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Histopathological images are used to characterize complex phenotypes such as tumor stage. Our goal is to associate features of stained tissue images with high-dimensional genomic markers. We use convolutional autoencoders and sparse canonical correlation analysis (CCA) on paired histological images and bulk gene expression to identify subsets of genes whose expression levels in a tissue sample correlate with subsets of morphological features from the corresponding sample image. We apply our approach, ImageCCA, to two TCGA data sets, and find gene sets associated with the structure of the extracellular matrix and cell wall infrastructure, implicating uncharacterized genes in extracellular processes. We find sets of genes associated with specific cell types, including neuronal cells and cells of the immune system. We apply ImageCCA to the GTEx v6 data, and find image features that capture population variation in thyroid and in colon tissues associated with genetic variants (image morphology QTLs, or imQTLs), suggesting that genetic variation regulates population variation in tissue morphological traits.The accelerating loss of tropical forests in the 21st century has eliminated cooling services provided by trees in low latitude countries. Cooling services can protect rural communities and outdoor workers with little adaptive capacity from adverse heat exposure, which is expected to increase with climate change. Yet little is still known about whether cooling services can mitigate negative impacts of heat on labor productivity among rural outdoor workers. Through a field experiment in Indonesia, we show that worker productivity was 8.22% lower in deforested relative to forested settings, where wet bulb globe temperatures were, on average, 2.84 °C higher in deforested settings. We demonstrate that productivity losses are driven by behavioral adaptations in the form of increased number of work breaks, and provide evidence that suggests breaks are in part driven by awareness of heat effects on work. Our results indicate that the cooling services from forests have the potential for increasing resilience and adaptive capacity to local warming.In recognizing the host cellular receptor and mediating fusion of virus and cell membranes, the spike (S) glycoprotein of coronaviruses is the most critical viral protein for cross-species transmission and infection. Here we determined the cryo-EM structures of the spikes from bat (RaTG13) and pangolin (PCoV_GX) coronaviruses, which are closely related to SARS-CoV-2. All three receptor-binding domains (RBDs) of these two spike trimers are in the "down" conformation, indicating they are more prone to adopt the receptor-binding inactive state. However, we found that the PCoV_GX, but not the RaTG13, spike is comparable to the SARS-CoV-2 spike in binding the human ACE2 receptor and supporting pseudovirus cell entry. 2-Aminoethanethiol in vivo We further identified critical residues in the RBD underlying different activities of the RaTG13 and PCoV_GX/SARS-CoV-2 spikes. These results collectively indicate that tight RBD-ACE2 binding and efficient RBD conformational sampling are required for the evolution of SARS-CoV-2 to gain highly efficient infection.Hepatitis B virus (HBV) is a highly contagious pathogen that afflicts over a third of the world's population, resulting in close to a million deaths annually. The formation and persistence of the HBV covalently closed circular DNA (cccDNA) is the root cause of HBV chronicity. However, the detailed molecular mechanism of cccDNA formation from relaxed circular DNA (rcDNA) remains opaque. Here we show that the minus and plus-strand lesions of HBV rcDNA require different sets of human repair factors in biochemical repair systems. We demonstrate that the plus-strand repair resembles DNA lagging strand synthesis, and requires proliferating cell nuclear antigen (PCNA), the replication factor C (RFC) complex, DNA polymerase delta (POLδ), flap endonuclease 1 (FEN-1), and DNA ligase 1 (LIG1). Only FEN-1 and LIG1 are required for the repair of the minus strand. Our findings provide a detailed mechanistic view of how HBV rcDNA is repaired to form cccDNA in biochemical repair systems.The COVID-19 pandemic has affected more than 100 million cases and caused immense burdens on governments and healthcare systems worldwide. Since its emergence in December 2019, research has been focused on treating the infected, identifying those at risk and preventing spread. There is currently no known biological biomarker that predicts the risk of infection. Several studies emerged suggesting an association between ABO blood group and the risk of COVID-19 infection. In this study, we used retrospective observational data in Bahrain to investigate the association between ABO blood group and risk of infection, as well as susceptibility to severe ICU-requiring infection. We found a higher risk associated with blood group B, and a lower risk with blood group AB. No association was observed between blood group and the risk of a severe ICU-requiring infection. We extended the analysis to study the association by antibodies; anti-a (blood groups B and O) and anti-b (blood groups A and O). No association between antibodies and both risk of infection or susceptibility to severe infection was found. The current study, along with the variation in blood group association results, indicates that blood group may not be an ideal biomarker to predict risk of COVID-19 infection.Violation of Bell's inequality in experiments shows that predictions of local realistic models disagree with those of quantum mechanics. However, despite the quantum mechanics formalism, there are debates on how does it happen in nature. In this paper by use of a model of polarizers that obeys the Malus' law and quantum steering concept, i.e. superluminal influence of the states of entangled pairs to each other, simulation of phenomena is presented. The given model, as it is intended to be, is extremely simple without using mathematical formalism of quantum mechanics. However, the result completely agrees with prediction of quantum mechanics. Although it may seem trivial, this model can be applied to simulate the behavior of other not easy to analytically evaluate effects, such as deficiency of detectors and polarizers, different value of photons in each run and so on. For example, it is demonstrated, when detector efficiency is 83% the S factor of CHSH inequality will be 2, which completely agrees with famous detector efficiency limit calculated analytically.
Website: https://www.selleckchem.com/products/2-aminoethanethiol.html
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