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{ "pile_set_name": "Pile-CC" }
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{ "pile_set_name": "OpenWebText2" }
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The present invention relates to a semiconductor memory including a so-called “differential-type cell” with two bit cells for storing opposite logic states to each other, respectively, for amplifying a difference between data stored in one of the bit cells and data stored in the other and outputting the amplified difference as readout data. Recently, with reduction in the size of fabrication processes, the thickness of transistor oxide films has been reduced more and more. Because of this, in a known memory cell, a leakage voltage and the like are generated in a gate oxide film of an MOS transistor and, due to the leakage voltage and the like, data holding properties are deteriorated. In a data determination method in which data determination is performed by comparing a voltage stored in a memory cell to a threshold voltage, it is difficult to suppress reduction in reliability resulting from the reduction in the size of fabrication processes. To cope with this problem, a so-called “differential-type cell” including two bit cells and a differential amplifier has been already devised (see Japanese Laid-Open Publication No. 3-120759). In a data write operation, different data indicating opposite logic states to each other are stored in the two bit cells, respectively, for example, according to the levels of respective threshold voltages of the bit cells. On the other hand, in a readout operation, the differential amplifier reads respective potentials of the two bit cells and a difference between the potentials is amplified and then output as readout data. The differential-type cell is less influenced by a leakage of electric charges, compared to the data determination method in which data determination is performed by comparing a stored voltage in a memory cell to a threshold, so that a large noise margin can be provided. Therefore, a semiconductor memory with excellent data holding properties can be achieved.
{ "pile_set_name": "USPTO Backgrounds" }
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Enhancement of pH stability and activity of glycerol dehydratase from Klebsiella pneumoniae by rational design. Glycerol dehydratase (GDHt) is a key and rate-limiting enzyme in the pathway of 1,3-propanediol (1,3-PD) synthesis. The improvement of GDHt's stability and enzymatic activity is desirable for the biosynthesis of 1,3-PD. The gldABC gene encoding GDHt of Klebsiella pneumoniae was cloned and expressed in Escherichia coli XL10-Gold, and the mutation sites of GDHt were obtained through prediction by PoPMuSiC program. Consequently, two mutants (KpG60 and KpG525) were developed by rational design through site-mutagenesis based on 3D structure which was constructed from homology modeling. Analyses of enzymatic properties showed that pH stability of the mutants was about 1.25-2 times higher than that of the wild type, and specific activity, V(max) and K(cat)/K(m) of KpG525 were about 1.5-2 times higher than those of the wild type. This work presented a simple and useful measure to improve the performance of industrial enzyme.
{ "pile_set_name": "PubMed Abstracts" }
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Q: How to implement bulk mailing using windows service on a schedule basis? I've a requirement in which i need to send 10000+ mails on a quarterly basis. For this purpose i used a windows service that triggers every day and executes the mailing functionality only after the third month. I've to fetch last three months records from database and need to send one mail for each record. The problem i faced was the mail server i used do not allow bulk mailing. How can i do this effectively by providing a delay between each sent (20 mails per minute)? A: There are many way to archieve this. We once had a similar requirement and solved it via a home grown service, which would fetch items from a special database table (mail queue) and sent each mail individially. The queue is filled over time by regular business logic. The necessary locking can also be done via db: a SCHEDULE column stores the expected scheduled time of sending the mail. That way the service collects only those mails wich are 'ready' for sending. After successfull send, another column (SENT_TIMESTAMP) is used to mark the success. We implemented the whole service in ASP and triggered it via regular Windows Task Planner jobs. In your case, the service would start every minute and the queue would provide the next 20 mails. An even easier way could be to utilize SQL Server Jobs. SQL Server is capable of delivering mails to a local SMTP server as well. If not done yet, please note that SO question as well: What is the best way to send large batches of emails in ASP.NET?
{ "pile_set_name": "StackExchange" }
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{ "pile_set_name": "Pile-CC" }
0.039039
[Characterization of the Laryngeal Adductor Reflex by Stimulation with Microdroplets Impulses (Microdroplet Impulse Testing)]. The larynx is considered a crossing point between breathing and swallowing pathways. During swallowing, the airway below the glottis must be protected against food components by an appropriate laryngeal closure mechanism. The laryngeal adductor reflex (LAR) with an early, probably di- or oligosynaptic interconnected ipsilateral LAR1- and a late ipsilateral and contralateral LAR2 polysynaptic component is believed to serve as such a mechanism. Here we aimed to measure and characterize the LAR in healthy volunteers and to compare the data obtained with previously published data. We designed a prospective pilot study. 10 healthy volunteers (22-57 years) participated. To elicit the LAR we used a newly designed microdroplet impulse testing (MIT) device: very small waterdroplets were shot onto the endolaryngeal mucosa. By simultaneously observing the anatomical structures with a high speed glottography system, the time between impact of the microdroplet on the mucosa and the beginning of the adduction movement and thus an approximate value for the reflex latency could be determined. An early adduction movement corresponding to LAR1 could not be detected. The measured LAR2 latency time was higher than the EMG LAR2 data. No significant latency difference between right and left stimulation was found. Since we were unable to demonstrate any LAR1 component it may be that muscle activity observable by EMG may not be sufficient to lead to a visible medial vocal cord movement. The longer LAR2 latency compared to EMG data may be explained by the fact that the visually vocal cord movement occurs after a delay although muscle activity already started as evidenced by EMG.Further studies on LAR are warranted, especially since our results also raise questions about the clinical significance of the LAR.
{ "pile_set_name": "PubMed Abstracts" }
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{ "pile_set_name": "OpenWebText2" }
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{ "pile_set_name": "Pile-CC" }
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sci-hub to open science Glaeser, E. L., & Luttmer, E. F. P. (2003). The Misallocation of Housing Under Rent Control. American Economic Review, 93(4), 1027–1046. doi:10.1257/000282803769206188 sci-hub.se/10.1257/000282803769206188 url to share this paper: to make knowledge free. support → Sci-Hub is a projectto make knowledge free.
{ "pile_set_name": "OpenWebText2" }
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{ "pile_set_name": "OpenWebText2" }
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#!/usr/bin/env python # Copyright (c) 2013 The Chromium Authors. All rights reserved. # Use of this source code is governed by a BSD-style license that can be # found in the LICENSE file. """Parser for Web IDL.""" # # IDL Parser # # The parser uses the PLY yacc library to build a set of parsing rules based # on Web IDL. # # Web IDL, and Web IDL grammar can be found at: # http://heycam.github.io/webidl/ # PLY can be found at: # http://www.dabeaz.com/ply/ # # The parser generates a tree by recursively matching sets of items against # defined patterns. When a match is made, that set of items is reduced # to a new item. The new item can provide a match for parent patterns. # In this way an AST is built (reduced) depth first. # # # Disable check for line length and Member as Function due to how grammar rules # are defined with PLY # # pylint: disable=R0201 # pylint: disable=C0301 from __future__ import print_function import os.path import sys import time # Can't use relative imports if we don't have a parent package. if __package__: from .idl_lexer import IDLLexer from .idl_node import IDLAttribute, IDLNode else: from idl_lexer import IDLLexer from idl_node import IDLAttribute, IDLNode SRC_DIR = os.path.abspath(os.path.dirname(__file__)) # Preserve sys.path[0] as is. # https://docs.python.org/3/library/sys.html?highlight=path[0]#sys.path sys.path.insert(1, os.path.join(SRC_DIR, os.pardir, os.pardir, 'third_party')) from ply import lex from ply import yacc # # ERROR_REMAP # # Maps the standard error formula into a more friendly error message. # ERROR_REMAP = { 'Unexpected ")" after "(".' : 'Empty argument list.', 'Unexpected ")" after ",".' : 'Missing argument.', 'Unexpected "}" after ",".' : 'Trailing comma in block.', 'Unexpected "}" after "{".' : 'Unexpected empty block.', 'Unexpected comment after "}".' : 'Unexpected trailing comment.', 'Unexpected "{" after keyword "enum".' : 'Enum missing name.', 'Unexpected "{" after keyword "struct".' : 'Struct missing name.', 'Unexpected "{" after keyword "interface".' : 'Interface missing name.', } _EXTENDED_ATTRIBUTES_APPLICABLE_TO_TYPES = [ 'Clamp', 'EnforceRange', 'StringContext', 'TreatNullAs'] def Boolean(val): """Convert to strict boolean type.""" if val: return True return False def ListFromConcat(*items): """Generate list by concatenating inputs""" itemsout = [] for item in items: if item is None: continue if type(item) is not type([]): itemsout.append(item) else: itemsout.extend(item) return itemsout def ExpandProduction(p): if type(p) == list: return '[' + ', '.join([ExpandProduction(x) for x in p]) + ']' if type(p) == IDLNode: return 'Node:' + str(p) if type(p) == IDLAttribute: return 'Attr:' + str(p) if type(p) == str: return 'str:' + p return '%s:%s' % (p.__class__.__name__, str(p)) # TokenTypeName # # Generate a string which has the type and value of the token. # def TokenTypeName(t): if t.type == 'SYMBOL': return 'symbol %s' % t.value if t.type in ['HEX', 'INT', 'OCT', 'FLOAT']: return 'value %s' % t.value if t.type == 'string' : return 'string "%s"' % t.value if t.type == 'SPECIAL_COMMENT': return 'comment' if t.type == t.value: return '"%s"' % t.value if t.type == ',': return 'Comma' if t.type == 'identifier': return 'identifier "%s"' % t.value return 'keyword "%s"' % t.value # TODO(bashi): Consider moving this out of idl_parser. def ExtractSpecialComment(comment): if not comment.startswith('/**'): raise ValueError('Special comment must start with /**') if not comment.endswith('*/'): raise ValueError('Special comment must end with */') # Remove comment markers lines = [] for line in comment[2:-2].split('\n'): # Remove characters until start marker for this line '*' if found # otherwise it will be blank. offs = line.find('*') if offs >= 0: line = line[offs + 1:].rstrip() else: # TODO(bashi): We may want to keep |line| as is. line = '' lines.append(line) return '\n'.join(lines) # There are two groups of ExtendedAttributes. # One group can apply to types (It is said "applicable to types"), # but the other cannot apply to types. # This function is intended to divide ExtendedAttributes into those 2 groups. # For more details at # https://heycam.github.io/webidl/#extended-attributes-applicable-to-types def DivideExtAttrsIntoApplicableAndNonApplicable(extended_attribute_list): if not extended_attribute_list: return [[], []] else: applicable_to_types = [] non_applicable_to_types = [] for ext_attribute in extended_attribute_list.GetChildren(): if ext_attribute.GetName() in _EXTENDED_ATTRIBUTES_APPLICABLE_TO_TYPES: applicable_to_types.append(ext_attribute) else: non_applicable_to_types.append(ext_attribute) return [applicable_to_types, non_applicable_to_types] # # IDL Parser # # The Parser inherits the from the Lexer to provide PLY with the tokenizing # definitions. Parsing patterns are encoded as functions where p_<name> is # is called any time a patern matching the function documentation is found. # Paterns are expressed in the form of: # """ <new item> : <item> .... # | <item> ....""" # # Where new item is the result of a match against one or more sets of items # separated by the "|". # # The function is called with an object 'p' where p[0] is the output object # and p[n] is the set of inputs for positive values of 'n'. Len(p) can be # used to distinguish between multiple item sets in the pattern. # # The rules can look cryptic at first, but there are a few standard # transforms from the CST to AST. With these in mind, the actions should # be reasonably legible. # # * Ignore production # Discard this branch. Primarily used when one alternative is empty. # # Sample code: # if len(p) > 1: # p[0] = ... # # Note no assignment if len(p) == 1 # # * Eliminate singleton production # Discard this node in the CST, pass the next level down up the tree. # Used to ignore productions only necessary for parsing, but not needed # in the AST. # # Sample code: # p[0] = p[1] # # * Build node # The key type of rule. In this parser, produces object of class IDLNode. # There are several helper functions: # * BuildProduction: actually builds an IDLNode, based on a production. # * BuildAttribute: builds an IDLAttribute, which is a temporary # object to hold a name-value pair, which is then # set as a Property of the IDLNode when the IDLNode # is built. # * BuildNamed: Same as BuildProduction, and sets the 'NAME' property. # * BuildTrue: BuildAttribute with value True, for flags. # # Sample code: # # Build node of type NodeType, with value p[1], and children. # p[0] = self.BuildProduction('NodeType', p, 1, children) # # # Build named node of type NodeType, with name and value p[1]. # # (children optional) # p[0] = self.BuildNamed('NodeType', p, 1) # # # Make a list # # Used if one node has several children. # children = ListFromConcat(p[2], p[3]) # p[0] = self.BuildProduction('NodeType', p, 1, children) # # # Also used to collapse the right-associative tree # # produced by parsing a list back into a single list. # """Foos : Foo Foos # |""" # if len(p) > 1: # p[0] = ListFromConcat(p[1], p[2]) # # # Add children. # # Primarily used to add attributes, produced via BuildTrue. # # p_StaticAttribute # """StaticAttribute : STATIC Attribute""" # p[2].AddChildren(self.BuildTrue('STATIC')) # p[0] = p[2] # # For more details on parsing refer to the PLY documentation at # http://www.dabeaz.com/ply/ # # The parser is based on the Web IDL standard. See: # http://heycam.github.io/webidl/#idl-grammar # # Productions with a fractional component in the comment denote additions to # the Web IDL spec, such as allowing string list in extended attributes. class IDLParser(object): def p_Definitions(self, p): """Definitions : SpecialComments ExtendedAttributeList Definition Definitions | ExtendedAttributeList Definition Definitions | """ if len(p) > 4: special_comments_and_attribs = ListFromConcat(p[1], p[2]) p[3].AddChildren(special_comments_and_attribs) p[0] = ListFromConcat(p[3], p[4]) elif len(p) > 1: p[2].AddChildren(p[1]) p[0] = ListFromConcat(p[2], p[3]) def p_Definition(self, p): """Definition : CallbackOrInterfaceOrMixin | Namespace | Partial | Dictionary | Enum | Typedef | IncludesStatement""" p[0] = p[1] # Error recovery for definition def p_DefinitionError(self, p): """Definition : error ';'""" p[0] = self.BuildError(p, 'Definition') def p_ArgumentNameKeyword(self, p): """ArgumentNameKeyword : ASYNC | ATTRIBUTE | CALLBACK | CONST | CONSTRUCTOR | DELETER | DICTIONARY | ENUM | GETTER | INCLUDES | INHERIT | INTERFACE | ITERABLE | MAPLIKE | NAMESPACE | PARTIAL | REQUIRED | SETLIKE | SETTER | STATIC | STRINGIFIER | TYPEDEF | UNRESTRICTED""" p[0] = p[1] def p_CallbackOrInterfaceOrMixin(self, p): """CallbackOrInterfaceOrMixin : CALLBACK CallbackRestOrInterface | INTERFACE InterfaceOrMixin""" p[0] = p[2] def p_InterfaceOrMixin(self, p): """InterfaceOrMixin : InterfaceRest | MixinRest""" p[0] = p[1] def p_InterfaceRest(self, p): """InterfaceRest : identifier Inheritance '{' InterfaceMembers '}' ';'""" p[0] = self.BuildNamed('Interface', p, 1, ListFromConcat(p[2], p[4])) # Error recovery for interface. def p_InterfaceRestError(self, p): """InterfaceRest : identifier Inheritance '{' error""" p[0] = self.BuildError(p, 'Interface') def p_Partial(self, p): """Partial : PARTIAL PartialDefinition""" p[2].AddChildren(self.BuildTrue('PARTIAL')) p[0] = p[2] # Error recovery for Partial def p_PartialError(self, p): """Partial : PARTIAL error""" p[0] = self.BuildError(p, 'Partial') def p_PartialDefinition(self, p): """PartialDefinition : INTERFACE PartialInterfaceOrPartialMixin | PartialDictionary | Namespace""" if len(p) > 2: p[0] = p[2] else: p[0] = p[1] def p_PartialInterfaceOrPartialMixin(self, p): """PartialInterfaceOrPartialMixin : PartialInterfaceRest | MixinRest""" p[0] = p[1] def p_PartialInterfaceRest(self, p): """PartialInterfaceRest : identifier '{' PartialInterfaceMembers '}' ';'""" p[0] = self.BuildNamed('Interface', p, 1, p[3]) def p_InterfaceMembers(self, p): """InterfaceMembers : ExtendedAttributeList InterfaceMember InterfaceMembers |""" if len(p) > 1: p[2].AddChildren(p[1]) p[0] = ListFromConcat(p[2], p[3]) # Error recovery for InterfaceMembers def p_InterfaceMembersError(self, p): """InterfaceMembers : error""" p[0] = self.BuildError(p, 'InterfaceMembers') def p_InterfaceMember(self, p): """InterfaceMember : PartialInterfaceMember | Constructor""" p[0] = p[1] def p_PartialInterfaceMembers(self, p): """PartialInterfaceMembers : ExtendedAttributeList PartialInterfaceMember PartialInterfaceMembers |""" if len(p) > 1: p[2].AddChildren(p[1]) p[0] = ListFromConcat(p[2], p[3]) # Error recovery for InterfaceMembers def p_PartialInterfaceMembersError(self, p): """PartialInterfaceMembers : error""" p[0] = self.BuildError(p, 'PartialInterfaceMembers') def p_PartialInterfaceMember(self, p): """PartialInterfaceMember : Const | Operation | Stringifier | StaticMember | Iterable | AsyncIterable | ReadonlyMember | ReadWriteAttribute | ReadWriteMaplike | ReadWriteSetlike""" p[0] = p[1] def p_Inheritance(self, p): """Inheritance : ':' identifier |""" if len(p) > 1: p[0] = self.BuildNamed('Inherit', p, 2) def p_MixinRest(self, p): """MixinRest : MIXIN identifier '{' MixinMembers '}' ';'""" p[0] = self.BuildNamed('Interface', p, 2, p[4]) p[0].AddChildren(self.BuildTrue('MIXIN')) def p_MixinMembers(self, p): """MixinMembers : ExtendedAttributeList MixinMember MixinMembers |""" if len(p) > 1: p[2].AddChildren(p[1]) p[0] = ListFromConcat(p[2], p[3]) # Error recovery for InterfaceMembers def p_MixinMembersError(self, p): """MixinMembers : error""" p[0] = self.BuildError(p, 'MixinMembers') def p_MixinMember(self, p): """MixinMember : Const | Operation | Stringifier | ReadOnly AttributeRest""" if len(p) == 2: p[0] = p[1] else: p[2].AddChildren(p[1]) p[0] = p[2] def p_IncludesStatement(self, p): """IncludesStatement : identifier INCLUDES identifier ';'""" name = self.BuildAttribute('REFERENCE', p[3]) p[0] = self.BuildNamed('Includes', p, 1, name) def p_CallbackRestOrInterface(self, p): """CallbackRestOrInterface : CallbackRest | INTERFACE InterfaceRest""" if len(p) < 3: p[0] = p[1] else: p[2].AddChildren(self.BuildTrue('CALLBACK')) p[0] = p[2] def p_Const(self, p): """Const : CONST ConstType identifier '=' ConstValue ';'""" value = self.BuildProduction('Value', p, 5, p[5]) p[0] = self.BuildNamed('Const', p, 3, ListFromConcat(p[2], value)) def p_ConstValue(self, p): """ConstValue : BooleanLiteral | FloatLiteral | integer""" if type(p[1]) == str: p[0] = ListFromConcat(self.BuildAttribute('TYPE', 'integer'), self.BuildAttribute('VALUE', p[1])) else: p[0] = p[1] def p_BooleanLiteral(self, p): """BooleanLiteral : TRUE | FALSE""" value = self.BuildAttribute('VALUE', Boolean(p[1] == 'true')) p[0] = ListFromConcat(self.BuildAttribute('TYPE', 'boolean'), value) def p_FloatLiteral(self, p): """FloatLiteral : float | '-' INFINITY | INFINITY | NAN """ if len(p) > 2: val = '-Infinity' else: val = p[1] p[0] = ListFromConcat(self.BuildAttribute('TYPE', 'float'), self.BuildAttribute('VALUE', val)) def p_ConstType(self, p): """ConstType : PrimitiveType Null | identifier Null""" if type(p[1]) == str: p[0] = self.BuildNamed('Typeref', p, 1, p[2]) else: p[1].AddChildren(p[2]) p[0] = p[1] def p_ReadonlyMember(self, p): """ReadonlyMember : READONLY ReadonlyMemberRest""" p[2].AddChildren(self.BuildTrue('READONLY')) p[0] = p[2] def p_ReadonlyMemberRest(self, p): """ReadonlyMemberRest : AttributeRest | MaplikeRest | SetlikeRest""" p[0] = p[1] def p_ReadWriteAttribute(self, p): """ReadWriteAttribute : INHERIT ReadOnly AttributeRest | AttributeRest""" if len(p) > 2: inherit = self.BuildTrue('INHERIT') p[3].AddChildren(ListFromConcat(inherit, p[2])) p[0] = p[3] else: p[0] = p[1] def p_AttributeRest(self, p): """AttributeRest : ATTRIBUTE TypeWithExtendedAttributes AttributeName ';'""" p[0] = self.BuildNamed('Attribute', p, 3, p[2]) def p_AttributeName(self, p): """AttributeName : AttributeNameKeyword | identifier""" p[0] = p[1] def p_AttributeNameKeyword(self, p): """AttributeNameKeyword : ASYNC | REQUIRED""" p[0] = p[1] def p_ReadOnly(self, p): """ReadOnly : READONLY |""" if len(p) > 1: p[0] = self.BuildTrue('READONLY') def p_DefaultValue(self, p): """DefaultValue : ConstValue | string | '[' ']' | '{' '}' | null""" if len(p) == 3: if p[1] == '[': p[0] = ListFromConcat(self.BuildAttribute('TYPE', 'sequence'), self.BuildAttribute('VALUE', '[]')) else: p[0] = ListFromConcat(self.BuildAttribute('TYPE', 'dictionary'), self.BuildAttribute('VALUE', '{}')) elif type(p[1]) == str: p[0] = ListFromConcat(self.BuildAttribute('TYPE', 'DOMString'), self.BuildAttribute('VALUE', p[1])) else: p[0] = p[1] def p_Operation(self, p): """Operation : RegularOperation | SpecialOperation""" p[0] = p[1] def p_RegularOperation(self, p): """RegularOperation : ReturnType OperationRest""" p[2].AddChildren(p[1]) p[0] = p[2] def p_SpecialOperation(self, p): """SpecialOperation : Special RegularOperation""" p[2].AddChildren(p[1]) p[0] = p[2] def p_Special(self, p): """Special : GETTER | SETTER | DELETER""" p[0] = self.BuildTrue(p[1].upper()) def p_OperationRest(self, p): """OperationRest : OptionalOperationName '(' ArgumentList ')' ';'""" arguments = self.BuildProduction('Arguments', p, 2, p[3]) p[0] = self.BuildNamed('Operation', p, 1, arguments) def p_OptionalOperationName(self, p): """OptionalOperationName : OperationName |""" if len(p) > 1: p[0] = p[1] else: p[0] = '' def p_OperationName(self, p): """OperationName : OperationNameKeyword | identifier""" p[0] = p[1] def p_OperationNameKeyword(self, p): """OperationNameKeyword : INCLUDES""" p[0] = p[1] def p_ArgumentList(self, p): """ArgumentList : Argument Arguments |""" if len(p) > 1: p[0] = ListFromConcat(p[1], p[2]) # ArgumentList error recovery def p_ArgumentListError(self, p): """ArgumentList : error """ p[0] = self.BuildError(p, 'ArgumentList') def p_Arguments(self, p): """Arguments : ',' Argument Arguments |""" if len(p) > 1: p[0] = ListFromConcat(p[2], p[3]) # Arguments error recovery def p_ArgumentsError(self, p): """Arguments : ',' error""" p[0] = self.BuildError(p, 'Arguments') def p_Argument(self, p): """Argument : ExtendedAttributeList OPTIONAL TypeWithExtendedAttributes ArgumentName Default | ExtendedAttributeList Type Ellipsis ArgumentName""" if len(p) > 5: p[0] = self.BuildNamed('Argument', p, 4, ListFromConcat(p[3], p[5])) p[0].AddChildren(self.BuildTrue('OPTIONAL')) p[0].AddChildren(p[1]) else: applicable_to_types, non_applicable_to_types = \ DivideExtAttrsIntoApplicableAndNonApplicable(p[1]) if applicable_to_types: attributes = self.BuildProduction('ExtAttributes', p, 1, applicable_to_types) p[2].AddChildren(attributes) p[0] = self.BuildNamed('Argument', p, 4, ListFromConcat(p[2], p[3])) if non_applicable_to_types: attributes = self.BuildProduction('ExtAttributes', p, 1, non_applicable_to_types) p[0].AddChildren(attributes) def p_ArgumentName(self, p): """ArgumentName : ArgumentNameKeyword | identifier""" p[0] = p[1] def p_Ellipsis(self, p): """Ellipsis : ELLIPSIS |""" if len(p) > 1: p[0] = self.BuildNamed('Argument', p, 1) p[0].AddChildren(self.BuildTrue('ELLIPSIS')) def p_ReturnType(self, p): """ReturnType : Type | VOID""" if p[1] == 'void': p[0] = self.BuildProduction('Type', p, 1) p[0].AddChildren(self.BuildNamed('PrimitiveType', p, 1)) else: p[0] = p[1] def p_Constructor(self, p): """Constructor : CONSTRUCTOR '(' ArgumentList ')' ';'""" arguments = self.BuildProduction('Arguments', p, 1, p[3]) p[0] = self.BuildProduction('Constructor', p, 1, arguments) def p_Stringifier(self, p): """Stringifier : STRINGIFIER StringifierRest""" p[0] = self.BuildProduction('Stringifier', p, 1, p[2]) def p_StringifierRest(self, p): """StringifierRest : ReadOnly AttributeRest | ReturnType OperationRest | ';'""" if len(p) == 3: p[2].AddChildren(p[1]) p[0] = p[2] def p_StaticMember(self, p): """StaticMember : STATIC StaticMemberRest""" p[2].AddChildren(self.BuildTrue('STATIC')) p[0] = p[2] def p_StaticMemberRest(self, p): """StaticMemberRest : ReadOnly AttributeRest | ReturnType OperationRest""" if len(p) == 2: p[0] = p[1] else: p[2].AddChildren(p[1]) p[0] = p[2] def p_Iterable(self, p): """Iterable : ITERABLE '<' TypeWithExtendedAttributes OptionalType '>' ';'""" childlist = ListFromConcat(p[3], p[4]) p[0] = self.BuildProduction('Iterable', p, 2, childlist) def p_OptionalType(self, p): """OptionalType : ',' TypeWithExtendedAttributes |""" if len(p) > 1: p[0] = p[2] def p_AsyncIterable(self, p): """AsyncIterable : ASYNC ITERABLE '<' TypeWithExtendedAttributes ',' TypeWithExtendedAttributes '>' ';'""" childlist = ListFromConcat(p[4], p[6]) p[0] = self.BuildProduction('AsyncIterable', p, 2, childlist) def p_ReadWriteMaplike(self, p): """ReadWriteMaplike : MaplikeRest""" p[0] = p[1] def p_MaplikeRest(self, p): """MaplikeRest : MAPLIKE '<' TypeWithExtendedAttributes ',' TypeWithExtendedAttributes '>' ';'""" childlist = ListFromConcat(p[3], p[5]) p[0] = self.BuildProduction('Maplike', p, 2, childlist) def p_ReadWriteSetlike(self, p): """ReadWriteSetlike : SetlikeRest""" p[0] = p[1] def p_SetlikeRest(self, p): """SetlikeRest : SETLIKE '<' TypeWithExtendedAttributes '>' ';'""" p[0] = self.BuildProduction('Setlike', p, 2, p[3]) def p_Namespace(self, p): """Namespace : NAMESPACE identifier '{' NamespaceMembers '}' ';'""" p[0] = self.BuildNamed('Namespace', p, 2, p[4]) # Error recovery for namespace. def p_NamespaceError(self, p): """Namespace : NAMESPACE identifier '{' error""" p[0] = self.BuildError(p, 'Namespace') def p_NamespaceMembers(self, p): """NamespaceMembers : NamespaceMember NamespaceMembers | """ if len(p) > 1: p[0] = ListFromConcat(p[1], p[2]) # Error recovery for NamespaceMembers def p_NamespaceMembersError(self, p): """NamespaceMembers : ExtendedAttributeList error""" p[0] = self.BuildError(p, 'NamespaceMembers') def p_NamespaceMember(self, p): """NamespaceMember : ExtendedAttributeList ReturnType OperationRest | ExtendedAttributeList READONLY AttributeRest""" if p[2] != 'readonly': applicable_to_types, non_applicable_to_types = \ DivideExtAttrsIntoApplicableAndNonApplicable(p[1]) if applicable_to_types: attributes = self.BuildProduction('ExtAttributes', p, 1, applicable_to_types) p[2].AddChildren(attributes) p[3].AddChildren(p[2]) if non_applicable_to_types: attributes = self.BuildProduction('ExtAttributes', p, 1, non_applicable_to_types) p[3].AddChildren(attributes) else: p[3].AddChildren(self.BuildTrue('READONLY')) p[3].AddChildren(p[1]) p[0] = p[3] def p_Dictionary(self, p): """Dictionary : DICTIONARY identifier Inheritance '{' DictionaryMembers '}' ';'""" p[0] = self.BuildNamed('Dictionary', p, 2, ListFromConcat(p[3], p[5])) # Error recovery for regular Dictionary def p_DictionaryError(self, p): """Dictionary : DICTIONARY error ';'""" p[0] = self.BuildError(p, 'Dictionary') # Error recovery for regular Dictionary # (for errors inside dictionary definition) def p_DictionaryError2(self, p): """Dictionary : DICTIONARY identifier Inheritance '{' error""" p[0] = self.BuildError(p, 'Dictionary') def p_DictionaryMembers(self, p): """DictionaryMembers : DictionaryMember DictionaryMembers |""" if len(p) > 1: p[0] = ListFromConcat(p[1], p[2]) # Error recovery for DictionaryMembers def p_DictionaryMembersError(self, p): """DictionaryMembers : ExtendedAttributeList error""" p[0] = self.BuildError(p, 'DictionaryMembers') def p_DictionaryMember(self, p): """DictionaryMember : ExtendedAttributeList REQUIRED TypeWithExtendedAttributes identifier Default ';' | ExtendedAttributeList Type identifier Default ';'""" if len(p) > 6: p[2] = self.BuildTrue('REQUIRED') p[0] = self.BuildNamed('Key', p, 4, ListFromConcat(p[2], p[3], p[5])) p[0].AddChildren(p[1]) else: applicable_to_types, non_applicable_to_types = \ DivideExtAttrsIntoApplicableAndNonApplicable(p[1]) if applicable_to_types: attributes = self.BuildProduction('ExtAttributes', p, 1, applicable_to_types) p[2].AddChildren(attributes) p[0] = self.BuildNamed('Key', p, 3, ListFromConcat(p[2], p[4])) if non_applicable_to_types: attributes = self.BuildProduction('ExtAttributes', p, 1, non_applicable_to_types) p[0].AddChildren(attributes) def p_PartialDictionary(self, p): """PartialDictionary : DICTIONARY identifier '{' DictionaryMembers '}' ';'""" p[0] = self.BuildNamed('Dictionary', p, 2, p[4]) # Error recovery for Partial Dictionary def p_PartialDictionaryError(self, p): """PartialDictionary : DICTIONARY error ';'""" p[0] = self.BuildError(p, 'PartialDictionary') def p_Default(self, p): """Default : '=' DefaultValue |""" if len(p) > 1: p[0] = self.BuildProduction('Default', p, 2, p[2]) def p_Enum(self, p): """Enum : ENUM identifier '{' EnumValueList '}' ';'""" p[0] = self.BuildNamed('Enum', p, 2, p[4]) # Error recovery for Enums def p_EnumError(self, p): """Enum : ENUM error ';'""" p[0] = self.BuildError(p, 'Enum') def p_EnumValueList(self, p): """EnumValueList : string EnumValueListComma""" enum = self.BuildNamed('EnumItem', p, 1) p[0] = ListFromConcat(enum, p[2]) def p_EnumValueListComma(self, p): """EnumValueListComma : ',' EnumValueListString |""" if len(p) > 1: p[0] = p[2] def p_EnumValueListString(self, p): """EnumValueListString : string EnumValueListComma |""" if len(p) > 1: enum = self.BuildNamed('EnumItem', p, 1) p[0] = ListFromConcat(enum, p[2]) def p_CallbackRest(self, p): """CallbackRest : identifier '=' ReturnType '(' ArgumentList ')' ';'""" arguments = self.BuildProduction('Arguments', p, 4, p[5]) p[0] = self.BuildNamed('Callback', p, 1, ListFromConcat(p[3], arguments)) def p_Typedef(self, p): """Typedef : TYPEDEF TypeWithExtendedAttributes identifier ';'""" p[0] = self.BuildNamed('Typedef', p, 3, p[2]) # Error recovery for Typedefs def p_TypedefError(self, p): """Typedef : TYPEDEF error ';'""" p[0] = self.BuildError(p, 'Typedef') def p_Type(self, p): """Type : SingleType | UnionType Null""" if len(p) == 2: p[0] = self.BuildProduction('Type', p, 1, p[1]) else: p[0] = self.BuildProduction('Type', p, 1, ListFromConcat(p[1], p[2])) def p_TypeWithExtendedAttributes(self, p): """ TypeWithExtendedAttributes : ExtendedAttributeList SingleType | ExtendedAttributeList UnionType Null""" if len(p) < 4: p[0] = self.BuildProduction('Type', p, 2, p[2]) else: p[0] = self.BuildProduction('Type', p, 2, ListFromConcat(p[2], p[3])) p[0].AddChildren(p[1]) def p_SingleType(self, p): """SingleType : DistinguishableType | ANY | PromiseType""" if p[1] != 'any': p[0] = p[1] else: p[0] = self.BuildProduction('Any', p, 1) def p_UnionType(self, p): """UnionType : '(' UnionMemberType OR UnionMemberType UnionMemberTypes ')'""" members = ListFromConcat(p[2], p[4], p[5]) p[0] = self.BuildProduction('UnionType', p, 1, members) def p_UnionMemberType(self, p): """UnionMemberType : ExtendedAttributeList DistinguishableType | UnionType Null""" if p[1] is None: p[0] = self.BuildProduction('Type', p, 1, p[2]) elif p[1].GetClass() == 'ExtAttributes': p[0] = self.BuildProduction('Type', p, 1, ListFromConcat(p[2], p[1])) else: p[0] = self.BuildProduction('Type', p, 1, ListFromConcat(p[1], p[2])) def p_UnionMemberTypes(self, p): """UnionMemberTypes : OR UnionMemberType UnionMemberTypes |""" if len(p) > 2: p[0] = ListFromConcat(p[2], p[3]) # Moved BYTESTRING, DOMSTRING, OBJECT to PrimitiveType # Moving all built-in types into PrimitiveType makes it easier to # differentiate between them and 'identifier', since p[1] would be a string in # both cases. def p_DistinguishableType(self, p): """DistinguishableType : PrimitiveType Null | identifier Null | SEQUENCE '<' TypeWithExtendedAttributes '>' Null | FROZENARRAY '<' TypeWithExtendedAttributes '>' Null | RecordType Null""" if len(p) == 3: if type(p[1]) == str: typeref = self.BuildNamed('Typeref', p, 1) else: typeref = p[1] p[0] = ListFromConcat(typeref, p[2]) if len(p) == 6: cls = 'Sequence' if p[1] == 'sequence' else 'FrozenArray' p[0] = self.BuildProduction(cls, p, 1, p[3]) p[0] = ListFromConcat(p[0], p[5]) # Added StringType, OBJECT def p_PrimitiveType(self, p): """PrimitiveType : UnsignedIntegerType | UnrestrictedFloatType | StringType | BOOLEAN | BYTE | OCTET | OBJECT""" if type(p[1]) == str: p[0] = self.BuildNamed('PrimitiveType', p, 1) else: p[0] = p[1] def p_UnrestrictedFloatType(self, p): """UnrestrictedFloatType : UNRESTRICTED FloatType | FloatType""" if len(p) == 2: typeref = self.BuildNamed('PrimitiveType', p, 1) else: typeref = self.BuildNamed('PrimitiveType', p, 2) typeref.AddChildren(self.BuildTrue('UNRESTRICTED')) p[0] = typeref def p_FloatType(self, p): """FloatType : FLOAT | DOUBLE""" p[0] = p[1] def p_UnsignedIntegerType(self, p): """UnsignedIntegerType : UNSIGNED IntegerType | IntegerType""" if len(p) == 2: p[0] = p[1] else: p[0] = 'unsigned ' + p[2] def p_IntegerType(self, p): """IntegerType : SHORT | LONG OptionalLong""" if len(p) == 2: p[0] = p[1] else: p[0] = p[1] + p[2] def p_OptionalLong(self, p): """OptionalLong : LONG | """ if len(p) > 1: p[0] = ' ' + p[1] else: p[0] = '' def p_StringType(self, p): """StringType : BYTESTRING | DOMSTRING | USVSTRING""" p[0] = self.BuildNamed('StringType', p, 1) def p_PromiseType(self, p): """PromiseType : PROMISE '<' ReturnType '>'""" p[0] = self.BuildNamed('Promise', p, 1, p[3]) def p_RecordType(self, p): """RecordType : RECORD '<' StringType ',' TypeWithExtendedAttributes '>'""" p[0] = self.BuildProduction('Record', p, 2, ListFromConcat(p[3], p[5])) # Error recovery for RecordType. def p_RecordTypeError(self, p): """RecordType : RECORD '<' error ',' Type '>'""" p[0] = self.BuildError(p, 'RecordType') def p_Null(self, p): """Null : '?' |""" if len(p) > 1: p[0] = self.BuildTrue('NULLABLE') # This rule has custom additions (i.e. SpecialComments). def p_ExtendedAttributeList(self, p): """ExtendedAttributeList : '[' ExtendedAttribute ExtendedAttributes ']' | """ if len(p) > 4: items = ListFromConcat(p[2], p[3]) p[0] = self.BuildProduction('ExtAttributes', p, 1, items) # Error recovery for ExtendedAttributeList def p_ExtendedAttributeListError(self, p): """ExtendedAttributeList : '[' ExtendedAttribute ',' error""" p[0] = self.BuildError(p, 'ExtendedAttributeList') def p_ExtendedAttributes(self, p): """ExtendedAttributes : ',' ExtendedAttribute ExtendedAttributes |""" if len(p) > 1: p[0] = ListFromConcat(p[2], p[3]) # https://heycam.github.io/webidl/#idl-extended-attributes # The ExtendedAttribute symbol in Web IDL grammar is very flexible but we # only support following patterns: # [ identifier ] # [ identifier ( ArgumentList ) ] # [ identifier = identifier ] # [ identifier = ( IdentifierList ) ] # [ identifier = identifier ( ArgumentList ) ] # [ identifier = ( StringList ) ] # The first five patterns are specified in the Web IDL spec and the last # pattern is Blink's custom extension to support [ReflectOnly]. def p_ExtendedAttribute(self, p): """ExtendedAttribute : ExtendedAttributeNoArgs | ExtendedAttributeArgList | ExtendedAttributeIdent | ExtendedAttributeIdentList | ExtendedAttributeNamedArgList | ExtendedAttributeStringLiteral | ExtendedAttributeStringLiteralList""" p[0] = p[1] # Add definition for NULL def p_null(self, p): """null : NULL""" p[0] = ListFromConcat(self.BuildAttribute('TYPE', 'NULL'), self.BuildAttribute('VALUE', 'NULL')) def p_IdentifierList(self, p): """IdentifierList : identifier Identifiers""" p[0] = ListFromConcat(p[1], p[2]) def p_Identifiers(self, p): """Identifiers : ',' identifier Identifiers |""" if len(p) > 1: p[0] = ListFromConcat(p[2], p[3]) def p_ExtendedAttributeNoArgs(self, p): """ExtendedAttributeNoArgs : identifier""" p[0] = self.BuildNamed('ExtAttribute', p, 1) def p_ExtendedAttributeArgList(self, p): """ExtendedAttributeArgList : identifier '(' ArgumentList ')'""" arguments = self.BuildProduction('Arguments', p, 2, p[3]) p[0] = self.BuildNamed('ExtAttribute', p, 1, arguments) def p_ExtendedAttributeIdent(self, p): """ExtendedAttributeIdent : identifier '=' identifier""" value = self.BuildAttribute('VALUE', p[3]) p[0] = self.BuildNamed('ExtAttribute', p, 1, value) def p_ExtendedAttributeIdentList(self, p): """ExtendedAttributeIdentList : identifier '=' '(' IdentifierList ')'""" value = self.BuildAttribute('VALUE', p[4]) p[0] = self.BuildNamed('ExtAttribute', p, 1, value) def p_ExtendedAttributeNamedArgList(self, p): """ExtendedAttributeNamedArgList : identifier '=' identifier '(' ArgumentList ')'""" args = self.BuildProduction('Arguments', p, 4, p[5]) value = self.BuildNamed('Call', p, 3, args) p[0] = self.BuildNamed('ExtAttribute', p, 1, value) # Blink extension: Add support for string literal Extended Attribute values def p_ExtendedAttributeStringLiteral(self, p): """ExtendedAttributeStringLiteral : identifier '=' StringLiteral""" def UnwrapString(ls): """Reach in and grab the string literal's "NAME".""" return ls[1].value value = self.BuildAttribute('VALUE', UnwrapString(p[3])) p[0] = self.BuildNamed('ExtAttribute', p, 1, value) # Blink extension: Add support for compound Extended Attribute values over # string literals ("A","B") def p_ExtendedAttributeStringLiteralList(self, p): """ExtendedAttributeStringLiteralList : identifier '=' '(' StringLiteralList ')'""" value = self.BuildAttribute('VALUE', p[4]) p[0] = self.BuildNamed('ExtAttribute', p, 1, value) # Blink extension: One or more string literals. The values aren't propagated # as literals, but their by their value only. def p_StringLiteralList(self, p): """StringLiteralList : StringLiteral ',' StringLiteralList | StringLiteral""" def UnwrapString(ls): """Reach in and grab the string literal's "NAME".""" return ls[1].value if len(p) > 3: p[0] = ListFromConcat(UnwrapString(p[1]), p[3]) else: p[0] = ListFromConcat(UnwrapString(p[1])) # Blink extension: Wrap string literal. def p_StringLiteral(self, p): """StringLiteral : string""" p[0] = ListFromConcat(self.BuildAttribute('TYPE', 'DOMString'), self.BuildAttribute('NAME', p[1])) # Blink extension: Treat special comments (/** ... */) as AST nodes to # annotate other nodes. Currently they are used for testing. def p_SpecialComments(self, p): """SpecialComments : SPECIAL_COMMENT SpecialComments | """ if len(p) > 1: p[0] = ListFromConcat(self.BuildSpecialComment(p, 1), p[2]) # # Parser Errors # # p_error is called whenever the parser can not find a pattern match for # a set of items from the current state. The p_error function defined here # is triggered logging an error, and parsing recovery happens as the # p_<type>_error functions defined above are called. This allows the parser # to continue so as to capture more than one error per file. # def p_error(self, t): if t: lineno = t.lineno pos = t.lexpos prev = self.yaccobj.symstack[-1] if type(prev) == lex.LexToken: msg = "Unexpected %s after %s." % ( TokenTypeName(t), TokenTypeName(prev)) else: msg = "Unexpected %s." % (t.value) else: last = self.LastToken() lineno = last.lineno pos = last.lexpos msg = "Unexpected end of file after %s." % TokenTypeName(last) self.yaccobj.restart() # Attempt to remap the error to a friendlier form if msg in ERROR_REMAP: msg = ERROR_REMAP[msg] self._last_error_msg = msg self._last_error_lineno = lineno self._last_error_pos = pos def Warn(self, node, msg): sys.stdout.write(node.GetLogLine(msg)) self.parse_warnings += 1 def LastToken(self): return self.lexer.last def __init__(self, lexer, verbose=False, debug=False, mute_error=False): self.lexer = lexer self.tokens = lexer.KnownTokens() self.yaccobj = yacc.yacc(module=self, tabmodule=None, debug=debug, optimize=0, write_tables=0) # TODO: Make our code compatible with defaulted_states. Currently disabled # for compatibility. self.yaccobj.defaulted_states = {} self.parse_debug = debug self.verbose = verbose self.mute_error = mute_error self._parse_errors = 0 self._parse_warnings = 0 self._last_error_msg = None self._last_error_lineno = 0 self._last_error_pos = 0 # # BuildProduction # # Production is the set of items sent to a grammar rule resulting in a new # item being returned. # # cls - The type of item being producted # p - Is the Yacc production object containing the stack of items # index - Index into the production of the name for the item being produced. # childlist - The children of the new item def BuildProduction(self, cls, p, index, childlist=None): try: if not childlist: childlist = [] filename = self.lexer.Lexer().filename lineno = p.lineno(index) pos = p.lexpos(index) out = IDLNode(cls, filename, lineno, pos, childlist) return out except: print('Exception while parsing:') for num, item in enumerate(p): print(' [%d] %s' % (num, ExpandProduction(item))) if self.LastToken(): print('Last token: %s' % str(self.LastToken())) raise def BuildNamed(self, cls, p, index, childlist=None): childlist = ListFromConcat(childlist) childlist.append(self.BuildAttribute('NAME', p[index])) return self.BuildProduction(cls, p, index, childlist) def BuildSpecialComment(self, p, index): name = ExtractSpecialComment(p[index]) childlist = [self.BuildAttribute('NAME', name)] return self.BuildProduction('SpecialComment', p, index, childlist) # # BuildError # # Build and Errror node as part of the recovery process. # # def BuildError(self, p, prod): self._parse_errors += 1 name = self.BuildAttribute('NAME', self._last_error_msg) line = self.BuildAttribute('LINENO', self._last_error_lineno) pos = self.BuildAttribute('POSITION', self._last_error_pos) prod = self.BuildAttribute('PROD', prod) node = self.BuildProduction('Error', p, 1, ListFromConcat(name, line, pos, prod)) if not self.mute_error: node.Error(self._last_error_msg) return node # # BuildAttribute # # An ExtendedAttribute is a special production that results in a property # which is applied to the adjacent item. Attributes have no children and # instead represent key/value pairs. # def BuildAttribute(self, key, val): return IDLAttribute(key, val) def BuildFalse(self, key): return IDLAttribute(key, Boolean(False)) def BuildTrue(self, key): return IDLAttribute(key, Boolean(True)) def GetErrors(self): # Access lexer errors, despite being private # pylint: disable=W0212 return self._parse_errors + self.lexer._lex_errors # # ParseData # # Attempts to parse the current data loaded in the lexer. # def ParseText(self, filename, data): self._parse_errors = 0 self._parse_warnings = 0 self._last_error_msg = None self._last_error_lineno = 0 self._last_error_pos = 0 try: self.lexer.Tokenize(data, filename) nodes = self.yaccobj.parse(lexer=self.lexer) or [] name = self.BuildAttribute('NAME', filename) return IDLNode('File', filename, 0, 0, nodes + [name]) except lex.LexError as lexError: sys.stderr.write('Error in token: %s\n' % str(lexError)) return None def ParseFile(parser, filename): """Parse a file and return a File type of node.""" with open(filename) as fileobject: try: out = parser.ParseText(filename, fileobject.read()) out.SetProperty('DATETIME', time.ctime(os.path.getmtime(filename))) out.SetProperty('ERRORS', parser.GetErrors()) return out except Exception as e: last = parser.LastToken() sys.stderr.write('%s(%d) : Internal parsing error\n\t%s.\n' % ( filename, last.lineno, str(e))) def main(argv): nodes = [] parser = IDLParser(IDLLexer()) errors = 0 for filename in argv: filenode = ParseFile(parser, filename) if (filenode): errors += filenode.GetProperty('ERRORS') nodes.append(filenode) ast = IDLNode('AST', '__AST__', 0, 0, nodes) print('\n'.join(ast.Tree())) if errors: print('\nFound %d errors.\n' % errors) return errors if __name__ == '__main__': sys.exit(main(sys.argv[1:]))
{ "pile_set_name": "Github" }
0
Q: Calling Grep inside Java gives incorrect results while calling grep in shell gives correct results I've got a problem where calling grep from inside java gives incorrect results, as compared to the results from calling grep on the same file in the shell. My grep command (called both in Java and in bash. I escaped the slash in Java accordingly): /bin/grep -vP --regexp='^[0-9]+\t.*' /usr/local/apache-tomcat-6.0.18/work/Catalina/localhost/saccitic/237482319867147879_1271411421 Java Code: String filepath = "/path/to/file"; String options = "P"; String grepparams = "^[0-9]+\\t.*"; String greppath = "/bin/"; String[] localeArray = new String[] { "LANG=", "LC_COLLATE=C", "LC_CTYPE=UTF-8", "LC_MESSAGES=C", "LC_MONETARY=C", "LC_NUMERIC=C", "LC_TIME=C", "LC_ALL=" }; options = "v"+options; //Assign optional params if (options.contains("P")) { grepparams = "\'"+grepparams+"\'"; //Quote the regex expression if -P flag is used } else { options = "E"+options; //equivalent to calling egrep } proc = sysRuntime.exec(greppath+"/grep -"+options+" --regexp="+grepparams+" "+filepath, localeArray); System.out.println(greppath+"/grep -"+options+" --regexp="+grepparams+" "+filepath); inStream = proc.getInputStream(); The command is supposed to match and discard strings like these: 85295371616 Hi Mr Lee, please be informed that... My input file is this: 85aaa234567 Hi Ms Chan, please be informed that... 85292vx5678 Hi Mrs Ng, please be informed that... 85295371616 Hi Mr Lee, please be informed that... 85aaa234567 Hi Ms Chan, please be informed that... 85292vx5678 Hi Mrs Ng, please be informed that... 85295371616 Hi Mr Lee, please be informed that... 85295371616 Hi Mr Lee, please be informed that... 85295371616 Hi Mr Lee, please be informed that... 85295371616 Hi Mr Lee, please be informed that... 85295371616 Hi Mr Lee, please be informed that... 8~!95371616 Hi Mr Lee, please be informed that... 85295371616 Hi Mr Lee, please be informed that... 852&^*&1616 Hi Mr Lee, please be informed that... 8529537Ax16 Hi Mr Lee, please be informed that... 85====ppq16 Hi Mr Lee, please be informed that... 85291234783 a3283784428349247233834728482984723333 85219299222 The commands works when I call it from inside bash (Results below): 85aaa234567 Hi Ms Chan, please be informed that... 85292vx5678 Hi Mrs Ng, please be informed that... 85aaa234567 Hi Ms Chan, please be informed that... 85292vx5678 Hi Mrs Ng, please be informed that... 8~!95371616 Hi Mr Lee, please be informed that... 852&^*&1616 Hi Mr Lee, please be informed that... 8529537Ax16 Hi Mr Lee, please be informed that... 85====ppq16 Hi Mr Lee, please be informed that... 85219299222 However, when I call grep again inside java, I get the entire file (Results below): 85aaa234567 Hi Ms Chan, please be informed that... 85292vx5678 Hi Mrs Ng, please be informed that... 85295371616 Hi Mr Lee, please be informed that... 85aaa234567 Hi Ms Chan, please be informed that... 85292vx5678 Hi Mrs Ng, please be informed that... 85295371616 Hi Mr Lee, please be informed that... 85295371616 Hi Mr Lee, please be informed that... 85295371616 Hi Mr Lee, please be informed that... 85295371616 Hi Mr Lee, please be informed that... 85295371616 Hi Mr Lee, please be informed that... 8~!95371616 Hi Mr Lee, please be informed that... 85295371616 Hi Mr Lee, please be informed that... 852&^*&1616 Hi Mr Lee, please be informed that... 8529537Ax16 Hi Mr Lee, please be informed that... 85====ppq16 Hi Mr Lee, please be informed that... 85291234783 a3283784428349247233834728482984723333 85219299222 What could be the problem that will cause the grep called by Java to return incorrect results? I tried passing local information via the environment string array in runtime.exec, but nothing seems to change. Am I passing in the locale information incorrectly, or is the problem something else entirely? A: The single quotes are used by the shell, and not seen by grep. You should not add them in java. Also, you should use the exec(String[], String[]) method instead of concatenating the parameters, so you have control over the separation of the parameters. And i agree with the other comments saying you should do this in pure java instead of starting grep in a separate process.
{ "pile_set_name": "StackExchange" }
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/* XXXXX XXXXXX XXXXXXX XXX XXX XXXXXXX XXXXX XXX XXX XXX XXX XX XXX XXX XXX XXXXXXXX XXX XXX XXXXXXX XXX XXX XXX XXX XXX XXXXXXXX XXXXXXX XXX XXX XXX XXX XXX XXX XXXXXXXX XXX XXX XXX XXX XXX XXX XX XXXXX XXXXXXXX XXX XXX XXXXX XXX XXX XXXXXXX XXX XXX XXX XXXXX XXX .v2b XXXXX ____________________ + enzyme ..v2b + | nzm rxbot mod .. | | private release * | | 04.26.05 | +____________________+ ____________________ + code from .. + | bcuzz | | stoney | | x-lock | | ionix | | phatty | | nesespray | | rbot dev team | +____________________+ ____________________ + read .. + | the docs | | don't .. | | mass distribute | +____________________+ */ enum {REALNICK, CONSTNICK, LETTERNICK, COMPNICK, COUNTRYNICK, OSNICK}; typedef char * (*rnref)(char *strbuf); typedef struct RNICK { char name[10]; int type; rnref rnfunc; } RNICK; #ifndef NO_REALNICK char *rndnickreal(char *strbuf); #endif char *rndnickconst(char *strbuf); char *rndnickletter(char *strbuf); char *rndnickcomp(char *strbuf); char *rndnickcountry(char *strbuf); char *rndnickos(char *strbuf); char *prefixnick(char *strbuf); char *rndnick(char *strbuf, int type=LETTERNICK, BOOL prefix=FALSE, char *name=NULL);
{ "pile_set_name": "Github" }
0.024406
Åbo IFK Åbo IFK (or ÅIFK for short) is a sports club from Turku, Finland. The club was founded in 1908, and originally represented the Swedish-speaking minority of Turku/Åbo. Background The greatest successes of ÅIFK have come in football where it has won three Finnish championship titles, in 1910, 1920 and 1924. It has played a total of 9 seasons in the Finnish premier division Mestaruussarja, the last occasion in 1967. It also won the Finnish Cup in 1965 and participated in the UEFA Cup Winners' Cup in the 1966–67 season, going out in the first round. Currently the ÅIFK football team is playing in the third tier Kakkonen. ÅIFK has also fared well in handball with both its men's and women's teams playing at the national top level at the moment. Currently the club has activities in football, handball, athletics and bowling. The highest ever attendance for a ÅIFK match was in 1967 when 5,861 people attended the home game with Turun Palloseura. Football honours Finnish Championship: Winners (3): 1910, 1920, 1924 Runners-up (5): 1911, 1913, 1915, 1916, 1917 Finnish Cup: Winners (1): 1965 (ÅIFK – TPS 1–0) Divisional movements since 1930 Top Level (9 seasons): 1930, 1932–35, 1963–65, 1967 Second Level (13 seasons): 1931, 1936, 1938–39, 1943/44-45, 1961–62, 1966, 1968–70, 2000 Third Level (34 seasons): 1937, 1940-1941, 1945-1949, 1952, 1954-1960, 1971, 1986, 1988–89, 1991, 1994–96, 1998–99, 2001, 2008–2015 Fourth Level (26 seasons) : 1950-1951, 1953, 1972-1982, 1985, 1987, 1990, 1992-1993, 1997, 2002-2007, 2016 to current Fifth Level (2 seasons) : 1983-1984 Season to season Club structure ÅIFK runs 2 men's teams, 1 veteran's teams, 7 boys teams, 1 ladies team, 4 girls teams and a Footballschool for girls. 2010 season For the current season Åbo IFK are competing in Section B of the Kakkonen. This is the third tier of the Finnish football system. In 2009 the team finished in ninth position in their Kakkonen section. Åbo IFK 2 are participating in the Nelonen administered by the Turku SPL. This team has taken over a club called Goose Park Rangers FC that competed at this level in 2009. Åbo IFK 3 are competing in the Vitonen administered by the Turku SPL. Last season Åbo IFK 2 were promoted to this level from the Kutonen. References External links Official Website Suomen Cup Category:Football clubs in Finland Category:Sport in Turku Category:Association football clubs established in 1908 Category:Bandy clubs established in 1908 Category:1908 establishments in Finland Category:Defunct bandy clubs in Finland Category:Multi-sport clubs in Finland
{ "pile_set_name": "Wikipedia (en)" }
0
More than 70 tyrosine kinase (TK) fusion genes have been identified in myeloid neoplasms as a consequence of reciprocal translocations or other genomic rearrangements. These TK fusions are generally primary drivers of myeloproliferation and important therapeutic targets, as well as being major criteria for the diagnosis of specific disorders. For example, chronic myeloid leukemia is defined by the presence of *BCR-ABL1*, and myeloid/lymphoid neoplasms with eosinophilia are defined by fusions involving *PDGFRA*, *PDGFRB*, *FGFR1* or *PCM1-JAK2*.[@R1] Other TK fusions have been described in patients with various subtypes of myeloproliferative neoplasms (MPN) or myelodysplastic/myeloproliferative neoplasms (MDS/MPN). Most of these individuals have pronounced eosinophilia,[@R2] but occasional cases have other phenotypes such as polycythemia vera (PV) or systemic mastocytosis.[@R2], [@R3] Apart from *FIP1L1-PDGFRA,* which is formed by a small deletion at 4q12,[@R4] TK fusions are almost always associated with visible karyotypic abnormalities. Despite their apparent prominence in the literature, TK fusions are in fact uncommon and the pathogenesis of the majority of MPN with eosinophilia (MPN-eo) remains unexplained. Some TK-fusion negative cases test positive for *KIT* D816V or *JAK2* V617F, whereas others are positive for mutations in a range of genes associated with myeloid disorders such as *TET2*, *ASXL1*, *EZH2* and *SETBP1*.[@R5],[@R6],[@R7] We hypothesized that hitherto undetected cryptic TK fusion genes may drive MPN-eo as well as other disorders such as *JAK2*-unmutated PV. We used RNAseq to search for TK fusion genes in cases with MPN-eo or hypereosinophilia of unknown significance (HE~US~) with a normal karyotype (n=14), PV with low or normal erythropoietin levels that tested negative for MPN phenotype driver mutations (n=6) and cell lines that were derived from MPN or MDS patients that had transformed to acute myeloid leukemia (F-36P, ELF-153, FKH-1, GDM-1, SKK-1, SKM-1). RNA extraction, polyA+ RNA-Seq library preparation, stranded RNAseq protocol and 100bp paired-end sequencing was performed with multiplexing for a minimum of 75 million reads/sample using an Illumina HiSeq 2000. Bowtie and TopHat-Fusion were used to align reads, resolve splice junctions, identify and filter potential TK fusions as previously described.[@R8] Confirmation and screening of fusions was performed by RT-PCR and Sanger sequencing ([Supplementary Table 1](#SD1){ref-type="supplementary-material"}). Of the 20 patient samples, two novel TK fusions were identified. In frame *DIAPH1-PDGFRB* and *ZMYM2-FLT3* fusion mRNAs ([Figure 1](#F1){ref-type="fig"}; [Supplementary Figures 1 and 2](#SD1){ref-type="supplementary-material"}) were found in single patients with MPN-eo. None of the cases were positive for *TNIP1-PDGFRB*, a recently described cryptic fusion in MPN-eo.[@R9] Unusually, the fusion breakpoints in our cases fell within exons of both the partner and TK genes. No TK fusions were detected in the PV cases, but the FKH-1 and SKK-1 cell lines were positive for *ETV6-ABL1* and *ETV6-NTRK3*, respectively ([Supplementary Figure 3](#SD1){ref-type="supplementary-material"}). Although these fusions have been described previously, neither line was known to be positive and the presence of these fusions was not suspected on the basis of the karyotype. [@R10], [@R11] *DIAPH1* and *PDGFRB* are located 8.5Mb apart at 5q31.3 and 5q32, respectively. They are both oriented from telomere to centromere and thus the fusion presumably arose as a consequence of a tandem duplication or a translocation t(5;5)(q31.3;q32), both of which would be difficult to detect by routine cytogenetics. The affected patient, a 37-year-old male, was diagnosed with an MPN-eo and contemporaneous T-cell lymphoblastic lymphoma, most likely representing extramedullary lymphoid blast phase [@R12]. The karyotype was normal. The patient received intensive chemotherapy and achieved complete hematological remission (CHR) with disappearance of the lymphadenopathy. Two weeks later he developed leukocytosis (119x10^9^/L) with significant eosinophilia (21x10^9^/L), hepatosplenomegaly but with no recurrence of lymphadenopathy. Consolidation intensive chemotherapy treatment was started without response. Molecular analyses revealed overexpression of *PDGFRB* [@R13] and the *DIAPH1-PDGFRB* fusion was subsequently identified by RNAseq analysis. He received imatinib 100 mg/day and achieved CHR within 4 weeks but died due to a rapidly progressive neurodegenerative disorder at month 27 whilst still in complete remission. To test if *DIAPH1-PDGFRB* is a recurrent abnormality, we screened 50 additional cases with MPN-eo by RT-PCR but did not identify any further positive cases. *ZMYM2* and *FLT3* are both located at 13q12 and are in opposite orientations. *ZMYM2-FLT3* is thus predicted to arise as a consequence of an 8Mb inversion ([Supplementary Figure 3](#SD1){ref-type="supplementary-material"}). *ZMYM2* is the fourth gene reported to fuse to *FLT3* in myeloid neoplasms[@R2] but the first *FLT3* fusion that is cytogenetically cryptic. We screened 105 additional cases with MPN-eo, HE~US~ or other atypical MPN by RT-PCR. One additional positive case was detected, with similar but not identical breakpoints to the initial case ([Figure 1](#F1){ref-type="fig"}). PCR analysis of genomic DNA for the second case (DNA was not available from Case 1) revealed that the cDNA and genomic breakpoints were identical, indicating the formation of a fusion exon by the inversion. We note that a third case with *ZMYM2-FLT3* has been reported recently in a patient with *BCR-ABL1*-like acute lymphoblastic leukemia.[@R14] Both cases with *ZMYM2-FLT3* had MPN-eo. Case 1, a 48 year old female, presented with leukocytosis (30 x 10^9^/L), eosinophilia (2 x 10^9^/L, elevated serum tryptase (37µg/L), splenomegaly and a hypercellular bone marrow (BM) with increased numbers of loosely scattered mast cells. Cytogenetics was normal, *FIP1L1-PDGFRA*, *KIT* D816V and *JAK2* V617F were all negative and no relevant mutations were identified by myeloid panel analysis (28 genes). After 10 months, she progressed to myeloid blast phase. Because the disease was resistant to AML-induction chemotherapy, an allogeneic peripheral blood stem cell transplant was performed from an unrelated donor 13 months after diagnosis. She died 6 months later from chronic graft versus host disease and septic shock; the *ZMYM2-FLT3* fusion was identified post mortem. Case 2, a 47 year old male, presented with eosinophilia (4.7 x 10^9^/L), elevated serum tryptase (42µg/L) and a hypercellular BM. Cytogenetics was normal and *FIP1L1-PDGFRA*, *KIT* D816V and *JAK2* V617F were all negative. There was no response to steroids or hydroxyurea. Following the finding of *ZMYM2-FLT3* positivity, treatment with sunitinib off-label at 50mg/day was commenced. Blood counts started to improve from day 4 and normalized after 3 weeks. During a pause of 3 weeks due to pulmonary infection, leukocytes/eosinophils rapidly increased, but normalized again within weeks after restart of sunitinib, initially at a dose of 25mg/day and then subsequently 35mg/day. The patient has been maintained on sunitinib for 10 months (since re-start) and remains in CHR ([Figure 2](#F2){ref-type="fig"}). In conclusion, we have found that *ZMYM2-FLT3* and *DIAPH1-PDGFRB* fusion genes are novel, cytogenetically cryptic and therapeutically targetable abnormalities in MPN-eo, and are thus reminiscent of *FIP1L1-PDGFRA* positive myeloid neoplasms. Due to their extensive diversity and clinical importance, we believe that genome wide or targeted RNAseq is rapidly becoming the method of choice to detect rare TK fusions. Supplementary Material {#SM} ====================== This work was supported by grant 13002 to NCPC from Bloodwise **Conflicts of interest** NCPC has received honoraria and research support from Novartis, and honoraria from Pfizer. AR has received honoraria and research support from Novartis. ![Fusion junctions for *DIAPH1-PDGFRB* and *ZMYM2-FLT3* identified by RNAseq analysis (panels A and B), plus the additional *ZMYM2-FLT3* positive case detected by RT-PCR screening.](emss-73457-f001){#F1} ![*ZMYM2-FLT3* fusion (case 2): longitudinal measurements of absolute leucocytes and eosinophil values during treatment with prednisolone (PRD in mg/day), hydroxyurea (HU in mg/day), and sunitinib (in mg/day).](emss-73457-f002){#F2}
{ "pile_set_name": "PubMed Central" }
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Q: Receive transformation map function to send into `List<>.mapNotNull()` Im trying to write a function like transform that receives a function that will be used inside of mapNotNull but I cant find a way to do it. Example val items: List<String?> = listOf(null, "cosa") fun transform(transformer: (String) -> String?) { items.mapNotNull(transformer) // <-------------------------------------- THIS DOES NOT COMPILE } fun main() { val items: List<String?> = listOf(null, "cosa") val transformer: (String) -> String? = { null } val map = transform(transformer) print(map) } You can check how this works here: play.kotlinlang How can I declare the parameter of fun transform to be able to pass it inside of the mapNotNull ? A: The mapNotNull function is defined as: public inline fun <T, R : Any> Iterable<T>.mapNotNull(transform: (T) -> R?): List<R> in other words, the type of the parameter to the transform lambda is T, where T is the type of the Iterable being operated on. In your case, your iterable is a List of type String?. Therefore, you need to declare your transformer as type (String?) -> String?, and only the non-null results of that transform will be included in the result. To update the code you supplied on play.kotlinlang, with a few additional modifications to make the type declarations a bit more idiomatic -- note, I've left the code mostly as-is, despite the odd use of the additional transform function: val items = listOf<String?>(null, "cosa") fun transform (transformer: (String?) -> String?): List<String> { return items.mapNotNull(transformer) } fun main() { val items = listOf<String?>(null, "cosa") val transformer: (String?) -> String? = { // this of course means the output of transform will always be empty null } val map = transform(transformer) print(map) }
{ "pile_set_name": "StackExchange" }
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Hot list of gay men in panties videos Law S Dirty Panties Crossdresser cums on my panties and cock. The Little Then Licking Them Panties undies ass oil and cum compilation. Men Who Full Length We Pretty Panty Cock Play.
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One Exercise, Four Minutes, 28 Days, New Body A fit body requests practicing frequently and eating a sound eating routine. Be that as it may, the vast majority are not ready to do this because of their boisterous calendar, so they’re searching for an approach to get fit immediately. Fortunately, there is a solitary exercise which will enable you to get fit in 28 days – the board! The board is a capable exercise which reinforces your arm, leg and butt cheek muscles and melts the overabundance fat superior to some other exercise! The board is basically holding up in the push-up position. Plank challenge The board challenge is a four-week challenge which builds the span of the activity bit by bit. Keeping in mind the end goal to perform it, take after these means: Begin by holding the position for 20 seconds, at that point increment the term step by step. On the most recent day of the test, you have to play out a 4-minute board! What’s the right plank position? The right board position includes resting your body weight staring you in the face and toes while keeping a straight line with your back. Take a full breath when you begin, and crush the abs. Ensure your weight is legitimately conveyed so you can keep the adjust and strain the glutes. 28-day plank challenge! Day 1 & 2: 20 seconds Day 3& 4: 30 seconds Day 5: Increase to 40 seconds Day 6: Take rest Day 7 & 8: Start with 45 seconds Day 9,10 & 11: 60 seconds Day 12: Increase to 90 seconds Day 13: Take rest Day 14 & 15: Again begin with 90 seconds Day 16 & 17: 120 seconds Day 18: Increase to 150 seconds Day 19: Take rest Day 20 & 21: 150 seconds Day 22 & 23: 180 seconds Day 24: 210 seconds Day 25: Take rest Day 26: Again begin with 210 seconds Day 27: Increase to 240 seconds Day 28: As long as possible for you You’ll see that the plank really works when you finish the challenge! Start today and get your body in shape!
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This sexy Japanese woman is accosted by a large group of men on the subway. They hold her down and grope at her boobs and tits. The men jerk off their cocks and cum all over the pantyhose. she has to walk home from the station covered in jizz.
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Teen Stretches Ass Teen Girl Black Angel Stretches Ass For the First Time (First Anal Quest)
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Duration and variability of normal pregnancy. Implications for clinical practice. To estimate the true biologic length and variability of normal pregnancy on the basis of early ultrasonography and to assess the implications for clinical practice. We reviewed the clinical case notes on 476 women whose pregnancies were routinely dated by measurement of the biparietal diameter in the second trimester. After excluding abnormal cases, 355 pregnancies were available for analysis. The duration of pregnancy was studied in relation to maternal characteristics and also to induction of labor for postmaturity. The mean +/- SD for the normal duration of pregnancy were 279.7 and 7.4 days. The length of pregnancy was weakly related to maternal height. Of the 41 women whose labor was induced for postmaturity, only 7 were truly postmature when gestational age was determined by sonography. The current definitions of preterm and postterm may need to be revised to allow the increased precision achieved by ultrasound. Inclusion of menstrual data for the determination of gestational age may lead to incorrect clinical decisions.
{ "pile_set_name": "PubMed Abstracts" }
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she gets the best multiple squirt orgasm of her life after a fast fuck
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Description 1. Micro Plain fabric is a durable fabric. It holds its shape, along with creases and folds, making it popular for clothing. It’s easy to care 2. Laminated Fabric: – We use laminated fabric for extra protection against Wind and Rain, waterproof layer is extremely thin and has less effect on the natural look and feel of the fabric. 3. DWR Fabric: – DWR (durable water repellent) is a coating added to fabrics at the factory to make them water-resistant. 4. WP Fabric: – Waterproof fabrics are fabrics that are inherently, or have been treated to become, resistant to penetration by water and wetting. 5. No smell or no maintenance to keep it dry or store as dry garment etc., no need to keep powder inside to keep it for long period. 6. Light weight with durability, non-Hazardous & non- injurious to Health 7. Seam Seal Tape: – On stitching we use Hot Air Seam Seal Tape instead of Gumming Tape, it is done by 700 C for make it 100% waterproof, entire width of the tape melted/adhered to the seam area to make sure that you have no gaps in your waterproofing. 8. Combinations of Contrast colour may get change in rain suit as per stock available. 9. Product colour may slightly vary due to photographic lighting sources or your monitor settings.
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A Schnurri/Mad/Medea complex attenuates the dorsal-twist gradient readout at vnd. Morphogen gradients are used in developing embryos, where they subdivide a field of cells into territories characterized by distinct cell fate potentials. Such systems require both a spatially-graded distribution of the morphogen, and an ability to encode different responses at different target genes. However, the potential for different temporal responses is also present because morphogen gradients typically provide temporal cues, which may be a potential source of conflict. Thus, a low threshold response adapted for an early temporal onset may be inappropriate when the desired spatial response is a spatially-limited, high-threshold expression pattern. Here, we identify such a case with the Drosophila vnd locus, which is a target of the dorsal (dl) nuclear concentration gradient that patterns the dorsal/ventral (D/V) axis of the embryo. The vnd gene plays a critical role in the "ventral dominance" hierarchy of vnd, ind, and msh, which individually specify distinct D/V neural columnar fates in increasingly dorsal ectodermal compartments. The role of vnd in this regulatory hierarchy requires early temporal expression, which is characteristic of low-threshold responses, but its specification of ventral neurogenic ectoderm demands a relatively high-threshold response to dl. We show that the Neurogenic Ectoderm Enhancer (NEE) at vnd takes additional input from the complementary Dpp gradient via a conserved Schnurri/Mad/Medea silencer element (SSE) unlike NEEs at brk, sog, rho, and vn. These results show how requirements for conflicting temporal and spatial responses to the same gradient can be solved by additional inputs from complementary gradients.
{ "pile_set_name": "PubMed Abstracts" }
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2017 Dalian Women's Tennis Open – Singles Kristýna Plíšková was the defending champion, but chose not to participate. Kateryna Kozlova won the title after defeating Vera Zvonareva 6–4, 6–2 in the final. Seeds Draw Finals Top half Bottom half Qualifying Seeds Qualifiers Lucky losers Qualifying draw First Qualifier Second Qualifier Third Qualifier Fourth Qualifier References Main Draw Qualifying Draw Dalian Women's Tennis Open - Singles 2017
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Telephone numbers in Algeria Calling formats To call in Algeria, the following format is used: 0 THE-AREA-CODE xx xx xx Calls within an area code 'The area code is a 2 digits number ex: 21,41,46' 021 xx xx xx Calls to Algiers from other area codes +213 yy xx xx xx Calls from outside Algeria 'yy is the area code' To call a mobile phone in Algeria ; use this format: +213 Y xx xx xx xx calls from outside Algeria Y is the Operator code ; 5 for ooredoo ,6 for Mobilis , 7 for Djezzy 0 Y xx xx xx xx To call any mobile phone number from Algeria List of area codes in Algeria References External links ITU allocations list Algerian dial codes - accessed 26 April 2010. New plan Algerian Tourism code list Algeria Category:Telecommunications in Algeria Telephone numbers
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Q: AWS Glue Dynamobd Connection Timed out Error import boto3 dynamodb = boto3.resource('dynamodb', region_name="us-east-1") table = dynamodb.Table('user_logs') response = table.scan() I got the following error for the above aws glue job script botocore.vendored.requests.exceptions.ConnectTimeout: HTTPSConnectionPool(host='dynamodb.us-east-1.amazonaws.com', port=443): Max retries exceeded with url: / (Caused by ConnectTimeoutError(<botocore.awsrequest.AWSHTTPSConnection object at 0x7f7c58942b50>, 'Connection to dynamodb.us-east-1.amazonaws.com timed out. (connect timeout=60)')) Any ideas why this is happening? A: if your glue script is pointing out to VPC then you need to create VPC endpoint for your configured VPC. go to AWS VPC > end point > create dynamo db end point for your VPC and then try.
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Q: Best way to get intersection of keys of two objects? I have two object literals like so: var firstObject = { x: 0, y: 1, z: 2, a: 10, b: 20, e: 30 } var secondObject = { x: 0, y: 1, z: 2, a: 10, c: 20, d: 30 } I want to get the intersection of the keys these two object literals have like so: var intersectionKeys = ['x', 'y', 'z', 'a'] I can obviously do a loop and see if a key with the same name exists in the other object, but I am wondering if this would be a good case for some functional programming and map / filter / reduce usage? I myself have not done that much functional programming, but I have a feeling, that there could exist a clean and clever solution for this problem. A: A solution without indexOf. var firstObject = { x: 0, y: 1, z: 2, a: 10, b: 20, e: 30 }, secondObject = { x: 0, y: 1, z: 2, a: 10, c: 20, d: 30 }; function intersection(o1, o2) { return Object.keys(o1).concat(Object.keys(o2)).sort().reduce(function (r, a, i, aa) { if (i && aa[i - 1] === a) { r.push(a); } return r; }, []); } document.write('<pre>' + JSON.stringify(intersection(firstObject, secondObject), 0, 4) + '</pre>'); Second attempt with O(n). var firstObject = { x: 0, y: 1, z: 2, a: 10, b: 20, e: 30 }, secondObject = { x: 0, y: 1, z: 2, a: 10, c: 20, d: 30 }; function intersection(o1, o2) { return Object.keys(o1).filter({}.hasOwnProperty.bind(o2)); } document.write('<pre>' + JSON.stringify(intersection(firstObject, secondObject), 0, 4) + '</pre>'); A: The given answers are nice and astonishing but there could be a problem in void's answer and that is: "What if one of property values intentionally set to undefined." Nina's answer is good (really fantastic) but as we are in era of fun JavaScript I think mine wont be too bad: var a = { x: undefined, y: 1, z: 2, a: 10, b: 20, e: 30 } var b = { x: 0, y: 1, z: 2, a: 10, c: 20, d: 30 } function intersect(o1, o2){ return Object.keys(o1).filter(k => k in o2) } document.write('<pre>' + JSON.stringify(intersect(a, b)) + '</pre>'); Update onalbi mentioned some performance issue in comments which is rational and therefore the code bellow seems to be a better way to handle the problem: var a = { x: undefined, y: 1, z: 2, a: 10, b: 20, e: 30}; var b = { x: 0, y: 1, z: 2, a: 10, c: 20, d: 30}; function intersect(o1, o2) { const [k1, k2] = [Object.keys(o1), Object.keys(o2)]; const [first, next] = k1.length > k2.length ? [k2, o1] : [k1, o2]; return first.filter(k => k in next); } document.write('<pre>' + JSON.stringify(intersect(a, b)) + '</pre>'); A: The procedure i will suggest is: Get the array of keys using Object.keys() for one of the objects. Find the intersection the array using .filter and checking if the second object contains a key matching the first array. var firstObject = { x: 0, y: 1, z: 2, a: 10, b: 20, e: 30 } var secondObject = { x: 0, y: 1, z: 2, a: 10, c: 20, d: 30 } function getIntKeys(obj1, obj2){ var k1 = Object.keys(obj1); return k1.filter(function(x){ return obj2[x] !== undefined; }); } alert(getIntKeys(firstObject, secondObject));
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FILED NOT FOR PUBLICATION OCT 21 2015 MOLLY C. DWYER, CLERK UNITED STATES COURT OF APPEALS U.S. COURT OF APPEALS FOR THE NINTH CIRCUIT FATIMA DEL CARMEN RIVAS MIER No. 12-72594 Y TERAN, Agency No. A087-183-891 Petitioner, v. MEMORANDUM* LORETTA E. LYNCH, Attorney General, Respondent. On Petition for Review of an Order of the Board of Immigration Appeals Submitted October 14, 2015** Before: SILVERMAN, BERZON, and WATFORD, Circuit Judges. Fatima del Carmen Rivas Mier y Teran, a native and citizen of Mexico, petitions for review of the Board of Immigration Appeals’ (“BIA”) order dismissing her appeal from an immigration judge’s decision denying her application for asylum, withholding of removal, and relief under the Convention * This disposition is not appropriate for publication and is not precedent except as provided by 9th Cir. R. 36-3. ** The panel unanimously concludes this case is suitable for decision without oral argument. See Fed. R. App. P. 34(a)(2). Against Torture (“CAT”). We have jurisdiction under 8 U.S.C. § 1252. We review for substantial evidence the agency’s factual findings. Zehatye v. Gonzales, 453 F.3d 1182, 1184-85 (9th Cir. 2006). We deny the petition for review. Rivas Mier y Teran does not contend she suffered past persecution in Mexico, but fears harm based on the kidnapping of her uncle in 1990, and related threats to harm his family. Even if Rivas Mier y Teran’s asylum application was timely, substantial evidence supports the agency’s determination that she failed to establish an objectively reasonable fear of future persecution. See Hakeem v. INS, 273 F.3d 812, 816 (9th Cir. 2001) (“[a]n applicant’s claim of persecution upon return is weakened, even undercut, when similarly-situated family members continue to live in the country without incident”); see also Nagoulko v. INS, 333 F.3d 1012, 1018 (9th Cir. 2003) (possibility of future persecution too speculative to establish objectively reasonable fear). Thus, Rivas Mier y Teran’s asylum claim fails. Because Rivas Mier y Teran failed to meet the lower burden of proof for asylum, her claim for withholding of removal necessarily fails. See Zehatye, 453 F.3d at 1190. Finally, substantial evidence supports the agency’s denial of Rivas Mier y Teran’s CAT claim because she failed to demonstrate that it is more likely than not 2 12-72594 she would be tortured by, or with the consent or acquiescence of the government if returned to Mexico. See Silaya v. Mukasey, 524 F.3d 1066, 1073 (9th Cir. 2008). The record does not support Rivas Mier y Teran’s contention that the BIA failed to consider the background evidence. PETITION FOR REVIEW DENIED. 3 12-72594
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Literature Translation Institute of Korea Literature Translation Institute of Korea (, LTI Korea, formerly known as Korean Literature Translation Fund) was founded in 1996 by the Government of South Korea with the aim of promoting Korean literature and culture overseas in order to contribute to the global culture. LTI Korea sponsors translation and publication to promote high-quality translation of Korean literature, and is pushing forward with various overseas exchange programs to strengthen the export base for Korean literature and establish a network for Korean and overseas publishers. It also works to foster professional translators to enhance the capacity of translation of Korean literature. History 1996 Korean Literature Translation Fund founded. 2001 Renamed as Korean Literature Translation Institute, organization expanded. Dr. Park Huan-Dok appointed as the founding president. 2003 Dr. Chin Hyung Joon appointed to succeed Dr. Park as LTI Korea’s second president. 2005 Declaration of a revision in the Culture and Arts Promotion Law. Status changed to a special corporation 2006 Dr. Yoon Jikwan appointed as the third president of LTI Korea. 2009 Dr. Joo Youn Kim appointed as the fourth president of LTI Korea. 2010 Change of the law authorizing LTI Korea (Publishing Industry Promotion Act §20(2) 2012 Dr. Kim, Seong-kon appointed as the fifth and sixth president of LTI Korea. 2016 LTI Korea’s foundation ordinance brought under the Literature Promotion Act, Article 13 2018 Kim Sa-in appointed as the seventh president of LTI Korea. Programs LTI Korea supports various programs designed to promote awareness of Korean literature and culture abroad. Each program focuses on a specific goal dedicated to building an understanding of Korean literature and culture overseas. Translation grants program Every quarter, LTI Korea selects and supports translations of various Korean works of literary fiction, poetry, plays, non-fiction, children’s and YA books, genre fiction, and graphic novels. Each application is judged for the quality of the translation and the original work. From 2014, LTI Korea does not support the complete translation of the original work. LTI Korea initially provides a grant for the translation of a sample, and the grant for the remainder of the work will be provided after the translator and the author sign a publication contract with an international publisher. Publication grants program Publication grants are offered to foreign publishers who have acquired copyrights to works that were translated with the support from LTI Korea. Since 2014, LTI Korea provides both translation and publication grants for foreign publishers who have acquired the rights to publish translated Korean literary works. Support for international cooperation In an effort to build a strong network between the translators, writers, and people engaged in the publishing business both inside and outside of Korea, LTI Korea holds and participates in various cultural events. The LTI Korea Forum was held in the US, France, Spain, China, Germany and Japan in 2011 with the most recent forum being held in Berlin, Germany in June 2012. Another significant event hosted by LTI Korea is Seoul International Writers’ Festival which is held once every other year. In the festival held in 2010, 24 prominent writers from all over the world got together and had reading and talking sessions under the theme "Fantasy and Empathy". Among the writers that participated were Korean writers Bae Suah, Park Hyoung-su, Jeong Chan, Pyun Hye-young, Kim Min-jeong, Kim Haeng-sook, Choi Seoung-ho, Ra Hee-duk, Kim Nam-joong, and Kim Hye-jin. Korean-American writer Min Jin Lee, who won the New York Times Editor’s Choice award for her debut novel “Free Food for Millionaires,” and Pulitzer Prize winner Junot Diaz were also among the list of participants. Education program LTI Korea holds translation academies in English, French, German, Spanish, Chinese, Japanese, and Russian. Designed to be a translator-training program, it currently teaches nearly 100 students, with the aim of expanding the number to 200. Aside from nurturing prospective translators, LTI Korea encourages new and existing translators by awarding them with Korean Literature Translation Awards. Another form of effort to promote the exchange of information is LTI Korea’s International Workshop on Translation and Publication of Korean Literature. The 11th International Workshop for Translation and Publication of Korean Literature discussed the globalization of Korean literature in times where Korean culture is receiving more attention than it ever did in the past, due to the popularity of K-pop singers. Information service Through the establishment and implementation of the LTI Korea medium and long-term strategy, its information services provide comprehensive information regarding Korean literature and publications and overseas publishing markets. By creating content relevant to the aforementioned in keeping with the new media environment, the information service ensures that LTI Korea's information services are integrated and up-to-date. LTI Korea library Opened to the public in 2007, the LTI Korea Library is the first library in Korea which contains collections of Korean books translated into various languages and published overseas. In addition to the translated editions of Korean books, it also collects periodicals on Korean literature, books on translation as well as CD's, DVDs and video tapes on Korean literature. Periodicals Korean Literature Now (formerly _list: Books from Korea), also known as KLN is an English literary magazine showcasing Korean literature and writers through interviews, excerpts, features, translators’ notes, and reviews of Korean literature published overseas. KLN has a circulation of about 5,000 including foreign publishers, agencies, Korean Studies programs, university libraries, cultural centers, and exclusive hotels in the Seoul-Gyeonggi-Incheon area. Korean literature in translation LTI Korea Library continues to collect and provide bibliographies of Korean books translated and published in more than 40 languages worldwide. Location Yeongdong-daero 112-gil 32 (Samseong-dong), Gangnam-gu, Seoul, Republic of Korea References External links Literature Translation Institute of Korea official website Korean Literature Now magazine Seoul International Writers' Festival website Translation Academy website LTI Korea Digital Library Category:Korean language Category:Korean literature
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#include "halp.h" #include "arccodes.h" #include "flash8k.h" #define I28F008SA_DEVICE_SIZE 0x100000 #define SET_READ_ARRAY 0xff #define SET_BYTE_WRITE 0x40 #define SET_ERASE_BLOCK 0x20 #define CONFIRM_ERASE_BLOCK 0xd0 #define READ_STATUS 0x70 #define RESET_STATUS 0x50 #define ID_REQUEST 0x90 #define MANUFACTURER_ID 0x89 #define DEVICE_ID 0xa2 #define BLOCK_SIZE 0x10000 #define BLANK_DATA 0xff #define TIMEOUT_VALUE 5000000 #define STATUS_READY 0x80 #define STATUS_ERASE_SUSP 0x40 #define STATUS_ERASE_ERR 0x20 #define STATUS_WRITE_ERR 0x10 #define STATUS_VPP_LOW 0x08 #define STATUS_CMD_SEQ_ERR (STATUS_WRITE_ERR | STATUS_READ_ERR) // // Local function prototypes // PFLASH_DRIVER I28F008SA_Initialize( IN PUCHAR NvRamPtr ); ARC_STATUS I28F008SA_SetReadMode( IN PUCHAR Address ); ARC_STATUS I28F008SA_WriteByte( IN PUCHAR Address, IN UCHAR Data ); ARC_STATUS I28F008SA_EraseBlock( IN PUCHAR Address ); ARC_STATUS I28F008SA_CheckStatus( IN PUCHAR Address, FLASH_OPERATIONS Operation ); PUCHAR I28F008SA_BlockAlign( IN PUCHAR Address ); UCHAR I28F008SA_ReadByte( IN PUCHAR Address ); BOOLEAN I28F008SA_OverwriteCheck( IN UCHAR OldData, IN UCHAR NewData ); ULONG I28F008SA_BlockSize( IN PUCHAR Address ); ULONG I28F008SA_GetLastError( VOID ); static VOID I28F008SA_SetLastError( ULONG FlashStatus ); FLASH_DRIVER I28F008SA_DriverInformation = { "Intel 28F008SA", I28F008SA_SetReadMode, // SetReadModeFunction I28F008SA_WriteByte, // WriteByteFunction I28F008SA_EraseBlock, // EraseBlockFunction I28F008SA_BlockAlign, // AlignBlockFunction I28F008SA_ReadByte, // ReadByteFunction I28F008SA_OverwriteCheck, // OverwriteCheckFunction I28F008SA_BlockSize, // BlockSizeFunction I28F008SA_GetLastError, // GetLastErrorFunction I28F008SA_DEVICE_SIZE, // DeviceSize BLANK_DATA // ErasedData }; static ULONG I28F008SA_LastError; PFLASH_DRIVER I28F008SA_Initialize( IN PUCHAR NvRamPtr ) { PFLASH_DRIVER ReturnDriver = NULL; UCHAR ManufacturerID; UCHAR DeviceID; NvRamPtr = I28F008SA_BlockAlign(NvRamPtr); WRITE_CONFIG_RAM_DATA(NvRamPtr, ID_REQUEST); ManufacturerID = READ_CONFIG_RAM_DATA(NvRamPtr); DeviceID = READ_CONFIG_RAM_DATA((PUCHAR)((ULONG)NvRamPtr + 1)); if ((ManufacturerID == MANUFACTURER_ID) && (DeviceID == DEVICE_ID)) { I28F008SA_LastError = 0; I28F008SA_SetReadMode(NvRamPtr); ReturnDriver = &I28F008SA_DriverInformation; } return ReturnDriver; } ARC_STATUS I28F008SA_SetReadMode( IN PUCHAR NvRamPtr ) { WRITE_CONFIG_RAM_DATA(NvRamPtr, SET_READ_ARRAY); HalpMb(); return ESUCCESS; } ARC_STATUS I28F008SA_WriteByte( IN PUCHAR NvRamPtr, IN UCHAR Data ) { ARC_STATUS ReturnStatus; I28F008SA_SetReadMode(NvRamPtr); WRITE_CONFIG_RAM_DATA(NvRamPtr, SET_BYTE_WRITE); WRITE_CONFIG_RAM_DATA(NvRamPtr, Data); ReturnStatus = I28F008SA_CheckStatus(NvRamPtr, FlashByteWrite); I28F008SA_SetReadMode(NvRamPtr); return ReturnStatus; } ARC_STATUS I28F008SA_EraseBlock ( IN PUCHAR NvRamPtr ) { ARC_STATUS ReturnStatus; WRITE_CONFIG_RAM_DATA(NvRamPtr, SET_ERASE_BLOCK); WRITE_CONFIG_RAM_DATA(NvRamPtr, CONFIRM_ERASE_BLOCK); ReturnStatus = I28F008SA_CheckStatus(NvRamPtr, FlashEraseBlock); I28F008SA_SetReadMode(NvRamPtr); return ReturnStatus; } ARC_STATUS I28F008SA_CheckStatus ( IN PUCHAR NvRamPtr, IN FLASH_OPERATIONS Operation ) { ARC_STATUS ReturnStatus = EIO; ULONG Timeout; UCHAR FlashStatus; // // Keep reading the status until the device is done with its // current operation. // Timeout = TIMEOUT_VALUE; do { WRITE_CONFIG_RAM_DATA(NvRamPtr, READ_STATUS); FlashStatus = READ_CONFIG_RAM_DATA(NvRamPtr); KeStallExecutionProcessor(1); Timeout--; } while (((FlashStatus & 0x80) == 0) && (Timeout > 0)); // // Check the status for the operation requested. // switch(Operation) { case FlashByteWrite: if ((FlashStatus & 0x18) == 0) { ReturnStatus = ESUCCESS; } else { I28F008SA_SetLastError(FlashStatus & 0x18); } break; case FlashEraseBlock: if (((FlashStatus & 0x28) == 0) && ((FlashStatus & 0x30) != 0x30)) { ReturnStatus = ESUCCESS; } else { I28F008SA_SetLastError(FlashStatus & 0x28); } break; } if ((FlashStatus & 0x80) == 0) { ReturnStatus = EIO; I28F008SA_SetLastError(0); } // // Clear the flash status register // This is a silent operation. The status that gets returned is the // status of the real operation as determined above. // WRITE_CONFIG_RAM_DATA(NvRamPtr, RESET_STATUS); Timeout = TIMEOUT_VALUE; do { WRITE_CONFIG_RAM_DATA(NvRamPtr, READ_STATUS); FlashStatus = READ_CONFIG_RAM_DATA(NvRamPtr); KeStallExecutionProcessor(1); Timeout--; } while (((FlashStatus & 0x80) == 0) && (Timeout > 0)); return ReturnStatus; } PUCHAR I28F008SA_BlockAlign( IN PUCHAR Address ) { return (PUCHAR)((ULONG)Address & ~(BLOCK_SIZE-1)); } UCHAR I28F008SA_ReadByte( IN PUCHAR Address ) { return READ_CONFIG_RAM_DATA(Address); } BOOLEAN I28F008SA_OverwriteCheck( IN UCHAR OldData, IN UCHAR NewData ) /*++ Return Value: Zero if OldData can be overwritten with NewData. Non-zero if device must be erased to write NewData. --*/ { return (~OldData & NewData) ? FALSE : TRUE; } ULONG I28F008SA_BlockSize( IN PUCHAR Address ) /*++ Return Value: The block size of the device. 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When Shell sold most of its Canadian tar sands operations last week, the Anglo-Dutch oil company took a modest step towards making good on its promise to be part of the solution on global warming, rather than the problem. Tar sands are reviled by climate change campaigners as one of the dirtiest forms of energy. The sands are a glutinous, bitumen-addled mix when extracted from the ground and a huge amount of energy is need to turn them into synthetic crude oil. Leading scientists have warned that exploiting tar sands would be “game over” for tackling climate change, and Shell has faced shareholder rebellions in the past over the risks it faced from exploiting the carbon-intensive oil. But the $7.25bn (£6bn) sale of the majority of its tar sands assets to an independent Canadian oil company is less about the company cleaning up its image than about cleaning up its debt. The deal is the largest single chunk so far in Shell’s $30bn divestment programme, to pay for borrowing it incurred after buying gas giant BG Group for £47bn. “There is a low-carbon element because these are some of the most carbon-intensive barrels in the oil sector. But it’s more about a general industry trend we’re seen around repositioning portfolios lower down the cost curve,” said Tom Ellacott, senior vice-president of research at oil analysts Wood Mackenzie. While the divestment programme and a move to cheaper sources of oil will have driven the sale, Ellacott said he was sure the carbon-intensiveness of the sands was part of the company’s thinking too. Tar sands are not just one of the dirtiest sources of oil, but one of the most expensive because of the high cost of turning them into usable fossil fuel. That is why big players are quitting the sector. Norwegian oil company Statoil completed the sale of its tar sands assets in January, and France’s Total has sold some of its holdings. US oil giants Chevron and Exxon both downgraded their tar sands reserves because of historically low oil prices that have further reduced the profitability of such a cost-intensive asset. Of course, Shell is not leaving the tar sands game entirely. It is retaining assets including an upgrader plant, the extremely energy-intensive element of the process of turning the bitumen extracted from the ground into crude oil. The company does not want to overstate the carbon benefits of reducing its share in the Athabasca Oil Sands Project in Alberta – although it is keeping a 10% stake – and selling several undeveloped tar sands fields in the province. But it says the sale will bring about an absolute reduction in carbon emissions from its operations, which were 72 million tonnes last year. “Shell is a long-time supporter of government-led carbon pricing mechanisms globally and has been a vocal supporter of both Canada’s and the state of Alberta’s climate plans,” said Ben van Beurden, Shell’s chief executive. He said retaining stakes in the tar sands would help both those plans to succeed. Compared with some of its peers, the company talks more strongly about taking global warming seriously. “We believe climate change is real. We believe action is going to be needed. We believe we are in the middle of an energy transition that is unstoppable,” Van Beurden said during the company’s quarterly results presentation last month. He said the company “wants to be in the vanguard” of that transition to cleaner energy. Shell created a new energy division last year which is targeting an annual spend of $1bn by the end of the decade, or 4% of the $25bn capital expenditure it plans this year. Staffers say that although the proportion may seem small compared with the rest of the company, they are determined to increase it. Shell has become more “gassy” and less “oily” in recent years, a trend accelerated by the acquisition of BG Group and helped by the tar sands sale. Production is around half oil and half gas, which is cleaner in carbon terms. Van Beurden is aware that getting out of tar sands has reputational benefits, as well as immediate financial ones. “The global energy system needs to evolve to one with net zero emissions,” he said, arguing that Shell had a critical role to play in that transition. “But for us to play this role effectively will require trust, and to help build that trust our industry needs to reduce its own carbon intensity.” Shell confirmed last week that it would tie 10% of executives’ bonuses to management of greenhouse gas emissions, although the company has not said what those carbon targets are. Nevertheless, campaigners maintain that Shell’s approach to climate change is not credible. Greg Muttitt, of the US-based NGO Oil Change International, said: “Shell is doing more to move from oil to gas than some of its competitors but that’s not the right move – the move needs to be to step away from fossil fuels [and into renewables].”
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Q: Errors with SPSS Logical Operators and Strings In a Simple Expression I'm having some unexpected errors in achieving the following functionality. In this example code, I have the temperature on several days of the week. For this generalized example, I'm interested in determining the days that are 72,74, or 65 degrees. As an output, a variable should be created that contains the day of the week that is within this temperature range. Also, please note that in these data there is only ever 1 day that would fall within have one of these temperatures. Monday Tuesday Wednesday Day of Interest 72 78 80 61 78 74 Monday Tuesday Wednesday Day of Interest 72 78 80 2 61 78 74 4 I wrote the following code, with the generous help of the great folks here at StackOverflow, IF (Monday = 65 OR 72 OR 74) Day_Of_Interest = 2. IF (Tuesday= 65 OR 72 OR 74) Day_Of_Interest = 3. IF (Wednesday = 65 OR '72' OR 74) Day_Of_Interest = 4. IF (Thursday = 65 OR 72 OR 74) Day_Of_Interest = 5. but sadly it returns an error: IF A relational operator may have two numeric operands or two character string operands. To compare a character string to a numeric quantity, consider using the STRING or NUMBER function.' I tried changing the code to be akin to '65' OR '72', but this produced another error. I would really appreciate if anyone had any thoughts on how to make this work. I know the example above isn't the best, but it's the best I could think of. If you need anymore details I'd be more than happy to oblige. Thanks so much for your help! Edit: I should say that this code does work if I am just looking for one number, say 72. A: Using IF with multiple comparisons will only work this way: IF (Monday = 65 OR Monday = 72 OR Monday = 74) Day_Of_Interest = 2. But in this situation ANY function will be more useful: IF any(Monday, 65, 72, 74) Day_Of_Interest = 2. Now if you want to do this for all weekdays, you can use a loop: do repeat day=Sunday Monday Tuesday Wednesday Thursday Friday Saturday /Dnum=1 2 3 4 5 6 7. IF any(day, 65, 72, 74) Day_Of_Interest = Dnum. end repeat. exe.
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A semi-biased commentary on British and American politics, culture and current affairs Following a week of vacation, I left Athens for London just hours after Greek Prime Minister Alexis Tsipras made his dramatic address to the nation, stating his intention to put the latest EU bailout offer to a referendum. While the popular islands and tourist areas of central Athens showed few outward signs of the unfolding drama, queues were already forming at ATMs in poorer and more residential areas. The following are my thoughts on the Greek crisis and the behaviour of the international institutions which increasingly supplant national democracy. No wonder the power brokers of Europe are dazed, confused and spitting with rage. Cyprus meekly fell into line when their turn came. Ireland whimpered and did what it was told. But Greece is displaying a puzzling degree of stubbornness and outright disrespect by failing to behave like a weak supplicant nation with no negotiating power, infuriating the finance ministers and leaders of the other eurozone countries in the process. It’s almost as though, in their arrogance, the Greek government actually believes that its primary duty is to the people of Greece rather than the multinational institutions which now seek to go through the country’s budget and the government’s manifesto with a red veto pen. But for as long as our world is built on the principle of the sovereign nation state, free people in a free country have the inviolable right to make their own bad choices and then take what measures they see fit to correct these errors through the democratic process. Unfortunately, when nation states are increasingly stripped of their power and influence – having vested them in political institutions like the European Union and monetary unions like the Euro – this is no longer possible. Suddenly, millions of people in far-flung places have a vested interest in decisions taken in one small country, and the democratic will of any one member state is only one consideration among many others competing for consideration. This is the Greek debt crisis in a nutshell. Since it was first foisted on the people without any popular mandate, citizens of the European Union member states have been told that first political union and then monetary union were possible without any real dilution of national democracy. Never mind the glaring red flags which warned otherwise – parliament buildings in Brussels and Strasbourg, a court of justice, an official flag and an anthem. These were all harmless trappings of European unity, we were told. Nothing to worry about. The unfolding Greek drama proves once and for all that this was a lie. The European Union and its institutions, supposedly intended to represent the unified will of the people – not that the peoples of Europe have ever been united in anything – have increasingly taken on a life and vested interests of their own. The survival of the multinational institutions now matter more than the well being of any one member state – or at least the fortunes of those smaller countries on the periphery. And if proving the ongoing viability of European monetary union means sacrificing Greece and condemning the Greek people to another lost decade of economic depression, so be it. In public, most EU leaders have tried to maintain a veneer of concern for the plight of Greece and the ordinary people suffering unemployment and all the lost opportunities of an economy in permanent recession. But behind closed doors, the institutions and bureaucrats holding Greece by the scruff of the neck are snarling and vindictive, telling the elected prime minister to shut up and going through the government’s proposals – detailed plans for how the democratically elected government will run the country – with a red veto pen. But surely the real madmen here are not the Greek Marxists at all. The real madmen are those who created the euro, this cock-eyed construct, who thought political dreams and vanity could trump economic sense and cultural and national differences, by creating a currency union on a vast continent without the necessary safeguards. Yet instead of facing these realities, and accepting that the EU model as currently constituted has had it, the Europhile leaders intone pompously about European Union values being agelessly sacrosanct. It is as though these men and women believe themselves to be functionaries of the Holy Roman Empire, rather than representatives of a modern botched-together political experiment that was only created in its latest form when German and French politicians misdiagnosed the consequences of the end of the Cold War as recently as 1989 and prescribed the euro. And so the EU (and especially the eurozone) remains determined to continue on their current course of explicit political integration, without any real mandate to do so from the people of the various member states. But monetary union is only possible if wealthier regions within the union (like Germany and France) are willing to make enormous transfer payments to poorer regions (like Greece). And public tolerance for such wealth transfers can only exist within the structure and confines of a nation state. The citizens of New York and California are willing to see their tax revenues effectively subsidise states like Alabama and Mississippi because the people share a common American bond – they all bleed red, white and blue. But this is simply not the case in the European Union. The comfortably prosperous middle class German taxpayer sees little reason why he should underwrite inefficiencies and corruption in the Greek economy, and when push comes to shove he will likely sit back and watch the Greek economy implode, because there is not enough common bond between the two peoples. No matter the wishful thinking of the EU elite, there is no common European identity. In the case of the EU, the structures and symbols of a nation state have been established despite there being no sense of common European identity superseding or even level with the distinct national identities. Greeks feel Greek first and foremost, and Germans feel German above all – or at least their willingness to view other people as sharing a common European identity is contingent upon those people operating according to German customs of industriousness and thrift. And so when monetary union requires the richer countries to subsidise the poorer ones, it is only ever done exceedingly grudgingly – and in the case of the Greek bailout programme, with so many growth-smothering conditions in place that the assistance offered is politically toxic to the debtor state. So yes, Greece is far from blameless in this crisis – successive Greek governments are to blame for failing to get a grip with that country’s corruption, inefficiency and political denialism, and the people themselves for failing to do any due diligence when selecting their leaders, believing that they could exist within the eurozone without accepting painful reforms. But democracy means having the right to make mistakes and then to take independent action to remedy these errors where necessary – or even to exacerbate them. It is not for the unelected technocrats of the IMF, the ECB and the Eurogroup to force a growth-sapping political settlement on the Greek economy against the will of the people, or to agitate and manoeuvre for Greek regime change whenever a democratically elected government does not behave in the collegial, give-and-take manner expected by the EU elite. If the euro is to survive as a currency and the European Union as an institution, wealthy creditor countries like Germany must accept that the price of their longed-for ever-closer political union is an onerous long-term obligation to subsidise and prop up the poorer and less developed economies of other member states such as Greece. It is as simple as that. But this reality is proving slow to sink in. The last few weeks and months have been no less than a screaming, foot-stamping collective hissy fit by the supposedly mature, dispassionate guardians of our technocratic world order – and all because one small country, feeling bullied and led to sacrificial slaughter, decided to say “no more”. Alexis Tsipras and his Syriza-led coalition government may not have the right answers – quite often they live in a left-wing alternate universe – but any mistakes and subsequent consequences are for the Greek people alone to make. The European and global financial institutions are already suffering from a huge crisis of legitimacy and a yawning democratic deficit. They will make nothing better by continuing to play hardball with a government and people who feel cornered, victimised and singled out for disproportionately harsh treatment. Furthermore, the sovereign countries most exposed to Greek government debt should have known that despite the overarching umbrella of the euro, they were still investing in Greece – a less developed and less efficient economy with all the added risk that such investments entail. To now demand that Greece – which is now running a primary budget surplus when debt repayments are factored out – should effectively socialise the losses of these (mostly eurozone) creditor countries is selfish and narrow-minded, not to mention extremely short-termist when one considers the risks and costs of wider contagion and the potential fragmentation of the Eurozone. By holding a referendum and potentially rejecting the most recent offer from the troika, Greece may well be going to her Armageddon. But that choice is for the Greek people alone, not for unelected technocrats from remote institutions far removed from the day-to-day suffering of the people. By forcing a depression-weary government and people into this corner, the sharp-suited members of the IMF, ECB and Eurozone could well be ushering in virtual Armageddon for thousand if not millions of people outside Greece – all in the service of trying to extract maximum returns on a crushing sovereign debt which all intelligent people recognise can never be repaid. And these unelected bureaucrats have absolutely no popular mandate to do this. Greek popular democracy with all its flaws, or the EU’s remote and elitist technocracy: though the birthplace of democracy is no more sinned against than sinning, it is Greece which stands on the right side of this argument, and on the right side of history.
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Bioethical considerations in translational research: primate stroke. Controversy and activism have long been linked to the subject of primate research. Even in the midst of raging ethical debates surrounding fertility treatments, genetically modified foods and stem-cell research, there has been no reduction in the campaigns of activists worldwide. Playing their trade of intimidation aimed at ending biomedical experimentation in all animals, they have succeeded in creating an environment where research institutions, often painted as guilty until proven innocent, have avoided addressing the issue for fear of becoming targets. One area of intense debate is the use of primates in stroke research. Despite the fact that stroke kills more people each year than AIDS and malaria, and less than 5% of patients are candidates for current therapies, there is significant opposition to primate stroke research. A balanced examination of the ethics of primate stroke research is thus of broad interest to all areas of biomedical research.
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Find Recycling Centres I see a lot of whining about the poor service at this place. What are they expecting? Champagne, cocktails and cucumber sandwiches? it is a tip, you take your rubbish there and then you don't have a big pile of rubbish in your house. Yes, the queues can be diabolical, yes the tailback down the dual carriage is a bit dodgy, I don't know what the site attendants are supposed to do about that though. I get the feeling they are more there to protect the site from idiots who can't read, rather than lug everyone's mess for them - but they helped everyone I heard ask them for help. The tailback would improve quite a lot if the people using the site read the signs and used both lanes to queue. There is a tailback out the gate and folks are beeping horns because their literate brethren are following instructions (the same people whining about queuing on the road i wonder?). Always nice to get out and see people being happy with each other. I've found the staff friendly and helpful on all visits. The location and the wait are often bad. Definitely helpful to use the Google's indications of when is least busy! Great furniture in good nick at great prices as well and the stock changes on a regular basis so you must keep visiting you will find what you're looking for and you should not be waiting to long to find it good place for the community and when you're on a budget 👍😉😃 Give and get free stuff. Here you will find lots of items that people are willing to give away, for FREE! This is instead of taking them to a local landfill site. The aim of this site is to reduce the amount of waste that goes to landfill (20.9 million tonnes of it last year in the UK) and recycling is great news for the environment. We all know that we need to recycle more - and this is a great way of doing it. This Microportal is built on the 2day Microportals platform which provides you with 3 click access to local and global information crucial both to your personal and working life. The platform provides live local data on transport, what's on, accommodation, eating out, shopping, sport, religion and weather as well as comprehensive reference and resource sections including TV, radio, online shopping, route planning, health, education and more. We are not responsible for the content of external internet sites to which any 2day supported sites are linked. We do not share any contact information with other providers. We use cookies to make our site work efficiently. More information on privacy and cookies.
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Caliente (Jay Santos song) "Caliente" is a 2013 Spanish language dance hit single by Jay Santos released on the Spanish Blanco y Negro Music record label. It was released on 26 February 2013 becoming the first solo charting hit of Jay santos, after his 2012 success as a featured artist on Spanish DJ and producer Jose de Rico and Spanis-Dominican singer Henry Mendez European hit "Noche de estrellas". Lyrics: La fiesta esta buena es pa beber pa bailar... Si tu estas soltera a mi gustaria probar Track listing "Caliente" (Radio Edit) (3:22) "Caliente" (Extended Version) (5:26) "Caliente" (Acapella) (3:22) Chart performance References Category:2012 singles Category:Spanish-language songs Category:2012 songs Category:Blanco y Negro Records singles
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This is one of my all time favourite lip balms. I am never without several pots of Carmex strewn around the house. It's my go to lip balm when my lips are cracked and sore because I know it will heal my lips within a few days. I normally steer away from balms with petrolatum in them, but this is the exception because it works. Due to the camphor and menthol there is a tingly feeling for a few minutes after application, however it goes away quickly and it's not unpleasant. If you haven't tried Carmex, run, don't walk, and get one (or two) now!
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6:14 HD Canela Skin and Megan Inky in an anal orgy 3 143 100% 8 months ago
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Lipid profile and genetic status in a familial hypercholesterolemia pediatric population: exploring the LDL/HDL ratio. Background Familial hypercholesterolemia (FH) is a genetic disorder caused by mutations in genes involved in low-density lipoprotein (LDL) uptake (LDLR, APOB and PCSK9). Genetic diagnosis is particularly useful in asymptomatic children allowing for the detection of definite FH patients. Furthermore, defining their genetic status may be of considerable importance as the compound heterozygous status is much more severe than the heterozygous one. Our study aims at depicting the genetic background of an Italian pediatric population with FH focusing on the correlation between lipid profile and genetic status. Methods Out of 196 patients with clinically suspected FH (LDL-cholesterol [LDL-C] levels above 3.37 mmol/L, cholesterol level above 6.46 mmol/L in a first-degree relative or the presence of premature cardiovascular acute disease in a first/second-degree relative), we screened 164 index cases for mutations in the LDLR, APOB and PCSK9 genes. Results Patients with mutations (129/164) showed increased levels of LDL-C, 95th percentile-adjusted LDL-C and LDL/high-density lipoprotein (HDL) ratio and decreased levels of HDL-C, adjusted HDL-C. The association of the LDL/HDL ratio with the presence of mutations was assessed independently of age, (body mass index) BMI, parental hypercholesterolemia, premature coronary artery disease (CAD), triglycerides by multivariate logistic regression (odds ratio [OR]=1.701 [1.103-2.621], p=0.016). The LDL/HDL ratio gradually increased from patients without mutations to patients with missense mutations, null mutations and compound heterozygotes. Conclusions In conclusion, the LDL/HDL ratio proved to be a better parameter than LDL-C for discriminating patients with from patients without mutations across different genetic statuses.
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ECS Season 2 - Team list finalised The list of participants for ECS Season 2 has been consolidated, with both the European and North American qualifiers concluded. The European and North American qualifiers for ECS Season 2 have concluded, with Team Dignitas finalising the list after breezing by tRICKED eSport. The team now joins the existing 19 qualified teams in the final stage of ECS Season 2, which will be running over the course of the next two months, with the LAN finals taking place on December 7th, 2016. As a reminder, ECS Season 2 is a follow-up of the very successful first season of the championship, the LAN finals of which took place at the Wembley Arena in London, United Kingdom. G2 Esports were the victors of the tourney, taking away $250,000 in prize money, as well as the Champions' bragging rights. The second season sports the same $1,750,000 prize pool, with the venue for the LAN finals yet to be disclosed. Europe North America
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22 Gen 2020 Ricette La pignolata messinese è un dolce eccezionale. Chiamata anche pignolata glassata, è una ricetta tipica del Carnevale, che si trova nelle pasticcerie in tutti i periodi dell’anno. La pignolata è inclusa nella lista siciliana dei prodotti agroalimentari tradizionali italiani (P.A.T) del Ministero delle Politiche Agricole, Alimentari e Forestali (Mipaaf) con la denominazione di pignolata di Messina. Tuttavia il dolce è molto popolare in tutta la Sicilia orientale e ve ne sono molte varianti come quella ragusana. Si chiama Pignolata perchè si presenta proprio come un mucchietto di pigne di varie dimensioni ricoperte da una glassa bianca al limone e da una glassa scura solitamente al cioccolato. L’odore di cedro o di bergamotto e cioccolato vanigliato vi trasportano in un altro mondo ricco di felicità. Le origini della pignolata La pignolata glassata trae origine dalla pignolata al miele, nella quale un mucchietto di “pigne” fritte venivano ricoperte da miele. Successivamente una nobile famiglia ordinò un dolce che fosse meno povero e più barocco e così venne fuori la pignolata che oggi tutti noi conosciamo con quella dolcissima copertura aromatizzata. Ricetta Pignolata Messinese Ingredienti per 6 persone Impasto Farina bianca tipo 00 (600 g) Uova intere (12) Tuorlo d’uovo (3) Alcool per liquori (30 g) (facoltativo) Limone (1) (facoltativo) Strutto (2 cucchiai scarsi) Glassa al limone Zucchero semolato (300 g) Limone (2) Albume d’uova (3) Glassa al cioccolato Zucchero semolato (300 g) Cacao (150 g) Procedimento Preparazione delle pignette Disporre a fontana la farina su una spianatoia e fare un buco al centro dove aggiungere le uova e lo strutto. Non fermatevi fino a quando non ottenete un composto morbido e liscio. A questo punto aggiungete lentamente l’alcol, della scorza di limone ed impastate nuovamente fino ad ottenere una pasta omogenea e consistente. Poi lasciate riposare per mezz’ora. Infine dividete la pasta in piccoli pezzi da schiacciare e stendere con un mattarello fino ad ottenere dei bastoncini della grandezza di un dito. Tagliateli in gnocchetti di 2 o 3 centimetri. Metteteli su una piastra da forno a temperatura moderata e cuoceteli per 10 minuti fino a quando non assumeranno il colorito classico di un biscotto. Quando i biscotti saranno pronti disponeteli in pila (come se voleste formare una montagna) e preparate la glassa con la quale ricoprirli. Preparazione della glassa bianca al limone Mettere lo zucchero in una casseruola e fatelo imbiondire mescolando sempre nello stesso verso. Montate a neve gli albumi ed incorporate piano piano gli albumi allo zucchero. Aggiungete quindi la buccia di limone grattugiata e mescolate energicamente. Quando la glassa sarà omogenea toglietela dal fuoco e fatela intiepidire prima di versarla su metà biscotti. Preparazione della glassa di cioccolato Mettere lo zucchero in una casseruola e fate imbiondire, mescolando sempre nello stesso verso. Quindi aggiungete del cacao e mescolate fino ad ottenere un composto liscio ed omogeneo. Quando la glassa sarà uniforme, toglietela dal fuoco e fatela intiepidire prima di versarla sulla seconda metà dei biscotti. Fate raffreddare naturalmente. Di Viola Dante Articoli correlati
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SINDY ROSE – SINDY ROSE IS BACK FOR MORE ANAL SEX AND CREAMPIE 277 0%
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Q: How to run pytorch computation in cuda as default Now, I want to run pytorch using cuda, then I use model.cuda(), and torch.cuda.LongTensor() for all tensor. Do I have to create tensor using .cuda. explicitly if I have used model.cuda()? Is there a way that makes all computation running in GPU as default? A: I do not think you can specify that you want to use cuda tensors by default. However you should have a look to the pytorch offical examples. In the imagenet training/testing script, they use a wrapper over the model called DataParallel. This wrapper has two advantages: it handles the data parallelism over multiple GPUs it handles the casting of cpu tensors to cuda tensors As you can see in L164, you don't have to cast manually your inputs/targets to cuda. Note that, if you have multiple GPUs and you want to use a single one, launch any python/pytorch scripts with the CUDA_VISIBLE_DEVICES prefix. For instance CUDA_VISIBLE_DEVICES=0 python main.py.
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Q: Adding multiple nodegroups to eks I would like to add multiple nodegroups to eks, each one with different labels. I have successfully deployed a second cloud formation stack and can see the new ec2 instances, but I cannot see the new nodes in the k8s dashboard. Am I missing something? A: I was able to fix this by going back and updating the aws-auth configmap, adding a second role map: apiVersion: v1 kind: ConfigMap metadata: name: aws-auth namespace: kube-system data: mapRoles: | - rolearn: OLD ARN username: system:node:{{EC2PrivateDNSName}} groups: - system:bootstrappers - system:nodes - rolearn: NEW ARN username: system:node:{{EC2PrivateDNSName}} groups: - system:bootstrappers - system:nodes
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Contents All of the red-black tree algorithms that have been proposed are characterized by a worst-case search time bounded by a small constant multiple of log N in a tree of N keys, and the behavior observed in practice is typically that same multiple faster than the worst-case bound, close to the optimal log N nodes examined that would be observed in a perfectly balanced tree. Specifically, in a left-leaning red-black 2-3 tree built from N random keys:
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Q: dom-repeat not reflecting data changes I tried computed properties and various other techniques, but the view is not reflecting my model. The model updates, but the view does not. View <div class="selection"> <ul> <template is="dom-repeat" items="{{state.selection}}"> <li> <a data-selection$="{{item.id}}" on-click="selection">{{item.name}}</a> </li> </template> </ul> </div> <div class="selection sub-selection"> <template is="dom-repeat" items="{{state.subSelection}}"> <ul id$="subselection-{{item.id}}" class$="[[item.active]]"> <template is="dom-repeat" items="{{item.selections}}"> <li> <a data-selection="{{item.id}}" on-click="selection">{{item.name}}</a> </li> </template> </ul> </template> </div> Model constructor(){ super() this.state = { selection: [ { id: 1, name: 'Selection One' }, { id: 2, name: 'Selection Two' } ], subSelection: [ { id: 1, name: 'Sub Selection One', active: 'active' }, { id: 2, name: 'Sub Selection Two', active: '' } ] } selection(event){ event.preventDefault(); let self = this; let id = parseInt(event.currentTarget.getAttribute('data-selection')); self.state.subSelection.forEach(function(key, index){ if(key.id === id){ key.active = 'active' }else{ key.active = '' } }); } The goal would be to click a item in "selection" get its id value and match it to and item in "subSelection" with the same id then changing the active value to "active" or "". All goes well except the view updating. A: So I ended up solving it by this.set(property, value). Polymer is very particular in how this should be achieved as well. But the following worked in my update function: selection(event){ event.preventDefault(); let self = this; let id = parseInt(event.currentTarget.getAttribute('data-selection')); self.state.subSelection.forEach(function(key, index){ if(key.id === id){ self.set("state.subSelection."+index+".active", 'active'); }else{ self.set("state.subSelection."+index+".active", ''); } ); }
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The invention relates to a field effect transistor. In particular, it relates to a depletion type n-channel MOS field effect transistor that is used in a circuit to protect against electrostatic breakdown of a magnetic head. For example, in the case of a magnetic head, such as a GMR magnetic head, incorporated into a magnetic recording device such as an HDD (hard disk drive), a depletion type n-channel MOS field effect transistor is utilized inside a preamplifier IC as a protective circuit to protect the magnetic head from an electrostatic breakdown. FIG. 8A is a plan view of a depletion type n-channel MOS field effect transistor according to the prior art. As shown in FIG. 8A, gate electrode 41 is formed in a p-type semiconductor region defined on a semiconductor substrate via a gate insulation film, and n-type source region 40S and drain region 40D are formed at surface parts of the p-type semiconductor region at either side part of gate electrode 41. Furthermore, an n-type channel region is formed on the surface part of the p-type semiconductor region immediately below gate electrode 41 so as to form a depletion type n-channel MOS field effect transistor. Due to increased speeds and capacities of HDDs, there is a demand for depletion type n-channel field effect transistors with lower on-resistances in order to improve the performance of ESD protection elements at low capacitances. To realize this, reductions in the on-resistance and the drain capacitance are required, and a technique for reducing the on-resistance while keeping the drain capacitance unchanged has been adopted. FIG. 8B is a plan view of a depletion type n-channel MOS field effect transistor according to the prior art. Two gate electrodes 41a and 41b are formed in a p-type semiconductor region provided on a semiconductor substrate via a gate insulation film; and source region 40Sa, drain region 40D, and source region 40Sb are formed in three respective regions that are separated by the two gate electrodes 41a and 41b on the surface part of the p-type semiconductor region. N-channel regions are formed in the p-type semiconductor regions immediately below the two gate electrodes 41a and 41b so as to form a depletion type n-channel MOS field effect transistor. As opposed to the field effect transistor with the configuration shown in FIG. 8A, in the case of the field effect transistor with the configuration shown in FIG. 8B, because the gate width is set approximately two times as wide while keeping the drain capacitance unchanged, the on-resistance is reduced to approximately one-half. That is, the drain capacitance per unit gate width is reduced by approximately one-half. However, in recent years, there is a greater demand for faster driving, and further reduction in the on-resistance and the drain capacitance is needed. The invention was devised in light of the aforementioned situation, and its objective is to present a field effect transistor by which the drain capacitance per unit gate width can be reduced further.
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Background ========== The prevalence of severe spinal deformity in patients with neuromuscular disorders is estimated between 50% and 80% \[[@B1]-[@B3]\]. The progression of untreated neuromuscular spinal deformities can cause aggravation of pain \[[@B4]-[@B6]\], decreased sitting balance \[[@B6]-[@B10]\], pressure sores, psychological problems (in patients without mental retardation), compromised pulmonary functions \[[@B11],[@B12]\] and increased mortality \[[@B13]\]. Surgical management has been a reliable option for these patients since introduction of spinal instrumentation by Harrington and subsequent advances by others; most notably by Luque and Cotrel-Dubousset \[[@B14],[@B15]\]. The use of hooks in the thoracic spine has been considered as a gold standard for the treatment of neuromuscular scoliosis. There has been a movement toward the use of thoracic pedicle screws in deformity surgery, based on the reports regarding clinical advantages of pedicle screw fixation in the lumbar spine in terms of enhanced correction and stabilization, when compared with a hook construct \[[@B5],[@B16],[@B17]\]. Uses of Luque rods or unit rod instrumentation have their own disadvantages such as loosening of wires, cutting out of wires, loss of fixation and loss of correction over time and in addition, delayed sitting and ambulation in post-operative phase. Controversy persists, which patient requires anterior release and/or fusion in combination with posterior instrumentation and arthrodesis to improve curve correction. Treatment of the neuromuscular scoliosis with posterior-only pedicle screw instrumentation is a recent concept, which obviates the need for additional anterior release, and thus risk to life. Main purpose of this study was to evaluate the outcome of single-stage posterior-only pedicle screw instrumentation and fusion for the definitive management of neuromuscular scoliosis. Specific emphasis was kept on correction of scoliosis and maintenance of that correction over time. Methods ======= Between 2003 and 2006, Twenty-six consecutive patients (17 male and 9 female) with progressive neuromuscular scoliosis underwent posterior only pedicle screw fixation and fusion by a single spine surgeon. We did not perform anterior surgery in any of these patients in the study. Seven patients had CP (cerebral palsy), 10 had DMD (Duchenne muscular dystrophy), 5 had SMA (Spinal muscular atrophy) and four (2 post poliomyelitis residual paralysis, 1 each multiple sclerosis and traumatic paraplegia) had other pathologies. Twelve, out of 26 patients, had right side curve and 14 had left side curve. Fifteen, out of the 26 patients, had apex at thoraco-lumbar junction. Fourteen patients had single curves and 12 had double curves. Pre-operatively, 18 patients were wheel chair bound while eight were in ambulatory status (walking independently or with the help of either crutches or walker). Pre-operative planning of each case was based on a total of eight radiographs, i.e. antero-posterior and lateral radiographs in the sitting and supine positions, lateral bending view and in maximal flexion and extension views. Entire group underwent pulmonary function tests (PFT) preoperatively. We retrospectively reviewed medical records, operative records and sequential radiographs of all patients. Radiographic measurements were recorded in terms of number of curves, amount of preoperative flexibility, preoperative, post-operative and final follow-up Cobb\'s angle, pelvic obliquity, thoracic kyphosis and lumbar lordosis. Skeletal maturity was assessed by documenting the Risser\'s sign. Pelvic obliquity was measured as the angle between the line joining two iliac crests and horizontal line. Thoracic kyphosis was measured form upper end-plate of T4 to lower end-plate of T12 and lumbar lordosis was measured form upper end-plate of L1 to lower end-plate of L5. The results of pulmonary function tests, duration of anesthesia, operating time and amount of blood loss were obtained from inpatient charts while postoperative complications and improvement in sitting balance and parents\' or care takers\' satisfaction were documented from follow up sheets. Operative procedure ------------------- All patients were operated in prone position with posterior-only approach. Spine was dissected, subperiosteally, up to the tip of the transverse processes at all levels. Pedicle screw inserted bilaterally with free hand technique at all preoperatively decided levels. Bilateral facetectomies was done at all levels,, including the apex, to facilitate the maximum rotational correction. Contouring of the rods were done manually with rod bender and mounted over pedicle screws bilaterally, with concave side being the first followed by the convex. Derotation maneuver was subsequently done, with or without in situ bending of rods, simultaneously on both sides. Rods were fixed by tightening of the caps over screws and posterior fusion achieved, after thorough decortications of posterior laminae, using bone grafts mixed with cancellous allograft. Wound was closed, over two-drainage tube, in layers. The entire patients underwent for radiogram and CT scan postoperatively, which were stored in our computerized PACS system with preoperative data. Posterior vertebral column resection (PVCR) was performed in those patients who had a stiff or rigid spine with a large curve (more than 90°). Pelvic fixation was done using poly-axial ilio-lumbar connectors developed by the authors in patients who had severe pelvic obliquity or contractures in lower extremities. We have statistically analyzed the results of pre operative and postoperative corrections in Cobb\'s angle and pelvic obliquity using paired t- test. In addition, we have divided the study group in two categories depending upon the severity of curve: group 1 (curve \< 90°) and group 2 (curve \> 90°). The correction rate of Cobb\'s angle and pelvic obliquity between group1 and group 2 were compared using unpaired t-test. P value less than 0.05 was considered the significant for all the tests. Results ======= The average age at the time of operation was 17.5 years (range 8 -- 44 years) and the average follow-up was 25 months (range, 18 -- 52 months) (table [1](#T1){ref-type="table"}). The average percentage of pre operative flexibility was 41% (11%--74%). Average preoperative, postoperative and final follow-up Cobb\'s angle, pelvic obliquity, thoracic kyphosis and lumbar lordosis are shown in table [2](#T2){ref-type="table"}. The average correction rate in Cobb\'s angle was 60.9% post operatively and 57.9% at final follow up. Similarly, the average correction rate in pelvic obliquity was 44.92% and 43.02% postoperatively and at final follow-up respectively. There has been statistically significant correction achieved, in Cobb\'s angle (p \< 0.0001, paired t-test) and pelvic obliquity (p \< 0.0001, paired t-test), post operatively which are maintained at final follow-up. The difference in average preoperative, postoperative and final follow-up thoracic kyphosis did not reveal any significant difference (p = 0.74, ANOVA) while the difference in preoperative, postoperative and final follow-up lumbar lordosis showed significant improvement (p = 0.001, ANOVA). ###### Patients\' demographics. (Age, diagnosis and level of apex) **No** **Age (years)** **Diagnosis** **Apex** **O peration** **F-U (months)** **Fixation Level** -------- ----------------- --------------- ---------- ---------------- ------------------ -------------------- 1 25 CP L1 PVCR 25 T5-Pelvis 2 17 CP L2 C & F 25 T2-Pelvis 3 18 CP L4 C & F 21 T3-L5 4 16 CP L1 C & F 22 T4-L4 5 14 CP T9 C & F 22 T2-L4 6 16 CP T8 C & F 25 T3-L2 7 20 CP T10 PVCR 23 T4-L4 8 12 DM D L2 C & F 52 T3-L5 9 11 DM D T12 C & F 27 T2-L5 10 8 DM D L1 C & F 24 T3-L4 11 14 DM D L2 C & F 24 T4-Pelvis 12 17 DM D L1 PVCR 26 T3-Pelvis 13 13 DM D L1 C & F 26 pPelvis 14 15 DM D L1 C & F 21 T4-L5 15 10 DM D L1 C & F 21 T2-L5 16 17 DM D T12 C & F 18 T3-L5 17 14 DM D T12 C & F 19 T2-Pelvis 18 9 SM A L1 C & F 33 T3-Pelvis 19 13 SM A L1 PVCR 31 T3-Pelvis 20 21 SM A L2 C & F 27 T3-Pelvis 21 10 SM A L3 C & F 27 T2-Pelvis 22 29 SM A T12 PVCR 23 T4-L5 23 34 PO LIO T7 PVCR 22 T3-L4 24 44 PO LIO L1 PVCR 20 T6-L5 25 13 M S T8 C & F 25 T3-L5 26 26 PARA T12 C & F 21 T5-L5 Abbreviations: F-U: follow-up, CP: cerebral palsy, DMD: Duchenne muscular dystrophy, SMA: spinal muscular atrophy, MS: multiple sclerosis, PARA: post traumatic paraplegia, PVCR: posterior vertebral column resection, C & F: correction and fusion. ###### Average preoperative, postoperative and final follow-up values for Cobb\'s angle, pelvic obliquity, thoracic kyphosis and lumbar lordosis. **Cobb\'s angle** **Pelvic obliquity** **thoracic kyphosis** **lumbar lordosis** ---- ------------------- ---------------------- ----------------------- --------------------- ---- ---- ----- ---- ---- ----- ----- ----- 1 108 76 80 37 23 24 3 16 15 -90 22 20 2 55 19 20 10 3 5 20 16 14 -21 38 44 3 69 10 11 26 6 8 39 27 33 17 29 26 4 52 23 25 7 2 2 33 22 23 40 36 37 5 95 31 30 10 10 8 41 36 33 62 50 38 6 48 14 36 4 1 2 26 10 10 39 32 37 7 94 60 62 6 6 5 30 23 27 34 27 28 8 65 25 24 5 2 2 1 17 20 -4 17 23 9 68 36 35 5 0 3 21 23 22 -38 24 24 10 51 15 16 15 7 9 44 35 33 34 35 36 11 70 21 23 33 12 13 2 18 14 -7 28 24 12 91 45 46 29 12 2 -13 4 3 -79 -15 -15 13 48 2 4 4 1 2 8 25 21 -16 24 23 14 88 32 33 33 20 20 5 3 5 -71 2 5 15 51 7 8 11 4 6 48 38 40 22 38 35 16 109 49 51 32 32 30 8 23 22 3 17 18 17 82 29 28 17 14 15 20 10 12 -40 26 27 18 59 5 6 15 8 10 13 17 16 6 19 20 19 101 26 25 25 14 16 25 24 25 -50 22 23 20 63 33 33 9 3 5 122 65 63 67 45 44 21 84 16 18 7 0 2 7 15 14 -7 28 30 22 123 50 55 40 32 30 31 25 26 38 31 34 23 123 70 68 7 9 7 26 32 33 47 35 39 24 107 64 62 4 2 2 65 29 30 27 37 40 25 55 4 6 6 2 2 34 22 23 6 15 17 26 83 36 38 26 8 11 20 16 15 30 25 26 Note: minus mark in lumbar lordosis indicates lumbar kyphosis and minus mark in thoracic kyphosis indicates thoracic lordosis. There were 17 patients with curve less than 90° (group 1) (figure [1](#F1){ref-type="fig"}) and 9 with curve more than 90° (Group 2) (figure [2](#F2){ref-type="fig"}) with average pre operative Cobb\'s angle of 64.18° and 105.67° respectively. Average preoperative pelvic obliquity was 14.94° for group 1 and 18.78° for group 2. The average post operative correction in Cobb\'s angle was 70.02% and 50.31% for group I and group II respectively; which did not show significant difference (p = 0.1284) in correction between both groups. Similarly, the post operative correction in pelvic obliquity did not reveal any significant difference (p = 0.3239) in correction between both groups. Seven patients underwent PVCR from group 1. Their average pre-operative Cobb angle was 106.71°, with 24% flexibility, had an average post-operative Cobb\'s angle 55.86° showing 47.65% correction, which is similar to other patients from group 1. ![**14 years male with CP**. shows a) preoperative AP and lateral radiogram; b) postoperative AP and lateral radiogram and c) final follow-up AP and lateral radiogram of spine in a fourteen years boy with cerebral palsy. (Patient 5)](1749-799X-3-23-1){#F1} ![**13 years girl with SMA**. shows a) preoperative AP and lateral radiogram; b) postoperative AP and lateral radiogram and c) final follow-up AP and lateral radiogram of spine in a thirteen years girl with spinal muscular atrophy. (Patient 19)](1749-799X-3-23-2){#F2} The average number of levels fused was 15. Out of the 26 patients, 23 underwent pulmonary function tests and three patients, all of them being cerebral palsy patients, were non co-operative. Average FVC was 51% (range, 22%--138%), average FEV was 53.5% (range, 15%--147%) and average PEFR was 70.3% (range, 21%--148%). The FVC, FEV1 and PEFR of patients with less than 90° curves were 58%, 63% and 65 % and more than 90° were 38%, 39% and 52% respectively (table [4](#T4){ref-type="table"}). Ten patients (4 DMD, 2 CP, 2 SMA, 1 Poliomyelitis, 1 paraplegia) had FVC less than 35% (22%--33%) and six of them needed post-op ventilation. However, we did not perform pulmonary function tests postoperatively. Abbreviations: WC: wheel-chair bound, WWS: walking without support, Crutch: walking with crutch, walker: walking with walker, PFT: pulmonary function test, PEF: peak expiratory flow, FVC: forced vital capacity, FEV1: forced expiratory volume during first second. The average operating time was 6 hours 45 minutes (4 hours 30 minutes--10 hours). The average duration of anesthesia was 8 hours 24 min (5 hours 50 minutes--11 hours and 30 minutes). There was not much difference in operating time between the group I (6 hours 7 minutes) and group II (7 hrs 58 min) (table [3](#T3){ref-type="table"}). The average intra-operative blood loss was 2773 mililiters (1000--9000 mililiters). The average blood loss for patients who underwent PVCR was 4535 mililiters, whereas it was 2123 mililiters for those who did not undergo PVCR. A total of 13 patients needed postoperative ICU care for an average of 28.3 hours, except one poliomyelitis patient who was in ICU for 2 weeks secondary to DIC and another patient with traumatic paraplegia who had severe bleeding from epidural vessels, was in ICU for 10 days. Six patients required postoperative ventilation (all of them underwent PVCR) for 24 to 36 hours except one poliomyelitis patient who required ventilation for 8 days. The average duration of hospitalization was 24.36 days. ###### Values for duration of anesthesia, duration for operation, post operative ICU stay, ventilator support, hospital stay and documentation of infection. **No** **Diagnosis** **Anaes time (Hour:Min)** **Op time (Hour:Min)** **EBL (mililiters)** **ICU (time)** **Ventilator (time)** **Infection** **Hospital Stay (Days)** -------- --------------- --------------------------- ------------------------ ---------------------- ---------------- ----------------------- --------------- -------------------------- 1 CP 11:10 10:00 4550 1 Day NO NO 32 2 CP 07:30 06:10 1250 NO NO NO 24 3 CP 06:50 04:30 1400 NO NO NO 30 4 CP 07:40 06:10 2100 NO NO NO 14 5 CP 08:00 06:40 1750 NO NO NO 26 6 CP 08:00 07:00 1000 NO NO NO 10 7 CP 09:00 07:20 5000 3 Days 36 Hours NO 42 8 DMD 08:10 06:30 2550 NO NO NO 24 9 DMD 07:45 05:30 1950 2 Days NO NO 15 10 DMD 06:50 04:50 1500 NO NO NO 10 11 DMD 07:00 06:00 2100 NO NO NO 17 12 DMD 11:35 09:00 4850 3 Days 25 Hours NO 19 13 DMD 08:40 07:30 2300 5 Hours NO NO 22 14 DMD 07:10 05:45 2750 6 Hours NO YES 7 15 DMD 06:40 04:50 1750 5.5 Days NO NO 18 16 DMD 08:20 06:40 2350 NO NO NO 18 17 DMD 08:25 06:10 2300 NO NO NO 17 18 SMA 05:50 04:50 1350 3 Hours NO NO 31 19 SMA 11:00 08:30 9000 NO NO NO 36 20 SMA 10:15 08:15 3750 NO NO NO 49 21 SMA 09:40 08:10 2600 NO NO NO 19 22 SMA 08:15 06:30 3150 1 Day 26 Hours NO 23 23 POLIO 10:50 08:50 3100 14 Days NO NO 18 24 POLIO 10:10 08:15 2100 1 Day 8 Days NO 38 25 MS 06:50 05:50 2100 2 Days NO NO 15 26 PARA 07:00 06:00 3500 10 Days 24 hours YES 60 Abbreviations: Anaes time: anaesthesia time, Op time: operation time, EBL: estimated blood loss, ICU: intensive care unit. Postoperatively all patients exhibited improvement in sitting balance. Two patients who were wheelchair bound preoperatively were able to walk with the help of walker postoperatively and one wheel chair bound patient was able to walk with the help of crutches (table [4](#T4){ref-type="table"}). One SMA patient who was able to walk with the help of walker preoperatively was able to walk with the help of crutches postoperatively. None of the patient had deterioration in sitting balance at final follow-up. Parents or care-takers of all patients exhibited better personal and hygienic care postoperatively. ###### Pre operative and postoperative ambulatory status with preoperative pulmonary function tests. **Walking status** **pre-operative PFT** ---- ------- -------------------- ----------------------- ------ ------ ---------- 1 CP WC Crutch FAIL FAIL FAIL 2 CP WWS WWS FAIL FAIL FAIL 3 CP WWS WWS 44 28 28 4 CP WWS WWS 121 97 95 5 CP WWS WWS 62 51 53 6 CP WWS WWS 66 46 Un Co-op 7 CP WWS WWS 41 24 25 8 DMD WC WC 46 33 29 9 DMD WC WC 63 71 74 10 DMD WC WC 32 14 15 11 DMD WC WC 61 49 53 12 DMD WC WC 42 31 32 13 DMD WC WC 73 60 61 14 DMD WC WC 73 69 72 15 DMD WC WC 148 138 147 16 DMD WC WC 43 38 41 17 DMD WC WC 43 23 21 18 SMA WWS WWS 80 91 82 19 SMA Walker Crutch 85 64 68 20 SMA WC WC 67 31 36 21 SMA WC WC 95 89 88 22 SMA WC WC 49 22 27 23 POLIO Crutch Crutch 51 33 31 24 POLIO WC Walker 70 65 63 25 MS WC WC 43 37 39 26 PARA WC Walker 37 24 28 Complications ------------- Deep wound infection was seen in one patient with paraplegia who had continuous bleeding from the operated site for which exploration of the wound revealed bleeding from an epidural vessel, which was cauterized. She developed wound dehiscence and deep infection and pus culture grew vancomycin resistant staphylococcus for which she received teicoplanin and regular dressings. One patient with poliomyelitis who had grade 3 power of the lower limbs pre-operatively, developed grade 2 power post-operatively but gradually improved to the pre-operative stage. He also had severe blood loss in the peri-operative period, went into DIC, and was in the ICU for 2 weeks. There was no mortality, pseudarthrosis or implant failurein the study. Discussion ========== Despite the magnitude of this surgery, successful outcome of an operation for spinal deformity, secondary to neuromuscular disease, is considered beneficial by most patients and/or their principal care providers \[[@B7],[@B15],[@B18],[@B19]\]. Aims of the surgery for neuromuscular scoliosis are safe correction of deformity, to stop curve progression, to maintain or recreate sitting balance and to achieve a solid fusion of the balanced spine in the frontal and sagittal planes \[[@B20],[@B21]\]. The average age of the patients in this study was 17.5 years. The increase in age results in increasing stiffness and rigidity of the curve and difficulty to achieve acceptable correction. The mean age in this study was much higher than majority of studies, where patients underwent earlier correction at around 12 years of age or earlier \[[@B20],[@B22],[@B23]\]. However we achieved acceptable correction in both Cobb\'s angle and pelvic obliquity over al period of 25 months without significant loss of postoperative correction. We found that there were significant differences in PFT values between curves greater than 90° and less than 90°. Sussman noted an increased risk of postoperative pulmonary problems when the FVC was less than 35% \[[@B13],[@B24]\]. In our study, 10 patients had FVC less than 35% and 6 of them needed postoperative ventilation, supporting Sussman\'s \[[@B25]\] findings. Postoperative PFT assessment is not being done as a routine basis in our patients. Post-operative PFT values would indicate whether there was any improvement of these parameters following surgery. Therefore, we think, this is the limitation of present study. Average blood loss for the patients who underwent PVCR was 4535 milliliters, while it was only 2123 milliliters for those who did not undergo PVCR. Other studies \[[@B21]\] with comparable number of fusion levels had average blood loss of 2.4 liters to 2.6 liters in normal fusions and 2.5 liters to 3.4 liters in patients who had associated PVCR. This was the disadvantage of PVCR because it resulted in severe blood loss, and in addition, all of them required postoperative ICU stay and six of the seven patients needed ventilation. Kannan et al \[[@B26]\] comparing blood loss during operation, found that the neuromuscular group had greater blood loss than idiopathic scoliosis. Average preoperative pelvic obliquity was 16° which decreased to 9° after the surgery, and remained same even at final follow-up. There is a growing controversy regarding the distal extent of fusion in patients with neuromuscular scoliosis (figure [1](#F1){ref-type="fig"}). There was a general trend to include the pelvis in all cases of neuromuscular scoliosis to correct pelvic obliquity or to prevent its development \[[@B20],[@B26]-[@B30]\]. With all the problems described in the literature associated with pelvis fusion \[[@B9],[@B31]\] few patients who had pelvic obliquity greater than 15° and other patients with pelvic obliquity less than 15° had severe lower extremity contractures were chosen for pelvic fusion \[[@B32]\]. Recently, Tsirikos, et al \[[@B33],[@B34]\] challenged the long-term belief that fusion should be avoided in ambulatory patients with CP. In our experience, we have noticed that patients who have gross pelvic obliquity, do not exhibit any problem with sitting balance without much progression over a short term. Therefore presently we do pelvic fixation in patients with pelvic obliquity more than 15° (figure [2](#F2){ref-type="fig"}) or with severe lower extremity contractures. Westerlund et al \[[@B35]\] reported 66% correction in Cobb\'s angle and 75% correction in pelvic obliquity in twenty-six neuromuscular scoliosis with posterior-only unit rod instrumentation. They did not perform any anterior procedure in their series and reported excellent results in immature spine. Boachie-Adjei, et al \[[@B4]\] in their study with 46 patients of neuromuscular scoliosis had an equal number of patients in both the spastic and flaccid group and concluded that corrections for scoliosis and pelvic obliquity were similar in both the groups. In present study, we have also found similar correction in both Cobb\'s angle and pelvic obliquity without any anterior procedure over a follow-up of 25 months. In addition, none of the patient displayed deterioration in thoracic kyphosis or lumbar lordosis at final follow-up and therefore we did not feel any need for anterior procedure for the correction. Improvements in thoracic kyphosis and lumbar lordosis resulted in to improved sitting balance. Various authors \[[@B1],[@B2],[@B36]\] have used combined anterior and posterior approaches to correct scoliosis, usually in the presence of a very large or stiff curve. Their curves were all less than 90° and they achieved correction rates from 41% to 71%, mostly by using Luque or Unit rod systems. In the group with curve greater than 90° and the group who underwent PVCR, we observed curve correction of 50.31% and 47.65% respectively. To achieve more correction, we prefer PVCR \[[@B21]\] at another extra level. The pedicle screw system has an advantage of being a consolidated fixation including all three columns \[[@B5],[@B16],[@B17]\]. This greatly enhances the ability to simultaneously correct the three dimensional nature of these complex spinal deformities. Using the advantages of both pedicle screw and PVCR, better correction can be expected. Various studies have shown that posterior instrumentation with fusion alone is sufficient to correct and to maintain even larger and stiffer curves in neuromuscular scoliosis and it also prevents crankshaft phenomenon in skeletally immature patients \[[@B20],[@B28],[@B37],[@B38]\]. Reports have also shown that the addition of an anterior procedure, whether staged or same-day, potentially contributes to the risk profile and morbidity in these patients which further supports our criteria of avoiding such measures unless clear benefit can be supported. Our results support that neither anterior release nor anterior arthrodesis is generally indicated to obtain acceptable curve correction in even severe cases. There are various reports suggesting use of hooks in thoracic level. The main purpose of using hook was to avoid any neurological complications intraoperatively. However other reports \[[@B5],[@B16],[@B17]\] suggested that use of pedicle screw provides stronger purchase and better rotational correction in thoracic spine. Therefore we have used pedicle screws all levels in the subjects and did not notice any major neurological injury postoperatively. Our results are also comparable with the hooks or any other implants. In present study, all patients underwent for posterior-only pedicle screw and fusion for neuromuscular scoliosis were consecutive and not randomized which is, we think, the limitation of study. If operations had been done in selected patients, results would have been better than this. However, majority of patients achieved acceptable correction in thoracic kyphosis and lumbar lordosis with improvement in sitting balance showed the success of treatment. In addition patients\' parents or care takers have also reported better nursing care after operation. Conclusion ========== In conclusion, our series demonstrates the efficacy of posterior-only spinal fusion using the pedicle screw fixation for the definitive management of neuromuscular scoliosis. Curves greater than 90 degrees or rigid curves may require additional PVCR at single level or if necessary, at second level to achieve better outcome. Appropriate care requires the availability of specialized personnel acting as a multidisciplinary team. Our results demonstrate that posterior-only pedicle screw fixation with PVCR if necessary is effective in obtaining and maintaining alignment in the neuromuscular scoliosis population. This technique may avoid those risks incumbent with the addition of an anterior approach. Competing interests =================== The authors declare that they have no competing interests. Authors\' contributions ======================= HNM has contributed in conception and design and acquisition of data, analysis and interpretation of data, drafting the manuscript and revising it critically, SWS has contributed in conception and design of data, drafting the manuscript and given the final approval of manuscript, HRS has contributed in acquisition of data, revising the manuscript critically and given the final approval, HMF has contributed in drafting the manuscript and designing of data and revising it critically and JHY has contributed in acquisition of data and analysis and interpretation of data. All authors read and approved the final manuscript. Acknowledgements ================ No acknowledgements Each author certifies that he has no commercial associations (e.g. consultancies, stock ownership, equity interests, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article.
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64 S.W.3d 182 (2001) EASTLAND COUNTY COOPERATIVE DISPATCH, Clay Coffey, Wayne Bradford, Ken Wheeler, and Gerald Cozart, Appellants, v. Elnor Maxine POYNER, Individually and as Independent Executor of the Estate of William Euell Poyner, and as sole heir of William Euell Poyner,[1] Appellee. Eastland County Cooperative Dispatch, Eastland County, and the City of Gorman, Appellants, v. Elnor Maxine Poyner, Individually and as Independent Executor of the Estate of William Euell Poyner, and as sole heir of William Euell Poyner, Appellee. Nos. 11-00-00184-CV, 11-00-00284-CV. Court of Appeals of Texas, Eastland. October 25, 2001. Rehearing Overruled January 10, 2002. *186 James T. Jeffrey, Law Offices of Jim Jeffrey, Arlington, for Eastland County Cooperative Dispatch. Stephen D. Henninger, Tom Brandt, Fanning, Harper & Martinson, P.C., Dallas, for Eastland County, Wayne Bradford and Clay Coffey. Joseph E. Byrne, Wendy H. Hermes, Berry, Byrne & Randall, Dallas, for City of Gorman, Ken Wheeler and Gerald Cozart. James J. Elliott, Richard D. Coan, Coan & Elliott, L.L.P., Garry Lewellen, McMillan & Lewellen, Stephenville, for Appellee. Panel consists of ARNOT, C.J., and WRIGHT, J., and McCALL, J. OPINION WRIGHT Justice. These appeals arise from the suit Elnor Maxine Poyner filed following the death of her husband William Euell Poyner who was killed in an armed encounter with law enforcement officers. Eastland County Cooperative Dispatch, Eastland County Sheriff Wayne Bradford, Eastland County Deputy Sheriff Clay Coffey, City of Gorman Chief of Police Ken Wheeler, and City of Gorman Reserve Officer Gerald Cozart moved for summary judgment and asserted various immunity claims. The trial court denied all motions for summary judgment, and No. 11-00-00184-CV is the interlocutory appeal from that order pursuant to TEX. CIV. PRAC. & REM. CODE ANN. § 51.014(a)(5) (Vernon Supp. *187 2001).[3] For the reasons stated in this opinion, we affirm the judgment denying official immunity to Deputy Coffey and Officer Cozart, but we reverse the judgment denying the motions for summary judgment in all other respects and dismiss those claims against all appellants. Eastland County Cooperative Dispatch is a governmental unit, and we do not have jurisdiction to hear its interlocutory appeal. See Section 51.014(a)(5). The appeal is dismissed as to Eastland County Cooperative Dispatch. By a 1997 amendment to TEX. CIV. PRAC. & REM. CODE ANN. § 51.014(a) (Vernon Supp.2001), the legislature added Section 51.014(a)(8) which provides that a governmental unit may file an interlocutory appeal from the denial of a plea to the jurisdiction. See Section 51.014(a)(8). See also Texas Department of Criminal Justice v. Miller, 51 S.W.3d 583, 586 n. 2, 44 Tex. Sup.Ct. J. 963, 964 n. 2 (2001). Eastland County, the City of Gorman, and Eastland County Cooperative Dispatch each filed pleas to the jurisdiction claiming immunity. The trial court denied those pleas to the jurisdiction, and No. 11-00-00284-CV is the appeal from those rulings. For the reasons stated in this opinion, we reverse the trial court's ruling upon the pleas to the jurisdiction and render judgment dismissing the claims against Eastland County, the City of Gorman, and Eastland County Cooperative Dispatch. Because the resolution of each of these appeals involves common questions, although under somewhat different standards of review, we will consider them together. We will first address the summary judgment rulings, and then we will discuss the rulings on the pleas to the jurisdiction. MOTIONS FOR SUMMARY JUDGMENT Standard of Review The standard of review in cases in which the trial court has denied a motion for summary judgment is the same standard used to review the granting of a motion for summary judgment. City of San Antonio v. Hernandez, 53 S.W.3d 404 (Tex.App.-San Antonio 2001, pet'n den'd); see also Bartlett v. Cinemark USA, Inc., 908 S.W.2d 229 (Tex.App.-Dallas 1995, no writ). The question is whether the movant has met its burden of showing that there are no genuine issues of material fact and that judgment should be granted as a matter of law. Nixon v. Mr. Property Management Company, Inc., 690 S.W.2d 546 (Tex.1985). All evidence favorable to the non-movant must be taken as true, and all reasonable doubts must be resolved in favor of the non-movant. Nixon v. Mr. Property Management Company, Inc., supra. In order to prevail upon a motion for summary judgment based upon an affirmative defense, the movant must come forward with summary judgment evidence for each element of the affirmative defense. American Tobacco Company, Inc. v. Grinnell, 951 S.W.2d 420, 425 (Tex. 1997); Nichols v. Smith, 507 S.W.2d 518 (Tex.1974). If the movant conclusively establishes the defense, then it is incumbent upon the non-movant to come forward with summary judgment evidence to the contrary. Torres v. Western Casualty and Surety Company, 457 S.W.2d 50 (Tex. 1970) Appellants filed their motions for summary judgment in accordance with TEX. *188 R.CIV.P. 166a(c) ("traditional" motion for summary judgment) and also in accordance with TEX.R.CIV.P. 166a(i) (a "no-evidence" motion for summary judgment), alleging that appellee had no evidence on one or more elements of the causes of action. Because our holding in connection with the "traditional" motions for summary judgment is dispositive of this appeal except as to Deputy Coffey and Officer Cozart, we need only discuss the "no-evidence" aspect of appellants' motions for summary judgment as to them. The summary judgment evidence presented in this case reveals that 96-year-old William Euell Poyner died as a result of gunshot wounds which he received during a confrontation with law enforcement personnel. Mr. Poyner and his wife, Elnor Maxine Poyner, lived in Eastland County, just outside the city limits of the City of Gorman. Mrs. Poyner was 81 years old. On the night of the shooting, Mrs. Poyner telephoned the Gorman Police Department. The summary judgment evidence showed that the call was made at 10:39 p.m. Calls to the Gorman Police Department were forwarded to the Eastland County Cooperative Dispatch, a governmental unit created pursuant to what is now TEX. GOV'T CODE ANN. § 791.001 et seq. (Vernon 1994 & Supp.2001). Dispatch provided 9-1-1 services within Eastland County; and it also conducted the law enforcement dispatch business for certain governmental bodies, including the County of Eastland and the City of Gorman. When she talked to the Dispatch employee, Mrs. Poyner informed him that Mr. Poyner mistakenly thought that she was involved with other men. She told Dispatch that, on this particular night, she had awakened Mr. Poyner to get him to stop snoring. Other summary judgment evidence shows that she eventually went into another room to sleep and turned the light off in the bedroom. Shortly after that, she noticed that the light in the bedroom was on again. When she went into the bedroom, Mrs. Poyner noticed that Mr. Poyner was fully dressed and was looking through a drawer for his "six shooter." She told Dispatch that Mr. Poyner had been looking for the "six shooter," that he had found another gun, and that he was probably out "on the carport." Lights from vehicles traveling down the highway in front of the Poyner's house would shine into their house, and Mr. Poyner thought that these lights were signals from Mrs. Poyner's boyfriends for her to come out. This particular night was high school graduation night, and there was a lot of traffic on the highway. Although he could not find his "six shooter," Mr. Poyner did find a shotgun. He told Mrs. Poyner: "I'm going to stop this tonight." Mrs. Poyner told Dispatch how to get to their house and that she would leave the porch light on. Gorman Police Officer Abel Saldana arrived at the Poyner residence first. After the Dispatch employee talked with Mrs. Poyner, Deputy Coffey was dispatched to the Poyner home. Eventually, Deputy Coffey and Officer Cozart arrived at the scene. Eastland County Constable Tipton was also there. The officers' vehicles were parked in such a manner that the headlights were shining toward the Poyner's house. Officer Cozart's vehicle was parked so that the headlights were shining at the back of the house. The red and blue emergency lights were turned off on all of the law enforcement vehicles, and Mr. Poyner had turned the lights off inside the house. When Officer Saldana talked with Mrs. Poyner, she appeared to be shaking and nervous. She told Officer Saldana that he needed to talk to Mr. Poyner and that Mr. Poyner had a gun and was accusing her of *189 running around on him. Mrs. Poyner was placed in a safe place away from the house, and Mr. Poyner was still in the house. While Deputy Coffey was talking to Mrs. Poyner, Officer Cozart told the others that Mr. Poyner was coming out of the house and that he had either a rifle or a shotgun. Mr. Poyner came out of the house very slowly and walked in a slow shuffling movement, which was his usual way of walking. Deputy Coffey came to the back of the house and began to approach Mr. Poyner. The summary judgment evidence presented by appellants shows that the officers told Mr. Poyner to drop the gun and called his name several times. Mr. Poyner suffered from a hearing problem, and that information had been conveyed to Deputy Coffey. Summary judgment evidence presented by appellee contains the statements as well as the deposition testimony of two non-law enforcement personnel. These witnesses testified that they did not hear the officers identify themselves nor did they hear the officers order Mr. Poyner to drop his weapon. However, the witnesses also said that they could not say that the command was not given and that, because they were on the other side of the house, they might not have heard it. The summary judgment record reveals that Officer Cozart first saw Mr. Poyner begin to raise his weapon to a firing position and that the officers began to fire multiple rounds at Mr. Poyner. The summary judgment evidence conclusively establishes that no other persons were in a position to see whether Mr. Poyner raised his weapon to a firing position prior to being fired upon by the officers. Mr. Poyner died as a result of the gunshot wounds. Mrs. Poyner, for herself and as executrix of Mr. Poyner's estate, sued appellants and sought damages under 42 U.S.C.A. § 1983 et seq. (West Pamph. Supp.2001), as well as for damages under state law brought about by claims of varying degrees of negligence and culpability of those persons and entities involved.[4] Each appellant filed motions for summary judgment. The motions for summary judgment implicated the doctrines of sovereign immunity, official immunity, and qualified immunity. The trial court denied all of the motions for summary judgment without giving reasons for denying the motions. The petition filed in the trial court by appellee contained multiple allegations. Although the petition does not constitute summary judgment evidence, we feel that it is appropriate to an understanding of the issues on appeal for us to detail the allegations made against appellants by appellee. Further, it is necessary for us to discuss the allegations in connection with the pleas to the jurisdiction filed by the governmental units. The live petition contained general allegations of wrongful acts of appellants and others, followed by certain specifically-enumerated allegations, and then follow other additional general allegations of wrongful acts. Generally, the allegations were that the officers at the scene trespassed with vehicles belonging to Eastland County and the City of Gorman and that they shined the headlights of the vehicles onto Mr. Poyner's property and into his face so that he could not identify those present as law enforcement officers. Further, appellee alleged that the officers intentionally and knowingly disguised their identity. Appellee also maintained that the officers used large caliber weapons to shoot and kill Mr. Poyner with reckless abandon. Appellee alleged that all of the conduct named "was done negligently, with reckless disregard *190 and conscious indifference to the rights of Decedent." Appellee also stated in the petition that the shooting was committed through the gross negligence of the officers, as well as through the incompetence of the officers, with conscious indifference to Mr. Poyner's rights. Further, appellee complained that, through the gross negligence of the City of Gorman, Eastland County, and Dispatch, false information was knowingly and with reckless disregard and conscious indifference to Mr. Poyner's rights transmitted to the responding officers, creating a false impression in the minds of the responding officers. In other general allegations, appellee stated that the City of Gorman, Eastland County, and Dispatch negligently and with conscious indifference to Mr. Poyner broadcasted false and misleading information throughout the entire episode. The allegations further complained of a negligent entrustment by the City of Gorman, Eastland County, Sheriff Bradford, and Chief Wheeler. Appellee also alleged that the named parties were negligent in hiring and in arming Deputy Coffee and Officer Cozart when they should have known of their incompetency, their inadequate training, and their propensity to "make mistakes and panic." Appellee alleged that such conduct was unconscionable. Appellee also alleged in her pleadings that Eastland County and the City of Gorman hired incompetent and mentally unstable officers and that those officers failed to heed advice given to them regarding the fact that there was a lack of any threat from Mr. Poyner. Appellee further alleged that the officers ignored information given to them regarding Mr. Poyner's physical condition. Appellee also pleaded that the officers failed to identify themselves to Mr. Poyner and that they also failed to advise him of the nature of their visit. The general allegations also provided that the officers created a situation in which Mr. Poyner could not identify them by failing to display their emergency overhead lights. In 22 specifically numbered allegations, appellee alleged negligence against all parties, except Dispatch. We quote those allegations exactly as they appeared in the live petition: 1. Negligent entrustment; 2. Negligent hiring; 3. Negligent in failing to check background of their police officers; 4. Negligent in failing to supervise their police officers and other employees; 5. Negligent in failing to properly train their police officers and other employees; 6. Negligent handling of citizen requests for assistance; 7. Negligently dispatching of officers; 8. Negligently drawing inaccurate conclusions and broadcasting the opinions and biases of the dispatch instead of the information received from Plaintiff; 9. Negligent in gross misrepresentations of fact to responding officers; 10. Negligent in using excessive force; 11. Negligent in not following usual and standard police methods and procedures, including methods involving the least necessary force; 12. Negligent use of firearms; 13. Negligent use of official vehicles; 14. Failure to warn the Decedent; 15. Wrongful entry on the Decedent's property without a warrant; 16. Use of excessive force; 17. Negligently failing to heed the advice and warnings of other officers who warned that the Decedent was old and deaf and could not hear officers; *191 18. Negligently failing to assess the situation, including the lack of any threat posed by Decedent and the physical condition of Decedent; 19. Failure to remove the officers that committed the homicide from active duty; 20. Allowing the officers who committed the homicide to participate in the crime scene investigation and, in fact, allowing them to control the crime scene and access evidence; 21. Negligently acting in a state of panic and failure to exercise standard police procedure; and 22. Negligent training and supervision. In 16 separately enumerated paragraphs, appellee alleges negligence against Dispatch. We again quote those allegations exactly as they appeared in the live petition: 1. Negligent entrustment; 2. Negligent hiring; 3. Negligent in failing to check background of their officers and employees; 4. Negligent in failing to supervise their officers and other employees; 5. Negligent in failing to properly train their officers and other employees; 6. Negligent handling of citizen requests for assistance; 7. Negligent dispatching of officers; 8. Negligently drawing inaccurate conclusions and broadcasting the opinions and biases of the dispatch and dispatch personnel instead of the information received from Plaintiff; 9. Negligent in gross misrepresentations of fact to responding officers; 10. Negligent in using or causing to be used excessive force; 11. Negligent in not following usual and standard police methods and procedures, including methods to advise officers properly so as to involve the least necessary force. 12. Use or causing to be used of excessive force; 13. Negligently failing to heed the advice of Plaintiff; 14. Negligently failing to assess the situation, including the lack of any threat posed by Decedent and the physical condition of Decedent; 15. Negligently acting in a state of panic or excitement and failure to exercise standard police procedure; and 16. Negligent training and supervision. Following those specifically enumerated allegations, appellee continued with additional general allegations. Appellee contended that the City of Gorman, Eastland County, Sheriff Bradford, and Chief Wheeler failed to give advice to their officers regarding coping with the stress of their jobs; that they failed to maintain proper policies or that the policies were inadequate regarding such things as use of deadly force and use of emergency overhead lights on the police vehicles; that they failed to evaluate the psychiatric, psychological, and emotional stability of the officers, including alcohol abuse and anger control; that Eastland County and the City of Gorman wrongfully delegated its duties to Dispatch and their untrained, uncertified employees; that the City of Gorman, Eastland County, Sheriff Bradford, and Chief Wheeler conspired to create a cover-up; that the officers improperly used cover; that the officers improperly advanced upon the victim; and that the officers failed to use a non-lethal means to resolve the issue. With this background for an understanding of the nature of the case and bearing in mind the standard of review in cases involving the denial of motions for summary judgments and pleas to the jurisdiction *192 based on immunity, we will examine the various types of immunity claims involved. Immunity Generally Governmental immunity is a common-law rule. Harris County Flood Control District v. Mihelich, 525 S.W.2d 506 (Tex.1975). Governmental immunity encompasses both sovereign immunity and official immunity. Federal Sign v. Texas Southern University, 951 S.W.2d 401 (Tex. 1997); Delaney v. University of Houston, 835 S.W.2d 56 (Tex.1992). As we will discuss later, governmental units are immune from suit in certain circumstances, and qualified immunity also is available for individuals under Section 1983. Therefore, in reaching a resolution of this case, we must examine and discuss three types of immunity: (1) official immunity, (2) qualified immunity, and (3) sovereign immunity. OFFICIAL IMMUNITY 1. Traditional Summary Judgment We must first determine whether Sheriff Bradford, Deputy Coffey, Chief Wheeler, and Officer Cozart are protected from individual liability in this case by virtue of the doctrine of official immunity. They have been sued not only in their official capacities but also in their individual capacities. Unlike sovereign immunity, the doctrine of official immunity is not a bar to suit (a jurisdictional issue) but is a bar to liability and shields the party claiming official immunity from liability in the suit individually. McCartney v. May, 50 S.W.3d 599 (Tex.App.-Amarillo 2001, no pet'n). Official immunity is an affirmative defense which protects government employees, in their individual capacities, from liability related to: (1) the performance of discretionary duties, (2) within the scope of the employee's authority, (3) if the employee acts in good faith. City of Lancaster v. Chambers, 883 S.W.2d 650 (Tex.1994). Because it is an affirmative defense, the burden is upon the movant to establish each element of the defense. Nichols v. Smith, supra. If the movant establishes the defense, then the non-movant must come forward with summary judgment evidence to the contrary. Torres v. Western Casualty and Surety Company, supra. First, we hold that the officers have shown that they were performing discretionary functions and that there is no summary judgment proof to the contrary. Officials perform discretionary acts when the actions are those which involve "personal deliberation, decision, and judgment." See Vasquez v. Hernandez, 844 S.W.2d 802, 804 (Tex.App.-San Antonio 1992, writ dism'd w.o.j.). Next, we hold that the officers have shown that they were performing those discretionary duties within the scope of their authority. Officers act within the scope of their authority if they are discharging duties generally assigned to them. City of Lancaster v. Chambers, supra. The question then becomes whether the officers acted in good faith. In official immunity cases, good faith is measured against a standard of objective legal reasonableness, and the subjective state of mind of the officer is irrelevant. City of Lancaster v. Chambers, supra. The test for good faith is analogous to an abuse of discretion standard. An officer acts in bad faith only if he could not have reasonably reached the decision in question. University of Houston v. Clark, 38 S.W.3d 578 (Tex.2000). In order to establish the "good faith" element of their defense of official immunity, it was necessary for the officers to establish that a reasonably prudent officer *193 could have believed that his or her actions were justified under the circumstances. City of Lancaster v. Chambers, supra; Alamo Workforce Development, Inc. v. Vann, 21 S.W.3d 428 (Tex.App.-San Antonio 2000, no pet'n). Once the officers establish that element, the non-movant must come forward with summary judgment evidence which shows "that no reasonable person in the officer's position could have thought that the facts justified the officer's acts." University of Houston v. Clark, supra at 581. The summary judgment evidence shows that, on the night of the shooting, Sheriff Bradford requested that Texas Ranger Bobby Grubbs conduct an investigation into the events of the evening. Ranger Grubbs performed that investigation, and the summary judgment evidence details his credentials and his investigation. After giving the details of his investigation, Ranger Grubbs testified that both Deputy Coffey and Officer Cozart acted as reasonable officers based on the information they had at the time. He saw nothing that would indicate that the use of force was not justified, and he also testified that all of the evidence considered by him shows that the use of force was justified. The summary judgment evidence also shows that Sheriff Bradford was of the same opinion regarding Deputy Coffey and stated that: "In my opinion, a reasonably prudent police officer, in the same situation as Deputy Coffey, could have believed that his actions were justified." Sheriff Bradford further testified regarding his hiring, training, and supervising practices. His testimony was also to the effect that, at all times pertaining to this lawsuit, Officer Coffey's actions were reasonable, proper, and necessary in connection with the performance of his duties. Chief Wheeler also provided summary judgment evidence. His testimony was that Officer Cozart acted reasonably with respect to the incident made the basis of this lawsuit and that Officer Cozart's use of his firearm was justified. He also testified regarding the policies of the Gorman Police Department, and it was his opinion that neither he nor any of his officers committed any act which constituted either negligence or proximate cause of any injury connected with the incident made the basis of this lawsuit.[5] After appellants produced the summary judgment evidence outlined above, it was incumbent upon appellee to come forward with summary judgment evidence "that no reasonable person in the officer's position could have thought that the facts justified the officer's acts." University of Houston v. Clark, supra at 581. Appellee's summary judgment evidence included an affidavit from an expert witness on law enforcement, Danny B. Steffenauer. Steffenauer outlined his credentials and gave the basis for his expert opinion. He swore that there was a lack of any sufficient policy in the Eastland County Sheriff's Office or the City of Gorman regarding deadly force and armed encounters. It was also Steffenauer's opinion that this lack was a negligent and proximate cause of the confrontation and the death of Mr. Poyner. He is of the further opinion that: [N]o reasonable and prudent police officer, acting under the same or similar *194 circumstances as those confronting the officers at the Poyner residence, would not have created or permitted such a fact situation ... which raised an issue of the need to use deadly force at all against [Mr.] Poyner. Poyner's death could have been avoided, without resorting to deadly force, had such officers followed even the most elemental concepts of the use of deadly force.[6] The affidavit sets forth the details upon which Steffenauer bases his opinion. Steffenauer's expert opinion was directed toward the policies of Eastland County and the City of Gorman and at the actions of Deputy Coffey and Officer Cozart while at the scene. Sheriff Bradford's and Chief Wheeler's summary judgment evidence regarding official immunity was not controverted by proof that no reasonable officer acting under the same or similar circumstances could have believed that the decisions which they made at any point in time complained of in this lawsuit were proper. The trial court erred when it failed to grant official immunity to Sheriff Bradford and Chief Wheeler in their individual capacities. Because appellee came forward with summary judgment proof to controvert the official immunity claims of Deputy Coffey and Officer Cozart, the trial court did not err in overruling their motions for summary judgment relating to official immunity from personal liability. 2. Deputy Coffey's and Officer Cozart's "No Evidence" Motions for Summary Judgment Because we have held that Deputy Coffey and Officer Cozart were not entitled to summary judgment under their "traditional" motions for summary judgment, it is necessary for us to discuss their claims to summary judgment under TEX. R.CIV.P. 166a(i) "no-evidence" motions for summary judgment. In this connection, we view only the evidence presented by the non-movant. Hight v. Dublin Veterinary Clinic, 22 S.W.3d 614 (Tex.App.-Eastland 2000, pet'n den'd). We will accept as true evidence that is favorable to non-movants, and we will indulge every reasonable inference and resolve all doubts in favor of non-movants. Lavy v. Pitts, 29 S.W.3d 353, 356 (Tex.App.-Eastland 2000, pet'n den'd). A no-evidence summary judgment is not proper if the non-movant presents more than a scintilla of evidence in answer to the motion for summary judgment. Lavy v. Pitts, supra. We have set forth the non-movant's summary judgment evidence. We again hold that appellee has presented more than a scintilla of evidence to prevent the application of the doctrine of official immunity to the individual claims against Deputy Coffey and Officer Cozart and that neither officer was entitled to a no-evidence summary judgment on this claim. SECTION 1983 CLAIMS We now review the trial court's action when it denied the motions for summary judgment filed by Sheriff Bradford, Chief Wheeler, Deputy Coffey, and Officer Cozart in connection with the Section 1983 claims. Those motions were based, in part, on the officials' claims to qualified immunity. "Qualified immunity is an entitlement not to stand trial or face the other burdens of litigation." Saucier v. Katz, 533 U.S. 194, 121 S.Ct. 2151, 150 L.Ed.2d 272, 281 (2001) (quoting Mitchell v. Forsyth, 472 U.S. 511, 526, 105 S.Ct. 2806, 86 *195 L.Ed.2d 411 (1985)). It is not a defense to liability; it is an immunity from suit. Saucier v. Katz, 121 S.Ct. 2151, 150 L.Ed.2d at 281. In Anderson v. Creighton, 483 U.S. 635, 107 S.Ct. 3034, 97 L.Ed.2d 523, 534 (1987), Justice Scalia, writing for a majority of the Court, stated: The general rule of qualified immunity is intended to provide government officials with the ability "reasonably [to] anticipate when their conduct may give rise to liability for damages." Where that rule is applicable, officials can know that they will not be held personally liable as long as their actions are reasonable in light of current American law. (Citations omitted) In discussing the reason behind the rule, the Court in Anderson v. Creighton, 107 S.Ct. 3034, 97 L.Ed.2d at 529 further stated: When government officials abuse their offices, "action[s] for damages may offer the only realistic avenue for vindication of constitutional guarantees." On the other hand, permitting damages suits against government officials can entail substantial social costs, including the risk that fear of personal monetary liability and harassing litigation will unduly inhibit officials in the discharge of their duties. (Citation omitted) Our cases have accommodated these conflicting concerns by generally providing government officials performing discretionary functions with a qualified immunity, shielding them from civil damages liability as long as their actions could reasonably have been thought consistent with the rights they are alleged to have violated. See, e.g., Malley v. Briggs, 475 U.S. 335, 341, 106 S.Ct. 1092, 89 L.Ed.2d 271 (1986) (qualified immunity protects "all but the plainly incompetent or those who knowingly violate the law"). It is important to remember that we are not reviewing this case on its merits with the standards attendant upon such a review and that we are only reviewing the application of immunity upon motions for summary judgment. In cases involving the preliminary review of the use of excessive force, whether qualified immunity is available and whether excessive force actually was used in a particular case are different inquiries. Saucier v. Katz, supra. The test for determining the existence of qualified immunity in this context is a two-part test. The first part of the inquiry is "whether a constitutional right would have been violated on the facts alleged." Saucier v. Katz, 121 S.Ct. 2151, 150 L.Ed.2d at 281. In other words, when we consider the summary judgment evidence in the light most favorable to the non-movant, does that evidence show that the conduct complained of violated a constitutional right? If the evidence does not show that a constitutional right has been violated, then the matter is at an end; and qualified immunity protects the official. If the favorable consideration of the evidence reveals that a violation of a constitutional right could be shown, then the next inquiry is whether that right was clearly established at the time. Saucier v. Katz, supra. Whether a right has been clearly established involves more than a broad, general proposition. Saucier v. Katz, supra. As an example, the court in Saucier noted that in Graham v. Connor, 490 U.S. 386, 109 S.Ct. 1865, 104 L.Ed.2d 443 (1989), it was established that the use of force, if excessive under the objective standard of reasonableness, violates the Fourth Amendment. However, when determining immunity, that is not enough. "The contours of the right must be sufficiently clear that a reasonable official would understand that what he is doing violates that right." Saucier v. Katz, 121 *196 S.Ct. 2151, 150 L.Ed.2d at 282. We must review the matter within "the specific context of the case, not as a broad general proposition." Saucier v. Katz, 121 S.Ct. 2151, 150 L.Ed.2d at 281. As the Court did in Saucier, we will assume, without deciding for purposes of this opinion, that a constitutional violation could have occurred under the summary judgment evidence based upon the general prohibition against excessive force. Was that general prohibition the source for clearly established law which the officers violated in this case? "The question is what the officer[s] reasonably understood [their] powers and responsibilities to be, when [they] acted, under clearly established standards." Saucier v. Katz, 121 S.Ct. 2151, 150 L.Ed.2d at 285. When considered in the light most favorable to appellee, the summary judgment evidence presented by appellee shows that Deputy Coffey was advancing as opposed to retreating when Mr. Poyner was shot. However, the undisputed evidence establishes that, at the time Mr. Poyner was shot, the officers had just seen him raise his weapon to a firing position. The clearly established standards at the time provided that an officer was justified in using deadly force to protect himself. City of Dallas v. Half Price Books, Records, Magazines, Inc., 883 S.W.2d 374 (Tex.App.-Dallas 1994, no writ). Because there was no clearly established rule which would prohibit Deputy Coffey and Officer Cozart from using the force which they did, when faced with Mr. Poyner's weapon, they are entitled to qualified immunity from Section 1983 claims; and the trial court erred when it failed to grant that immunity to them.[7] Claims against Sheriff Bradford and Chief Wheeler basically related to matters connected with hiring, supervising, and training Deputy Coffey and Officer Cozart. Unless those policies and practices were entered into or conducted with conscious disregard or deliberate indifference to the risk that Deputy Coffey or Officer Cozart would commit the particular constitutional violation in question, they are entitled to immunity from suit under Section 1983. Board of the County Commissioners of Bryan County, Oklahoma v. Brown, 520 U.S. 397, 117 S.Ct. 1382, 137 L.Ed.2d 626, 641 (1997). Sheriff Bradford and Chief Wheeler both brought forth summary judgment evidence which established their hiring, training, and supervision practices. Viewing the summary judgment evidence in the light most favorable to appellee, no fact issue has been raised by the summary judgment evidence that any of the practices and procedures of which complaint is made were the result of deliberate indifference on the part of either Sheriff Bradford or Chief Wheeler. Sheriff Bradford and Chief Wheeler are entitled to immunity in connection with the Section 1983 claims, and the trial court erred when it failed to grant them that immunity. PLEA TO THE JURISDICTION When determining a plea to the jurisdiction, it is now clear that we consider *197 not only the plaintiff's pleadings but also the evidence before the trial court. Texas Department of Criminal Justice v. Miller, supra; Bland Independent School District v. Blue, 34 S.W.3d 547 (Tex.2000). In Texas Department of Criminal Justice v. Miller, supra, 51 S.W.3d at 587, 44 Tex. Sup. Ct. J. at 964-65, the court stated: "Under Jones, we must examine the plaintiff's pleadings to decide whether sovereign immunity has been waived." (Citing Texas Department of Transportation v. Jones, 8 S.W.3d 636, 639 (Tex.1999)). The court also said that it must "decide whether [the plaintiff] has `affirmatively demonstrate[d] the court's jurisdiction to hear the cause'" and that it will "consider the facts alleged by the plaintiff, and to the extent it is relevant to the jurisdictional issue, the evidence submitted by the parties." See also Texas Natural Resource Conservation Commission v. White, 46 S.W.3d 864, 868 (Tex.2001). Sovereign Immunity The government, its agencies, and its officials are protected from suit under the doctrine of sovereign immunity. Federal Sign v. Texas Southern University, supra. A governmental unit is clothed with sovereign immunity unless that immunity has been waived by the legislature. See City of San Antonio v. Hernandez, supra; see also Harris County v. Dillard, 883 S.W.2d 166 (Tex.1994). An employee of a governmental unit is also entitled to a claim of sovereign immunity in claims against him in his official capacity. McCartney v. May, supra. The doctrine of sovereign immunity implicates jurisdictional considerations. Vincent v. West Texas State University, 895 S.W.2d 469 (Tex.App.-Amarillo 1995, no writ). The legislature has provided for waiver of sovereign immunity in certain instances set forth in the Texas Tort Claims Act.[8] These instances of waiver are limited and are narrowly defined. Texas Department of Criminal Justice v. Miller, supra. It is the prerogative of the legislature to waive or not to waive the protection afforded by sovereign immunity. Federal Sign v. Texas Southern University, supra. Those instances in which the legislature has provided for waiver of immunity, as relevant here, are set forth in Section 101.021 of the Texas Tort Claims Act which provides: A governmental unit in this state is liable for: (1) property damage, personal injury, and death proximately caused by the wrongful act or omission or the negligence of an employee acting within his scope of employment if: (A) the property damage, personal injury, or death arises from the operation or use of a motor-driven vehicle or motor-driven equipment; and (B) the employee would be personally liable to the claimant according to Texas law; and (2) personal injury and death so caused by a condition or use of tangible personal or real property if the governmental unit would, were it a private person, be liable to the claimant according to Texas law. Although immunity might be waived under the provisions of Section 101.021, certain acts are exempted from that waiver of immunity. Those circumstances include instances in which the act complained of is an intentional one. See Section 101.057(2). The pleadings and proof did not establish that the death in this case arose *198 from the operation or use of a motor-driven vehicle or from a condition or use of tangible personal or real property, except for the weapons involved. Even assuming that the pleadings and evidence showed negligence or other wrongful acts, that conduct must involve a condition or use of tangible personal or real property. In Kassen v. Hatley, 887 S.W.2d 4, 14 (Tex. 1994), the supreme court stated that Section 101.021 "requires the property's condition or use to cause the injury." The fact that some property is involved is not enough. As the Miller court stated: "Using that property must have actually caused the injury." Texas Department of Criminal Justice v. Miller, supra, 51 S.W.3d at 588, 44 Tex. Sup. Ct. J. at 965. In this case, the alleged "use" of property was the headlights on patrol vehicles, emergency overhead lights, and similar uses of the vehicles. However, Mr. Poyner's death did not "arise from" the use of such property but, rather, from the intentional use of the weapons. The use of property must be such that it was the "direct device" causing the death, and there must be a "causal nexus" for liability; this has not been established. Holder v. Mellon Mortgage Company, 954 S.W.2d 786 (Tex.App.-Houston [14st Dist.] 1997), rev'd on other grounds, 5 S.W.3d 654 (Tex. 1999). Further, it is not enough that the property merely furnish the condition which makes the injury possible. Union Pump Company v. Allbritton, 898 S.W.2d 773 (Tex.1995); City of San Antonio v. Hernandez, supra. Likewise, failure to train, supervise, perform background checks, and other like claims made by appellee are not such that implicate the use of tangible personal or real property. While those are independent causes of action, under Section 101.021, the requirement that the claim be based upon the condition or the use of tangible personal or real property remains. See Texas Department of Public Safety v. Petta, 44 S.W.3d 575 (Tex.2001). The difficulty in applying the "use" provisions of the Texas Tort Claims Act has been the subject of discussion for many years. We note that the Texas Supreme Court has invited the attention of the legislature to this difficulty on several occasions. See Texas Department of Criminal Justice v. Miller, supra, 51 S.W.3d at 588-89, 44 Tex. Sup. Ct. J. 963 at 966, and cases cited therein. The matter of waiver of sovereign immunity is one addressed to the legislature, and any waiver must be "by clear and unambiguous language." DeWitt v. Harris County, 904 S.W.2d 650, 652 (Tex.1995). The legislature recently spoke to the issue of clear and unambiguous language when it enacted Act of June 15, 2001, 77th Leg., R.S., ch. 1158, § 8, 2001 Tex. Sess. Law Serv. ___ (Vernon) (to be codified at TEX. GOV'T CODE ANN. § 311.034): In order to preserve the legislature's interest in managing state fiscal matters through the appropriations process, a statute shall not be construed as a waiver of sovereign immunity unless the waiver is effected by clear and unambiguous language. In a statute, the use of "person," as defined by § 311.005 to include governmental entities, does not indicate legislative intent to waive sovereign immunity unless the context of the statute indicates no other reasonable construction. All of the remaining claims except one relate to the handling, mishandling, or ignoring of information, and similar claims. Those types of claims have long been held not to be subject to the waiver provisions of the Texas Tort Claims Act and do not involve the condition or the use or misuse of tangible personal or real property. See Texas Department of Public Safety v. Petta, *199 supra; see also University of Texas Medical Branch at Galveston v. York, 871 S.W.2d 175 (Tex.1994). Those claims pertaining to the use of firearms are the claims which remain for our discussion in connection with sovereign immunity. The pleadings and evidence suggest nothing other than that the officers intended to shoot Mr. Poyner. Merely claiming that an act is negligent does not change its nature. Medrano v. City of Pearsall, 989 S.W.2d 141 (Tex. App.-San Antonio 1999, no pet'n). While it provides for waiver of sovereign immunity in certain enumerated circumstances, the Texas Tort Claims Act also provides that the waiver does not apply in certain instances, such as where the injury or death is the result of an intentional tort. See Section 101.057(2). An intentional tort, as opposed to negligence, is one in which the actor has the specific intent to inflict injury. Reed Tool Company v. Copelin, 689 S.W.2d 404 (Tex.1985). The pleadings and evidence before the court show that Mr. Poyner's death was due to an intentional act which has been excluded from the waiver provisions of the Texas Tort Claims Act. Because the pleadings and evidence do not show that sovereign immunity was waived in this case and because the injury and death was caused by an intentional act, the trial court erred when it did not grant the pleas to the jurisdiction. For the same jurisdictional reasons, Sheriff Bradford, Deputy Coffey, Chief Wheeler, and Officer Cozart are also entitled to sovereign immunity in their official capacities. For the reasons stated in the above discussion concerning Section 1983 claims against Sheriff Bradford and Chief Wheeler, we determine that the trial court also erred when it denied the pleas to the jurisdiction filed by Eastland County, the City of Gorman, and Dispatch. We note that, while Dispatch has raised immunity issues regarding the state claims and the civil rights claims made under Section 1983, Eastland County and the City of Gorman raised immunity issues only under the state claims. However, Section 1983 immunity is jurisdictional and, therefore, must be addressed and may be raised at any time. See Monell v. Department of Social Services of the City of New York, 436 U.S. 658, 98 S.Ct. 2018, 56 L.Ed.2d 611 (1978). HOLDING IN CAUSE NO. 11-00-00184-CV The judgment of the trial court is affirmed in part and reversed and rendered in part. Insofar as it denied official immunity to Eastland County Deputy Sheriff Clay Coffey and City of Gorman Reserve Officer Gerald Cozart, the summary judgment is affirmed. Insofar as it denied summary judgment as to Eastland County Sheriff Wayne Bradford and City of Gorman Chief of Police Ken Wheeler, the judgment of the trial court is reversed and judgment is rendered granting Sheriff Bradford's and Chief Wheeler's motions for summary judgment. The interlocutory appeal filed by Eastland County Cooperative Dispatch is premature and is dismissed for want of jurisdiction. HOLDING IN CAUSE NO. 11-00-00284-CV The judgment of the trial court is reversed, and judgment is rendered dismissing the suit against Eastland County Cooperative Dispatch, Eastland County, and the City of Gorman brought by Elnor Maxine Poyner, Individually and as Independent Executor of the Estate of William Euell Poyner, and as sole heir of William Euell Poyner. NOTES [1] Mrs. Poyner is now deceased, and the suits are being prosecuted by Joan Johnson as executrix of both estates. Pursuant to the direction of TEX.R.APP.P. 7.1(a)(1), these appeals retain the original styles. [3] The trial court also denied motions for summary judgment filed by Eastland County and the City of Gorman. Those entities are not parties to the appeal in Cause No. 11-00-00184-CV. [4] All references to Section 1983 throughout this opinion refer to 42 U.S.C.A. § 1983. [5] We note that summary judgment evidence similar to that provided by Sheriff Bradford and Chief Wheeler was held sufficient in connection with summary judgment proof in City of Hidalgo v. Prado, 996 S.W.2d 364 (Tex. App.-Corpus Christi 1999, no pet'n). Appellants also provided the affidavit of another expert witness, Merlyn D. Moore, Ph.D. However, that affidavit was stricken by the trial court, and it will not be considered here. [6] While this portion of the affidavit actually stated that no reasonable officer would not have taken the action, it is clear from the context of the affidavit that the expert witness was expressing the opinion that "no reasonable and prudent officer ... would have" created the situation. [7] In a post-submission letter brief, appellee urges that the "state created danger" doctrine applies to the facts of this case. The cases which recognize the "state created danger" doctrine are distinguishable in that in those cases the State employees created a situation which increased the danger to the victim from third parties. Here, no third parties were involved. Further, in those cases recognizing the doctrine, the victims played no part in the harm that came to them. See, e.g., McClendon v. City of Columbia, 258 F.3d 432 (5th Cir.2001); Piotrowski v. City of Houston, 51 F.3d 512 (5th Cir.1995); Johnson v. Dallas Independent School District, 38 F.3d 198 (5th Cir.1994). The "state created danger" doctrine does not apply in this case. [8] All references to the Texas Tort Claims Act refer to TEX. CIV. PRAC. & REM. CODE ANN. § 101.001 et seq. (Vernon 1997 & Supp.2001).
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PREMIERS South Sydney are under attack from rival clubs, with Manly and the Warriors attempting to poach English international Tom Burgess. The Sunday Telegraph has learned the Warriors have offered Burgess, 22, $700,000-a-season to move to Auckland, while the Sea Eagles are using older brother Luke Burgess to talk up a move to the northern beaches. The off-contract Burgess, who will start Sunday’s match against Wests Tigers from the interchange bench, has assured Rabbitohs faithful his preference is to remain alongside twin, George. At the same time, money talks all languages and cashed-up NRL rivals are intent on pricing Souths out of the market for the emerging forward. FUN:Aaron Woods looking forward to Burgess battle INGLIS:‘It’s not about money’ “I’m in negotiations with Souths, we’ll see how we go with that,” Burgess said. “My manager lives in England so there’s a bit of emailing going back and forth and we had the chance to catch up when we were over there for the World Club Challenge. “We’ll hopefully get that sorted soon. I’ve loved my time at Souths. Souths is my first priority, but we’ll see what happens.” Burgess was the last of the brothers to move to Australia, serving his apprenticeship playing for the North Sydney Bears in the NSW Cup. He has played 28 NRL matches and won five Test caps for England. While George has established himself among the best front-rowers in the NRL, Tom is still a work in progress. The Sea Eagles’ interest in Burgess was initially made public in January when coach Geoff Toovey and new CEO Joe Kelly had a heated row in the Manly football offices at Narrabeen. Numerous staff had to be cleared out of the office as the pair let rip. The Sunday Telegraph has been told the club always intended to target Tom once they had Luke signed and sealed at Narrabeen. media_camera Burgess is rated a raw talent with plenty of potential. Armed with the biggest cheque book in the NRL, the Sea Eagles have also identified Sam Burgess as a potential­­­ ­target for next season. On the prospect of the Clive Churchill medallist quitting a stint in English rugby to return to the NRL with the Sea Eagles, Burgess said: “I speak to him every day and he’s enjoying the challenge. “With every game he plays he gets more of a feel for it. It’s quite technical. “Every club would probably target him, any club would be lucky to have him. I think his head’s pretty focused on what he wants to do over there.” George Burgess, who has begun this season as arguably the best front-rower in the NRL, said he was hopeful of convincing his twin to remain at Redfern. “It’s a great club to be at and why move somewhere if you’re happy at a club,” Burgess said. “Hopefully we can get the big boy signed up and enjoy it for a few years longer.”
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Reece Oxford and Nathan Trott have both been called up to the England U19s squad for the upcoming UEFA European Championships in Georgia. Both will join up with Keith Downing’s squad next week when they head to Murcia, Spain for a six-day training camp. The team will then return to St. George’s Park before flying out to Tbilisi, Georgia for the Euros, which begin on July 2. Oxford is hugely experienced on the international stage and could captain the side in Georgia, whereas Trott will be hoping to make his first appearance in a Three Lions jersey. The 18-year-old stopper was called-up to the squad for the three Elite Round qualifiers in March, but had to watch from the sidelines. He’ll be pushing for a starting spot in the first group fixture against Bulgaria on Monday 3 July. "It's a great feeling to get a call-up again," said Trott. "I've had a really good season and it's always an honour when you get a call-up to play for England. "It's been a long wait to get my first cap and hopefully during this camp for the Euros, I can impress the coach enough for me to get a start." The Young Lions they face the Netherlands three days laters before rounding of their Group B campaign against Germany on Sunday 9 July.
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Introduction ============ Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent disease that results from excessive fat accumulation in the liver. NAFLD not only affects the adult population (about 20--40% of adults in Western countries have fatty liver) \[[@b1]\], but is also the most common cause of paediatric liver disease \[[@b2]\]. NAFLD is now recognized as the hepatic manifestation of the metabolic syndrome (MS). In fact, there is a nearly universal association between MS comorbidities and NAFLD, because obesity, type 2 diabetes and hyperlipidaemia are known to co-exist in patients with fatty liver. NAFLD is also related to increased risk of cardiovascular diseases, such as carotid atherosclerosis \[[@b3]\]. Although many risk factors of NAFLD are well defined, its pathogenesis remains poorly understood. Recent evidence has implicated insulin resistance as a major contributor to the pathogenesis and disease progression of NAFLD \[[@b4]\]. In addition, NAFLD is associated with increased fatty acid β-oxidation, hepatic oxidative stress and mitochondrial structural defects \[[@b5]\]. For instance, crystalline inclusions are observed in hepatic mitochondria in non-alcoholic steatohepatitis (NASH), and their presence has been correlated either with an adaptive process or mitochondrial injury \[[@b6]\]. Mitochondrial function is critical in the physiopathology of NAFLD because liver mitochondria is a primary site for the oxidation of fatty acids and oxidative phosphorylation -- a process that requires multiple enzymes that are encoded by both nuclear DNA (nDNA) and mitochondrial DNA (mtDNA). Previous studies have revealed that qualitative and quantitative changes in skeletal muscle mtDNA are involved in the pathogenesis of type 2 diabetes \[[@b7]\]. Moreover, mtDNA content in peripheral blood leucocytes has been associated with insulin resistance in children and adult \[[@b8], [@b9]\]. These findings suggest that mitochondrial density and mtDNA copy number play a role in the mitochondrial dysfunction associated with MS-related phenotypes. However, its role in NAFLD is not well understood. An interesting mechanism recently related to the pathogenesis of NAFLD is the association between mitochondrial dysfunction and hepatocyte sensitivity to hypoxic stress \[[@b10]\]. Although imbalance in oxygen homeostasis is a well-known mechanism in many pathophysiological processes, including cardiovascular and cerebrovascular disease, cancer, etc., its role in NAFLD is scarcely explored. Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor involved in cellular and systemic homeostatic response to hypoxia; HIF-1 is a heterodimeric protein complex comprising two subunits, among which, the redox-sensitive HIF-1α is considered to be the major regulator of O~2~-tension-sensitive genes in cells \[[@b11]\]. Interestingly, HIF-1α has been described as an important regulator of mitochondrial biogenesis in muscle \[[@b12]\], whereas sustained hypoxia in brain has been associated with an increase in neuronal mtDNA content \[[@b13]\]. In view of the evidence described earlier, we evaluated the molecular mechanisms that may be involved in the regulation of liver mtDNA content in a high-fat-induced rat model of NAFLD. In particular, we tested the hypothesis that liver mtDNA copy number is associated with liver expression of *HIF-1α*. We also examined liver mRNA abundance of master nuclear genes involved in the regulation of mitochondrial biogenesis and mtDNA transcription and replication. Furthermore, the occurrence of oxidative stress in the liver of high-fat solid diet (HFD)-induced NAFLD was also assessed. Finally, the effect of pharmacological reversion of hepatic steatosis on liver mtDNA content was evaluated. For the intervention experiment we chose telmisartan, an angiotensin II receptor blocker considered also to act as a partial agonist of PPARγ, as we and others previously demonstrated its efficacy in reducing hepatic lipid accumulation and reverting liver steatosis in a rat model of NAFLD \[[@b14], [@b15]\]. Materials and methods ===================== Animals ------- Twelve-week-old male Sprague-Dawley rats weighing 280 ± 20 g were purchased from the Research Animal Facility of School of Veterinary Medicine, University of Buenos Aires. All the animals were housed individually with food and water freely available and were maintained at room temperature (23 + 1°C) under a 12 hr light/dark cycle. All the animals received humane care, and the studies were conducted according to the regulations for the use and care of experimental animals. After acclimatization for 1 week, the rats were randomly divided into two experimental groups. One group included 10 rats that received standard chow diet (SCD) for 20 weeks, and the quantity of the diet was restricted to that spontaneously consumed at the beginning of the experiment (control group, SCD). The other group, including 15 animals, was allowed *ad libitum* access to HFD (40% (w/w) bovine and porcine fat added to the standard chow, as previously described \[[@b16]\] for the same period of time. In all the animals, food intake and body weight were monitored weekly for the 20 week period. At the completion of the study, the animals were anesthetized with pentobarbital and killed. Blood from individual rats was collected by cardiac puncture to determine the plasma and serum levels of different biochemical parameters. Food was withdrawn from 8:00 a.m. to 4:00 p.m., before the rats were killed, and the intraperitoneal and retroperitoneal fats were measured by weighting them directly. Liver was quickly snap-frozen and stored at −76°C until gene expression analysis. A portion of each liver was fixed in 10% formalin for histological analysis. Two additional samples of liver tissue (150 mg) were stored at −80°C for quantifying liver lipids. Biochemical measurements ------------------------ Serum and sodium ethylenediaminetetraacetic acid plasma were obtained by centrifugation and stored at −80°C until needed. Fasting glucose and serum alanine aminotransferase (ALT) were measured by an automatic biochemical analytical system (Architect, Abbott, Buenos Aires, Argentina). The plasma insulin levels were determined using a commercial quantitative ultrasensitive ELISA rat kit according to the manufacturer's instructions (CRYSTAL CHEM, INC., Downers Grove, IL, USA). Insulin resistance was calculated using the homeostasis model of assessment (HOMA) index (fasting plasma insulin \[μU/ml\]× fasting plasma glucose \[mmol/l\]/22.5). Histological analysis of liver tissue ------------------------------------- Formalin-fixed liver tissue was processed, and 5-μm-thick paraffin sections were stained with haematoxylin and eosin and Masson's trichrome (for selective demonstration of collagen fibres and fibrin) and Gomori's reticulin silver impregnation (for the evaluation of reticular fibres and collagen type III/IV) for histological analysis. In both experimental groups, osmium tetroxide staining was also carried out to estimate the degree of hepatic steatosis. The degree of steatosis was assessed irrespective of the experimental groups as previously described \[[@b17]\], based on the percentage of hepatocytes containing macrovesicular fat droplets: grade 0, no steatosis or steatosis \<5%; grade 1, \>5% to \<33% of hepatocytes-containing macrovesicular fat droplets; grade 2, \>33--66% of hepatocytes-containing macrovesicular fat droplets and grade 3, \>66% of hepatocytes containing macrovesicular fat droplets. Electron microscopy ------------------- Electron microscopy studies were performed on liver specimens by immersion in 3% glutaraldehyde buffered by cacodile buffer of pH 7.4, and then post-fixed in 1% osmium tetroxide and embedded in epoxy resin (Polibed®, Poly-Sciences, Warrington, PA, USA). The samples were examined and photographed in an electron microscope (Zeiss EM 109, Zeiss, Oberkochen, Germany), and the sections were evaluated by an electron microscopist (NL). Measurement of liver triglyceride content ----------------------------------------- The liver triglyceride content was determined using an automatic biochemical analytical system (Architect, Abbott), and the results were expressed as micrograms of triglyceride per milligram of liver tissue (μg/mg liver). RNA preparation and Real-Time RT-PCR for quantitative assessment of mRNA expression ----------------------------------------------------------------------------------- Total RNA was prepared from rat livers using phenol extraction step method, with an additional DNAse digestion. For RT-PCR, 3 μg of total RNA was reverse-transcribed using random hexamers and Moloney murine leukaemia virus (MMLV) reverse transcriptase (Promega, Madison, WI, USA). Real-time PCR was performed for quantitative assessment of mRNA expression in an iCycler thermocycler (BioRad, Hercules, CA, USA) using the fluorescent dye, SYBR-Green (Invitrogen, Buenos Aires, Argentina). All the real-time PCR reactions were run in triplicate and all the samples of the experimental groups were tested. The relative expression of target genes' mRNA was normalized to the amount of a housekeeping gene (peptidylprolyl isomerase A, PPIA, also termed as cyclophilin A) to carry out comparisons between the groups. Cyclophilin was found to be the most stable reference gene for testing liver mRNA expression among other housekeeping genes tested before starting the experiment \[β-actin, TATA box binding protein, and glyceraldehyde-3-phosphate dehydrogenase (*GAPDH*)\]. The levels of mRNA were expressed as the ratio of the estimated amount of the target gene relative to the *PPIA* mRNA levels using fluorescence threshold cycle values (Ct) calculated for each sample, and the estimated efficiency of the PCR for each product was expressed as the average of each sample efficiency value obtained \[[@b18]\]. The specificity of amplification and absence of primer dimers were confirmed using melting curve analysis at the end of each run. The primer sequences and the resulting PCR product lengths are shown [Table 1](#tbl1){ref-type="table"}. ###### Primers Used for the mRNA gene expression--PCR reaction and quantification of mtDNA **Gene name** **Primer sequence** **Amplicon size (bp)** ------------------------------------------------------- ----------------------------------------------------------------------------------------- ------------------------ HIF1-α Forward 5′-TGT GTG TGT GAA TTA TGT TG-3′ Reverse 5′-GTC CTC AGA TTC CAC TTT AG-3′ 142 PGC1α Forward 5′-AAA AGC TTG ACT GGC GTC AT-3′ Reverse 5′-TCA GGA AGA TCT GGG CAA AG-3′ 129 Tfam Forward 5′-GGC AGA AAC GCC TAA AGA AG-3′ Reverse 5′-TCA TCC TTA GCC TCC TGG AA-3′ 127 *NRF-1* Forward 5′-CGC AGT GAC GTC CGC ACA GA-3′ Reverse 5′-AAG GTC CTC CCG CCC ATG CT-3′ *PPARδ* Forward 5′-AGG CCT CAG GCT TCC ACT AC-3′ Reverse 5′-TTG CGG TTC TTC TTC TGG AT-3′ 130 COX4I1 Forward 5′-CTT GTC CTG ATC TGG GAG AA-3′ Reverse 5′-GAC CTT CAT GTC CAG CAT CC-3′ 105 PGC1*b* Forward 5′-TTG ACA GTG GAG CTT TGT GG-3′ Reverse 5′-CTG TGC TTG GTG TCC TGC T-3′ 101 Bax Forward 5′-CTG CAG AGG ATG ATT GCT GA-3′ Reverse 5′-GGG CAC TTT AGT GCA CAG G-3′ 165 Bcl2 Forward 5′-GAT AAC GGA GGC TGG GAT G-3′ Reverse 5′-CTC ACT TGT GGC CCA GGT AT-3′ 151 Casp3 Forward 5′-GGA CCT GTG GAC CTG AAA AA-3′ Reverse 5′-ATA CCG CAG TCC AGC TCT GT-3′ 122 Col1a1 Forward 5′-GCG TGC TAT GCA AAG AAG ACT-3′ Reverse 5′-TGA CTT CTG CGT CTG GTG AT-3′ 105 Acta2 Forward 5′-TCG GGA CCT CAC TGA CTA CC-3′ Reverse 5′-AAT CCA GGG CGA CAT AAC AC-3′ 122 PPIA Forward 5′-AGC ACT GGG GAG AAA GGA TT-3′ Reverse 5′-CTT GCC ACC AGT GCC ATT AT-3′ 111 β-actin Forward 5′-TTC CTG GGT ATG GAA TCC TG-3′ Reverse 5′-CAG CAA TGC CTG GGT ACA T-3′ 136 GAPDH Forward 5′-CTG ACA TGC CGC CTG GAG AAA C-3′ Reverse 5′-CCA GCA TCA AAG GTG GAA GAA T-3′ 161 TBP Forward 5′-TGG GAT TGT ACC ACA GCT CCA-3′ Reverse 5′-CTC ATG ATG ACT GCA GCA AAC C-3′ 132 The primer sequences for mtDNA and nDNA amplification Rnr2 Forward 5′-AGC TAT TAA TGG TTC GTT TGT-3′ Reverse 5-AGG AGG CTC CAT TTC TCT TGT-3′ 132 bp GAPDH Forward 5′-GGA AAG ACA GGT GTT TTG CA-3′ Reverse 5-AGG TCA GAG TGA GCA GGA CA-3′ 129 bp HIF-1α: hypoxia-inducible factor 1, α subunit (basic helix-loop-helix transcription factor); PGC1α: peroxisome proliferator-activated receptor gamma, coactivator 1α; T*fam*: mitochondrial transcription factor A; COX4I1: cytochrome c oxidase subunit IV isoform 1; NRF-1: Nuclear respiratory factor 1; PPARδ: Peroxisome proliferator-activated receptor γ; PGC1β: peroxisome proliferator-activated receptor gamma, coactivator 1β; *Col1a1*: collagen, type I, α~1~; *Acta2*: smooth muscle α-actin; *Bax*: Bcl2-associated X protein; *Bcl2: B-cell*CLL/lymphoma 2; *Casp3*: caspase 3; PPIA: peptidylprolyl isomerase A (cyclophilin A) (relative quantification of gene expression); GAPDH: glyceraldehyde 3-phosphate dehydrogenase; TBP: TATA box binding protein; Rnr2: mitochondrially encoded 16S RNA. Quantification of mtDNA ----------------------- An assay based on real-time quantitative PCR was used for both nDNA and mtDNA quantification using SYBR-Green as the fluorescent dye (Invitrogen). For the detection of liver nDNA, we selected *GAPDH* between the nucleotides 1443 and 1571, and for the detection of mtDNA, we selected mitochondrially encoded 16S RNA (*Rnr2*) between the nucleotides 2451 and 2583 \[[@b19]\]. The results were presented as the mtDNA/nDNA ratio. The primer sequences for both mtDNA and nDNA for loading normalization are given in [Table 1](#tbl1){ref-type="table"}. Triplicate amplifications of mitochondrial and nuclear products were performed separately. Real-time quantitative PCR was carried out in a BioRad iCycler (Bio-Rad Laboratories, Hercules, CA, USA). The calculation of DNA copy number involved extrapolation from the fluorescence readings in the mode of background subtracted from the readings of BioRad iCycler according to the above-described procedure for gene expression. The specificity of amplification and absence of primer dimers were confirmed using the melting curve analysis at the end of each run. The two target amplicon sequences (mtDNA and nDNA) were visualized in 2% agarose and purified using Qiagen Qiaex II, Gel extraction Kit (Tecnolab, Buenos Aires, Argentina). The dilutions of the purified amplicons were used as the standard curve to verify the PCR-efficiency values estimated by using the procedure described earlier. Western blot analysis of liver HIF-1α protein --------------------------------------------- Nuclear proteins from liver tissue were denatured in SDS sample buffer, separated with 8% SDS-acrylamide gel and electrotransferred to Hybond-hydrophobic polyvinylidene difluoride (PVDF) membranes (GE Healthcare UK Limited, Buckinghamshire, UK). After blocking with 5% non-fat dry milk in tris-buffered saline tween (TBST) buffer (20 mmol/l of Tris-HCl \[pH 7.6\], 137 mmol/l of NaCl, 0.25% of Tween-20), the membranes were probed with rabbit polyclonal anti-HIF-1a (1:1.000) (GeneTex, Inc., GTX30603, Irvine, CA, USA), followed by incubation with horseradish peroxidase (HRP)-conjugated anti-rabbit polyclonal immunoglobulin G secondary antibody (1:15.000) (GeneTex, Inc., GTX26795). Equal protein loading was confirmed by reblotting of the membranes with a goat polyclonal antibody against rabbit polyclonal anti-β-actin (1:500) (GeneTex, Inc., GTX16039). Binding of the antibody was subsequently visualized with enhanced chemiluminescence reagent (GE Healthcare UK Limited), and the band images were detected and analysed using the Lab Works Analysis Software (Ultra-Violet Products Ltd., Cambridge, UK). Measurement of liver 8-isoprostane ---------------------------------- Measurement of 8-isoprostane (also known as 15-isoprostane F2t, 8-epi-PGF2α, or 8-iso-PGF2α) in liver tissue was carried out using ELISA by employing ethyl acetate extraction method, according to the manufacturer's instruction (Detroit R&D, Inc., Detroit, MI, USA). Statistical analysis -------------------- Quantitative data were expressed as mean ± S.E. Pairwise mean differences were evaluated using nonparametric Mann-Whitney test, as most of the variables were ratios and not normally distributed, and non-homogeneous variances between the groups were evident. For the comparison of more than two groups, we used the Kruskal--Wallis test. For testing the differences in steatosis gradation (as a categorical response variable), we used a model with ordinal multinomial distribution and probit as a link function, with animal length and adipose tissue as continuous predictor variables. The correlation between two variables was determined using Spearman rank correlation test. Logistic and multiple regressions were used on log-transformed variables for testing multivariate association between variables or for adjusting the cofactors. The data were also adjusted for body weight whenever applicable. A value of *P* \< 0.05 was considered to be statistically significant. We used the Statistica program package, StatSoft (Tulsa, OK, USA), to perform all the analyses. Experimental results ==================== Effect of HFD on liver histology and organ fat accumulation ----------------------------------------------------------- HFD-fed rats developed severe hepatic microvesicular and macrovesicular steatosis ([Fig. 1](#fig01){ref-type="fig"}). As shown in [Figure 1G](#fig01){ref-type="fig"}, quantitative evaluation of steatosis score from haematoxylin and eosin and osmium tetroxide staining of liver sections at the end of the experiment demonstrated significant differences between the groups ([ancova]{.smallcaps} with steatosis gradation as a categorical response variable with ordinal multinomial distribution and probit as a link function, with animal length and adipose tissue as continuous predictor variables). This finding was confirmed by biochemical analysis of hepatic triglyceride content ([Fig. 1H](#fig01){ref-type="fig"}). ![Left panel: Liver histology of a representative animal from each experimental group. Haematoxylin and eosin (A and B), Masson's trichrome (C and D), and osmium tetroxide (E and F) staining of liver sections at the end of the experiment. The livers of rats fed with SCD show normal histology and absence of fat accumulation. The livers of rats fed with HFD show severe panlobular micro and macrovesicular steatosis. Arrows indicate large or small droplet steatosis, and lipid globules appear black after osmium tetroxide staining (F). Original magnification: 400×. (G) Quantitative evaluation of steatosis score. Steatosis was given a score from 0 to 3 as described in the 'Materials and methods' section. The data are presented as mean ± S.E. (H) Biochemical analysis of hepatic triglyceride content. The results (μg/mg liver) are expressed as mean ± S.E.](jcmm0015-1329-f1){#fig01} Furthermore, plasma glucose in the HFD group was not significantly different from that in the SCD group (199 ± 6 mg/dl and 186 ± 7 mg/dl, respectively). Similarly, the plasma insulin levels and HOMA index, despite being lower in the SCD group (96 ± 35 and 45 ± 19 μU/l, respectively), were not statistically different when compared with those observed in the HFD group (187 ± 30 and 96 ± 16 μU/l, respectively). Furthermore, ALT levels (UI/l) were similar in both groups (33 ± 3.2 in SCD rats and 39 ± 2.8 in HFD rats), and HFD rats showed higher visceral fat content at the end of the experiment (26.9 ± 4.5 g) when compared with that in the controls (12.5±5.2 g), *P* \< 0.05. Effect of HFD on liver mtDNA content and liver mitochondrial density -------------------------------------------------------------------- As shown in [Figure 2A](#fig02){ref-type="fig"}, we observed that HFD induced a significant increase in liver mtDNA content when compared with that in the SCD rats. In addition, the liver mtDNA/nDNA ratio was significantly correlated with the liver triglyceride content (*R*: 0.29, *P* \< 0.05). ![(A) Liver mtDNA/nDNA ratio assessed by quantitative real-time PCR in each experimental group. Each bar represents the mean ± S.E. values of 10 and 15 animals in SCD and HFD, respectively. mtDNA copy number was calculated as the ratio of *GAPDH* to 16S RNA gene. The results are shown as mtDNA/nDNA ratio. (B) Electron microscopic images depicting the difference in the abundance of the liver mitochondrial density with respect to the mtDNA content. The left-hand picture shows an exemplar of low mtDNA/nDNA ratio, and the right-hand picture shows an exemplar of high mtDNA/nDNA ratio. Original magnification: 12,000×.](jcmm0015-1329-f2){#fig02} Furthermore, electron microscopic evaluation of liver tissue showed that the observed increase in liver mtDNA copy number was accompanied by higher mitochondrial density ([Fig. 2B](#fig02){ref-type="fig"}). Liver expression of *HIF-1α* mRNA was significantly associated with liver mtDNA content --------------------------------------------------------------------------------------- To address the question of whether the increase in liver mtDNA copy number is associated with *HIF-1α*, we examined the liver expression of *HIF-1α* mRNA, and observed a significant positive correlation between liver mtDNA/nDNA ratio and hepatic levels of *HIF-1α* mRNA (*R*: 0.37, *P* \< 0.001). We found that the level of *HIF-1α* mRNA was significantly higher in the HFD group ([Fig. 3A](#fig03){ref-type="fig"}). Western blot analysis showed that the level of protein, in parallel with the liver mRNA *HIF-1α* expression, was also significantly higher in the livers with increased mtDNA/nDNA ratio ([Fig. 3B](#fig03){ref-type="fig"}). ![(A) Liver expression analysis of *HIF-1α* mRNA by quantitative real-time PCR in each experimental group. Each bar represents the mean ± S.E. values of 10 and 15 animals in SCD and HFD, respectively. In each sample, the gene expression was normalized to the expression of cyclophilin A and multiplied by 100. (B) Representative Western blot analysis of liver *HIF-1α* protein expression in each experimental group. Hypoxia-positive control (H) obtained from a rat ischemic skeletal muscle. β-actin was used as loading control.](jcmm0015-1329-f3){#fig03} Liver expression of cytochrome c oxidase subunit IV isoform 1 (*COX4I1*) mRNA was significantly associated with liver mtDNA content ----------------------------------------------------------------------------------------------------------------------------------- Cytochrome c oxidase (COX), located in the inner mitochondrial membrane, is a dimer in which each monomer consists of 13 subunits; subunit IV (COX4) is regulated in an O~2~-dependent manner and is also a terminal enzyme in the mitochondrial respiratory chain, which catalyses the electron transfer from reduced cytochrome c to molecular oxygen. COX4 subunit determines the efficiency of mitochondrial respiration in response to different oxygen tensions. In addition, *COX4I1* is a marker of mitochondrial mass. Thus, we evaluated liver *COX4I1* mRNA expression and provided further evidence for an increase in liver mtDNA content, probably mediated by the effect of oxygen concentration in the liver, as the mtDNA/nDNA ratio was positively correlated with *COX4I1* expression (*R*: 0.30, *P* \< 0.02). Multiple regression analysis showed that liver mtDNA/nDNA ratio was strongly correlated with the expression of *HIF-1α* (β: 0.32, S.E.: ±0.12, *P* \< 0.009) and *COX4I1* (β 0.37, S.E. ± 0.14, *P* \< 0.01) mRNA in the liver. However, backward stepwise regression showed that the expression of *HIF-1α* mRNA in the liver was the only variable that was retained in the model and was strongly correlated with liver mtDNA/nDNA ratio (β: 0.40, S.E.: 0.11, *P* \< 0.001). Measurement of liver 8-isoprostane as a biomarker of local oxidative stress --------------------------------------------------------------------------- Isoprostanes are prostaglandin-like compounds produced by free-radical-mediated peroxidation of lipoproteins. Numerous studies have shown that the quantification of isoprostanes is an accurate measure of oxidative stress \[[@b20], [@b21]\]. Evidence from both human and animal studies showed that liver steatosis increases oxidative stress \[[@b22]\]; intracellular levels of reactive oxygen species (ROS) have been found to be associated with changes in mtDNA copy number \[[@b23]\]. To determine whether oxidative stress is related to both hepatic steatosis and mtDNA content, we measured the liver 8-isoprostane levels in both experimental groups, and observed that they were significantly correlated with liver fat content (*R*: 0.42, *P* \< 0.004). Nevertheless, no significant association was observed either with liver mtDNA content or liver *HIF-1α* mRNA expression. The liver abundance of mRNA of master nuclear genes that regulate normal mitochondrial biogenesis and replication was not associated with the liver mtDNA content ----------------------------------------------------------------------------------------------------------------------------------------------------------------- To evaluate whether the hepatic expression of other transcription factors was associated with the observed increase in liver mtDNA content, we measured the following: mitochondrial transcription factor (*Tfam*) mRNA (a key regulator of mtDNA copy number required for the replication and maintenance of mtDNA \[[@b24]\]), peroxisome proliferator-activated receptor gamma coactivator-1-α (*PGC-1α*) and -β (*PGC-1β*) mRNA (physiological transcriptional regulators of oxidative metabolism and mitochondrial biogenesis \[[@b24]\]); *PGC-1β* is also considered to preferentially induce the expression of genes involved in the removal of ROS, nuclear respiratory factor-1 (*NRF-1*) mRNA (a gene involved in oxidative stress induced mitochondrial biogenesis \[[@b23]\]), and peroxisome proliferator-activated receptor δ (*PPARδ*) mRNA (a nuclear receptor capable of increasing the skeletal muscle mitochondria even in the absence of an increase in *PGC-1α* mRNA). On the whole, we observed that the mRNA expression of the above-mentioned genes in the liver was not significantly associated with the liver mtDNA/nDNA ratio. In addition, we found no differences between the groups (HFD *versus* SCD) with regard to the mRNA expression of either of these genes ([Fig. 4](#fig04){ref-type="fig"}). ![Liver mRNA expression of mitochondrial biogenesis genes assessed by quantitative real-time PCR in each experimental group. Each bar represents the mean ± S.E. values of 10 and 15 animals in SCD and HFD, respectively. In each sample, the gene expression was normalized to the expression of cyclophilin A and multiplied by 100. T*fam*: mitochondrial transcription factor A; PPARδ: peroxisome proliferator-activated receptor γ; PGC-1α: peroxisome proliferator-activated receptor gamma coactivator-1α; PGC-1β: peroxisome proliferator-activated receptor gamma coactivator-1β; NRF-1: nuclear respiratory factor 1; PPIA: peptidylprolyl isomerase A (cyclophilin A); NS: not significant.](jcmm0015-1329-f4){#fig04} Evaluation of hepatic mRNA expression of apoptosis-related genes (Bcl-2, Bax and caspase-3), and fibrosis-related genes (collagen type Iα~1~ and smooth muscle α-actin) ----------------------------------------------------------------------------------------------------------------------------------------------------------------------- Hepatocyte apoptosis and caspase activation are prominent features of human NALFD \[[@b25], [@b26]\]. In our experimental model, the liver tissue of HFD rats did not show histological signs of liver injury, inflammation or liver fibrosis, and this observation is in agreement with other reports \[[@b27]\]. Even so, to understand the potential role that early events associated with hepatocyte apoptosis might have in the *HIF-1α*-induced increase of the liver mtDNA content, we measured the hepatic mRNA expression of three apoptotic genes, such as: caspase 3 -- a marker of early apoptosis and a reliable indicator of apoptotic rate -- and two members of the Bcl-2 superfamily of proteins, the pro-apoptotic Bax and the anti-apoptotic Bcl-2, which act regulating the permeability of the mitochondrial membrane. Interestingly, the liver mRNA expression of none of the above-mentioned genes was significantly associated with the liver mtDNA/nDNA ratio. In addition, there was no significant difference in the liver Bax/Bcl-2 expression ratio between the groups (HFD *versus* SCD), [Figure 5A](#fig05){ref-type="fig"}. Nevertheless, the levels of hepatic mRNA expression of caspase 3 were significantly higher in the HFD group ([Fig. 5A](#fig05){ref-type="fig"}). ![Liver mRNA expression of apoptosis-related genes (*Bax*, *Bcl2* and *caspase 3*) (A) and a fibrosis-related gene (*Col1a1*) (B), assessed by quantitative real-time PCR in each experimental group. Each bar represents the mean ± S.E. values of 10 and 15 animals in SCD and HFD, respectively. In each sample, the gene expression was normalized to the expression of cyclophilin A and multiplied by 100/1000 as shown. *Bax:* Bcl2-associated X protein; *Bcl2*: *B-cell* CLL/lymphoma 2; *Casp3*: caspase 3; *Col1a1*: collagen type I α~1~. (C) Gomori's reticulin silver impregnation of liver sections at the end of the experiment using a representative rat from each experimental group. Figure shows comparisons of the reticulin pattern of the portal tract and hepatic parenchyma across groups.](jcmm0015-1329-f5){#fig05} We further evaluated the liver mRNA expression of collagen type I α~1~-- an extracellular matrix component, and smooth muscle α-actin, a marker of activation of resident stellate cells to myofibroblast-like cells, to gauge potential progression along the fibrosis development. There were no significant differences between the groups about liver collagen type I α~1~ mRNA expression ([Fig. 5B](#fig05){ref-type="fig"}); the abundance of smooth muscle α-actin mRNA was completely undetectable in both experimental groups, by our real-time PCR-based method. Moreover, neither the trichrome ([Fig. 1C and D](#fig01){ref-type="fig"}) nor the reticulin stains showed alterations of the collagenous stroma ([Fig. 5C](#fig05){ref-type="fig"}). Effect of reversion of hepatic steatosis on liver mtDNA content and liver *HIF-1α* mRNA expression -------------------------------------------------------------------------------------------------- To further understand the role of liver steatosis in *HIF-1α*-mediated increase in the liver mtDNA content, we evaluated the effect of telmisartan -- a type 1 angiotensin II receptor blocker also considered to act as a partial agonist of PPARγ-- on both liver *HIF-1α* mRNA expression and liver mtDNA/nDNA ratio. We chose this pharmacological agent because we previously demonstrated that telmisartan could revert fatty liver in an HFD-induced rat model of NAFLD \[[@b14]\]. In addition, previous evidence also showed that telmisartan could inhibit the generation of ROS and lipid peroxidation products in kidney \[[@b28]\]. The animals were given HFD for 8 weeks and after this period, for 12 weeks, they received vehicle (HFD) or telmisartan (Bago, Buenos Aires, Argentina) at 10 mg/kg intraperitoneally for every 24 hrs, along with the same access to HFD (T + HFD). The liver tissue was then collected to determine the mtDNA content, *HIF-1α,* mitochondria-related mRNA gene expression levels, and liver 8-isoprostane, as described earlier. Telmisartan was associated with a significant decrease in the liver mtDNA/nDNA ratio ([Fig. 6A](#fig06){ref-type="fig"}) and liver *HIF-1α* mRNA expression ([Fig. 6B](#fig06){ref-type="fig"}). The liver HIF-1α protein level was also decreased in the T + HFD group when compared with the HFD group and SCD group ([Fig. 6D](#fig06){ref-type="fig"}). As shown in [Figure 6C](#fig06){ref-type="fig"}, fatty liver was efficiently reverted by telmisartan. Interestingly, rats treated with telmisartan showed a significant decrease in liver 8-isoprostane levels when compared with the HFD group ([Fig. 6E](#fig06){ref-type="fig"}). ![Effect of telmisartan on the reversion of hepatic steatosis, liver mtDNA content, *HIF-1α* mRNA and protein abundance, and liver 8-isoprostane levels. (A) Liver mtDNA/nDNA ratio assessed by quantitative real-time PCR in each experimental group. \**P* \< 0.029, HFD *versus* SCD; ^\#^*P* \< 0.006, T + HFD *versus* HFD. (B) *HIF-1α* mRNA analysed using quantitative real-time PCR in each experimental group. \**P* \< 0.03, HFD *versus* SCD; ^\#^*P* \< 0.0001, T + HFD *versus* HFD. (C) Liver histology of a representative animal from each experimental group. Haematoxylin and eosin, Masson's trichrome and osmium tetroxide staining of liver sections at the end of the experiment using a representative rat from each experimental group as described in the 'Materials and methods' section. (D) Representative Western blot analysis of liver *HIF-1α* protein levels in each experimental group. Hypoxia-positive control (H) obtained from a rat ischemic skeletal muscle. β-actin was used as loading control. (E) Liver 8-isoprostane levels as a biomarker of local oxidative stress, assessed by ELISA in each experimental group. The results expressed as ng/mg liver protein. \**P* \< 0.004, HFD *versus* SCD; ^\#^*P* \< 0.0001, T + HFD *versus* HFD, adjusted by liver triglyceride content using ANCOVA. SCD: standard chow diet, HFD: high-fat diet; T + HFD: telmisartan plus high-fat diet.](jcmm0015-1329-f6){#fig06} Discussion ========== Progress in the understanding of the pathophysiology of NAFLD has been partly made through the evaluation of the molecular events that occur in the liver of experimental models. Using an HFD-induced rat model of NAFLD, we reproduced the features of human liver steatosis to evaluate the liver mtDNA content. We observed that feeding of rats with HFD resulted in an increase in the liver mtDNA/nDNA ratio, and this increase, was modestly but significantly correlated with the liver triglyceride content. We also found that livers of rats with increased mtDNA copy number also appear to have higher mitochondrial density, as assessed by electron microscopy. We further suggested that this increase in mtDNA copy number might be regulated by liver *HIF-1α*. Thus, this study, for the first time, demonstrated that the observed increase in the liver mtDNA/nDNA ratio was associated with the expression of *HIF-1α* mRNA in the liver. In addition, we provided further evidence to the hypoxic-mediated increase in liver mitochondrial biogenesis by demonstrating that liver *COX4I1* mRNA expression was positively correlated with liver mtDNA content. We found that an increase in the mitochondrial mass was also supported by the increased expression of *COX4I1* mRNA. Furthermore, we also evaluated the mRNA expression in the liver of several key transcriptional factors, which are known to regulate normal mitochondrial biogenesis, including, *PGC-1α, PGC-1*β, *NRF-1*, *PPARδ* and *Tfam*, and observed that the increase in liver mitochondrial biogenesis was not related to the expression of the genes that commonly regulate mtDNA content. Additionally, we also observed that oxidative stress, although increased by HFD, was not directly involved in the *HIF-1α*-mediated increase in mtDNA copy number. Similarly, while liver caspase 3 mRNA levels were higher in the HFD group suggesting the presence of early apoptotic events, they were not associated with the changes observed in the liver mtDNA content. Finally, to explore whether the observed events were related to the presence of liver steatosis, we evaluated the liver mtDNA content and *HIF-1α* mRNA expression in rats treated with telmisartan (a pharmacological agent that was found to efficiently revert back fatty liver \[[@b14]\]). Treatment of rats with telmisartan resulted in a significant decrease in liver mtDNA/nDNA ratio as well as liver *HIF-1α* mRNA and protein level. Otherwise, telmisartan may be involved directly in the modulation of *HIF-1α*. This observation is supported by previous evidence that showed that chronic hypoxia is associated with activation of the renin--angiotensin system \[[@b29], [@b30]\]. Thus, it is reasonable to hypothesize that the blockade of the renin--angiotensin system may directly prevent the effects of the induction of *HIF-1α*. Although these results are novel, they are in agreement with earlier studies that showed that HFD could induce increase in mitochondrial enzymes and mitochondrial biogenesis in muscle \[[@b31], [@b32]\]. Furthermore, the central finding of our study, *i.e. HIF-1α*-associated increase in liver mtDNA content, is also supported by previous experimental observations on other tissues. For instance, neuronal mitochondrial biogenesis was highly increased after hypoxia or hypoxic--ischemic injury \[[@b13], [@b33]\]. Interestingly, although hypoxia has been well defined as an important mediator of inflammation and insulin resistance \[[@b34]\], its role in fatty liver disease, particularly in modulating liver mtDNA content, was never described previously. The most important finding of our study is the potential role that hypoxia seems to have in the molecular events related to the increased accumulation of fat in the liver, and its impact on mitochondrial function. This concept was initially described in ethanol-induced steatohepatitis \[[@b35]\]. Moreover, Mantena *et al*. showed that chronic exposure of rats to HFD could affect liver mitochondrial function and cause hepatocyte hypoxia \[[@b10]\]. These findings were also replicated in human studies. Fisher *et al*. recently evaluated the microsomes isolated from human liver samples, and observed that NAFLD progression was correlated with elevated *HIF-1α* expression \[[@b36]\]. Finally, the increased hepatocyte lipid content was shown as a key determinant of hepatocyte sensitivity to hypoxia, an observation that has a direct clinical impact on, for instance, decreased viability of donor steatotic liver after liver transplantation \[[@b37]\]. In summary, accumulating evidence suggests a major role of mitochondrial dysfunction in the physiopathology of NAFLD. Nevertheless, only a few studies have explained how lipid accumulation in the hepatocytes affects liver mtDNA content. We consider that the main objective of our study was to provide evidence on the notion that hypoxia may play a role in the mitochondrial changes associated with NAFLD. In addition, the biological and prognostic implications of our findings are as follows. Based on our experimental results, it seems reasonable to speculate that the observed increase in mtDNA content is an adaptive mechanism either to enhance the liver mitochondrial function to manage the increased mitochondrial β-oxidation as well as protect the hepatocytes against lipid peroxidation, or to compensate the hypoxic condition resulting from microcirculatory disturbances associated with fatty liver \[[@b38]\]. However, this aspect deserves further investigation. It is worth mentioning that we did not observe either inflammatory changes or fibrosis in the liver, and that the histological lesions were limited to the accumulation of lipids in the hepatocytes -- a morphological change also known as simple steatosis. This seems to be a hallmark as well as a limitation of this particular rodent model. Hence, we can hypothesize that changes in mtDNA precede liver lipotoxicity damage with the subsequent progression to more severe disease, which is in agreement with previous works that have demonstrated that either intermittent or sustained exposure to hypoxia results in steatohepatitis \[[@b39], [@b40]\]. This observation has clinical relevance because the observed changes in mtDNA can be reverted using any intervention that can improve liver steatosis. Furthermore, our observations on the effects of telmisartan on improving fatty liver infiltration as well as decreasing liver mtDNA content and expression of *HIF-1α* in the liver are in agreement with this finding. Finally, the presence of increased mtDNA content in the steatotic liver, either as an outcome of chronic effects of hepatocyte hypoxia or an adaptive mechanism to enhance mitochondrial function, needs to be assessed further in the context of advanced lesions of NAFLD, including necroinflammatory response and fibrosis, to evaluate whether the increase in liver mtDNA confers a physiological advantage during the initial stages of NAFLD. This study was partially supported by the grants PICT 2006--124 (Agencia Nacional de Promoción CientÌfica y Tecnológica) and UBACYT M055 (Universidad de Buenos Aires). A.B., M.S.R., T.F.G., C.J.P. and S.S. are members of Consejo Nacional de Investigaciones CientÌficas. Conflict of interest ==================== The authors confirm that there are no conflicts of interest. [^1]: These authors should be considered as first authors.
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Microsoft Toughen Windows Security Microsoft Toughen Windows Security Microsoft was in talks to buy the firm for US$100 million, according to earlier published reports. However, Microsoft and Hexadite did not disclose terms of the official agreement. The acquisition will help bolster the company’s efforts to help commercial Windows 10 customers deal with advanced attacks on their networks, Microsoft said. It currently offers Windows Defender Advanced Threat Protection to detect zero-day attacks, ransomware and other advanced threats, and the Hexadite technology will build on that. The acquisition will include Hexadite’s endpoint security automated remediation. Support for activations of WDATP, which currently protects 2 million devices, will continue. “Our vision is to deliver a new generation of security capabilities that helps our customers protect, detect and respond to the constantly evolving and ever-changing cybersecurity landscape,” said Terry Myerson, EVP of the Windows and devices group at Microsoft. Automation and Orchestration “Hexadite is not detection technology,” said Dan Cummins, senior analyst for security at 451 Research. “Rather, it is incident response automation and orchestration, fed by data that originates — usually — on detection sensors or systems and then is processed by a SIEM, where it’s correlated and perhaps enriched with other data, internal or external,” he explained. “Hexadite further enriches and prioritizes,” Cummins told the E-Comerce Times. “Their primary differentiation, I believe, is their belief in nearly full automation of investigation, response and closeout, even for complex incidents,” he noted. Good Fit “Broadly speaking, IT vendors pursue acquisitions because buying existing technology is generally faster and cheaper than building it themselves,” noted Charles King, principal analyst at Pund-IT. “The technology being acquired should fit well within the buyer’s strategy and skill sets. That’s clearly the case here, given both companies’ focus on and innovative work in proactive security services, AI, machine learning and the needs of enterprise customers,” he told the E-Commerce Times. “In addition, it helps if there are existing connections between the companies,” King continued. “One of Hexadite’s early investors is Moshe Lichtman of Israel Venture Partners, who spent two decades as a senior executive with Microsoft, including five years running the company’s Israel R&D center,” he noted. “It doesn’t require a stretch of the imagination to consider how Lichtman may have vetted and facilitated the deal.” Rapid Detection Hexadite was cofounded in 2014 by CEO Eran Barak, Chief Product Officer Barak Klinghofer and CTO Idan Levin. The three executives previously worked at Elbit Systems, where Barak led the company’s cybertraining and simulation team, Klinghofer was cybersolutions architect, and Levin was a cybersoftware engineer. The founders developed a new ground-up method of rapid detection and response to cyberthreats after working on military and other threat scenarios. “After seeing first hand how companies around the world investigated threats and anticipated a massive increase in subsequent alerts compounded by a global skills shortage, they knew that automation would be the only way security teams had a chance,” said Nathan Burke, marketing director for Hexadite. The company’s Automated Incident Response Solution uses technology that is able to detect, investigate and respond to cyberthreats within minutes, compared to more traditional methods, which could take weeks to deal with similar situations. Hexadite early last year received $8 million in series A funding from Hewlett Packard Ventures, Ten Eleven Ventures and YL Ventures, which also had invested in the company’s seed round. At the time, Hexadite had grown to protect more than 500,000 devices worldwide across various industries, based on initial seed money of about $2.5 million. Hexadite’s customers include IDT, Nuance and Telit. In connection with that early investment, Mark Hatfield, cofounder of Ten Eleven Ventures, joined the Hexadite board. Hatfield has a strong track record in the technology industry, with prior investments in Cylance, CounterTack, Trust Digital, Resilient Systems (CO3) and Digital Guardian. Hexadite and HPE last year entered a reseller agreement, which [provided that Hexadite’s AIRS technology would be offered in combination with HPE’s Arcsite detection technology, using AI to manage cyberthreats. The acquisition of Hexadite provides Microsoft with important resources for enterprise security based on AI, said Jim McGregor, principal analyst at Tirias Research. “Hexadite appears to provide multiple benefits to Microsoft,” he told the E-Commerce Times, including “a security service for enterprise and cloud solutions, customers for security services, and valuable IP and expertise for AI applications.” Automation/orchestration is a growing area in cybersecurity, noted Ed Cabrera, chief cybersecurity officer at Trend Micro. Trend Micro earlier this year entered a partnership with CyberSponse to provide automated incidence response to cyberthreats, he told the E-Commerce Times. Main Focus The deal represents one of Microsoft’s most important cybersecurity acquisitions since its 2015 purchase of Adallom, a specialist in cloud security, for about $250 million. Microsoft used Adallom’s technology to bolster its ability to protect its Azure and Office 365 services from cyberthreats. Dealing with security threats has been top of mind a Microsoft. The company was at the center of the massive Wannacry Ransomware attack in May, which hit more than 300,000 computers in at least 150 countries worldwide. The attack was linked to the Shadow Brokers’ suspected theft of hacking tools — originally developed by the National Security Agency — that attacked legacy Windows systems that were not properly patched. Microsoft earlier this year announced a series of upgrades to its enterprise security toolkit, including Azure SQL Database Threat Detection, which uses machine learning to find suspicious database activity; and Enterprise Threat Detection, which uses machine analytics and proprietary telemetry sources to monitor for advanced threats. The rollout was part of a $1 billion annual investment that Microsoft made in addressing security threat issues. Microsoft has called for a Digital Geneva Convention, which would create a global regulatory system to manage cybersecurity issues. Hexadite, which has a team of researchers in Tel Aviv, will be fully absorbed into Microsoft’s Windows and Devices group at the close of the acquisition
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