110 research outputs found

    TöRF: Time-of-Flight Radiance Fields for Dynamic Scene View Synthesis

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    Neural networks can represent and accurately reconstruct radiance fields for static 3D scenes (e.g., NeRF). Several works extend these to dynamic scenes captured with monocular video, with promising performance. However, the monocular setting is known to be an under-constrained problem, and so methods rely on data-driven priors for reconstructing dynamic content. We replace these priors with measurements from a time-of-flight (ToF) camera, and introduce a neural representation based on an image formation model for continuous-wave ToF cameras. Instead of working with processed depth maps, we model the raw ToF sensor measurements to improve reconstruction quality and avoid issues with low reflectance regions, multi-path interference, and a sensor's limited unambiguous depth range. We show that this approach improves robustness of dynamic scene reconstruction to erroneous calibration and large motions, and discuss the benefits and limitations of integrating RGB+ToF sensors that are now available on modern smartphones.Comment: Accepted to NeurIPS 2021. Web page: https://imaging.cs.cmu.edu/torf/ NeurIPS camera ready updates -- added quantitative comparisons to new methods, visual side-by-side comparisons performed on larger baseline camera sequence

    HyperReel: High-Fidelity 6-DoF Video with Ray-Conditioned Sampling

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    Volumetric scene representations enable photorealistic view synthesis for static scenes and form the basis of several existing 6-DoF video techniques. However, the volume rendering procedures that drive these representations necessitate careful trade-offs in terms of quality, rendering speed, and memory efficiency. In particular, existing methods fail to simultaneously achieve real-time performance, small memory footprint, and high-quality rendering for challenging real-world scenes. To address these issues, we present HyperReel -- a novel 6-DoF video representation. The two core components of HyperReel are: (1) a ray-conditioned sample prediction network that enables high-fidelity, high frame rate rendering at high resolutions and (2) a compact and memory-efficient dynamic volume representation. Our 6-DoF video pipeline achieves the best performance compared to prior and contemporary approaches in terms of visual quality with small memory requirements, while also rendering at up to 18 frames-per-second at megapixel resolution without any custom CUDA code.Comment: Project page: https://hyperreel.github.io

    International cancer microbiome consortium consensus statement on the role of the human microbiome in carcinogenesis

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    Objective In this consensus statement, an international panel of experts deliver their opinions on key questions regarding the contribution of the human microbiome to carcinogenesis.Design International experts in oncology and/or microbiome research were approached by personal communication to form a panel. A structured, iterative, methodology based around a 1-day roundtable discussion was employed to derive expert consensus on key questions in microbiome-oncology research.Results Some 18 experts convened for the roundtable discussion and five key questions were identified regarding: (1) the relevance of dysbiosis/an altered gut microbiome to carcinogenesis; (2) potential mechanisms of microbiota-induced carcinogenesis; (3) conceptual frameworks describing how the human microbiome may drive carcinogenesis; (4) causation versus association; and (5) future directions for research in the field.The panel considered that, despite mechanistic and supporting evidence from animal and human studies, there is currently no direct evidence that the human commensal microbiome is a key determinant in the aetiopathogenesis of cancer. The panel cited the lack of large longitudinal, cohort studies as a principal deciding factor and agreed that this should be a future research priority. However, while acknowledging gaps in the evidence, expert opinion was that the microbiome, alongside environmental factors and an epigenetically/genetically vulnerable host, represents one apex of a tripartite, multidirectional interactome that drives carcinogenesis.Conclusion Data from longitudinal cohort studies are needed to confirm the role of the human microbiome as a key driver in the aetiopathogenesis of cancer

    A high-risk gut microbiota configuration associates with fatal hyperinflammatory immune and metabolic responses to SARS-CoV-2.

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    Protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and associated clinical sequelae requires well-coordinated metabolic and immune responses that limit viral spread and promote recovery of damaged systems. However, the role of the gut microbiota in regulating these responses has not been thoroughly investigated. In order to identify mechanisms underpinning microbiota interactions with host immune and metabolic systems that influence coronavirus disease 2019 (COVID-19) outcomes, we performed a multi-omics analysis on hospitalized COVID-19 patients and compared those with the most severe outcome (i.e. death, n = 41) to those with severe non-fatal disease (n = 89), or mild/moderate disease (n = 42), that recovered. A distinct subset of 8 cytokines (e.g. TSLP) and 140 metabolites (e.g. quinolinate) in sera identified those with a fatal outcome to infection. In addition, elevated levels of multiple pathobionts and lower levels of protective or anti-inflammatory microbes were observed in the fecal microbiome of those with the poorest clinical outcomes. Weighted gene correlation network analysis (WGCNA) identified modules that associated severity-associated cytokines with tryptophan metabolism, coagulation-linked fibrinopeptides, and bile acids with multiple pathobionts, such as Enterococcus. In contrast, less severe clinical outcomes are associated with clusters of anti-inflammatory microbes such as Bifidobacterium or Ruminococcus, short chain fatty acids (SCFAs) and IL-17A. Our study uncovered distinct mechanistic modules that link host and microbiome processes with fatal outcomes to SARS-CoV-2 infection. These features may be useful to identify at risk individuals, but also highlight a role for the microbiome in modifying hyperinflammatory responses to SARS-CoV-2 and other infectious agents

    A systematic approach to mapping recessive disease genes in individuals from outbred populations

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    The identification of recessive disease-causing genes by homozygosity mapping is often restricted by lack of suitable consanguineous families. To overcome these limitations, we apply homozygosity mapping to single affected individuals from outbred populations. In 72 individuals of 54 kindred ascertained worldwide with known homozygous mutations in 13 different recessive disease genes, we performed total genome homozygosity mapping using 250,000 SNP arrays. Likelihood ratio Z-scores (ZLR) were plotted across the genome to detect ZLR peaks that reflect segments of homozygosity by descent, which may harbor the mutated gene. In 93% of cases, the causative gene was positioned within a consistent ZLR peak of homozygosity. The number of peaks reflected the degree of inbreeding. We demonstrate that disease-causing homozygous mutations can be detected in single cases from outbred populations within a single ZLR peak of homozygosity as short as 2 Mb, containing an average of only 16 candidate genes. As many specialty clinics have access to cohorts of individuals from outbred populations, and as our approach will result in smaller genetic candidate regions, the new strategy of homozygosity mapping in single outbred individuals will strongly accelerate the discovery of novel recessive disease genes

    B-cell Zone Reticular Cell Microenvironments Shape CXCL13 Gradient Formation

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    Through the formation of concentration gradients, morphogens drive graded responses to extracellular signals, thereby fine-tuning cell behaviors in complex tissues. Here we show that the chemokine CXCL13 forms both soluble and immobilized gradients. Specifically, CXCL13+ follicular reticular cells form a small-world network of guidance structures, with computer simulations and optimization analysis predicting that immobilized gradients created by this network promote B-cell trafficking. Consistent with this prediction, imaging analysis show that CXCL13 binds to extracellular matrix components in situ, constraining its diffusion. CXCL13 solubilization requires the protease cathepsin B that cleaves CXCL13 into a stable product. Mice lacking cathepsin B display aberrant follicular architecture, a phenotype associated with effective B cell homing to but not within lymph nodes. Our data thus suggest that reticular cells of the B cell zone generate microenvironments that shape both immobilized and soluble CXCL13 gradient

    Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

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    Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

    Disruption of AP1S1, Causing a Novel Neurocutaneous Syndrome, Perturbs Development of the Skin and Spinal Cord

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    Adaptor protein (AP) complexes regulate clathrin-coated vesicle assembly, protein cargo sorting, and vesicular trafficking between organelles in eukaryotic cells. Because disruption of the various subunits of the AP complexes is embryonic lethal in the majority of cases, characterization of their function in vivo is still lacking. Here, we describe the first mutation in the human AP1S1 gene, encoding the small subunit σ1A of the AP-1 complex. This founder splice mutation, which leads to a premature stop codon, was found in four families with a unique syndrome characterized by mental retardation, enteropathy, deafness, peripheral neuropathy, ichthyosis, and keratodermia (MEDNIK). To validate the pathogenic effect of the mutation, we knocked down Ap1s1 expression in zebrafish using selective antisens morpholino oligonucleotides (AMO). The knockdown phenotype consisted of perturbation in skin formation, reduced pigmentation, and severe motility deficits due to impaired neural network development. Both neural and skin defects were rescued by co-injection of AMO with wild-type (WT) human AP1S1 mRNA, but not by co-injecting the truncated form of AP1S1, consistent with a loss-of-function effect of this mutation. Together, these results confirm AP1S1 as the gene responsible for MEDNIK syndrome and demonstrate a critical role of AP1S1 in development of the skin and spinal cord

    Computational strategies to combat COVID-19: useful tools to accelerate SARS-CoV-2 and coronavirus research

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    SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is a novel virus of the family Coronaviridae. The virus causes the infectious disease COVID-19. The biology of coronaviruses has been studied for many years. However, bioinformatics tools designed explicitly for SARS-CoV-2 have only recently been developed as a rapid reaction to the need for fast detection, understanding and treatment of COVID-19. To control the ongoing COVID-19 pandemic, it is of utmost importance to get insight into the evolution and pathogenesis of the virus. In this review, we cover bioinformatics workflows and tools for the routine detection of SARS-CoV-2 infection, the reliable analysis of sequencing data, the tracking of the COVID-19 pandemic and evaluation of containment measures, the study of coronavirus evolution, the discovery of potential drug targets and development of therapeutic strategies. For each tool, we briefly describe its use case and how it advances research specifically for SARS-CoV-2. All tools are free to use and available online, either through web applications or public code repositories.Peer Reviewe
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