969 research outputs found

    Monoidal computer III: A coalgebraic view of computability and complexity

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    Monoidal computer is a categorical model of intensional computation, where many different programs correspond to the same input-output behavior. The upshot of yet another model of computation is that a categorical formalism should provide a much needed high level language for theory of computation, flexible enough to allow abstracting away the low level implementation details when they are irrelevant, or taking them into account when they are genuinely needed. A salient feature of the approach through monoidal categories is the formal graphical language of string diagrams, which supports visual reasoning about programs and computations. In the present paper, we provide a coalgebraic characterization of monoidal computer. It turns out that the availability of interpreters and specializers, that make a monoidal category into a monoidal computer, is equivalent with the existence of a *universal state space*, that carries a weakly final state machine for any pair of input and output types. Being able to program state machines in monoidal computers allows us to represent Turing machines, to capture their execution, count their steps, as well as, e.g., the memory cells that they use. The coalgebraic view of monoidal computer thus provides a convenient diagrammatic language for studying computability and complexity.Comment: 34 pages, 24 figures; in this version: added the Appendi

    Loss of LMOD1 impairs smooth muscle cytocontractility and causes megacystis microcolon intestinal hypoperistalsis syndrome in humans and mice

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    Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is a congenital visceral myopathy characterized by severe dilation of the urinary bladder and defective intestinal motility. The genetic basis of MMIHS has been ascribed to spontaneous and autosomal dominant mutations in actin gamma 2 (ACTG2), a smooth muscle contractile gene. However, evidence suggesting a recessive origin of the disease also exists. Using combined homozygosity mapping and whole exome sequencing, a genetically isolated family was found to carry a premature termination codon in Leiomodin1 (LMOD1), a gene preferentially expressed in vascular and visceral smooth muscle cells. Parents heterozygous for the mutation exhibited no abnormalities, but a child homozygous for the premature termination codon displayed symptoms consistent with MMIHS. We used CRISPR-Cas9 (CRISPR-associated protein) genome editing of Lmod1 to generate a similar premature termination codon. Mice homozygous for the mutation showed loss of LMOD1 protein and pathology consistent with MMIHS, including late gestation expansion of the bladder, hydronephrosis, and rapid demise after parturition. Loss of LMOD1 resulted in a reduction of filamentous actin, elongated cytoskeletal dense bodies, and impaired intestinal smooth muscle contractility. These results define LMOD1 as a disease gene for MMIHS and suggest its role in establishing normal smooth muscle cytoskeletal-contractile coupling

    Pocket Part 1988

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    The 1988 Pocket Part includes a section devoted to “Hofstra Law Fashions,” candid images of students and the law school, and a message from Dean Eric J. Schmertz. The Editor-in-Chief is Pamela D. Faison.https://scholarlycommons.law.hofstra.edu/yearbooks/1013/thumbnail.jp

    Evaluation of current prediction models for Lynch syndrome: updating the PREMM5 model to identify PMS2 mutation carriers

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    Until recently, no prediction models for Lynch syndrome (LS) had been validated for PMS2 mutation carriers. We aimed to evaluate MMRpredict and PREMM5 in a clinical cohort and for PMS2 mutation carriers specifically. In a retrospective, clinic-based cohort we calculated predictions for LS according to MMRpredict and PREMM5. The area under the operator receiving characteristic curve (AU

    Models of HoTT and the Constructive View of Theories

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    Homotopy Type theory and its Model theory provide a novel formal semantic framework for representing scientific theories. This framework supports a constructive view of theories according to which a theory is essentially characterised by its methods. The constructive view of theories was earlier defended by Ernest Nagel and a number of other philosophers of the past but available logical means did not allow these people to build formal representational frameworks that implement this view

    Validation of the present day annual cycle in heavy precipitation over the British Islands simulated by 14 RCMs

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    The representation of the annual cycle of heavy daily precipitation events across the United Kingdom within 14 regional climate models (RCMs) and the European observation data set (E-OBS) over the 1961-2000 period is investigated. We model extreme precipitation as an inhomogeneous Poisson process with a non-stationary threshold and use a sinusoidal model for the location and scale parameter of the corresponding generalized extreme value distribution and a constant shape parameter. First we fit the statistical model to the UK Met Office 5 km gridded precipitation data set (UKMO). Second the statistical model is fitted to 14 reanalysis driven 25 km resolution RCMs from the ENSEMBLES project and to E-OBS. The resulting characteristics from the RCMs and from E-OBS are compared with those from UKMO. We study the peak time of the annual cycle of the monthly return levels, the relative amplitude of their annual cycle and the relative bias of their absolute values. We show that the performance of the RCMs depends strongly on the region. The RCMs show deficits in modeling the characteristics of the annual cycle, especially in modeling its relative amplitude and mainly in Eastern England. However the peak time of the annual cycle is adequately simulated by most RCMs. E-OBS exhibits considerable biases in the absolute values of all monthly return levels, but the relative amplitude and the phase of the annual cycle of heavy precipitation are well represented. Our results imply that studies which rely on the explicit annual cycle of simulated heavy precipitation should be carefully considered

    Transmission of HIV drug resistance and the predicted effect on current first-line regimens in Europe

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    BACKGROUND: Numerous studies have shown that baseline drug resistance patterns may influence the outcome of antiretroviral therapy. Therefore guidelines recommend drug resistance testing to guide the choice of initial regimen. In addition to optimizing individual patient management, these baseline resistance data enable transmitted drug resistance (TDR) to be surveyed for public health purposes. The SPREAD-program systematically collects data to gain insight into TDR occurring in Europe since 2001. METHODS: Demographic, clinical and virological data from 4,140 antiretroviral-naive HIV-infected individuals from 26 countries who were newly diagnosed between 2008 and 2010 were analyzed. Evidence of TDR was defined using the WHO list for surveillance of drug resistance mutations. Prevalence of TDR was assessed over time by comparing the results to SPREAD data from 2002-2007. Baseline susceptibility to antiretroviral drugs was predicted using Stanford HIVdb v7.0. RESULTS: The overall prevalence of TDR did not change significantly over time and was 8.3% (95%CI 7.2-9.5) in 2008-2010. The most frequent indicators of TDR were NRTI-mutations (4.5%), followed by NNRTI-mutations (2.9%) and PI-mutations (2.0%). Baseline mutations were most predictive of reduced susceptibility to initial NNRTI-based regimens: 4.5% and 6.5% of patient isolates were predicted to have resistance to regimens containing efavirenz or rilpivirine respectively, independent of current NRTI backbones. CONCLUSIONS: Although TDR was highest for NRTIs, the impact of baseline drug resistance patterns on susceptibility was largest for NNRTIs. The prevalence of TDR assessed by epidemiological surveys does not clearly indicate to what degree susceptibility to different drug classes is affecte
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