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This nasty Chinese slut knows how to have a good time and she fucking loves her toy. How can you not love this whore? And she is not shy to masturbate for her lover and she definitely loves the taste of cum. This whore drives me crazy. She will do anything to please her lover.
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// Copyright 2009 The Go Authors. All rights reserved. // Use of this source code is governed by a BSD-style // license that can be found in the LICENSE file. // +build amd64,solaris package unix func setTimespec(sec, nsec int64) Timespec { return Timespec{Sec: sec, Nsec: nsec} } func setTimeval(sec, usec int64) Timeval { return Timeval{Sec: sec, Usec: usec} } func (iov *Iovec) SetLen(length int) { iov.Len = uint64(length) } func (msghdr *Msghdr) SetIovlen(length int) { msghdr.Iovlen = int32(length) } func (cmsg *Cmsghdr) SetLen(length int) { cmsg.Len = uint32(length) }
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Shirley, I shall call with my phone number for Thu through Sun morning. Sunday evening to Monday evening I can be reached at 011 48 42 213 71 62 Vince
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Monday, October 25, 2010 Well it has certainly been a while since our last update. We have been especially busy this month trying to get things set for a couple weddings and going to weddings...as guests =). In between...well...life. Its fast and fun!! Seeing that we have another wedding this weekend, this will be a quickie post just to give you some eye candy and to let you know we haven't forgotten about you. These coming couple of months will be a great time for PPW. We have some updating and re-vamping to do....as well as some non-wedding projects that are near and dear to us as the holidays fast approach and we will definitely share them with you. Speaking of holidays...Halloween is right around the corner and it def makes for some good themed weddings. From candied apples, to pumpkins, a popping palette using Black, orange or purple with fun patterns in between (ie: damask)...you can really dec out if your wedding is Halloween weekend/themed...and don't be fooled by the theme.....these weddings definitely don't come out Gothic looking or dead, dreary and scary (unless that's what your going for)...It's actually quite the opposite.
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Where afterthoughts are yellow and sticky.
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Descripción: All I had to get this slut to do EVERYTHING was ask. She fingered her ass and licked her fingers. She fingered her pussy. And she admitted to being a slut for stripping and eating cum And as you can hear agreed that I post this
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Q: Model not editable on a different PC I am using ArcGIS 10.1 model builder on windows 8 to create create models for my processes. But when I open the model using Arc GIS 10.1 open model for editing with Arc GIS 10.1 running on Windows 7 it appears not to be editable. I can run the model but I cannot edit it. When I open the model in ArcGIS 10.1 running on windows 7 the model appears as on the screenshot attached below...!Does anyone have an idea what the problem might be Could? I am yet to check if I will have the same problem when I try and edit the model on another windows 8 platform... The model does not use additional tool from extensions like "spatial analyst and so on..." it only uses data management tools. Thank you in advance. A: I sometimes have a similar problem. Simply copy and pasting the contents of the whole model into a new model usually fixes it.
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Background ========== Conceptual analysis is the process of mapping from natural language texts to a formal representation of the objects and predicates (together, the concepts) meant by the text. The history of attempts to build programs to do conceptual analysis dates back to at least 1967 \[[@B1]\]. Recent advances in the availability of high quality ontologies, in the ability to accurately recognize named entities in texts, and in language processing methods generally have made possible a significant advance in concept analysis, arguably the most difficult and general natural language processing task. Here we report on the design, implementation and several evaluations of OpenDMAP, an ontology-driven, integrated concept analysis system that significantly advances the state of the art. We also discuss its application to three important information extraction tasks in molecular biology. Information extraction (IE) efforts are widely acknowledged to be important in harnessing the rapid advance of biomedical knowledge, particularly in areas where important factual information is published in a diverse literature. In a recent *PLoS Biology*essay Rebholz-Schuhmann \[[@B2]\] argued, \"It is only a matter of time and effort before we are able to extract facts \[from articles in the primary literature\] automatically. The consequences are likely to be profound.\" Existing examples include extraction of information about gene-gene interactions \[[@B3]\], alternative splicing \[[@B4]\], functional analysis of mutations \[[@B5]\], phosphorylation sites \[[@B6]\], and regulatory sites \[[@B7]\]. The primary significance of OpenDMAP to these efforts is that it leverages the large-scale efforts being made in biomedical ontology development, such as the Open Biomedical Ontologies Foundry (OBO Foundry) \[[@B8]\]. Logical representations of reality, such as those built on the OBO Foundry, use a set of predicates that formally describe properties of, or relationships among, objects. Predicates are defined with a specific number and type of admissible arguments. For example, the predicate *expresses*might be specified to take two arguments, a gene and a cell type, meaning that the specified gene is expressed in all normal cells of the specified type. Such predicates can also be related to each other through abstraction (\"is a\") and packaging (\"part of\") hierarchies, as done in the OBO Foundry. The semantics defined by the predicates and hierarchies in such ontologies provide a powerful tool for natural language processing. Independently constructed ontologies have played at best a modest role in prior natural language processing systems. Guarino \[[@B9]\] characterizes various uses of ontologies in information systems: only systems that use an ontology at run time (rather than during system construction) to explicitly represent the domain knowledge exploited by the system qualified for what Guarino called an \"ontology-driven information system proper.\" To our knowledge, OpenDMAP is the first system developed to exploit a community consensus ontology as the central organizing principle of an information extraction system; for example, none of the systems that participated in the 2004 TREC Genomics evaluation for recognizing instances of Gene Ontology terms in text \[[@B10]\] meet the Guarino definition. Other language processing systems have used either small, *ad hoc*conceptual representations developed specifically for the application, or structured linguistic resources, such as WordNet \[[@B11]\], which do not meet the logical requirements for an ontology. While the implementation reported below exploits only a small portion of the OBO Foundry, and the crucial Relationship Ontology component of the Foundry is still in an early stage of development, the organizing principles of OpenDMAP generalize straightforwardly. The MetaMap system \[[@B12]\] identifies biomedical concepts from free-form textual inputs and maps them to entries in the Unified Medical Language System (UMLS) metathesaurus; SemRep \[[@B13]\] is a related system that maps to predications drawn from the UMLS semantic network, and SemGen \[[@B14],[@B15]\] is another related system that is focused on mapping to UMLS terms relevant to the etiology of genetic disease. These systems and their extensions have been used to extract semantic relationships relevant to pharmacogenomics \[[@B16]\] and to compare alternative sources of information \[[@B17]\], among other applications. OpenDMAP is like MetaMap and its descendents in that it can only produce output drawn from a predefined semantic representation. The main difference is that MetaMap, SemRep and SemGen are structured as traditional NLP systems, with a lexicon that enumerates possible concepts that might be associated with a word or phrase. Multiple possible mappings are returned, with rankings. OpenDMAP provides an alternative method of organizing knowledge about language, so that each concept has associated with it a set of patterns that describe how that concept can be realized in language; there is no explicit lexicon. To appreciate the differences between OpenDMAP and previous work in biomedical text mining, it is also useful to contrast its handling of syntactic structure and of semantic content with other systems. At one end of the spectrum are systems that employ essentially asyntactic representations. Early in the modern period of genomic natural language processing, some such systems were able to achieve significant (and in some cases ground-breaking) results using techniques based on text literals only. These include \[[@B18]-[@B20]\]. One line of subsequent work has attempted to increase the coverage of these early systems, which utilized manually-built patterns, by automatically acquiring considerably larger sets of patterns -- see, for example, Huang et al. 2004 \[[@B21]\]. Another line of subsequent work has focused on adding a modest, but still useful, level of linguistic abstraction by explicitly including either lexical categories (parts of speech), word stems, or both \[[@B22],[@B23]\]. These systems were essentially agrammatical; in contrast, OpenDMAP utilizes a classic form of \"semantic grammar,\" freely mixing text literals, semantically typed basal syntactic constituents, and semantically defined classes of entities. Although OpenDMAP is capable of utilizing full syntactic parses, the patterns for the three separate tasks discussed in this paper utilize primarily shallow syntactic parses (the development phase of the transport project reports results using syntactic dependency information). It remains to be seen what depth of syntactic parsing is useful in biomedical text mining. Some early systems explored full parsing \[[@B24],[@B25]\], but they were not generally fruitful, and typical systems have employed at most shallow parsing \[[@B26]-[@B28]\]; only recently has productive attention returned to syntactically ambitious approaches to biomedical text \[[@B29]-[@B31]\], much of it taking a dependency-based, rather than a constituent-based, approach. All of the systems discussed thus far have in common the fact that they employ some notion of explicit patterns, be they agrammatical, syntactic, or semantic. In a separate line of work, patterns are entirely implicit -- that is, they exist only to the extent that they are captured by orthogonal features. This work approaches relation extraction as a classification problem; a classic example is the work of Craven and Kumlein 1999 \[[@B32]\]. Bunescu et al. 2005 \[[@B33]\] presents a detailed analysis of a number of classification-based approaches; the state of the art is characterized by the participants in the recent BioCreative protein-protein interaction shared task \[[@B34]\]. OpenDMAP has been applied in three domains: protein transport, protein-protein interaction and the expression of a gene in a particular cell type. The three application domains are independently significant. Protein transport, the directed movement of proteins from one cellular compartment to another, is a broadly important biological phenomenon. Although protein subcellular localization information is centralized (e.g. through ontological annotations at NCBI and in various model organism databases), information about transport is not. Protein transport information is published throughout the scientific literature, but no previous method was able to capture it systematically. Protein-protein interaction extraction has been the subject of dozens of systems (see, e.g. a review in \[[@B35]\]). Widely used web resources such as IHOP \[[@B3]\] and Chilibot \[[@B36]\] are based entirely on automated extraction of protein-protein interactions from text. This task was used in the BioCreative community evaluation, described below. The third application area, extraction of assertions that a particular gene is expressed in a particular cell type, is of significance since it appears to be the predicate found most frequently in the biomedical literature; a form of the verb \"express,\" usually its nominalization \"expression,\" appears in nearly 20% of NCBI\'s GeneRIFs \[[@B37]\]. The protein transport task is illustrative of another distinguishing aspect of the OpenDMAP approach: it provides mechanisms for handling relationships involving more than two entities. Note that the protein transport predicate has at least three arguments: what protein is transported, from where, and to where (our model also includes a fourth argument: the transporting protein). Although some linguistic expressions of the concept may elide an argument, the predicate itself inherently describes a greater than binary relationship. Wattarujeekrit et al. \[[@B38]\] and Cohen and Hunter \[[@B39]\] present evidence that many important predicates in biomedicine require more than two arguments. However, most previous efforts at extracting relationships from biomedical text have addressed exclusively binary relationships. Geneways \[[@B40]\] and RLMPS-P \[[@B41]\] are the only other biomedical IE systems of which we are aware that extracted greater than binary relationships, and neither is ontology-driven. Assessing the accuracy of an information extraction system is a very labor-intensive activity. In order to identify information that could have been extracted, but was not (a \"false negative\"), a person must go through a large volume of text to determine all of the relevant assertions. To estimate the reliability of these manually derived assertions, at least two people must complete that task to assess inter-rater reliability. Once such data is used for one evaluation and system developers have seen it, further use of the data will generate upwardly biased accuracy estimates as system developers fit their systems to it. For these reasons, large-scale community evaluations of information extraction systems are particularly important. The second Critical Assessment of Information Extraction in Biology, (BioCreative) \[[@B34],[@B42]\], community evaluation included a test of systems designed to extract human protein-protein interaction information from the full texts of hundreds of journal articles, called the IPS task. Human curators from the IntAct database \[[@B43]\] manually extracted interaction assertions from these articles using the same curatorial standards as for the database. The results produced by human experts were compared to the results submitted from 45 systems developed by laboratories around the world, providing the best current assessment of the accuracy of protein interaction information extraction systems. The performance of OpenDMAP on the protein interaction task was evaluated as part of this shared task. More limited evaluations of the accuracy in the other applications are also reported in the results section. The accuracy of an information extraction system depends on the genre of texts on which it operates \[[@B44]\]. This report demonstrates the application of OpenDMAP to full texts of scientific journal articles, to Medline abstracts, and to GeneRIFs (single sentences or sentence fragments that are selected by human curators for relevance to the function of a particular gene product). GeneRIFs are particularly attractive targets for information extraction, due to their roughly sentential length (identified by \[[@B44]\] as the optimum), breadth of coverage, manual preselection for relevance, and association with at least one normalized gene reference. Despite these attractive features, this is the first report of an information extraction system targeting them. Results ======= OpenDMAP information extraction systems were produced for extracting protein transport assertions (transport), protein-protein interaction assertions (interaction) and assertions that a gene is expressed in a cell type (expression). Each of these systems was run over all abstracts in Medline as of June 18, 2007, producing a total of 72,460 transport instances, 265,795 interaction instances and 176,153 expression instances. These results are provided in RDF format in the Additional Files [1](#S1){ref-type="supplementary-material"}, [2](#S2){ref-type="supplementary-material"}, [3](#S3){ref-type="supplementary-material"}, [4](#S4){ref-type="supplementary-material"}. One particularly striking result is the diversity of journals from which these assertions were mined. The transport relationships were extracted from 2,340 different journals; the interaction relationships from 4,103 different journals; and the expression relationships from 2,984 different journals. A total of 4,434 unique journals contributed to these results, nearly 40% of the journals indexed in Medline each year (see Figure [1](#F1){ref-type="fig"}). ![**OpenDMAP coverage of MEDLINE**. The gray bars indicate the number of journals indexed by MEDLINE each year. The red bars indicate the number of journal abstracts from which OpenDMAP extracted at least one assertion regarding transport, interaction or expression. In recent years, more than 40% of biomedical journals contain such information. 2007 is partial data (through July 1).](1471-2105-9-78-1){#F1} For the BioCreative evaluation, the interaction system was run on the full texts of all of the 359 articles in the test set, producing 385 interaction assertions. Performance was averaged per article, since a few articles had a very large number of interactions and would have dominated a per assertion calculation. OpenDMAP\'s average F-measure of 0.29 was 10% higher than the next best scoring system, and more than three standard deviations above the mean performance. OpenDMAP\'s recall was similar to the other high scoring systems; its advantage arose from being substantially more precise (fewer false positives), achieving an average precision of 0.39, more than 20% better than the next best system. Due to IntAct\'s curation criteria, which require clear experimental evidence for an interaction in the text, these results are quite conservative. Many \"false positives\" were in fact assertions of interactions, but fell short of the evidential requirements for IntAct curation. A manual evaluation of the performance of the protein transport recognition system was based on all 570 GeneRIFs containing a form of the word \"translocate\" (382 of which were about protein transport, and 188 were about the transport of something else). Since transport is a greater than binary relationship, the extraction was only counted as correct if all of the components extracted matched the human annotation. For that strict criterion, OpenDMAP achieved precision of 0.75 and a recall of 0.49 (F-score of 0.59). If incomplete extractions are counted as correct, precision is unchanged at 0.75 and recall rises to 0.67 (F-score of 0.71). A substantial proportion of the errors were due to imperfect recognition of proteins; if OpenDMAP is given correct protein identifications as inputs, precision is 0.77, strict recall is 0.67 (F-score of 0.72) and incomplete recall is 0.85 (F-score of 0.81). A manual evaluation of the performance of the expression recognition system was based on 324 GeneRIFs containing a form of the word \"express,\" (these sentences contained 469 assertions about expression, 205 of which were about gene expression in 178 different cell types). Open DMAP had a precision of 0.64, but missed many statements that annotators identified as expression assertions, achieving a recall of only 0.16 (F-score of 0.26). A substantial portion of these errors were due to imperfect recognition of gene names; if OpenDMAP is given correct gene identifications as input, precision is 0.85 and recall is 0.36 (F-score of 0.51). Many other failures to identify expression assertions were related to coordination; the test set had an average of more than two expression assertions per sentence, but the IE system extracted only about 1.3 assertions per sentence. Discussion ========== As demonstrated by its performance in the community evaluation, OpenDMAP advances the state of the art for extracting protein-protein interaction predications from the full texts of biomedical research articles. Furthermore, this level of performance appears to generalize to other information extraction tasks, including extracting information about predicates of more than two arguments. There are several reasons why OpenDMAP exhibits better performance than any other biomedical information extraction system to date. OpenDMAP is an extension of the Direct Memory Access Parsing (DMAP) paradigm described in \[[@B45]\] and \[[@B46]\]. Three innovations distinguish the present work from those prior efforts. First, the ontology component of OpenDMAP is independent of the rest of the system. The knowledge representation component is the well-established, open source Protégé ontology development system \[[@B47],[@B48]\], and OpenDMAP concept analyzers can be associated with any ontology compatible with Protégé, for example, the OBO Foundry. Second, OpenDMAP is fully integrated with the open source Unstructured Information Management Architecture, (UIMA) \[[@B49]-[@B51]\], which allows the results of any text processing application interfaced to UIMA to be exploited by the OpenDMAP system. As demonstrated below, this mechanism facilitates the use of many external language processing systems, including tokenizers, sentence boundary detectors, entity recognition systems, and syntactic parsers. Since the inputs and outputs of each system are mapped by UIMA to a common annotation structure accessed by OpenDMAP, the use, comparison and combination of various approaches to language processing can all be fully integrated into OpenDMAP patterns. The third innovation in the OpenDMAP system is an expanded pattern language for specifying how concepts can be expressed in text. The pattern language not only allows specifications of mixtures of any concepts available from either the ontology (e.g. a protein transport process) or the results of UIMA text processing (e.g. the head of a noun phrase), but it also has new features that allow more flexible concept ordering than previous DMAP analyzers (see the description of the pattern language in the Methods section for details). The intimate connection between the ontology and the natural language processing system provides two significant advantages over prior information extraction systems generally. First, the output of the information extraction system is always constructed from elements of the ontology, ensuring that the knowledge representation is grounded with respect to a carefully constructed model of reality. In contrast, the outputs of most natural language processing systems are grounded only in substrings of text, not normalized to any model at all. Progress in normalizing biological entities recognized in text to specific database identifiers \[[@B52]-[@B54]\] has made the output of text processing systems much more valuable. Mapping the properties and relationships extracted to a community ontology similarly provides a significant increment in the value of the output from text processing systems. The second advantage of the OpenDMAP approach is that all of the knowledge used by the system to recognize concepts is structured by the ontology. In contrast, the nearly universal alternative approach is to embody knowledge of language into a lexicon, which associates individual lexical items with their possible semantic interpretations. In the OpenDMAP approach, information about which concepts are potentially relevant to the analysis of a particular text passage straightforwardly places limits on the linguistic knowledge relevant to analyzing that passage. This approach finesses many difficult ambiguity resolution problems faced by lexicon-driven systems, since these limits on the knowledge applied to conceptual analysis prevent many multiple interpretation problems from arising at all. For example, the string \"hunk\" refers to a cell type (human natural killer cells), a gene (hormonally upregulated Neu-associated kinase), and the general English word meaning a large piece of something without definite shape. A traditional, lexicon-driven system would have an explicit method for assigning the correct word sense to any occurrence of the string \"hunk.\" However, OpenDMAP patterns specify expectations of semantic classes (e.g. in the transport application described below, the transported entity must be a protein or a molecular complex); if it is possible to construe a string as an instance of an expected class, the pattern matches. The fact that there might be possible alternative interpretations of the matching string has no consequence, and no explicit ambiguity resolution step is necessary. Ambiguity is a leading cause of errors in text processing systems, and this approach is one of the contributing factors to OpenDMAP\'s superior performance. Our top-down approach to restricting possible interpretations does not address all problems due to ambiguity in language; for example, errors in preprocessing systems (e.g. syntactic parsing, see below) are not effected. The use of UIMA greatly facilitates the incorporation of various applications as input to OpenDMAP. The outputs of NLP tools integrated into the system are described by the extensible UIMA type system. In the case that a new type of information is produced by a preprocessor, OpenDMAP patterns would have to be modified to take advantage of the new type of information available. For example, the first time an external cell type tagging system is added, the UIMA type of the result of that processor must be linked to a cell-type concept in an OpenDMAP ontology in order for it to be used in patterns. However, if a new NLP tool produces a UIMA output type that has been used by OpenDMAP previously, then no changes in the ontology or patterns are needed. We believe that the outputs of information extraction systems are not likely to useful until the F-score (or at least the precision) is greater than about 0.85 \[[@B34]\], so the various sources of error in these systems must be addressed. A significant cause of errors in the OpenDMAP system as evaluated is incorrect identification of gene and protein names. The UIMA architecture makes it trivial to adopt and exploit better gene/protein recognition systems as they are developed. The best gene name identification and normalization systems from the BioCreative assessment achieved F-scores greater than 0.8, significantly above the \~0.7 F-score of the ABNER system \[[@B55]\] used by OpenDMAP to achieve the reported performance. Use of such a system should improve the performance of OpenDMAP. Error analysis of the false positives in the transport data set indicates that more than 80% are due to errors in the syntactic analysis. For example, in the sentence \"Rho protein regulates the tyrosine phosphorylation of FAK through translocation from the nucleus to the membrane,\" the subject of the translocation was incorrectly identified as FAK (rather than Rho) by the Stanford parser. That parser was developed for general English rather than biomedical text, so using specialized syntactic analysis systems may improve the precision of OpenDMAP. Remaining problems in false positives are due to problematic tokenization, failures to properly resolve anaphoric reference, and, rarely, negation. False negatives are due to gaps in concept recognition patterns, more than half of which arise from a failure to properly handle coordinated clauses and conjunctions. Addressing these issues remains an open area of research. Another issue was that the Stanford parser was too slow to use in the application of the transport system to all of Medline, so it wasn\'t run. OpenDMAP ignores aspects of patterns that require inputs that aren\'t present, so the patterns that contained syntactic dependencies did not have to be altered. These syntactic constraints are important for accuracy, however. Tested on the gold standard set for the system without the parser precision drops to 0.62, while strict recall remains largely unchanged, rising to 0.51. Conclusion ========== Despite OpenDMAP elevating the state of the art for biomedical information extraction significantly beyond previous levels, error rates remain high. In the most challenging BioCreative task, finding curatable assertions in full text documents, only about 29% of the relevant assertions were found, and only about 39% of the extracted assertions were completely correct. Such error rates mean that automatically generated databases cannot replace manual curation efforts. However, the evidence is quite clear that manual curation cannot keep up with the rate of data generation \[[@B56]\]. The surprisingly large number of journals that contained information relevant to these three IE tasks suggests that the temporal approach taken in \[[@B56]\] may actually underestimate the severity of the problem. Although the outputs produced by large-scale IE systems are not yet suitable for producing factual databases for direct use by biomedical researchers, the current level of performance provides two important facilities to the research community. First, the results of these efforts can be used to significantly increase the efficiency of manual curation efforts. Each extracted assertion is tied to a specific text, which can be used to direct the attention of manual curators both to relevant documents and to specific relevant passages within a document. Effective integration of IE results into curatorial workflows will require the development of new tools. OpenDMAP developers are working with curators at IntAct to address these issues. The open source availability of OpenDMAP will facilitate the work of others addressing this issue as well. The second important use of the sorts of results that IE systems are currently able to generate is in statistical integration with multiple sources of noisy data, such as those described in \[[@B57]\] and \[[@B58]\]. As demonstrated in the latter, the proper addition of even noisy data from the literature substantially improves the quality and coverage of protein-protein interaction networks for several species. Methods ======= OpenDMAP uses Protégé \[[@B47]\] to provide an object model for the possible concepts (predicates and objects) that might be found in a text. Protégé models concepts (including actions) as classes that participate in abstraction and packaging hierarchies, and relationships as class-specific slots. For example, protein transport is modeled as a class (called PROTEIN-TRANSPORT) and the relationship between a transport event and the protein transported in that event is represented as a slot in that class (called \[TRANSPORTED-ENTITY\]). Slots can take on values, which can be constrained to be instances of other classes. For example, the \[TRANSPORTED-ENTITY\] slot of the PROTEIN-TRANSPORT class is constrained to be an instance of either of the classes PROTEIN or MOLECULAR-COMPLEX. Figure [2](#F2){ref-type="fig"} shows a portion of the model used for the transport, which includes biological entities, such as molecular complexes and cellular components, and biological processes, particularly protein transport. This model is drawn almost entirely from the Gene Ontology (GO) \[[@B53]\] although the relationships that define the four slots shown in Figure [2](#F2){ref-type="fig"} are from a provisional submission to the OBO Foundry Relationship Ontology and are not official. Preprocessing tools (ABNER \[[@B55]\] and LingPipe \[[@B59]\]) were applied to tag instances of proteins, genes, and cell types. ![**Screenshot of the Protégé ontology for the protein transport task**. The slots of the protein transport class are shown in the lower right panel of this screen shot. Note that the subclasses of Cellular Component and Protein Transport are not shown.](1471-2105-9-78-2){#F2} For the transport task, patterns were produced for 30 ontology concepts; eight directly related to transport and 22 others for cellular components that are the sources and destinations of transport. A large number of other concepts (e.g. genes, proteins and cell types) do not have explicit patterns associated with them, but are instead tagged as such by UIMA tools during preprocessing. The protein-protein interaction task involved producing patterns for nine concepts, and the cell expression task required patterns for six additional concepts. The UIMA architecture \[[@B49]\] manages the processing of document sets. The collection of document processing tools interfaced through UIMA includes the LingPipe tools for sentence boundary detection and tokenization \[[@B59]\], both the LingPipe and ABNER \[[@B55]\] tools for recognizing protein mentions, ABNER for recognizing mentions of cell types, the Stanford Parser \[[@B60]\] to provide syntactic trees, and a locally produced implementation of the Modified Hobbs algorithm \[[@B61]\] for anaphora resolution. Various combinations of these tools were used in the different applications. For example, the GeneRIFs used in the transport application did not require sentence segmentation, and the applications to all medline abstracts did not use syntactic elements in patterns because the Stanford Parser was too slow to run over all of Medline. The results of this preprocessing are stored in UIMA\'s common annotation structure. In order to be able to recognize a concept in text, OpenDMAP associates one or more patterns with each concept. A pattern describes the words, phrases, parts of speech, syntactic structures or concepts that should cause an instance of the associated concept to be recognized. A simple pattern, such as the one shown in equation 1, enumerates a disjunction of words that should trigger recognition of a concept. The patterns for all of the CELLULAR-COMPONENT concepts were derived from the GO term names and synonyms, supplemented with derivational variants, such as the adjectival \"nuclear\" in equation 1. Twenty-two GO cellular component terms were used, along with 19 synonyms associated with the GO terms, and 78 additional derivational variants generated by inspection of the training corpus. More complex patterns can include references to non-terminals, particularly other concepts. Equation 2 is one of the patterns for recognizing instances of the PROTEIN-TRANSPORT concept. This pattern specifies that a reference to PROTEIN-TRANSPORT can appear in text as a reference to a concept that can fill the \[TRANSPORTED-ENTITY\] slot, followed by the word \"translocation\" followed optionally by a phrase beginning with the word \"from\", possibly including a word with the part of speech determiner, and a concept that could fill the \[TRANSPORT-ORIGIN\] slot, also followed optionally by a similar phrase that regarding the \[TRANSPORT-DESTINATION\] slot. $$\begin{matrix} {PROTEIN - TRANSPORT\text{~:=}\left\lbrack {TRANSPORTED - ENTITY} \right\rbrack translocation} \\ {\left( {from\left\{ {\det} \right\}?\left\lbrack {TRANSPORT - ORIGIN} \right\rbrack} \right)\text{?}} \\ {\left( {to\left\{ {\det} \right\}?\left\lbrack {TRANSPORT - DESTINATION} \right\rbrack} \right)\text{?;}} \\ \end{matrix}$$ When a pattern that includes a slot name is matched, the instance created has its slots filled with the concepts that matched the slot names in the pattern. For example, the above pattern matches the GeneRIF that contains \"\... Bax translocation to mitochondia\...\" (from Entrez GeneID 27113). Bax, which is recognized as a protein by ABNER, will cause an instance of the protein concept to be created; an instance of a protein matches one of the constraints on filler of the \[TRANSPORTED-ENTITY\] slot, which causes that slot to match to the Bax protein concept. The word \"translocation\" matches, and, while the optional \"from\" clause does not match, the \"to\" clause does match, since \"mitochondria\" matches one of the patterns for a subclass of CELLULAR-COMPONENT, the constraint on the filler of the \[TRANSPORT-DESTINATION\]. Since the entire pattern matches, an instance of PROTEIN-TRANSPORT is created, with the Bax protein concept in its \[TRANSPORTED-ENTITY\] slot and an instance of the mitochondria concept (from GO\'s cellular component hierarchy) in its \[TRANSPORT-DESTINATION\] slot. OpenDMAP patterns can express variability in word and phrase order. Note, for example, that equation 2 would fail to match the phrase \"Bax translocation to mitochondria from the cytosol.\" The special pattern marker @ is used to identify a set of subpatterns that are both optional and can occur before or after a required phrase; multiple @ marked phrases can occur in any order. For example, equation 2 can be modified with this marker to recognize the above text: $$\begin{matrix} \text{PROTEIN-TRANSPORT~:=~([TRANSPORTED-ENTITY]~translocation)} \\ \text{@~(from~\{det\}?~[TRANSPORT-ORIGIN])} \\ \text{@~(to~\{det\}?~[TRANSPORT-DESTINATION]);} \\ \end{matrix}$$ Many sentences in the literature express multiple concepts, making extraction of even simple assertions problematic. Consider the following GeneRIF from GeneID:29560: \"\...HIF-1alpha which is present in glomus cells translocates to the nucleus\....\" The intervening phrase \"which is present in glomus cells\" prevents the pattern in equation 3 from matching that sentence. OpenDMAP does have a wildcard character (underscore) that could be added to the pattern in equation 3, between the \[TRANSPORTED-ENTITY\] concept and the word \"translocation,\" allowing this sentence to be matched. However, using such a wild card would make any protein mentioned before the word \"translocation\" match the pattern, which is too promiscuous. To address this problem, OpenDMAP allows patterns to specify syntactic constraints on potential matches. For example, the \[TRANSPORTED-ENTITY\] slot can be constrained to have a syntactic dependency on the head of a phrase that contains the translocate action, thereby constraining it both semantically (it must be a protein or molecular complex) and syntactically (it must be the subject, object or modifier of the translocation). Furthermore, the reliance on the exact word \"translocation\" can be relaxed to be any reference to a transport action word, including both verbal and nominal forms of multiple terms (e.g., transported, translocation). The PROTEIN-TRANSPORT class is extended to have an \[action\] slot that specifies the type of transportation action, to keep track of the term that was used. Equation 4 demonstrates the pattern language for specifying syntactic constraints: $$\begin{array}{l} \text{PROTEIN-TRANSPORT~:=~([TRANSPORTED-ENTITY~dep:x]~\_} \\ {\text{[action~ACTION-TRANSPORT~head:x])}} \\ {\text{~~~~~}\text{@~(from~\{det\}?~[TRANSPORT-ORIGIN])}} \\ {\text{~~~~~}\text{@~(to~\{det\}?~[TRANSPORT-DESTINATION]);}} \\ \end{array}$$ The use of the variable \"x\" in the specification identifies a specific syntactic unit, linking the dependency to the head of a phrase. Multiple variables can be used to specify constraints on different syntactic units within a sentence. OpenDMAP patterns are very powerful. Only five such patterns, shown in equations 5--9 were required for the transport extraction system performance noted above. These patterns were devised manually, based on expert knowledge of the domain and on a small training set of sample GeneRIFs. $$\begin{matrix} \text{PROTEIN-TRANSPORT~:=~[TRANSPORT-DESTINATION]~[action~ACTION-TRANSPORT]~\_} \\ \text{(of~\{det\}?~~[TRANSPORTED-ENTITY])?} \\ \text{(by~\{det\}?~[TRANSPORTING-ENTITY])?;} \\ \end{matrix}$$ $$\begin{array}{l} \text{PROTEIN-TRANSPORT~:=~([TRANSPORTED-ENTITY~dep:x]~\_} \\ {\text{[TRANSPORT-DESTINATION]}} \\ {\text{[action~ACTION-TRANSPORT~head:x])}} \\ {\text{(by~\{det\}?~[TRANSPORTING-ENTITY])?;}} \\ \end{array}$$ $$\begin{array}{l} \text{PROTEIN-TRANSPORT~:=~[action~ACTION-TRANSPORT]} \\ {\text{@~(of~\{det\}?~~[TRANSPORTED-ENTITY])}} \\ {\text{@~(by~\{det\}?~[TRANSPORTING-ENTITY])}} \\ {\text{@~(from~\{det\}?~[TRANSPORT-ORIGIN])}} \\ {\text{~~~~~}\text{@~(to|toward|towards|into~\{det\}?}} \\ {\text{[TRANSPORT-DESTINATION]);}} \\ \end{array}$$ $$\begin{array}{l} \text{PROTEIN-TRANSPORT~:=~([TRANSPORTED-ENTITY~dep:x]~\_} \\ {\text{[action~ACTION-TRANSPORT~head:x])}} \\ {\text{@~(by~\{det\}?~[TRANSPORTING-ENTITY])}} \\ {\text{@~(from~\{det\}?~[TRANSPORT-ORIGIN])}} \\ {\text{@~(to|toward|towards|into~\{det\}?}} \\ {\text{[TRANSPORT-DESTINATION]);}} \\ \end{array}$$ $$\begin{array}{l} \text{PROTEIN-TRANSPORT~:=~([TRANSPORTED-ENTITY]~(is|were|are|was)} \\ {\text{[action~ACTION-TRANSPORT-PASSIVE])}} \\ {\text{@~(by~\{det\}?~[TRANSPORTING-ENTITY])}} \\ {\text{@~(from~\{det\}?~[TRANSPORT-ORIGIN])}} \\ {\text{@~(to|toward|towards|into~\{det\}?}} \\ {\text{[TRANSPORT-DESTINATION]);}} \\ \end{array}$$ These patterns were augmented with 119 cellular component patterns. The test data used in the transport and expression evaluations were marked up by domain experts trained in conceptual annotation, using the Knowtator annotation tool \[[@B62]\]. Availability of data and software ================================= The OpenDMAP platform-independent Java 1.5 source code, including UIMA wrappers for the tools used in this work and the patterns for the three tasks, is available from <http://bionlp.sourceforge.net/> under the Mozilla Public License v1.1 (OpenDMAP) and GPL v2.0 license (UIMA wrappers). The results of the information extraction effort are available as RDF format files in the Additional Files [1](#S1){ref-type="supplementary-material"}, [2](#S2){ref-type="supplementary-material"}, [3](#S3){ref-type="supplementary-material"}, [4](#S4){ref-type="supplementary-material"}. Authors\' contributions ======================= LH conceived of the project, supervised the design and implementation of the system and wrote the manuscript. ZL was responsible for the transport project, including writing the patterns and analyzing the results; he also contributed suggestions for the interaction task. JRF implemented the OpenDMAP pattern recognition engine and its UIMA wrapper. WAB wrote all other infrastructure software, including the other UIMA wrappers, managed the data, applied OpenDMAP to all of MEDLINE, and designed and built other software. HLJ was responsible for the interaction and expression projects, including writing the patterns, analyzing the results, and doing the associated error analyses. PVO managed the creation of the gold standard data for transport and contributed to the design of the pattern language syntax. KBC managed the team, selected the preprocessing tools, coordinated and supervised the interaction and expression task efforts, and provided linguistic and software design contributions during all phases of the project. All authors have read and approved this manuscript. Supplementary Material ====================== ###### Additional file 1 **Transport instances from MEDLINE**. This file contains the RDF formatted instances of *transport*, mined from MEDLINE with OpenDMAP. ###### Click here for file ###### Additional file 2 **Interaction instances from MEDLINE, part 1**. The *interaction*data set is very large. This file contains the first half of RDF formatted instances of *interaction*, mined from MEDLINE with OpenDMAP. ###### Click here for file ###### Additional file 3 **Interaction instances from MEDLINE, part 2**. The *interaction*data set is very large. This file contains the second half of RDF formatted instances of *interaction*, mined from MEDLINE with OpenDMAP. ###### Click here for file ###### Additional file 4 **Expression instances from MEDLINE**. This file contains the RDF formatted instances of *expression*, mined from MEDLINE with OpenDMAP. ###### Click here for file Acknowledgements ================ This work was funded by NIH grants R01NLM008111 and R01NLM009254 to LH. ZL was also supported in part by the Intramural Research Program of the NIH, NLM. We gratefully acknowledge Martha Palmer\'s invaluable advice regarding error analysis for the expression project; Martin Krallinger and Alfonso Valencia\'s coordination of the BioCreative 2 protein-protein interaction shared task; Michael Bada\'s management of the creation of the gold standard for the expression project; Jesse Paquette\'s development of the species identification code that we used in the interaction task; and Sue Brozowski and Fonteini Davrazou\'s annotation of data for the transport and expression projects.
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/* Any copyright is dedicated to the Public Domain. * http://creativecommons.org/publicdomain/zero/1.0/ */ /* global Services, requestLongerTimeout, TestUtils, BrowserTestUtils, ok, info, dump, is, Ci, Cu, Components, ctypes, gBrowser, add_task, addEventListener, removeEventListener, ContentTask */ "use strict"; // Running this test in ASAN is slow. requestLongerTimeout(2); /** * Removes a file from a directory. This is a no-op if the file does not * exist. * * @param directory * The nsIFile representing the directory to remove from. * @param filename * A string for the file to remove from the directory. */ function removeFile(directory, filename) { let file = directory.clone(); file.append(filename); if (file.exists()) { file.remove(false); } } /** * Returns the directory where crash dumps are stored. * * @return nsIFile */ function getMinidumpDirectory() { let dir = Services.dirsvc.get("ProfD", Ci.nsIFile); dir.append("minidumps"); return dir; } /** * Checks that the URL is correctly annotated on a content process crash. */ add_task(async function test_content_url_annotation() { let url = "https://example.com/browser/toolkit/content/tests/browser/file_redirect.html"; let redirect_url = "https://example.com/browser/toolkit/content/tests/browser/file_redirect_to.html"; await BrowserTestUtils.withNewTab( { gBrowser, }, async function(browser) { ok(browser.isRemoteBrowser, "Should be a remote browser"); // file_redirect.html should send us to file_redirect_to.html let promise = BrowserTestUtils.waitForContentEvent( browser, "RedirectDone", true, null, true ); BrowserTestUtils.loadURI(browser, url); await promise; // Crash the tab let annotations = await BrowserTestUtils.crashFrame(browser); ok("URL" in annotations, "annotated a URL"); is( annotations.URL, redirect_url, "Should have annotated the URL after redirect" ); } ); });
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--- layout: post title: ! 'Propel Queries: Now With Manual Binding, Too' published: true --- <p>Propel is quite good at guessing the binding type to use in your queries. But sometimes you need to force a binding type which is not the one Propel would have guessed. Starting with the next minor release (1.6.4), Propel will be able to do it.<!--more--></p> <h3>Propel Guesses Binding Types From Your Schema</h3> <p>Consider the following query:</p> <div class="CodeRay"> <div class="code"><pre>$books = BookQuery::create() -&gt;filterByTitle('War%') -&gt;filterByPrice(array('max' =&gt; 20)) -&gt;find();</pre></div> </div> <p>Propel translates this query into the following SQL prepared statement:</p> <div class="CodeRay"> <div class="code"><pre>SELECT book.* FROM book WHERE book.TITLE LIKE ? AND book.PRICE &lt; ?</pre></div> </div> <p>Then, when you call <code>find()</code>, Propel uses PDO to <em>bind</em> the question mark placeholders with the values used in the <code>filterByXXX()</code> methods. Propel uses the binding type of the column as declared in the schema. Continuing on the previous example, where the <code>book.TITLE</code> column is a <code>VARCHAR</code> and the <code>book.PRICE</code> column is a <code>INTEGER</code>, Propel binds the values as follows:</p> <div class="CodeRay"> <div class="code"><pre>$stmt = $con-&gt;prepare($sql); $stmt-&gt;bindValue(1, 'War%', PDO::PARAM_STR); // book.TITLE is a VARCHAR $stmt-&gt;bindValue(2, 20, PDO::PARAM_INT); // book.PRICE is an INTEGER $stmt-&gt;execute();</pre></div> </div> <p>But what if you want to use another binding type?</p> <h3>Cases When You Need a Custom Binding Type</h3> <p>The <code>filterByXXX()</code> methods are always tied to a column, so for these Propel always knows what binding to use. However, when you use the <a href="http://www.propelorm.org/reference/model-criteria.html#relational_api">relational API</a>, you can create conditions on more than just columns.</p> <p>For instance:</p> <div class="CodeRay"> <div class="code"><pre>$books = BookQuery::create() -&gt;where(&quot;LOCATE('War', Book.Title) = ?&quot;, true) -&gt;find();</pre></div> </div> <p>In this case, the binding should use <code>PDO::PARAM_BOOL</code>, and not <code>PDO::PARAM_STR</code>, which is the type Propel uses for the <code>book.TITLE</code> column, declared as <code>VARCHAR</code>.</p> <p>Another example is when using <code>having()</code>:</p> <div class="CodeRay"> <div class="code"><pre>$books = BookQuery::create() -&gt;withColumn('SUBSTRING(Book.Title, 1, 4)', 'title_start') -&gt;having('title_start = ?', 'foo') -&gt;find();</pre></div> </div> <p>Here, Propel simply refuses the query, failing with a loud:</p> <div class="CodeRay"> <div class="code"><pre>PropelException: Cannot determine the column to bind to the parameter in clause 'title_start = ?'</pre></div> </div> <p>This is because the virtual column <code>title_start</code> has no intrinsec type, so Propel cannot determine which binding to use.</p> <p>Concretely, that means that the <code>having()</code> support is somehow broken in Propel 1.6. Apart from concatenating the value to the SQL clause (and risking SQL injection), you cannot add a <code>HAVING</code> clause using <code>ActiveQuery</code>...</p> <h3>Forcing a Custom Binding Type.</h3> <p>...until now. A way to force a custom binding type <a href="https://github.com/propelorm/Propel/pull/182">has just made its way</a> to the <a href="https://github.com/propelorm/Propel">Propel 1.6 master branch</a> - and that means that it will be available in Propel 1.6.4.</p> <p>It's as simple as it should be: just add the desired binding type as third parameter of either <code>where()</code> or <code>having()</code>, and you're good to go:</p> <div class="CodeRay"> <div class="code"><pre>// custom binding in where() $books = BookQuery::create() -&gt;where(&quot;LOCATE('War', Book.Title) = ?&quot;, true, PDO::PARAM_BOOL) -&gt;find(); // custom binding in having() $books = BookQuery::create() -&gt;withColumn('SUBSTRING(Book.Title, 1, 4)', 'title_start') -&gt;having('title_start = ?', 'foo', PDO::PARAM_STR) -&gt;find();</pre></div> </div> <p>No more errors, no more SQL injection risk. You're in control of the binding type when you need it.</p> <p>More than ever, there is no limit to what you can do with Propel - and less limits to what you can do with the awesome PropelQuery API.</p>
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Could Ebola go airborne? That’s the fear set off last week by a New York Times op-ed entitled “What We’re Afraid to Say about Ebola” from Michael Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota. Although clinicians readily agree that the Ebola virus leaps from one person to the next via close contact with blood and other bodily fluids, Osterholm warned that the risk of airborne transmission is “real” and “until we consider it, the world will not be prepared to do what is necessary to end the epidemic.” But interviews with several infectious diseases experts reveal that whereas such a mutation—or more likely series of mutations—might physically be possible, it’s highly unlikely. In fact, there’s almost no historical precedent for any virus to change its basic mode of transmission so radically. “We have so many problems with Ebola, let’s not make another one that, of course, is theoretically possible but is pretty way down on the list of likely issues," says infectious diseases expert William Schaffner of Vanderbilt University. "Everything that is happening now can easily be comprehensively explained by person-to-person spread via body contact. We don’t have to invoke anything else.” Here is what it would take for it to become a real airborne risk: First off, a substantial amount of Ebola virus would need to start replicating in cells that reside in the throat, the bronchial tubes and possibly in the lungs. Second, the airborne method would have to be so much more efficient than the current extremely efficient means of transmission that it would overcome any genetic costs to the virus stemming from the mutation itself. Substantial natural hurdles make it unlikely that either event will occur. Currently, Ebola typically gains entry into the body through breaks in the skin, the watery fluid around the eye or the moist tissues of the nose or mouth. Then it infects various cells of the immune system, which it tricks into making more copies of itself. The end result: a massive attack on the blood vessels, not the respiratory system. Even viruses that are well adapted to attacking the respiratory system often have a hard time getting transmitted through the airways. Consider the experience so far with avian flu, which is easily transmitted through the air in birds but hasn’t yet mutated to become easily spreadable in that fashion among people. What's the hold-up? “The difficulty is that those [flu] viruses don’t have the protein attachments that can actually attach to cells in the upper airway. They have to develop attachments to do that,” Schaffner says. So even if a virus were exhaled, it would need to lodge onto something in another person’s cells that are already prepared for it in the upper airway. “Since the virus doesn’t have attachment factors that can work in the upper airway, it’s very rare for it to go human to human, and then it almost always stops and doesn’t get to a third person,” Schaffner notes. Similarly for Ebola, the virus would have to develop attachments that would allow it to easily attach receptors in the upper respiratory pathway—something that neither it (nor any of its viral cousins) has been known to do in the wild. And yet Ebola already spreads very easily without such mutations. The delicate lock-and-key protein–virus fit required for the virus to successfully latch onto and replicate in the airway has not developed because there is no evolutionary pressure for it to do so; it simply would not be an efficient option. Epidemiologists can take some comfort in that. As the virus continues to circulate through west Africa, it may like any other pathogen continue to acquire genetic mutations. So far, however, there is no indication that Ebola is mutating in a way that could allow it to make the leap from becoming transmissible via contact with body fluids (as it is now) to become a germ that could be transmitted by breathing the same air, according to WHO. With Ebola, "I don't think we have the information at this time to know what the real risk is but it is probably not zero,” says Ebola expert Thomas Geisbert, a virologist at The University of Texas Medical Branch at Galveston. The incident that put the specter of airborne Ebola on the map was chronicled in the book The Hot Zone, wherein, in 1989, the virus was apparently spread via the air from monkey to monkey (although it did not make the leap to humans working in the lab). But experts have subsequently wondered if that lone circumstance of primate-to-primate air transmission was fueled by the lab setting and man-made systems. As Osterholm notes in his piece, in 2012 researchers found that a strain of Ebola was spread from pigs to nonhuman primates via the air in a different lab setting. The virus, however, did not then spread from monkey-to-monkey in those circumstances. Questions remain about the current strain of Ebola thriving in west Africa. Apart from the environmental, economic and social circumstances that have fueled its spread, does the virus itself have special characteristics that set it apart? Is it, for example, growing faster or at higher viral concentrations than previous strains? But the jury is still out on this and other questions. Right now we have few answers about this Ebola strain, yet we do know that a massive injection of finances and personnel will be needed to contain it in the months ahead. As of Friday it had claimed more than 2,400 lives.
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Q: The number of ordered pairs $(x,y)$ satisfying the equation The number of ordered pairs $(x,y)$ satisfying the equation $\lfloor\frac{x}{2}\rfloor+\lfloor\frac{2x}{3}\rfloor+\lfloor\frac{y}{4}\rfloor+\lfloor\frac{4y}{5}\rfloor=\frac{7x}{6}+\frac{21y}{20}$,where $0<x,y<30$ It appears that $\frac{x}{2}+\frac{2x}{3}=\frac{7x}{6}$ and $\frac{y}{4}+\frac{4y}{5}=\frac{21y}{20}$ but $\frac{x}{2}$ and $\frac{2x}{3}$ being inside the floor function,i can not add them up directly,same problem here,i cannot add $\frac{y}{4}$ and $\frac{4y}{5}$ because they are inside the floor function.What should i do to solve it? A: Note that $$\Bigl\lfloor\frac x2\Bigr\rfloor\le\frac x2\ ,$$ and likewise for the other terms. So we always have $LHS\le RHS$, and the only way they can be equal is if $$\Bigl\lfloor\frac x2\Bigr\rfloor=\frac x2\ ,$$ and likewise for the other terms. So $$\frac x2\ ,\quad \frac{2x}3\ ,\quad \frac y4\ ,\quad\frac{4y}5$$ must all be integers. Can you take it from here?
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The district attorney’s office Monday confirmed the dismissal of vehicular manslaughter and DUI charges filed against an Indio resident following a crash that killed a young woman, as authorities continue investigating who may have been driving the involved car that veered off a roadway and overturned in the parking lot of a Coachella casino. Alezia Carmona, 22, of El Centro, died at the scene of the June 2 crash, which occurred just after 6 a.m. when the Nissan Maxima she was riding in tumbled off the right shoulder of state Route 86 and into the parking lot of the Spotlight 29 Casino. Annalee Montemayor, 22, of Indio, was identified by authorities shortly after the crash as the Maxima’s driver. She was hospitalized with major injuries and later arrested and charged with DUI, gross vehicular manslaughter and evading a peace officer causing injury or death. Those charges were dismissed earlier this month, according to district attorney’s spokesman John Hall. “During the continuing investigation into this case, our office obtained evidence that Ms. Montemayor may not have been the driver of the involved vehicle,” he said. “The investigation is ongoing and the case is still active.” The District Attorney’s Office would not elaborate on the new evidence, but the California Highway Patrol initially stated that in addition to Carmona and Montemayor, at least one other person was in the car. The CHP could not immediately be reached for comment on the dismissal of charges against Montemayor. Montemayor was being held in a county jail on $1 million bail, but prosecutors moved to dismiss the charges against her on Sept. 7 and released her from custody. CHP investigators have also said that the Maxima passed a white Pontiac Aztek just prior to the crash. After the Maxima ran off the roadway, surveillance footage shows that the Pontiac stopped “for a minimal amount of time” before proceeding “straight onto northbound state Route 86,” according to the CHP. A photo of the witness’ vehicle, captured by a nearby surveillance camera, was released to the public in June. Anyone with information regarding the crash was asked to contact CHP Officer Solis at (760) 772-5300.
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Q: Should we use Firebase or Google Compute Engine? Our clients will send two numbers to this server-side compute engine, and we want this server to notify all those clients who sent numbers that add up > 10. Researching online it seems Google Compute Engine can do this but we’re not sure if it can send notifications. Should we use Firebase or Google Cloud Platform ? Any pre-existing APIs we can use here ? This is our first time setting up something like this so we are confused how to go about it A: As far as I understood you want a simple push notification mechanism. Firebase is part of the GCP so when you decide to use Firebase, actually you are using a GCP project. Consider taking a look at this link to understand their relationship better. On the other hand, there is no more separate cloud messaging only for GCP according to this. Now your only option if you want to stay faithful to google platform for that matter is Firebase Cloud Messaging
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Q: Check if List contains an instance equal to a given one I don't want to loop through the list comparing each property. Something with this functionality: class myClass { public int I { get; set; } } class Program { static void Main(string[] args) { List<myClass> l = new List<myClass>(); myClass x = new myClass(); x.I = 1; l.Add(x); myClass y = new myClass(); y.I = 2; l.Add(y); myClass z = new myClass(); z.I = 2; if (l.ContainsAnInstanceEqualTo(z)) Console.WriteLine("Contains"); Console.ReadLine(); } } IMPORTANT: I have no control over the class and there are a few properties which should have the same value. A: You should make myClass implement IEquatable<myClass> (or at least override Equals(object)) and then just use: if (l.Contains(z)) (You should also rename the class to follow .NET naming conventions...) If you don't provide an Equals method, you've got to specify what sort of equality you're interested in somehow. You can do this via something like Find with a predicate: var found = l.Find(c => c.I == z.I); if (found != null) { ... } Or using LINQ: var any = l.Any(c => c.I == z.I); but it would be better to override Equals if there is a natural sense of equality. (List<T>.Contains won't use your implementation of GetHashCode, but you should implement it in line with your Equals method anyway...) A: This is my try at creating an EqualityComparer that should compare public instance properties of any class: using System; using System.Collections.Generic; using System.Linq; using System.Text; using System.Reflection; namespace ConsoleApplication2 { class MyClass { public int I { get; set; } public string S { get; set; } } class Program { static void Main(string[] args) { HashSet<MyClass> hs = new HashSet<MyClass>(new SamePublicPropertiesInstance()); MyClass x = new MyClass(); x.I = 1; x.S = "1"; hs.Add(x); MyClass y = new MyClass(); y.I = 2; y.S = "1"; hs.Add(y); MyClass z = new MyClass(); z.I = 2; z.S = "1"; hs.Add(z); foreach (MyClass m in hs) { Console.WriteLine("I: {0} S: {1}", m.I, m.S); } Console.ReadLine(); } } } class SamePublicPropertiesInstance : EqualityComparer<object> { public override bool Equals(object o1, object o2) { PropertyInfo[] pInfos = o1.GetType().GetProperties(BindingFlags.Public | BindingFlags.Instance); string pName; bool equal; MethodInfo methodInfo; foreach (PropertyInfo pInfo in pInfos) { pName = pInfo.Name.ToString(); methodInfo = o1.GetType().GetProperty(pName).GetGetMethod(); equal = methodInfo.Invoke(o1, null).ToString() == methodInfo.Invoke(o2, null).ToString(); if (!equal) return false; } return true; } public override int GetHashCode(object o) { return 1.GetHashCode(); } }
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Q: Windows Appending Domain Suffix To All Lookups I have a recurring DNS problem that has been plaguing our users occasionally causing their laptops to appended our companies domain to the end of all DNS queries. The problem only occurs when users are offsite and it appears to be fairly random. It will work one day and then out of the blue it will show the invalid entry. This affects mostly Windows XP users but has recently been seen on Vista as well. Here is an example using nslookup. C:\Users\Username>nslookup www.yahoo.com Server: Linksys Address: 192.168.0.1 Non-authoritative answer: Name: www.yahoo.com.EXAMPLE.COM Address: 192.0.2.99 I have replaced the IP address that is reported with a placeholder but I can tell you that what it returns is the default *. entry on our Network Solutions configuration. Since obviously www.yahoo.com.EXAMPLE.COM doesn't exist this makes sense. I believe the user's internal equipment is functioning properly. Internally we run a Windows 2k3 Active Directory w/ Windows based DHCP and DNS servers. Eventually the problem resolves itself usually over a couple of hours or a number of reboots. Has anyone seen this behavior before? A: If you launch nslookup and turn on debugging you'll see that Windows always tries to append its suffix first. C:\>nslookup Default Server: itads.example.com Address: 0.0.0.0 > set debug=true > www.yahoo.com Server: itads.example.com Address: 0.0.0.0 ------------ Got answer: HEADER: opcode = QUERY, id = 2, rcode = NXDOMAIN header flags: response, auth. answer, want recursion, recursion avail. questions = 1, answers = 0, authority records = 1, additional = 0 QUESTIONS: www.yahoo.com.example.com, type = A, class = IN AUTHORITY RECORDS: -> example.com ttl = 3600 (1 hour) primary name server = itads.example.com responsible mail addr = itads.example.com serial = 12532170 refresh = 1200 (20 mins) retry = 600 (10 mins) expire = 1209600 (14 days) default TTL = 3600 (1 hour) ------------ ------------ Got answer: HEADER: opcode = QUERY, id = 3, rcode = NOERROR header flags: response, want recursion, recursion avail. questions = 1, answers = 4, authority records = 0, additional = 0 QUESTIONS: www.yahoo.com, type = A, class = IN ANSWERS: -> www.yahoo.com canonical name = www.wa1.b.yahoo.com ttl = 241 (4 mins 1 sec) -> www.wa1.b.yahoo.com canonical name = www-real.wa1.b.yahoo.com ttl = 30 (30 secs) -> www-real.wa1.b.yahoo.com internet address = 209.131.36.158 ttl = 30 (30 secs) -> www-real.wa1.b.yahoo.com internet address = 209.191.93.52 ttl = 30 (30 secs) ------------ Non-authoritative answer: Name: www-real.wa1.b.yahoo.com Addresses: 209.131.36.158, 209.191.93.52 Aliases: www.yahoo.com, www.wa1.b.yahoo.com As you can see above my machine tried to look for www.yahoo.com.example.com first, and the DNS server responded NXDOMAIN (entry not found). You can confirm this by running nslookup www.yahoo.com. (note the dot at the end of .com!) and you'll see that it is resolved normally. What's happening is that your external DNS server is responding that they have an entry for "www.yahoo.com.example.com" and is returning your IP address for the root of your site. I'm not sure what service you use but I'm guessing that you have a wildcard mapping that tells your server to respond to any unknown query with a valid response, rather than returning NXDOMAIN. You'll need to double check your settings for the server and confirm that it is only set to respond to queries for entries it actually has (example.com, www.example.com, mail.example.com, etc.). Remember that DNS works by checking the configured server and working its way up from there. The DNS query can take a path like the following pattern (of course this is just a example, it is probably wrong): Machine -> Local Router DNS (linksys) -> ISP DNS -> (2nd ISP DNS?) -> Root Server DNS -> TLD DNS -> Your External DNS server. Someone along that path is saying that www.yahoo.com.example.com exists. Chances are it's your external DNS server. EDIT I figured I'd include one more tidbit about the randomness you mention. If this is really happening sporadically you may have a misconfigured external DNS server or their ISP could be providing a DNS hijacking service. Unfortunately I've seen more and more residential ISPs provide a "search service" for invalid domain names. Since almost all end users use their ISP DNS servers, the ISPs are now starting to redirect invalid domain entries to a search page - one usually laden with ads, irrelevant links and a small "Did you mean www.example.com?" with some results that may or may not be related to the domain name. I know that Verizon and Comcast are starting to do this, I believe Quest is starting to as well. Another possibility is OpenDNS, since they provide the same "search for a related domain" if it doesn't exist (it's their revenue after all). My problem with suggesting that as the problem, though, is the fact that you say it's returning the address of your root record, which none of these would do if they were trying to search for it, they'd give you an IP of one of their web servers to handle the search. A: After drunken totalling my Windows 7 tcpip registry settings, I had the same problem. In: HKEY_LOCAL_MACHINE\SYSTEM\CurrentControlSet\services\Tcpip\Parameters make sure your entry for domain is the same as your entry for dhcpdomain, then you are good to go.
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Owned by a snowy bunny Main Menu When the bizarre Spirited Away becomes ‘normal’ When I was 15, Spirited Away to me was nothing more than a nightmare-ish animated film and how I hated watching it because it only reminded me of unusual dreams, which I’d rather really be not reminded of. But fast forward to 23, the film suddenly appeared to be a replica of the society we have today. 8 years later, it started to look a lot like normal to me. Perhaps this is because 8 years ago, I wasn’t aware how in life, there really are instances when parents unknowingly make bad decisions and then their children will have to figure it all out on their own later on; and that in life, there really are Yubabas who wait for vulnerable souls to take advantage of, and that there are Hakus who will help and will (with all his might) stand up for what is right; and that the “real world” can (sadly) be filled with human frogs—souls that failed to notice how they slowly got eaten by the template of the conventional, with Lins who are not yet human frogs but are already starting to look like one, & with No Face who, when given even just the shortest time under the limelight, can lose himself to greed; and that someone who looks the weirdest, like Kamaji, can actually be the most reliable and the most full of love; and that a seemingly helpless naive can try and win in standing up on his/her own; and that someone who bears an unlikely appearance, like Zeniba (Yubaba’s identical twin), can be truly good and warm inside. Had I surrendered to the thought that Spirited Away is “just plain weird,” I would have missed the wonderful opportunity to see how two unidentical realms (the Spirited Away universe and the real world) can actually be each other’s reflection in the mirror. And had I chosen to leave the characters alone (because they are strange!), I would never have been able to see how I actually have the ability and the tendency to be a Chihiro, a Haku, a Zeniba, a Kamaji, a Lin, a No Face, a human frog, or even a Yubaba in real life. Had I shelved Spirited Away as “nonsense and not to be watched again,” I would have completely lost touch with an art that can actually help always keep my morale in check. Both my hands are forever down to the Hayao Miyazaki for this timeless work of art.
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// Copyright 2015 The Go Authors. All rights reserved. // Use of this source code is governed by a BSD-style // license that can be found in the LICENSE file. // Package utf8internal contains low-level utf8-related constants, tables, etc. // that are used internally by the text package. package utf8internal // The default lowest and highest continuation byte. const ( LoCB = 0x80 // 1000 0000 HiCB = 0xBF // 1011 1111 ) // Constants related to getting information of first bytes of UTF-8 sequences. const ( // ASCII identifies a UTF-8 byte as ASCII. ASCII = as // FirstInvalid indicates a byte is invalid as a first byte of a UTF-8 // sequence. FirstInvalid = xx // SizeMask is a mask for the size bits. Use use x&SizeMask to get the size. SizeMask = 7 // AcceptShift is the right-shift count for the first byte info byte to get // the index into the AcceptRanges table. See AcceptRanges. AcceptShift = 4 // The names of these constants are chosen to give nice alignment in the // table below. The first nibble is an index into acceptRanges or F for // special one-byte cases. The second nibble is the Rune length or the // Status for the special one-byte case. xx = 0xF1 // invalid: size 1 as = 0xF0 // ASCII: size 1 s1 = 0x02 // accept 0, size 2 s2 = 0x13 // accept 1, size 3 s3 = 0x03 // accept 0, size 3 s4 = 0x23 // accept 2, size 3 s5 = 0x34 // accept 3, size 4 s6 = 0x04 // accept 0, size 4 s7 = 0x44 // accept 4, size 4 ) // First is information about the first byte in a UTF-8 sequence. var First = [256]uint8{ // 1 2 3 4 5 6 7 8 9 A B C D E F as, as, as, as, as, as, as, as, as, as, as, as, as, as, as, as, // 0x00-0x0F as, as, as, as, as, as, as, as, as, as, as, as, as, as, as, as, // 0x10-0x1F as, as, as, as, as, as, as, as, as, as, as, as, as, as, as, as, // 0x20-0x2F as, as, as, as, as, as, as, as, as, as, as, as, as, as, as, as, // 0x30-0x3F as, as, as, as, as, as, as, as, as, as, as, as, as, as, as, as, // 0x40-0x4F as, as, as, as, as, as, as, as, as, as, as, as, as, as, as, as, // 0x50-0x5F as, as, as, as, as, as, as, as, as, as, as, as, as, as, as, as, // 0x60-0x6F as, as, as, as, as, as, as, as, as, as, as, as, as, as, as, as, // 0x70-0x7F // 1 2 3 4 5 6 7 8 9 A B C D E F xx, xx, xx, xx, xx, xx, xx, xx, xx, xx, xx, xx, xx, xx, xx, xx, // 0x80-0x8F xx, xx, xx, xx, xx, xx, xx, xx, xx, xx, xx, xx, xx, xx, xx, xx, // 0x90-0x9F xx, xx, xx, xx, xx, xx, xx, xx, xx, xx, xx, xx, xx, xx, xx, xx, // 0xA0-0xAF xx, xx, xx, xx, xx, xx, xx, xx, xx, xx, xx, xx, xx, xx, xx, xx, // 0xB0-0xBF xx, xx, s1, s1, s1, s1, s1, s1, s1, s1, s1, s1, s1, s1, s1, s1, // 0xC0-0xCF s1, s1, s1, s1, s1, s1, s1, s1, s1, s1, s1, s1, s1, s1, s1, s1, // 0xD0-0xDF s2, s3, s3, s3, s3, s3, s3, s3, s3, s3, s3, s3, s3, s4, s3, s3, // 0xE0-0xEF s5, s6, s6, s6, s7, xx, xx, xx, xx, xx, xx, xx, xx, xx, xx, xx, // 0xF0-0xFF } // AcceptRange gives the range of valid values for the second byte in a UTF-8 // sequence for any value for First that is not ASCII or FirstInvalid. type AcceptRange struct { Lo uint8 // lowest value for second byte. Hi uint8 // highest value for second byte. } // AcceptRanges is a slice of AcceptRange values. For a given byte sequence b // // AcceptRanges[First[b[0]]>>AcceptShift] // // will give the value of AcceptRange for the multi-byte UTF-8 sequence starting // at b[0]. var AcceptRanges = [...]AcceptRange{ 0: {LoCB, HiCB}, 1: {0xA0, HiCB}, 2: {LoCB, 0x9F}, 3: {0x90, HiCB}, 4: {LoCB, 0x8F}, }
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Oxidative N-Heterocyclic Carbene-Catalyzed γ-Carbon Addition of Enals to Imines: Mechanistic Studies and Access to Antimicrobial Compounds. The reaction mechanism of the γ-carbon addition of enal to imine under oxidative N-heterocyclic carbene catalysis is studied experimentally. The oxidation, γ-carbon deprotonation, and nucleophilic addition of γ-carbon to imine were found to be facile steps. The results of our study also provide highly enantioselective access to tricyclic sulfonyl amides that exhibit interesting antimicrobial activities against X. oryzae, a bacterium that causes bacterial disease in rice growing.
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[Drug fatalities from the forensic medicine viewpoint. 10 years experiences of the Vienna Institute of Forensic Medicine]. The problem of illicit drug abuse has of course not spared Austria. In fact, considering only the increase in the official figures on drug-related deaths over the past few years, this problem has dramatically worsened in Austria. Drug-related deaths represent the most serious consequence of substance abuse, but according to the Pompidou Group classification such deaths are only one of eight indicators in assessing the extent of drug abuse in a community. We analyzed reports on all postmortems classified as drug-related deaths according to the official definition of the Austrian Federal Ministry of Internal Affairs undertaken at the Institute of Forensic Medicine in Vienna between 1984 and 1993. The annual number of drug-related deaths increased nearly ten-fold during the study period. In about a third of the cases accidental single substance overdosage (of mainly a morphine-containing drug) was the cause of death. In the majority of the corpses more than one drug, including alcohol, was detected. During the past 10 years there was an evident trend towards a multisubstance abuse pattern. Since the plateau reached in 1988, the incidence of HIV-1 infection among decreased drug injectors has decreased.
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Gross Point Blank Keeping it real I'm a newspaper junkie. I love to read news stories both online and in print. Because of my appreciation for solid reporting, it's astounding when people that I interview request to see what I'm going to print before it goes to press. Do you like to read news stories? Could you imagine what you'd be reading if every person interviewed was granted the OK to edit their words? When I was a cub reporter many years ago, I saw nothing wrong with granting the request. I'd bang out my copy and share it before it went to press. It didn't take long before I learned why this is bad practice. Suddenly, my words were out of order, my voice as a reporter lost. What I had written would become stiff and inflexible, and, well, basically over edited and unnatural. We're not even talking about potentially controversial stories. I handled little to none of those in my cub days. Granted, there are times when I'll be writing about something, maybe an insect whose name I can't pronounce let alone spell, and I will have to copy and paste that into an email, send it off and get some fact checking done. And sports stories, too. I don't understand the terminology so at times I have to run it by someone so as not to make an ass out of myself. Usually though, once me and the person I've interviewed are done with our dialogue, then it's up to me to put the pieces together and tell the story.
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Slaying Goliath Blurb When BELINDA COMPTON meets JOSH MCCLEAN at a party on a cold New York night, it’s like finding a piece of gravel in a box of diamonds. The other men look shiny and are worth a lot of money, but he’s different. Josh is gorgeous, complicated, mysterious, and flawed. She is drawn to him, his intense eyes, his soft kiss, and the silence that envelopes him. Josh is damaged. One fight, that was all it took, a crushed larynx and his career was history. There is no such thing as a mute actor. Forced to recreate himself, Goliath was born and, as an erotic dancer, he was back in the spotlight. But large pieces of him were left behind. His disability makes everything difficult, people treat him like a porn star, and the women in his life are only interested in Goliath and not Josh. He’s given up on love, but Belinda isn’t expected. With her, he starts to hope. Belinda Compton has a well-established story. She knows where she is from and where she is going. Her accountancy career is her life and she is prepared to sacrifice everything for her ambition. Then she meets Josh. She’s left questioning her priorities, and this isn’t a good time for her to lose focus. #FIRST DRAFT EDITION Chapter 1 Slaying Goliath The night air embraced him. Its cold fingers reached out and touched him with an honesty he found refreshing. The light from the glass doors cut through the blanket of darkness with its harsh glare and accompanying din, reminding him that he wasn’t alone. Behind him, the room was brimming with glossy people, celebrities, rich A-listers and corporate types. The event was being hosted by some Finance corporation who was using it to paint themselves charitable and wholesome by donating the proceeds to the latest must-have cause. The tickets cost an astronomical amount and the motives were contrived but, unfortunately, he was still here. Everyone was smiling, drinking and laughing. Everyone except him, he was hiding. The room, from which he’d fled, occupied the entire floor and had high ceilings, chandeliers and polished wood floors. The music came from a string quartet who had set up shop in the corner. It looked more like an art gallery, with multiple leather sofas, chairs and a bar, than an accountancy firms’ function room. One whole wall was punctuated with floor to roof French doors with lace curtains blocking the million-dollar view. The doors led onto a long balcony that overlooked the park and the city lights. He would have liked to take the time to admire the art that hung on the walls inside and the sculptures dotted around the open room, but that wasn’t possible. Not now that the space was overflowing with men in expensive suits and women draped in dresses that cost more than they should given the amount of fabric employed. These people didn’t stop to admire the art, they were too busy looking at their own reflections in the glass that framed the masterpieces. He knew this because he used to be one of them. The night had called to him with its promise of solitude. He’d opened one of the French doors and was now pressed against the brickwork of the building taking in the view from the balcony. He wanted to leave but this view was spectacular, and Sam would give him ‘that-look’ if he went home this early. Sam seemed to think that he could do this. That being here was a good thing for him. Sam was wrong. He glanced into the bright room. A man in an Armani suit laughed as a woman in a tiny black dress and wearing a necklace of precious gems, that would have been impressive if it was fake, touched his arm. His hair was styled, his skin was moisturised, and his fingernails would be manicured. Josh knew this man. He had no idea what his name was, but he was a cardboard cut-out of the man Josh used to be. He closed his eyes blocking his view of the couple, that wasn’t his life anymore. When he opened them they were still there, the woman whispered something to the man who’s hand ventured lower down to the hem of the dress. They would be heading for the door soon. Heading for the a near vertical position and some heavy breathing. He knew the look in that woman’s eyes but that was ancient history for him. He would stay another half-an-hour out here before heading home. That would make it sound like he was making-an-effort. He pushed himself further into the darkness and said one final thank-you that the event organisers didn’t expect anyone out here on such a wintery night. The external lighting, directly above him, wasn’t on. He was cold outside but if he went inside he would have to stand there in those bright lights, standing out like the six-foot-seven mountain he was, and someone would eventually place him. Then the whispering would buzz from person to person, the tittering would flitter around the room and eyes would turn to him. It was inevitable. No one admitted to it but somehow everyone seemed to know him. It was his cross to bear. His fingers drummed on the brickwork as turned to lean his right shoulder against the wall. He relaxed one of his long legs while he counted the seconds. He could wait. It wouldn’t kill him. Twenty minutes more. He wished he’d worn something warmer. The door moved sending the lace curtains fluttering outwards and introducing a wave of sound into his sanctuary. A face emerged through the curtains. The woman didn’t look around. She closed her eyes and breathed in the night air as if surfacing from the ocean water. Then her shoulders broke through the drapes showing her smooth pale skin. She arched her back slightly as she took another breath, thrusting her full breasts out. He held his breath. He was facing her. If he reached out he could have skimmed his fingers over her skin. Was it as silky smooth as it looked? She didn’t turn to him even though his heartbeat seemed to be announcing his hiding place. Without opening her eyes, she burst forth, the window dressing billowing as she practically fell forward, grasping a hold of the wrought iron balustrade, and leaning over into the void and long drop to the street below. He pushed himself off the brickwork, arms moving towards her, propelling himself from his hiding spot to catch her fall. She was leaning outward putting all her weight on that light framework of dark metal. He stopped himself inches from her, as she straightened up and arched her back, hands gripping, and arms outstretched. Her eyes remained tightly closed. He wondered if she was drunk or high. She wasn’t behaving rationally. Her hair was a light brown caramel colour and was long and loose, hanging where it wanted to without any restraints. Her face was relaxed and showed only light natural makeup, or possibly no makeup at all. She fell forward again and, as she did, she breathed out in one long breath. Her shoulders dropped as did her head. She looked downwards, still hanging onto the metal rail as her forearms lay along the cold length. Her tight little ass pointing towards him. The dress she wore was a grape colour, it was wrapped around her in gentle folds and hung from little more than a string looping over each shoulder. The whole affair looked like it was made from soft tissue paper and would easily flutter away if either string was severed. The shoes didn’t match. The fragile dress should have been paired with sexy stilettoes not the sturdy black, thick low-heeled footwear she wore. She was tall. Maybe her partner didn’t want her towering over him. He silently returned to the darkness. He should leave. He should take the opportunity to escape. But he found that his feet didn’t agree with him. His patent leather shoes seemed to be rooted in place. A waft of a floral scent had him breathing deeply. He glanced at the door. Where was her partner? A man should be following, wrapping his arms around her waist and kissing her down that long neck of hers. As if she’d heard his thoughts, she shivered, and he had to fight the impulse to smoother her bare back in his warmth. This wasn’t good. He looked at his feet. Why wasn’t he leaving. He needed to go before the talking started. “Oh,” a soft musical voice had him looking up, “I’m sorry. I didn’t see you there.” She was smiling into the space he occupied, as she did her face up lit up and it took his breath away. Her arms were now wrapped around her as she leaned against the decorative twisting wrought iron. Her skin glowed in the moonlight and the light filtering out the lace curtains. She looked angelic. The smile lessened as the silence stretched out. She was now looking at his silhouette with wide innocent eyes and her lips were parted. She looked like she didn’t know what to do either. He was staring at her, knowing that he should be doing something, but nothing seemed to work. He wanted to charm her. He wanted to talk to her. If only he could say something. When nothing happened, and the silence became increasingly uncomfortable, she edged away, away from the light and from him. She must have realised that she was standing out here with an idiot. He had to say try something, before she gave up on him entirely. “You’re fine,” his voice was low and gravelly as the words were forced out. Then he cursed an expelled breath at the double meaning in the words before saying in a laboured growl, “You know.” He grimaced. His voice today was as good as it gets, it was better today than it was yesterday. Even so, it was broken, rough and made him sound like he was stupid. If he’d thought of something clever to say with the few words available to him, it might have helped. Instead he’d said that. It was bad enough that he was practically mute, he didn’t need her adding mentally challenged to the list of his failings. He rubbed his throat and wished for the billionth time that his voice would magically return. She tilted her head to the side as her eyes searched the darkness. Then she smiled and breathed out. Without a word she slowly moved to stand against the building on the other side of the French door. He was surprised how disappointed he felt now that he couldn’t see her. “Thanks for sharing your hiding place,” she sounded relieved, “It’s a piranha pit in there. They might look like ornamental tropical fish but show any weakness, and they’re ruthless.” She was still there. He couldn’t detect the pity in her voice and she wasn’t politely excusing herself from his company. Instead she’d smiled and said something amusing. She’d started a line of conversation that didn’t involve asking him what was wrong with his voice. He knew it was a short-term thing, she would soon realise that he couldn’t talk to her and that silence was the best she could hope for. Then she would find a good reason to re-join the party. He could feel her there, so close but so far. She was leaning her head against the brickwork looking out at the city lights. She wasn’t asking any questions yet, but he guessed that they would be bubbling in her head. It wouldn’t be long now before she would explode, and then the interrogation would start. Women were all the same. They had to ask. They had to know. The silence stretched on. He turned to see if she was still breathing. She hadn’t moved. She wasn’t talking. Why wasn’t she talking? “Belinda?” a hand parted the curtains as the too loud male voice punctured through the air, “Are you out there?” Josh was looking at her. He held his breath and edged back. He waited for her to acknowledge the man and pivot into his waiting arms, vanishing from his life. Instead silence followed, confused he focused on her and was surprised to see her cowering away. He felt the anger rise in him. Who was this man who had her so afraid? Had he hurt her? What had he done to scare her? The hand disappeared as quickly as it had appeared. She slumped with relief. He couldn’t see her face, but he could see the way her body relaxed. “What, he do?” his rough voice cut through the silence with its harsh uneven tone. “Anthony?” she scoffed, leaned against the brickwork and looked across in his direction, “He invited me to this. He said it was a networking event.” A small fire in his gut had him clench his fists against his thighs. Anthony, that must be her boyfriend. “I should have known better,” she continued, “When he loaned me this dress from his wife’s collection, I should have known that I wouldn’t be taken seriously wearing this.” Wife? Did that make her the mistress then? He turned his attention back to his shoes. “He might be a friend of my Father,” she huffed, “But I swear if he introduces me to another eligible bachelor, I might just thwack him one.” He glanced at her, the men in that room weren’t just eligible, they were every woman’s daydream. They had credentials, pedigree, huge bank accounts, and bright futures. Most women would be falling over backwards to get an introduction to just one of those men. And ‘thwack’? What was that? Who used a word like that? “I’m Belinda, by the way,” she said, then laughed, “But you already know that.” Her laugh was musical. He wanted to say something funny so that she would laugh again but that wasn’t going to happen. Who was this woman? “Josh,” his voice croaked before he realised that he was going to answer her. “So, Josh,” she said lightly, “You know my story, what brings you out here?” “Avoiding,” he whispered. “That makes us allies,” she smiled, “What’s stopping you from leaving?” “Friend,” he glanced inside wondering where Sam was. “We’re in the same boat then,” she thrust her hand across the lit space that separated them, “Nice to meet you Josh, do you have an escape plan yet?” His hand met hers before he released what he was doing. She tightened her grip as she shook it just long enough for him to feel the promise in that firm small hand. She wasn’t like anyone he knew. She was different in a way that he couldn’t even comprehend. He was intrigued. He watched her as she lapsed back into silence. Who was this woman who wasn’t impressed by anything and didn’t ask any questions? Belinda was angry with herself. She should have known better. She was smart, or at least smart enough to avoid coming to parties like this one. She closed her eyes, Anthony. He was in trouble. He’d promised her that it was corporate networking opportunity not a meat market. She couldn’t believe she’d trusted him. And now she was stuck out here, in the freezing night air wearing a dress that was ridiculous. It would have been pretty if it was a summer dress, but this was mid-winter in New York City. She should have worn a suit. At least she’d vetoed the shoes he’d offered. She might be half naked, but it was a blessing that her feet didn’t hurt. She glanced at Josh. He was a mystery. He was like finding a piece of gravel in a jewellery store. The men inside sparkled and were worth a lot of money, but this guy was interesting. How did he get here and why wasn’t he inside? She might be a good accountant but that wasn’t what got her to where she was. To be vying for a partnership in Mitchell, Sandford and Thainstone, you needed to be good a reading people and good at knowing how far you could push them and in which direction. The man on the balcony wasn’t an open book. But that was probably because he’d hardly spoken five words to her. He must have been out here for a while. That was a good point, if she was out here for too much longer she’d lose her voice too. She had a presentation to the board next week, she couldn’t afford to catch a cold. It was time to form that plan. She glanced through the doors just in time to see that moron with the quaffed hair and Harvard tie looking around the room. She knew that if she was cornered by another one of these morons she wouldn’t be able to control her contempt. This might not a corporate event, but it was attended by all the firms’ partners and many clients. She took a deep breath, it wouldn’t be acceptable behaviour for her to knee the son-of-some-Senator in the balls. That wasn’t the sort of etiquette that MS&T would find acceptable. Disappointing but true. “I should be home,” she sighed, “I’ve got too much work to do to be here. I have a problem Josh, I’m going to need your help. Can I count on you?” “Do what?” his voice sounded like rough sandpaper on course wood. It reminded her of her Grandfather and his obsession for restoring wooden sailing boats. “I don’t know you,” Belinda frowned, this was probably a bad idea. “And I know I’m asking a lot, but I need you to pretend to be my date.” He didn’t say anything for a long time. She waited. This guy was out here because he was either shy or looked like Quasimodo, either way he was hiding because he didn’t belong in there. If he agreed to this she might be jumping out of the frying pan into the fire. It was a gamble, but it was one she felt that she had to take. “Alright,” he growled slowly like he wasn’t sure himself, “Just to door.” “Agreed,” she smiled relieved that he didn’t expect more than that. Pushing off the cold wall she crossed the gap between them and stood waiting for him to join her. He hesitated for long enough for her to wonder if he did look like a hunchback monster. When he straightened up from his slouched position in the dark pocket between the French doors, she was surprised to find that he was tall and broad. She found it hard to find a man who matched her height, but Josh was a head taller and his build was perfectly proportioned. The tall men she met looked like string beans with their thin limbs and lack of muscle tone. She had the impression that if she ran her fingers down Josh’s chest she would find more than just skin stretched over ribcage. Before she could be distracted by that thought, she held out her hand to him. He seemed reluctant again and this had her wondering if it was her? Did she have something on her face, stuck in her teeth or something gooey in her hair? With her other hand, she tried to be subtle as she ran it over her cheek and smoothed it through her hair. Nothing obvious. Slowly he put his large hand in hers and stepped out of the darkness. Quasimodo he was not. His hair was long, dark and wavy. He had it swept back into a low ponytail at the back of his head. His facial hair was trimmed close to the skin to give him more than a shadow but not quite a beard. She wondered if it would be scratchy on her skin? The thought shocked her, and she blinked bringing her eyes up to his. He was watching her wearily. It looked like he was expecting her to start screaming and running with her arms flapping wildly over her head. “Ready?” she took a deep breath and steeled herself. Just another man, same as all men. With this mantra running through her head, she linked her hand with his and tried to ignore her rapidly beating heart. He nodded once and that was enough for her. She had to do this before she froze to death or, now that his hand was in hers, before she burst into a fireball of desire. She turned and pulled him through the door and into that room. They walked together, hand in hand, around the edge of the party. She did her best not to look at him. She had caught a glimpse of his gorgeous face in one of the mirrors and noticed that his eyes were light blue, his face was perfectly proportioned, and his skin was the warm brown of someone who had just returned from a tropical island holiday. Why was this guy hiding? He was by far the hottest man in the room. “Belinda?” The voice came from Mr Harvard. She stopped in her tracks and closed her eyes. Damn, she tried to breathe away her annoyance. “There you are,” he was now standing next to her, “I’ve been looking for you, where were you? I was telling you about my new Porsche and I turned around and you were gone. It was most inconsiderate.” “Bugging you?” the rough voice came from the other man who had let go of her hand, wrapped his arm around her waist and was pulling her close to him so that her hips were flush with his. She looked up at him and instantly regretted it. He was looking down at her with those intense eyes. She took a deep breath then forgot what to do next. He was staring at her searching her eyes while his body held her like she was someone worth holding. She lifted her face to his, her lips parted, and lost herself in his gaze. He was mesmerising and made her feel like she belonged there in his arms. Then he dipped his head down to hers and brushed his lips across hers. It was the briefest of kisses, but it was enough to completely disarm her. Her brain went to mush, her breath hitched, and she was left standing there looking at him like there was no one else in the room. It was lucky that he’d wrapped his arms around her because her knees didn’t feel like they were connected to her legs. He steadied her without taking his eyes off her. “Beat it, she’s mine,” his halted growl was possessive and made her toes curl. Somewhere in the background Mr Harvard muttered something that might have been rude, she didn’t care. Josh’s arms enveloped her, and she pressed herself against him with the sole desire to stay like this forever. His brow furrowed slightly and then he slowly loosened his grip on her. He edged away taking his warmth with him. With his arms still around her, he dragged his eyes from her and swung his head around surveying the room as if he expected an attack. She couldn’t take her eyes off the man, he was magnetic. His eyes came back to her briefly, his expression became pained, then he took control. He left one arm around her waist as he steered her out of the room. “Coat?” he asked and then took the token from her leaving her leaning against the wall. Without using words, he collected their belongings from the Cloakroom. He handed her the black woollen coat and without delay he pulled on his own, he had his thick woolly cap on before she had even registered that she needed to move. She slowly slid her arms into the coat which cost a fraction of what his dark grey, thick, designer coat would have cost. Who was this man? He had the money and the looks to be at home with the people inside. But instead he looked at them like they were the enemy. He might have hidden from them on the balcony, but he wasn’t hiding the disgust and apprehension he felt now he was out in the open. She wrapped her scarf around her as she watched his jaw flinch as he glanced towards the opening where people mingled. He turned towards the elevator while he flipped the deep hood of his coat up to obscure his face. Watching him, she walked beside him. She lamented the loss of his hand. Her hand hung loose at her side wishing he would find it and intertwine his fingers with hers again. He hadn’t put on his gloves yet, was she bold enough to reclaim his touch? The elevator pinged, signally it’s arrival and evaporating her plan to capture his touch. He didn’t say anything, but he did glance at her once before he held the door and signalled that she need to step into the empty space, she did as she was told. He joined her, and they stood in silence, his face and body obscured by that deep hood and long concealing coat. “Thank you,” she muttered confused by his behaviour. He dipped his head but said nothing. She took that as the conclusion of their relationship. That was the arrangement, but it didn’t stop her chest constricting with disappointment. It wasn’t surprising that he wasn’t interested in her, she wasn’t in his league. What was surprising, was how interested in him she’d become. Stormie Stafford: I loved the plot of this story. It was unique and I thoroughly enjoyed it..The only thing I could see was missing words in between sentences.There were only a few grammatical errors that I could see. I would definitely love to see a sequel to this novel. I want to know what happens after. Great J... Altairxox: Everything is perfect. I personally like stories that are written in first person however this story is like a bite into a very sweet cake. I really hope this story does well in the future :) Other Collections About Us: Inkitt is the world’s first reader-powered book publisher, offering an online community for talented authors and book lovers. Write captivating stories, read enchanting novels, and we’ll publish the books you love the most based on crowd wisdom.
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This Dick Is Far Too Big For Sensi Pearl
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CANADA STOCKS-TSX falls with banks; resource stocks offset loss TORONTO, Sept 26 (Reuters) - Canada's main stock index fell in early trade on Monday, weighed down by financial and some consumer stocks, with losses offset by gains among energy and materials companies as oil prices rallied. The Toronto Stock Exchange's S&P/TSX composite index was down 63.27 points, or 0.43 percent, at 14,634.66 shortly after the open. Eight of its 10 main sectors fell. (Reporting by Alastair Sharp Editing by W Simon)
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About An artblog for my fucked up porn, and all the sexy, delicious porn I find. ♥♦♣♠ New Blog now @ Bureau-of-Chicanery-Play
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Q: .htaccess file gives 500 internal server error I receive 500 internal server error on my website. I think this is because of .htaccess file, but I don't know what's wrong with it. Server: DirectAdmin, Linux-based Contents of the .htaccess file is as the following: # BEGIN All In One WP Security #AIOWPS_BLOCK_WP_FILE_ACCESS_START <files license.txt> order allow,deny deny from all </files> <files wp-config-sample.php> order allow,deny deny from all </files> <files readme.html> order allow,deny deny from all </files> #AIOWPS_BLOCK_WP_FILE_ACCESS_END #AIOWPS_BASIC_HTACCESS_RULES_START <files .htaccess> order allow,deny deny from all </files> ServerSignature Off LimitRequestBody 10240000 <files wp-config.php> order allow,deny deny from all </files> #AIOWPS_BASIC_HTACCESS_RULES_END #AIOWPS_PINGBACK_HTACCESS_RULES_START <IfModule mod_alias.c> RedirectMatch 403 /(.*)/xmlrpc\.php$ </IfModule> #AIOWPS_PINGBACK_HTACCESS_RULES_END #AIOWPS_DISABLE_INDEX_VIEWS_START Options All -Indexes #AIOWPS_DISABLE_INDEX_VIEWS_END #AIOWPS_DISABLE_TRACE_TRACK_START RewriteEngine On RewriteCond %{REQUEST_METHOD} ^(TRACE|TRACK) RewriteRule .* - [F] #AIOWPS_DISABLE_TRACE_TRACK_END #AIOWPS_FIVE_G_BLACKLIST_START # 5G BLACKLIST/FIREWALL (2013) # @ http://perishablepress.com/5g-blacklist-2013/ # 5G:[QUERY STRINGS] <IfModule mod_rewrite.c> RewriteEngine On RewriteBase / RewriteCond %{QUERY_STRING} (\"|%22).*(<|>|%3) [NC,OR] RewriteCond %{QUERY_STRING} (javascript:).*(\;) [NC,OR] RewriteCond %{QUERY_STRING} (<|%3C).*script.*(>|%3) [NC,OR] RewriteCond %{QUERY_STRING} (\\|\.\./|`|='$|=%27$) [NC,OR] RewriteCond %{QUERY_STRING} (\;|'|\"|%22).*(union|select|insert|drop|update|md5|benchmark|or|and|if) [NC,OR] RewriteCond %{QUERY_STRING} (base64_encode|localhost|mosconfig) [NC,OR] RewriteCond %{QUERY_STRING} (boot\.ini|echo.*kae|etc/passwd) [NC,OR] RewriteCond %{QUERY_STRING} (GLOBALS|REQUEST)(=|\[|%) [NC] RewriteRule .* - [F] </IfModule> # 5G:[USER AGENTS] <IfModule mod_setenvif.c> # SetEnvIfNoCase User-Agent ^$ keep_out SetEnvIfNoCase User-Agent (binlar|casper|cmsworldmap|comodo|diavol|dotbot|feedfinder|flicky|ia_archiver|jakarta|kmccrew|nutch|planetwork|purebot|pycurl|skygrid|sucker|turnit|vikspider|zmeu) keep_out <limit GET POST PUT> Order Allow,Deny Allow from all Deny from env=keep_out </limit> </IfModule> # 5G:[REQUEST STRINGS] <IfModule mod_alias.c> RedirectMatch 403 (https?|ftp|php)\:// RedirectMatch 403 /(https?|ima|ucp)/ RedirectMatch 403 /(Permanent|Better)$ RedirectMatch 403 (\=\\\'|\=\\%27|/\\\'/?|\)\.css\()$ RedirectMatch 403 (\,|\)\+|/\,/|\{0\}|\(/\(|\.\.\.|\+\+\+|\||\\\"\\\") RedirectMatch 403 \.(cgi|asp|aspx|cfg|dll|exe|jsp|mdb|sql|ini|rar)$ RedirectMatch 403 /(contac|fpw|install|pingserver|register)\.php$ RedirectMatch 403 (base64|crossdomain|localhost|wwwroot|e107\_) RedirectMatch 403 (eval\(|\_vti\_|\(null\)|echo.*kae|config\.xml) RedirectMatch 403 \.well\-known/host\-meta RedirectMatch 403 /function\.array\-rand RedirectMatch 403 \)\;\$\(this\)\.html\( RedirectMatch 403 proc/self/environ RedirectMatch 403 msnbot\.htm\)\.\_ RedirectMatch 403 /ref\.outcontrol RedirectMatch 403 com\_cropimage RedirectMatch 403 indonesia\.htm RedirectMatch 403 \{\$itemURL\} RedirectMatch 403 function\(\) RedirectMatch 403 labels\.rdf RedirectMatch 403 /playing.php RedirectMatch 403 muieblackcat </IfModule> # 5G:[REQUEST METHOD] <ifModule mod_rewrite.c> RewriteCond %{REQUEST_METHOD} ^(TRACE|TRACK) RewriteRule .* - [F] </IfModule> # 5G:[BAD IPS] <limit GET POST PUT> Order Allow,Deny Allow from all # uncomment/edit/repeat next line to block IPs # Deny from 123.456.789 </limit> #AIOWPS_FIVE_G_BLACKLIST_END #AIOWPS_BLOCK_SPAMBOTS_START <IfModule mod_rewrite.c> RewriteCond %{REQUEST_METHOD} POST RewriteCond %{REQUEST_URI} ^(.*)?wp-comments-post\.php(.*)$ RewriteCond %{HTTP_REFERER} !^http://(.*)?\.spna\.co\.ir [NC,OR] RewriteCond %{HTTP_USER_AGENT} ^$ RewriteRule .* http://127.0.0.1 [L] </IfModule> #AIOWPS_BLOCK_SPAMBOTS_END # END All In One WP Security # BEGIN W3TC Browser Cache <IfModule mod_deflate.c> <IfModule mod_headers.c> Header append Vary User-Agent env=!dont-vary </IfModule> AddOutputFilterByType DEFLATE text/css text/x-component application/x-javascript application/javascript text/javascript text/x-js text/html text/richtext image/svg+xml text/plain text/xsd text/xsl text/xml image/x-icon application/json <IfModule mod_mime.c> # DEFLATE by extension AddOutputFilter DEFLATE js css htm html xml </IfModule> </IfModule> # END W3TC Browser Cache # BEGIN W3TC Page Cache core <IfModule mod_rewrite.c> RewriteEngine On RewriteBase / RewriteCond %{HTTP:Accept-Encoding} gzip RewriteRule .* - [E=W3TC_ENC:_gzip] RewriteCond %{REQUEST_METHOD} !=POST RewriteCond %{QUERY_STRING} ="" RewriteCond %{REQUEST_URI} \/$ RewriteCond %{HTTP_COOKIE} !(comment_author|wp\-postpass|w3tc_logged_out|wordpress_logged_in|wptouch_switch_toggle) [NC] RewriteCond "%{DOCUMENT_ROOT}/wp-content/cache/page_enhanced/%{HTTP_HOST}/%{REQUEST_URI}/_index.html%{ENV:W3TC_ENC}" -f RewriteRule .* "/wp-content/cache/page_enhanced/%{HTTP_HOST}/%{REQUEST_URI}/_index.html%{ENV:W3TC_ENC}" [L] </IfModule> # END W3TC Page Cache core # BEGIN WordPress <IfModule mod_rewrite.c> RewriteEngine On RewriteBase / RewriteRule ^index\.php$ - [L] RewriteCond %{REQUEST_FILENAME} !-f RewriteCond %{REQUEST_FILENAME} !-d RewriteRule . /index.php [L] </IfModule> # END WordPress And here's what the Apache Error Log says: [Thu Jan 16 00:19:08 2014] [alert] [client 157.55.35.85] /home/sapna/domains/spna.co.ir/public_html/.htaccess: Option All not allowed here I would be grateful if you help me find out what causes the 500 internal server error. Thanks. A: Often 500 Internal Server Error happens if you fail to load the mod_rewrite module. To enable RewriteEngine On you need to run the following command: sudo a2enmod rewrite A: In Local mechine Create your project folder. Create .htaccess file in your project root directory like below. .htaccess RewriteEngine on RewriteCond %{REQUEST_FILENAME} !-d RewriteCond %{REQUEST_FILENAME} !-f RewriteCond %{REQUEST_FILENAME} !-l RewriteRule ^(.*)$ index.php?url=$1 [QSA,L] Save .htaccess file. Now click on wamp / lamp / xamp server icon and click on apache and select "rewire_module". In Cpanel Directly you need to create .htaccess file with above code and save. Note: - Please don't write any spelling mistakes in cpanel. If you write any spelling mistakes it will gives you an internal server error (500). A: Problem is this line due to your Apache cnfig: Options All -Indexes change this to: Options -Indexes
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Ingredients In a saucepan, sauté butter and onion until translucent; set aside. In a casserole dish, mix rice and soup. Stir in onion and butter mixture and top with shredded cheese. Bake covered at 350ºF for an Directions Directions: In a saucepan, sauté butter and onion until translucent; set aside. In a casserole dish, mix rice and soup. Stir in onion and butter mixture and top with shredded cheese. Bake covered at 350ºF for an hour or until all liquid has been absorbed. You may want to uncover the dish during the last 10 minutes of baking time to lightly brown the top. This casserole makes a perfect side dish to beef entrées. Serves 4 – 6. Keyingredient.com uses 'cookies' to give you the best, most relevant experience. Using this website means you're ok with this. You can change which cookies are set at any time and find out more about them by following this link.
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No sure if need to pee Or horny 138 shares
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We will accept a check if you do a cartwheel for us. (Not really. Just contact our office to OK payment by check.) Holiday services will be charged a 50% non-refundable deposit one week prior to departure. Tips/Gratuities: You may leave CASH for your Huggable Specialist(s) or add an online gratuity at the time of your booking. If you would like us to add the tip, email our Huggable office with your request, we will gladly add it for you. Cancellation Policy: In the event of early return home, Client must notify Huggable Muggs® promptly to avoid being charged for unnecessary visit(s). Any remaining balance will be credited to your account for future use. Refunds made upon request. Surcharge/Holiday Policy: Short notice: A late booking fee applies to visits scheduled less than 24 hours in advance. Emergency Care Policy: In the event of pet illness or other medical emergency and specified vet is unavailable, pet will be taken to closest vet or South Metro Animal Emergency Care. Client understands and agrees that attempts will be made to contact them in case of emergency and if Client is unreachable, Pet Care Specialist has permission to authorize any care that the vet deems necessary for pet’s health, safety and survival. Client agrees to reimburse Huggable Muggs® for any additional fees and all costs relating to vet care during their absence, as well as an emergency medical transport fee. Guest Policy: In the event friends, neighbors or family members will be entering the home while it is under our care, Huggable Muggs® must be notified in advance. Huggable Muggs® Pet Care Specialist will not allow entry to any person we have not been made aware of. Huggable Muggs® will not be held responsible for any damages incurred to Client’s home or pet(s) by said visitors. Huggable Muggs® Pet Care Specialist may contact police if we suspect intruders or suspicious acts. Vaccination Policy: For the safety of your pet and others, pets must have current vaccinations. Should our Pet Care Specialist or third party be bitten or otherwise exposed to any disease or ailment received from Client’s animal which has not been properly vaccinated, it will be the Client’s responsibility to pay all costs and damages incurred by the victim. Please contact Huggable Muggs® directly to discuss pets which have medical exemptions to vaccinations. Extra Fees / Charges Policy:Huggable Muggs® reserves the right to invoice/bill, at our prescribed half hour rate or any portion thereof, for additional time spent over booked appointment time deemed necessary for the care of Client’s pet(s) and home. This includes service and time for the following, but not limited to: all veterinary trips; pet illness; excessive clean-up resulting from pet incontinence, accidents or frequent vomiting; complications administering medications; obtaining pet food, medication or supplies; wait time for emergency home repair. Client will be held responsible for all expenses incurred and reimburse Huggable Muggs® upon return. Home Access: Lock boxes are required: We feel this is a better option for your protection as well as ours. With lock boxes our Huggable clients are always in control of their keys. We offer lock boxes for purchase or you may provide your own. Infrequent/out of town clients – Huggable lock box plus garage code. We must always have two ways to access your home. Regularly scheduled Dog Walking clients – garage code and/or Huggable lock box for sitter key. You must be in town if we only have a garage code for access. Client expressly gives Huggable Muggs® and Pet Care Specialist authority to employ a locksmith in the event of malfunction of the lock, keys or automatic door opener. Client will be responsible for all expenses incurred and will reimburse Huggable Muggs® upon return. TERMS & CONDITIONS Due to the extreme unpredictability of animals, Huggable Muggs® and Pet Care Specialists cannot be held responsible for any unusual mishaps (i.e., pet’s refusal to take medication, escaping from the yard, biting, eating or destroying household items, damage to inside/outside of home, personal injury/accidental death). If Client requests pet(s) to have outside access, Client releases Huggable Muggs® and Pet Care Specialists from all liability for loss, fines, injury or death to pet(s). Client is liable for injury or damage to Third Parties. Client authorizes Huggable Muggs® and Pet Care Specialists to take photos of Client’s pet for their file and for business Face Book page. All photos taken are the property of Huggable Muggs®. Visit times are approximate and subject to change based on the needs of all pets under our Pet Care Specialist. Huggable Muggs® Pet Care Specialist is entrusted to use best judgment in caring for pet(s) and home, in the event of an emergency situation, severe inclement weather or natural disasters. Huggable Muggs® and their Pet Care Specialists will be held harmless for consequences related to such decisions. In the event of personal emergency, illness or other emergency circumstances of assigned Pet Care Specialist. Pet care will be performed by another Pet Care Specialist. Client authorizes Huggable Muggs® to arrange for a back-up Specialist to fulfill all duties as outlined in this agreement. Huggable Muggs® reserves the right to terminate this agreement at any time before or during its term if our Pet Care Specialist determines that Client’s pet poses a danger to the health or safety of themselves or others. If concerns prohibit our Pet Care Specialist from caring for said pet, Client authorizes pet to be placed in a boarding facility or local vet clinic with all charges, including transportation fees and excess time fees to be paid to Client. Huggable Muggs® and Pet Care Specialists agree to provide the services stated in this agreement in a reliable, caring and trustworthy manner. In consideration of these services, the Client expressly waives and relinquishes any and all claims against Huggable Muggs® except those arising from negligence or willful misconduct on the part of Huggable Muggs® or Pet Care Specialist. Website Usage and Privacy Policy This website includes a Hibu pixel that enables cookies (not the delicious kind… the computer tracking kind) to be dropped onto your machine. These cookies may be used to target ads to you on third party websites within Hibu’s network. To learn more about this, or to opt out of being targeted for any behavioral advertising by any member of the Internet Advertising Bureau, including, Hibu, visit www.youradchoices.com
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Gia Giancarlo in What to do when youre late with the rent – Image Gallery – Horny old MILF slut whore naked and fucked Gia Giancarlo in What to do when youre late with the rent – Image Gallery – Horny old MILF slut whore naked and fucked Cute Asian-American Mia Li is collared with C-U-N-T lipsticked over her tits, her arms locked in restraint and a fluffy animal tail butt plug inserted. Through a masochistic masturbation session she whimpers submissively. Fetish director Aiden Starr gives her a key, and she struggles to free herself from bondage. Mia masturbates with a plug-in wand, and metal nipple clips indent her areolae. She fucks her cunt with a glass dildo. Aiden sticks electrodes on her thighs and turns up the juice. A leather mask covers masturbating Mia’s face. Clothespins pinch her nipples and an electric shocker zaps her butt cheeks. Mia buzzes off with that wand, electrodes and fluffy butt plug still in place! Gia Giancarlo in What to do when youre late with the rent – Image Gallery – Horny old MILF slut whore naked and fucked
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Not sure if she left to avoid sex... Or if she left to get ready for sex 228 shares
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/* -*-mode:java; c-basic-offset:2; indent-tabs-mode:nil -*- */ /* Copyright (c) 2005-2015 ymnk, JCraft,Inc. All rights reserved. Redistribution and use in source and binary forms, with or without modification, are permitted provided that the following conditions are met: 1. Redistributions of source code must retain the above copyright notice, this list of conditions and the following disclaimer. 2. Redistributions in binary form must reproduce the above copyright notice, this list of conditions and the following disclaimer in the documentation and/or other materials provided with the distribution. 3. The names of the authors may not be used to endorse or promote products derived from this software without specific prior written permission. THIS SOFTWARE IS PROVIDED ``AS IS'' AND ANY EXPRESSED OR IMPLIED WARRANTIES, INCLUDING, BUT NOT LIMITED TO, THE IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE ARE DISCLAIMED. IN NO EVENT SHALL JCRAFT, INC. OR ANY CONTRIBUTORS TO THIS SOFTWARE BE LIABLE FOR ANY DIRECT, INDIRECT, INCIDENTAL, SPECIAL, EXEMPLARY, OR CONSEQUENTIAL DAMAGES (INCLUDING, BUT NOT LIMITED TO, PROCUREMENT OF SUBSTITUTE GOODS OR SERVICES; LOSS OF USE, DATA, OR PROFITS; OR BUSINESS INTERRUPTION) HOWEVER CAUSED AND ON ANY THEORY OF LIABILITY, WHETHER IN CONTRACT, STRICT LIABILITY, OR TORT (INCLUDING NEGLIGENCE OR OTHERWISE) ARISING IN ANY WAY OUT OF THE USE OF THIS SOFTWARE, EVEN IF ADVISED OF THE POSSIBILITY OF SUCH DAMAGE. */ package com.jcraft.jsch.jce; import com.jcraft.jsch.Cipher; import javax.crypto.spec.*; public class AES128CBC implements Cipher{ private static final int ivsize=16; private static final int bsize=16; private javax.crypto.Cipher cipher; public int getIVSize(){return ivsize;} public int getBlockSize(){return bsize;} public void init(int mode, byte[] key, byte[] iv) throws Exception{ String pad="NoPadding"; byte[] tmp; if(iv.length>ivsize){ tmp=new byte[ivsize]; System.arraycopy(iv, 0, tmp, 0, tmp.length); iv=tmp; } if(key.length>bsize){ tmp=new byte[bsize]; System.arraycopy(key, 0, tmp, 0, tmp.length); key=tmp; } try{ SecretKeySpec keyspec=new SecretKeySpec(key, "AES"); cipher=javax.crypto.Cipher.getInstance("AES/CBC/"+pad); synchronized(javax.crypto.Cipher.class){ cipher.init((mode==ENCRYPT_MODE? javax.crypto.Cipher.ENCRYPT_MODE: javax.crypto.Cipher.DECRYPT_MODE), keyspec, new IvParameterSpec(iv)); } } catch(Exception e){ cipher=null; throw e; } } public void update(byte[] foo, int s1, int len, byte[] bar, int s2) throws Exception{ cipher.update(foo, s1, len, bar, s2); } public boolean isCBC(){return true; } }
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// **************************************************************** // Copyright 2008, Charlie Poole // This is free software licensed under the NUnit license. You may // obtain a copy of the license at http://nunit.org // **************************************************************** using System; using NUnit.Framework; namespace NUnit.Tests.Assemblies.BBB { /// <summary> /// Summary description for Class1. /// </summary> [TestFixture] public class Class3 : BaseClass { [Test] public void Test1() { } [Test] public void Test2() { } [Test] public void Test3() { } [Test] public void Test4() { } [Test] public void Test5() { } [Test] public void Test6() { } [Test] public void Test7() { } [Test] public void Test8() { } [Test] public void Test9() { } [Test] public void Test10() { } [Test] public void Test11() { } [Test] public void Test12() { } [Test] public void Test13() { } [Test] public void Test14() { } [Test] public void Test15() { } [Test] public void Test16() { } [Test] public void Test17() { } [Test] public void Test18() { } [Test] public void Test19() { } [Test] public void Test20() { } [Test] public void Test21() { } [Test] public void Test22() { } [Test] public void Test23() { } [Test] public void Test24() { } [Test] public void Test25() { } [Test] public void Test26() { } [Test] public void Test27() { } [Test] public void Test28() { } [Test] public void Test29() { } [Test] public void Test30() { } [Test] public void Test31() { } [Test] public void Test32() { } [Test] public void Test33() { } [Test] public void Test34() { } [Test] public void Test35() { } [Test] public void Test36() { } [Test] public void Test37() { } [Test] public void Test38() { } [Test] public void Test39() { } [Test] public void Test40() { } [Test] public void Test41() { } [Test] public void Test42() { } [Test] public void Test43() { } [Test] public void Test44() { } [Test] public void Test45() { } [Test] public void Test46() { } [Test] public void Test47() { } [Test] public void Test48() { } [Test] public void Test49() { } [Test] public void Test50() { } } }
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/* * Real Time Clock interface for Linux on Atmel AT91RM9200 * * Copyright (C) 2002 Rick Bronson * * Converted to RTC class model by Andrew Victor * * Ported to Linux 2.6 by Steven Scholz * Based on s3c2410-rtc.c Simtec Electronics * * Based on sa1100-rtc.c by Nils Faerber * Based on rtc.c by Paul Gortmaker * * This program is free software; you can redistribute it and/or * modify it under the terms of the GNU General Public License * as published by the Free Software Foundation; either version * 2 of the License, or (at your option) any later version. * */ #include <linux/module.h> #include <linux/kernel.h> #include <linux/platform_device.h> #include <linux/time.h> #include <linux/rtc.h> #include <linux/bcd.h> #include <linux/interrupt.h> #include <linux/spinlock.h> #include <linux/ioctl.h> #include <linux/completion.h> #include <linux/io.h> #include <linux/of.h> #include <linux/of_device.h> #include <linux/uaccess.h> #include "rtc-at91rm9200.h" #define at91_rtc_read(field) \ __raw_readl(at91_rtc_regs + field) #define at91_rtc_write(field, val) \ __raw_writel((val), at91_rtc_regs + field) #define AT91_RTC_EPOCH 1900UL /* just like arch/arm/common/rtctime.c */ struct at91_rtc_config { bool use_shadow_imr; }; static const struct at91_rtc_config *at91_rtc_config; static DECLARE_COMPLETION(at91_rtc_updated); static unsigned int at91_alarm_year = AT91_RTC_EPOCH; static void __iomem *at91_rtc_regs; static int irq; static DEFINE_SPINLOCK(at91_rtc_lock); static u32 at91_rtc_shadow_imr; static void at91_rtc_write_ier(u32 mask) { unsigned long flags; spin_lock_irqsave(&at91_rtc_lock, flags); at91_rtc_shadow_imr |= mask; at91_rtc_write(AT91_RTC_IER, mask); spin_unlock_irqrestore(&at91_rtc_lock, flags); } static void at91_rtc_write_idr(u32 mask) { unsigned long flags; spin_lock_irqsave(&at91_rtc_lock, flags); at91_rtc_write(AT91_RTC_IDR, mask); /* * Register read back (of any RTC-register) needed to make sure * IDR-register write has reached the peripheral before updating * shadow mask. * * Note that there is still a possibility that the mask is updated * before interrupts have actually been disabled in hardware. The only * way to be certain would be to poll the IMR-register, which is is * the very register we are trying to emulate. The register read back * is a reasonable heuristic. */ at91_rtc_read(AT91_RTC_SR); at91_rtc_shadow_imr &= ~mask; spin_unlock_irqrestore(&at91_rtc_lock, flags); } static u32 at91_rtc_read_imr(void) { unsigned long flags; u32 mask; if (at91_rtc_config->use_shadow_imr) { spin_lock_irqsave(&at91_rtc_lock, flags); mask = at91_rtc_shadow_imr; spin_unlock_irqrestore(&at91_rtc_lock, flags); } else { mask = at91_rtc_read(AT91_RTC_IMR); } return mask; } /* * Decode time/date into rtc_time structure */ static void at91_rtc_decodetime(unsigned int timereg, unsigned int calreg, struct rtc_time *tm) { unsigned int time, date; /* must read twice in case it changes */ do { time = at91_rtc_read(timereg); date = at91_rtc_read(calreg); } while ((time != at91_rtc_read(timereg)) || (date != at91_rtc_read(calreg))); tm->tm_sec = bcd2bin((time & AT91_RTC_SEC) >> 0); tm->tm_min = bcd2bin((time & AT91_RTC_MIN) >> 8); tm->tm_hour = bcd2bin((time & AT91_RTC_HOUR) >> 16); /* * The Calendar Alarm register does not have a field for * the year - so these will return an invalid value. When an * alarm is set, at91_alarm_year will store the current year. */ tm->tm_year = bcd2bin(date & AT91_RTC_CENT) * 100; /* century */ tm->tm_year += bcd2bin((date & AT91_RTC_YEAR) >> 8); /* year */ tm->tm_wday = bcd2bin((date & AT91_RTC_DAY) >> 21) - 1; /* day of the week [0-6], Sunday=0 */ tm->tm_mon = bcd2bin((date & AT91_RTC_MONTH) >> 16) - 1; tm->tm_mday = bcd2bin((date & AT91_RTC_DATE) >> 24); } /* * Read current time and date in RTC */ static int at91_rtc_readtime(struct device *dev, struct rtc_time *tm) { at91_rtc_decodetime(AT91_RTC_TIMR, AT91_RTC_CALR, tm); tm->tm_yday = rtc_year_days(tm->tm_mday, tm->tm_mon, tm->tm_year); tm->tm_year = tm->tm_year - 1900; dev_dbg(dev, "%s(): %4d-%02d-%02d %02d:%02d:%02d\n", __func__, 1900 + tm->tm_year, tm->tm_mon, tm->tm_mday, tm->tm_hour, tm->tm_min, tm->tm_sec); return 0; } /* * Set current time and date in RTC */ static int at91_rtc_settime(struct device *dev, struct rtc_time *tm) { unsigned long cr; dev_dbg(dev, "%s(): %4d-%02d-%02d %02d:%02d:%02d\n", __func__, 1900 + tm->tm_year, tm->tm_mon, tm->tm_mday, tm->tm_hour, tm->tm_min, tm->tm_sec); /* Stop Time/Calendar from counting */ cr = at91_rtc_read(AT91_RTC_CR); at91_rtc_write(AT91_RTC_CR, cr | AT91_RTC_UPDCAL | AT91_RTC_UPDTIM); at91_rtc_write_ier(AT91_RTC_ACKUPD); wait_for_completion(&at91_rtc_updated); /* wait for ACKUPD interrupt */ at91_rtc_write_idr(AT91_RTC_ACKUPD); at91_rtc_write(AT91_RTC_TIMR, bin2bcd(tm->tm_sec) << 0 | bin2bcd(tm->tm_min) << 8 | bin2bcd(tm->tm_hour) << 16); at91_rtc_write(AT91_RTC_CALR, bin2bcd((tm->tm_year + 1900) / 100) /* century */ | bin2bcd(tm->tm_year % 100) << 8 /* year */ | bin2bcd(tm->tm_mon + 1) << 16 /* tm_mon starts at zero */ | bin2bcd(tm->tm_wday + 1) << 21 /* day of the week [0-6], Sunday=0 */ | bin2bcd(tm->tm_mday) << 24); /* Restart Time/Calendar */ cr = at91_rtc_read(AT91_RTC_CR); at91_rtc_write(AT91_RTC_CR, cr & ~(AT91_RTC_UPDCAL | AT91_RTC_UPDTIM)); return 0; } /* * Read alarm time and date in RTC */ static int at91_rtc_readalarm(struct device *dev, struct rtc_wkalrm *alrm) { struct rtc_time *tm = &alrm->time; at91_rtc_decodetime(AT91_RTC_TIMALR, AT91_RTC_CALALR, tm); tm->tm_yday = rtc_year_days(tm->tm_mday, tm->tm_mon, tm->tm_year); tm->tm_year = at91_alarm_year - 1900; alrm->enabled = (at91_rtc_read_imr() & AT91_RTC_ALARM) ? 1 : 0; dev_dbg(dev, "%s(): %4d-%02d-%02d %02d:%02d:%02d\n", __func__, 1900 + tm->tm_year, tm->tm_mon, tm->tm_mday, tm->tm_hour, tm->tm_min, tm->tm_sec); return 0; } /* * Set alarm time and date in RTC */ static int at91_rtc_setalarm(struct device *dev, struct rtc_wkalrm *alrm) { struct rtc_time tm; at91_rtc_decodetime(AT91_RTC_TIMR, AT91_RTC_CALR, &tm); at91_alarm_year = tm.tm_year; tm.tm_hour = alrm->time.tm_hour; tm.tm_min = alrm->time.tm_min; tm.tm_sec = alrm->time.tm_sec; at91_rtc_write_idr(AT91_RTC_ALARM); at91_rtc_write(AT91_RTC_TIMALR, bin2bcd(tm.tm_sec) << 0 | bin2bcd(tm.tm_min) << 8 | bin2bcd(tm.tm_hour) << 16 | AT91_RTC_HOUREN | AT91_RTC_MINEN | AT91_RTC_SECEN); at91_rtc_write(AT91_RTC_CALALR, bin2bcd(tm.tm_mon + 1) << 16 /* tm_mon starts at zero */ | bin2bcd(tm.tm_mday) << 24 | AT91_RTC_DATEEN | AT91_RTC_MTHEN); if (alrm->enabled) { at91_rtc_write(AT91_RTC_SCCR, AT91_RTC_ALARM); at91_rtc_write_ier(AT91_RTC_ALARM); } dev_dbg(dev, "%s(): %4d-%02d-%02d %02d:%02d:%02d\n", __func__, at91_alarm_year, tm.tm_mon, tm.tm_mday, tm.tm_hour, tm.tm_min, tm.tm_sec); return 0; } static int at91_rtc_alarm_irq_enable(struct device *dev, unsigned int enabled) { dev_dbg(dev, "%s(): cmd=%08x\n", __func__, enabled); if (enabled) { at91_rtc_write(AT91_RTC_SCCR, AT91_RTC_ALARM); at91_rtc_write_ier(AT91_RTC_ALARM); } else at91_rtc_write_idr(AT91_RTC_ALARM); return 0; } /* * Provide additional RTC information in /proc/driver/rtc */ static int at91_rtc_proc(struct device *dev, struct seq_file *seq) { unsigned long imr = at91_rtc_read_imr(); seq_printf(seq, "update_IRQ\t: %s\n", (imr & AT91_RTC_ACKUPD) ? "yes" : "no"); seq_printf(seq, "periodic_IRQ\t: %s\n", (imr & AT91_RTC_SECEV) ? "yes" : "no"); return 0; } /* * IRQ handler for the RTC */ static irqreturn_t at91_rtc_interrupt(int irq, void *dev_id) { struct platform_device *pdev = dev_id; struct rtc_device *rtc = platform_get_drvdata(pdev); unsigned int rtsr; unsigned long events = 0; rtsr = at91_rtc_read(AT91_RTC_SR) & at91_rtc_read_imr(); if (rtsr) { /* this interrupt is shared! Is it ours? */ if (rtsr & AT91_RTC_ALARM) events |= (RTC_AF | RTC_IRQF); if (rtsr & AT91_RTC_SECEV) events |= (RTC_UF | RTC_IRQF); if (rtsr & AT91_RTC_ACKUPD) complete(&at91_rtc_updated); at91_rtc_write(AT91_RTC_SCCR, rtsr); /* clear status reg */ rtc_update_irq(rtc, 1, events); dev_dbg(&pdev->dev, "%s(): num=%ld, events=0x%02lx\n", __func__, events >> 8, events & 0x000000FF); return IRQ_HANDLED; } return IRQ_NONE; /* not handled */ } static const struct at91_rtc_config at91rm9200_config = { }; static const struct at91_rtc_config at91sam9x5_config = { .use_shadow_imr = true, }; #ifdef CONFIG_OF static const struct of_device_id at91_rtc_dt_ids[] = { { .compatible = "atmel,at91rm9200-rtc", .data = &at91rm9200_config, }, { .compatible = "atmel,at91sam9x5-rtc", .data = &at91sam9x5_config, }, { /* sentinel */ } }; MODULE_DEVICE_TABLE(of, at91_rtc_dt_ids); #endif static const struct at91_rtc_config * at91_rtc_get_config(struct platform_device *pdev) { const struct of_device_id *match; if (pdev->dev.of_node) { match = of_match_node(at91_rtc_dt_ids, pdev->dev.of_node); if (!match) return NULL; return (const struct at91_rtc_config *)match->data; } return &at91rm9200_config; } static const struct rtc_class_ops at91_rtc_ops = { .read_time = at91_rtc_readtime, .set_time = at91_rtc_settime, .read_alarm = at91_rtc_readalarm, .set_alarm = at91_rtc_setalarm, .proc = at91_rtc_proc, .alarm_irq_enable = at91_rtc_alarm_irq_enable, }; /* * Initialize and install RTC driver */ static int __init at91_rtc_probe(struct platform_device *pdev) { struct rtc_device *rtc; struct resource *regs; int ret = 0; at91_rtc_config = at91_rtc_get_config(pdev); if (!at91_rtc_config) return -ENODEV; regs = platform_get_resource(pdev, IORESOURCE_MEM, 0); if (!regs) { dev_err(&pdev->dev, "no mmio resource defined\n"); return -ENXIO; } irq = platform_get_irq(pdev, 0); if (irq < 0) { dev_err(&pdev->dev, "no irq resource defined\n"); return -ENXIO; } at91_rtc_regs = ioremap(regs->start, resource_size(regs)); if (!at91_rtc_regs) { dev_err(&pdev->dev, "failed to map registers, aborting.\n"); return -ENOMEM; } at91_rtc_write(AT91_RTC_CR, 0); at91_rtc_write(AT91_RTC_MR, 0); /* 24 hour mode */ /* Disable all interrupts */ at91_rtc_write_idr(AT91_RTC_ACKUPD | AT91_RTC_ALARM | AT91_RTC_SECEV | AT91_RTC_TIMEV | AT91_RTC_CALEV); ret = request_irq(irq, at91_rtc_interrupt, IRQF_SHARED, "at91_rtc", pdev); if (ret) { dev_err(&pdev->dev, "IRQ %d already in use.\n", irq); goto err_unmap; } /* cpu init code should really have flagged this device as * being wake-capable; if it didn't, do that here. */ if (!device_can_wakeup(&pdev->dev)) device_init_wakeup(&pdev->dev, 1); rtc = rtc_device_register(pdev->name, &pdev->dev, &at91_rtc_ops, THIS_MODULE); if (IS_ERR(rtc)) { ret = PTR_ERR(rtc); goto err_free_irq; } platform_set_drvdata(pdev, rtc); dev_info(&pdev->dev, "AT91 Real Time Clock driver.\n"); return 0; err_free_irq: free_irq(irq, pdev); err_unmap: iounmap(at91_rtc_regs); return ret; } /* * Disable and remove the RTC driver */ static int __exit at91_rtc_remove(struct platform_device *pdev) { struct rtc_device *rtc = platform_get_drvdata(pdev); /* Disable all interrupts */ at91_rtc_write_idr(AT91_RTC_ACKUPD | AT91_RTC_ALARM | AT91_RTC_SECEV | AT91_RTC_TIMEV | AT91_RTC_CALEV); free_irq(irq, pdev); rtc_device_unregister(rtc); iounmap(at91_rtc_regs); return 0; } #ifdef CONFIG_PM_SLEEP /* AT91RM9200 RTC Power management control */ static u32 at91_rtc_imr; static int at91_rtc_suspend(struct device *dev) { /* this IRQ is shared with DBGU and other hardware which isn't * necessarily doing PM like we are... */ at91_rtc_imr = at91_rtc_read_imr() & (AT91_RTC_ALARM|AT91_RTC_SECEV); if (at91_rtc_imr) { if (device_may_wakeup(dev)) enable_irq_wake(irq); else at91_rtc_write_idr(at91_rtc_imr); } return 0; } static int at91_rtc_resume(struct device *dev) { if (at91_rtc_imr) { if (device_may_wakeup(dev)) disable_irq_wake(irq); else at91_rtc_write_ier(at91_rtc_imr); } return 0; } #endif static SIMPLE_DEV_PM_OPS(at91_rtc_pm_ops, at91_rtc_suspend, at91_rtc_resume); static struct platform_driver at91_rtc_driver = { .remove = __exit_p(at91_rtc_remove), .driver = { .name = "at91_rtc", .owner = THIS_MODULE, .pm = &at91_rtc_pm_ops, .of_match_table = of_match_ptr(at91_rtc_dt_ids), }, }; module_platform_driver_probe(at91_rtc_driver, at91_rtc_probe); MODULE_AUTHOR("Rick Bronson"); MODULE_DESCRIPTION("RTC driver for Atmel AT91RM9200"); MODULE_LICENSE("GPL"); MODULE_ALIAS("platform:at91_rtc");
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0.025316
Americans desperate for news from the Syrian front, where an alleged chemical attack has prompted the Trump administration to consider a military strike against Damascus, are in for a real disappointment. Any balanced discussion of a possible military offensive against Syria, which Moscow has warned would have “grave consequences,” has been swept clean from the news slate. On Wednesday morning, in an apparent state of wishful thinking mixed with a dash of masochism, I consulted multiple US news sites to see how the Syrian crisis was being reported. Expecting to find large-font headlines warning of a possible military offensive, not to mention World War 3, I was greeted instead with multi-layered stories on former porn star, Stormy Daniels, and her 10-year old affair with Donald Trump. I’m guessing there was a Russian connection to that salacious story somewhere, but exactly where I could not immediately say. The lead story in the Bezos-owned Washington Post, for example, was headlined, “Investigators sought Trump lawyer’s records on two women who alleged affairs with president.” Next to that salacious piece of bozo journalism was another nothing burger, at least as far as the Syrian crisis is concerned, which discussed the current trials and tribulations of Facebook CEO Mark Zuckerberg (“Zuckerberg apologizes, promises reform during hours-long Senate grilling over Facebook’s failings”). While that may seem like important news to some, it pales in comparison with the prospect of the US launching an attack on the Syrian government. Buried deep below that media debris and detritus was a single story devoted to Syria, headlined: “Nerve gas in Syria attack, leaving victims ‘foaming at the mouth,’ evidence suggests.” This glaringly one-sided narrative, much like the one used last month in the Salisbury ‘chemical attack’ that allegedly sickened Sergey Skripal and his daughter, is tenuous at best, a bald-faced lie at worst. Indeed, judging by an examination of the site carried out by Russian experts and the Syrian Red Cross, no trace of chemical weapons could be found. A switch to CNN provided a near duplicate of The Post’s paucity of pickings, albeit with a slightly different twist. “Trump considering firing Rosenstein, sources say,” was the headline of the main story, which shows that the ‘Russiagate’ show trial is beginning to eat its tail, yet the media – after almost two years – just can’t resist reporting on it. Next to that show-stopper, US media consumers are provided yet another cure for insomnia with riveting details on Zuckerberg’s 5-hour grilling by the US Senate. Finally, a CNN article on Syria. Yet the headline says everything we need to know as far as what the American consumer of mainstream media fare is permitted to think: “Haley says Russia chose 'protecting a monster' over Syrian people” (Incidentally, this is same way US political elections are carried out. There is freedom, but only a severely limited freedom that allows the populace to ‘freely’ choose between candidates that have already been carefully selected by the powers-that-be). Below that gratuitous bugle blast for war is an open letter to the US leader, entitled, “President Trump, now is not the time for half-baked military action.” Translation: “President Trump, now is the time for full-blown military action” Here is CNN opinionator Sam Kiley inveighing against the Syrian government, using cheap emotional imagery as a substitute for hardnosed facts: “Outrage over the images of children frozen in death, their mouths gagged with foam as the alleged victims of another Syrian government gas attack on its own people, has led Nikki Haley, the US ambassador to the UN, to call the perpetrator behind the attack "a monster." “Such passionate intensity is understandable,” Kiley continues, building up momentum for a hysterical Hitler analogy. “There's something visceral about killing with gas. It recalls the Holocaust. It conjures up almost identical photographs of Saddam Hussein's attack on the Kurds of Halabja.” Ah, yes. The sweet sound of impartial journalism. What is so deplorable about this brand of so-called reporting is that it refuses to consider the very high probability that it was not the Syrian government that resorted to chemical weapons in Douma, but rather the rebel forces, who were suffering on every military front up until that point. Would President Bashar Assad really be so reckless to risk a chemical attack at the very moment he was bringing to an end an 8-year struggle against terrorist-infiltrated militants in his country? Common sense would say no. It’s not that the American people are inherently stupid to believe such absurd claims; it’s that they are woefully misinformed by a media machine that is marching in lockstep – sometimes even owned – by the military industrial complex. Mark Twain summed up the Catch-22 situation confronting Americans: “If you don't read the newspaper, you're uninformed. If you read the newspaper, you're mis-informed.” And it is not just the run-of-the-mill news sources that are serving as cheerleaders for imperialistic regime change operations. The purportedly intelligent ‘thinking man’ publications are also peddling a shameless pro-war stance, which takes the government line for granted. In this month’s issue of The Atlantic, for example, investigative journalism is reduced to roadkill in the rush to war. In an article entitled, “The Logic of Assad’s Brutality,” it is obvious that the magazine has already predetermined Assad’s guilt. Yet the UN weapons inspectors have not even reached Syria to begin their investigative work? What kind of journalist could put his name on an article that could only be called an elaborate piece of pro-war propaganda? And then there is the ‘conservative’ journal Foreign Policy, which argued in an article entitled ‘Macron needs to Attack Syria’: “It’s not clear whether France can count on the United States to commit to the enforcement of any red lines against the Assad regime. But this should only concentrate Macron’s mind. If the United States abstains, he should prepare, for the sake of not only his personal credibility, but French national interests, to strike alone.” No call for restraint, no call for evidence, no suggestion that the terrorists may have been to blame. Just a reckless gunshot from the hip to settle matters, and who cares if it may trigger a global conflagration. This only serves to prove that the United States, and its people, learned absolutely nothing from the Iraq War, which saw the same brazen disregard for legal precedent by launching an attack against Saddam Hussein in 2003, the consequences of which we are experiencing to this day. As the UN weapon inspectors were on the ground, practically screaming that they could not locate weapons of mass destruction, the Bush administration shrugged off these uncomfortable truths and carried out its diabolical designs anyways. In reality, the US did learn one valuable lesson from the Iraq War. It learned it can manipulate the opinions of the people to an astonishing degree. By using the entire media leviathan to coordinate a hate campaign against one state leader, in this case Bashar Assad, it can make the people forget legal precedent, not to mention common sense. Wake up, America, before it’s too late.
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0.000136
Introduction {#Sec1} ============ Neutrophil extracellular traps (NETs) are webs of chromatin fibers (DNA and histones) coated with antimicrobial granular proteins including the enzymes neutrophil elastase (NE) and myeloperoxidase (MPO). Released by neutrophils into the extracellular space upon activation, NETs were discovered to trap and kill bacteria as part of the innate immune system over a decade ago \[[@CR1]\] and have since then been implicated in several pathological conditions. In addition to a pro-thrombotic activity in deep vein thrombosis \[[@CR2], [@CR3]\], acute coronary syndrome \[[@CR4]--[@CR6]\] and ischemic stroke \[[@CR7]--[@CR9]\], NETs have been shown to impair fibrinolysis and induce tissue and organ damage in sepsis \[[@CR10], [@CR11]\], promote the autoimmune response in small vessel vasculitis \[[@CR12]\], contribute to endothelial damage in systemic lupus erythematosus \[[@CR13], [@CR14]\], and acute lung injury \[[@CR15]\], as well as impair wound healing in diabetes \[[@CR16]\]. A role in cancer is also emerging, where NETs have been implicated in cancer-associated thrombosis \[[@CR17]\], tumor growth, and progression \[[@CR18], [@CR19]\]. In light of the emerging data on the adverse role of NETs, pre-clinical studies are now starting to explore the possibility of alleviating the effects of NETs with new therapeutic agents that degrade NETs or inhibit their formation \[[@CR3], [@CR8], [@CR20]\]. In this context, a reliable and specific biomarker of NETs would play a central role in prediction of risk, prognosis, and therapeutic effects. Studies of NET formation in the above disease settings rely largely upon in vitro stimulation of neutrophils and subsequent NET formation assessing the susceptibility of neutrophils to undergo NETosis. Quantification of surrogate NET markers in plasma, such as cell-free DNA (cfDNA), nucleosomes, and the NET-associated enzymes NE and MPO by commercially available enzyme-linked immunosorbent assay (ELISA) kits, has also been implemented. Data obtained with these assays should be interpreted with caution, as events unrelated to NETosis, such as tissue injury, apoptosis, and necrosis, may generate circulating cfDNA as well as nucleosomes, whereas circulating NE and MPO may reflect neutrophil and/or macrophage activation not related to NET generation. Some studies also identified circulating levels of MPO-DNA complexes using a capture ELISA \[[@CR11], [@CR12], [@CR21]\]. However, MPO is a highly positively charged secreted protein \[[@CR22]\], which can bind to the negatively charged cfDNA released in the plasma following tissue injury, thus questioning its specificity as a NET marker. Prior to releasing NETs, peptidylarginine deiminase 4 (PAD4), an enzyme that is primarily expressed in neutrophils, translocates to the nucleus and converts peptidylarginine to peptidylcitrulline on histone H3. The citrullination of positively charged arginine residues leads to uncharged citrulline residues, loss of ionic interactions, and subsequent chromatin decondensation, the initial step of NETosis. Citrullinated Histone H3 (H3Cit) is thereby considered a NET-specific biomarker \[[@CR23]\]. An assay to estimate the levels of the NET biomarker H3Cit in plasma would allow for a more specific assessment of a circulating NET burden. We therefore aimed to validate and optimize an ELISA-based assay recently shown to detect H3Cit in plasma of patients with ischemic stroke \[[@CR9]\]. Materials and methods {#Sec2} ===================== Reagents and equipment {#Sec3} ---------------------- Microplates with 96 streptavidin pre-coated wells, monoclonal anti-histone-biotin antibodies, and incubation buffer (all from Cell Death Detection ELISA PLUS kit, Roche, Cat. No. 11 774 425 001). Phosphate buffered saline (PBS; Life Technologies, Cat. No. 14190-250), tween 20 (Sigma-Aldrich, Cat. No. A9418), rabbit polyclonal anti-histone H3 (citrulline R2 + R8 + R17) antibody (Abcam, Cat. No. AB5103), bovine serum albumin, BSA (Sigma-Aldrich, Cat. No. A9418), goat anti-rabbit IgG horseradish-peroxidase (HRP) conjugate (BioRad, Cat. No. 170-6515), 3,3′, 5,5′-tetramethylbenzidine (TMB) liquid substrate (Sigma-Aldrich, Cat. No. T0440), stop solution (Thermo Scientific, Cat. No. N600), Trizma base (Sigma-Aldrich, Cat. No. T1503), CaCl~2~ (Sigma-Aldrich C1016), phenylmethylsulfonyl fluoride (PMSF) protease inhibitor (Life Technologies, Cat. No. 36978), dithiothreitol, DTT (Invitrogen, Cat. No. P2325), human recombinant PAD4 (Cayman Chemical, Cat. No. 10500), human recombinant histone H3 (Cayman Chemical, Cat. No. 10263), ELISA reader (Tecan Sunrise) Preparation of standard {#Sec4} ----------------------- A working stock solution of H3Cit was made as described previously \[[@CR24]\]. Briefly, human recombinant PAD4 and human recombinant histones H3 at a ratio 2.5 U of PAD4 per microgram of histones were incubated at 37 °C for 1 h in reaction buffer (50 mM Trizma base with 4 mM CaCl~2~, pH 7.6, 4 mM DTT, and 1 mM PMSF). A final concentration of 10,000 ng/mL H3Cit was obtained by adding PBS-1% BSA. The stock solution was aliquoted, frozen on dry ice, and stored at −80 °C until later use. Samples {#Sec5} ------- Samples were taken from healthy individuals prior to and 3--4 h after receiving intravenous injection of lipopolysaccharide (LPS; 2 ng/kg of body weight *Escherichia coli* endotoxin, Lot H0K354 CAT number 1235503, United States Pharmacopeia, Rockville, MD, USA) or from healthy volunteers. Plasma samples were prepared from citrated whole blood following immediate centrifugation for 20 min at 2000×*g* after which they were stored at −80 °C until further analysis. At time of anal-ysis, samples were thawed on ice and diluted 1:2 in PBS unless otherwise indicated. All study individuals gave written informed consent for the use of their plasma, and the study complied with the Declaration of Helsinki. ELISA methodology {#Sec6} ----------------- The microplate and diluents were kept at room temperature 30 min prior to starting the assay. Stock solution, antibodies, and samples were thawed on ice and kept on ice until loading of microplate. All incubations were at room temperature and washes were repeated four times with PBS-Tween (0.05%) with 20 s soaking for each wash. The concentrations of the standard curve, incubation times, and dilutions of samples were optimized in preliminary experiments. The assay was performed as follows (Fig. [1](#Fig1){ref-type="fig"}): 100 μL of anti-histone biotin (1:10 in incubation buffer) was added to Streptavidin pre-coated wells and incubated for 2 h. After washing, 50 μL of standard solutions or samples was added to each well and incubated for 1.5 h, then washed again. 100 μL of anti-histone H3 (citrulline R2 + R8 + R17; anti-H3Cit) antibody (1:2000 in 1% BSA in PBS) was applied to each well for 1 h incubation. After washing, the wells were incubated for another hour with 100 μL anti-rabbit HRP conjugate antibody (1:5000 in 1% BSA in PBS), followed by washing. For detection, 100 μL TMB was added to each well and incubated for 20 min in the dark. The reaction was stopped by adding 50 μL stop solution. The optical density (O.D.) was measured at a wavelength of 450 nm with a reference correction wavelength at 620 nm using an automatic plate reader.Fig. 1Schematic of the H3Cit ELISA procedure. *A* Anti-histone biotin (the capture antibody) is coated to streptavidin pre-coated wells during the first incubation. Samples are pipetted into the wells and histones bind to the capture antibody during the second incubation. *B* After washing, anti-H3Cit is added to the wells, binding to immobilized H3Cit but not to histones H3 that are not citrullinated, during the third incubation. *C* In the fourth incubation, an HRP conjugated anti-rabbit antibody is added and binds to the anti-H3Cit, after which TMB is added for detection Assay validation {#Sec7} ---------------- For validation of the assay, we assessed the following: linearity, stability, limit of detection, specificity, recovery, and precision. Trueness could not be determined as no reference analyte of known concentration is available, and there is no available assay for the quantification of H3Cit in plasma for comparison. The linear interval was defined as the linear section of the best-fit standard curve. Each standard curve was fitted using a four-parameter logistic (4PL) regression, and the 95% confidence interval (95% CI) was considered. The limit of detection was approximated from the intersection of the lower asymptote of the upper 95% CI with the 4PL fit of the standard data. Specificity was assessed by the ability to detect citrullinated histone H3 but not non-citrullinated histone H3 in similar conditions by preparing a standard without PAD4, thus preventing the citrullination of histone H3. Recovery and the effect of the matrix were assessed by spiking plasma samples from four healthy volunteers with known concentrations of in vitro PAD4-citrullinated histone H3, comparing this to the detector response obtained for the same concentrations of in vitro PAD4-citrullinated histone H3 diluted in PBS-1% BSA. Precision was expressed by the intra- and inter-assay coefficient of variation (%CV, defined as the ratio between standard deviation and mean value). The maximum accepted %CV for intra- and inter-assay variability were set to 15%. Stability was assessed by comparing the detector response obtained from freshly prepared and frozen aliquots of H3Cit standard and comparing standard curves from frozen aliquots from three different batches of H3Cit that had been citrullinated on three different days. One versus two freeze-thaw cycles of plasma samples were also compared. Statistical analyses {#Sec8} -------------------- O.D. was fitted versus nominal log concentration applying a sigmoidal 4PL regression to the calibration curve. 4PL curves were compared by *F*-test. Data were analyzed using GraphPad Prism 6 (GraphPad Software, Inc., La Jolla, CA, USA). Results {#Sec9} ======= Standard preparation and linearity {#Sec10} ---------------------------------- As no international standard preparation is available for H3Cit, we generated a standard curve using in vitro PAD4-citrullinated H3Cit, as previously described \[[@CR24]\]. The stock was serially diluted 1:2 in PBS-1% BSA to obtain a standard curve and applied to a streptavidin-coated plate using an anti-histone biotin antibody as capture and an anti-H3Cit antibody for detection. To determine the suitable linear interval, we interpolated the detected O.D. from the serial dilutions of H3Cit to different regressions. The best-fit curve was a sigmoidal 4PL curve rendering a linear interval of the curve between ≈ 0.3 and 3.5 O.D., corresponding to concentrations between ≈5 and ≈300 ng/mL (Fig. [2](#Fig2){ref-type="fig"}a).Fig. 2In vitro PAD4-citrullinated histone H3 standard. **a** Standard curves. The detector response when preparing standard curves from frozen aliquots from three different batches of PAD4-citrullinated histone H3 on three different days (STD 1--3) were not significantly different (*F* (DFn, DFd) = 2.6 (8, 9); *p* = 0.088). **b** Standard curves generated from freshly made or frozen aliquot of H3Cit standards. No significant difference was observed when comparing the detector response of the freshly made versus frozen standards (*F* (DFn, DFd) = 0.2 (4, 52); *p* = 0.916. **c** Data obtained when a standard curve was prepared with histone H3 incubated in the same conditions as our standard preparation of H3Cit, but without PAD4, rendering non-citrullinated histones, representative of three different experiments. There was a low amount of antibody antigen detection when large amounts of non-citrullinated histone H3 were present, but the antibody antigen detection was specific for H3Cit in the linear interval of the assay Stability {#Sec11} --------- The detector response when preparing standards from freshly citrullinated H3Cit was very similar to the detector response obtained from frozen aliquots of the same standards (Fig. [2](#Fig2){ref-type="fig"}b). Moreover, the detector response when preparing standard curves from frozen aliquots from three different batches of H3Cit citrullinated on three different days were not significantly different (Fig. [2](#Fig2){ref-type="fig"}a), allowing for a good reproducibility. Limit of detection {#Sec12} ------------------ To determine the limit of detection, we approximated the lowest detectable concentration determined from the curve to ≈5 ng/mL. This concentration corresponded to the intersection of the lower asymptote of the upper 95% CI with the 4PL fit of the standard curve. The limit of detection with stated probability was therefore set to approximately 5 ng/mL. Specificity {#Sec13} ----------- To assess the specificity of the assay, we prepared a standard curve with histone H3 incubated under the same conditions as our standard preparation of H3Cit, but without PAD4, rendering non-citrullinated histones, and compared this to our standard curve with in vitro PAD4-citrullinated H3Cit. Although there was a low amount of antibody antigen detection when large amounts of non-citrullinated histone H3 were present, the antibody antigen detection was specific for citrullinated H3Cit in the linear interval of the assay (Fig. [2](#Fig2){ref-type="fig"}c). Effect of the matrix {#Sec14} -------------------- To evaluate whether components of the sample matrix (i.e., plasma), such as proteins, phospholipids, carbohydrates, or various metabolites, interfered with the binding of H3Cit to either the capture antibody or the detection antibody, we spiked known concentrations of H3Cit to plasma diluted 1:2 from four healthy volunteers. This gave a significantly lower detector response compared to the detector response obtained from the standard diluted in PBS-1% BSA (Fig. [3](#Fig3){ref-type="fig"}a), suggesting an effect of the matrix. To further study this effect, we prepared the standard in pooled plasma from healthy donors diluted 1:20, 1:10, and 1:5 in PBS, rendering a dose response of the detector with increasing dilutions of plasma (Fig. [3](#Fig3){ref-type="fig"}b). However, the citrullinated histones used for these spiking experiments were free citrullinated histones, as opposed to the citrullinated histones in our samples which are hypothesized to be bound to cfDNA in nucleosomes, suggesting that there are components in plasma either interfering with the antibody detection of free histones or degrading free histones in plasma, aggravating the attempt to recover free histones in plasma.Fig. 3Detection of H3Cit in plasma samples. **a** At baseline, no H3Cit was detected in plasma from healthy volunteers, whereas the spiking of known concentrations of H3Cit into these plasmas diluted 1:2 gave a significantly lower detector response compared to the detector response obtained from the standard diluted in PBS-1% BSA, suggesting an effect of the matrix. **b** Standards prepared from H3Cit diluted in pooled plasma from healthy donors at various dilutions, rendered an obvious increase in detector response with increasing dilutions of plasma. **c** The quantification of H3Cit in plasma of healthy volunteers before LPS injections were under the detection limit of approximately 5 ng/mL. An increase in the levels of H3Cit in all plasma samples taken from the same individuals 3--4 h after LPS was observed, ranging from 28.7 to 93.2 ng/mL Concentrations of H3Cit in plasma in a human model of LPS-induced inflammation {#Sec15} ------------------------------------------------------------------------------ Surrogate markers of NETs (cfDNA, nucleosomes and MPO-DNA complexes) have been identified in the plasma of septic patients \[[@CR10], [@CR11], [@CR25], [@CR26]\] and in murine models of lipopolysaccharide (LPS)-induced septic shock \[[@CR11], [@CR27], [@CR28]\]. Furthermore, H3Cit was detected by western blot in plasma of mice shortly after LPS injection \[[@CR27], [@CR28]\]. With the intention to perform the assay validation with samples containing H3Cit, we therefore used samples from healthy volunteers receiving intravenous LPS in an experimental model of inflammation. The samples were taken at baseline (before LPS injection) and after 3--4 h, with the hypothesis that LPS injection would induce a systemic NET formation resulting in elevated and detectable levels of H3Cit in plasma. Indeed, the levels of H3Cit in all samples taken at baseline were under the detection limit of approximately 5 ng/mL, and the levels of H3Cit in all samples taken from the same individuals 3--4 h after LPS injection ranged from 28.7 to 93.2 ng/mL (Fig. [3](#Fig3){ref-type="fig"}c). These concentrations were all calculated from detection of optical density within the linear interval of the standard curve following a 1:2 dilution of plasma samples (Fig. [2](#Fig2){ref-type="fig"}a). However, repeated freeze-thaw cycles of plasma samples with known concentrations of H3Cit rendered a mean reduction of 13.4 ± 2.3% after a second freeze-thaw cycle. Freeze-thaw cycles of the plasma are therefore not recommended when applying this assay. Precision and reproducibility {#Sec16} ----------------------------- To assess the precision of the assay, we performed the assay on six replicates of eight samples (1-8) within the same assay run as well as duplicates of the same eight samples in four different assay runs performed on four different days. The CV were all \<15%, with the intra-assay ranging from 2.13 to 5.15% and the inter-assay ranging from 5.80 to 12.55%, showing a high precision with good repeatability and reproducibility of the assay (Table [1](#Tab1){ref-type="table"}).Table 1Precision, intra-assay repeatability, and four different days inter-assay reproducibilitySample12345678Coefficient of variation (%) intra-assay (*n* = 6)5.14.55.082.74.353.582.133.1Coefficient of variation (%) inter-assay (*n* = 4)11.5410.2712.558.59.610.535.813.5 Discussion {#Sec17} ========== Our study establishes an assay allowing for the fast and reliable quantification of the NET-specific biomarker H3Cit in human plasma. We also show, for the first time, an elevation of H3Cit in plasma in a human model of LPS-induced inflammation. The validation of the assay revealed a high specificity for H3Cit as well as a high stability of the custom-made standard, rendering a good precision and reproducibility. Although we show a clear dose-dependent effect of the matrix on the detection of free citrullinated histones added to plasma, we can only speculate on whether the citrullinated histones in our samples are protected by surrounding DNA as part of nucleosomes. Free histones are highly positively charged and have been shown to bind to negatively charged components such as proteins and heparins in plasma \[[@CR29]\], potentially blocking the binding sites of the antibodies in the assay. Free histones have also been shown to bind to phospholipids such as phosphatidylserine and phosphatidylethanolamine present on microparticles \[[@CR30]\], as well as to platelets \[[@CR31]\] and platelet adhesion molecules such as vWF and fibrinogen \[[@CR32]\]. Furthermore, histones could in their free form be subject to rapid degradation by free proteases within the plasma such as activated protein C \[[@CR33]\], or the NET-associated enzymes NE, MPO \[[@CR34]\], and cathepsins \[[@CR35]\]. Indeed, the degradation of free histones in plasma was recently shown by western blotting assessing histone degradation over time in plasma from healthy volunteers spiked with free calf thymus histones, revealing a very rapid degradation with a half-life of 4.6 min \[[@CR36]\]. However, H3Cit bound to DNA in nucleosomes, the endpoint of interest in the detection and quantification of circulating NETs, could be protected against degradation and/or further binding and subsequent blocking of the antibody binding site in the assay. It is therefore our hypothesis that the amount of H3Cit quantified by this assay is in fact the amount of H3Cit protected by the NET complex, excluding a possible portion of free H3Cit in plasma. On the other hand, the standard of H3Cit used in our assay comprises in vitro citrullinated H3Cit, and the concentration of H3Cit in the standard curve is therefore an estimation based on the assumption that all histones were citrullinated, assuming the optimal enzymatic activity of PAD4 at a ratio of 2.5 U/μg of histones. A possible underestimation of the concentration in our samples can therefore not be ruled out. However, the assay provides a reproducible estimate of the concentrations of detectable H3Cit in plasma with high specificity, stability, and precision, rendering a robust and reliable assay for the comparison of the levels of detectable H3Cit in human plasma. Interestingly, all samples taken at baseline in the LPS-induced model of inflammation were below the limit of detection, suggesting that healthy people do not have a baseline systemic NET burden. This is in line with a recent study revealing a low amount of H3Cit in plasma of healthy individuals when applying a similar assay but without concentrations derived from a standard curve \[[@CR9]\]. Furthermore, in accordance with previous studies showing elevations of surrogate markers of NETs in septic patients \[[@CR10], [@CR11], [@CR25], [@CR26]\] as well as the detection of H3Cit by western blotting in murine models of LPS-induced septic shock \[[@CR27], [@CR28]\], our results support an inflammatory induction of a systemic NET burden by showing clear intra-individual elevations of H3Cit in healthy individuals receiving LPS injection. Further studies are now warranted to confirm these elevations in a clinical setting of sepsis. There is an emerging interest in the role of NETs in various disease settings. Apart from its role as a central player of the innate immune system in both bacterial \[[@CR1], [@CR10], [@CR11], [@CR25]--[@CR28], [@CR33], [@CR36]\] and viral infection \[[@CR15], [@CR37]\], NETs are now being implicated in several common and widespread diseases such as arterial and venous thrombosis \[[@CR2]--[@CR9]\], cancer \[[@CR17]--[@CR19]\], and diabetes \[[@CR16]\]. Prior studies rely largely upon the detection and quantification of surrogate markers of NETs, such as cfDNA, NE, and MPO. There is therefore an unmet need for a more specific assessment of a systemic NET burden to explore the potential of NETs in disease prediction and progression. Moreover, with the use of a detection antibody widely shown to recognize citrullinated histone H3 in plasma and cells from mouse and human \[[@CR9], [@CR16], [@CR17], [@CR19], [@CR38]\] we believe that our method has the potential to detect NET burden not only in human plasma but also in disease mouse models and in vitro research. In conclusion, we believe that this assay could be of great value in further studies of a systemic NET burden. If quantifiable levels of H3Cit in plasma prove to be useful as a prognostic marker in conditions such as sepsis or prediction of diseases such as thrombosis and cancer, further development of this assay would allow for its implementation in several clinically important settings. We thank Elisee Wiita, Lena Gabrielsson, Katherina Aguilera, and Ann-Christine Samuelsson for their help and assistance with the study. This work was supported by the Helleday Foundation (C.T.) and the Torsten and Ragnar Söderberg Foundation (T.H.).
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Football 2 Futbol Whether you are a fan of the round ball or the weird shaped pigskin one, there's a little bit on this podcast for everyone. Sean Garmer, Gary Vaughan, Matt Pollard, and other various special guests discuss what's going on every week in the NFL, College Football, and American Soccer. Don't fret though, we do try to touch on the NBA, NHL, MLB, and International soccer leagues when we can too.
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Transanal endorectal pull-through versus transabdominal approach for Hirschsprung's disease: a systematic review and meta-analysis. Transanal endorectal pull-through (TERPT) has become popular for single-stage treatment of Hirschsprung's disease. The benefits of TERPT over the conventional transabdominal approach (TAB) are still unclear. We performed a comprehensive meta-analysis comparing the clinical outcomes of TERPT and TAB. Original articles published from 1998 to 2012 were searched from Medline, Embase, and Cochrane databases. Randomized controlled trials (RCT) and observational clinical studies (OCS) comparing TERPT and TAB were included. Outcomes evaluated included operative time, hospital stay and incidence of postoperative incontinence/soiling, constipation and enterocolitis. Pooled odds ratios (OR) were calculated for dichotomous variables; pooled mean differences (MD) were measured for continuous variables. Of 93 studies, 1 RCT and 11 OCS were included, comprising 444 cases of TERPT and 348 cases of TAB (215 Soave, 94 Duhamel, 24 Swenson, 15 Rehbein procedures). TERPT had shorter operative time (MD=-57.85 min; 95% confidence interval [CI], -83.11 to -32.60; P<0.00001) and hospital stay (MD=-7.06 days; 95% CI, -10.95 to -3.16; P=0.0004). TERPT had less postoperative incontinence/soiling (OR=0.58; 95% CI 0.37-0.90; P=0.01) and constipation (OR=0.49; 95% CI 0.30-0.81; P=0.005). There was no difference in incidence of postoperative enterocolitis. TERPT is superior to TAB in operative time, hospital stay, postoperative incontinence and constipation. However, more randomized controlled trials are necessary to verify the benefit of TERPT for Hirschsprung's disease.
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A new approach to the analysis of nicarbazin and ionophores in eggs by HPLC/MS/MS. An HPLC/MS/MS method has been developed and validated for the quantification and confirmation of nicarbazin and ionophores (lasalocid, monensin, salinomycin, and narasin) in eggs. Nicarbazin is determined in the negative electrospray mode with a basic mobile phase that supports creation of negative ions. Consequently, our ability to maintain instrument sensitivity over time has significantly improved. The analysis of the ionophores is done in the positive electrospray mode using ammonium buffer for HPLC separation. Monitoring ammonium adduct parent ions resulted in enhanced sensitivity and better reproducibility of the ionophore analysis. The validation of this improved HPLC/MS/MS method for the detection of nicarbazin and the ionophores demonstrated excellent precision of below 10% RSD and lower LOD values (microg/kg) for nicarbazin (0.018), lasalocid (0.015), monensin (0.015), salinomycin (0.033), and narasin (0.039).
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Petite slut and her chubby girlfriend get fucked in the bangbus
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[Lectin staining of a Merkel cell tumor]. The authors studied a Merkel's cell tumor with lectins. There is pattern of normal epidermis, but we see the N-acetyl-glucosamine an oligosaccharide not present in epidermis.
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United States Court of Appeals FOR THE EIGHTH CIRCUIT ________________ No. 06-1356 ________________ Allison Sanders, Individually and * as Trustee for the heirs and next of * kin of Alfred Charles Sanders, * * Appellant, * * v. * Appeal from the United States * District Court for the City of Minneapolis, Minnesota; * District of Minnesota. Robert Olson, Chief of Police; * Minneapolis Police Department; * [PUBLISHED] Valorie Gogligowski; Hien Dinh; * Lupe Herrera; Matthew Blade; * Josef Garcia; Augsburg College * Security and Wolf Protection * Agency; Steven Manhood; * Minneapolis Park Police, * * Appellees. * ________________ Submitted: January 15, 2007 Filed: January 23, 2007 ________________ Before WOLLMAN, HANSEN, and COLLOTON, Circuit Judges. ________________ HANSEN, Circuit Judge. Alison1 Sanders appeals the district court's2 dismissal of her civil lawsuit related to the shooting death of her husband, Alfred Sanders, by Minneapolis police officers. Although the incident was tragic, the facts do not support the claims, and we affirm. Alfred Sanders suffered from a bipolar disorder. On October 31, 2000, his friends contacted Minneapolis police in an attempt to have him committed to a crisis center, but the police were unable to locate him. Around 7:00 a.m. the next morning, during his patrol, Josef Garcia, a security guard for Augsburg College, noticed a vehicle (which turned out to be driven by Alfred) driving on the sidewalk of a street adjacent to the campus. Garcia followed the car and radioed Augsburg dispatch, requesting it to contact the Minneapolis Police Department. Garcia continued to follow the vehicle, which drove erratically, for approximately fifteen to twenty minutes until it pulled into the north end of an alley and parked in a parking space just off the alley. Garcia parked in the middle of the alley and stood by his vehicle, waiting for the police to arrive. Meanwhile, the Minneapolis police dispatched two squad cars to respond to an erratic driver, relaying the vehicle's location from the Augsburg dispatch. One squad, comprised of Officers Matthew Blade and Hien Dinh, had responded to the crisis call the previous day. They reported to the other officers and to dispatch that this call may involve a crisis candidate. The squad cars entered the south end of the alley about two minutes after Alfred parked in the alley, and the officers exited their vehicles. A fifth officer, Steven Manhood of the Minneapolis Park and Recreation Board police department, responded to the call as well and reached the scene a few seconds after the other officers. Officer 1 We use the correct spelling of the parties names, including Alison Sanders and Valorie Goligowski, throughout the opinion, though they are spelled differently in the official case caption. 2 The Honorable Ann D. Montgomery, United States District Judge for the District of Minnesota. -2- Valorie Goligowski approached Alfred's car, telling him to put his hands where she could see them. Alfred did not respond, but put his car in reverse and backed into Garcia's security vehicle, next to which Garcia was standing. The officers believed Garcia would be trapped or hit by Alfred's car. Alfred then put the vehicle in drive and accelerated down the alley toward Officers Blade and Lupe Herrera, who were on foot. Officer Blade was a few feet directly in front of Alfred's car, and he fired two shots from his revolver through the windshield as Alfred's vehicle drove toward him. Goligowski believed that Blade was trapped under Alfred's car, and she fired her weapon at Alfred. Alfred's car continued down the alley toward Officer Herrera, who was able to jump out of its path, until it collided with one of the squad cars. Each of the police officers fired at Alfred's car as it passed them and continued down the alley. Alfred was shot 14 times and was pronounced dead at the scene. Each of the officers believed that Alfred was attempting to run over Officers Blade and Herrera, and they feared for their lives or the lives of their fellow officers. Alison Sanders brought a civil lawsuit against each of the individual officers, their employing agencies, Mr. Garcia, and Augsburg College. Ms. Sanders alleged violations of 42 U.S.C. § 1983; 42 U.S.C. § 1985; the Americans with Disabilities Act (ADA); and she brought claims for failure to train under Monell v. New York City Dep't of Soc. Servs., 436 U.S. 658 (1978), and state law negligence. The district court granted summary judgment to all defendants on all claims. Ms. Sanders appeals the dismissal of the § 1983 claim, the Monell failure to train claim, and the ADA claim. She also appeals the $4,500 sanction entered against her attorney for failing to timely withdraw an expert witness. Summary judgment is appropriate if there are no genuine issues of material fact and the moving party is entitled to judgment as a matter of law. Fed. R. Civ. P. 56(c). The court must view all evidence in the light most favorable to the nonmoving party. Mershon v. St. Louis Univ., 442 F.3d 1069, 1073 (8th Cir. 2006). The nonmoving party may not rest on her pleadings "but must demonstrate on the record the existence -3- of specific facts which create a genuine issue for trial." Krenik v. County of Le Sueur, 47 F.3d 953, 957 (8th Cir. 1995). We review the district court's grant of summary judgment de novo, applying the same standards applied by the district court. Mershon, 442 F.3d at 1073. Section 1983 imposes civil liability on government officials, including police officers, who violate an individual's constitutional rights. 42 U.S.C. § 1983. Officers are entitled to qualified immunity, however, "if 'their conduct does not violate clearly established statutory or constitutional rights of which a reasonable person would have known.'" McCaslin v. Wilkins, 183 F.3d 775, 778 (8th Cir. 1999) (quoting Harlow v. Fitzgerald, 457 U.S. 800, 818 (1982)). In addressing an officer's claimed entitlement to qualified immunity, the court must first determine whether the allegations amount to a constitutional violation, and then, whether that right was clearly established. Saucier v. Katz, 533 U.S. 194, 201 (2001). A § 1983 claim alleging the use of deadly force implicates the Fourth Amendment's protection against unreasonable seizures. See Graham v. Connor, 490 U.S. 386, 394-95 (1989). However, "[w]here the officer has probable cause to believe that the suspect poses a threat of serious physical harm, either to the officer or to others, it is not constitutionally unreasonable to prevent escape by using deadly force." Brosseau v. Haugen, 543 U.S. 194, 197-98 (2004) (per curiam) (internal marks omitted and alteration in original); see also Hernandez v. Jarman, 340 F.3d 617, 622 (8th Cir. 2003). The undisputed evidence reveals that Officer Goligowski told Alfred to show his hands, that Alfred did not respond but instead backed his car into the security guard's vehicle, and that he then accelerated down the alley toward other officers, two of whom were close to his vehicle and directly in its path. Sanders has provided no admissible evidence to contradict the officers' testimony that they each believed Alfred was trying to run over Officers Blade and Herrera. Given the quickly evolving -4- scenario, the officers' actions in shooting Alfred in an attempt to stop him from injuring the officers in his path were objectively reasonable and did not violate Alfred's Fourth Amendment right to be free from unreasonable seizures. See Hernandez, 340 F.3d at 623-24 (finding no constitutional violation where officer shot victim after the victim rammed a fellow officer's vehicle and appeared to be driving toward the shooting officer, despite discrepancies in the testimony about when exactly the shots were fired); Troupe v. Sarasota County, Fla., 419 F.3d 1160, 1168-69 (11th Cir. 2005) (holding officers' actions of shooting driver to be objectively reasonable where the driver refused to obey commands to put his hands up and his car suddenly lurched forward, leaving the officers "to make split-second decisions of whether they could escape before anyone suffered serious injury"), cert. denied, 126 S. Ct. 1914 (2006). The district court properly disregarded the unsworn statements to a police investigator by an eyewitness, who was 150 feet from the action and whose view was blocked by the squad cars. The statements constituted double hearsay and were not exempted by any of the hearsay exceptions. See United States v. Taylor, 462 F.3d 1023, 1026 (8th Cir. 2006); Sallis v. Univ. of Minn., 408 F.3d 470, 474 (8th Cir. 2005) (requiring admissible evidence to rebut summary judgment). The fact that Alfred may have been experiencing a bipolar episode does not change the fact that he posed a deadly threat against the police officers. "Knowledge of a person's disability simply cannot foreclose officers from protecting themselves, the disabled person, and the general public when faced with threatening conduct by the disabled individual." See Bates ex rel. Johns v. Chesterfield County, Va., 216 F.3d 367, 372 (4th Cir. 2000). Without a constitutional violation by the individual officers, there can be no § 1983 or Monell failure to train municipal liability. See City of Los Angeles v. Heller, 475 U.S. 796, 799 (1986) (per curiam); Walker v. Bonenberger, 438 F.3d 884, -5- 890 (8th Cir. 2006). To the extent Sanders appeals the dismissal of the § 1983 claims against Garcia and Augsburg College, we note that "[p]rivate actors may incur section 1983 liability only if they are willing participants in a joint action with public servants acting under color of state law." Johnson v. Outboard Marine Corp., 172 F.3d 531, 536 (8th Cir. 1999). Neither Garcia, who did nothing more than follow Alfred, nor Augsburg College was acting under color of state law. See Reasonover v. St. Louis County, Mo., 447 F.3d 569, 584 (8th Cir. 2006) (to be deemed a state actor, private party must perform a function "traditionally exclusively reserved to the state" (internal marks omitted)); Young v. Harrison, 284 F.3d 863, 870 (8th Cir. 2002); Youngblood v. Hy-Vee Food Stores, Inc., 266 F.3d 851, 855 (8th Cir. 2001). Further, since Sanders has "failed to establish that a state actor violated [Alfred's] rights under the Constitution or laws of the United States, [her] claim[] against the private actors must also fail." Johnson, 172 F.3d at 536. The district court properly granted summary judgment to all of the defendants on Sanders' § 1983 claims and the Monell claim against the City of Minneapolis. The ADA provides that "no qualified individual with a disability shall, by reason of such disability, . . . be denied the benefits of the services, programs, or activities of a public entity, or be subjected to discrimination by any such entity." 42 U.S.C. § 12132. Sanders does not identify the "benefits . . ., programs, or activities," id., that were denied to Alfred, but argues that had the City properly trained its officers in how to approach individuals with mental illnesses, the situation would not have escalated to the point of needing to use deadly force. It was not the City's failure to train its officers, but Alfred's apparent attempt to run over the officers that precipitated the shooting. See Hainze v. Richards, 207 F.3d 795, 801 (5th Cir.) ("Hainze was not denied the benefits and protections of Williamson County's mental health training by the County, Sheriff Richards, or the officers. Rather, Hainze's assault of Allison with a deadly weapon denied him the benefits of that program."), cert. denied, 531 U.S. 959 (2000); see also Bates, 216 F.3d at 373 (rejecting an ADA claim because "the stop, the use of force, and the arrest of Bates [an autistic teenager] were not by reason of Bates' -6- disability, but because of Bates' objectively verifiable misconduct. Such reasonable police behavior is not discrimination."). The City of Minneapolis, the only public entity at issue, see 42 U.S.C. § 12132, did not violate Alfred's rights under the ADA. We review the imposition of sanctions for an abuse of discretion. United States v. Pugh, 445 F.3d 1066, 1068 (8th Cir. 2006). The defendants asked Sanders' attorney to withdraw Sanders' expert on July 18, 2005, based on misrepresentations and falsehoods contained in the expert's curriculum vitae. Sanders' attorney asked for fourteen days to consider the request, but did not respond for two-and-a-half months, and then only after the defendants filed a Motion to Strike the expert. The district court's $4,500 sanction, in light of the reported $40,000 cost to challenge the expert, was not an abuse of discretion. The district court's judgment is affirmed. The motion to strike portions of the appellant's appendix is denied. ______________________________ -7-
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Refined structure of basic phospholipase A2 from venom of Agkistrodon halys Pallas in orthorhombic crystal form I at 0.25 nm resolution. The basic phospholipase A2 from the venom of Agkistrodon halys Pallas is a potent hemolytic toxin and anticoagulant. The accurate rotation and translation parameters of the molecules in orthorhombic crystal form I were successfully obtained using the fitting refinement technique. The structure was refined in the resolution range of 0.6-0.25 nm using least square refinement with non-crystallographic two fold symmetry restraint, and resulted in the final R factor of 20.1 %, and the rms deviations from ideal stereochemistry were 0.001 3 nm for bond lengths and 1.32 degrees for bond angles. The overall architecture of the present structure was similar to that of the determined structure of the orthorhombic crystal form II, with a few differences in the regions of the beta-wing and Ca(2+) -binding Imp. The dimers formed by the two molecules in the asymmetric unit in both crystal forms were also similar. However, one of the monomers showed an orientational difference of 5.5 degrees along the dimer interface in the two crystal forms, suggesting the flexibility of the interface of the dimer to some degree. The molecular packing of the dimer in crystal form I was much more compact than that in crystal form II.
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Q: Non-asymptotic bound on the variance of largest singular value of gaussian matrix Let $A$ be a gaussian matrix of size $d \times n$ where all the coefficients are drawn i.i.d. from $ \mathcal{N}(0, 1)$ and denote by $s_{\text{max}}$ its largest singular value. Theorem 2.6 of http://www-personal.umich.edu/~rudelson/papers/rv-ICM2010.pdf mentions that : $$ \mathbb{E} (s_{\text{max}}) \leq \sqrt{n}+\sqrt{d} $$ Hence : $$ \mathbb{E} (\frac{s_{\text{max}}}{\sqrt{n}}-1 ) \leq \sqrt{\frac{d}{n}} $$ I'm looking for a non-asymptotic upper-bound on $ s_{\text{max}}^2 $ that would look like : $$ \mathbb{E} (~| \frac{s_{\text{max}}^2}{n}-1 |~) \leq C~ \frac{d}{n} $$ C being a constant. This is the same as bounding $ \frac{AA^T }{n} - I $, and the Frobenius norm already gives a bound in order of $ \frac{d^2}{n} $. A: Say $d\le n$. For an upper bound on the size of $s_{\max}$, for a matrix with sub-Gaussian entries we actually have the upper tail bound $P(s_{\max}\ge C\sqrt{n}) \le e^{-cn}$ for some absolute constants $C,c>0$. See for instance Fact 2.4 here (which gives explicit constants): http://www-personal.umich.edu/~rudelson/papers/rand-matr.pdf This gives $E(s_{\max}^2)\le C'n$ for some constant $C'>0$. If you want a bound on the variance of $s_{\max}$, note that a bound of constant order follows quickly from Gaussian concentration. Indeed, $s_{\max}$ is a 1-Lipschitz function on the space of $d\times n$ Gaussian matrices with the Hilbert-Schmidt norm. Of course, the Tracy-Widom law suggests a better than constant-order bound. Edit: for your new question about whether we have $\mathbb{E}(|\frac{s_{\max}^2}{n}-1|)\le C\frac{d}{n}$, note that this is false for $d=1$ (and sufficiently large $n$). In this case $s_{\max}^2$ is just the squared norm of a Gaussian vector of length $n$, so $\mathbb{E}(|s_{\max}^2-n|)$ is of order $\sqrt{n}$.
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Sleep loss is extremely prevalent during adolescence. The causes of sleep restriction in adolescence are the result of brain/behavior/social context interactions in sleep-wake and circadian regulation. Biological changes at puberty create a natural tendency to prefer staying up late as well as increased sleepiness. However the key sleep behaviors (patterns of staying up late and erratic sleep/wake schedules) are largely an interaction between these biologic tendencies and the social environment (i.e., effects of artificial light, stimulating social media such as texting and the internet, and other highly rewarding activities combined with early school start times). Moreover, these interactions are conspiring to rob youth of sleep at a time of critical maturational changes in physical, social, and affective development. Sleep disruption in adolescence may initiate a negative cascade of impaired reward and emotion processing; affective and behavioral dysregulation; further sleep problems; and ultimately, clinical depression and substance abuse. The broad goal of this research is to elucidate potential biopsychosocial mechanisms linking sleep problems with the development of depression and substance abuse in adolescence. Understanding the mechanisms by which sleep loss contributes to vulnerabilities for affective dysfunction and behavioral and mental health problems triggered during adolescence can provide leverage for developing more effective early interventions, including both clinical and social policy-level efforts aimed at the social environment (i.e., school start times, parental and youth education programs, and behavioral interventions). As a first step to address this goal, the proposed study will evaluate the effects of well-controlled laboratory manipulations of sleep duration and social context on activity in neural systems supporting reward and emotion regulation, and on related affective behaviors. Our specific aims are: (1) to investigate the impact of transient sleep restriction and peer social context on reward and risk-taking; and (2) to investigate the impact of transient sleep restriction and peer social context on emotional reactivity/ regulation. Using a within-subjects crossover design, youth in middle adolescence will be studied under two experimental conditions: (1) sleep restriction (two nights of 4 hours time in bed) and (2) sleep extension (two nights of 10 hours time in bed). Polysomnographically-monitored sleep conditions will be followed by functional magnetic resonance imaging (fMRI) and behavioral testing the next day. We will employ validated reward and emotion processing neuroimaging tasks to examine cortical-subcortical activation in response to appetitive and aversive stimuli. Participants will be studied in pairs of friends, enabling us to examine the influence of the peer social context on affective functioning. We will also examine neural and behavioral responses to socially- relevant stimuli.
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Q: Node.js: extracting data from form and submitting to Mongo db Using Node and Express. How would I go about saving all the request data to an array, and then insert each item from the array to a mongo collection? My route is currently setup like this: app.post("/addbulletin", routes.addbulletin(db)); And I'm handling the view and processing the data like so: exports.addbulletin = function(db) { return function(req, res) { // Get our form values. These rely on the "name" attributes var date = req.body.date, name = req.body.name; // and many more... // Submit to the DB collection.insert({ "date" : date, "name" : name // and many more... }, function (err, data) { if (err) { res.send("There was a problem adding the information to the database."); } else { res.location("index"); res.redirect("/"); } }); } } The problem with this way is that I have to know all of the items that need sent to the database. What if I don't know what fields will be on a page to grab the data from? That's exactly the situation I'm in currently, because I have a form that's populating inputs based upon a user selection. So I don't want to have to put every single possible req.body.whatever in a variable. I'd instead want to just say req.body.all, for example, and save just the data that was submitted to variables, then insert those into the database, extracting the name for each field too, of course. A: You can save the req.body to mongodb directly: // Submit to the DB collection.insert(req.body, function (err, data) { if (err) { res.send("There was a problem adding the information to the database."); } else { res.location("index"); res.redirect("/"); } }); Just persist the req.body object. Keep in mind to filter (delete) some properties like _id: delete req.body.__id
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Q: Change google maps location onclick I found a great code on web and I am trying to move the marker to another location with a button. I think I need to trigger variable "targetLocation" with a click event but I couldn't find out how. Or should I create variables like targetlocation2 and marker2 ? location1: 41.118555", 28.2743889 location2: 38.9152733, -111.6676686 html: <a href="#location1">Address 1</a> <a href="#location2">Address 2</a> code: if ($("#map .google-maps").length) { var directionsService = new google.maps.DirectionsService(); var directionsDisplay = new google.maps.DirectionsRenderer(); var targetLocation = new google.maps.LatLng("41.118555", "28.2743889"); var myOptions = { center: targetLocation, mapTypeId: google.maps.MapTypeId.ROADMAP, zoom: 13, scrollwheel: false, streetViewControl: false, mapTypeControl: false, disableDoubleClickZoom: true, styles: [ { featureType: "all", stylers: [ {saturation: -100} ] } ] } var map = new google.maps.Map($("#map .google-maps")[0], myOptions); directionsDisplay.setMap(map); var marker = new google.maps.Marker({ position: targetLocation, map: map, icon: "marker.png", visible: true }); } A: Use setPosition in your event handler. $(selector).on('click', function(){ newLocation = new google.maps.LatLng(0,0); marker.setPosition( newLocation ); });
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The Blog In addition to the strong rumors we reported yesterday, it has been confirmed from reliable sources that Who Wants to be a Millionaire: Play It! at Disney MGM Studios will close and cease operation on August 19th. This is assumed to make way for the new Midway Mania attraction. Further details on the rumor can be found below in the prior update (the one with the MGM hat).
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Over 1,000 people from Antofagasta in far north to Los Rios in south affected, with some housed in shelters By Rosalba O'Brien SANTIAGO, Aug 9 (Reuters) - Heavy rain and winds hit the southern cone of South America over the weekend, battering the Chilean coastline and leading to the precautionary suspension of work at some mines in the top copper exporter. Over 1,000 people from Antofagasta in the far north to Los Rios in the south of Chile were affected, with some being housed in shelters after being evacuated or losing their homes to floods, and over 120,000 were left without electricity, the emergency service Onemi said on Sunday. Mud landslides wiped out roads in and around the city of Tocopilla in the Antofagasta region, leading to three deaths, while another three were killed in accidents along the coast, local media reported. Over 15 millimeters (0.6 inch) of rain had fallen in six hours in normally bone-dry Antofagasta, the interior ministry said. After months of drought, the rains that began early last week in central Chile and have since spread north have brought some relief to farmers and ski resort owners, but spelled more potential bad news for Chile's key copper mining industry, mostly based in the north of the country and already hit by floods once this year. State-owned Codelco, the world's top copper exporter, said it had suspended operations at Chuquicamata, its second largest mine, from around 2 p.m. local time (1700 GMT) on Sunday as a safety measure. Chuquicamata produced around 340,000 tonnes last year out of Chile's total 5.7 million. Codelco said it had also temporarily stopped operations at its Radomiro Tomic mine during the morning but had resumed work. An ongoing strike has already halted work at its Salvador mine and led to a partial suspension at Ministro Hales. The company did not report problems at El Teniente, its biggest mine. London-listed Chilean miner Antofagasta said all its mines were operating normally. Companies running other mines could not immediately be reached for comment. Meanwhile, Chile's central coast faced some of its heaviest sea swell in over three decades, with waves up to 10 metres (33 feet) high. The seafront along tourist resort Vina del Mar was seriously damaged, with cars and fishing boats smashed. The heavy rains extended into neighboring Argentina, complicating voting in presidential primaries there. The meterological office forecast dry weather in northern Chile for Monday, although more rain is expected for the central part of the country. (Reporting by Rosalba O'Brien; Editing by Eric Walsh) Our Standards: The Thomson Reuters Trust Principles.
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Assessment of Clinical Meaningfulness of Endpoints in the Generation Program by the Insights to Model Alzheimer's Progression in Real Life (iMAP) Study. We are launching the Insights to Model Alzheimer's Progression in Real Life study in parallel with the Alzheimer Prevention Initiative Generation Program. This is a 5-year, multinational, prospective, longitudinal, non-interventional cohort study that will collect data across the spectrum of Alzheimer's disease. The primary objective is to assess the ability of the Alzheimer's Prevention Initiative Cognitive Composite Test Score and Repeatable Battery for the Assessment of Neuropsychological Status to predict clinically meaningful outcomes such as diagnosis of mild cognitive impairment or dementia due to Alzheimer's disease, and change in Clinical Dementia Rating - Global Score. This study is the first large-scale, prospective effort to establish the clinical meaningfulness of cognitive test scores that track longitudinal decline in preclinical Alzheimer's disease. This study is also expected to contribute to our understanding of the relationships among outcomes in different stages of Alzheimer's disease as well as models of individual trajectories during the course of the disease.
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