 entities and 64 innovative entities licensed in the US, 505 and 20, respectively, were subsidized by the VANF. In the UK, this was 1020 and 58 (1016 and 58 NHS subsidized); in Australia, this was 879 and 49 (567 and 30 PBS subsidized); and in NZ, this was 765 and 39 (503 and 19 PHARMAC subsidized). With the exception of the UK, entities licensed in the US were newer than elsewhere. The median ages were as follows: 6607 days in the US (VANF subsidized 8203 days; p < 0.001); 7319 days in the UK (NHS subsidized 7319 days; p = 0.903); 7795 days in Australia (PBS subsidized 8065 days; p = 0.406); and 8936 days in NZ (PHARMAC subsidized 10 724 days; p < 0.001). NHS subsidized entities were newer than elsewhere. VANF and PHARMAC subsidized entities were significantly older than licensed entities in their respective countries. The single-payer systems examined differ in the number and age of licensed and subsidized entities, along with access to innovative entities. The NHS subsidized the most entities, the newest entities and the most innovative entities. NZ's PHARMAC system subsidized the fewest and oldest entities, and the fewest innovative entities. The VANF and PBS consistently fell between the other two systems in terms of the number of subsidized entities, age of subsidized entities and number of subsidized innovative entities.

we need a guess now. Stan wants a first pass by tomorrow afternoon - we should be able to ballpark this number. -----Original Message----- From: Centilli, James Sent: Thursday, February 07, 2002 10:13 AM To: Howard, Kevin A.; Hayslett, Rod; Thames, Davis; Geaccone, Tracy; Ratner, Michael; Donoho, Lindy Subject: RE: tw subscription rolloff template Facilty Planning personnel are out of office today, but will return in the morning. I have ask for their estimate no later than Monday morning. They may be able to give me something tommorrow. I will complete the project model when I get a description of facilities and cost estimates. James -----Original Message----- From: Howard, Kevin A. Sent: Thursday, February 07, 2002 9:59 AM To: Hayslett, Rod; Thames, Davis; Geaccone, Tracy; Ratner, Michael; Donoho, Lindy; Centilli, James Subject: RE: tw subscription rolloff template James: Can you roll each of the expansions that we discussed into Rod's project model? Michael Ratner will then link those into the TW financial model. Kevin -----Original Message----- From: Hayslett, Rod Sent: Thursday, February 07, 2002 9:24 AM To: Howard, Kevin A.; Thames, Davis; Geaccone, Tracy; Ratner, Michael; Donoho, Lindy; Centilli, James Subject: RE: tw subscription rolloff template Project model -----Original Message----- From: Howard, Kevin A. Sent: Thursday, February 07, 2002 8:28 AM To: Thames, Davis; Geaccone, Tracy; Ratner, Michael; Donoho, Lindy; Centilli, James Cc: Hayslett, Rod Subject: RE: tw subscription rolloff template Attached is the actual contract roll off info by segment prepared by Shelley Corman for our bank due diligence. We need to use this and assume we re-subscribe the roll off capacity at an "average rate" - Lindy, we will need your assistance in developing this avg. rate by segment. For the expansions we discussed, Rod will circulate an expansion model that we can layer into the financial model. Tracy: call me when you get in and we can discuss. Kevin -----Original Message----- From: Thames, Davis Sent: Wednesday, February 06, 2002 9:49 PM To: Howard, Kevin A.; Geaccone, Tracy; Ratner, Michael; Donoho, Lindy; Centilli, James Subject: tw subscription rolloff template I have attached a template to use to summarize the capacity rolloff issue discussed today. I just filled in a bunch of numbers as an example - if they don't make any sense, you can guess why! Lindy, if you could use this to fill in the required data, then either Michael or I will incorporate it into the TW model. Thanks- Davis

Theres all kinds of cards you can toss in but some need to be flashed. If you have to change out the motherboard your best bet is to get a hold of a MDD or a G5. Some reason the "secret" site for editing video cards for macs has rejected my membership so I have no idea what is the fastest compatible card that will work. Just look at a card you would like to use and google for a mac compatible card or see if theres a flash hack for it. TCP thanks for the reply I think the bottle neck is with the slow AGP 2x on the board. THe vid card is the ATI 9800 pro 256 MAC edition, that was a pricey card so I will stick with it. I think the highest I can go per gigadesigns site on my dual 1.4 is a quicksilver 2002 board.Would a QS 2002 board fit in the gigabit case? TCP thanks for the reply I think the bottle neck is with the slow AGP 2x on the board. THe vid card is the ATI 9800 pro 256 MAC edition, that was a pricey card so I will stick with it. I think the highest I can go per gigadesigns site on my dual 1.4 is a quicksilver 2002 board.Would a QS 2002 board fit in the gigabit case? You are exactly right about the 2X AGP being your bottleneck. Don't expect AGP 4X to be twice as fast though. In my experiences its maybe 1.5X faster. A 9800 may even be overkill for AGP 4X so buying a new video card will just be wasting money. If you are comfortable doing a bit of case modification you could get a QS board in there. The main boost you would get with a QS board is the 133MHz bus vs. the 100MHz on your Gigabit. Hope this info helps.. good luck in your quest for PowerPC speed. I myself have a real thing for dual PowerPC systems. You could almost say they give me wood. HAHAHA You havent said why you want faster graphics. Games? If so, you need a new machine. For pro apps though, you should be just fine, unless you are using Motion, then you still need a new machine. You wont get much faster unless you go with a MDD or G5 and for the bucks, I say go with mactel. That said, you have a very fine machine. The QS board will not fit without some mods and to be honest, it is on the whole, cheaper to buy the whole machine as they are going for around 200 bucks right now. Another thought.. if you're determined to get AGP 4x by adding a new board then you're better off going with a Digital Audio board. It would fit in your case with less modification and still has the 133MHz bus. Although a DA doesn't take DDR memory it doesn't really matter on a QS or any G4 tower that took DDR ram. Why? Because the system bus isn't fast enough to allow the memory to run at 2X the speed. DDR memory is a tad faster on G4's but not even close to enough to make it worth replacing all your memory. Another thought.. if you're determined to get AGP 4x by adding a new board then you're better off going with a Digital Audio board. It would fit in your case with less modification and still has the 133MHz bus. Although a DA doesn't take DDR memory it doesn't really matter on a QS or any G4 tower that took DDR ram. Why? Because the system bus isn't fast enough to allow the memory to run at 2X the speed. DDR memory is a tad faster on G4's but not even close to enough to make it worth replacing all your memory. Is the memory PC133 or PC100? thanks for the reply, i love to mess with hardware and take old machines and max them out, its fun. the ram is pc100m, so the DA will fit better than a QS? You havent said why you want faster graphics. Games? If so, you need a new machine. For pro apps though, you should be just fine, unless you are using Motion, then you still need a new machine. You wont get much faster unless you go with a MDD or G5 and for the bucks, I say go with mactel. That said, you have a very fine machine. The QS board will not fit without some mods and to be honest, it is on the whole, cheaper to buy the whole machine as they are going for around 200 bucks right now. Thanks for the reply, no not games... i have a PC game rig that i enjoyed putting together while saving up for a mac pro some day. for now the pc runs a liquid cooled e6400 OCed to 3.4ghz and ram to just under 1k. I love G4's and cannot help to want to max them out and experiment with them. I wish I were more familiar with them, thus the questions. I already put good money into it via the chip and video card. I just noticed the cpu getting tapped much more than i expected and then i saw that the AGP was 2x and the bus 100. So, maybe a slight push for the fun of modding. The only issue is that the vid is AGP 2x and 4x compat and the new gigadesign chip only works with the AGP line. So I am trying to get to the max within reasonable limits of the machine. So the MDD or what machine is gong for 200?Right now I use the G4 for everyday use and mainly photoshop. Xplain's use of MacNews, AppleCentral and AppleExpo are not affiliated with Apple, Inc. MacTech is a registered trademark of Xplain Corporation. AppleCentral, MacNews, Xplain, "The journal of Apple technology", Apple Expo, Explain It, MacDev, MacDev-1, THINK Reference, NetProfessional, MacTech Central, MacTech Domains, MacForge, and the MacTutorMan are trademarks or service marks of Xplain Corp. Sprocket is a registered trademark of eSprocket Corp. Other trademarks and copyrights appearing in this printing or software remain the property of their respective holders. All contents are Copyright 1984-2010 by Xplain Corporation. All rights reserved. Theme designed by Icreon.

Alastair Cook and Kevin Pietersen during the 2013-14 Ashes According to the Daily Mirror, Alastair Cook and a host of members in the English cricket team’s backroom staff had informed higher authorities that they would quit if Kevin Pietersen was brought back into the English team. Cook had threatened to quit not only from his role as captain, but also retire from international cricket. England’s new director of cricket Andrew Strauss, on Tuesday, had said that there is no way Pietersen could return to the national team this summer due to “trust issues”. Strauss took full responsibility for the decision and faced severe criticism, with #StraussLogic even trending on Twitter. I see the head boy is making English cricket the laughing stock again! #StraussLogic — Graeme Smith (@GraemeSmith49) May 12, 2015 It now seems that the former Test opening batsman made the call because of added pressure from other sources. Cook is said to gone to the extent of giving a ‘us or him’ ultimatum to the England and Wales Cricket Board (ECB). “There are people who would absolutely have walked away rather than deal with Kevin again. He has made life incredibly difficult for a large number of people over the years and the idea that he might be back horrified them,” a source told the Mirror. Speaking to the media for the first time since his appointment, Strauss had said: "Now is the time for some really honest and open conversation about Kevin Pietersen. No one has ever doubted his ability as a batsman or as a cricket player. “Over the months and years the trust has eroded it is not in the best short-term interests of the side for Kevin Pietersen to be in the team this summer but he is not banned from the side. At the moment we are quite estranged. This is not about Kevin Pietersen it is about the future of English cricket. My job is to develop a side that is capable of winning matches over the next four years,"

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Evaluation of platelets and hemostasis during hemodialysis with six different membranes. Hemodialysis induces thrombocytopenia and activation of coagulation. The severity of this reaction depends on the kind of membrane. In this study, we present the results of determination of platelet count, and of different factors of coagulation in 10 stable dialysis patients. Measurements were performed at the start and after 15 and 45 min of dialysis. Samples were taken before and after the dialyzer. All 10 patients were treated consecutively and in a random order during 14 days with the following membranes: polyacrylonitrile (Filtral 12, Hospal), hemophan (GFS 120 Plus, Gambro, and Bio-Nephros HF Andante, Organon), polysulfone (F6, Fresenius), cuprammonium (AM50-BIO, Asahi) and cellulose acetate (Duo-Flux, Cordis-Dow). The cellulose acetate membrane induced a small but significant drop of mean platelet count [results are mean (SEM)]: from 245,000 (17,000) to 224,000 (16,000)/microliters after 15 min. With the same membrane a dramatic increase after 15 min was noted of 6-keto-PGF1 alpha from 56.3 (9) to 146.7 (35.7) pg/ml. The other membranes did not influence significantly prostanoid levels and platelet count. During dialysis no significant changes of fibrinopeptide A (FPA) and von Willebrand factor (VWF) were observed. Nevertheless, predialysis FPA and beta-thromboglobulin (beta TG) concentrations were lowest after 14 days of treatment with cellulose acetate and polyacrylonitrile membranes. It is concluded that the activation of coagulation depends on the membrane used. The activation may be dominated by one single system (e.g. prostanoids). The different predialysis concentration of some of the factors suggests interference of the dialysis membrane with the activation of coagulation during the interdialytic period.

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Sure, the Central Michigan football team didn't have one of it’s most memorable campaigns last season. The Chippewas finished with a final record of 6-7 after being completely demolished by Tulsa, 55-10, in the Miami Beach Bowl on Dec. 19. CMU started the season showing promise at 3-0, however, and made one of the most memorable college football plays to beat Oklahoma State at Boone-Pickens Stadium 30-27. It gave the 2016 Chippewas something to be remembered by. Junior wide receiver Corey Willis received a pitch from senior tight end Jesse Kroll, who caught the deep pass from senior quarterback Cooper Rush for one of the craziest scoring scenarios fans had ever witnessed. However, the play shouldn't have counted. The referees admitted that on the play before that outstanding Hail Mary pass, the intentional grounding penalty on fourth down against the Cowboys shouldn't have kept the game going. It should have been the final play of the game. But it wasn’t. CMU won. Oklahoma State lost. It’s in the NCAA record books. The Cowboys went on to have a great season, finishing 10-3 after beating Colorado 38-8 in the Alamo Bowl on Dec. 29. In addition to the CMU loss, Oklahoma State fell to Baylor and Oklahoma. Just a couple of days ago, the Cowboys unveiled their flashy Alamo Bowl champion rings. They are orange, black and silver with the OSU logo set on a star background, the Alamo Bowl logo. It also displays their final record, which reads 11-2. No, I’m not kidding. That's the record they have on their rings. You would think at the Division I level of college football, immaturity wouldn't come into play like this but it has in Cowboy land. It’s like when you're playing Madden and you start to lose a game in dynasty mode, so you simply quit the game. The loss didn't count and you can just play it over again until you win. That’s pretty much what OSU did, but they never won the game. They lost. Regardless if the play counted or not, it went in the win column for the Chippewas and in the loss column for the Cowboys. OSU had a good season, they bounced back from that loss against CMU early in the season, and went on to a double-digit winning season. CMU went on to lose seven of their final 10 games. The Cowboys were the better team, and they still had the chance to stop CMU on that final play. The odds were still in their favor, and they just didn't get the job done. I’ve watched college football since I was a little kid. I’ve seen teams lose on Hail Mary’s before. I have even been at a game to see it live, when the Green Bay Packers beat the Detroit Lions on Dec. 3, 2015 when the “rebound pass” from Aaron Rodgers to Richard Rodgers gave the Lions a key loss in their season. On the play before, their was a questionable face mask on Rodgers that shouldn't have ever been called, and kept the game alive to eventually give Green Bay that chance to win the game. Here’s the difference: the Lions counted the loss like a professional organization. OSU is obviously still hurt about the loss, and is doing everything in their power to take it away from CMU. Nevertheless, it doesn't matter what they do. It counted for CMU, and it didn't for the Cowboys. While the Chippewas didn't have the greatest season, they can always look back on that play and know it was one of the greatest plays in college football history, whether it should have counted or not. Even if OSU will never see or attempt to understand that, everyone else will.

#load "..\TestCs\ReferencedClass.cs" #load "ReferencedScript.csx" //Write using supplied ScriptContext Output.WriteLine("namespace TestNamespace{class TestClass{public void TestMethod(){}}}"); //With referenced script Output.WriteLine($"// we have multiplied {Go4th(2, 3)}"); //Create instance from intercepted class var rc1 = new ReferencedClass(Context); Output.WriteLine($"// Emitting prop with backing field {rc1.PropertyWithBackingField}"); rc1.Owl($"// using the referenced class to output")

Q: How to analyze preference / comparison on a likert scale User participants experienced method A and then method B of a computer interface. Afterwards, we asked them to indicate which method they preferred regarding certain aspects. For example, for ease of use, which do you prefer, A or B, from 1 to 7 (Likert scale), where 1 = definitely method A, 4 = Neutral, and 7 = definitely method B. Here are my questions: Since we are directly asking them to compare methods on this Likert scale and thus receive only 1 response, does it make sense to do a statistical analysis? I guess we cannot compare the participants' answers based on different methods because there is only 1 response. If the answer to #1 is no, then do we simply aggregate the data and see how many users prefer A vs. B? If the answer to #1 is yes, then do we statistically analyze if the responses vary from some "neutral" distribution? What's the best method/way to analyze this? A: I believe this is an instance of having 0 independent variables and thus we should use the one-sample median test, a.k.a. the Wilcoxon signed rank test (see this table). This is what I ended up using.

Perinephric abscess (presenting as abdominal pain) due to Listeria monocytogenes. A 5-year-old malnourished child was admitted with a 1-week history of paroxysmal abdominal pain. Evaluation finally revealed a left-sided perinephric abscess caused by Listeria monocytogenes. The child was successfully treated by drainage of the abscess and antibiotic therapy. Renal abscess should be kept in mind in the differential diagnosis of abdominal pain, and Listeria, an unusual pathogen, should be considered as a possible aetiology.

GP putter, HBB 56 & Chipping golf club Description You have all 3 golf clubs The GP putter come in left or right handed and different size for your height. The HBB 56 degree wedge is for a normal golf swing and come in left or right handed and has 11 degree of bounce. The chipping golf club come only in RIGHT handed for now and is 38 inches long. Additional information Weight 5 lbs Dimensions 54 x 5 x 5 in GP hand Right handed, Left Handed GP size 40 inches long if your height is 4’6″ or 4’7″ and 137 cm to 141 cm, 41 inches long if your height is 4’8″ or 4’9″ and 142 cm to 146 cm, 42 inches long if your height is 4’10” or 4’11” and 147 cm to 151 cm, 43 inches long if your height is 5’0″ or 5’1″ and 152 cm to 156 cm, 44 inches long if your height is 5’2″ or 5’3″ and 157 cm to 161 cm, 45 inches long if your height is 5’4″ or 5’5″ and 162 cm to 166 cm, 46 inches long if your height is 5’6″ or 5’7″ and 167 cm to 171 cm, 47 inches long if your height is 5’8″ or 5’9″ and 172 cm to 176 cm, 48 inches long if your height is 5’10” or 5’11” and 177 cm to 181 cm, 49 inches long if your height is 6’0″ or 6’1″ and 182 cm to 186 cm, 50 inches long if your height is 6’2″ or 6’3″ and 187 cm to 192 cm, 51 inches long if your height is 6’4″ or 6’5″ and 193 cm to 197 cm, 52 inches long if your height is 6’6″ or 6’7″ and 198 cm to 202 cm, 53 inches long if your height is 6’8″ and up and 203 cm and up

The University of Naples Federico II was established in 1224 through an Imperial Charter of Frederick II Hohenstaufen, King of Sicily and Holy Roman Emperor. It was the first publicly funded university in Europe. Nowadays the university offers courses in essentially all academic disciplines, leading to one hundred fiftyfive graduate level degrees. Research facilities provide support to all these courses. Students are given the opportunity to pursue intellectual development as well as the acquisition of professional skills. Current student enrollment nears 86,000 and the academic personnel, at this time, is 2532. The university is made up of three Schools - the Polytechnical and Basic Sciences School, the School of Medicine and the School of Human and Social Sciences - and 26 Departments which operate as semi independent bodies for the teaching and research management being anyway part of a School. In addition, the University of Naples Federico II includes a cluster of fourteen highly specialised Museums, covering a wide range of fields, and two botanical gardens hosting unique species. The central library facility is linked to the division and school libraries; it runs many digital programmes designed to provide free access and the widest possible dissemination of published material to the academic staff. There are seventeen inter-departmental research centres (see organisational chart) open to scholars of all departments and schools and twentyone service and study centres. The University Federico II has a tradition of promoting and supporting student associations. There are more than fifty student associations currently active, which bring together students, of widely varied cultural and social background. These associations give rise to initiatives and activities of different nature, including sporting events, arts, social and political forums. The venue of the university has changed many times, over the many centuries of its history (see History). Nowadays, the size of the university is such that its venues are spread throughout the city of Naples and its immediate surroundings. The three major campuses are located in the centre of town, its Northern and Western outskirts. The Senate House and the main administrative offices, along with the Department of Law and Liberal Art are in central Naples; the much newer campuses on the hill of Camaldoli (North) and the Fuorigrotta (West) areas, host the Departments of Medicine, Pharmacy and Biotechnologies and the Departments of Sciences and Economics, respectively. The School of Medicine includes a large University Hospital, as part of a much larger hospital system, which includes the multi-speciality ‘Cardarelli' Hospital, the largest hospital of Southern Italy the Cancer Institute and the Hospital for Infectious diseases. The University Federico II is striving to become a world university and, to this end, places the highest priority in nurturing relationships, both within Italy and internationally. Our students are relentlessly encouraged in the pursuit of excellence, at home and abroad. Our staff and students take part in a variety of exchange programmes, within Europe, the Americas and Asia. While promoting cooperation with the more scientifically advanced research institutions of the affluent world, we are making every effort to help the less fortunate. Citizens of Northern Uganda have one doctor out of each 40,000 people: ‘Gulunap' is the interuniversity cooperative project undertaken by the University of Naples Federico II and the School of Medicine of the city of Gulu in Northern Uganda. The project, started in 2004, aims at training doctors for the specific needs of the local communities, first call treatments, promotion of preventive medicine and an integrated therapeutic approach. Four years down the road, the school has nearly twohundred students coming from all over Uganda but also from Kenya, Sudan and Congo. Cognizant of the changing needs of education and research, the Federico II University of Naples is making every effort to raise its international standings and to become more attractive for international students. Its educational network is being geared towards the establishment of life-long, high level professional training programmes, while maintaining excellence in all fields of education and research.

The US Food and Drug Administration (FDA) cleared a screening test which predicts a patient’s future coronary heart disease (CHD) events such as heart attacks, according to a statement. While the test is approved for all adults with no history of heart disease, the FDA reviewed studies which demonstrated the test is best suited for black women. “A cardiac test that helps better predict future CHD risk in women, and especially black women, may help health care professionals identify these patients before they experience a serious CHD event, like a heart attack,” Alberto Gutierrez, director of the Office of In Vitro Diagnostics and Radiological Health in the FDA’s Center for Devices and Radiological Health, said in a press release. “We hope the clearance of this test will improve preventative care and reduce CHD-related mortality and morbidity in these patients.” The new test is called the PLAC Test for Lp-PLA2 Activity, designed by the California based diaDexus company, which measures the activity of lipoprotein associated phospholipase A 2 in a patient’s blood. The Lp-PLA2 is a biomarker in blood that indicates vascular inflammation which is associated with the buildup of plaque in the arteries. This artery buildup can lead to CHD, which the PLAC Test aims to prevent. Patients whose test results show Lp-PLA2 activity greater than 225 nmol/min/mL are at increased risk for CHD. If test results are lower than 225 nmol/min/mL, patients are at a decreased risk for CHD events. The FDA’s approval was based on a sub study of the National Institutes of Health’s national Reasons for Geographic and Racial Differences in Stroke study. The study included 4,598 patients targeted based on gender and race who were aged 45 to 92 years with no history of CHD. The study cohort consisted of 41.7 percent men, 58.3 percent women, 41.5 percent blacks, and 58.5 percent whites. The patients in the longitudinal study were observed for several years (median 5.3 years) to determine which patients experienced CHD related events. Participants whose test results were higher than 225 nmol/min/mL had a CHD event rate of 7 percent, while patients whose test results were below that level had a CHD rate of 3.3 percent. The FDA requested further subgroup analysis, including black women, because the study demonstrated a strong correlation between black women and the rate of CHD events compared to other participants in the study whose test results were higher than 225 nmol/min/mL. The test labeling will reflect different performance data for black women, black men, white women, and white men. The US Centers for Disease Control and Prevention acknowledged the leading cause of death is heart disease for people of most races — blacks, Hispanics, and whites are all at risk. There is also no difference between CHD event risk between men and women. Most importantly, nearly two thirds of women and half of men who die suddenly of CHD demonstrate no prior symptoms.

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Q: How granular should a command be in a CQ[R]S model? I'm considering a project to migrate part of our WCF-based SOA over to a service bus model (probably nServiceBus) and using some basic pub-sub to achieve Command-Query Separation. I'm not new to SOA, or even to service bus models, but I confess that until recently my concept of "separation" was limited to run-of-the-mill database mirroring and replication. Still, I'm attracted to the idea because it seems to provide all the benefits of an eventually-consistent system while sidestepping many of the obvious drawbacks (most notably the lack of proper transactional support). I've read a lot on the subject from Udi Dahan who is basically the guru on ESB architectures (at least in the Microsoft world), but one thing he says really puzzles me: As we get larger entities with more fields on them, we also get more actors working with those same entities, and the higher the likelihood that something will touch some attribute of them at any given time, increasing the number of concurrency conflicts. [...] A core element of CQRS is rethinking the design of the user interface to enable us to capture our users’ intent such that making a customer preferred is a different unit of work for the user than indicating that the customer has moved or that they’ve gotten married. Using an Excel-like UI for data changes doesn’t capture intent, as we saw above. -- Udi Dahan, Clarified CQRS From the perspective described in the quotation, it's hard to argue with that logic. But it seems to go against the grain with respect to SOAs. An SOA (and really services in general) are supposed to deal with coarse-grained messages so as to minimize network chatter - among many other benefits. I realize that network chatter is less of an issue when you've got highly-distributed systems with good message queuing and none of the baggage of RPC, but it doesn't seem wise to dismiss the issue entirely. Udi almost seems to be saying that every attribute change (i.e. field update) ought to be its own command, which is hard to imagine in the context of one user potentially updating hundreds or thousands of combined entities and attributes as it often is with a traditional web service. One batch update in SQL Server may take a fraction of a second given a good highly-parameterized query, table-valued parameter or bulk insert to a staging table; processing all of these updates one at a time is slow, slow, slow, and OLTP database hardware is the most expensive of all to scale up/out. Is there some way to reconcile these competing concerns? Am I thinking about it the wrong way? Does this problem have a well-known solution in the CQS/ESB world? If not, then how does one decide what the "right level" of granularity in a Command should be? Is there some "standard" one can use as a starting point - sort of like 3NF in databases - and only deviate when careful profiling suggests a potentially significant performance benefit? Or is this possibly one of those things that, despite several strong opinions being expressed by various experts, is really just a matter of opinion? A: On the topic of "every attribute change" I think you missed the point. Mr. Udi Dahan is saying you should capture the user's intent as a command. An end-user is concerned with being able to indicate that a customer has moved. Depending on the context that command could contain a customer identification, the new address (split up into street, streetnumber, zipcode, ...), optionally a new phone number (not uncommon when you move - maybe less so with all these cellphones). That's hardly one attribute. A better question is "how do I design commands?". You design them from a behavioral perspective. Each use-case, flow, task an end-user is trying to complete, will be captured in one or more commands. What data goes with those commands comes naturally, as you start reasoning about them in more detail. The thing to watch out for is data that gets interpreted as "logic flow control" on the server side. That might be an indication that you need to split up the command. I hope you never find that standard with regard to command granularity. Good question though!

Search template localisation Introduction The Modern UI supports internationalisation/localisation of form files, allowing a single form file to provide search results in a variety of languages: A set of translations can be defined per language, and the form file will be displayed with the relevant translations according to the language selected by the search user. Quickstart Create $SEARCH_HOME/conf/<collection>/_default/ui.en_US.cfg with the following content: Specifying the locale at query time There are multiple ways to specify which locale should be used to process a search at query time: Using auto-detection This is the default mechanism which will detect the best locale based on the information sent by the search user browser (The Accept-Language request header). Setting the lang CGI parameter Setting this parameter will affect both the user interface locale, as well as the language used in the query processor. Please consult the documentation of the langquery processor option for more details. Setting the lang.ui CGI parameter Setting this parameter will only affect the user interface, not the query processor. It allows you to use a given locale for the form file, but a different lang parameter for the query processor.The locale must be specified as a ISO 639 language code such as en or fr. Additionally, a ISO 3166 country code can be appended with an underscore, i. e. en_GB or fr_BE. Examples: ...&lang=en... ...&lang=en_GB... ...&lang=en&lang.ui=fr_FR... The locale is available in the data model under the question.locale node. Defining translations Translations should be defined in configuration files, either on a global scope that will be available for all collections, or on a per-collection/profile basis. Translations for the global scope should be created under $SEARCH_HOME/conf/ and per-collection/profile translations should be created in the profile directory under the collection configuration directory $SEARCH_HOME/conf/<collection>/<profile>. The file format is the usual key/value format. Translation files must be encoded in UTF-8. Lines starting with a hash are treated as comments. For example: # French translations as of July 2012 search=Rechercher results_found=%d résultats trouvés ... The value can contain format specifiers such as %d, %s, etc. These specifiers will be replaced with provided values, allowing the translations to be dynamic when needed. In the previous example the %d would be replaced by the number of results found (See below the section about accessing the translations in the form file for more information). The formatting system is based on Java Formatter class, please refer to this documentation for more details. File naming conventions and precedence order A file must be created for each locale, containing the translations for that locale. In addition, a generic locale-independent file can be created to contain fall-back values when a translation is missing for a specific term. The locale-independent file is named ui.cfg Locale specific files are named ui.<locale>.cfg. For the en locale, the file must be named ui.en.cfg. For the en_GB locale, the file must be named ui.en_GB.cfg For example for an en and en_GB locales, the following files could be created: $SEARCH_HOME/conf/ui.cfg: Locale-independent values, for all collections $SEARCH_HOME/conf/ui.en.cfg: Generic translations for all collections for the 'en' locale $SEARCH_HOME/conf/ui.en_GB.cfg: Generic translations for all collections for the 'en_GB' locale $SEARCH_HOME/conf/intranet/_default_preview/ui.cfg: Locale-independent values, specific to the intranet collection and the _default_preview profile $SEARCH_HOME/conf/intranet/_default_preview/ui.en.cfg: Translations specific to the intranet collection and the _default_preview profile, for the en locale $SEARCH_HOME/conf/intranet/_default_preview/ui.en_GB.cfg: Translations specific to the intranet collection and the _default_preview profile, for the en_GB locale Note: Translation files under the collection folder (outside a profile folder) are not supported. These files will be ignored. If multiple translation files are found, they will be merged together with the more specific specific values overriding the more global ones. The priority order is shown below, with later values overriding earlier ones. $SEARCH_HOME/conf/ui.cfg $SEARCH_HOME/conf/<collection>/<profile>/ui.cfg $SEARCH_HOME/conf/ui.<lang>.cfg $SEARCH_HOME/conf/<collection>/<profile>/ui.<lang>.cfg $SEARCH_HOME/conf/ui.<lang>_<country>.cfg $SEARCH_HOME/conf/<collection>/<profile>/ui.<lang>_<country.cfg> For example if every file contains a different translation for the key search, the one in $SEARCH_HOME/conf/<collection>/<profile>/ui.fr_BE.cfg would take precedence because it is the most specific. Accessing translations in the template Translations are included in the data model under the response.translations node, as a key-value map. Only the translations for the current locale (and the locale-independent ones) are available. This means that if your current locale is fr_BE you will only find one entry for the key search with the value Rechercher. If you switch the locale to en, the value for search will become Search. The map uses the same keys as in the translation files and can be accessed as a regular FreeMarker map: ${response.translations["search"]} or ${response.translations.search} The FreeMarker syntax also allows a fall-back value to be specified with the standard default value operator: ${response.translations.search!"Rechercher"} In addition a custom FreeMarker tag is available, which supports passing arguments to be inserted within the translations: In addition you can take advantage of the built-in FreeMarker localisation support of the #include directive to have per-locale sub-templates. Please refer to the FreeMarker documentation for more information.

Ready Lisp version 20090130 now available - vrs http://www.newartisans.com/blog/2009/01/ready-lisp-version-20090125-now-available.html ====== DenisM From site: What is Ready Lisp? It’s a binding together of several popular Lisp packages for OS X, including: Aquamacs, SBCL and SLIME. Once downloaded, you’ll have a single application bundle which you can double-click — and find yourself in a fully configured Common Lisp REPL. It’s ideal for OS X users who want to try out Lisp with a minimum of hassle. The download is approximately 73 megabytes. ------ vikram It works fine. But doesn't have sb-threads enabled so, at best you can use it for fun or development. Webservers like hunchentoot will give errors if you open a second request at the same time. The way to fix this is, to do a which sbcl to find out where it's installed for me it was in /opt/local/ then download the source from <http://www.sbcl.org> In the sbcl folder create a file called customize-target-features.lisp and put the following code in it... (lambda (features) (flet ((enable (x) (pushnew x features)) (disable (x) (setf features (remove x features)))) ;;; Threading support, available only on x86/x86-64 Linux, x86 Solaris ;;; and x86 Mac OS X (experimental). (enable :sb-thread))) now sh make.sh and then export INSTALL_ROOT=/opt/local/ and sudo sh install.sh Try sbcl if you get an error that it can't find the core then copy the core in output folder in sbcl to where it says it can't find sbcl.core that'll give you sbcl with threads on macosx and Aquamacs that loads it in a fraction of a second.

Q: Windows Licensing Question This is slightly off topic of programming but still has to do with my programming project. I'm writing an app that uses a custom proxy server. I would like to write the server in C# since it would be easier to write and maintain, but I am concerned about the licensing cost of Windows Server + CALS vs a Linux server (obviously, no CALS). There could potentially be many client sites with their own server and 200-500 users at each site. The proxy will work similar to a content filter. Take returning web pages, process based on the content, and either return the webpage, or redirect to a page on another webserver. There will not be any use of SQL server, user authentication, etc. Will I need Cals for this? If so, about how much would it cost to setup a Windows Server with proper licensing (per server, in USA)? A: This really is an OT question. In any case, there is nothing easier than contacting your local MS distributor. As stackoverflow is by nature an international site, asking a question like that, where the answer is most likely to vary by location (MS license prices really are highly variable and country-specific) is in my opinion not likely to receive an useful answer. A: I realize this isn't exactly answering your question but if you want to use Linux, maybe you want to look into using Mono. .Net on Linux. A: If users will not be actually connecting to any MS server apps (such as Exchange, SQL Server, etc) and won't be using any OS features directly (i.e. connecting to UNC paths) then all that should be required is the server license for the machine to run the OS. You need Windows Server CALs when clients connect to shares, Exchange CALs for mail clients, and SQL Server CALs for apps that connect to your databases. If the clients of your server won't be connecting to anything but the ports offered by your service, you should be in the clear, and it shouldn't cost any more to build a server for 100 users than 10.

The present invention relates to an automatic figure drawing apparatus and method, and particularly relates to an automatic figure drawing apparatus and method in a computer aided design system (hereinafter abbreviated as "CAD system"). CAD (Computer Aided Design) is an art which has the purposes of making design high in speed, high in quality, and so on. In a CAD system, in order to attain these objectives, it is important to make automatic figure drawing efficient by re-using figure data and using standard parts figure data. FIGS. 9(a)-(c) are block system diagrams illustrating a conventional automatic figure drawing apparatus. FIG. 9(a) shows an apparatus for figure drawing by a parametric system, in which data described in a book or the like, such as inner and outer diameters, width, etc. of a bearing are put into a CAD system, and automatic figure drawing is performed in accordance with a drawing program of this CAD system. There have been problems in this case in that if erroneous data is put into a CAD system, an erroneous figure is drawn on the basis of the erroneous data, and in that it is troublesome to input data in accordance with the order of a predetermined format. The figure drawing by a parametric system is that in which, for example, a parallelogram is expressed by variables a, b and .alpha. as shown in FIG. 8(c); a regular square being expressed if a=b and .alpha.=90.degree., a rectangle being expressed if a b and .alpha.=90.degree., a parallelogram being expressed if a b and .alpha. 90.degree.. Thus, various quadrilaterals different in kind or size can be expressed in accordance with the variables a, b and .alpha.. There is another figure drawing system, which is called a vector data system. This is a system to express a regular square and a regular triangle by variables a' and b' as shown in FIGS. 8(a) and 8(b) respectively; the variable a' can express only a regular square, while the variable b' can express only a regular triangle. That is, for example, if a rectangle is to be expressed, other variables, such as x and y are used. In the above-mentioned example of quadrilaterals, this system has co-ordinates of start and end points of respective lines as data; in the regular square in FIG. 8(a), its four sides are expressed by co-ordinates a1, a2, a3 and a4 of the constant a', and in the quadrilateral in FIG. 8(c), its four sides are expressed by co-ordinates b1, b2, b3 and b4. Those co-ordinates vary if the size of the figure vary. Being different from a figure drawing method using a figure drawing program as shown in FIG. 9(a), a figure drawing method shown in FIG. 9(b) is such that necessary data is selected, by inputting a command, from figure data (so-called electronic catalog data) stored in advance in a memory means such as a magnetic disk in which a data base is built. Being different from the case where a person reads catalog data values in a book and inputs the read-out catalog data values into a CAD system as shown in FIG. 9(a), figure data entry error is less because of the electronic catalog data on a magnetic medium. There are however problems in that all the necessary figure data must be stored on a magnetic medium, so that a magnetic disk having a large capacity is required which thereby results in a disadvantage in cost and space, and in the case of using floppy disks, the number of the disks becomes large which results in combersome management thereof. A figure drawing method shown in FIG. 9(c) is a method in which figure data for CAD is produced by a figure drawing program of a parametric system having a data base which is not running on CAD, and the figure data are read into a CAD system to perform figure drawing. In the method, therefore, there has been a problem of troublesome operation in that another CAD system is required and switching is also necessary.

1. Field of the Invention The present invention relates to a single use lancet assembly which is substantially compact, yet effective for piercing a patient's finger or other body part to obtain a blood sample. The single use lancet device is further configured to be substantially safe to transport and to ensure that subsequent uses of a contaminated lancet tip cannot occur. 2. Description of the Related Art Lancets are commonly utilized instruments which are employed both in hospitals and other medical facilities, as well as by private individuals, such as diabetics, in order to prick or pierce a patient's skin, typically on a finger of a patient, thereby leading to the generation of a blood sample which can be collected for testing. Because of the wide spread use of such lancets, there are a variety of lancet devices which are available for utilization by patients and/or practitioners in a variety of different circumstances. For example, a typical lancet may merely include a housing with a sharp piercing tip that is pushed into the patient's skin. More commonly, however, lancet devices, which house a piercing tip and/or a lancet, have been developed which effectively encase and fire the lancet into the patient's skin, thereby eliminating the need for the person taking the sample to actually push the lancet tip into the skin. Within the various types of specialized lancet devices, one variety is typically configured for multiple and/or repeated uses, while another category is particularly configured for single use, after which the entire device is disposed of. Looking in particular to the single use, disposable lancet devices, such devices typically include a housing which contains and directs or drives a piercing tip into the patient's skin, and which is disposed of along with the used lancet. Naturally, so to make such disposable devices cost effective for frequent use, such devices tend to be rather simplistic in nature providing only a sufficient mechanism for firing, and not overly complicating the design so as to minimize that cost. While existing single use devices are generally effective for achieving the piercing of the skin required for effective operation, such single use, disposable devices typically do not incorporate a large number of safety features to ensure the safe use and disposal of the device. For example, one primary area of safety which must be addressed with all lancet devices pertains to the purposeful and/or inadvertent reuse of a contaminated lancet. Unfortunately, most currently available single use lancet devices are configured such that after a use thereof has been achieved, it is possible for a patient to re-cock the device, thereby allowing for a subsequent, inappropriate use. As a result, it would be highly beneficial to provide a single use lancet device which is substantially compact and disposable, can be manufactured in a substantially cost effective manner, and which nevertheless is substantially safe to utilize, affirmatively preventing re-use, once contaminated.

Yet another Soviet attempt to soft-land a Ye-6 probe on the lunar surface ended in failure when the Blok L upper stage failed to fire for the translunar injection burn. Instead, the spacecraft remained stranded in Earth orbit. A later investigation indicated that there had been a short circuit in an inverter within the I-100 guidance system of the spacecraft (which also controlled the Blok L stage) preventing engine ignition. The spacecraft's orbit decayed five days later. Key Dates 12 Mar 1965: Launch Status: Unsuccessful Fast Facts This was the Soviet Union's 30th interplanetary launch. A short circuit prevented engine ignition, stranding the spacecraft in Earth orbit. The Soviet gave this Luna series spacecraft a Kosmos Earth-orbiting designation to conceal the fact it failed to make it to the Moon as planned.

For indispensable reporting on the coronavirus crisis, the election, and more, subscribe to the Mother Jones Daily newsletter. House Speaker Nancy Pelosi on Sunday issued a warning to Republicans: If the Trump administration blocks the disclosure of a whistleblower complaint involving the president’s interactions with his counterpart in Ukraine, then “they will be entering a grave new chapter of lawlessness.” The letter comes four days before Acting Director of National Intelligence Joseph Maguire is set to testify before the House Intelligence Committee. Trump has refused to release the whistleblower complaint or the transcript of his call with Ukrainian President Volodymyr Zelensky, ignoring demands from Democratic House and Senate leadership. Pelosi first urged the administration to release the complaint on Friday and followed up with a pointed letter to her Republican colleagues on Sunday. .@SpeakerPelosi to Congress:If Trump admin persists in blocking whistleblower from disclosing to Congress a serious possible breach of constitutional duties by @POTUS they’ll be entering a grave new chapter of lawlessness which will take us into a whole new stage of investigation pic.twitter.com/jOIOsZkQHr — David Begnaud (@DavidBegnaud) September 22, 2019 Pelosi, who has not called for Trump’s impeachment, warned that preventing the whistleblower complaint’s disclosure would amount to a violation of federal statute. “The Administration is endangering our national security and having a chilling effect on any future whistleblower who sees wrongdoing,” she noted. “If the Administration persists in blocking this whistleblower from disclosing to Congress a serious possible breach of constitutional duties by the President, they will be entering a grave new chapter of lawlessness which will take us into a whole new stage of investigation,” Pelosi concluded. On Sunday, Trump admitted to reporters that he had discussed former vice president Joe Biden with Ukraine’s president but insisted there was no “quid pro quo” between the two leaders. Meanwhile, consensus is growing that Trump’s request of the Ukrainian president constitutes an impeachable offense. Schiff told CNN’s Jake Tapper that if Trump withheld foreign aid to Ukraine hoping for an inquiry into a political opponent, then impeachment proceedings “may be the only remedy.”

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Bioreducible PEI-functionalized glycol chitosan: A novel gene vector with reduced cytotoxicity and improved transfection efficiency. Non-viral gene delivery has been well recognised as a potential way to address the main safety limitations of viral gene carriers. A new redox-responsive PEI derivative was designed, synthesized and evaluated for non-viral delivery applications of GFP DNA. Glycol chitosan was covalently attached to highly branched LMW PEI via bio-cleavable disulfide bonds to synthesize a new redox-responsive gene carrier (GCS-ss-PEI). Results showed the enhanced buffering capacity of GCS-ss-PEI, 43.1%, compared to the buffering capacities of both LMW PEI and HMW PEI, 23.2% and 31.5%, respectively, indicating more likely endosomal escape of the entrapped gene for GCS-ss-PEI. Moreover, electrophoretic gel retardation assay, performed to investigate the binding strength of GCS-ss-PEI to GFP DNA, showed stronger complexation with GFP DNA in GCS-ss-PEI at non-GSH condition. Employing GCS and incorporation of disulfide bonds in the structure of the PEI-based gene carrier resulted in improved redox-responsivity, reduced toxicity, enhanced endosomal escape and GFP DNA transfection. The facilitated intracellular gene release along with excellent redox-responsive characteristics and dropped cytotoxicity suggests the potential of GCS-ss-PEI as a candidate for developing highly efficient and safe gene vectors.

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--- abstract: 'In the context of cosmological perturbation theory, we derive the second order Boltzmann equation describing the evolution of the distribution function of radiation without a specific gauge choice. The essential steps in deriving the Boltzmann equation are revisited and extended given this more general framework: i) the polarisation of light is incorporated in this formalism by using a tensor-valued distribution function; ii) the importance of a choice of the tetrad field to define the local inertial frame in the description of the distribution function is emphasized; iii) we perform a separation between temperature and spectral distortion, both for the intensity and for polarisation for the first time; iv) the gauge dependence of all perturbed quantities that enter the Boltzmann equation is derived, and this enables us to check the correctness of the perturbed Boltzmann equation by explicitly showing its gauge-invariance for both intensity and polarization. We finally discuss several implications of the gauge dependence for the observed temperature.' author: - 'Atsushi Naruko$^{1}$, Cyril Pitrou$^{2,3}$, Kazuya Koyama$^{4}$, Misao Sasaki$^{5}$' date: 'May 8, 2013' title: 'Second order Boltzmann equation : gauge dependence and gauge invariance' --- Introduction ============ The non-Gaussianity in the Cosmic Microwave Background (CMB) has been one of the hottest topics in cosmology because it could open a new window for probing the primordial universe. Recent CMB observations, especially WMAP [@Komatsu:2010fb] and Planck [@Ade:2013ydc], have confirmed to a very high accuracy that the primordial curvature perturbations have a nearly scale invariant initial power spectrum and the associated statistics is nearly Gaussian. These observations are consistent with the predictions of an early inflationary era driven by a single slow-rolling scalar field. The possibility of non-Gaussianity in the primordial curvature perturbations was discussed for the first time quantitatively by Komatsu and Spergel [@Komatsu:2001rj]. They parameterized the level of non-Gaussianity in the potential $\Phi(x)$ (the curvature potential in the Newton or Poisson gauge) by $$\Phi (x) = \Phi_{{\mathrm{L}}} (x) + f_{{\mathrm{NL}}}^{{\mathrm{local}}} \Bigl[ \Phi^2_{{\mathrm{L}}} (x) - \langle \Phi_{{\mathrm{L}}}^2 (x) \rangle \Bigr] \,.$$ Here, $\Phi_{{\mathrm{L}}} (x)$ denotes the Gaussian part of the perturbation, or in perturbation theory its linear part, and $\langle \cdots \rangle$ designates the statistical average. This type of non-Gaussianity leads to a non-vanishing three point correlation function, or equivalently in reciprocal space to a non-vanishing bispectrum. The prediction for the possible values of this parameter $f^{{\mathrm{local}}}_{{{\mathrm{NL}}}}$ from a phase of single-field slow-roll inflation was first performed by Maldacena [@Maldacena:2002vr], and it was shown that it is of order of the slow-roll parameters and thus highly suppressed. Hence, if a $f^{{\mathrm{local}}}_{{{\mathrm{NL}}}}$ of order unity or greater is detected, this simplest model of inflation will be ruled out. Unfortunately, the interpretation of the measured non-Gaussianity is not so straightforward because we do not observe directly the primordial non-Gaussianity in the curvature perturbation but its effect on the CMB fluctuations. Therefore, to relate the primordial curvature perturbation to CMB, we first have to compute the evolution of perturbations after inflation. These effects can be split unambiguously in two parts: i) a linear transfer that cannot create a non-Gaussian signal if the initial conditions are purely Gaussian, and ii) a non-linear transfer that generates a non-Gaussian signal in the observables even if the initial conditions are purely Gaussian. The resulting non-Gaussian signal from i) is often called [*primordial non-Gaussianity*]{} and all the possible sources of non-linear evolutions which enter the category ii) are called [*secondary non-Gaussianity*]{}. Recently the Planck collaboration provided a constraint $f^{{\mathrm{local}}}_{{{\mathrm{NL}}}} = 2.7 \pm 5.8$ [@Ade:2013ydc]. This result was obtained by subtracting one of the secondary non-Gaussianities that arises from the correlation between the lensing and integrated Sachs-Wolfe effect. This clearly demonstrates the importance of subtracting all the secondary non-Gaussianity consistently in order to obtain an accurate constraint on the primordial non-Gaussianity. The evolution of the perturbations on super-horizon scales is well understood, even fully non-linearly using either a covariant approach [@Langlois:2005ii; @Langlois:2005qp; @Enqvist:2006fs; @Pitrou:2007xy], or a separate universe approach with the so-called $\delta N$ formalism [@Comer:1994np; @Kolb:2004jg; @Lyth:2004gb], since it leads to a conservation law for the curvature perturbations in the case of adiabatic perturbations. On the other hand, the evolution for modes below the horizon scale is not so simple analytically, especially at the non-linear order, and the use of a kinetic description cannot be avoided on small scales since radiation starts to develop an anisotropic stress. In order to obtain numerical results for the non-linear evolution, we need to derive and solve without approximations the coupled system of non-linear a) Einstein equation for the metric, b) conservation and Euler equations for fluids and c) Boltzmann equation for radiation (photons and neutrinos). Note that the conservation and Euler equations can always be deduced from the lowest moments of the Boltzmann equation, and the full set of equations is often only referred to as [*Einstein-Boltzmann system*]{} of equations. In order to follow this roadmap, the second order Boltzmann equation was written down in the Poisson gauge in Refs. [@Bartolo:2006cu; @Bartolo:2006fj; @Pitrou:2008hy; @Pitrou:2008ut; @Pitrou:2010sn; @Beneke:2010eg]. The gauge dependence of the distribution function was obtained at linear order [@Durrer:1993db] and then at second order [@Pitrou:2007jy] but leaving aside the problem of polarisation. It was then extended to include polarised light in Ref. [@Pitrou:2008hy]. The system of equations was then solved numerically in Fourier space in Poisson gauge in [@Pitrou:2010sn], and it was reported that the secondary effects around the last-scattering surface could mimic a primordial signal of $f_{{\mathrm{N L}}}^{{\mathrm{local}}} \sim 4$. Recently there have been a huge progress in improving the numerical calculations and clarifying the amplitude of various secondary non-Gaussianities at recombination [@Huang:2012ub; @Su:2012gt; @Pettinari:2013he], and a consensus emerged that when including all the non-linear effects around recombination *and* the integrated early effects after recombination, it could mimic a primordial signal of $f_{{\mathrm{N L}}}^{{\mathrm{local}}} \sim 0.8$, as expected from analytic approximations [@Creminelli:2011sq]. The description of the spectral dependence of the distribution function is also crucial at second order. Indeed, at first order there are no spectral distortions and the perturbation of the photon distribution function can be understood as a single, spectrum-independent temperature fluctuation. However, at second order, there appears a deviation from the Planck distribution, resulting in a continuum of spectral distortions, which in principle must superimpose the thermal Sunyaev-Zeldovich effect [@Ade:2013qta]. To describe this distortion, we use a direction and position dependent Compton $y$ parameter [@Stebbins:2007ve; @Pitrou:2009bc], and also introduce a similar tensor-valued variable to describe the distortion in the polarisation, thus extending the formalism introduced in Ref. [@Pitrou:2009bc]. In this paper, we derive the second order Boltzmann equation without restricting to a specific gauge, and including polarisation. Reflecting on the above, our motivation is two-fold. First, since the structure of the second order Einstein and Boltzmann equations depends very much on a choice of the gauge, we have to find a gauge in which we can numerically solve this system accurately and quickly. Therefore, it is preferable not to specify the gauge from the beginning but to formulate the equations without specifying it. We can impose different gauge restrictions in their final form to explore the stability and efficiency of the numerical integration. Second, we would like to check the equations derived in Refs. [@Pitrou:2008hy; @Pitrou:2010sn; @Beneke:2010eg]. As a direct check, we recover them in the specific case of the Poisson gauge. Then, as an indirect check, we revisit the transformation properties of the distribution function and the metric perturbations and confirm that the perturbed Boltzmann equation is gauge-invariant up to second order in perturbations, thus increasing our confidence in the rather lengthy derivation. In Ref. [@Pettinari:2013he], it was found that the inclusion or omission of certain line of sight terms can make a large impact on the estimation of the bias to the primordial non-Gaussianity due to the secondary non-Gaussianity. In Refs [@Huang:2012ub; @Pettinari:2013he] all physical effects were included except for lensing and time-delay. These time-integrated effects require a separate analysis because at later times small-scale multipoles get excited and numerically it is very difficult to evolve the equations. In this paper, we point out that the separation of these effects depends on a gauge. Given that the lensing-ISW cross correlation gives the largest bias to the primordial local type non-Gaussianity, one should bear this gauge dependence in mind when separating these time integrated effects in the calculations. The choice of the gauge and the associated choice of the tetrad field for the distribution function is also crucial in the interpretation of the quantities as observables. These subtle details do not affect our interpretation of observables in the linear theory since it is only relevant for the monopole and the dipole. However it is no longer the case at second order in perturbations. We must understand the transformation properties of the distribution function under a gauge transformation or a change of the inertial frame and determine what is a gauge and a choice of inertial frame that is related to CMB experiments. The structure of this paper is as follows. In section \[sec:def\], we give the definitions of the variables that we use for the metric, momentum and distribution function. Especially, to express the perturbation of the metric, we use a geometrical $(3+1)$ decomposition, or the ADM [@Arnowitt:1962hi] parametrisation of the metric. At first order, there is no particular advantage in using this formalism, but various expressions are simplified at second order for the choice of the inertial frame that we make. In section \[sec:Boltz\], we derive the second order Boltzmann equation with polarisation without restricting to a specific gauge. In section \[sec:gauge\], we discuss the gauge dependence of the variables. We carefully investigate the gauge transformation of the metric, momentum and the distribution function. We then check explicitly the gauge invariance of the perturbed Boltzmann equation up to second order as a consistency test. Finally, in Section \[sec:conc\], we summarize our results and we comment briefly on the relevance of our formalism for the observed CMB anisotropy. Useful technical details are gathered in the appendices. Definitions {#sec:def} =========== In this section we build all the tools which are used for the description of polarized radiation in cosmology. We first review briefly the parametrization of cosmological perturbations, and explain how a photon momentum can be uniquely described by its energy and direction once a suitable tetrad choice has been made. We then introduce the tensor-valued distribution function which is used to treat statistically a gas of polarized photons, and which is the key object in the Boltzmann equation, and we finally present how it can be decomposed into its main spectral components. Spacetime coordinates and local inertial frame {#ssec:deftet} ---------------------------------------------- We shall use the ADM formalism to write down the expression of the perturbed metric where the metric can be decomposed as $$\begin{aligned} \label{MetricADM} {{\rm d}}s^2 &= a^2(\eta) \Bigl[ - N^2 {{\rm d}}\eta^2 + \gamma_{ij} ({{\rm d}}x^i + \beta^i {{\rm d}}\eta) ({{\rm d}}x^j + \beta^j {{\rm d}}\eta) \Bigr] \nonumber\\ &= a^2(\eta) \Bigl[ - (N^2 - \gamma_{i j} \beta^i \beta^j) {{\rm d}}\eta^2 + 2 \gamma_{ij} \beta^j {{\rm d}}x^i {{\rm d}}\eta + \gamma_{ij} {{\rm d}}x^i {{\rm d}}x^j \Bigr] \,,\end{aligned}$$ where $N$ is the lapse function, $\beta^i$ is the shift vector, $\gamma_{i j}$ is the spatial metric, and indices of the Latin type ($i,j,k\cdots$) run from $1$ to $3$. To describe the perturbations around the flat Friedmann-Lemaître-Robertson-Walker (FLRW) space-time, perturbation variables, $\alpha$ and $h_{i j}$, are introduced as $$\label{DefPertNNi} N \equiv 1 + \alpha \,, \qquad \gamma_{i j} \equiv \delta_{i j} + 2 h_{i j} \,.$$ For simplicity, we use the following definitions $$\beta_i\equiv \delta_{ij} \beta^j \,, \quad h^i{}_j \equiv \delta^{ik} h_{kj} \,, \quad h^{ij} \equiv \delta^{ik} \delta^{jl}h_{kl} \,,$$ where the spatial indices are raised and lowered with $\delta_{ij}$ and $\delta^{ij}$, rather than with $\gamma_{ij}$ and $\gamma^{ij}$. As is clearly seen below, the ADM form of the metric perturbation will simplify the expressions of the perturbed Boltzmann equation. Any perturbation $X$ will be expanded into its first and second order parts as $$X= X^{(1)} + \frac{1}{2} X^{(2)}\,.$$ The relations between the ADM variables and the usual definitions of cosmological perturbations are provided in Appendix \[app:ADM\]. The Boltzmann equation is better formulated by explicitly using a local inertial frame at every point of the space-time and this can be achieved by using a tetrad field. It is a set of four vector fields which satisfy $$\eta_{(a) (b)} = g_{\mu \nu} e_{(a)}{}^\mu e_{(b)}{}^\nu \,, \qquad g_{\mu \nu} = \eta_{(a) (b)} e^{(a)}{}_\mu e^{(b)}{}_\nu \,.$$ These conditions determine the choice of tetrad only up to rotations and boosts. Here the following particular tetrads are chosen up to second order accuracy $$\begin{aligned} e^{(0)}{}_\mu &= a (- N, 0, 0, 0) \,,\qquad e^{(i)}{}_\mu = a \left( \beta^i + h^i{}_j \beta^j, \delta^i{}_j + {h^i}_j - \frac{1}{2} h^{i k} h_{k j} \right) \,, \label{tetrads}\end{aligned}$$ and the inverse tetrads are given by $$\begin{aligned} e_{(0)}{}^\mu = - e^{(0) \mu} &= - \frac{1}{a} \left( \frac{1}{N}, - \frac{\beta^i}{N} \right) \,, \qquad e_{(i)}{}^\mu = \frac{1}{a} \left[ 0, \delta_{(i) (k)} \left( \delta^{j k} - h^{j k} + \frac{3}{2} h^{j l} h_l{}^k \right) \right] \,.\end{aligned}$$ The time-like tetrad is chosen to be orthogonal to the constant time hypersurfaces since ${\bm e}^{(0)} \propto {{\rm d}}\eta$. As for the spatial tetrads, this choice corresponds to asking that there is no rotation between the background and the perturbed tetrads [@Pitrou:2007jy]. Momentum -------- To facilitate the separation between the magnitude of the momentum and its direction in a covariant manner, let us consider the projection of the momentum of photon $p^\mu$ onto the set of tetrads, $$\begin{aligned} p^{(a)} = e^{(a)}{}_\mu p^\mu \,. \end{aligned}$$ We introduce the conformal momentum of photon rather than the physical momentum $p^{(a)}$ $$\label{defpP} q^{(a)} \equiv a p^{(a)} \,.$$ Since the momentum of photon satisfies the null condition $p^\mu p_\mu = 0$, or equivalently $q^{(a)} q_{(a)} = 0$, only three components among four are independent, that is $$\begin{aligned} q^{(a)} q_{(a)} = 0 \,, \quad \Leftrightarrow \quad (q^{(0)})^2 = \delta_{(i) (j)} q^{(i)} q^{(j)} \,. \end{aligned}$$ Thus the three spatial components $q^{(i)}$ can be regarded as such independent variables. Furthermore, $q^{(i)}$ can be decomposed into its magnitude $q$ and direction $n^{(i)}$ as $$\begin{aligned} q \equiv \sqrt{\delta_{(i) (j)} q^{(i)} q^{(j)}} = |q^{(0)}| \,, \qquad n^{(i)} \equiv \frac{q^{(i)}}{q} \,. \end{aligned}$$ Physically the above $q$ can be understood as the conformal (re-scaled) energy, $q = a E_{{\mathrm{phys}}}$, seen by an observer orthogonal to time constant hypersurfaces. From Eq. (\[defpP\]), the components of momentum $p^{\mu}$ are expressed as functions of $(q, n^{(i)})$ up to the second order as $$\begin{aligned} \label{p0pi} p^0 &= \frac{q}{a^2} (1 - \alpha + \alpha^2) \,, \\ p^i &= \frac{q}{a^2} \left( n^{(i)} - \beta^i - {h^i}_j n^{(j)} + \alpha \beta^i + \frac{3}{2} h^{i k} h_{k j} n^{(j)} \right) \,. \label{momentum}\end{aligned}$$ Conversely, ($q, n^{(i)}$) are given by the components of momentum as $$\begin{aligned} q &= a^2 (1 + \alpha) p^0 \,, \label{def:q} \\ n^{(i)} &= \left[ (1 - \alpha + \alpha^2) \delta^i{}_j + (1 - \alpha) h^i{}_j - \frac{1}{2} h^{ik} h_{k j} \right] \frac{p^j}{p^0} + (1 - \alpha) \beta^i + \beta^j {h^i}_j \,. \label{def:n^i}\end{aligned}$$ One can introduce a projection operator in terms of $e^{(0)}{}_\mu$ and $n_\mu$. The projection operator, often called the screen projector, is defined as $$\begin{aligned} S_{\mu \nu} &\equiv g_{\mu \nu} + e^{(0)}{}_\mu e^{(0)}{}_\nu - n_\mu n_\nu \,,\end{aligned}$$ where $n^\mu$, the direction vector of photon, is defined by $$\begin{aligned} n^\mu \equiv e_{(i)}{}^\mu n^{(i)} \,. \end{aligned}$$ Clearly $S_{\mu \nu}$ is a projection of the tangent space onto a two dimensional plane orthogonal to both $e^{(0)}{}_\mu$ and $n_\mu$ since $S^{\mu \nu} e^{(0)}{}_\mu$ and $S^{\mu \nu} n_\mu$ vanish. Its expression in tetrad components reduces necessarily to the identity of the two-dimensional subspace which is left invariant by the projector, that is $$\begin{aligned} S_{(i) (j)} = \delta_{(i) (j)} - n_{(i)} n_{(j)} \,,\qquad S_{(0) (0)}=S_{(0) (i)}=0 \,.\end{aligned}$$ Distribution function for photons and Stokes parameters {#ssec:f} ------------------------------------------------------- In order to describe the polarisation of radiation, we introduce a tensor-valued distribution function $f_{\mu \nu}$, which is complex valued and Hermitian. The construction of this distribution function is discussed in Appendix \[app:Dist\]. It is independent of the choice of the electromagnetic gauge and contains only four physical degrees of freedom since it satisfies the conditions $$f_{\mu\nu} e_{(0)}{}^\mu = f_{\mu\nu} e_{(0)}{}^\nu = f_{\mu\nu} n^\mu = f_{\mu\nu} n^\nu = 0 \,.$$ Note that the distribution function depends on the observer’s velocity, $u^\mu \equiv e_{(0)}{}^{\mu}$, used in its definition. As long as no confusion arises from such dependence, we omit to specify it. In the case where this is needed, mainly when studying the transformation properties of such a quantity, we shall use the notation $f_{\mu\nu}^{\bm{e}_{(0)}}$ to stress that the tensor-valued distribution function is dependent on the observer’s velocity and thus on the choice of the tetrad field. The four degrees of freedom can be extracted by decomposing $f_{\mu \nu}$ into a trace part, a symmetric traceless part and an antisymmetric part as $$f_{\mu \nu} \equiv \frac{1}{2} I S_{\mu \nu} + P_{\mu \nu}+ \frac{{{\rm i}}}{2} \epsilon_{\rho \mu \nu \sigma} e_{(0)}{}^\rho n^\sigma V \,, \label{Pol}$$ where the antisymmetric tensor is defined by $$\begin{gathered} \epsilon_{\alpha \beta \gamma \delta} = \epsilon_{[ \alpha \beta \gamma \delta] } \,, \quad \epsilon_{0 1 2 3} = \sqrt{- g} \,, \qquad {\rm or} \qquad \epsilon_{(0)(1)(2)(3)}=-\epsilon^{(0)(1)(2)(3)} = 1 \,.\end{gathered}$$ [*I*]{} is the intensity and $V$ is the degree of circular polarisation. $P_{\mu \nu}$ encodes the two degrees of linear polarisation (so called $Q$ and $U$ Stokes parameters). All these functions, together with the original tensor-valued distribution function, are functions of the position on space-time $x^\mu=(\eta,x^i)$ and on the point in tangent space. This point in the tangent space can be chosen to be parametrized either by the components $p^\mu$ in the basis canonically associated with the coordinates system, or alternatively by their Cartesian counterparts $p^{(a)}$. In fact we will choose to parametrize the tangent space by the components of the conformal momentum in tetrad space, $q^{(i)} = a p^{(i)}$, expressed in their spherical coordinates $q$ and $n^{(i)}$, as this leads to the most simple form for the Boltzmann equation as we shall see further. Spectral distortion ------------------- On the background space-time, the distribution function, which is characterized only by the intensity $I$, is given by a Planck distribution whose temperature $\bar T$ depends only on $\eta$ due to the symmetries of the FLRW universe. As we will check later, the background temperature scales as $\propto 1/a$. We thus have $$\bar I(\eta,q) = {{I_{\rm BB}}}\left[\frac{q}{a(\eta)\bar T(\eta)}\right] \,, \quad \text{with} \quad {{I_{\rm BB}}}(x) \equiv \frac{2}{( e^x - 1 )} \,.$$ At first order in perturbation, the fluctuation of intensity can be described as a fluctuation of temperature $\delta T$ which is independent of $q$. There are two reasons for this. First, as we shall discuss further, gravitational interactions do not induce spectral distortions in the sense that they shift all wavelengths by the same ratio. Second, the collisions at linear order in perturbation do not induce spectral distortions and the redistribution of the photon directions resulting from it can be described by a direction dependent temperature. A similar procedure can be followed for the description of polarisation at first order. However at second order the situation becomes more complicated since the Compton scattering at this order of perturbation induces spectral distortions which cannot be reabsorbed in a simple direction dependent temperature. As a result, the photon distribution is not described by a Planck distribution function, but fortunately it is sufficient to use two direction dependent quantities. The first remains the temperature and the second describes the type of spectral distortion generated at second order. Actually in general, at the $n$-th order, $n$ directional dependent functions would be needed [@Stebbins:2007ve; @Pitrou:2009bc] to characterize fully the spectrum. In order to parametrize this distortion, we introduce on top of the temperature $T$, the so-called Compton $y$ parameter. In this section we will omit the dependence of all quantities on the coordinates $x^\mu$ and we will focus on the dependence on the tangent space coordinates $(q,n^{(i)})$. The distribution function can be expanded around a Planck distribution in the so-called Fokker-Planck expansion as  [@Stebbins:2007ve] $$\begin{aligned} \label{defy} I \Bigl( q,n^{(i)} \Bigr) &\simeq {{I_{\rm BB}}}\left( \frac{q}{a T} \right) + y \bigl( n^{(i)} \bigr) q^{-3} {{\frac{\partial}{\partial \ln q}}}\left[ q^3 {{\frac{\partial}{\partial \ln q}}}{{I_{\rm BB}}}\left( \frac{q}{a T} \right) \right] \notag\\ &= {{I_{\rm BB}}}\left( \frac{q}{a T} \right) + y \bigl( n^{(i)} \bigr) {{\cal D}}_q^2{{I_{\rm BB}}}\left( \frac{q}{aT} \right) \,,\end{aligned}$$ where $${{\cal D}}_q^2 \equiv q^{-3} {{\frac{\partial}{\partial \ln q}}}\left( q^3 {{\frac{\partial}{\partial \ln q}}}\right) = {{\frac{\partial^2}{\partial \ln q^2}}}+3 {{\frac{\partial}{\partial \ln q}}}\,.$$ Because the number density of photon is given by $n \propto a^{-3}\int I q^2 {{\rm d}}q$, the $y$ term does not contribute to the photon number density and the temperature $T$ is the temperature of the black-body that would have the same number density (see Ref. [@Pitrou:2010sn] for a discussion on other possible definitions for the temperature) and we call it here [*number density temperature*]{}. It can be expanded around the background temperature as $$T \bigl( n^{(i)} \bigr) \equiv \bar T(\eta) \left[ 1 + \Theta \bigl( n^{(i)} \bigr) \right] \,.$$ Note that the expansion (\[defy\]) is not the same as Eq. ($11$) nor Eq. ($15$) of Ref. [@Stebbins:2007ve]. Indeed, the temperature of the Planck spectrum around which we expand is neither the physically motivated logarithmic averaged temperature of Ref. [@Stebbins:2007ve] nor a fiducial temperature, but another physically motivated temperature (the number density temperature) that suits better to describe the spectral distortion of the type that appears in CMB. However, when performing perturbations in cosmology, we need to refer to the background space-time temperature $\bar T$, not to the local number density temperature. Thus it is convenient to expand the distribution function around a Planck distribution at $\bar T$ rather than $T$. Expanding Eq. (\[defy\]) in $\Theta$ up to the second order, we obtain the expansion as $$\begin{aligned} I &= {{I_{\rm BB} \left( \frac{q}{a \bar T} \right)}}- \bigl( \Theta+\Theta^2 \bigr) {{\frac{\partial}{\partial \ln q}}}{{I_{\rm BB} \left( \frac{q}{a \bar T} \right)}}+\left( y + \frac{1}{2} \Theta^2 \right) {{\cal D}}_q^2 {{I_{\rm BB} \left( \frac{q}{a \bar T} \right)}}\,, \label{intensity}\end{aligned}$$ where we used the fact that $y$ is at least a second order quantity. Here, in order to simplify the notation, it is implied that $\Theta$ and $y$ depend on $x^\mu$ and $n^{(i)}$. For a given $I$, the spectral components $\Theta$ and $y$ can be extracted by performing different types of integrals on $q$ (see appendix \[AppExtraction\] for details). This expansion is similar to Eq. ($11$) of Ref. [@Stebbins:2007ve] when only second derivatives of the Planck distribution are kept. Now we want to obtain a similar decomposition for polarisation. Indeed, when dealing with polarisation we also need to expand its spectral dependence in a way similar to what has been performed for the intensity in Eqs. (\[defy\]) and (\[intensity\]), that is we want to separate the polarisation tensor into a spectral distortion $Y_{\mu\nu}$ and non-distorted component ${{\cal P}}_{\mu \nu}$. However, this separation is slightly different given that there is no polarisation on the background and hence there is no term corresponding to the first term in Eq. (\[intensity\]). In the appendix of Ref. [@Stebbins:2007ve], it has been shown that the expansion should be $$\label{defyPbase} P_{\mu \nu} \Bigl( q, n^{(i)} \Bigr) \simeq - {{\cal P}}_{\mu\nu} \bigl( n^{(i)} \bigr) {{\frac{\partial}{\partial \ln q}}}{{I_{\rm BB}}}\left( \frac{q}{a T} \right) + Y_{\mu \nu} \bigl( n^{(i)} \bigr) {{\cal D}}_q^2 {{I_{\rm BB}}}\left( \frac{q}{a T} \right) \,,$$ which is just a consequence of the fact that there is no background polarisation. We will check that $Y_{\mu\nu}$ vanishes at first order as it is not generated by collisions at this order. Similarly to the expansion of the intensity part, we want to expand the distribution function around a Planck spectrum at the background temperature $\bar T$ rather than the local number density temperature $T$. Thus we expand Eq. (\[defyPbase\]) in $\Theta$ up to first order to get $$\begin{aligned} \label{defyP} P_{\mu \nu} &= - (1 + 3 \Theta) {{\cal P}}_{\mu\nu} {{\frac{\partial}{\partial \ln q}}}{{I_{\rm BB} \left( \frac{q}{a \bar T} \right)}}+ (Y_{\mu \nu} + \Theta {{\cal P}}_{\mu\nu}) {{\cal D}}_q^2 {{I_{\rm BB} \left( \frac{q}{a \bar T} \right)}}\,.\end{aligned}$$ Again here, in order to simplify the notation, it is implied that $\Theta$, ${{\cal P}}_{\mu \nu}$ and $Y_{\mu\nu}$ depend on $x^\mu$ and $n^{(i)}$. Boltzmann equation {#sec:Boltz} ================== Now that we have all the tools at hand, we are ready to formulate the Boltzmann equation for polarized radiation in the cosmological context, and extract its spectral components. This section is entirely dedicated to this task. Given that the complete and detailed derivation can be rather lengthy, all details which are not necessary in a first reading are gathered in Appendix \[app:Boltz\_pol\]. We first present the general expression of the Boltzmann equation for a tensor-valued distribution function. Since the Boltzmann equation is the description of how this distribution function evolves along a photon geodesic, it is necessary to perturb the geodesic equation up to second order. We then show how the Boltzmann equation can be split into its main spectral components, that is into a temperature and a distortion. Finally we write the explicit forms of the free-streaming part and the collision part of the Boltzmann equation. Boltzmann equation {#boltzmann-equation} ------------------ The evolution of the tensor-valued distribution function is dictated by the Boltzmann equation [@Tsagas:2007yx] $$\label{Evolfmunu} S_\mu{}^\rho S_\nu{}^\sigma \frac{{{\cal D}}f_{\rho \sigma}}{{{\cal D}}\lambda} = C_{\mu \nu} \,,$$ where ${{\cal D}}/ {{\cal D}}\lambda$ is the covariant derivative along a photon trajectory $x^{\mu}(\lambda)$ and the momentum and $C_{\mu \nu}$ is the associated collision term. The explicit form of ${{\cal D}}f_{\mu \nu}/ {{\cal D}}\lambda$ is $$\frac{{{\cal D}}f_{\mu \nu}}{{{\cal D}}\lambda} \equiv \nabla_\rho f_{\mu \nu} \frac{{{\rm d}}x^\rho}{{{\rm d}}\lambda} + \frac{{{\partial}}f_{\mu \nu}}{{{\partial}}q^{(i)}} \frac{{{\rm d}}q^{(i)}}{{{\rm d}}\lambda} \,,$$ where $\nabla_\mu$ indicates a covariant derivative associated with $g_{\mu \nu}$. Using spherical coordinates $(q,n^{(i)})$ instead of $q^{(i)}$ for the momentum space, the Liouville operator, that is the l.h.s of Eq. (\[Evolfmunu\]), reads $$\label{DDLoperatortensor} S_\mu{}^\rho S_\nu{}^\sigma \frac{{{\cal D}}f_{\rho \sigma}}{{{\cal D}}\lambda} = S_\mu{}^\rho S_\nu{}^\sigma \nabla_\tau f_{\rho \sigma} \frac{{{\rm d}}x^\tau}{{{\rm d}}\lambda} + \frac{{{\partial}}f_{\mu \nu}}{{{\partial}}\ln q} \frac{{{\rm d}}\ln q}{{{\rm d}}\lambda} + D_{(i)} f_{\mu \nu} \frac{{{\rm d}}n^{(i)}}{{{\rm d}}\lambda} \,,$$ where $D_{(i)}$ is a covariant derivative for momentum. The detail of the construction of such derivative is discussed in Appendix \[sapp:covp\]. Thanks to the operation of the projection $S_\mu{}^\rho S_\nu{}^\sigma$ onto $ {{\cal D}}f_{\rho \sigma} / {{\cal D}}\lambda$, the left hand side of the Boltzmann equation can be decomposed into the $I$, $V$ and $P_{\mu \nu}$ parts similarly to Eq. (\[Pol\]); $$\begin{gathered} S_\mu{}^\rho S_\nu{}^\sigma \frac{{{\cal D}}f_{\rho \sigma}}{{{\cal D}}\lambda} = \frac{1}{2} L[I] S_{\mu \nu} + L[{\bf P}\,]_{\mu \nu} + \frac{{{\rm i}}}{2} L[V] \epsilon_{\rho \mu \nu \sigma} e_{(0)}{}^\rho n^\sigma \,,\end{gathered}$$ where the corresponding Liouville operators are defined as $$\label{defofLs} L[I] \equiv \frac{{{\cal D}}I}{{{\cal D}}\lambda} \,, \qquad L[{\bf P} \, ]_{\mu \nu} \equiv S_\mu{}^\rho S_\nu{}^\sigma \frac{{{\cal D}}P_{\rho \sigma}}{{{\cal D}}\lambda} \,, \qquad L[V]\equiv \frac{{{\cal D}}V}{{{\cal D}}\lambda} \,.$$ Here, the operator ${{\cal D}}/ {{\cal D}}\lambda$ on a scalar distribution function $f$, takes the simpler form $$\frac{{{\cal D}}f}{{{\cal D}}\lambda} \Bigl( x^\mu, q, n^{(i)} \Bigr) \equiv {{\partial}}_\mu f \frac{{{\rm d}}x^\mu}{{{\rm d}}\lambda} + \frac{{{\partial}}f}{{{\partial}}\ln q} \frac{{{\rm d}}\ln q}{{{\rm d}}\lambda} + D_{(i)} f \frac{{{\rm d}}n^{(i)}}{{{\rm d}}\lambda}\,.$$ In a similar manner, one can also decompose the collision term, that is the r.h.s of Eq. (\[Evolfmunu\]) as $$\begin{gathered} C_{\mu \nu} \equiv \frac{1}{2} C^I S_{\mu \nu} + C^P_{\mu \nu} + \frac{{{\rm i}}}{2} C^V \epsilon_{\rho \mu \nu \sigma} e_{(0)}{}^\rho n^\sigma \,, \label{PolC}\end{gathered}$$ so that after extracting the trace, symmetric traceless and antisymmetric parts we get obviously $L[I]=C^I$, $L[{\bf P}]_{\mu\nu} = C^P_{\mu\nu}$ and $L[V]=C^V$. Beware that this does not mean that the intensity, linear polarization and circular polarization evolve independently, since for instance $C^I$ is the “intensity part” of the collision term but it may involve in general all components $I$, $P_{\mu\nu}$ and $V$ of the tensor-valued distribution function. As a matter of fact, Compton collision does indeed intermix intensity and linear polarization, whereas circular polarization evolves independently. Geodesic equation and momentum evolution ---------------------------------------- From Eq (\[p0pi\]) and the definition of momentum, ${{\rm d}}x^\mu/{{\rm d}}\lambda=p^\mu$ we obtain $$\begin{aligned} \frac{{{\rm d}}\eta}{ {{\rm d}}\lambda} &= \frac{q}{a^2} (1 - \alpha) \,, \label{eta-evo} \\ \frac{{{\rm d}}x^i}{ {{\rm d}}\lambda} &= \frac{q}{a^2} \left( n^{(i)} - \beta^i - {h^i}_j n^{(j)} \right) \,, \label{xi-evo}\end{aligned}$$ where only the first order terms are kept. In terms of $(q, n^{(i)})$, the geodesic equation leads to the evolution equation for the conformal energy $$\begin{aligned} \frac{{{\rm d}}\ln q}{{{\rm d}}\lambda} &= \frac{q}{a^2} \Bigl[ - \alpha_{,i} n^{(i)} + \beta_{i, j} n^{(i)} n^{(j)} - h_{ij}{}' n^{(i)} n^{(j)} + \alpha \Bigl( \alpha_{,i} n^{(i)} - \beta_{i, j} n^{(i)} n^{(j)} + h_{ij}{}' n^{(i)} n^{(j)} \Bigr) \notag\\ & \qquad \qquad + \alpha_{, j} h^j{}_i n^{(i)} + \beta^k h_{i j, k} n^{(i)} n^{(j)} + (\beta_{k, i} - \beta_{i ,k} + 2 h_{i k}{}') h^k{}_j n^{(i)} n^{(j)} \Bigr] \,. \label{q-evo}\end{aligned}$$ As for the direction evolution, up to first order in perturbations, we obtain $$\frac{{{\rm d}}n^{(i)}}{{{\rm d}}\lambda} = -\frac{q}{a^2} S^{(i) (j)} \Bigl[ \alpha_{,j} - (\beta_{k ,j} - h_{j k}{}') n^{(k)} + (h_{j l,k} - h_{k l,j}) n^{(k)}n^{(l)} \Bigr] \,. \label{n-evo}$$ It is obvious that $n_{(i)}{{\rm d}}n^{(i)}/{{\rm d}}\lambda=1$ as it ought to be since $n^{(i)}$ is a unit vector. We need these expressions only at first order, except for the evolution of $q$ because the background distribution function is constant in space-time (see below). Before closing this subsection, we mention that we are free to choose another affine parameter than $\lambda$, to label a point on a geodesic. A convenient choice is to take the conformal time $\eta$ at each point of space-time crossed by the geodesic. The advantage of such choice, is that for photons having the same direction (and which thus follow the same path), but not the same energy, the same conformal time $\eta$ would correspond to the same point of the geodesic. We can trade $\lambda$ for $\eta$ using Eq (\[eta-evo\]), that is with $$\begin{aligned} \frac{{{\rm d}}\eta}{ {{\rm d}}\lambda} = \frac{q}{a^2} (1 - \alpha) \quad & \Longrightarrow \quad \frac{{{\rm d}}\lambda}{ {{\rm d}}\eta} = \frac{a^2}{q} (1 + \alpha ) \,.\end{aligned}$$ The evolution of position, conformal energy, and direction, take then the form $$\begin{aligned} \frac{{{\rm d}}x^i}{{{\rm d}}\eta} = \frac{{{\rm d}}x^i}{ {{\rm d}}\lambda} \frac{{{\rm d}}\lambda}{{{\rm d}}\eta} &= n^{(i)} + \alpha n^{(i)} - \beta^i - {h^i}_j n^{(j)} \,, \\ \frac{{{\rm d}}\ln q}{{{\rm d}}\eta} = \frac{{{\rm d}}\ln q}{ {{\rm d}}\lambda} \frac{{{\rm d}}\lambda}{{{\rm d}}\eta} &= - \alpha_{,i} n^{(i)} + \beta_{i, j} n^{(i)} n^{(j)} - h_{ij}{}' n^{(i)} n^{(j)} \notag\\ & \qquad + \alpha_{, j} h^j{}_i n^{(i)} + \beta^k h_{i j, k} n^{(i)} n^{(j)} + (\beta_{k, i} - \beta_{i ,k} + 2 h_{i k}{}') h^k{}_j n^{(i)} n^{(j)} \,, \\ \frac{{{\rm d}}n^{(i)}}{{{\rm d}}\eta} = \frac{{{\rm d}}n^{(i)}}{ {{\rm d}}\lambda} \frac{{{\rm d}}\lambda}{{{\rm d}}\eta} &= - S^{(i) (j)} \left[ \alpha_{,j} - (\beta_{k ,j} - h_{j k}{}') n^{(k)} + (h_{j l,k} - h_{k l,j}) n^{(k)}n^{(l)} \right] \,.\end{aligned}$$ Spectral decomposition of the Boltzmann equation ------------------------------------------------ We are now in position of writing down explicitly the Boltzmann equation, expanding the orders of perturbations, and separating the spectral components. Let us first look at the formal structure of the Boltzmann equation, especially focusing on the spectral decomposition. At the background level, the Boltzmann equation yields $$\label{EqbackgroundI} \frac{{{\cal D}}}{{{\cal D}}\lambda} {{I_{\rm BB} \left( \frac{q}{a \bar T} \right)}}= \frac{q}{a^2} \left. \frac{{{\partial}}{{I_{\rm BB}}}(x)}{{{\partial}}\eta} \right|_{q} = - \frac{{{\rm d}}\ln (a \bar T)}{{{\rm d}}\lambda} \left.\frac{{{\rm d}}{{I_{\rm BB}}}(x)}{{{\rm d}}\ln x} \right|_{x=q/(a\bar T)} = 0 \,.$$ This implies that $\bar I$ has no time dependence and $\bar T$ scales as $1/a$. One can conclude that the Planck distribution does not change in time if the initial distribution is given by the Planck one. This does not mean that the radiation is not losing energy as the universe expands. Indeed, since the physical energy of a photon is not the conformal energy $q$ but $q/a$, then $\bar \rho \propto \int \bar I (q/a)^3 {{\rm d}}q/a \propto a^{-4}$ as expected. This background result for the scaling of $\bar T$ is useful as it implies that only the partial derivative with respect to $q$ on ${{I_{\rm BB}}}[q/(a \bar T)]$ are relevant, and this motivates our use of the conformal energy. Now the action of the Liouville operator on the intensity, Eq (\[intensity\]), is expanded up to the second order as $$\begin{aligned} L[I] &= \frac{{{\rm d}}\ln q}{{{\rm d}}\lambda} {{\frac{{{\partial}}I_{\rm BB}}{{{\partial}}\ln q}}}- L \Bigl[ \Theta + \Theta^2 \Bigr] {{\frac{{{\partial}}I_{\rm BB}}{{{\partial}}\ln q}}}- \Theta \frac{{{\rm d}}\ln q}{{{\rm d}}\lambda} \frac{{{\partial}}^2 {{I_{\rm BB}}}}{{{\partial}}\ln q^2} + L \left[ y + \frac{1}{2} \Theta^2 \right] {{\cal D}}_q^2 {{I_{\rm BB}}}\notag\\ &= - \left[ L [\Theta] - \frac{{{\rm d}}\ln q}{{{\rm d}}\lambda} - \Theta \frac{{{\rm d}}\ln q}{{{\rm d}}\lambda} + 2 \Theta \left( L [\Theta] - \frac{{{\rm d}}\ln q}{{{\rm d}}\lambda} \right) \right] {{\frac{{{\partial}}I_{\rm BB}}{{{\partial}}\ln q}}}+ \left[ L [y] + \Theta \left( L [\Theta] - \frac{{{\rm d}}\ln q}{{{\rm d}}\lambda} \right) \right] {{\cal D}}^2_q {{I_{\rm BB}}}\,, \label{original}\end{aligned}$$ where we used ${{\partial}}{{I_{\rm BB}}}/{{\partial}}\eta = 0$. When we compare this formulation of the Liouville operator with the spectral decomposition (\[intensity\]), we are tempted to say that the expression inside the first square brackets contributes to the evolution of the temperature due to free-streaming, and that the expression inside the second square brackets is very closely related to the evolution of the distortion. It order to give a clear meaning to this assertion we decompose Eq. (\[original\]) according to $$\label{spectraldecI} L[I] \equiv \frac{q}{a^2} \left[ - \Bigl( {{\cal L}}^\Theta + 2 \Theta {{\cal L}}^\Theta \Bigr) {{\frac{{{\partial}}I_{\rm BB}}{{{\partial}}\ln q}}}+ \Bigl( {{\cal L}}^Y + \Theta {{\cal L}}^\Theta \Bigr) {{\cal D}}^2_q {{I_{\rm BB}}}\right] \,.$$ This spectral decomposition is motivated by the fact that i) in the case where the conformal energy is not affected by free-streaming, ${{\rm d}}\ln q / {{\rm d}}\lambda = 0$, then $(q/a^2) {{\cal L}}^\Theta$ simply reduces to $L[\Theta]$; and ii) the prefactor $q/a^2$ is introduced because the Liouville term is expected to be proportional to $q/a^2$, as it can be inferred from the explicit form (\[eta-evo\]) of ${{\rm d}}\eta/{{\rm d}}\lambda$. From a comparison of Eq (\[original\]) with this decomposition, we have $$\begin{aligned} \label{SpectraldecLI} \frac{q}{a^2}{\cal L}^\Theta&=L[\Theta] -(1+ \Theta )\frac{{{\rm d}}\ln q}{{{\rm d}}\lambda}\,,\\ \frac{q}{a^2}{\cal L}^Y&=L[y]\,.\end{aligned}$$ We must bear in mind that in these expressions, even though the operator $L[.]$ has been defined in Eq. (\[defofLs\]) for functions of $(\eta,x^i,q,n^{(i)})$, it is applied on the spectral components $\Theta$ and $y$ which do not depend on $q$. Since the Liouville operator is equated to the collision term in the Boltzmann equation, it is convenient to decompose the collision term in the same manner as the Liouville term. That is, it is decomposed as $$C^I \equiv \frac{q}{a^2} \left[ - \Bigl( {{\cal C}}^\Theta + 2 \Theta {{\cal C}}^\Theta \Bigr) {{\frac{{{\partial}}I_{\rm BB}}{{{\partial}}\ln q}}}+ \Bigl( {{\cal C}}^Y + \Theta {{\cal C}}^\Theta \Bigr) {{\cal D}}^2_q {{I_{\rm BB}}}\right] \,,$$ such that the spectral components of the Boltzmann equation can be formally very simple and are given by $$\begin{aligned} {{\cal L}}^\Theta= {{\cal C}}^\Theta \,,\qquad {{\cal L}}^Y={{\cal C}}^Y. \end{aligned}$$ This decomposition means that once the spectral decomposition of the collision term is known (${\cal C}^\Theta$ and ${\cal C}^Y$), then we only need to obtain the spectral decomposition of the Liouville term from Eqs (\[SpectraldecLI\]). We follow the same logic for polarization. First, the corresponding Liouville operator reads $$\begin{aligned} L [ {\bf P} ]_{\mu \nu} &= - L \Bigl[ (1 + 3 \Theta) {{\cal P}}_{\mu\nu} \Bigr] {{\frac{{{\partial}}I_{\rm BB}}{{{\partial}}\ln q}}}- {{\cal P}}_{\mu \nu} \frac{{{\rm d}}\ln q}{{{\rm d}}\lambda} \frac{{{\partial}}^2 {{I_{\rm BB}}}}{{{\partial}}\ln q^2} + L \Bigl[ Y_{\mu \nu} + \Theta {{\cal P}}_{\mu \nu} \Bigr] {{\cal D}}_q^2 {{I_{\rm BB}}}\notag\\ &= - \left[ (1 + 3 \Theta) L [ {\bm {{\cal P}}} ]_{\mu \nu} + 3 \left(L[\Theta]- \frac{{{\rm d}}\ln q}{{{\rm d}}\lambda}\right) {{\cal P}}_{\mu \nu} \right] {{\frac{{{\partial}}I_{\rm BB}}{{{\partial}}\ln q}}}+ \left[ L [ {\bf Y} ]_{\mu \nu} + \left(L[\Theta]- \frac{{{\rm d}}\ln q}{{{\rm d}}\lambda}\right){{\cal P}}_{\mu \nu} + \Theta L [{\bm {{\cal P}}}]_{\mu \nu} \right] {{\cal D}}_q^2 {{I_{\rm BB}}}\,. \end{aligned}$$ For the same reasons as in the case of intensity, it appears natural to decompose this Liouville operator into spectral components according to $$\label{spdec:calP_lhs} L [ {\bf P} ]_{\mu \nu}\equiv\frac{q}{a^2} \left\{ - \Bigl[ (1 + 3 \Theta) {{\cal L}}_{\mu \nu}^P + 3 {{\cal L}}^\Theta {{\cal P}}_{\mu \nu} \Bigr] {{\frac{{{\partial}}I_{\rm BB}}{{{\partial}}\ln q}}}+ \Bigl( {{\cal L}}^Y_{\mu \nu} + {{\cal L}}^\Theta {{\cal P}}_{\mu \nu} + \Theta {{\cal L}}_{\mu \nu}^P \Bigr) {{\cal D}}_q^2 {{I_{\rm BB}}}\right\} \,,$$ which implies that the spectral components are given by $$\label{SpectraldecLP} \frac{q}{a^2} {{\cal L}}_{\mu \nu}^P \equiv L [ {\bm {{\cal P}}} ]_{\mu \nu},\qquad \frac{q}{a^2} {{\cal L}}_{\mu \nu}^Y \equiv L [ {\bf Y} ]_{\mu \nu} \,.$$ The collision term must then follow the same type of decomposition, that is $$\begin{aligned} C^P_{\mu \nu} &= \frac{q}{a^2} \left\{ - \Bigl[ (1 + 3 \Theta) {{\cal C}}_{\mu \nu}^P + 3 {{\cal C}}^\Theta {{\cal P}}_{\mu \nu} \Bigr] {{\frac{{{\partial}}I_{\rm BB}}{{{\partial}}\ln q}}}+ \Bigl( {{\cal C}}^Y_{\mu \nu} + {{\cal C}}^\Theta {{\cal P}}_{\mu \nu} + \Theta {{\cal C}}_{\mu \nu}^P \Bigr) {{\cal D}}_q^2 {{I_{\rm BB}}}\right\} \,, \label{spdec:calP_rhs}\end{aligned}$$ so that, again, the spectral components of the polarized part of the Boltzmann equation take the formally simple form $$\label{eq:Boltz_pol_dis} {{\cal L}}^P_{\mu \nu}={{\cal C}}^P_{\mu \nu} \,,\qquad {{\cal L}}^Y_{\mu \nu} ={{\cal C}}^Y_{\mu \nu} \,.$$ Again, this decomposition means that once the spectral decomposition of the collision term is known (${\cal C}^P_{\mu\nu}$ and ${\cal C}^Y_{\mu\nu}$), then we only need to obtain the spectral decomposition of the Liouville term from Eqs (\[SpectraldecLP\]) bearing in mind that the Liouville operator $L[.]$ applies on functions which do not depend on $q$, but only on $(\eta,x^i,n^{(i)})$. Temperature and spectral distortion of Liouville operators ---------------------------------------------------------- Now that the spectral separation of the Boltzmann equation is performed, it is time to expand the equations obtained in orders of perturbations. In the next two sections, we present such expansion for the temperature and spectral distortion parts of the Boltzmann equation. The case of polarization is reported in Appendix \[sapp:Boltzeq\_pol\]. At first order in perturbation, with Eqs. (\[eta-evo\]) and (\[q-evo\]), the Boltzmann equation leads to $$\begin{aligned} {\cal L}^\Theta&= \Theta' + \Theta_{, i} n^{(i)} + \alpha_{, i} n^{(i)} - \beta_{i, j} n^{(i)} n^{(j)} + h_{i j}{}' n^{(i)} n^{(j)} \,.\end{aligned}$$ Note that there is absolutely no q-dependence, nor scale factor $a$ in this expression, meaning that our spectral decomposition performed in Eq. (\[spectraldecI\]) is adequate. Concerning the spectral distortion part, the Liouville part at first order is ${\cal L}^Y= y'+y_{,i} n^{(i)}$, but since ${\cal C}^Y=0$ at first order (see section \[ssec:Collision\]), one can conclude that only the temperature part evolves at first order and no spectral distortion is induced. Up to the second order, the Boltzmann equation for the temperature is given by $$\begin{aligned} \label{LCThetanotOpened} {\cal L}^\Theta &= \frac{a^2}{q}\left[L[\Theta] - (1 + \Theta) \frac{{{\rm d}}\ln q}{{{\rm d}}\lambda}\right] \notag\\ &= \Theta' + \Theta_{, i} n^{(i)} + \alpha_{, i} n^{(i)} - \beta_{i, j} n^{(i)} n^{(j)} + h_{i j}{}' n^{(i)} n^{(j)} \notag\\ & \qquad +\frac{a^2}{q} \left[ \left. \frac{{{\rm d}}\eta}{{{\rm d}}\lambda} \right|^{(1)} \Theta' + \left. \frac{{{\rm d}}x^i}{{{\rm d}}\lambda} \right|^{(1)} \Theta_{, i} + \left. \frac{{{\rm d}}n^{(i)}}{{{\rm d}}\lambda} \right|^{(1)} D_i \Theta - \left. \frac{{{\rm d}}\ln q}{{{\rm d}}\lambda} \right|^{(1) \times (1)} - \Theta \left. \frac{{{\rm d}}\ln q}{{{\rm d}}\lambda} \right|^{(1)} \right] = {{\cal C}}^\Theta \,.\end{aligned}$$ As for the spectral distortion, the Boltzmann equation is given, even at second order by $$\begin{aligned} {\cal L}^Y &= y' + y_{, i} n^{(i)} = {{\cal C}}^Y \,.\end{aligned}$$ This means simply that gravitational effects do not induce spectral distortions, and this result holds actually non-perturbatively. Before ending this subsection, for the sake of completeness, we shall write down the most general form of the second order Boltzmann equation for the intensity. Using Eqs. (\[eta-evo\]), (\[q-evo\]), (\[xi-evo\]) and (\[n-evo\]), the detailed form of the evolution equation for temperature obtained in Eq. (\[LCThetanotOpened\]) is $$\begin{aligned} {\cal L}^\Theta=& \Theta' + \Theta_{, i} n^{(i)} + \alpha_{,i} n^{(i)} - \beta_{i ,j} n^{(i)} n^{(j)} + h_{i j}{}' n^{(i)} n^{(j)} \notag\\ & \quad - \alpha \Theta' - (\beta^i + h^i{}_j n^{(j)}) \Theta_{, i} - \Bigl[ \alpha_{,i} - (\beta_{j ,i} - h_{i j}{}') n^{(j)} + (h_{k i, j} - h_{j k, i}) n^{(j)} n^{(k)} \Bigr] D^i \Theta \notag\\ & \quad - \Bigl( \alpha \alpha_{,i} + \alpha_{, j} h^j{}_i \Bigr) n^{(i)} - \Bigl[ \alpha (- \beta_{i ,j} + h_{i j}{}') + \beta^k h_{i j, k} + (\beta_{k, i} - \beta_{i, k} + 2 h_{i k}{}') h^k{}_j \Bigr] n^{(i)} n^{(j)} \notag\\ & \quad - \Theta n^{(i)} \Bigl( - \alpha_{,i} + \beta_{i ,j} n^{(j)} - h_{i j}{}' n^{(j)} \Bigr) = {{\cal C}}^\Theta \,.\end{aligned}$$ Temperature and spectral distortion of collision terms {#ssec:Collision} ------------------------------------------------------ The expression of the collision term has been derived by taking into account only the intensity in [@Dodelson1993; @Bartolo:2006cu] and then it was extended to include the effect of polarisation in [@Pitrou:2008hy; @Pitrou:2008ut; @Beneke:2010eg]. Here we summarize the result obtained by Beneke et al. [@Beneke:2010eg] applying the decomposition of the distribution function into intensity and linear polarisation. The complete expression of the collision term for intensity is given by $$\begin{aligned} {{\cal C}}^\Theta &= a \, \bar{n}_e \sigma_T \left( - \Theta + \langle \Theta \rangle - \frac{3}{4} S^{(i) (j)} \Bigl[ \langle \Theta m_{(i) (j)} \rangle - 2 \langle {{\cal P}}_{(i) (j)} \rangle \Bigr] + v^{(i)} n_{(i)} + {{\cal S}}^T + S^{(i) (j)} {{\cal Q}}^T_{(i) (j)} + \delta_e {{\cal C}}^\Theta \right) \,, \\ {{\cal C}}^Y &= a \, \bar{n}_e \sigma_T \left( - y + \langle y \rangle - \frac{3}{4} S^{(i) (j)} \Bigl[ \langle y m_{(i) (j)} \rangle - 2 \langle Y_{(i) (j)} \rangle \Bigr] + {{\cal S}}^Y + S^{(i) (j)} {{\cal Q}}^Y_{(i) (j)} \right) \,,\end{aligned}$$ where ${{\cal S}}^T$, ${{\cal S}}^Y$, ${{\cal Q}}^T_{(i) (j)}$ and ${{\cal Q}}^Y_{(i) (j)}$ are quadratic contributions defined by $$\begin{aligned} {{\cal S}}^T &= \Theta^2 + \langle \Theta^2 \rangle - 2 \Theta \langle \Theta \rangle - \Theta v^{(i)} n_{(i)} + 2 \langle \Theta \rangle v^{(i)} n_{(i)} - 2 \langle \Theta n_{(i)} \rangle v^{(i)} - \frac{1}{5} v^{(i)} v_{(i)} + (v^{(i)} n_{(i)})^2 \,, \\ {{\cal S}}^Y &= \frac{1}{2} \Theta^2 + \frac{1}{2} \langle \Theta^2 \rangle - \Theta \langle \Theta \rangle - \Theta v^{(i)} n_{(i)} + \langle \Theta \rangle v^{(i)} n_{(i)} - \langle \Theta n_{(i)} \rangle v^{(i)} + \frac{1}{5} v^{(i)} v_{(i)} + \frac{1}{2} (v^{(i)} n_{(i)})^2 \,, \end{aligned}$$ $$\begin{aligned} {{\cal Q}}^T_{(i) (j)} &= - \frac{3}{4} \langle \Theta^2 m_{(i) (j)} \rangle + \frac{3}{2} \Theta \langle \Theta m_{(i) (j)} \rangle + \frac{3}{4} \Bigl[ \langle \Theta n_{(j)} \rangle v_{(i)} + \langle \Theta n_{(i)} \rangle v_{(j)} \Bigr] \notag\\ & \qquad - \frac{3}{4} n^{(k)} \Bigl[ v_{(j)} \langle \Theta m_{(i) (k)} \rangle + v_{(i)} \langle \Theta m_{(j) (k)} \rangle \Bigr] - \frac{3}{4} v^{(k)} \Bigl[ 2 n_{(k)} \langle \Theta m_{(i) (j)} \rangle + \langle \Theta m_{(i) (j)} n_{(k)} \rangle \Bigr] - \frac{1}{5} v_{(i)} v_{(j)} \notag\\ & \qquad + \frac{9}{2} \langle \Theta {{\cal P}}_{(i) (j)} \rangle - 3 \Theta \langle {{\cal P}}_{(i) (j)} \rangle + \frac{3}{2} n^{(k)} \Bigl[ v_{(j)} \langle {{\cal P}}_{(i) (k)} \rangle + v_{(i)} \langle {{\cal P}}_{(j) (k)} \rangle \Bigr] \notag\\ & \qquad + \frac{3}{2} v^{(k)} \Bigl[ \langle {{\cal P}}_{(i) (k)} n_{(j)} \rangle + \langle {{\cal P}}_{(j) (k)} n_{(i)} \rangle \Bigr] - \frac{3}{2} v^{(k)} \Bigl[ \langle {{\cal P}}_{(i) (j)} n_{(k)} \rangle - 2 n_{(k)} \langle {{\cal P}}_{(i) (j)} \rangle \Bigr] \,, \\ {{\cal Q}}^Y_{(i) (j)} &= - \frac{3}{8} \langle \Theta^2 m_{(i) (j)} \rangle + \frac{3}{4} \Theta \langle \Theta m_{(i) (j)} \rangle - \frac{3}{4} v^{(k)} \Bigl[ n_{(k)} \langle \Theta m_{(i) (j)} \rangle - \langle \Theta m_{(i) (j)} n_{(k)} \rangle \Bigr] - \frac{1}{20} v_{(i)} v_{(j)} \notag\\ & \qquad + \frac{3}{2} \langle \Theta {{\cal P}}_{(i) (j)} \rangle - \frac{3}{2} \Theta \langle {{\cal P}}_{(i) (j)} \rangle + \frac{3}{2} v^{(k)} \Bigl[ n_{(k)} \langle {{\cal P}}_{(i) (j)} \rangle - \langle {{\cal P}}_{(i) (j)} n_{(k)} \rangle \Bigr] \,,\end{aligned}$$ and $m_{(i) (j)} \equiv n_{(i)} n_{(j)} - \delta_{(i) (j)}/3$. Note that we have introduced the notation $\langle Q \rangle = \int_{\Omega} Q = \int {{\rm d}}^2 n^{(i)} Q$, which corresponds to a multipole extraction that we do not perform explicitly here. Note also that $\delta_e=\delta n_e/\bar n_e$ is the fractional perturbation of the baryons number density, and $v^{(i)}$ are the tetrad components of the baryons spatial velocity. Again, we also defer the expression of the collision term for polarisation to Appendix \[sapp:Boltzeq\_pol\]. Gauge dependence of the distribution function {#sec:gauge} ============================================= Now that we have established the Boltzmann equation, up to second order, with its spectral components separated, we investigate the gauge dependence of its constituents. Eventually the Boltzmann equation itself should be gauge-invariant, so if we are able to check explicitly that the Boltzmann equation is gauge-invariant, this means that it is very likely that i) the perturbative expansion of the equation is correct; and ii) the gauge transformation rules for all its constituents (metric and distribution function perturbations) are correctly understood. We thus consider this verification as a *consistency test*. This section is dedicated entirely to this task. We first review the gauge dependence for tensors, and deduce how it can be extended to a scalar distribution function. The case of a tensor-valued distribution function, even though it is the less trivial part, is treated in appendix \[AppGTtensor\]. We then infer what should be the transformation rule of the Liouville and collision operators, and in order to complete the consistency test, we check that the perturbed expressions of the Liouville and collision operators do indeed transform following these rules. Coordinates on the manifold --------------------------- We need to specify how the functional dependence of the quantities appearing in the Boltzmann equation (and in the Einstein equation) is obtained. If we consider a scalar function $f:{\cal M}\mapsto {\mathbb{R}}$ on the space-time manifold ${\cal M}$, then the choice of a coordinates system [^1] $c:{\mathbb{R}}^4 \mapsto {\cal M}$ does not affect the geometrical meaning of this function, but it affects its functional form $f \circ c:{\mathbb{R}}^4 \mapsto {\mathbb{R}}$, where $\circ$ designates the composition rule, in the sense that for another coordinates system $\tilde c:{\mathbb{R}}^4 \mapsto {\cal M}$, then $f\circ \tilde c \neq f \circ c$. The confusion only arises from the fact that we often refer to $f \circ c$ as $f$ only. A distribution function $f$ (that we take as a scalar-valued for simplicity here) is a function on the tangent bundle $T {\cal M}$ of the manifold and can be regarded as a function on manifold ${\cal M}$ describing the space-time and on the tangent space ${\mathbb{R}}^4$ (more precisely a restriction to the mass shell ${\mathbb{R}}^3$) of each point. It is thus a function $$f: (T{\cal M})\mapsto {\mathbb{R}}\,.$$ Again the particular choice of coordinates on the tangent space does not affect the geometrical meaning of the function but its functional form. Once a choice $c$ of coordinates on the manifold ${\cal M}$ has been made, there is a natural basis, called canonical basis, that is made of the partial derivatives with respect to the coordinates. This leads to a natural coordinates system $Tc$ for the tangent space at each point. Thus $(c,Tc) : {\mathbb{R}}^4 \times {\mathbb{R}}^3 \mapsto T{\cal M}$, is a coordinates system for the tangent bundle. In order to simplify the notation we will note $(c,Tc)$ as simply as $c$. Furthermore, in this paper we use coordinates in the tangent space described by the tetrad components. More specifically we use the components of the conformal momentum in spherical coordinates in this tetrad basis, $(q,n^{(i)})$. There is a problem with such a choice since the tetrad basis is not unique. However, once a choice $c$ of coordinates on the manifold ${\cal M}$ has been made, the tetrad basis might be completely fixed from the metric through a prescription described in § \[ssec:deftet\]. Once a coordinates system $c$ has been chosen, and the tetrad is fixed thanks to this choice, we obtain the functional form of $f$ in the form $f \circ c:{\mathbb{R}}^4\times {\mathbb{R}}^3\mapsto {\mathbb{R}}$. Geometrical interpretation of the gauge --------------------------------------- When performing perturbations around a background FLRW space-time, we need to have a one-to-one correspondence between the background space-time $\overline{\cal M}$ and the physical (and perturbed) space-time ${\cal M}$. This can be completely defined geometrically [@Bruni:1996im] but we take a shorter approach. If we have two sets of coordinates [^2] $\bar c:{\mathbb{R}}^4 \mapsto \overline{\cal M}$ and $c:{\mathbb{R}}^4 \mapsto {\cal M}$ on the background and the perturbed space-time, then we identify points with the same coordinates, that is, we identify points with $c \circ \bar c^{-1}:\overline{\cal M}\mapsto {\cal M}$. Since we could have chosen different sets of coordinates, there is some freedom in this choice, which is known as the gauge freedom. On the background, the symmetries can justify that we can find a preferred choice of coordinates. For instance for a flat FLRW space-time within a given background cosmology, it is enough to choose that the time coordinate is the proper time of observers with 4-velocity orthogonal to the homogeneous surfaces, that is the proper time of comoving observers. On a given homogeneous surface, there are preferred choices of Cartesian coordinates, since it is conformally related to ${\mathbb{R}}^3$, and all these Cartesian systems on the spatial homogeneous surfaces are related by global translation and rotation in ${\mathbb{R}}^3$ which are irrelevant given the homogeneity. And once a coordinate system has been chosen on a homogeneous surface it can be Lie dragged by the comoving observers to any homogeneous surface. So essentially there is a unique mapping $\bar c$ from ${\mathbb{R}}^4$ to the background manifold $\overline{\cal M}$. This point is illustrated in the left part of Fig. \[fig1\]. However on the physical space-time we could consider another coordinates system $\tilde c:{\mathbb{R}}^4 \mapsto {\cal M}$, and this leads to a different identification through $\tilde c \circ \bar c^{-1}$. The fact that we fix the system of coordinates on the background space-time but there is still some freedom on the physical space-time for the choice of coordinates leads to a freedom in the identification between points of these two space-times. With $c$, a given point $P \in {\cal M}$ would be labelled by the coordinates $x^\mu$, that is $c( {\bm x}) = P$, and with $\tilde c$ it would be labeled by the coordinates $\tilde x^\mu$, that is $\tilde c( \tilde{\bm x}) = P$ (see the upper part of Fig. \[fig1\]). For every point, there exist four numbers ${\xi}^\mu= ({ T},{ L}^i)$ such that $$\begin{gathered} \label{Trulexmu} \tilde{x}^\mu( {\bm x}) = x^\mu + {\xi}^\mu( {\bm x}) \,.\end{gathered}$$ We should note that, although there is an index in the notation, ${\xi}^\mu$ is not a vector field on ${\cal M}$ nor on $\overline{\cal M}$, but it can be seen as a vector field on ${\mathbb{R}}^4$. In the literature, a vector field $\zeta^\nu$ is often used to generate a coordinate transformation  [@Bruni:1996im] $$\tilde x^\mu = \exp\left({\cal L}_{{{\boldsymbol{\zeta}}}}\right)x^\mu =x^\mu+\zeta^\mu+\frac{1}{2}\zeta^\mu{}_{,\nu} \zeta^\nu+\cdots\,.$$ In this paper we adopt the former definition Eq. (\[Trulexmu\]) and care must be taken when comparing our transformation rules with those in the literature. Note that in the rest of this section, we will use extensively the notation $$\tilde{\bm x} \equiv \tilde x^\mu\,,\qquad {\bm x}\equiv x^\mu\,,$$ even though $x^\mu$ and $\tilde x^\mu$ are not vectors but just coordinates. ![\[fig1\] In this figure, we represent all four dimensional spacetimes with only two dimensions. First, we have noted that there is essentially a unique way to map ${\mathbb{R}}^4$ to the background manifold, that is to relate the top-left to the bottom left. However, there are several ways to relate ${\mathbb{R}}^4$ to the perturbed manifold, and consequently to relate the background manifold to the perturbed manifold. We represented a coordinates system $c$ and another coordinates system $\tilde c$ which relate ${\mathbb{R}}^4$ (top-left) to the physical manifold (top-right). For each point $P$ of the physical manifold, there is a set of four numbers $x^\mu$ and another set of four numbers $\tilde x^\mu$ such that $c(x^\mu) = \tilde c(\tilde x^\mu)$. Furthermore, each coordinates system has different surfaces of constant time, and thus different set of tetrads, given that the null tetrad is always chosen to be orthogonal to the constant-time surfaces. When using the tetrad field to extract the components of a given momentum (that is a point in the tangent bundle), this will lead to different components, depending on the coordinates system chosen, but since this is the same momentum at the same point and the tetrad are normalized, we can relate the components by a Lorentz transformation. For a given point of the tangent bundle, that is, for a given point of the manifold and a given momentum, we always have $c(x^\mu,p^{(a)})=\tilde c(\tilde x^\mu, p^{\tilde{(a)}})$.](PlotGauge.pdf){width="\textwidth"} Metric transformation --------------------- In general the coordinate transformation rule of any tensorial quantity is given by $$\label{GTTensor} {\bm T} \circ \tilde c{(\tilde {\bm x})} = {\bm T}\circ c({\bm x})\,.$$ This means that it is invariant under a coordinates transformation since it is geometrically defined and independent of the coordinates used to parametrise the manifold. From this we can deduce the gauge transformation of its components, which is defined as the transformation when the tensors are compared at the same coordinate in two different coordinates systems. Let us consider in particular the metric. Since $g_{\mu \nu} \equiv {\bm g}({{\partial}}/{{\partial}}x^\mu,{{\partial}}/{{\partial}}x^\nu)$ and $g_{\tilde \mu \tilde \nu} \equiv {\bm g}({{\partial}}/{{\partial}}\tilde x^\mu,{{\partial}}/{{\partial}}\tilde x^\nu)$, we then deduce the usual coordinate transformation rule of a 2-form $$\label{Transfog1} g_{\tilde \mu \tilde \nu} \circ \tilde c{(\tilde {\bm x})} = \frac{{{\partial}}x^\alpha}{{{\partial}}\tilde x^\mu} \frac{{{\partial}}x^\beta}{{{\partial}}\tilde x^\nu} g_{\alpha \beta}\circ c({\bm x})\,.$$ Expanding the left hand side which is evaluated at $\tilde {\bm x}$ around ${\bm x}$ leads the gauge transformation rule up to the second order $$\begin{gathered} \label{EqTmetric} g_{\tilde \alpha \tilde \beta}\circ \tilde c{\left({\bm x}\right)} = g_{\alpha \beta}\circ c({\bm x}) - {{\cal L}}_{{{{\boldsymbol{\xi}}}}} g_{\alpha \beta}\circ c({\bm x}) + \frac{1}{2} {{\cal L}}^2_{{{{\boldsymbol{\xi}}}}} g_{\alpha \beta}\circ c({\bm x}) + \frac{1}{2} {{\cal L}}_{{{{\boldsymbol{\xi}}}} {{{\boldsymbol{\xi}}}}} g_{\alpha \beta}\circ c({\bm x}) \,,\end{gathered}$$ where ${{{\boldsymbol{\xi}}}} {{{\boldsymbol{\xi}}}}$ designates the quantity ${\xi}^\mu{}_{,\nu}{\xi}^\nu$. We emphasize that the coordinate transformation  is the transformation of components at the same point of space-time, whereas the gauge transformation  is the transformation of the components at different points which have the same coordinates in two different coordinates systems. Since the notation can become rather cumbersome if we specify which coordinates system $c$ or $\tilde c$ is to be used, we shall indicate it only when it is the new coordinates system $\tilde c$. Throughout this paper, we use the symmetrization and anti-symmetrization definitions $$X_{(\mu\nu)} \equiv \frac{1}{2}\left(X_{\mu\nu}+ X_{\nu\mu}\right) \,, \qquad X_{[\mu\nu]} \equiv \frac{1}{2}\left(X_{\mu\nu}-X_{\nu\mu}\right)\,.$$ Up to second order, from the transformation (\[EqTmetric\]) and the decomposition (\[MetricADM\]), we obtain the gauge transformation for the ADM variables as \[TrulemetricADM\] $$\begin{aligned} \tilde{\alpha} &= \alpha - {{\cal H}}T - T' + \frac{1}{2} ({{\cal H}}^2 + {{\cal H}}') T^2 + {{\cal H}}(2 T' T + T_{,i} L^i) - {{\cal H}}\alpha T \notag\\ & \qquad - \alpha T' - \alpha' T - \alpha_{,i} L^i + \beta^i T_{,i} + T'' T + T'{}^2 + T'_{,i} L^i + \frac{1}{2} T^{, i} T_{, i} \,, \\ \tilde{\beta}^i &= \beta^i + T^{,i} - L^i{}' + 2 \alpha T^{, i} - \beta^i T' - \beta^i{}' T + \beta^j L^i{}_{,j} - \beta^i{}_{,j} L^j - 2 h^{i j} T_{,j} \notag\\ & \qquad - (2 T' T^{, i} + T T'{}^{, i}) + T L^i{}'' + T' L^i{}' + T_{,j} L^{i ,j} - T^{, i}{}_{,j} L^j + L^i{}_{,j}{}' L^j \,, \\ 2 \tilde{h}_{i j} &= 2 h_{i j} - 2 {{\cal H}}T \delta_{i j} - 2 L_{(i ,j)} - 4 {{\cal H}}T h_{i j} + (2 {{\cal H}}^2 + {{\cal H}}') T^2 \delta_{i j} + 2 {{\cal H}}( T T' + T_{,k} L^k) \delta_{i j} \notag\\ & \qquad + 4 {{\cal H}}T L_{(i ,j)} - 2 \beta_{(i} T_{,j)} - 2 h_{i j}{}' T - 2 h_{i j, k} L^k - 4 h_{(i| k} L^k{}_{,|j)} \notag\\ & \qquad - T_{,i} T_{,j} + 2 T L_{(i ,j)}{}' + 2 T_{(,i} L_{j)}{}' + 2 L_{(i ,j) k} L^k + 2 L_{(i|, k} L^k{}_{,|j)} + L_{k, i} L^k{}_{, j} \,.\end{aligned}$$ These relations must be understood as follows. $a^2 \alpha$ at first order is the $00$ component of the first order metric in the $c$ coordinates system, and taken at the point of coordinates ${\bm x}$, and is thus equal to $-\frac{1}{2}g^{(1)}_{00}\circ c({\bm x})$. Instead, $a^2 \tilde \alpha$ which means $a^2 \tilde \alpha({\bm x})$, when considered at first order is the $\tilde 0 \tilde 0$ component of the first order metric in the $\tilde c$ coordinates system, but also taken at the point of coordinates ${\bm x}$, that is $-\frac{1}{2}g^{(1)}_{\tilde 0 \tilde 0}\circ \tilde c{({\bm x})}$. Tangent space basis and tetrads ------------------------------- As discussed in Section \[ssec:f\], the transformation of the basis on the tangent space is entirely linked to the coordinates change in the base manifold. Usually, the canonical basis ${{\partial}}/{{\partial}}x^\mu$ and the corresponding forms ${{\rm d}}x^\mu$ are used as a basis of the tangent space and they transform according to $$\label{TruleCanonicalBasis} \frac{{{\partial}}}{{{\partial}}\tilde x^\mu}\circ \tilde c{(\tilde{\bm x})} = \frac{{{\partial}}x^\nu}{{{\partial}}\tilde x^\mu} \frac{{{\partial}}}{{{\partial}}x^\nu}{({\bm x})} \,, \qquad {{\rm d}}\tilde x^\mu \circ \tilde c {(\tilde{\bm x})} = \frac{{{\partial}}\tilde x^\mu}{{{\partial}}x^\nu} {{\rm d}}x^\nu {c({\bm x})} \,.$$ When we consider the components of the metric, these components refer to this canonical basis. However we will use the tetrad field as a basis for the tangent space. We thus need to relate $\tilde{\bm e}_{(a)}\circ \tilde c{(\tilde{\bm x})}$ with ${\bm e}_{(a)}\circ c{({\bm x})}$ in a similar fashion. Since this is a relation between two orthonormal basis at the same point of space-time, there exists a Lorentz transformation $\Lambda^{(a)}_{~~ (b)}$ such that we can relate the two tetrad fields associated with the coordinates systems $c$ and $\tilde c$ (see the bottom right part of Fig. \[fig1\] for an illustration of this) as $$\tilde{\bm e}_{(a)}\circ \tilde c{(\tilde{\bm x})} = \Lambda_{(a)}^{~~ (b)} ({\bm x}) {\bm e}_{(b)} ({\bm x}) \,,\qquad \tilde{\bm e}^{(a)} \circ \tilde c{(\tilde{\bm x})} = \Lambda^{(a)}_{~~ (b)} ({\bm x}) {\bm e}^{(b)} ({\bm x})\,,\qquad \eta_{(c) (d)} \Lambda^{(c)}_{~~ (a)} \Lambda^{(d)}_{~~ (b)} = \eta_{(a) (b)} \,.$$ The components of this Lorentz transformation are given, up to first order, by $$\label{Reltetradssamephysicalpoint} \Lambda^{(0)}_{~~ (0)} = 1 \,,\qquad \Lambda^{(0)}_{~~ (i)} = \Lambda^{(i)}_{~~ (0)} = {{\partial}}_i T \,,\qquad \Lambda^{(i)}_{~~ (j)} = \delta^{(i)}_{~~ (j)} +L^{[i}_{~~ , j]}\,.$$ At second order, it proves more useful to relate the components of these quantities, that is, to relate $\widetilde{e}_{(a)}{}^{\widetilde{\mu}}\circ \tilde c{(\tilde{\bm x})} \equiv {{\rm d}}\tilde x^\mu\circ \tilde c{(\tilde{\bm x})} [\widetilde{\bm e}_{(a)}]$ to $ e_{(a)}{}^\mu({\bm x})\equiv {{\rm d}}x^\mu({\bm x})[{\bm e}_{(a)}]$. For the former components, we must use  with $a(\tilde{\eta})$, $\tilde \alpha(\tilde{\bm x})$, $\tilde \beta_i(\tilde{\bm x})$ and $\tilde h_{ij}(\tilde{\bm x})$ \[that is $g_{\tilde \mu \tilde \nu}\circ \tilde c{(\tilde{\bm x})}$\] which can be deduced from the rule  just by shifting the argument of the left hand side of the rules  from ${\bm x}$ to $\tilde{\bm x}$. For the latter we must use  with $a(\eta)$, $\alpha({\bm x})$, $\beta_i({\bm x})$ and $h_{ij}({\bm x})$ \[that is $g_{\mu \nu}{({\bm x})}$\]. We do not report the corresponding expression since we will work instead directly with the perturbation components of the metric in the next section. Momentum, energy $q$ and direction $n^{(i)}$ -------------------------------------------- The components of the momentum of a particle in the canonical basis transform as $$\label{Transfopmu} p^{\widetilde{\mu}}\circ \tilde c(\tilde{\bm x}) = \frac{{{\partial}}\tilde{x}^\mu}{{{\partial}}x^\nu} p^\nu({\bm x})\,, \qquad \text{with} \qquad p^{\widetilde{\mu}} \equiv {{\rm d}}\tilde x^\mu({\bm p})\,,\quad p^{\mu} \equiv {{\rm d}}x^\mu({\bm p})\,.$$ However, we are going to use the tetrad basis in the tangent space rather than the canonical basis. We thus want to express $p^{\widetilde{(a)}}\circ \tilde c{(\tilde{\bm x})} \equiv \widetilde{\bm e}^{{(a)}}\circ \tilde c{(\tilde{\bm x})}[{\bm p}]$, \[or $\tilde q\circ \tilde c{(\tilde{ \bm x})}$ [^3] and $n^{\widetilde{(\imath)}}\circ \tilde c{(\tilde{ \bm x})}$\] as a function of $p^{(a)}({\bm x}) \equiv {\bm e}^{{(a)}} ({\bm x})[{\bm p}]$ \[or $q({\bm x})$ and $n^{(i)}({\bm x})$\]. Eventually, we will prefer to use $q$ and $n^{(i)}$ rather than $p^{(i)}$. From the definition of $q$, Eq (\[def:q\]) we then obtain the desired transformation relation $$\begin{aligned} \tilde{q}\circ \tilde c{(\tilde{\bm x})} &\equiv q ({\bm x})+\delta q ({\bm x}) \equiv q ({\bm x})[1+\delta \ln q ({\bm x})] \,, \end{aligned}$$ as $$\begin{aligned} \label{EqTp} \tilde{q}\circ \tilde c{(\tilde{\bm x})} &\equiv a^2(\tilde \eta) \tilde{N} p^{\tilde{0}} \circ \tilde c{(\tilde{\bm x})} \notag\\ &= q ({\bm x}) \left[ 1 + {{\cal H}}T + T_{,i}n^{(i)} + \frac{1}{2} ({{\cal H}}' + {{\cal H}}^2) T^2 + {{\cal H}}T T_{,i}n^{(i)} - T' T_{,i}n^{(i)} + \frac{1}{2} T^{,i} T_{,i} + T_{,i} \left( \alpha n^{(i)} - h^i{}_j n^{(j)} \right)\right] \,,\end{aligned}$$ As for $n^{(i)}$ from Eq (\[def:n\^i\]), its transformation $$\begin{aligned} n^{\widetilde{(i)}}\circ \tilde c{(\tilde{\bm x})} &\equiv n^{(i)}({\bm x}) + \delta n^{(i)}({\bm x}) \,,\end{aligned}$$ is given by $$\begin{aligned} n^{\widetilde{(i)}}\circ \tilde c{(\tilde{\bm x})} &\equiv \left[ \tilde{\beta}^i + \left( \frac{1}{\tilde{N}} \delta^i{}_j + \tilde{h}^i{}_j \right) \frac{p^{\tilde{j}}}{p^{\tilde{0}}} \right] \circ \tilde c{(\tilde{\bm x})} \notag\\ &= n^{(i)}({\bm x}) + S^{(i)(j)} T_{,j} + L^{[i,j]} n_{(j)} \,. \end{aligned}$$ Here when the argument is not specified, it is $({\bm x})$. Note that for future use, we have defined in these expressions the differences $\delta q$, $\delta \ln q$, and $\delta n^{(i)}$. The first order and second order perturbation of these can be read directly from the expressions above. We also define $\delta q^{(i)}\equiv q\Bigl[(\delta \ln q) n^{(i)} + \delta n^{(i)}\Bigr]$. It is worth stressing that these differences are measured at the same point. For instance $\delta n^{(i)}({\bm x})= n^{\widetilde{(i)}} \circ \tilde c{(\tilde{\bm x})} - n^{(i)}({\bm x}) $, and they do not vanish because in one case we use the tetrads ${\bm e}^{(i)}$ associated with the coordinate system $c$ to obtain the components, and in another case we use the tetrads $\tilde{\bm e}^{(i)}$ associated with the coordinate system $\tilde c$. It is the basis at a given point of space-time that changes when we change the coordinate system, not the momentum itself. This point is illustrated in the bottom right part of Fig. (\[fig1\]) Scalar distribution function ---------------------------- If we were using the natural basis associated with a coordinate system (the canonical basis) for the tangent space, then any scalar function on the tangent bundle $T{\cal M}$, that is a function of the space-time position and of the tangent space at each point, would transform as $$I \circ \tilde c{(\tilde {\bm x},p^{\widetilde{\mu}})} = I({\bm x},p^\mu) \,,$$ where $\tilde {\bm x}$ and ${\bm x}$ are related by  and $p^{\widetilde{\mu}}$ and $p^{\mu}$ are related by . Again this rule is a statement that the function is invariant under a change of coordinates because it is defined purely geometrically. However, as mentioned earlier, we use the basis of the tetrad field, ${\bm e}_{(i)}$ and ${\bm e}^{(i)}$, to obtain the components of momentum not the canonical basis. The tetrads are also completely determined by the choice of coordinates due to our prescription . The tetrad field, though being of tensorial nature, is not invariant as in Eq. . Furthermore, as mentioned earlier, we also work with the conformal momentum ${\bm q}$ rather than the momentum itself ${\bm p}$. Given this choice for the basis of the tangent space, the scalar function transforms as $$\label{Trulef} I\circ \tilde c{(\tilde {\bm x},q^{\widetilde{(\imath)}})} = I ({\bm x},q^{(\imath)})\,,$$ that is, it is unchanged when it is evaluated at the same point of the tangent bundle. On the other hand, the gauge transformation is a transformation rule at the same coordinate point and it is the relation between $I\circ \tilde c{({\bm x},q^{{(i)}})}$ and $I{( {\bm x},q^{{(i)}})}$. We then need the expressions of $q^{\widetilde{(\imath)}}\circ \tilde c{(\tilde{\bm x})}$ in terms of $q^{{(\imath)}}({\bm x})$ in spherical coordinates, which are derived in the previous section in . At first order, using the fact that the background distribution function cannot depend on the direction $n^{(i)}$, we obtain $$I \circ \tilde c{({\bm x},q,n^{(i)})} + \left(\xi^\mu{{\partial}}_\mu +\delta q \frac{{{\partial}}}{{{\partial}}q}\right) I \circ \tilde c{({\bm x},q,n^{(i)})}= I ({\bm x},q,n^{(i)})\,.$$ Given that the background distribution function also depends neither on time nor on space but only on $q$, we obtain $$I^{(1)}\circ \tilde c{({\bm x},q,n^{(i)})} = I^{(1)} ({\bm x},q,n^{(i)})-\delta \ln q \,{{\frac{\partial \bar I{(q)}}{\partial \ln q}}}\,.$$ At second order, we obtain $$I \circ \tilde c{({\bm x},q,n^{(i)})} + \left(\xi^\mu{{\partial}}_\mu +\delta q \frac{{{\partial}}}{{{\partial}}q} +\delta n^{(i)} D_{(i)} +\frac{1}{2}\delta q^2\frac{{{\partial}}^2 }{{{\partial}}q^2}\right) I \circ \tilde c{({\bm x},q,n^{(i)})}= I ({\bm x},q,n^{(i)}) \,.$$ Using the first order expressions, the gauge transformation rule reads $$\begin{aligned} \label{GaugeTRuleI2} \frac{1}{2}I^{(2)}\circ \tilde c{({\bm x},q,n^{(i)})} &=& \frac{1}{2} I^{(2)} ({\bm x},q,n^{(i)}) - \left(\xi^\mu{{\partial}}_\mu +\delta \ln q {{\frac{\partial}{\partial \ln q}}}+\delta n^{(i)} D_{(i)}\right) I^{(1)}{({\bm x},q,n^{(i)})}\nonumber\\* &&+ \left(\xi^\mu{{\partial}}_\mu +\delta n^{(i)}\frac{{{\partial}}}{{{\partial}}n^{(i)}}\right) (\delta \ln q) {{\frac{\partial}{\partial \ln q}}}\bar I{(q)} +\frac{1}{2}(\delta \ln q)^2 \left({{\cal D}}_q^2-2 {{\frac{\partial}{\partial \ln q}}}\right)\bar I(q)\,,\end{aligned}$$ where we used ${{\partial}}\delta \ln q / {{\partial}}\ln q = 0$. This transformation rule can be applied to $I$ or $V$ since these are scalar valued distribution functions. However we are interested in the transformation rule for the spectral components of $I$. Using the decomposition Eq (\[intensity\]) for $I$ we obtain that the temperature is transforming under a gauge transformation as (noting for simplicity $\tilde \Theta \equiv \Theta \circ \tilde c$) $$\begin{aligned} \tilde{\Theta}^{(1)} &= \Theta^{(1)} + (\delta \ln q)^{(1)} \,,\\ \frac{1}{2} \tilde{\Theta}^{(2)} &= \frac{1}{2} \Theta^{(2)} + \frac{1}{2} (\delta \ln q)^{(2)} +\Theta^{(1)} (\delta \ln q)^{(1)} - \left(\xi^\mu \frac{{{\partial}}}{{{\partial}}x^\mu}+\delta n^{(i)} D_{(i)} \right) \Bigl[ \Theta^{(1)}+(\delta \ln q)^{(1)} \Bigr]\,,\end{aligned}$$ where it is implied that all quantities are evaluated either at ${\bm x}$ or at $({\bm x},q,n^{(i)})$. The detailed form of the transformation rule can then be obtained just by considering the perturbations of $q$ and $n^i$, $\delta \ln q$ and $\delta n^{(i)}$, which have been obtained in Eqs. (\[EqTp\]). For completeness we report it here $$\begin{aligned} \tilde{\Theta} &= \Theta + {{\cal H}}T + T_{,i}n^{(i)} + \frac{1}{2} ({{\cal H}}^2 - {{\cal H}}') T^2 + {{\cal H}}T (T_{, i} n^{(i)} - T') - (T' T_{,i} + T T_{, i}') n^{(i)} \notag\\ &\qquad + T_{,i} \Bigl( \alpha n^{(i)} - h^i{}_j n^{(j)} \Bigr) - L^i ({{\cal H}}T_{, i} + T_{, i j} n^{(j)}) + \left( n^{(i)}n^{(j)} - \frac{1}{2} \delta^{i j} \right) T_{,j} T_{, i} - L^{[i}{}_{,j]} T_{, i} n^{(j)} \notag\\ &\qquad + ({{\cal H}}T + T_{, i} n^{(i)}) \Theta - \xi^\mu \Theta_{, \mu} - \Bigl( S^{(i) (j)} T_{,j} + L^{[i}{}_{,j]} n^{(j)} \Bigr) D_{(i)} \Theta \,.\end{aligned}$$ Finally, the gauge transformation of $y$ is trivial. Since $y$ vanishes at first order, $y$ is gauge invariant at second order, and it can also be checked directly by extracting $y$ out of the transformation rule of $I$ at second order . Baryons fluid description ------------------------- In order to obtain the complete gauge transformation of the collision term, we need the gauge transformation rule of the baryons fluid velocity in the tetrad frame up to second order, since it appears in the collision term. We obtain $$\begin{aligned} v^{\widetilde{(\imath)}}\circ \tilde c{({\bm x})} &= v^{(i)}({\bm x}) + T^{, i} + \alpha T^{, i} - h^i{}_j T^{, j} - T' T^{, i} + L^{[i}{}_{, j]} (v^{(j)} + T^{, j}) - T (v^{(i)}{}' + T^{, i}{}') - L^j (v^{(i)} + T^{, i})_{, j} \,.\end{aligned}$$ We also need the gauge transformation rule up to first order of the electrons density and it is easily obtained to be $$\delta_e\circ \tilde c{({\bm x})} = \delta_e({\bm x}) + 3 {\cal H} T n_e \,.$$ Gauge dependence of the Boltzmann equation and Gauge invariant form {#ssec:lc} ------------------------------------------------------------------- Having derived all the necessary gauge transformation rules, it is now possible to check the gauge dependence of the derived second order Boltzmann equation and collision term explicitly. More precisely we shall check that the Liouville and the collision terms of the Boltzmann equation transform as they should do. The Liouville term and the Collision term are distribution functions (scalar or tensor valued depending whether or not we are considering the intensity or polarisation). From the transformation rule of a scalar distribution function  and the spectral decomposition (\[spectraldecI\]) we deduce that ${\cal L}^Y$ and ${{\cal C}}^Y$ are gauge invariant and ${{\cal L}}^\Theta$ and ${{\cal C}}^\Theta$ should transforms up to the second order as (noting $\widetilde{{{\cal L}}^\Theta} \equiv {{\cal L}}^\Theta \circ \tilde c$ and $\widetilde{{{\cal C}}^\Theta} \equiv {{\cal C}}^\Theta \circ \tilde c$ ) $$\begin{aligned} \widetilde{{{\cal L}}}^\Theta &= {{\cal L}}^\Theta - \Bigl( \xi^\mu {{\partial}}_\mu + \delta n^{(i)} D_{(i)} \Bigr) {{\cal L}}^{\Theta\,(1)} + 2 {{\cal H}}T {{\cal L}}^{\Theta\,(1)} \,, \\ \widetilde{{{\cal C}}^\Theta} &= {{\cal C}}^\Theta - \Bigl( \xi^\mu {{\partial}}_\mu + \delta n^{(i)} D_{(i)} \Bigr) {{\cal C}}^{\Theta (1)} + 2 {{\cal H}}T {{\cal C}}^{\Theta (1)} \,. \end{aligned}$$ After very long and tedious but straightforward calculations using all the transformation rules derived so far for the distribution function, the metric components and the baryons velocity and energy density, we have checked that the Liouville operator ${{\cal L}}^\Theta$ and the collision term ${{\cal C}}^\Theta$ actually transform as in the above equations. This completes the consistency test of the Boltzmann equation that we have derived as well as all the gauge transformation rules obtained for its constituents. The same property is found of course for the circular polarisation since in that case the collision term vanishes. As for polarisation, we have also checked that the Liouville operator ${{\cal L}}^P_{(i)(j)}$ and the collision term ${{\cal C}}^P_{(i)(j)}$ transform like tensor valued quantities (see the details in Appendix \[AppGTLC\]). More importantly, we have checked that the Liouville and collision terms for the spectral distortions (${{\cal L}}^Y_{(i)(j)}$ and ${{\cal C}}^Y_{(i)(j)}$) are gauge invariant as it should be since they vanish on the background and first-order spacetimes. The gauge invariance of the Boltzmann equation, as in the case of Einstein equation and in general for covariant equations, enables us to write it down in terms of gauge invariant variables. In practice, it is equivalent to completely fix the gauge and write down the equations in term of the perturbation in this gauge. Summary and discussion {#sec:conc} ====================== In this paper we derived the second order Boltzmann equation in the most general manner incorporating polarisation and without fixing a gauge. In order to describe the polarisation of photon, we used a formalism based on a tensor-valued distribution function. We performed the separation between temperature and spectral distortion for the intensity and we also extended this separation to polarisation. We then derived the gauge transformation rules for the metric, the momentum and the distribution function to see how those quantities are mixed under the gauge transformation. As an application, we checked the gauge dependence of the derived Boltzmann equation under a gauge transformation and obtained consistent transformation rules. This is a non-trivial check of the correctness of the derived equations as well as the gauge transformation rules. We now discuss two issues related to the gauge dependence in the Boltzmann equation. Gauge dependence of lensing term -------------------------------- It is well known that the lensing term $$\begin{aligned} {{\cal L}}\supset \frac{{{\rm d}}n^{(i)}}{{{\rm d}}\lambda} D_i \Theta ~ : ~ ({{\mathrm{lensing ~ term}}}) \,,\end{aligned}$$ which is written in terms of the conventional lensing potential in the Newtonian gauge significantly affects the bispectrum of CMB [@Hanson:2009kg; @Lewis:2011fk; @Ade:2013ydc]. Indeed, the correlation between the lensing and ISW effect is the dominant contribution to the bias for the local-type non-Gaussianity in Planck. However it is very hard to include this contribution in the line of sight integration and evaluate it until today. Usually, the lensing effect is added separately to the final result obtained in the Poisson gauge. However the effect from this lensing term depends on the gauge choice. Actually, as we have seen above, the lensing term is mixed with other terms under the gauge transformation. This means that some of lensing effects in a specific gauge are absorbed into other effects in another gauge. In principle, there exists a gauge where we can avoid the difficult computation of this lensing term to some extent by evaluating other more tractable terms. Since we have derived the Boltzmann equation without choosing any specific gauge, it should be possible to investigate this possibility further. Observed temperature anisotropies --------------------------------- Here we make a comment on the observed temperature anisotropies. In the main part of this paper, we have shown that the second order Boltzmann equation is gauge invariant and thus it can be written in terms of gauge invariant quantities. However, there is a subtlety in the meaning of “gauge invariance”. This originates from our choice of the local inertial frame. As is clear from Eq (\[tetrads\]), we always choose the local inertial frame so that the three-velocity vanishes, $\hat{v}^i=0$ and there is no rotation of the spatial axis relative to the background spatial coordinate axis, let us call $\theta_i=0$. In order to achieve this, the local inertial frame has to be changed when we perform a gauge transformation. If we were to identify this local inertial frame as the one of an observer, we would be lead to consider different observers in different gauges. This is clear from the gauge transformation at the first order: $$\Theta \to \Theta + {\cal H} T + T_{,i} n^i\,. \label{1sttempg}$$ The last term comes from a change of local inertial frame. By fixing the gauge we can promote $\Theta$ to the gauge invariant temperature fluctuations but these are temperature fluctuations observed by an observer with $\hat{v}^i=0$ and $\theta_i=0$ in this gauge. In order to evaluate temperature fluctuations observed by a different observer, we need to change the local inertial frame. Alternatively, we can perform a gauge transformation keeping the conditions $\hat{v}^i=0$ and $\theta_i=0$ for the local inertial frame so that this frame coincides with the one of the observer. In all the literature, the second order temperature anisotropies are calculated in the Poisson gauge so far, with a specific choice of the local inertial frame. Strictly speaking this is not the temperature anisotropies that we observe as there is no reason for us to be comoving with the local inertial frame associated with such a gauge. One thus needs to change the local inertial frame or change a gauge. At first order, this was not an issue. As is clear from (\[1sttempg\]), the change of gauge and the local inertial frame only affect the monopole $\ell =0$ and dipole $\ell =1$ if we expand the temperature anisotropies into multipole components. Thus, the $\ell \geq 2$ modes are not affected by the change of observers. However this is no longer the case at the second order. In the second order gauge transformation, there are terms that are convolutions of the first order temperature anisotropies and the gauge transformation; $$\begin{aligned} \Theta \to \Theta - \xi^\mu \Theta_{, \mu} - \delta n^{(i)} D_{(i)} \Theta + \cdots \,. \end{aligned}$$ These terms affect the observed temperatures even for the $\ell \geq 2$ modes. In order to define the "observed temperature anisotropies”, we should keep the conditions $\hat{v}^i=0$ and $\theta_i=0$ for the local inertial frame and specify the gauge so that this local inertial frame coincides with our local inertial frame where we perform experiments. Thus special care must be taken when we compare theoretical predictions to observations. Our formula for the gauge transformation will be useful to investigate this issue further. A.N is grateful to Shuichiro Yokoyama and Ryo Saito for their continuous encouragement and fruitful discussion. This work was supported in part by Monbukagaku-sho Grant-in-Aid for the Global COE programs, "The Next Generation of Physics, Spun from Universality and Emergence” at Kyoto University, by JSPS Grant-in-Aid for Scientific Research (A) No. 21244033, and by the Long-term Workshop at Yukawa Institute on Gravity and Cosmology 2012, YITP-T-12-03. AN is partly supported by Grant-in-Aid for JSPS Fellows No. 21-1899 and JSPS Postdoctoral Fellowships for Research Abroad. CP was supported by the STFC (UK) grant ST/H002774/1 during the first part of this research, and was then supported by French state funds managed by the ANR within the Investissements d’Avenir programme under reference ANR-11-IDEX-0004-02. K.K. is supported by STFC grant ST/H002774/1, ST/K0090X/1, the European Research Council and the Leverhulme trust. ADM variables and usual perturbation variables {#app:ADM} ============================================== From the form of the metric in the ADM parametrisation (\[MetricADM\]), and the perturbation of the lapse function and the spatial metric given in the equations (\[DefPertNNi\]), the perturbed metric is expressed up to second order as $${{\rm d}}s^2 = a^2 (\eta) \Bigl[ - (1 + 2 \alpha + \alpha^2 - \beta_i \beta^i) {{\rm d}}\eta^2 + 2 (\delta_{i j} + 2 h_{i j}) \beta^j {{\rm d}}x^i {{\rm d}}\eta + (\delta_{i j} + 2 h_{i j}) {{\rm d}}x^i {{\rm d}}x^j \Bigr] \,.$$ This has to be compared with the usual parametrisation of the perturbations of the metric which is in the form $$\begin{gathered} {{\rm d}}s^2 = a^2 (\eta) \Bigl[ - (1 + 2 A) {{\rm d}}\eta^2 + 2 B_i {{\rm d}}x^i {{\rm d}}\eta + (\delta_{i j} + 2 C_{i j}) {{\rm d}}x^i {{\rm d}}x^j \Bigr] \,, \end{gathered}$$ where $C_{i j}$ can be further split into 2 scalar, 2 vector and 2 tensor degrees of freedom. By a direct comparison of these two parametrisations, the relation between the two metric parametrisations is $$\begin{aligned} g_{0 0} &: 1 + 2 \alpha + \alpha^2 - \beta_i \beta^i = 1 + 2 A\,,\\ g_{0 i} &: \beta_i + 2 h_{i j} \beta^j = B_i\,, \\ g_{i j} &: \delta_{i j} + 2 h_{i j} = \delta_{i j} + 2 C_{i j}\,.\end{aligned}$$ At first order we obtain $$\begin{gathered} A^{(1)} = \alpha^{(1)} \,, \qquad B_i^{(1)} = \beta^{(1)}_i \,, \qquad C_{i j}^{(1)} = h_{i j}^{(1)} \,,\end{gathered}$$ and the two parametrisations are the same. However, at second order we get the relations $$\begin{gathered} A^{(2)}= \alpha^{(2)} + \alpha^{(1) 2} - \beta^{(1)}_i \beta^{(1) i} \,, \qquad B_i^{(2)} = \beta^{(2)}_i + 4 h_{i j}^{(1)} \beta^{(1) j} \,,\qquad C_{i j}^{(2)} = h_{i j}^{(2)} \,.\end{gathered}$$ Construction of the distribution function for polarised light {#app:Dist} ============================================================= We consider a two-dimensional polarisation plane defined by two unit complex vectors $\hat {{\boldsymbol{\epsilon}}}_{({{\mathrm{I}}})}$ and $\hat {{\boldsymbol{\epsilon}}}_{({{\mathrm{II}}})}$, which are mutually orthogonal, $\hat \epsilon_{({{\mathrm{A}}})}{}^{\star\mu} \hat \epsilon_{({{\mathrm{B}}})}{}^\nu g_{\mu\nu} =\delta_{({{\mathrm{A}}})({{\mathrm{B}}})}$. Any polarisation $\boldsymbol{\epsilon}$ can be represented by a superposition of $\hat {{\boldsymbol{\epsilon}}}_{(A)}$ in the form $${{\boldsymbol{\epsilon}}}= \sum_{A={{\mathrm{I}}},{{\mathrm{II}}}} \epsilon^A \hat {{\boldsymbol{\epsilon}}}_{(A)} \label{pol}\,.$$ The orthogonal vectors $\hat {{\boldsymbol{\epsilon}}}_{(A)}$ define a polarisation plane and we choose them to be orthogonal to the direction of the photon $n^{(i)}$ and to the observer velocity ${\bm e}_{(0)}$, $$\label{EqProjepsilons} \hat \epsilon_{(A)}{}^\mu n^{\nu} g_{\mu \nu} = \hat \epsilon_{(A)}{}^\mu {e}_{(0)}{}^\nu g_{\mu\nu}=0\,.$$ We can also associate canonically polarisation forms through $\hat \epsilon^{(A)}{}_\mu \equiv g_{\mu\nu} \hat \epsilon_{(A)}{}^\nu$, and they will be also complex unit forms and mutually orthogonal. The polarisation density matrix $f_{A B}$ is defined so that the expected number of photon in a phase-space element with a polarisation state ${{\boldsymbol{\epsilon}}}$ is given by $$\begin{gathered} f( {\bf x}, {\bf p}, {{\boldsymbol{\epsilon}}}) \equiv f_{A B}({\bf x}, {\bf p}) \epsilon^{\star A} \epsilon^B \,. \end{gathered}$$ With such a parametrisation, all the electromagnetic gauge degrees of freedom have been fixed and we parametrise the physical degrees of freedom of this density matrix by the usual Stokes parameters as $$\begin{gathered} f_{A B} = \frac{1}{2} \begin{pmatrix} I + Q & U - i V \\ U + i V & I - Q \end{pmatrix} \,,\end{gathered}$$ where it is implied that $f_{AB}$ and the Stokes parameters depend on the position $x^\mu$ and on the momentum $p^\mu$ \[or $(q,n^{(i)})$ in spherical coordinates\]. $f_{AB}$ is a Hermitian matrix since $f_{AB}=f_{BA}^\star$. From the four-dimensional point of view, the polarisation density matrix is a tensor-valued distribution function. It is a 2-form defined by $$\begin{gathered} f_{\mu \nu} \equiv f_{A B} \epsilon^{\star(A)}{}_\mu \epsilon^{(B)}{}_\nu \,,\end{gathered}$$ and the expected number of photon in a phase-space element for a polarisation state ${{\boldsymbol{\epsilon}}}$ is given by $$\label{Eqdefffromfmunu} f ({\bf x}, {\bf p}, {{\boldsymbol{\epsilon}}}) \equiv f_{\mu\nu} ({\bf x}, {\bf p}) \epsilon^{\star\mu} \epsilon^\nu \,.$$ This can be viewed as a multipolar expansion in the polarisation state. From (\[EqProjepsilons\]), the tensor-valued distribution function is a projected quantity such that $$f_{\mu \nu} =S_\mu{}^\alpha S_{\mu}{}^\beta f_{\alpha \beta}\,.$$ It is then straightforward to realize that it can be decomposed according to (\[Pol\]). Boltzmann equation for the tensor-valued distribution function {#app:Boltz_pol} ============================================================== From a scalar valued to a tensor-valued distribution function ------------------------------------------------------------- In this section, we explain in detail how the Boltzmann equation for the tensor-valued distribution function can be obtained from the Boltzmann equation of a scalar distribution function. Since this scalar distribution function $f$ depends on $x^\mu,p^\mu$ but also on $\epsilon^\mu$, the action of the Liouville operator is given by $$\label{CrudeBoltzmann} \frac{{{\cal D}}}{{{\cal D}}\lambda} f (x^\mu, p^\mu, \epsilon^\mu) = \frac{{{\rm d}}x^\alpha}{{{\rm d}}\lambda} \frac{{{\partial}}f}{{{\partial}}x^\alpha} + \frac{{{\rm d}}p^\alpha}{{{\rm d}}\lambda} \frac{{{\partial}}f}{{{\partial}}p^\alpha} + \frac{{{\rm d}}\epsilon^\alpha}{{{\rm d}}\lambda} \frac{{{\partial}}f}{{{\partial}}\epsilon^\alpha} = C [f]\,.$$ In the geometric optics approximation, $p^\mu$ and $\epsilon^\mu$ are parallel transported and we obtain $$\begin{aligned} 0 =& \frac{{{\cal D}}p^\alpha}{{{\cal D}}\lambda} = \frac{{{\rm d}}p^\alpha}{{{\rm d}}\lambda} + \Gamma^\alpha_{\beta \gamma} p^\beta p^\gamma \,, \\ 0 =& \frac{{{\cal D}}\epsilon^\alpha}{{{\cal D}}\lambda} = \frac{{{\rm d}}\epsilon^\alpha}{{{\rm d}}\lambda} + \Gamma^\alpha_{\beta \gamma} \epsilon^\beta p^\gamma \,.\end{aligned}$$ Using (\[Eqdefffromfmunu\]), the term involving the evolution of polarisation is obtained as $$\begin{gathered} \frac{{{\rm d}}\epsilon^\alpha}{{{\rm d}}\lambda} \frac{{{\partial}}f}{{{\partial}}\epsilon^\alpha} = f_{\alpha \beta} \frac{{{\rm d}}\epsilon^{\alpha}}{{{\rm d}}\lambda} \epsilon^{* \beta} + f_{\alpha \beta} \frac{{{\rm d}}\epsilon^{\star \beta}}{{{\rm d}}\lambda} \epsilon^{\alpha} = - \Gamma^{\alpha}_{\gamma \delta} \epsilon^\gamma p^\delta f_{\alpha \beta} \epsilon^{* \beta} - \Gamma^{\beta}_{\gamma \delta} \epsilon^{\star\gamma} p^\delta f_{\alpha \beta} \epsilon^{\alpha}\,.\end{gathered}$$ Combining this result with the space-time derivative term of the Liouville operator, we get $$\begin{gathered} p^\alpha \frac{{{\partial}}f}{{{\partial}}x^\alpha} + \frac{{{\rm d}}\epsilon^\alpha}{{{\rm d}}\lambda} \frac{{{\partial}}f}{{{\partial}}\epsilon^\alpha} = p^\gamma \epsilon^\alpha (\nabla_\gamma f_{\alpha \beta}) \epsilon^{* \beta} \,,\end{gathered}$$ and thus the Boltzmann equation (\[CrudeBoltzmann\]) can be rewritten as $$\label{EqBoltzmannfee} \frac{{{\cal D}}f}{{{\cal D}}\lambda} = \epsilon^\mu \left( p^\alpha \nabla_\alpha f_{\mu \nu} + \frac{{{\rm d}}p^\alpha}{{{\rm d}}\lambda} \frac{{{\partial}}f_{\mu \nu}}{{{\partial}}p^\alpha} \right) \epsilon^{* \nu} = C [f] \equiv \epsilon^\mu C_{\mu \nu} \epsilon^{* \nu} \,.$$ The last equality defines the tensor-valued collision term. If we do fix the electromagnetic gauge condition for the collision term in the same manner as what we did for $f_{\mu \nu}$, that is, if $C_{\mu \nu} =S_\mu{}^\alpha S_{\nu}{}^\beta C_{\alpha \beta}$, then the Boltzmann equation for $f_{\mu\nu}$ is given by $$\label{EqBaseBoltzmann} S_\mu{}^\alpha S_{\mu}{}^\beta \frac{{{\cal D}}f_{\alpha \beta}}{{{\cal D}}\lambda} \equiv S_\mu{}^\alpha S_{\mu}{}^\beta \left(p^\sigma \nabla_\sigma f_{\alpha \beta} + \frac{{{\rm d}}p^\sigma}{{{\rm d}}\lambda} \frac{{{\partial}}f_{\alpha \beta}}{{{\partial}}p^\sigma}\right) = C_{\mu\nu}\,.$$ Note that the use of the projectors is required because the components of the equation which are not in the polarisation plane are not fixed by (\[EqBoltzmannfee\]). From the canonical basis to the tetrad basis {#sapp:covp} -------------------------------------------- In the equation (\[EqBaseBoltzmann\]), the Greek indices refer to a given coordinate system and its canonical basis for the tangent space, and the distribution function is a function of $(x^\mu,p^\mu)$. If we want to use instead an orthonormal basis for the tangent space, that is, to use the components $p^{(i)}=e^{(i)}{}_\mu p^\mu$ or the conformal momentum components $q^{(i)} = a p^{(i)}$ in the tetrad basis, then the Boltzmann equation can be modified accordingly. In order to do so, we need to be explicit about the partial derivatives to emphasize which variables are to be kept constant when the partial derivatives are evaluated. The Boltzmann equation reads indeed $$\label{Boltzbaseopen} S_\mu{}^\alpha S_{\nu}{}^\beta \frac{{{\cal D}}f_{\alpha \beta}}{{{\cal D}}\lambda} = S_\mu{}^\alpha S_{\nu}{}^\beta \left( p^\gamma \left.\frac{{{\partial}}f_{\alpha \beta}}{{{\partial}}x^\gamma}\right|_{p^\mu} - p^\gamma \Gamma^\delta_{\gamma \alpha} f_{\delta \beta} - p^\gamma \Gamma^\delta_{\gamma \beta} f_{\alpha \delta} + \left.\frac{{{\rm d}}p^\gamma}{{{\rm d}}\lambda} \frac{{{\partial}}f_{\alpha \beta}}{{{\partial}}p^\gamma}\right|_{x^\mu}\right) \,.$$ Using the properties $$\left.\frac{{{\partial}}f_{\alpha \beta}}{{{\partial}}x^\mu} \right|_{p^\mu} = \left.\frac{{{\partial}}f_{\alpha \beta}}{{{\partial}}x^\mu}\right|_{q^{(i)}} + \frac{{{\partial}}f_{\alpha \beta}}{{{\partial}}q^{(i)}} \frac{{{\partial}}(a e^{(i)}{}_\nu)}{{{\partial}}x^\mu}p^\nu \,, \qquad \left.\frac{{{\partial}}f_{\alpha \beta}}{{{\partial}}p^\mu}\right|_{x^\mu} = \left.\frac{{{\partial}}f_{\alpha \beta}}{{{\partial}}q^{(i)}}\right|_{x^\mu} ae^{(i)}{}_\mu \,, \qquad \frac{{{\rm d}}q^{(i)}}{{{\rm d}}\lambda} = a e^{(i)}{}_\mu \frac{{{\rm d}}p^\mu}{{{\rm d}}\lambda} + p^\mu \frac{{{\rm d}}(a e^{(i)}{}_\mu)}{{{\rm d}}\lambda} \,,$$ we then deduce that $$\begin{aligned} \label{Boltzbasetetrad} S_\mu{}^\alpha S_{\nu}{}^\beta \frac{{{\cal D}}f_{\alpha \beta}}{{{\cal D}}\lambda} &=S_\mu{}^\alpha S_\nu{}^\beta \left(p^\gamma \left.\frac{{{\partial}}f_{\alpha \beta}}{{{\partial}}x^\gamma} \right|_{q^{(i)}} - p^\gamma \Gamma^\delta_{\gamma \alpha} f_{\delta \beta} - p^\gamma \Gamma^\delta_{\gamma \beta} f_{\alpha\delta} + \left.\frac{{{\rm d}}q^{(i)}}{{{\rm d}}\lambda} \frac{{{\partial}}f_{\alpha \beta}}{{{\partial}}q^{(i)}} \right|_{x^\mu}\right) \notag\\ &= S_\mu{}^\alpha S_{\mu}{}^\beta \left(p^\gamma \nabla_\gamma f_{\alpha \beta} + \frac{{{\rm d}}q^{(i)}}{{{\rm d}}\lambda} \frac{{{\partial}}f_{\alpha \beta}}{{{\partial}}q^{(i)}}\right)\,.\end{aligned}$$ Comparing Eqs. (\[Boltzbaseopen\]) and (\[Boltzbasetetrad\]), we notice that the notation $p^\gamma \nabla_\gamma f_{\alpha \beta}$ could be ambiguous. Indeed if we use the canonical coordinate system for the tangent space, then ${{\partial}}/{{\partial}}x^\mu$ is to be taken at $p^\mu$ fixed, but if we take the tetrad basis (or another coordinate system for the tangent space), then ${{\partial}}/{{\partial}}x^\mu$ is to be taken with $q^{(i)}$ fixed. Eq. (\[Boltzbasetetrad\]) is not exactly the desired form of the Boltzmann equation when the distribution function depends on $(x^\mu,q^{(i)})$. In fact, the use of the tetrad basis makes it natural to work with spherical coordinates in the tangent space. In order to introduce them, we first relate the Cartesian derivative in the tangent space, that is, the derivative with respect to $q^{(i)}$, to the covariant derivative on the unit sphere which is described by the possible directions $n^{(i)}$ of the momentum. We must stress that at any point of space-time, $x^\mu$, a distribution function (tensor-valued like $f_{\mu\nu}$ or scalar valued like its trace $I$) which depends on $(x^\mu,q^{(i)})$ can be considered as a field in the tangent space because the tangent space at a given point can be considered as a flat three-dimensional manifold whose points are labelled by $q^{(i)}$ and the natural covariant derivative in this manifold is ${{\partial}}/{{\partial}}q^{(i)}$. Using that $q^{(i)} = q n^{(i)}$, and the property $$\label{ExtrinsicK} \frac{{{\partial}}n^{(i)}}{{{\partial}}q^{(j)}} = \frac{1}{q} S^{(i)}{}_{(j)} \,,$$ it is possible to show the following relations; $$\begin{aligned} \label{Expandderpi} q \frac{{{\partial}}T_{\mu\nu}}{{{\partial}}q^{(i)}} &= \frac{{{\partial}}T_{\mu\nu}}{{{\partial}}\ln q} n_{(i)} + D_{(i)} T_{\mu\nu} - e_{(i)}{}^\rho (T_{\mu \rho} n_{\nu} + T_{\nu \rho}n_{\mu}) \,, &\quad\text{with}\quad & D_{(i)} T_{\mu\nu} \equiv q S_{(i)}{}^{(j)} S_\mu{}^\alpha S_\nu{}^\beta \frac{{{\partial}}T_{\alpha\beta}}{{{\partial}}q^{(j)}} \,, \\* q \frac{{{\partial}}S}{{{\partial}}q^{(i)}} &= \frac{{{\partial}}S}{{{\partial}}\ln q} n^{(i)} + D_{(i)} S \,, &\quad\text{with}\quad & D_{(i)} S \equiv q S_{(i)}{}^{(j)} \frac{{{\partial}}S}{{{\partial}}q^{(j)}} \,,\end{aligned}$$ where $T_{\mu\nu}(q^{(i)})$ is a projected tensor field in the tangent space such that $T_{\mu\nu}(q^{(i)}) n^{\nu}=T_{\mu\nu}(q^{(i)}) n^{\nu}=0$, and $S(q^{(i)})$ is a scalar field in the tangent space. Here $D_{(i)}$ is the covariant derivative on the two-sphere associated with the unit direction vector $n^{(i)}$, and it appears naturally as an induced derivative on the sphere, given that this is the surface orthogonal to $n^{(i)}$ (see Ref. [@Gourgoulhon:2007ue] for more details on induced derivatives). We can then deduce the useful property $$\label{KeyRuleForCovDSpherical} q S_\mu{}^\alpha S_\nu{}^\beta \frac{{{\partial}}f_{\alpha \beta}}{{{\partial}}q^{(i)}} = \frac{{{\partial}}f_{\mu\nu}}{{{\partial}}\ln q} n_{(i)} + D_{(i)} f_{\mu\nu} \,.$$ Given that $$\frac{{{\rm d}}q^{(i)}}{{{\rm d}}\lambda} = q \left(\frac{{{\rm d}}\ln q }{{{\rm d}}\lambda} n^{(i)} + \frac{{{\rm d}}n^{(i)}}{{{\rm d}}\lambda} \right)\,,$$ from Eqs. (\[Expandderpi\]) and Eq. (\[Boltzbasetetrad\]), we then find that the Boltzmann equation takes the form $$S_\mu{}^\alpha S_\nu{}^\beta \frac{{{\cal D}}f_{\alpha \beta}}{{{\cal D}}\lambda} = S_\mu{}^\alpha S_\nu{}^\beta \nabla_\gamma f_{\alpha \beta} \frac{{{\rm d}}x^\gamma}{{{\rm d}}\lambda} + \frac{{{\partial}}f_{\mu \nu}}{{{\partial}}\ln q} \frac{{{\rm d}}\ln q}{{{\rm d}}\lambda} + D_{(i)} f_{\mu \nu} \frac{{{\rm d}}n^{(i)}}{{{\rm d}}\lambda} = C_{\mu \nu} \,.$$ Decomposition of the Boltzmann equation --------------------------------------- In order to obtain equations for the components of $f_{\mu\nu}$, $I, P_{\mu \nu}$ and $V$, we want to apply the same type of decomposition on the equation itself. Applying ${{\cal D}}/{{\cal D}}\lambda$ on the decomposition  of $f_{\mu\nu}$ leads to $$\begin{gathered} \frac{{{\cal D}}f_{\mu \nu}}{{{\cal D}}\lambda} = \frac{1}{2} \left( \frac{{{\cal D}}I}{{{\cal D}}\lambda} S_{\mu \nu} + I \frac{{{\cal D}}S_{\mu \nu}}{{{\cal D}}\lambda} \right) + \frac{{{\cal D}}P_{\mu \nu}}{{{\cal D}}\lambda} + \frac{{{\rm i}}}{2} \epsilon_{\alpha \mu \nu \beta} \left( \frac{{{\cal D}}V}{{{\cal D}}\lambda} e_{(0)}{}^\alpha n^\beta + V \frac{{{\cal D}}(e_{(0)}{}^\alpha n^\beta)}{{{\cal D}}\lambda} \right) \,.\end{gathered}$$ We then need to screen-project this equation in order to obtain the tensor-valued Boltzmann equation. Then the last two terms vanish. Indeed, first $$S_\mu{}^\alpha S_\nu{}^\beta \frac{{{\cal D}}S_{\alpha \beta}}{{{\cal D}}\lambda} = S_\mu{}^\alpha S_\nu{}^\beta \left[ \frac{{{\rm d}}p}{{{\rm d}}\lambda} \left( - \frac{p_\alpha e^{(0)}{}_\beta + e^{(0)}{}_\alpha p_\beta}{p^2} + 2 \frac{ p_\alpha p_\beta}{p^3} \right) + \frac{1}{p} \left( p_\alpha \frac{{{\cal D}}e^{(0)}{}_\beta}{{{\cal D}}\lambda} + \frac{{{\cal D}}e^{(0)}{}_\alpha}{{{\cal D}}\lambda} p_\beta \right) \right] = 0\,.$$ Second, from the normalization condition of $e_{(0)}{}^\mu$ and $n^\mu$, we can show that $$e^{(0)}{}_\mu \frac{{{\cal D}}e_{(0)}{}^\mu}{{{\cal D}}\lambda} = 0 \,, \qquad n_\mu \frac{{{\cal D}}n^\mu}{{{\cal D}}\lambda} = 0 \,.$$ This means that the derivative of $e_{(0)}{}^\mu$ is orthogonal to $e^{(0)}{}_\mu$ and the derivative of $n^\mu$ is orthogonal to $n_\mu$. We thus find that $$S_\mu{}^\alpha S_\nu{}^\beta \epsilon_{\gamma \alpha \beta \delta} \frac{{{\cal D}}(e_{(0)}{}^\gamma n^\delta)}{{{\cal D}}\lambda} = S_\mu{}^\alpha S_\nu{}^\beta \epsilon_{\gamma \alpha \beta \delta} \left( \frac{{{\cal D}}e_{(0)}{}^\gamma}{{{\cal D}}\lambda} n^\delta + e_{(0)}{}^{\gamma} \frac{{{\cal D}}n^\delta}{{{\cal D}}\lambda} \right) = 0 \,.$$ Finally, we obtain that the Boltzmann equation for the tensor-valued distribution functions can be split into the desired form as $$\begin{gathered} S_\mu{}^\alpha S_\nu{}^\beta \frac{{{\cal D}}f_{\alpha \beta}}{{{\cal D}}\lambda} = \frac{1}{2} \frac{{{\cal D}}I}{{{\cal D}}\lambda} S_{\mu \nu} + S_\mu{}^\alpha S_\nu{}^\beta \frac{{{\cal D}}P_{\alpha \beta}}{{{\cal D}}\lambda} + \frac{{{\rm i}}}{2} \frac{{{\cal D}}V}{{{\cal D}}\lambda} \epsilon_{\alpha \mu \nu \beta} e_{(0)}{}^\alpha n^\beta = C_{\mu \nu} \,.\end{gathered}$$ Expression of the Boltzmann equation for polarisation {#sapp:Boltzeq_pol} ----------------------------------------------------- First of all, the Boltzmann equation for the circular polarisation is the same as that for the intensity, but with $\bar V=0$ and with a vanishing collision term since it is not generated by the Compton scattering. We shall not study further the equation dictating the evolution of $V$ since it should remain null at all time unless generated by other types of collisions. As for the linear polarisation, let us write down the basic equations for the tetrad components as commonly done at first order. By moving to the tetrad components, one can rewrite the covariant derivative in the Liouville operator as $$\begin{aligned} e_{(a)}{}^\mu e_{(b)}{}^\nu L [{\bf P}\,]_{\mu \nu} &= S_{(a)}{}^{(c)} S_{(b)}{}^{(d)} \left( P_{(c) (d) | (e)} e^{(e)}{}_\mu \frac{{{\rm d}}x^\mu}{{{\rm d}}\lambda} + \frac{{{\partial}}P_{(c) (d)}}{{{\partial}}\ln q} \frac{{{\rm d}}\ln q}{{{\rm d}}\lambda} + D_{(i)} P_{(c) (d)} \frac{{{\rm d}}n^{(i)}}{{{\rm d}}\lambda} \right) \,,\end{aligned}$$ where $$\begin{aligned} f_{(a) (b) | (c)} &\equiv e_{(c)}{}^\mu {{\partial}}_\mu f_{(a) (b)} - w^{(d)}{}_{(a) (c)} f_{(d) (b)} - w^{(d)}{}_{(b) (c)} f_{(a) (d)} \,,\end{aligned}$$ and $w^{(a)}{}_{(b) (c)}$ is the Ricci rotation coefficient defined by $w^{(a)}{}_{(b) (c)} \equiv e^{(a)}{}_\mu \nabla_{(c)} e_{(b)}{}^\mu$. Here we also notice that only the spatial component has non-vanishing term because the projection of $S_\mu{}^\nu$ onto $e^\mu{}_{(0)}$ vanishes by construction. After the decomposition of the Boltzmann equation for polarisation, one obtains the following equation for the temperature part as in Eq. (\[eq:Boltz\_pol\_dis\]) up to the second order $$\begin{aligned} {{\cal L}}^P_{(i) (j)} &= {{\cal P}}_{(i) (j)}{}' + {{\cal P}}_{(i) (j), k} n^{(k)} + \frac{a^2}{q}\left[\left. \frac{{{\rm d}}\eta}{{{\rm d}}\lambda} \right|^{(1)} {{\cal P}}_{(i) (j)}{}' + \left. \frac{{{\rm d}}x^k}{{{\rm d}}\lambda} \right|^{(1)} {{\cal P}}_{(i) (j), k} + \left. \frac{{{\rm d}}n^{(k)}}{{{\rm d}}\lambda} \right|^{(1)} D_{(k)} {{\cal P}}_{(i) (j)}\right] \notag\\ & \qquad - a\Bigl( w^{(k)}{}_{(l) (0)} + w^{(k)}{}_{(l) (m)} n^{(m)} \Bigr)^{(1)} \Bigl( S_{(i)}{}^{(l)} {{\cal P}}_{(k) (j)} + S_{(j)}{}^{(l)} {{\cal P}}_{(k) (i)} \Bigr)\,.\end{aligned}$$ As for the spectral distortion, the equation is given by $$\begin{aligned} {{\cal L}}^Y_{(i) (j)} &= Y_{(i) (j)}{}' + Y_{(i) (j), k} n^{(k)} \,.\end{aligned}$$ The complete expression of the collision term for the linear polarisation is given by $$\begin{aligned} {{\cal C}}_{(i) (j)}^P &= a \, \bar{n}_e \sigma_T \left( - {{\cal P}}_{(i) (j)} - \frac{3}{4} {{\cal T}}_{(i) (j)}{}^{(k) (l)} \Bigl[ \langle \Theta m_{(k) (l)} \rangle - 2 \langle {{\cal P}}_{(k) (l)} \rangle \Bigr] + v^{(k)} n_{(k)} {{\cal P}}_{(i) (j)} \right) \notag\\ &\qquad + a \, \bar{n}_e \sigma_T \biggl( {{\cal T}}_{(i) (j)}{}^{(k) (l)} \Bigl[ {{\cal Q}}_{(k) (l)}^T - \Theta {{\cal Q}}_{(k) (l)}^{T ~~~ (1)} \Bigr] - 3 {{\cal C}}^\Theta {{\cal P}}_{(i) (j)} + \delta_e {{\cal C}}^P_{(i) (j)} \biggr) \,, \\ C^Y_{(i) (j)} &= a \, \bar{n}_e \sigma_T \left( - Y_{(i) (j)} - \frac{3}{4} {{\cal T}}_{(i) (j)}{}^{(k) (l)} \Bigl[ \langle y m_{(k) (l)} \rangle - 2 \langle Y_{(k) (l)} \rangle \Bigr] + {{\cal T}}_{(i) (j)}{}^{(k) (l)} {{\cal Q}}_{(k) (l)}^Y - {{\cal C}}^\Theta {{\cal P}}_{(i) (j)} \right) \,,\end{aligned}$$ where ${{\cal T}}_{(i) (j)}{}^{(k) (l)}$ is a traceless projection operator with respect to $S_{(i) (j)}$ $$\begin{aligned} {{\cal T}}_{(i) (j)}{}^{(k) (l)} \equiv S_{(i)}{}^{(k)} S_{(j)}{}^{(l)} - \frac{1}{2} S^{(k) (l)} S_{(i) (j)} \,.\end{aligned}$$ Finally before closing this section let us explicitly write down the equation for the temperature part for the sake of completeness. It is of the form $$\begin{aligned} {{\cal L}}^P_{(i) (j)} = {{\cal C}}_{(i) (j)}^P \,, \end{aligned}$$ and using that at first order $$w^{(k)}{}_{(l) (0)} = \frac{1}{a}\beta^{[k}{}_{, l]} \,,\qquad w^{(k)}{}_{(l) (m)} =\frac{2}{a} h_m{}^{[k}{}_{, l]} \,,$$ the explicit form of ${{\cal L}}^P_{(i) (j)}$ is $$\begin{aligned} {{\cal L}}_{(i) (j)}^P \equiv &{{\cal P}}_{(i) (j)}{}' + {{\cal P}}_{(i) (j), k} n^{(k)} \,, - \alpha {{\cal P}}_{(i) (j)}{}' - (\beta^k + h^k{}_l n^{(l)}) {{\cal P}}_{(i) (j), k} \notag\\ & \qquad - \Bigl( \alpha_{, k} - \beta_{l, k} n^{(l)} + h_{k l}{}' n^{(l)} + 2 h_{m [k, l]} n^{(l)} n^{(m)} \Bigr) D^{(k)} {{\cal P}}_{(i) (j)} \notag\\ & \qquad \qquad - \Bigl( \beta^{[k}{}_{, l]} + 2 h_m{}^{[k}{}_{, l]} n^{(m)} \Bigr) \Bigl( S_{(i)}{}^{(l)} {{\cal P}}_{(k) (j)} + S_{(j)}{}^{(l)} {{\cal P}}_{(k) (i)} \Bigr) \,.\end{aligned}$$ Technical details about linear polarisation =========================================== Gauge transformation of a tensor-valued distribution function {#AppGTtensor} ------------------------------------------------------------- In this section, we investigate the transformation property of the distribution matrix up to the second order. The transformation properties of $I$ and $V$, which are scalar distribution functions, have already been investigated in the main text. In this section we focus on the case of the linear polarisation and set $I=V=0$ such that $f_{\mu\nu}=P_{\mu\nu}$. Since the polarisation matrix is at least first order, this means that we need only to keep terms which are first order in the coordinates transformation $(T,L^i)$. First we must understand the transformation properties of the screen projector. As for the tetrads, it is not a purely geometric quantity and it is not invariant under a change of coordinates. Indeed, it is defined with respect to the time-like tetrad which depends on the choice of coordinates. We thus have the two related screen projectors $${\bm S}({\bm p})={\bm g}+{\bm e}^{(0)} \otimes {\bm e}^{(0)}-{\bm n}\otimes{\bm n}\,,\quad \tilde{\bm S}({\bm p})={\bm g}+\tilde {\bm e}^{(0)} \otimes \tilde {\bm e}^{(0)}-\tilde{\bm n}\otimes\tilde{\bm n}\,,\quad\text{with}\quad {\bm n}\equiv \frac{{\bm p}}{{p}^\mu{e}^{(0)}_\mu}-{\bm e}^{(0)}\,,\quad \tilde{\bm n}\equiv \frac{{\bm p}}{{p}^\mu \tilde {e}^{(0)}_\mu}-\tilde{\bm e}^{(0)}\,.$$ If we use the transformation rule at the same point  we find that at first order in the transformation the relation between these projectors is given by  [@Tsagas:2007yx] $$\label{RelSStilde} \tilde S_{\mu \nu}\circ \tilde c{(\tilde{\bm x},q^{\widetilde{(a)}})}= S_{\mu\nu}({\bm x},q^{(a)})+ 2 \left(e^{(0)}_{(\mu}+n_{(\mu}\right) S_{\nu) \alpha}({\bm x},q^{(a)}) V^\alpha\,,\quad \text{with}\quad {\bm V} \equiv -\Lambda^{(i)}_{\,\,(0)} {\bm e}_{(i)}=-{{\partial}}^i T {\bm e}_i\,.$$ Note that if we use tetrad coordinates for the argument of the screen projectors, then $${\bm S}(q,n^{(i)})={\bm g}+{\bm e}^{(0)} \otimes {\bm e}^{(0)}-n_{(i)} n_{(j)}{\bm e}^{(i)}\otimes {\bm e}^{(j)}\,,\qquad \tilde{\bm S}\circ \tilde c{(q,n^{(i)})}={\bm g}+\tilde{\bm e}^{(0)} \otimes \tilde{\bm e}^{(0)}-n_{(i)} n_{(j)}\tilde {\bm e}^{(i)} \otimes \tilde {\bm e}^{(j)}\,.$$ This means that when the coordinates of the projectors are expressed in the tetrad basis associated with the corresponding coordinates system, we obtain $$\label{SijisSij} S_{(i)(j)}(q,n^{(k)})=\delta_{ij}-n_{(i)}n_{(j)} = \tilde S_{\widetilde{(i)}\widetilde{(j)}}\circ \tilde c{(q,n^{(k)})}\,.$$ Thus in any gauge, the expression of the related screen projector in the tetrad basis is the same by construction, and $S_{(i)(j)}$ depends actually only on $n^{(k)}$. However it must remain clear that these two tensors are geometrically different since they are associated with different coordinates systems and indeed their relation is given at first order by . The distribution tensor is also not geometrically invariant since for every observer used to define the screen projector, we must consider a different distribution tensor. However all the possible distribution matrices are related through projections and we find that the distribution tensors defined by the tetrad $\tilde{\bm e}_{(0)}$ and ${\bm e}_{(0)}$ are related at the same point of the tangent bundle by [@Tsagas:2007yx] $$f^{\tilde{\bm e}_{(0)}}_{\mu\nu}\circ \tilde c{(\tilde {\bm x},q^{\widetilde{(\imath)}})} = \tilde S_\mu^\alpha \circ \tilde c{(\tilde {\bm x},q^{\widetilde{(\imath)}})} \tilde S_\nu^\beta \circ \tilde c{(\tilde {\bm x},q^{\widetilde{(\imath)}})} f^{{\bm e}_{(0)}}_{\alpha \beta}({\bm x},q^{(\imath)})\,.$$ This means that the only requirement is to project the distribution function so that it is projected with respect to the new observer and the new direction. Combining this transformation rule with  we obtain at first order the transformation rule as $$f^{\tilde{\bm e}_{(0)}}_{\mu\nu}\circ \tilde c{(\tilde {\bm x},q^{\widetilde{(\imath)}})} = f^{{\bm e}_{(0)}}_{\mu \nu}({\bm x},q^{(\imath)}) + 2 \left(e^{(0)}_{(\mu}+n_{(\mu}\right) f^{{\bm e}_{(0)}}_{\nu)\alpha}({\bm x},q^{(\imath)})V^\alpha\,.$$ If we project this expression onto the tetrad components, and noting $\tilde f_{(i)(j)}\equiv f^{\tilde{\bm e}_{(0)}}_{(i)(j)}$ and $f_{(i)(j)}\equiv f^{{\bm e}_{(0)}}_{(i)(j)}$, we obtain $$\label{Rulefijstrange} \tilde f_{\widetilde{(i)}\widetilde{(j)}}\circ \tilde c{(\tilde {\bm x},q^{\widetilde{(\imath)}})} = f_{(i)(j)}({\bm x},q^{(\imath)}) - f_{(i)(k)}({\bm x},q^{(\imath)})L_{\,\,\,,j]}^{[k} -f_{(k)(j)}({\bm x},q^{(\imath)})L_{\,\,\,,i]}^{[k} - 2 n_{((i)} f_{(j))(k)}({\bm x},q^{(\imath)}){{\partial}}^k T\,,$$ find the transformation rule under a gauge transformation, we need to expand the left hand side around $({\bm x},q^{(\imath)})$. At first order we get $$\begin{aligned} \tilde f_{\widetilde{(i)}\widetilde{(j)}}\circ \tilde c{(\tilde {\bm x},q^{\widetilde{(\imath)}})} &\simeq\left(1+\xi^\mu \frac{{{\partial}}}{{{\partial}}x^\mu} +\delta q^{(i)}\frac{{{\partial}}}{{{\partial}}q^{(i)}} \right) \tilde f_{\widetilde{(i)}\widetilde{(j)}}\circ \tilde c{({\bm x},q^{{(\imath)}})}+\cdots \nonumber\\ &\simeq \tilde f_{\widetilde{(i)}\widetilde{(j)}}\circ \tilde c{({\bm x},q^{{(\imath)}})} + \left(\xi^\mu \frac{{{\partial}}}{{{\partial}}x^\mu}+\delta q^{(i)}\frac{{{\partial}}}{{{\partial}}q^{(i)}} \right) f_{{(i)}{(j)}}+\cdots \,.\end{aligned}$$ Using the expansion (\[Expandderpi\]) we then obtain the gauge transformation rule for the tensor valued distribution function in tetrad coordinates. Noting $\widetilde{f_{(i)(j)}} \equiv \tilde f_{\widetilde{(i)}\widetilde{(j)}}\circ \tilde c$ for simplicity, this reads $$\label{Gaugeruletensor} \widetilde{f_{{(i)}{(j)}}} = f_{(i)(j)}-\left(\xi^\mu \frac{{{\partial}}}{{{\partial}}x^\mu}+\delta \ln q {{\frac{\partial}{\partial \ln q}}}+\delta n^{(i)}D_{(i)} \right)f_{(i)(j)}-f_{(i)(k)} L_{\,\,\,,l]}^{[k}S^{(l)}_{(j)} -f_{(k)(j)} L_{\,\,\,,l]}^{[k} S^{(l)}_{(i)}\,,$$ where it is implied that all quantities are evaluated either at ${\bm x}$ or at $({\bm x},q,n^{(i)})$. For completeness we report the explicit form of the gauge transformation for ${{\cal P}}_{(i) (j)}$ which is obtained from the above transformation rule and the spectral decomposition (\[defyP\]) $$\begin{aligned} \label{GT:calP} \tilde{{{\cal P}}}_{(i) (j)} &= {{\cal P}}_{(i) (j)} - L^{[k}{}_{, l]} \Bigl( S^{(l)}{}_{(i)} {{\cal P}}_{(k) (j)} + S^{(l)}{}_{(j)} {{\cal P}}_{(k) (i)} \Bigr) - \xi^\mu {{\partial}}_\mu {{\cal P}}_{(i) (j)} - \delta n^{(k)} D_{(k)} {{\cal P}}_{(i) (j)} \,. \end{aligned}$$ It is also found, as expected, that the spectral distortion $Y_{(i)(j)}$ part is gauge invariant since it vanishes on the background and at first order. Gauge transformation for Liouville and Collision terms {#AppGTLC} ------------------------------------------------------ We deduce from the transformation rule (\[GT:calP\]) and the spectral decomposition (\[spdec:calP\_lhs\]) and (\[spdec:calP\_rhs\]) that the spectral distortion part, ${{\cal L}}^Y_{(i)(j)} $ and ${{\cal C}}^Y_{(i)(j)}$, must be gauge invariant. Concerning the temperature part, they should transform as (noting $\widetilde{{{\cal L}}^P_{(i)(j)}} \equiv {{\cal L}}^P_{\tilde{(i)}\tilde{(j)}} \circ \tilde c$ and $\widetilde{{{\cal C}}^P_{(i)(j)}} \equiv {{\cal C}}^P_{\tilde{(i)}\tilde{(j)}} \circ \tilde c$ ) $$\begin{aligned} \widetilde{{{\cal L}}^P_{(i)(j)}} &= {{\cal L}}^P_{(i)(j)} - L^{[k}{}_{, l]} \Bigl( S^{(l)}{}_{(i)} {{\cal L}}^P_{(k) (j)} + S^{(l)}{}_{(j)} {{\cal L}}^P_{(k) (i)} \Bigr) - \xi^\mu {{\partial}}_\mu {{\cal L}}^P_{(i)(j)} - \delta n^{(k)} D_{(k)} {{\cal L}}^P_{(i) (j)} \,, \\ \widetilde{{{\cal C}}^P_{(i)(j)}} &= {{\cal C}}^P_{(i)(j)} - L^{[k}{}_{, l]} \Bigl( S^{(l)}{}_{(i)} {{\cal C}}^P_{(k) (j)} + S^{(l)}{}_{(j)} {{\cal C}}^P_{(k) (i)} \Bigr) - \xi^\mu {{\partial}}_\mu {{\cal C}}^P_{(i)(j)} - \delta n^{(k)} D_{(k)} {{\cal C}}^P_{(i) (j)} \,. \end{aligned}$$ Using the transformation rules derived in this paper, we checked that this is indeed the case when using the detailed form of the Liouville and collision operators. Extraction of temperature and spectral distortion {#AppExtraction} ================================================= The functions $y$ and $\Theta$ can be extracted thanks to the integrals of the type $${{\cal M}}_n[f]\equiv \frac{\int f q^{2+n} {{\rm d}}q}{(3+n) \int \bar I(q) q^{2+n} {{\rm d}}q} \,,$$ just by applying them order by order to $I(q)$, using that ${{\cal M}}_0[{{\cal D}}_q^2 \bar I]=0$. We then obtain $$\begin{aligned} \Theta^{(1)} &= {{\cal M}}_1 [I^{(1)}] = {{\cal M}}_0[I^{(1)}] \,, \label{ExtractTheta1} \\ \frac{1}{2}\Theta^{(2)} &= \frac{1}{2} {{\cal M}}_0[I^{(2)}]-\Theta^{(1)2} \,, \\ \frac{1}{2}y^{(2)} &= \frac{1}{2} \left( {{\cal M}}_1[I^{(2)}] - {{\cal M}}_0 [I^{(2)}] \right) - \frac{1}{2}\Theta^{(1)}{}^2 \,.\end{aligned}$$ Similarly to what can be done for the intensity part, the spectral components of polarisation can be extracted thanks to $$\begin{aligned} {{\cal P}}^{(1)}_{\mu\nu} &= {{\cal M}}_1 [{\bf P}_{\mu\nu}^{(1)}] = {{\cal M}}_0 [P_{\mu\nu}^{(1)}] \,, \\ \frac{1}{2} {{\cal P}}^{(2)}_{\mu\nu} &= \frac{1}{2} {{\cal M}}_0 [P_{\mu\nu}^{(2)}] - 3 \Theta^{(1)} {{\cal P}}^{(1)}_{\mu\nu} \,,\\ \frac{1}{2}Y^{(2)}_{\mu\nu} &= \frac{1}{2} \Bigl( {{\cal M}}_1[P_{\mu\nu}^{(2)}]-{{\cal M}}_0[P_{\mu\nu}^{(2)}] \Bigr) - \Theta {{\cal P}}^{(1)}_{\mu\nu} \,.\end{aligned}$$ [10]{} WMAP, E. Komatsu [*et al.*]{}, Astrophys. J. Suppl. 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N. Bartolo, S. Matarrese, and A. Riotto, JCAP [**0606**]{}, 024 (2006), arXiv:astro-ph/0604416. N. Bartolo, S. Matarrese, and A. Riotto, JCAP [**0701**]{}, 019 (2007), arXiv:astro-ph/0610110. C. Pitrou, Class. Quant. Grav. [**26**]{}, 065006 (2009), arXiv:0809.3036. C. Pitrou, Gen.Rel.Grav. [**41**]{}, 2587 (2009), arXiv:0809.3245. C. Pitrou, J.-P. Uzan, and F. Bernardeau, JCAP [**1007**]{}, 003 (2010), arXiv:1003.0481. M. Beneke and C. Fidler, Phys. Rev. [**D82**]{}, 063509 (2010), arXiv:1003.1834. R. Durrer, Fund.Cosmic Phys. [**15**]{}, 209 (1994), arXiv:astro-ph/9311041. C. Pitrou, Class. Quant. Grav. [**24**]{}, 6127 (2007), arXiv:0706.4383. Z. Huang and F. Vernizzi, (2012), arXiv:1212.3573. S.-C. Su, E. A. Lim, and E. Shellard, (2012), arXiv:1212.6968. G. W. Pettinari, C. Fidler, R. Crittenden, K. Koyama, and D. Wands, (2013), arXiv:1302.0832. P. Creminelli, C. Pitrou, and F. Vernizzi, JCAP [**1111**]{}, 025 (2011), arXiv:1109.1822. Planck Collaboration, P. Ade [*et al.*]{}, (2013), arXiv:1303.5081. A. Stebbins, (2007), arXiv:astro-ph/0703541. C. Pitrou, F. Bernardeau, and J.-P. Uzan, JCAP [**1007**]{}, 019 (2010), arXiv:0912.3655. R. L. Arnowitt, S. Deser, and C. W. Misner, (1962), arXiv:gr-qc/0405109. C. G. Tsagas, A. Challinor, and R. Maartens, Phys. Rept. [**465**]{}, 61 (2008), arXiv:0705.4397. S. Dodelson and J. M. Jubas, Astrophys. J. [**439**]{}, 503 (1995), astro-ph/9308019. M. Bruni, S. Matarrese, S. Mollerach, and S. Sonego, Class. Quant. Grav. [**14**]{}, 2585 (1997), arXiv:gr-qc/9609040. D. Hanson, K. M. Smith, A. Challinor, and M. Liguori, Phys.Rev. [**D80**]{}, 083004 (2009), arXiv:0905.4732. A. Lewis, A. Challinor, and D. Hanson, JCAP [**1103**]{}, 018 (2011), arXiv:1101.2234. E. Gourgoulhon, (2007), arXiv:gr-qc/0703035. [^1]: We assume for the simplicity of the argument that one system of coordinates is enough to cover the entire manifold. [^2]: Again here for simplicity, we assume that such coordinates system covers the whole manifold. [^3]: Under our conventions, $\tilde q \equiv a p^{\widetilde{(0)}}$.

[In vivo bioequivalence study of Sulpirid (GYKI-Alkaloida) and Dogmatil fort (Delagrange) 200 mg sulpiride tablets in healthy volunteers]. A single-dose, "crossover" bioequivalence study was conducted in healthy volunteers by comparing sulpiride serum levels after oral administration of the Test Product Sulpiride (200 mg) (GYKI-Alkaloida) in fasting subjects with those produced after oral administration of a marketed reference product (200 mg) (Delagrange Co., France). Statistical comparisons of Cmax, Tmax and AUC0-infinity have been performed utilizing ANOVA with subject, group, subject within group, period and product as sources of variance. No significant differences between the Test Drug and the Reference Drug considering the pharmacokinetic parameters Cmax, Tmax and AUC0-infinity were found. The 95% confidence intervals were as follows: AUC0-infinity: -20.46% and 31.19%, Cmax: -28.05% and 26.65% and Tmax: -43.53% and 20.67%. In the study for the analysis of Sulpiride a specific HPLC procedure with uv detection (lambda = 228 nm) and an internal standard were applied according to P. Nicolas et al. with modification. Sulpiride levels in serum reached a maximum at 4.4 hr +/- 1.5 (S.D.) following administration of Sulpiride tablet and at 5.0 hr +/- 0.8 (S.D.) after Dogmatil fort tablet. The maximal serum concentrations were 506.1 ng/ml +/- 87.2 (S.D.) and 509.1 ng/ml +/- 101.9 (S.D.) for Sulpiride and Dogmatil fort, respectively. The half-life of Sulpiride in serum was 9.9 hr +/- 1.3 (S.D.) following dosing with Dogmatil fort tablet and 12.2 hr +/- 3.0 (S.D.) following dosing with Sulpiride tablet.

Thermally and electrically switchable gratings based on polymer-ball-type polymer-dispersed liquid-crystal films. We focus on the fabrication and study of controllable holographic gratings based on azo-dye-doped and undoped polymer-ball-type polymer-dispersed liquid-crystal films. Experimental results indicate that the next step of photopolymerization of the sample with the illumination of Ar+ laser beams after UV curing causes a latent density grating to be recorded. This grating is formed by a selective secondary photopolymerization. Heating and applying a voltage change the structure of the liquid crystal and induce the appearance of the latent grating. Diffraction efficiencies versus temperature, voltage, and state of polarization are studied for both dye-doped and undoped cells and are found to be quite different. This discrepancy is attributable to the reorientation effect of liquid crystals through their interaction with the photo-induced adsorption of the doped dyes on the surface of polymer balls in the dye-doped cell.

[TRAM flap in conjunction with latissimus dorsi muscle flap for breast reconstruction]. To investigate a method to reconstruct the breast and repair the chest wall defects at the same time. The operation procedure combined the transverse rectus abdominis myocutaneous (TRAM) flap with the latissimus dorsi muscle(LDM) flap for breast reconstruction and repair of chest wall defect. Two patients underwent delayed breast reconstruction using this technique. 8 flaps in the four patients survived completely. The aesthetic results were very good. This method can be used to reconstruct breast and repair the defect of chest wall at the same time, avoiding the disadvantage in the flap transfer of TRAM or LDM.

Measuring 18 mm at its widest point and 22 mm long this heart disc comes suspended on an 18 inch sterling silver contemporary chain and features our signature Sheenashona charm at the fastening. The sterling silver heart comes precision laser engraved to the front with up to 3 characters/letters. This pendant is designed to sit perfectly on your décolleté and is a key essential in any good jewellery collection. Designed to be worn any time of the day this pendant makes a wonderful personalised gift for treasured friends and family not to mention yourself. This item comes luxuriously gift wrapped along with a complementary gift card, which you can personalise with a message during the checkout process Please complete the engraving message box with up to 3 letters/initials before adding this item to your bag. Once you are ready to check out you can also check your engraving choice in your shopping bag where it may also be amended if required. As a precision engraved jewellery item please allow up to 3 working days for dispatch. If you have any questions please feel free to contact our personal shopper by email at personalshopper@sheenashonajewellery.com or by telephone week days between 9am-5pm GMT on (UK) 0845 034 2108.

dnl mpn_rshift2 dnl Copyright 2009 Jason Moxham dnl This file is part of the MPIR Library. dnl The MPIR Library is free software; you can redistribute it and/or modify dnl it under the terms of the GNU Lesser General Public License as published dnl by the Free Software Foundation; either version 2.1 of the License, or (at dnl your option) any later version. dnl The MPIR Library is distributed in the hope that it will be useful, but dnl WITHOUT ANY WARRANTY; without even the implied warranty of MERCHANTABILITY dnl or FITNESS FOR A PARTICULAR PURPOSE. See the GNU Lesser General Public dnl License for more details. dnl You should have received a copy of the GNU Lesser General Public License dnl along with the MPIR Library; see the file COPYING.LIB. If not, write dnl to the Free Software Foundation, Inc., 51 Franklin Street, Fifth Floor, dnl Boston, MA 02110-1301, USA. include(`../config.m4') C ret mpn_rshift2(mp_ptr,mp_ptr,mp_size_t) C rax rdi, rsi, rdx ASM_START() PROLOGUE(mpn_rshift2) mov %rdx,%rcx lea 24(%rsi),%rsi lea 24(%rdi),%rdi xor %eax,%eax xor %edx,%edx sub $4,%rcx jc skiplp ALIGN(16) lp: mov (%rsi,%rcx,8),%r8 mov -8(%rsi,%rcx,8),%r9 mov -16(%rsi,%rcx,8),%r10 mov -24(%rsi,%rcx,8),%r11 add %rax,%rax rcr $1,%r8 rcr $1,%r9 rcr $1,%r10 rcr $1,%r11 sbb %rax,%rax add %rdx,%rdx rcr $1,%r8 rcr $1,%r9 rcr $1,%r10 rcr $1,%r11 mov %r11,-24(%rdi,%rcx,8) sbb %rdx,%rdx mov %r8,(%rdi,%rcx,8) sub $4,%rcx mov %r9,24(%rdi,%rcx,8) mov %r10,16(%rdi,%rcx,8) jnc lp skiplp: cmp $-2,%rcx ja case3 je case2 jp case1 case0: lea (%rax,%rdx,2),%rax neg %rax shl $62,%rax ret ALIGN(16) case3: mov (%rsi,%rcx,8),%r8 mov -8(%rsi,%rcx,8),%r9 mov -16(%rsi,%rcx,8),%r10 add %rax,%rax rcr $1,%r8 rcr $1,%r9 rcr $1,%r10 sbb %rax,%rax add %rdx,%rdx rcr $1,%r8 rcr $1,%r9 rcr $1,%r10 sbb %rdx,%rdx mov %r8,(%rdi,%rcx,8) mov %r9,-8(%rdi,%rcx,8) mov %r10,-16(%rdi,%rcx,8) lea (%rax,%rdx,2),%rax neg %rax shl $62,%rax ret ALIGN(16) case2: mov (%rsi,%rcx,8),%r8 mov -8(%rsi,%rcx,8),%r9 add %rax,%rax rcr $1,%r8 rcr $1,%r9 sbb %rax,%rax add %rdx,%rdx rcr $1,%r8 rcr $1,%r9 sbb %rdx,%rdx mov %r8,(%rdi,%rcx,8) mov %r9,-8(%rdi,%rcx,8) lea (%rax,%rdx,2),%rax neg %rax shl $62,%rax ret ALIGN(16) case1: mov (%rsi,%rcx,8),%r8 add %rax,%rax rcr $1,%r8 sbb %rax,%rax add %rdx,%rdx rcr $1,%r8 sbb %rdx,%rdx mov %r8,(%rdi,%rcx,8) lea (%rax,%rdx,2),%rax neg %rax shl $62,%rax ret EPILOGUE()

Antje Huber Antje Huber (23 May 1924 – 30 September 2015) was a German politician who was the Federal Minister for Youth, Family and Health from 1976 to 1982. She served as a member of the Bundestag for the SPD between 1969 and 1987. References Category:1924 births Category:2015 deaths Category:People from Szczecin Category:People from the Province of Pomerania Category:Social Democratic Party of Germany politicians Category:20th-century German women politicians Category:Knights Commander of the Order of Merit of the Federal Republic of Germany Category:Female members of the Bundestag

9 Year Old Girl Becomes Microsoft Certified "Professional" - ojbyrne http://gizmodo.com/5116747/9-year-old-girl-becomes-the-youngest-microsoft-certified-professional ====== Eliezer Jeeblus, what's wrong with you people? If she'd gotten a high score on the SAT, would you be telling her how boring and useless the SAT is? High scores on adult tests at a young age, _almost no matter the test_ , are something to congratulate her for. But instead you're dumping on her because of "Microsoft" in the title? If you're going to dump on someone, dump on Microsoft! And even that is a backhanded insult to her. There are just some very bright 9-year-olds out there. ~~~ randomwalker I'm from the same part of India that this girl is. This kind of crap is very common there. The kids who do this are not necessarily intelligent, they usually just crammed for years. Nor do they have a say in the matter. Everything is orchestrated by the parents. It's like a dog show -- the parents compete using their kids. Needless to say, the kid's childhood and normal development are completely derailed (I've seen it in person). The parents aren't evil; it's just a facet of the hyper-competitive society. The best way to describe it is that it's India's version of the contest in Little Miss Sunshine. The negative comments here don't come close to capturing how messed up this is. ~~~ gruseom I've seen this kind of thing a lot - it's not limited to India - and completely agree with you that it's almost always the parent(s) pushing the kid, and very sad. Every now and then you see some 11-year-old or 13-year-old finishing an undergraduate degree, paraded in front of foolish journalists who dutifully put out the next "genius" story. Same thing with most musical prodigies - the 9-year old performing with the local philharmonic or what have you. Kids don't care about super-achievement of credentials. Mostly they just want to know their parents love them and to be like other kids. It's parents who perversely put their children through this, to fill their own ego needs. Your dog show analogy is unfortunately apt. ~~~ DaniFong Actually, kids can be hyper-focused on credentials. That's why they're so susceptible. The very same behavioral triggers can create obsessions in videogames, especially RPG's. The nice thing about 'real-world' credentials is that they have a path leading out of that mess, whereas videogames often don't. ~~~ gruseom I'm unconvinced. Sure, children can internalize anything very quickly - the question is why this rather than that? I'm sure that little girl was very focused on achieving her Microsoft certification. But I'll bet you the task itself was originally handed to her by a parent, and that her motivation had everything to do with pleasing that parent. As for "a path leading out of that mess", the only path I know is growing as a person. What's sad about these manufactured prodigies is that they end up having to do a lot of that the hard way, if they do it at all. ~~~ DaniFong I think you underestimate the agency that a nine year old can have, and the influence of the extended family, friends, and role models. It's probable that the specific task was handed to her, yes. And it's often true that parents push their children too far. But I think it's also possible she decided to do it on her own after reading or hearing some inspirational story. I am _projecting_ my own experience as a child onto her, but when I was her age I heard about Microsoft credentials. I considered trying for them, but my mother's friend told me they were a distraction, and gave me a copy of Turbo C++ instead. I can't remember ever thinking about pleasing my parents. It never entered my conscious thought. I just knew I wanted to learn to program computers, and I couldn't, in that time, be interested in computers as a kid and envision Microsoft's credentials with the disdain that I do now. I suspect it's the same now, in India. It's true that the only way out of credentialism is growing oneself as a person, and finding a way to develop a self-referent identity. The _advantage_ is that one grows while striving, and one can often find oneself in much better place, with better social support, and deeper values. It's a lot more difficult to see this in the construct of an RPG, or in most public high- schools. ~~~ gruseom Yes, I acknowledge what you're talking about is real (<http://news.ycombinator.com/item?id=400286>), and the two phenomena are quite different, though they may be difficult to distinguish from the outside. ------ biohacker42 During the .COM 1.0 recession, back in the stone age, one of my fellow fresh faced and unemployed CS grads was considering getting MCTS certified in order to improve his job prospects. I used the then popular story about a 12 year old Pakistani girl who got the same certificate, to dissuade my friend. And so I encourage all of today's fresh faced and unemployed hackers to think of that 9 year old when the current recession is wearing them down. Do you really think that MCTS will help? ~~~ nostrademons I thought about getting a MCP when I was 15. Then everyone I knew in the computer field told me it was a waste of time. So I learned Perl instead, which honestly helped my career a whole lot more. ~~~ sigh400 How old are you now? When I was 14 there were no certs -- I got a job in a local PC shop as a stock boy. I am convinced I worked for Korean gangsters now; However back then I thought it was a kick ass job (Since nobody I knew was working.) I still own one fried 8088 mobo (black to black wha?) and the three surfboards I managed to buy whilst working. In reality it was one of the worst jobs I have ever had, as I had to work in an attic sorting PC parts and fetching orders in 100+ attic heat with a 4ft ceiling (I kid not) and had to get to work Sundays @ 5am to unload "orders" from Mexico from the meanest people I have ever met. I learned more about life in that year then I have in the last 20. ~~~ nostrademons 27\. This was about 1997. I was in kindergarten when people were still using 8088s. ------ mattmcknight Shouldn't the practical test consist of misconfigured ActiveDirectory permissions to fix,spyware uninstallation, and a registry to clean? The general tip to choose whichever option requires buying more Microsoft licenses worked when I took the test 10 years ago. ------ simpleenigma I've always thought that these certification programs were more of a game of trivial pursuit then a good gage of abilities. ------ mixmax maybe this says more about the certification than the girl. ~~~ socratees For any Microsoft certification, there are dumps everywhere on the internet. I'd rather be happy if the girl became a SJCP. ~~~ RavingGoat Meh, dumps exist for SJCP too... just not the whole test. Years ago when I took it for an employer about 1/3 of the questions were in dumps at the time. A co-worker said almost all his questions were from dumps when he took the SJCP exam. Sun does a better job than Microsoft but not much better. ------ natch Scarred for life. Someone should call child protective services. ~~~ DaniFong You know this how? Being threatened with being taken away from her family would be any better? ~~~ Leon I think it was a joke... ~~~ DaniFong _nods_ Point taken. Some people actually do stuff like this, though, and I don't think jokes like this should be propagated (or at least unopposed) on HN. ~~~ natch Noted. I do try to hold back my silly humor somewhat on HN. Thanks for the nudge back on course. ------ seshagiric With all the exam dumps available it is no longer difficult to clear any certification exam. However still, if this 9 year old sits in front of a PC, I will be sure she knows what she is doing. That in itself is an achievement for her age. ------ liamQ this proves that MCTS certifications are bullshit (btw - I have an exam scheduled for January) ~~~ wynand She might be unusually gifted. The article states that she has a fairly excellent memory. And it is conceivable that she has a fairly high IQ. We wouldn't have scoffed as much if she mastered a branch of Mathematics instead. ~~~ mechanical_fish We also wouldn't have scoffed as much if she were merely three years older, and a boy, and working in PHP and Javascript instead of Microsoft technologies: <http://news.ycombinator.com/item?id=156863> Can't we just congratulate the kid and move on? I mean, vital as it is to teach her that credentials are bullshit, can't we let her turn _ten_ before breaking the bad news? She's already much closer to figuring it out for herself than I was at that age. ~~~ blasdel He did something creative, she just passed a helpdesk test. ~~~ mechanical_fish Perhaps when she is _thirty-three percent older_ she'll be more creative, too! Or, instead of showing off her chops, perhaps she'll prefer to quietly rake in the cash as a Windows programmer. It's not like she'd be the only one to make that choice. ~~~ tome So your first argument is that he's "merely three years older", and then your response to a rebuttal is that he's as much as "thirty-three percent older". ~~~ mechanical_fish The sad thing is, I actually noticed this inconsistency. But I decided to leave it in just to see who noticed. ;) But if you want to be more serious about it: Sure, I concede the rebuttal. Gaskin's a very creative programmer. He also works on stuff that I actually care about. I agree that passing a Microsoft certification is not in the same league as the _least_ thing that the guy has done. And I agree that cramming for Microsoft tests is not an especially great activity to encourage a nine- year-old to do. None of which alters my initial reaction: Congratulate the girl and move on. Just because she's no Gaskin doesn't mean she deserves to be the scapegoat for things that are not her fault (the purported meaninglessness of her prized credential; the bureaucratic, credentialist nature of the Microsoft IT consulting ecosystem; the existence of cram schools and dominating parents; the insecurity of Western IT folks about the rise of the Indian software industry; and the fact that she is _nine years old_ and can't necessarily be expected to understand any of this). She's a living, breathing kid who may be reading this thread _right now_ \-- a kid with the potential to become creative and talented, who may _already be_ creative and talented when she's not being paraded in front of news cameras. She's not a hypothetical pawn in our intellectual game. ------ known And 11-Year-Old Becomes Network Admin for Alabama School <http://news.slashdot.org/article.pl?sid=08/03/30/1443202> ------ kirubakaran I always wondered why MS chose a title that abbreviates to MCP, which means Male Chauvinist Pig in the non-tech world. I once created an infamous 'Production Metrics Spreadsheet' which the female members of my team were justifiably referring to as PMS. Operation Iraqi Liberation comes to mind. ------ grouchyOldGuy Gee, it must be extraordinarily difficult to become a Mouse Certified Professional. ------ gaius What's remarkable is that grown adults become MCPs. ~~~ jeroen 2 out of 4 previous employers (I'm a freelancer now) gave me a raise whenever I passed an MCP exam. That's enough motivation for me, since it's not very hard to pass MCP exams (at least MSCD related ones) when you have decent practical experience. ~~~ ciscoriordan Do you think the certifications have an impact on your freelancer rates? ~~~ rbanffy Well... I can tell I wouldn't pay more for one. Even if I used something Microsoft ;-) ------ trezor I think I smell "bias" against Microsoft in the headline.

EEG beta 1 oscillation and sucrose sensitization in fibromyalgia with chemical intolerance. Patients with fibromyalgia (FM) have diffuse musculoskeletal pain; half report concomitant intolerance for low levels of environmental chemicals (CI). Previous investigators have hypothesized that the chronic pain and chemical intolerance reflect sensitization of different central nervous system limbic and/or mesolimbic reward pathways. We evaluated electroencephalographic (EEG) beta activity and blood glucose responses of FM patients with and without CI and normals during three repeated sucrose ingestion sessions and during a final, water-only session (testing for conditioning). The FM with CI exhibited oscillation (reversal in direction of change from session to session) at rest and then sensitization (progressive amplification) of EEG beta 1 over time across the 3 sucrose sessions versus controls. FM with CI showed sensitization of blood glucose over the 3 sucrose sessions, which, like the EEG findings, reverted toward baseline in the final water-only session. The data suggest that the subset of FM patients with CI have increased susceptibility to oscillation and physiological sensitization without conditioning, perhaps contributing to fluctuations in their chronic course.

CLAYTON, N.J. (CBS) — Gloucester County prosecutor Sean Dalton announced the arrest of two teenage brothers Tuesday in connection with the death of 12-year-old Autumn Pasquale. Dalton said Autumn was lured to the home of the 15 and 17-year-old brothers where the crime was allegedly committed for the purpose of obtaining parts from her BMX bike. Dalton said the juveniles’ mom contacted police about postings on her son’s Facebook page and that call helped police lead them to the suspects. The mother did not speak to reporters. Friends say she is devastated. “She says that she is really hurt for the family. She said her heart goes out to the family more than her boys right now,” said one woman, who did not wish to be identified. “A preliminary cause of death is blunt force trauma consistent with strangulation,” said Dalton, who also said there are no signs of sexual assault. The suspects have been charged with first degree murder, conspiracy to commit murder, tampering with evidence, theft, disposing of a body and the 15-year-old is also charged with one count of luring. Dalton said they are considering waiving the juveniles to adult court. “Today we mourn the loss of a young girl … whose life was cut short before it really began. Our thoughts and prayers go out to her parents, her family. It is my hope that the arrests today provide a measure of closure, that the individuals responsible for their daughter’s death will be held responsible,” said Dalton. Pasquale’s body was found late Monday evening in a recycling bin on a property near the corner of Vine Street and Clayton Avenue in Clayton, New Jersey. The Odyssey BMX bicycle she was last seen riding, was located hours later at the suspect’s home near where her body was discovered. Autumn was last seen at 12:30 p.m. Saturday, reported missing later that night after failing to return home by her 8 p.m. curfew, and had been the subject of an in-depth search in and around the quiet town of Clayton. WEB EXTRA: Clayton Police Chief Dennis Marchei Speaks On Autumn Pasquale Case Hundreds of volunteers searched for Autumn for over two days, but their worst fears had been realized. “Our hearts go out to the family and to all the residents of Clayton who stood together in support of this little girl,” Dalton said. The family of Autumn Pasquale, who would have turned 13 a week from Monday, thanked the community for the thousands of man-hours that went into the search for their beloved 12-year-old, saying they wish the result had been different, but they’re thankful they have closure. Grief counselors will be on hand at Autumn’s school throughout the week to assist grieving classmates and staff, and a prayer service and vigil was held Tuesday night at the First Baptist Church on Delsea Drive. Officials stressed Gloucester County and the borough of Clayton are safe communities and urged parents to do what they’ve always done. “You’re going to hold your children close and take the necessary steps to protect your children like you’ve always had,” said Dalton.

Neo Solar Power Corp. operates in the Semiconductors and related devices sector. In addition to historical fundamental analyses, the complete report available to purchase compares Neo Solar Power Corp. with three other companies in this sector in Taiwan: San Chih Semiconductor Company (2016 sales of 15.64 billion Taiwanese Dollars [US$535.43 million] of which 98% was Solar Energy Wafer), Chipbond Technology Corp (17.26 billion Taiwanese Dollars [US$590.85 million] of which 100% was Manufacture of Semiconductors), and Orient Semiconductor Electronics Limited (15.79 billion Taiwanese Dollars [US$540.52 million] of which 67% was IC Semiconductor). Sales Analysis. Neo Solar Power Corp. reported sales of 16.54 billion Taiwanese Dollars (US$566.23 million) for the year ending December of 2016. This represents a sharp decrease of 25.6% versus 2015, when the company's sales were 22.21 billion Taiwanese Dollars. Contributing to the drop in overall sales was the 54.0% decline in Others, from 169.76 million Taiwanese Dollars to 78.06 million Taiwanese Dollars. There were also decreases in sales in Solar Cells (down 36.6% to 10.42 billion Taiwanese Dollars) and Power Plant (down 40.9% to 621.37 million Taiwanese Dollars) . However, these declines were partially offset by the increase in sales of Module Department (up 19.0% to 5.42 billion Taiwanese Dollars) .

Pilot study of homeostatic alterations of mineral elements in serum of patients with age-related macular degeneration via elemental and isotopic analysis using ICP-mass spectrometry. Age-related macular degeneration (AMD), the main cause of irreversible blindness in people over 60 years of age, is an eye disease that evolves with loss of central vision. Although AMD manifests itself in the eye, blood is continuously flowing through the macular region, such that potential alterations in this region could be reflected in the composition of whole blood or plasma/serum. Therefore, the potential clinical relevance of analysis of serum samples was assessed because of the low degree of invasiveness of blood sampling. 40 initial samples (20 from controls and 20 from patients with the dry form of AMD) have been analysed in this work to investigate the possible occurrence of homeostatic alterations of essential mineral elements caused by the disease. Both major (Na, Mg, P and K) and trace (Fe, Cu and Zn) essential mineral elements were determined in blood serum using single-collector ICP-mass spectrometry. Also, the isotopic composition of Cu (an element proposed to be directly involved in the onset of AMD) was determined using multi-collector ICP-mass spectrometry. Unexpected light Cu isotopic compositions in three individuals assumed as controls, resulted in a re-evaluation of their clinical information and a later exclusion due to pathologies initially not accounted for. In this pilot study, a significant alteration in the δ65Cu value has been found between the two final cohorts (AMD patients: n = 20; controls n = 17), with lower δ65Cu values (i.e. an enrichment in the light 63Cu isotope) in the case of AMD. Also, higher serum concentrations of the elements P and Zn were established in AMD at a systemic level.

Reproducibility of quantitative 99Tcm-MAG 3 measurements in rats. Repetitive quantitative renal extraction studies of 99Tcm-MAG 3, performed in nine rats, demonstrated excellent reproducibility of successive measurements. These results are better than with 99Tcm-DTPA, due to the higher renal extraction of the 99Tcm-MAG 3. The % of renal uptake 10 min after the injection was not influenced by the elapsed time between the end of the 99Tcm-MAG 3 preparation and its i.v. administration.

I Bet I Bet may refer to: "I Bet" (Ciara song), 2015 "I Bet" (TLC song), 2005

Evaluating & Choosing Private Intelligence Providers How does management identify and monitor these threats in different locations around the world? Many companies subscribe to one or more of the private security intelligence providers that are available. While some of these firms use the term intelligence to describe their products and services, others use terms like risk reporting, assessment & analysis and information services. For purposes of clarity and consistency the term intelligence or security intelligence will be used throughout this article. These firms either solely provide security intelligence or offer it as one of a number of other services such as security consulting, evacuation support, executive protection services, traveler tracking, etc. The quality, depth, level of coverage and other factors vary widely in these intelligence products. Some providers may offer a greater level of detail, more flexibility for customization, better qualified analysts, greater brevity or may be stronger in one geographical area than another. For this reason – and because it is important to get a range of perspectives – it is strongly recommended that the company’s security department utilize several different providers with strengths in different areas. The following are some examples of the types of providers that might be encountered and their relative strengths and weaknesses: Provider A: Very good general information and alerts presented in a brief format via email that is easy to read. Most information is taken directly from open source publications and websites with little vetting, perspective or analysis. Foreign media sources are checked as well as US media. Cost is low. Provider B: Detailed website with security briefs for multiple cities and countries as well as detail email briefs that offer analysis and perspective. Analysts come from a variety of backgrounds and generally have lived or traveled in their respective regions. Good quality information but little room for customization. Cost is high. Provider C: Detailed website with security briefs for multiple cities and countries (though not as extensive as Provider B), email briefs and alerts that are sometimes taken directly from open sources with little analysis. Analysts are mainly recent college graduates often with limited or no practical experience living or working in their region. There is a high degree of customization in terms of reports, specialized monitoring and consultations. Cost is medium. Provider D: Provides totally customized intelligence reports and risk assessments. Most analysts have a military intelligence or government intelligence agency background with a sprinkling of academics. Most analysts have extensive experience in their region, a network of local contacts and often language skills. Cost is high. Looking at these four examples of different types of private intelligence providers it is easy to see how an organization would benefit by using several of these firms rather than just one. When evaluating and choosing providers it is important to determine what the organization’s needs are, what each potential provider’s strong and weak points are, and select several providers based on these factors.

Photosensitive erythema multiforme and erythema multiforme-like polymorphous light eruption. Photosensitive erythema multiforme (EM) is a rare disorder. It usually occurs only if a herpes virus infection or ingestion of drugs precedes exposure to sunlight in selected patients. We report a 37-year-old man who had recurrent EM eruptions following sun exposures over a period of 20 years. Lesions were prevalently located on exposed skin, but unexposed skin and mucosa of the oropharynx were also affected. The patient had poor tolerance to sunlight and denied having herpes simplex infection or using drugs. Provocative phototest induced clinically and histologically similar lesions at low dose thresholds of UVA (10 J/cm2) and UVB (100 mJ/cm2). On the basis of clinical and histological findings and results of phototesting, a diagnosis of photosensitive EM was made. The EM-like variant of polymorphous light eruption is discussed in the differential diagnosis.

Sexual health. 1: Sexuality and nurses' role in sexual health. This article, the first of two, looks at the issue of sexuality in health care. Sexuality underpins much of what a person is and has significance in everyone's life. Through sexuality, people express their most intimate feelings of individuality and their need for emotional closeness with other human beings. Sexuality is not just about sexual intercourse, it is about the concept of people as men and women--about their manliness or femininity. Sexuality also affects the way people see themselves or would like to be seen, their appearance and behaviour, and their desire to attract those who matter to them. It is about the fears and fantasies people have about themselves and others. Nurses need to have an understanding of sexuality as they may have a crucial part to play in its dynamic progress.

Q: XAML ImageBrush using a BitmapImage without a URI I have the following XAML that displays a cover image for a book using a URI: <Rectangle.Fill> <ImageBrush ImageSource="{Binding CoverUrl}" /> </Rectangle.Fill> However, the image I would like to use is not on disk anywhere or accessible via a URI; it comes from inside a binary file that I parse out into a BitmapImage object. When I create a BitmapImage object via code, the resulting object's BaseUri and UriSource properties are null. How can I get the ImageBrush to use a BitmapImage that resides in memory instead of reading it in from a URI? A: The ImageSource property is of type ImageSource, not Uri or string... actually, a conversion happens when you assign a Uri to it. You can bind the ImageBrush directly to a property that returns an ImageSource <Rectangle.Fill> <ImageBrush ImageSource="{Binding Cover}" /> </Rectangle.Fill> private ImageSource _cover; public ImageSource Cover { get { if (_cover == null) { _cover = LoadImage(); } return _cover; } }

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Specializing in affordable tax preparation, Life and Health Insurance. We can prepare.FTC v. Consumer Defense, LLC, No. 18-15462 (9th Cir. 2019) Matthew Enterprise, Inc. v. chrysler group llc, No. 13-cv-04236-BLF (N.D. Cal. the court noted that it was not aware of any Ninth circuit case law holding that the Robinson-Patman Act applies to. I happened to notice a sign with the words "get feathered" I had no idea what it meant. You might have guessed by now I am not very trendy. Well, it appears rooster feathers are the new hot "it" item. Let me just say the only ones sporting feathers here at Dog Trot Farm will be my chickens. Loretta is a Mille Fluer, a very sweet and social gal. Contents Crunch time. yesterday 2 myths holding horrible slaveholding family Month. home prices rose 0.7 Inexpensive. wsfs financial Modification status: remodifications@onemainfinancial. holy crow this is crunch time. yesterday I made some headway, and that headway had to go to the Read more. Holy crow this is crunch time. Yesterday I made some headway, and that headway had to go to the electric bill, gas for the truck, 100lbs of feed, and phone company. The reality of needing to earn money through this blog and farm is that I am not able to just earn it for one expense.

Q: How to convert DOM node text value to UTF-8 in JavaScript? I need to send a text content of an HTML node over Ajax request, but first convert it to UTF-8. Is that possible? Thanks! A: function encode_utf8( s ) { return unescape( encodeURIComponent( s ) ); } function decode_utf8( s ) { return decodeURIComponent( escape( s ) ); } from http://ecmanaut.blogspot.com/2006/07/encoding-decoding-utf8-in-javascript.html use it like this... encode_utf8(document.getElementById(id).textContent);