Notes

Outcomes of attention lowers made up of a variety of 3% diquafosol sodium as well as tocopherol acetate (vitamin e d-alpha) for the ocular the surface of murine dried out eyesight.
The CR3022 antibody, selected from a group of SARS-CoV monoclonal antibodies for its ability to cross-react with SARS-CoV-2, has been examined for its ability to bind to the ectodomain of the SARS-CoV-2 spike glycoprotein. Using cryo-electron microscopy we show that antibody binding requires rearrangements in the S1 domain that result in dissociation of the spike.The Serengeti ecosystem spans an extensive network of protected areas in Tanzania, eastern Africa, and a UNESCO Wold Heritage Site. It is home to some of the largest animal migrations on the planet. Here, we describe a dataset consisting of the sample counts of three age classes (infant, juvenile and adult) of 13 ungulate and one ostrich species. Sample counts were tallied visually from the ground, or, in some instances, aerial photographs, during a period extending from 1926 to 2018. Observed animals were assigned to age classes based on specific criteria for each species. For nine of the 14 species of this dataset, the number of sampling years is over 30. This resulted in a total of 533 different records of count across age classes. By computing age-class ratios, these data can be used to measure long-term recruitment success at different ages of the tallied species. In particular, the temporal extent of these data allows comparison of patterns to other long-term processes, such as the El Niño-Southern Oscillation (ENSO).The deviation of the electron density around the nuclei from spherical symmetry determines the electric field gradient (EFG), which can be measured by various types of spectroscopy. Nuclear Quadrupole Resonance (NQR) is particularly sensitive to the EFG. The EFGs, and by implication NQR frequencies, vary dramatically across materials. Consequently, searching for NQR spectral lines in previously uninvestigated materials represents a major challenge. Calculated EFGs can significantly aid at the search's inception. To facilitate this task, we have applied high-throughput density functional theory calculations to predict EFGs for 15187 materials in the JARVIS-DFT database. This database, which will include EFG as a standard entry, is continuously increasing. Given the large scope of the database, it is impractical to verify each calculation. However, we assess accuracy by singling out cases for which reliable experimental information is readily available and compare them to the calculations. We further present a statistical analysis of the results. check details The database and tools associated with our work are made publicly available by JARVIS-DFT ( https//www.ctcms.nist.gov/~knc6/JVASP.html ) and NIST-JARVIS API ( http//jarvis.nist.gov/ ).Propionic acidemia/aciduria (PA) is an ultra-rare, life-threatening, inherited metabolic disorder caused by deficiency of the mitochondrial enzyme, propionyl-CoA carboxylase (PCC) composed of six alpha (PCCA) and six beta (PCCB) subunits. We herein report an enzyme replacement approach to treat PA using a combination of two messenger RNAs (mRNAs) (dual mRNAs) encoding both human PCCA (hPCCA) and PCCB (hPCCB) encapsulated in biodegradable lipid nanoparticles (LNPs) to produce functional PCC enzyme in liver. In patient fibroblasts, dual mRNAs encoded proteins localize in mitochondria and produce higher PCC enzyme activity vs. single (PCCA or PCCB) mRNA alone. In a hypomorphic murine model of PA, dual mRNAs normalize ammonia similarly to carglumic acid, a drug approved in Europe for the treatment of hyperammonemia due to PA. Dual mRNAs additionally restore functional PCC enzyme in liver and thus reduce primary disease-associated toxins in a dose-dependent manner in long-term 3- and 6-month repeat-dose studies in PA mice. Dual mRNAs are well-tolerated in these studies with no adverse findings. These studies demonstrate the potential of mRNA technology to chronically administer multiple mRNAs to produce large complex enzymes, with applicability to other genetic disorders.An amendment to this paper has been published and can be accessed via a link at the top of the paper.Clonal diversity is a consequence of cancer cell evolution driven by Darwinian selection. Precise characterization of clonal architecture is essential to understand the evolutionary history of tumor development and its association with treatment resistance. Here, using a single-cell DNA sequencing, we report the clonal architecture and mutational histories of 123 acute myeloid leukemia (AML) patients. The single-cell data reveals cell-level mutation co-occurrence and enables reconstruction of mutational histories characterized by linear and branching patterns of clonal evolution, with the latter including convergent evolution. Through xenotransplantion, we show leukemia initiating capabilities of individual subclones evolving in parallel. link2 Also, by simultaneous single-cell DNA and cell surface protein analysis, we illustrate both genetic and phenotypic evolution in AML. Lastly, single-cell analysis of longitudinal samples reveals underlying evolutionary process of therapeutic resistance. Together, these data unravel clonal diversity and evolution patterns of AML, and highlight their clinical relevance in the era of precision medicine.Recent advances have enabled the direct induction of human tissue-specific stem and progenitor cells from differentiated somatic cells. However, it is not known whether human hepatic progenitor cells (hHepPCs) can be generated from other cell types by direct lineage reprogramming with defined transcription factors. Here, we show that a set of three transcription factors, FOXA3, HNF1A, and HNF6, can induce human umbilical vein endothelial cells to directly acquire the properties of hHepPCs. These induced hHepPCs (hiHepPCs) propagate in long-term monolayer culture and differentiate into functional hepatocytes and cholangiocytes by forming cell aggregates and cystic epithelial spheroids, respectively, under three-dimensional culture conditions. After transplantation, hiHepPC-derived hepatocytes and cholangiocytes reconstitute damaged liver tissues and support hepatic function. The defined transcription factors also induce hiHepPCs from endothelial cells circulating in adult human peripheral blood. These expandable and bipotential hiHepPCs may be useful in the study and treatment of human liver diseases.The presence of plastic in the environment has sparked discussion amongst scientists, regulators and the general public as to how industrialization and consumerism is shaping our world. Here we discuss restrictions on the intentional use of primary microplastics small solid polymer particles in applications ranging from agriculture to cosmetics. Microplastic hazards are uncertain, and actions are not similarly prioritized by all actors. In some instances, replacement is technically simple and easily justified, but in others substitutions may come with more uncertainty, performance questions and costs. Scientific impact assessment of primary microplastics compared to their alternatives relies on a number of factors, such as microplastic harm, existence of replacement materials and the quality, cost and hazards of alternative materials. Regulations need a precise focus and must be enforceable by these measurements. Policymakers must carefully evaluate under which contexts incentives to replace certain microplastics can stimulate innovation of new, more competitive and environmentally conscious materials.Supported self-management is a vital component of routine asthma care. Completion of an agreed personalised asthma action plan is integral to implementation of this care, and traditionally this requires a face-to-face consultation. We aimed to assess the practical feasibility and potential utility of using screen-sharing technologies to complete asthma action plans remotely. Assisted by people with diverse technological ability and using a range of devices, we tested the technological feasibility of completing action plans in remote consultations using two leading video-conference systems. We used a semi-structured topic guide to check functionality and lead feedback discussions. Themes were interpreted using the Model for ASsessment of Telemedicine applications (MAST). Discussions with ten participants (age 20-74 years) revealed that screen-sharing was practical on most devices. link3 Joint editing of an action plan (as was possible with Zoom) was considered to encourage participation and improve communication. Attend Anywhere had less functionality than Zoom, but the NHS badging was reassuring. Most participants appreciated the screen-sharing and considered it enabled a meaningful discussion about their action plan. Online shared completion of action plans is feasible with only a few (potentially remediable) practical problems. These findings suggest this may be a fruitful approach for further study-made more urgent by the imperative to develop remote consultations in the face of a global pandemic.Adaptive optics (AO) is critical in astronomy, optical communications and remote sensing to deal with the rapid blurring caused by the Earth's turbulent atmosphere. But current AO systems are limited by their wavefront sensors, which need to be in an optical plane non-common to the science image and are insensitive to certain wavefront-error modes. Here we present a wavefront sensor based on a photonic lantern fibre-mode-converter and deep learning, which can be placed at the same focal plane as the science image, and is optimal for single-mode fibre injection. By measuring the intensities of an array of single-mode outputs, both phase and amplitude information on the incident wavefront can be reconstructed. We demonstrate the concept with simulations and an experimental realisation wherein Zernike wavefront errors are recovered from focal-plane measurements to a precision of 5.1 × 10-3 π radians root-mean-squared-error.Exome sequencing is widely used in the diagnosis of rare genetic diseases and provides useful variant data for analysis of complex diseases. There is not always adequate population-specific reference data to assist in assigning a diagnostic variant to a specific clinical condition. Here we provide a catalogue of variants called after sequencing the exomes of 45 babies from Rio Grande do Nord in Brazil. Sequence data were processed using an 'intersect-then-combine' (ITC) approach, using GATK and SAMtools to call variants. A total of 612,761 variants were identified in at least one individual in this Brazilian Cohort, including 559,448 single nucleotide variants (SNVs) and 53,313 insertion/deletions. Of these, 58,111 overlapped with nonsynonymous (nsSNVs) or splice site (ssSNVs) SNVs in dbNSFP. As an aid to clinical diagnosis of rare diseases, we used the American College of Medicine Genetics and Genomics (ACMG) guidelines to assign pathogenic/likely pathogenic status to 185 (0.32%) of the 58,111 nsSNVs and ssSNVs. Our data set provides a useful reference point for diagnosis of rare diseases in Brazil. (169 words).5-Fluorouracil (5-FU) remains the first-line treatment for colorectal cancer (CRC). Although 5-FU initially de-bulks the tumor mass, recurrence after chemotherapy is the barrier to effective clinical outcomes for CRC patients. Here, we demonstrate that p53 promotes WNT3 transcription, leading to activation of the WNT/β-catenin pathway in ApcMin/+/Lgr5EGFP mice, CRC patient-derived tumor organoids (PDTOs) and patient-derived tumor cells (PDCs). Through this regulation, 5-FU induces activation and enrichment of cancer stem cells (CSCs) in the residual tumors, contributing to recurrence after treatment. Combinatorial treatment of a WNT inhibitor and 5-FU effectively suppresses the CSCs and reduces tumor regrowth after discontinuation of treatment. These findings indicate p53 as a critical mediator of 5-FU-induced CSC activation via the WNT/β-catenin signaling pathway and highlight the significance of combinatorial treatment of WNT inhibitor and 5-FU as a compelling therapeutic strategy to improve the poor outcomes of current 5-FU-based therapies for CRC patients.
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