437 research outputs found

    When do diffusion-limited trajectories become memoryless?

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    Stochastic description of cellular dynamics by the chemical master equation assumes the exponential distribution of intervals between reaction events. Diffusion-limited reactions violate this assumption. Using the example of the target search we investigate the conditions under which a peaked waiting-time distribution can be approximated by the exponential function. We link the steady-state flux and the dynamic property of the diffusion, the mean first-passage time

    Implementation of the Vectorized Position-Specific Iterated Smith-Waterman Algorithm with Heuristic Filtering Algorithm on Cray Architecture

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    ABSTRACT: Smith-Waterman is the algorithm for finding local optimal alignments of two amino acid sequences, but is too slow for use in regular large database scanning. We have implemented SW algorithm on Cray X1 architecture, exploiting vectorization and parallelization. In addition we have proposed heuristic database filtering algorithm, which is particularly well suited for the Cray architecture, exploiting possibilities given by the BMM unit

    Automatic detection of spatio-temporal signaling patterns in cell collectives.

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    Increasing experimental evidence points to the physiological importance of space-time correlations in signaling of cell collectives. From wound healing to epithelial homeostasis to morphogenesis, coordinated activation of biomolecules between cells allows the collectives to perform more complex tasks and to better tackle environmental challenges. To capture this information exchange and to advance new theories of emergent phenomena, we created ARCOS, a computational method to detect and quantify collective signaling. We demonstrate ARCOS on cell and organism collectives with space-time correlations on different scales in 2D and 3D. We made a new observation that oncogenic mutations in the MAPK/ERK and PIK3CA/Akt pathways of MCF10A epithelial cells hyperstimulate intercellular ERK activity waves that are largely dependent on matrix metalloproteinase intercellular signaling. ARCOS is open-source and available as R and Python packages. It also includes a plugin for the napari image viewer to interactively quantify collective phenomena without prior programming experience

    Proteomics analysis of bladder cancer invasion: targeting EIF3D for therapeutic intervention

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    Patients with advanced bladder cancer have poor outcomes, indicating a need for more efficient therapeutic approaches. This study characterizes proteomic changes underlying bladder cancer invasion aiming for the better understanding of disease pathophysiology and identification of drug targets. High resolution liquid chromatography coupled to tandem mass spectrometry analysis of tissue specimens from patients with non-muscle invasive (NMIBC, stage pTa) and muscle invasive bladder cancer (MIBC, stages pT2+) was conducted. Comparative analysis identified 144 differentially expressed proteins between analyzed groups. These included proteins previously associated with bladder cancer and also additional novel such as PGRMC1, FUCA1, BROX and PSMD12, which were further confirmed by immunohistochemistry. Pathway and interactome analysis predicted strong activation in muscle invasive bladder cancer of pathways associated with protein synthesis e.g. eIF2 and mTOR signaling. Knock-down of eukaryotic translation initiation factor 3 subunit D (EIF3D) (overexpressed in muscle invasive disease) in metastatic T24M bladder cancer cells inhibited cell proliferation, migration, and colony formation in vitro and decreased tumor growth in xenograft models. By contrast, knocking down GTP-binding protein Rheb (which is upstream of EIF3D) recapitulated the effects of EIF3D knockdown in vitro, but not in vivo. Collectively, this study represents a comprehensive analysis of NMIBC and MIBC providing a resource for future studies. The results highlight EIF3D as a potential therapeutic target

    Topographical anatomy of the left ventricular summit: implications for invasive procedures

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    Background: Recent clinical reports have emphasized the clinical significance of the left ventricular summit (LVS), a specific triangular epicardial area, as the source of ventricular arrhythmias where radiofrequency ablation is of great difficulty. Materials and methods: The macroscopic morphology of the LVS has been assessed in 80 autopsied and 48 angio-CT human hearts. According to Yamada’s equation, the size was calculated based on the distance to the first, most prominent septal perforator. Results: The size of the LVS varies from 33.69 to 792.2 mm2, is highly variable, and does not correlate with BMI, sex, or age in general. The mean size of the LVS was 287.38 ± 144.95mm2 in autopsied and angio-CT (p=0.44). LVS is mostly disproportionately bisected by cardiac coronary veins to superior – inaccessible and inferior–accessible areas. The superior aspect dominates over the inferior in both groups (p=0.04). The relation between superior and inferior groups determines three possible arrangements: the most common type is superior domination (50.2%), then inferior domination (26.6%), and finally, equal distribution (17.2%). In 10.9 %, the inferior aspect is absent. Only 16.4% of the LVS were empty, without additional trespassing coronary arteries. Conclusions: The difference in size and content of the LVS is significant, with no correlation to any variable. The size depends on the anatomy of the most prominent septal perforator artery. The superior, inaccessible aspect dominates, and the LVS is seldom free from additional coronary vessels, thus making this region hazardous for electrophysiological procedures

    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

    Search for stop and higgsino production using diphoton Higgs boson decays

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    Results are presented of a search for a "natural" supersymmetry scenario with gauge mediated symmetry breaking. It is assumed that only the supersymmetric partners of the top-quark (stop) and the Higgs boson (higgsino) are accessible. Events are examined in which there are two photons forming a Higgs boson candidate, and at least two b-quark jets. In 19.7 inverse femtobarns of proton-proton collision data at sqrt(s) = 8 TeV, recorded in the CMS experiment, no evidence of a signal is found and lower limits at the 95% confidence level are set, excluding the stop mass below 360 to 410 GeV, depending on the higgsino mass
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