943 research outputs found

    Constitutional Crisis over the Proposed Supreme Court for the United Kingdom

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    The International Contracting Practices Survey Project: an Empirical Study of the Value and Utility of the United Nations Convention On the International Sale Of Goods (Cisg) and the UNIDROIT Principles of International Commercial Contracts to Practitione

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    In an era of globalization it is perplexing that so many U.S. practitioners, jurists, and legal academics continue to view contract issues as governed exclusively by state common law and the Uniform Commercial Code. In essence, a significant number of lawyers may be defaulting to the wrong law, in the absence of an effective choice of law clause, when trying to determine the rights and responsibilities arising out of international commercial transactions. The object of the International Commercial Contracting Practices Survey Project was to learn more about how and why this occurs

    Compensation to a police woman for the reassignation of her police dog : Keohane vs. Commissioner of Police for the Metropolis ET/3300265/2011 & ET/3300293/2012 19 September 2012

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    Una mujer policía fue indemnizada por decisión de un Tribunal laboral inglés como consecuencia del hecho de que el departamento de policía reasignó su perro policía, indemnización que fue obtenida en el marco de una demanda de discriminación interpuesta debido a la baja maternal de la policía.A policewoman won compensation in an English employment tribunal when the police department reassigned her police dog, in connection with a discrimination claim regarding her maternity leave

    Use of a targeted, combinatorial next-generation sequencing approach for the study of bicuspid aortic valve

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    BACKGROUND: Bicuspid aortic valve (BAV) is the most common type of congenital heart disease with a population prevalence of 1-2%. While BAV is known to be highly heritable, mutations in single genes (such as GATA5 and NOTCH1) have been reported in few human BAV cases. Traditional gene sequencing methods are time and labor intensive, while next-generation high throughput sequencing remains costly for large patient cohorts and requires extensive bioinformatics processing. Here we describe an approach to targeted multi-gene sequencing with combinatorial pooling of samples from BAV patients. METHODS: We studied a previously described cohort of 78 unrelated subjects with echocardiogram-identified BAV. Subjects were identified as having isolated BAV or BAV associated with coarctation of aorta (BAV-CoA). BAV cusp fusion morphology was defined as right-left cusp fusion, right non-coronary cusp fusion, or left non-coronary cusp fusion. Samples were combined into 19 pools using a uniquely overlapping combinatorial design; a given mutation could be attributed to a single individual on the basis of which pools contained the mutation. A custom gene capture of 97 candidate genes was sequenced on the Illumina HiSeq 2000. Multistep bioinformatics processing was performed for base calling, variant identification, and in-silico analysis of putative disease-causing variants. RESULTS: Targeted capture identified 42 rare, non-synonymous, exonic variants involving 35 of the 97 candidate genes. Among these variants, in-silico analysis classified 33 of these variants as putative disease-causing changes. Sanger sequencing confirmed thirty-one of these variants, found among 16 individuals. There were no significant differences in variant burden among BAV fusion phenotypes or isolated BAV versus BAV-CoA. Pathway analysis suggests a role for the WNT signaling pathway in human BAV. CONCLUSION: We successfully developed a pooling and targeted capture strategy that enabled rapid and cost effective next generation sequencing of target genes in a large patient cohort. This approach identified a large number of putative disease-causing variants in a cohort of patients with BAV, including variants in 26 genes not previously associated with human BAV. The data suggest that BAV heritability is complex and polygenic. Our pooling approach saved over $39,350 compared to an unpooled, targeted capture sequencing strategy

    Modeling the transmission and thermal emission in a pupil image behind the Keck II adaptive optics system

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    The design and performance of astronomical instruments depend critically on the total system throughput as well as the background emission from the sky and instrumental sources. In designing a pupil stop for background- limited imaging, one seeks to balance throughput and background rejection to optimize measurement signal-to-noise ratios. Many sources affect transmission and emission in infrared imaging behind the Keck Observatory’s adaptive optics systems, such as telescope segments, segment gaps, secondary support structure, and AO bench optics. Here we describe an experiment, using the pupil-viewing mode of NIRC2, to image the pupil plane as a function of wavelength. We are developing an empirical model of throughput and background emission as a function of position in the pupil plane. This model will be used in part to inform the optimal design of cold pupils in future instruments, such as the new imaging camera for OSIRIS
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