787 research outputs found

    Determinantal Beam Search

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    Beam search is a go-to strategy for decoding neural sequence models. The algorithm can naturally be viewed as a subset optimization problem, albeit one where the corresponding set function does not reflect interactions between candidates. Empirically, this leads to sets often exhibiting high overlap, e.g., strings may differ by only a single word. Yet in use-cases that call for multiple solutions, a diverse or representative set is often desired. To address this issue, we propose a reformulation of beam search, which we call determinantal beam search. Determinantal beam search has a natural relationship to determinantal point processes (DPPs), models over sets that inherently encode intra-set interactions. By posing iterations in beam search as a series of subdeterminant maximization problems, we can turn the algorithm into a diverse subset selection process. In a case study, we use the string subsequence kernel to explicitly encourage n-gram coverage in text generated from a sequence model. We observe that our algorithm offers competitive performance against other diverse set generation strategies in the context of language generation, while providing a more general approach to optimizing for diversity

    Expression, regulation and function of phosphofructo-kinase/fructose-biphosphatases (PFKFBs) in glucocorticoid-induced apoptosis of acute lymphoblastic leukemia cells

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    <p>Abstract</p> <p>Background</p> <p>Glucocorticoids (GCs) cause apoptosis and cell cycle arrest in lymphoid cells and constitute a central component in the therapy of lymphoid malignancies, most notably childhood acute lymphoblastic leukemia (ALL). PFKFB2 (6-phosphofructo-2-kinase/fructose-2,6-biphosphatase-2), a kinase controlling glucose metabolism, was identified by us previously as a GC response gene in expression profiling analyses performed in children with ALL during initial systemic GC mono-therapy. Since deregulation of glucose metabolism has been implicated in apoptosis induction, this gene and its relatives, PFKFB1, 3, and 4, were further analyzed.</p> <p>Methods</p> <p>Gene expression analyses of isolated lymphoblasts were performed on Affymetrix HGU133 Plus 2.0 microarrays. GCRMA normalized microarray data were analyzed using R-Bioconductor packages version 2.5. Functional gene analyses of <it>PFKFB2-15A </it>and <it>-15B </it>isoforms were performed by conditional gene over-expression experiments in the GC-sensitive T-ALL model CCRF-CEM.</p> <p>Results</p> <p>Expression analyses in additional ALL children, non-leukemic individuals and leukemic cell lines confirmed frequent <it>PFKFB2 </it>induction by GC in most systems sensitive to GC-induced apoptosis, particularly T-ALL cells. The 3 other family members, in contrast, were either absent or only weakly expressed (<it>PFKFB1 </it>and <it>4</it>) or not induced by GC (<it>PFKFB3</it>). Conditional PFKFB2 over-expression in the CCRF-CEM T-ALL <it>in vitro </it>model revealed that its 2 splice variants (PFKFB2-15A and PFKFB2-15B) had no detectable effect on cell survival. Moreover, neither PFKFB2 splice variant significantly affected sensitivity to, or kinetics of, GC-induced apoptosis.</p> <p>Conclusions</p> <p>Our data suggest that, at least in the model system investigated, PFKFB2 is not an essential upstream regulator of the anti-leukemic effects of GC.</p

    Factors influencing the in vitro maturation (IVM) of human oocyte

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    In vitro maturation (IVM) of oocytes is a promising assisted reproductive technology (ART) deemed as a simple and safe procedure. It is mainly used in patients with impaired oocyte maturation and in fertility preservation for women facing the risk of losing fertility. However, to date, it is still not widely used in clinical practice because of its underperformance. The influencing factors, such as biphasic IVM system, culture medium, and the supplementation, have a marked effect on the outcomes of oocyte IVM. However, the role of different culture media, supplements, and follicular priming regimens in oocyte IVM have yet to be fully clarified and deserve further investigation

    FAM111A is a novel molecular marker for oocyte aging

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    Aging is the main cause of decline in oocyte quality, which can further trigger the failure of assisted reproductive technology (ART). Exploring age-related genes in oocytes is an important way to investigate the molecular mechanisms involved in oocyte aging. To provide novel insight into this field, we performed a pooled analysis of publicly available datasets, using the overlapping results of two statistical methods on two Gene Expression Omnibus (GEO) datasets. The methods utilized in the current study mainly include Spearman rank correlation, the Wilcoxon signed-rank test, t-tests, Venn diagrams, Gene Ontology (GO), Protein–Protein Interaction (PPI), Gene Set Enrichment Analysis (GSEA), Gene Set Variation Analysis (GSVA), and receiver operating characteristic (ROC) curve analysis. We identified hundreds of age-related genes across different gene expression datasets of in vitro maturation-metaphase II (IVM-MII) oocytes. Age-related genes in IVM-MII oocytes were involved in the biological processes of cellular metabolism, DNA replication, and histone modifications. Among these age-related genes, FAM111A expression presented a robust correlation with age, seen in the results of different statistical methods and different datasets. FAM111A is associated with the processes of chromosome segregation and cell cycle regulation. Thus, this enzyme is potentially an interesting novel marker for the aging of oocytes, and warrants further mechanistic study

    HnRNP L and L-like cooperate in multiple-exon regulation of CD45 alternative splicing

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    CD45 encodes a trans-membrane protein-tyrosine phosphatase expressed in diverse cells of the immune system. By combinatorial use of three variable exons 4–6, isoforms are generated that differ in their extracellular domain, thereby modulating phosphatase activity and immune response. Alternative splicing of these CD45 exons involves two heterogeneous ribonucleoproteins, hnRNP L and its cell-type specific paralog hnRNP L-like (LL). To address the complex combinatorial splicing of exons 4–6, we investigated hnRNP L/LL protein expression in human B-cells in relation to CD45 splicing patterns, applying RNA-Seq. In addition, mutational and RNA-binding analyses were carried out in HeLa cells. We conclude that hnRNP LL functions as the major CD45 splicing repressor, with two CA elements in exon 6 as its primary target. In exon 4, one element is targeted by both hnRNP L and LL. In contrast, exon 5 was never repressed on its own and only co-regulated with exons 4 and 6. Stable L/LL interaction requires CD45 RNA, specifically exons 4 and 6. We propose a novel model of combinatorial alternative splicing: HnRNP L and LL cooperate on the CD45 pre-mRNA, bridging exons 4 and 6 and looping out exon 5, thereby achieving full repression of the three variable exons

    Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

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    Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis

    Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

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    Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio

    Juxtaposing BTE and ATE – on the role of the European insurance industry in funding civil litigation

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    One of the ways in which legal services are financed, and indeed shaped, is through private insurance arrangement. Two contrasting types of legal expenses insurance contracts (LEI) seem to dominate in Europe: before the event (BTE) and after the event (ATE) legal expenses insurance. Notwithstanding institutional differences between different legal systems, BTE and ATE insurance arrangements may be instrumental if government policy is geared towards strengthening a market-oriented system of financing access to justice for individuals and business. At the same time, emphasizing the role of a private industry as a keeper of the gates to justice raises issues of accountability and transparency, not readily reconcilable with demands of competition. Moreover, multiple actors (clients, lawyers, courts, insurers) are involved, causing behavioural dynamics which are not easily predicted or influenced. Against this background, this paper looks into BTE and ATE arrangements by analysing the particularities of BTE and ATE arrangements currently available in some European jurisdictions and by painting a picture of their respective markets and legal contexts. This allows for some reflection on the performance of BTE and ATE providers as both financiers and keepers. Two issues emerge from the analysis that are worthy of some further reflection. Firstly, there is the problematic long-term sustainability of some ATE products. Secondly, the challenges faced by policymakers that would like to nudge consumers into voluntarily taking out BTE LEI

    Penilaian Kinerja Keuangan Koperasi di Kabupaten Pelalawan

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    This paper describe development and financial performance of cooperative in District Pelalawan among 2007 - 2008. Studies on primary and secondary cooperative in 12 sub-districts. Method in this stady use performance measuring of productivity, efficiency, growth, liquidity, and solvability of cooperative. Productivity of cooperative in Pelalawan was highly but efficiency still low. Profit and income were highly, even liquidity of cooperative very high, and solvability was good

    Mechanical stability of the CMS strip tracker measured with a laser alignment system

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