3,035 research outputs found

    Prediction of CsrA-regulating small RNAs in bacteria and their experimental verification in Vibrio fischeri

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    The role of small RNAs as critical components of global regulatory networks has been highlighted by several recent studies. An important class of such small RNAs is represented by CsrB and CsrC of Escherichia coli, which control the activity of the global regulator CsrA. Given the critical role played by CsrA in several bacterial species, an important problem is the identification of CsrA-regulating small RNAs. In this paper, we develop a computer program (CSRNA_FIND) designed to locate potential CsrA-regulating small RNAs in bacteria. Using CSRNA_FIND to search the genomes of bacteria having homologs of CsrA, we identify all the experimentally known CsrA-regulating small RNAs and also make predictions for several novel small RNAs. We have verified experimentally our predictions for two CsrA-regulating small RNAs in Vibrio fischeri. As more genomes are sequenced, CSRNA_FIND can be used to locate the corresponding small RNAs that regulate CsrA homologs. This work thus opens up several avenues of research in understanding the mode of CsrA regulation through small RNAs in bacteria

    Teaching with Big Data: Report from the 2016 Society for Neuroscience Teaching Workshop

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    As part of a series of workshops on teaching neuroscience at the Society for Neuroscience annual meetings, William Grisham and Richard Olivo organized the 2016 workshop on Teaching Neuroscience with Big Data. This article presents a summary of that workshop. Speakers provided overviews of open datasets that could be used in teaching undergraduate courses. These included resources that already appear in educational settings, including the Allen Brain Atlas (presented by Joshua Brumberg and Terri Gilbert), and the Mouse Brain Library and GeneNetwork (presented by Robert Williams). Other resources, such as NeuroData (presented by William R. Gray Roncal), and OpenFMRI, NeuroVault, and Neurosynth (presented by Russell Poldrack) have not been broadly utilized by the neuroscience education community but offer obvious potential. Finally, William Grisham discussed the iNeuro Project, an NSF-sponsored effort to develop the necessary curriculum for preparing students to handle Big Data. Linda Lanyon further elaborated on the current state and challenges in educating students to deal with Big Data and described some training resources provided by the International Neuroinformatics Coordinating Facility. Neuroinformatics is a subfield of neuroscience that deals with data utilizing analytical tools and computational models. The feasibility of offering neuroinformatics programs at primarily undergraduate institutions was also discussed

    System Safety Engineering for Social and Ethical ML Risks: A Case Study

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    Governments, industry, and academia have undertaken efforts to identify and mitigate harms in ML-driven systems, with a particular focus on social and ethical risks of ML components in complex sociotechnical systems. However, existing approaches are largely disjointed, ad-hoc and of unknown effectiveness. Systems safety engineering is a well established discipline with a track record of identifying and managing risks in many complex sociotechnical domains. We adopt the natural hypothesis that tools from this domain could serve to enhance risk analyses of ML in its context of use. To test this hypothesis, we apply a "best of breed" systems safety analysis, Systems Theoretic Process Analysis (STPA), to a specific high-consequence system with an important ML-driven component, namely the Prescription Drug Monitoring Programs (PDMPs) operated by many US States, several of which rely on an ML-derived risk score. We focus in particular on how this analysis can extend to identifying social and ethical risks and developing concrete design-level controls to mitigate them.Comment: 14 pages, 5 figures, 3 tables. Accepted to 36th Conference on Neural Information Processing Systems, Workshop on ML Safety (NeurIPS 2022

    The Transit Light Curve Project. VII. The Not-So-Bloated Exoplanet HAT-P-1b

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    We present photometry of the G0 star HAT-P-1 during six transits of its close-in giant planet, and we refine the estimates of the system parameters. Relative to Jupiter's properties, HAT-P-1b is 1.20 +/- 0.05 times larger and its surface gravity is 2.7 +/- 0.2 times weaker. Although it remains the case that HAT-P-1b is among the least dense of the known sample of transiting exoplanets, its properties are in accord with previously published models of strongly irradiated, coreless, solar-composition giant planets. The times of the transits have a typical accuracy of 1 min and do not depart significantly from a constant period.Comment: To appear in AJ [19pg, 3 figures]. New co-author added. Minor revisions to match published versio

    Detector dead-time effects and paralyzability in high-speed quantum key distribution

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    Recent advances in quantum key distribution (QKD) have given rise to systems that operate at transmission periods significantly shorter than the dead times of their component single-photon detectors. As systems continue to increase in transmission rate, security concerns associated with detector dead times can limit the production rate of sifted bits. We present a model of high-speed QKD in this limit that identifies an optimum transmission rate for a system with given link loss and detector response characteristics

    Ethnically diverse urban transmission networks of Neisseria gonorrhoeae without evidence of HIV serosorting

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    Objective We aimed to characterise gonorrhoea transmission patterns in a diverse urban population by linking genomic, epidemiological and antimicrobial susceptibility data. Methods Neisseria gonorrhoeae isolates from patients attending sexual health clinics at Barts Health NHS Trust, London, UK, during an eleven-month period underwent whole-genome sequencing and antimicrobial susceptibility testing. We combined laboratory and patient data to investigate the transmission network structure. Results One hundred and fifty-eight isolates from 158 patients were available with associated descriptive data. One hundred and twenty-nine (82%) patients identified as male and 25 (16%) as female; 4 (3%) records lacked gender information. Self-described ethnicities were: 51 (32%) English/Welsh/Scottish; 33 (21%) White, other; 23 (15%) Black British/Black African/Black, other; 12 (8%) Caribbean; 9 (6%) South Asian; 6 (4%) mixed ethnicity; 10 (6%) other; data were missing for 14 (9%). Self-reported sexual orientations were 82 (52%) men who have sex with men; 49 (31%) heterosexual; 2 (1%) bisexual; data missing for 25 individuals. Twenty-two (14%) patients were HIV-positive. Whole genome sequence data were generated for 151 isolates, which linked 75 (50%) patients to at least one other case. Using sequencing data, we found no evidence of transmission networks related to specific ethnic groups (p=0.64) or of HIV serosorting (p=0.35). Of 82 MSM/bisexual patients with sequencing data, 45 (55%) belonged to clusters of ≥2 cases, compared to 16/44 (36%) heterosexuals with sequencing data (p=0.06). Conclusion We demonstrate links between 50% of patients in transmission networks using a relatively small sample in a large cosmopolitan city. We found no evidence of HIV serosorting. Our results do not support assortative selectivity as an explanation for differences in gonorrhoea incidence between ethnic groups

    Syntaxin 8 regulates platelet dense granule secretion, aggregation, and thrombus stability.

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    Platelet secretion not only drives thrombosis and hemostasis, but also mediates a variety of other physiological and pathological processes. The ubiquitous SNARE machinery and a number of accessory proteins have been implicated in regulating secretion in platelet. Although several platelet SNAREs have been identified, further members of the SNARE family may be needed to fine-tune platelet secretion. In this study we identified expression of the t-SNARE syntaxin 8 (STX8) (Qc SNARE) in mouse and human platelets. In mouse studies, whereas STX8 was not essential for α-granule or lysosome secretion, Stx8(-/-) platelets showed a significant defect in dense granule secretion in response to thrombin and CRP. This was most pronounced at intermediate concentrations of agonists. They also showed an aggregation defect that could be rescued with exogenous ADP and increased embolization in Stx8(-/-) mice in vivo consistent with an important autocrine and paracrine role for ADP in aggregation and thrombus stabilization. STX8 therefore specifically contributes to dense granule secretion and represents another member of a growing family of genes that play distinct roles in regulating granule release from platelets and thus platelet function in thrombosis and hemostasis

    Evidence for Local Regulatory Control of Escape from Imprinted X Chromosome Inactivation

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    X chromosome inactivation (XCI) is an epigenetic process that almost completely inactivates one of two X chromosomes in somatic cells of mammalian females. A few genes are known to escape XCI and the mechanism for this escape remains unclear. Here, using mouse trophoblast stem (TS) cells, we address whether particular chromosomal interactions facilitate escape from imprinted XCI. We demonstrate that promoters of genes escaping XCI do not congregate to any particular region of the genome in TS cells. Further, the escape status of a gene was uncorrelated with the types of genomic features and gene activity located in contacted regions. Our results suggest that genes escaping imprinted XCI do so by using the same regulatory sequences as their expressed alleles on the active X chromosome. We suggest a model where regulatory control of escape from imprinted XCI is mediated by genomic elements located in close linear proximity to escaping genes

    fourSig: a method for determining chromosomal interactions in 4C-Seq data

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    The ability to correlate chromosome conformation and gene expression gives a great deal of information regarding the strategies used by a cell to properly regulate gene activity. 4C-Seq is a relatively new and increasingly popular technology where the set of genomic interactions generated by a single point in the genome can be determined. 4C-Seq experiments generate large, complicated data sets and it is imperative that signal is properly distinguished from noise. Currently, there are a limited number of methods for analyzing 4C-Seq data. Here, we present a new method, fourSig, which in addition to being precise and simple to use also includes a new feature that prioritizes detected interactions. Our results demonstrate the efficacy of fourSig with previously published and novel 4C-Seq data sets and show that our significance prioritization correlates with the ability to reproducibly detect interactions among replicates
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