123 research outputs found

    Time-dependent structural transformation analysis to high-level Petri net model with active state transition diagram

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    <p>Abstract</p> <p>Background</p> <p>With an accumulation of <it>in silico </it>data obtained by simulating large-scale biological networks, a new interest of research is emerging for elucidating how living organism functions over time in cells.</p> <p>Investigating the dynamic features of current computational models promises a deeper understanding of complex cellular processes. This leads us to develop a method that utilizes structural properties of the model over all simulation time steps. Further, user-friendly overviews of dynamic behaviors can be considered to provide a great help in understanding the variations of system mechanisms.</p> <p>Results</p> <p>We propose a novel method for constructing and analyzing a so-called <it>active state transition diagram </it>(ASTD) by using time-course simulation data of a high-level Petri net. Our method includes two new algorithms. The first algorithm extracts a series of subnets (called <it>temporal subnets</it>) reflecting biological components contributing to the dynamics, while retaining positive mathematical qualities. The second one creates an ASTD composed of unique temporal subnets. ASTD provides users with concise information allowing them to grasp and trace how a key regulatory subnet and/or a network changes with time. The applicability of our method is demonstrated by the analysis of the underlying model for circadian rhythms in <it>Drosophila</it>.</p> <p>Conclusions</p> <p>Building ASTD is a useful means to convert a hybrid model dealing with discrete, continuous and more complicated events to finite time-dependent states. Based on ASTD, various analytical approaches can be applied to obtain new insights into not only systematic mechanisms but also dynamics.</p

    ケンチク レコード ノ モクロク ヘンセイ モデル スタンダード シリーズ カラ カンガエル

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    アーカイブズ学に基づく建築レコードの管理に際して、「増加が続く記録の作成量」「個人文書と法人記録が併存する性質」は、事態をより困難にする。本論では、この課題に応じるかたちで考案された「スタンダード・シリーズ」をめぐり、建築レコードの管理事例とアーカイブズ学上の理論に従って評価を試みた。はじめに、「スタンダード・シリーズ」を生み出したカリフォルニア大学バークレー校の1990年代後半のプロジェクトを紹介した。次に、2000年以降のアメリカ・アーキビスト協会の活動および建築レコード目録の作成事例から、「スタンダード・シリーズ」の影響を確認した。最後に、マイケル・クックの理論をヒントにしてアーカイブズ学における機能分類の観点から「スタンダード・シリーズ」を分析し、理解を深めた。その結果、この手法が建築レコードの量と質の課題に対して有効であることに加えて、ユーザビリティを考慮した編成方法であることを明らかにした。There are two challenges for architectural records in archival science:one related to bulk emerging from the creation of mass records nowadays and the other related to human behavior accumulating a combination of personal papers and office records.Based on records management practices and archival science theory for architectural records,this paper evaluates the Standard Series as a method for addressing these challenges.First,this project of the University of California at Berkeley in the late 1990s,is introduced to explain the origin of the method.The impact of the Standard Series on the activities of the Society of American Archivists and on certain catalogs created since 2000 is then examined.Finally,the method is analyzed as a function-based classification system of archival science,with reference to Michael Cook\u27s theory.As a result,we found that the Standard Series is an effective method for addressing quantity and quality challenges of architectural records and can be considered a user-friendly model for researchers.論

    1970ネンダイ ノ ベイコク デ オキタ アーカイブズ ノ ヘンヨウ ト ソノ エイキョウ フランク ボールズ アーカイヴァル アプレイザル カラ サグル

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    本稿では、フランク・ボールズの『アーカイヴァル・アプレイザル』等の米国のアプレイザル研究にそって、1970 年代から20 世紀末までを中心に、米国のアーカイブズの歩みを把握した。その際、各時代の相互関係─40年代から50 年代の連邦政府記録を対象とした試み、70年代のアーカイブズを取り巻く社会環境の変化とアプレイザル対象の拡大、80年代の民間記録を対象とした実践と理論的枠組みの整備、90年代の新たな課題の台頭─に注目して、理解を深めた。ボールズは、このうち1970年代以降にアーカイブズの対象を拡張した米国の固有性を「米国型〈包括的〉視点」と表現した。この「視点」は、欧州の伝統的アーカイブズに比べると特異であるが、現在も続く米国型アーカイブズの独自性をもたらした

    Semantics of Probabilistic Programs using s-Finite Kernels in Coq

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    International audienceProbabilistic programming languages are used to write probabilistic models to make probabilistic inferences. A number of rigorous semantics have recently been proposed that are now available to carry out formal verification of probabilistic programs. In this paper, we extend an existing formalization of measure and integration theory with s-finite kernels, a mathematical structure to interpret typing judgments in the semantics of a probabilistic programming language. The resulting library makes it possible to reason formally about transformations of probabilistic programs and their execution

    ExonMiner: Web service for analysis of GeneChip Exon array data

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    <p>Abstract</p> <p>Background</p> <p>Some splicing isoform-specific transcriptional regulations are related to disease. Therefore, detection of disease specific splice variations is the first step for finding disease specific transcriptional regulations. Affymetrix Human Exon 1.0 ST Array can measure exon-level expression profiles that are suitable to find differentially expressed exons in genome-wide scale. However, exon array produces massive datasets that are more than we can handle and analyze on personal computer.</p> <p>Results</p> <p>We have developed ExonMiner that is the first all-in-one web service for analysis of exon array data to detect transcripts that have significantly different splicing patterns in two cells, e.g. normal and cancer cells. ExonMiner can perform the following analyses: (1) data normalization, (2) statistical analysis based on two-way ANOVA, (3) finding transcripts with significantly different splice patterns, (4) efficient visualization based on heatmaps and barplots, and (5) meta-analysis to detect exon level biomarkers. We implemented ExonMiner on a supercomputer system in order to perform genome-wide analysis for more than 300,000 transcripts in exon array data, which has the potential to reveal the aberrant splice variations in cancer cells as exon level biomarkers.</p> <p>Conclusion</p> <p>ExonMiner is well suited for analysis of exon array data and does not require any installation of software except for internet browsers. What all users need to do is to access the ExonMiner URL <url>http://ae.hgc.jp/exonminer</url>. Users can analyze full dataset of exon array data within hours by high-level statistical analysis with sound theoretical basis that finds aberrant splice variants as biomarkers.</p

    Modification of a loop sequence between α-helices 6 and 7 of virus capsid (CA) protein in a human immunodeficiency virus type 1 (HIV-1) derivative that has simian immunodeficiency virus (SIVmac239) vif and CA α-helices 4 and 5 loop improves replication in cynomolgus monkey cells

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    <p>Abstract</p> <p>Background</p> <p>Human immunodeficiency virus type 1 (HIV-1) productively infects only humans and chimpanzees but not cynomolgus or rhesus monkeys while simian immunodeficiency virus isolated from macaque (SIVmac) readily establishes infection in those monkeys. Several HIV-1 and SIVmac chimeric viruses have been constructed in order to develop an animal model for HIV-1 infection. Construction of an HIV-1 derivative which contains sequences of a SIVmac239 loop between α-helices 4 and 5 (L4/5) of capsid protein (CA) and the entire SIVmac239 <it>vif </it>gene was previously reported. Although this chimeric virus could grow in cynomolgus monkey cells, it did so much more slowly than did SIVmac. It was also reported that intrinsic TRIM5α restricts the post-entry step of HIV-1 replication in rhesus and cynomolgus monkey cells, and we previously demonstrated that a single amino acid in a loop between α-helices 6 and 7 (L6/7) of HIV type 2 (HIV-2) CA determines the susceptibility of HIV-2 to cynomolgus monkey TRIM5α.</p> <p>Results</p> <p>In the study presented here, we replaced L6/7 of HIV-1 CA in addition to L4/5 and <it>vif </it>with the corresponding segments of SIVmac. The resultant HIV-1 derivatives showed enhanced replication capability in established T cell lines as well as in CD8+ cell-depleted primary peripheral blood mononuclear cells from cynomolgus monkey. Compared with the wild type HIV-1 particles, the viral particles produced from a chimeric HIV-1 genome with those two SIVmac loops were less able to saturate the intrinsic restriction in rhesus monkey cells.</p> <p>Conclusion</p> <p>We have succeeded in making the replication of simian-tropic HIV-1 in cynomolgus monkey cells more efficient by introducing into HIV-1 the L6/7 CA loop from SIVmac. It would be of interest to determine whether HIV-1 derivatives with SIVmac CA L4/5 and L6/7 can establish infection of cynomolgus monkeys <it>in vivo</it>.</p

    Irinotecan Plus Mitomycin C as Second-Line Chemotherapy for Advanced Gastric Cancer Resistant to Fluoropyrimidine and Cisplatin: A Retrospective Study

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    Background. S-1 plus cisplatin has been established to be standard first-line chemotherapy for advanced gastric cancer in Japan. The optimal second-line treatment refractory to S-1 plus cisplatin remains unclear. Methods. We retrospectively studied the efficacy, toxicity, and survival of irinotecan plus mitomycin C in patients with advanced gastric cancer refractory to a fluoropyrimidine plus cisplatin. Results. Twenty-four patients were studied. Prior chemotherapy was S-1 plus cisplatin in 15 patients, S-1 plus cisplatin and docetaxel in 8, and 5-fluorouracil plus cisplatin with radiotherapy in 1. The overall response rate was 17.4%. The median overall survival was 8.6 months, and the median progression-free survival was 3.6 months. Grade 3 or 4 toxicities included leukopenia (33%), neutropenia (50%), anemia (33%), thrombocytopenia (4%), anorexia (13%), diarrhea (4%), and febrile neutropenia (13%). Conclusion. A combination of irinotecan and mitomycin C is potentially effective in patients with advanced gastric cancer refractory to a fluoropyrimidine plus cisplatin
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