74 research outputs found

    Exploiting Semi-Directional Transceivers for Localization in Communication Systems

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    Localization is the process of determining relative, as well as absolute, positions of communicating devices. Traditionally, the process is conducted using range or directional estimates. In contrast, this research uses weak information to form relatively tight bounds on possible locations of communicating devices. Under certain conditions, achieved location estimation results are strong. However, these results are highly sensitive to the operating conditions of the proposed networks. More significant results were obtained from specialized cases and that the application yields somewhat limited information for a general randomized network topology. Feasible localization results were found to be attainable but not necessarily practical for multiple experiments. This is due to the brute force nature of the implemented localization algorithm which experiences an exponential increase in runtime as the number of nodes increases

    A regional, early spring bloom of Phaeocystis pouchetii on the New England continental shelf

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    Author Posting. © American Geophysical Union, 2021. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research: Oceans 126(2), (2021): e2020JC016856, https://doi.org/10.1029/2020JC016856.The genus Phaeocystis is distributed globally and has considerable ecological, biogeochemical, and societal impacts. Understanding its distribution, growth and ecological impacts has been limited by lack of extensive observations on appropriate scales. In 2018, we investigated the biological dynamics of the New England continental shelf and encountered a substantial bloom of Phaeocystis pouchetii. Based on satellite imagery during January through April, the bloom extended over broad expanses of the shelf; furthermore, our observations demonstrated that it reached high biomass levels, with maximum chlorophyll concentrations exceeding 16 ”g L−1 and particulate organic carbon levels > 95 ”mol L−1. Initially, the bloom was largely confined to waters with temperatures <6°C, which in turn were mostly restricted to shallow areas near the coast. As the bloom progressed, it appeared to sink into the bottom boundary layer; however, enough light and nutrients were available for growth. The bloom was highly productive (net community production integrated through the mixed layer from stations within the bloom averaged 1.16 g C m−2 d−1) and reduced nutrient concentrations considerably. Long‐term coastal observations suggest that Phaeocystis blooms occur sporadically in spring on Nantucket Shoals and presumably expand onto the continental shelf. Based on the distribution of Phaeocystis during our study, we suggest that it can have a significant impact on the overall productivity and ecology of the New England shelf during the winter/spring transition.This project was supported by the US National Science Foundation (Grants 1657855, 1657803, and 1657489). NES‐LTER contributions were supported by grants to HMS from NSF (Grant 1655686) and the Simons Foundation (Grant 561126). VPR operations were supported by the Dalio Explore Fund.2021-07-1

    Selective deforestation and exposure of African wildlife to bat-borne viruses

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    Proposed mechanisms of zoonotic virus spillover often posit that wildlife transmission and amplification precede human outbreaks. Between 2006 and 2012, the palm Raphia farinifera, a rich source of dietary minerals for wildlife, was nearly extirpated from Budongo Forest, Uganda. Since then, chimpanzees, black-and-white colobus, and red duiker were observed feeding on bat guano, a behavior not previously observed. Here we show that guano consumption may be a response to dietary mineral scarcity and may expose wildlife to bat-borne viruses. Videos from 2017–2019 recorded 839 instances of guano consumption by the aforementioned species. Nutritional analysis of the guano revealed high concentrations of sodium, potassium, magnesium and phosphorus. Metagenomic analyses of the guano identified 27 eukaryotic viruses, including a novel betacoronavirus. Our findings illustrate how “upstream” drivers such as socioeconomics and resource extraction can initiate elaborate chains of causation, ultimately increasing virus spillover risk

    Selective deforestation and exposure of African wildlife to bat-borne viruses

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    Proposed mechanisms of zoonotic virus spillover often posit that wildlife transmission and amplification precede human outbreaks. Between 2006 and 2012, the palm Raphia farinifera, a rich source of dietary minerals for wildlife, was nearly extirpated from Budongo Forest, Uganda. Since then, chimpanzees, black-and-white colobus, and red duiker were observed feeding on bat guano, a behavior not previously observed. Here we show that guano consumption may be a response to dietary mineral scarcity and may expose wildlife to bat-borne viruses. Videos from 2017–2019 recorded 839 instances of guano consumption by the aforementioned species. Nutritional analysis of the guano revealed high concentrations of sodium, potassium, magnesium and phosphorus. Metagenomic analyses of the guano identified 27 eukaryotic viruses, including a novel betacoronavirus. Our findings illustrate how “upstream” drivers such as socioeconomics and resource extraction can initiate elaborate chains of causation, ultimately increasing virus spillover risk.Peer reviewe

    Natural HLA Class I Polymorphism Controls the Pathway of Antigen Presentation and Susceptibility to Viral Evasion

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    HLA class I polymorphism creates diversity in epitope specificity and T cell repertoire. We show that HLA polymorphism also controls the choice of Ag presentation pathway. A single amino acid polymorphism that distinguishes HLA-B*4402 (Asp116) from B*4405 (Tyr116) permits B*4405 to constitutively acquire peptides without any detectable incorporation into the transporter associated with Ag presentation (TAP)-associated peptide loading complex even under conditions of extreme peptide starvation. This mode of peptide capture is less susceptible to viral interference than the conventional loading pathway used by HLA-B*4402 that involves assembly of class I molecules within the peptide loading complex. Thus, B*4402 and B*4405 are at opposite extremes of a natural spectrum in HLA class I dependence on the PLC for Ag presentation. These findings unveil a new layer of MHC polymorphism that affects the generic pathway of Ag loading, revealing an unsuspected evolutionary trade-off in selection for optimal HLA class I loading versus effective pathogen evasion

    Unlocking the bottleneck in forward genetics using whole-genome sequencing and identity by descent to isolate causative mutations

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    Forward genetics screens with N-ethyl-N-nitrosourea (ENU) provide a powerful way to illuminate gene function and generate mouse models of human disease; however, the identification of causative mutations remains a limiting step. Current strategies depend on conventional mapping, so the propagation of affected mice requires non-lethal screens; accurate tracking of phenotypes through pedigrees is complex and uncertain; out-crossing can introduce unexpected modifiers; and Sanger sequencing of candidate genes is inefficient. Here we show how these problems can be efficiently overcome using whole-genome sequencing (WGS) to detect the ENU mutations and then identify regions that are identical by descent (IBD) in multiple affected mice. In this strategy, we use a modification of the Lander-Green algorithm to isolate causative recessive and dominant mutations, even at low coverage, on a pure strain background. Analysis of the IBD regions also allows us to calculate the ENU mutation rate (1.54 mutations per Mb) and to model future strategies for genetic screens in mice. The introduction of this approach will accelerate the discovery of causal variants, permit broader and more informative lethal screens to be used, reduce animal costs, and herald a new era for ENU mutagenesis.The High-Throughput Genomics Group at the Wellcome Trust Centre for Human Genetics is funded by Wellcome Trust grant reference 090532/Z/09/Z and MRC Hub grant G0900747 91070. This study was supported by Wellcome Trust Strategic Award 082030 (CCG), Wellcome Trust Studentship 094446/Z/10/Z (KRB), the Oxford NIHR Biomedical Research Centre, and the MRC Human Immunology Unit (RJC). AJR and GL were supported by Wellcome Trust grant 090532/Z/ 09/Z, CCG and AE by a Major initiative Award from the Clive and Vera Ramaciotti Foundation, and AE by an NHMRC Career Development Award. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

    Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

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    Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

    Development of synchronous VHL syndrome tumors reveals contingencies and constraints to tumor evolution

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    This is an Open Access article distributed under the terms of the Creative Commons Attribution License.-- et al.[Background]: Genomic analysis of multi-focal renal cell carcinomas from an individual with a germline VHL mutation offers a unique opportunity to study tumor evolution. [Results]: We perform whole exome sequencing on four clear cell renal cell carcinomas removed from both kidneys of a patient with a germline VHL mutation. We report that tumors arising in this context are clonally independent and harbour distinct secondary events exemplified by loss of chromosome 3p, despite an identical genetic background and tissue microenvironment. We propose that divergent mutational and copy number anomalies are contingent upon the nature of 3p loss of heterozygosity occurring early in tumorigenesis. However, despite distinct 3p events, genomic, proteomic and immunohistochemical analyses reveal evidence for convergence upon the PI3K-AKT-mTOR signaling pathway. Four germline tumors in this young patient, and in a second, older patient with VHL syndrome demonstrate minimal intra-tumor heterogeneity and mutational burden, and evaluable tumors appear to follow a linear evolutionary route, compared to tumors from patients with sporadic clear cell renal cell carcinoma. [Conclusions]: In tumors developing from a germline VHL mutation, the evolutionary principles of contingency and convergence in tumor development are complementary. In this small set of patients with early stage VHL-associated tumors, there is reduced mutation burden and limited evidence of intra-tumor heterogeneity.RF and JL received funding from EU FP7 (PREDICT project), EB is a Rosetrees Trust fellow, NM received funding from the Rosetrees Trust, MG is funded by the UK Medical Research Council, IV is funded by Spanish Ministerio de EconomĂ­a y Competitividad subprograma RamĂłn y Cajal, and CS is a senior Cancer Research UK clinical research fellow and is funded by Cancer Research UK, the Rosetrees Trust, EU FP7 (projects PREDICT and RESPONSIFY, ID:259303), the Prostate Cancer Foundation, and the Breast Cancer Research Foundation. This study was supported by researchers at the National Institute for Health Research Biomedical Research Centres at University College London Hospitals and at the Royal Marsden Hospital.Peer Reviewe

    Sustained increases in atmospheric oxygen and marine productivity in the Neoproterozoic and Palaeozoic eras

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    A geologically rapid Neoproterozoic oxygenation event is commonly linked to the appearance of marine animal groups in the fossil record. However, there is still debate about what evidence from the sedimentary geochemical record—if any—provides strong support for a persistent shift in surface oxygen immediately preceding the rise of animals. We present statistical learning analyses of a large dataset of geochemical data and associated geological context from the Neoproterozoic and Palaeozoic sedimentary record and then use Earth system modelling to link trends in redox-sensitive trace metal and organic carbon concentrations to the oxygenation of Earth’s oceans and atmosphere. We do not find evidence for the wholesale oxygenation of Earth’s oceans in the late Neoproterozoic era. We do, however, reconstruct a moderate long-term increase in atmospheric oxygen and marine productivity. These changes to the Earth system would have increased dissolved oxygen and food supply in shallow-water habitats during the broad interval of geologic time in which the major animal groups first radiated. This approach provides some of the most direct evidence for potential physiological drivers of the Cambrian radiation, while highlighting the importance of later Palaeozoic oxygenation in the evolution of the modern Earth system
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