145 research outputs found

    Black Male Student-Athletes and Racial Inequities in NCAA Division I College Sports

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    The purpose of this report is to make transparent racial inequities in NCAA Division I college sports. Specifically, the authors offer a four-year analysis of Black men's representation on football and basketball teams versus their representation in the undergraduate student body on each campus. The report concludes with recommendations for the NCAA and commissioners of the six major sports conferences, college and university leaders, coaches and athletics directors, journalists, and Black male student-athletes and their families

    Systemic AAV vectors for widespread and targeted gene delivery in rodents

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    We recently developed adeno-associated virus (AAV) capsids to facilitate efficient and noninvasive gene transfer to the central and peripheral nervous systems. However, a detailed protocol for generating and systemically delivering novel AAV variants was not previously available. In this protocol, we describe how to produce and intravenously administer AAVs to adult mice to specifically label and/or genetically manipulate cells in the nervous system and organs, including the heart. The procedure comprises three separate stages: AAV production, intravenous delivery, and evaluation of transgene expression. The protocol spans 8 d, excluding the time required to assess gene expression, and can be readily adopted by researchers with basic molecular biology, cell culture, and animal work experience. We provide guidelines for experimental design and choice of the capsid, cargo, and viral dose appropriate for the experimental aims. The procedures outlined here are adaptable to diverse biomedical applications, from anatomical and functional mapping to gene expression, silencing, and editing

    Relative Burden of Large CNVs on a Range of Neurodevelopmental Phenotypes

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    While numerous studies have implicated copy number variants (CNVs) in a range of neurological phenotypes, the impact relative to disease severity has been difficult to ascertain due to small sample sizes, lack of phenotypic details, and heterogeneity in platforms used for discovery. Using a customized microarray enriched for genomic hotspots, we assayed for large CNVs among 1,227 individuals with various neurological deficits including dyslexia (376), sporadic autism (350), and intellectual disability (ID) (501), as well as 337 controls. We show that the frequency of large CNVs (>1 Mbp) is significantly greater for ID–associated phenotypes compared to autism (p = 9.58×10−11, odds ratio = 4.59), dyslexia (p = 3.81×10−18, odds ratio = 14.45), or controls (p = 2.75×10−17, odds ratio = 13.71). There is a striking difference in the frequency of rare CNVs (>50 kbp) in autism (10%, p = 2.4×10−6, odds ratio = 6) or ID (16%, p = 3.55×10−12, odds ratio = 10) compared to dyslexia (2%) with essentially no difference in large CNV burden among dyslexia patients compared to controls. Rare CNVs were more likely to arise de novo (64%) in ID when compared to autism (40%) or dyslexia (0%). We observed a significantly increased large CNV burden in individuals with ID and multiple congenital anomalies (MCA) compared to ID alone (p = 0.001, odds ratio = 2.54). Our data suggest that large CNV burden positively correlates with the severity of childhood disability: ID with MCA being most severely affected and dyslexics being indistinguishable from controls. When autism without ID was considered separately, the increase in CNV burden was modest compared to controls (p = 0.07, odds ratio = 2.33)

    Detection of astrophysical tau neutrino candidates in IceCube

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    High-energy tau neutrinos are rarely produced in atmospheric cosmic-ray showers or at cosmic particle accelerators, but are expected to emerge during neutrino propagation over cosmic distances due to flavor mixing. When high energy tau neutrinos interact inside the IceCube detector, two spatially separated energy depositions may be resolved, the first from the charged current interaction and the second from the tau lepton decay. We report a novel analysis of 7.5 years of IceCube data that identifies two candidate tau neutrinos among the 60 “High-Energy Starting Events” (HESE) collected during that period. The HESE sample offers high purity, all-sky sensitivity, and distinct observational signatures for each neutrino flavor, enabling a new measurement of the flavor composition. The measured astrophysical neutrino flavor composition is consistent with expectations, and an astrophysical tau neutrino flux is indicated at 2.8σ\sigma significance

    Understanding the retinal basis of vision across species

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    The vertebrate retina first evolved some 500 million years ago in ancestral marine chordates. Since then, the eyes of different species have been tuned to best support their unique visuoecological lifestyles. Visual specializations in eye designs, large-scale inhomogeneities across the retinal surface and local circuit motifs mean that all species' retinas are unique. Computational theories, such as the efficient coding hypothesis, have come a long way towards an explanation of the basic features of retinal organization and function; however, they cannot explain the full extent of retinal diversity within and across species. To build a truly general understanding of vertebrate vision and the retina's computational purpose, it is therefore important to more quantitatively relate different species' retinal functions to their specific natural environments and behavioural requirements. Ultimately, the goal of such efforts should be to build up to a more general theory of vision

    Measurement of Astrophysical Tau Neutrinos in IceCube's High-Energy Starting Events

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    We present the results of a search for astrophysical tau neutrinos in 7.5 years of IceCube's high-energy starting event data. At high energies, two energy depositions stemming from the tau neutrino charged-current interaction and subsequent tau lepton decay may be resolved. We report the first detection of two such events, with probabilities of ∌76%\sim 76\% and ∌98%\sim 98\% of being produced by astrophysical tau neutrinos. The resultant astrophysical neutrino flavor measurement is consistent with expectations, disfavoring a no-astrophysical tau neutrino flux scenario with 2.8σ\sigma significance.Comment: This article is supported by a long-form paper that discusses the high-energy starting event selection titled: "The IceCube high-energy starting event sample: Description and flux characterization with 7.5 years of data.

    A search for time-dependent astrophysical neutrino emission with IceCube data from 2012 to 2017

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    High-energy neutrinos are unique messengers of the high-energy universe, tracing the processes of cosmic-ray acceleration. This paper presents analyses focusing on time-dependent neutrino point-source searches. A scan of the whole sky, making no prior assumption about source candidates, is performed, looking for a space and time clustering of high-energy neutrinos in data collected by the IceCube Neutrino Observatory between 2012 and 2017. No statistically significant evidence for a time-dependent neutrino signal is found with this search during this period since all results are consistent with the background expectation. Within this study period, the blazar 3C 279, showed strong variability, inducing a very prominent gamma-ray flare observed in 2015 June. This event motivated a dedicated study of the blazar, which consists of searching for a time-dependent neutrino signal correlated with the gamma-ray emission. No evidence for a time-dependent signal is found. Hence, an upper limit on the neutrino fluence is derived, allowing us to constrain a hadronic emission model

    Dendritic cells in cancer immunology and immunotherapy

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    Dendritic cells (DCs) are a diverse group of specialized antigen-presenting cells with key roles in the initiation and regulation of innate and adaptive immune responses. As such, there is currently much interest in modulating DC function to improve cancer immunotherapy. Many strategies have been developed to target DCs in cancer, such as the administration of antigens with immunomodulators that mobilize and activate endogenous DCs, as well as the generation of DC-based vaccines. A better understanding of the diversity and functions of DC subsets and of how these are shaped by the tumour microenvironment could lead to improved therapies for cancer. Here we will outline how different DC subsets influence immunity and tolerance in cancer settings and discuss the implications for both established cancer treatments and novel immunotherapy strategies.S.K.W. is supported by a European Molecular Biology Organization Long- Term Fellowship (grant ALTF 438– 2016) and a CNIC–International Postdoctoral Program Fellowship (grant 17230–2016). F.J.C. is the recipient of a PhD ‘La Caixa’ fellowship. Work in the D.S. laboratory is funded by the CNIC, by the European Research Council (ERC Consolidator Grant 2016 725091), by the European Commission (635122-PROCROP H2020), by the Ministerio de Ciencia, Innovación e Universidades (MCNU), Agencia Estatal de Investigación and Fondo Europeo de Desarrollo Regional (FEDER) (SAF2016-79040-R), by the Comunidad de Madrid (B2017/BMD-3733 Immunothercan- CM), by FIS- Instituto de Salud Carlos III, MCNU and FEDER (RD16/0015/0018-REEM), by Acteria Foundation, by Atresmedia (Constantes y Vitales prize) and by Fundació La Marató de TV3 (201723). The CNIC is supported by the Instituto de Salud Carlos III, the MCNU and the Pro CNIC Foundation, and is a Severo Ochoa Centre of Excellence (SEV-2015-0505).S

    LeptonInjector and LeptonWeighter: A neutrino event generator and weighter for neutrino observatories

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    We present a high-energy neutrino event generator, called LeptonInjector, alongside an event weighter, called LeptonWeighter. Both are designed for large-volume Cherenkov neutrino telescopes such as IceCube. The neutrino event generator allows for quick and flexible simulation of neutrino events within and around the detector volume, and implements the leading Standard Model neutrino interaction processes relevant for neutrino observatories: neutrino-nucleon deep-inelastic scattering and neutrino-electron annihilation. In this paper, we discuss the event generation algorithm, the weighting algorithm, and the main functions of the publicly available code, with examples.Comment: 28 pages, 10 figures, 3 table
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