Notes

Advancement of physiologic and autonomic phenotype in ROHHAD over the 10 years coming from age group with analysis.
Neuro-evolution is an appealing approach to generating collective behaviors for robot swarms. In its typical application, known as off-line automatic design, the neural networks controlling the robots are optimized in simulation. It is understood that the so-called reality gap, the unavoidable differences between simulation and reality, typically causes neural network to be less effective on real robots than what is predicted by simulation. In this paper, we present an empirical study on the extent to which the reality gap impacts the most popular and advanced neuro-evolutionary methods for the off-line design of robot swarms. The results show that the neural networks produced by the methods under analysis performed well in simulation, but not in real-robot experiments. Further, the ranking that could be observed in simulation between the methods eventually disappeared. We find compelling evidence that real-robot experiments are needed to reliably assess the performance of neuro-evolutionary methods and that the robustness to the reality gap is the main issue to be addressed to advance the application of neuro-evolution to robot swarms.Genes underneath signals from genome-wide association studies (GWAS) for kidney function are promising targets for functional studies, but prioritizing variants and genes is challenging. By GWAS meta-analysis for creatinine-based estimated glomerular filtration rate (eGFR) from the Chronic Kidney Disease Genetics Consortium and UK Biobank (n = 1,201,909), we expand the number of eGFRcrea loci (424 loci, 201 novel; 9.8% eGFRcrea variance explained by 634 independent signal variants). Our increased sample size in fine-mapping (n = 1,004,040, European) more than doubles the number of signals with resolved fine-mapping (99% credible sets down to 1 variant for 44 signals, ≤5 variants for 138 signals). Cystatin-based eGFR and/or blood urea nitrogen association support 348 loci (n = 460,826 and 852,678, respectively). Our customizable tool for Gene PrioritiSation reveals 23 compelling genes including mechanistic insights and enables navigation through genes and variants likely relevant for kidney function in human to help select targets for experimental follow-up.Small-molecule modulators of TLR8 have drawn much interests as it plays pivotal roles in the innate immune response to single-stranded RNAs (ssRNAs) derived from viruses. However, their clinical uses are limited because they can invoke an uncontrolled, global inflammatory response. The efforts described herein culminate in the fortuitous discovery of a tetrasubstituted imidazole CU-CPD107 which inhibits R848-induced TLR8 signaling. In stark contrast, CU-CPD107 shows unexpected synergistic agonist activities in the presence of ssRNA, while CU-CPD107 alone is unable to influence TLR8 signaling. CU-CPD107's unique, dichotomous behavior sheds light on a way to approach TLR agonists. CU-CPD107 offers the opportunity to avoid the undesired, global inflammation side effects that have rendered imidazoquinolines clinically irrelevant, providing an insight for the development of antiviral drugs.A key challenge to realizing practical electrochemical N2 reduction reaction (NRR) is the decrease in the NRR activity before reaching the mass-transfer limit as overpotential increases. While the hydrogen evolution reaction (HER) has been suggested to be responsible for this phenomenon, the mechanistic origin has not been clearly explained. Herein, we investigate the potential-dependent competition between NRR and HER using the constant electrode potential model and microkinetic modeling. We find that the H coverage and N2 coverage crossover leads to the premature decrease of NRR activity. The coverage crossover originates from the larger charge transfer in H+ adsorption than N2 adsorption. The larger charge transfer in H+ adsorption, which potentially leads to the coverage crossover, is a general phenomenon seen in various heterogeneous catalysts, posing a fundamental challenge to realize practical electrochemical NRR. We suggest several strategies to overcome the challenge based on the present understandings.Histone H3 lysine 9 (H3K9) methylation is a central epigenetic modification that defines heterochromatin from unicellular to multicellular organisms. In mammalian cells, H3K9 methylation can be catalyzed by at least six distinct SET domain enzymes Suv39h1/Suv39h2, Eset1/Eset2 and G9a/Glp. We used mouse embryonic fibroblasts (MEFs) with a conditional mutation for Eset1 and introduced progressive deletions for the other SET domain genes by CRISPR/Cas9 technology. Compound mutant MEFs for all six SET domain lysine methyltransferase (KMT) genes lack all H3K9 methylation states, derepress nearly all families of repeat elements and display genomic instabilities. Strikingly, the 6KO H3K9 KMT MEF cells no longer maintain heterochromatin organization and have lost electron-dense heterochromatin. This is a compelling analysis of H3K9 methylation-deficient mammalian chromatin and reveals a definitive function for H3K9 methylation in protecting heterochromatin organization and genome integrity.Inland fisheries and their freshwater habitats face intensifying effects from multiple natural and anthropogenic pressures. Selleck FEN1-IN-4 Fish harvest and biodiversity data remain largely disparate and severely deficient in many areas, which makes assessing and managing inland fisheries difficult. Expert knowledge is increasingly used to improve and inform biological or vulnerability assessments, especially in data-poor areas. Integrating expert knowledge on the distribution, intensity, and relative influence of human activities can guide natural resource management strategies and institutional resource allocation and prioritization. This paper introduces a dataset summarizing the expert-perceived state of inland fisheries at the basin (fishery) level. An electronic survey distributed to professional networks (June-September 2020) captured expert perceptions (n = 536) of threats, successes, and adaptive capacity to fisheries across 93 hydrological basins, 79 countries, and all major freshwater habitat types. This dataset can be used to address research questions with conservation relevance, including demographic influences on perceptions of threat, adaptive capacities for climate change, external factors driving multi-stressor interactions, and geospatial threat assessments.
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