Notes

Earlier the child years being a parent along with teen violence actions: Evidence coming from a randomized treatment in ten-year follow-up.
The regulation of polymer topology and the precise control over the monomer sequence is crucial and challenging in polymer science. Herein, we report an efficient solution-phase synthetic strategy to prepare regio- and sequence-controlled conjugated polymers with topological variations via the usage of methyliminodiacetic acid (MIDA) boronates. Based on the solubility of MIDA boronates and their unusual binary affinity for silica gel, the synthesized regio- and sequence-defined conjugated oligomers can be rapidly purified via precipitation or automatic liquid chromatography. These synthesized discrete oligomers can be used for iterative exponential and sequential growth to obtain linear and dendrimer-like star polymers. Moreover, different topological sequence-controlled conjugated polymers are conveniently prepared from these discrete oligomers via condensation polymerization. By investigating the structure-property relationship of these polymers, we find that the optical properties are strongly influenced by the regiochemistry, which may give inspiration to the design of optoelectronic polymeric materials.Recent advancements in the field of electronics have paved the way to the development of new applications, such as tattoo electronics, where the employment of ultraconformable devices is required, typically achievable with a significant reduction in their total thickness. Organic materials can be considered enablers, owing to the possibility of depositing films with thicknesses at the nanometric scale, even from solution. However, available processes do not allow obtaining devices with thicknesses below hundreds of nanometres, thus setting a limit. Here, we show an all-organic field effect transistor that is less than 150 nm thick and that is fabricated through a fully solution-based approach. Such unprecedented thickness permits the device to conformally adhere onto nonplanar surfaces, such as human skin, and to be bent to a radius lower than 1 μm, thereby overcoming another limitation for field-effect transistors and representing a fundamental advancement in the field of ultrathin and tattoo electronics.Karyotype alterations have emerged as on-target complications from CRISPR-Cas9 genome editing. However, the events that lead to these karyotypic changes in embryos after Cas9-treatment remain unknown. Here, using imaging and single-cell genome sequencing of 8-cell stage embryos, we track both spontaneous and Cas9-induced karyotype aberrations through the first three divisions of embryonic development. We observe the generation of abnormal structures of the nucleus that arise as a consequence of errors in mitosis, including micronuclei and chromosome bridges, and determine their contribution to common karyotype aberrations including whole chromosome loss that has been recently reported after editing in embryos. Together, these data demonstrate that Cas9-mediated germline genome editing can lead to unwanted on-target side effects, including major chromosome structural alterations that can be propagated over several divisions of embryonic development.Inadequate oxygenation is a major challenge in cell encapsulation, a therapy which holds potential to treat many diseases including type I diabetes. Selleckchem RRx-001 In such systems, cellular oxygen (O2) delivery is limited to slow passive diffusion from transplantation sites through the poorly O2-soluble encapsulating matrix, usually a hydrogel. This constrains the maximum permitted distance between the encapsulated cells and host site to within a few hundred micrometers to ensure cellular function. Inspired by the natural gas-phase tracheal O2 delivery system of insects, we present herein the design of a biomimetic scaffold featuring internal continuous air channels endowed with 10,000-fold higher O2 diffusivity than hydrogels. We incorporate the scaffold into a bulk hydrogel containing cells, which facilitates rapid O2 transport through the whole system to cells several millimeters away from the device-host boundary. A computational model, validated by in vitro analysis, predicts that cells and islets maintain high viability even in a thick (6.6 mm) device. Finally, the therapeutic potential of the device is demonstrated through the correction of diabetes in immunocompetent mice using rat islets for over 6 months.In children with spinal cord injury (SCI), scoliosis due to trunk muscle paralysis frequently requires surgical treatment. Transcutaneous spinal stimulation enables trunk stability in adults with SCI and may pose a non-invasive preventative therapeutic alternative. This non-randomized, non-blinded pilot clinical trial (NCT03975634) determined the safety and efficacy of transcutaneous spinal stimulation to enable upright sitting posture in 8 children with trunk control impairment due to acquired SCI using within-subject repeated measures study design. Primary safety and efficacy outcomes (pain, hemodynamics stability, skin irritation, trunk kinematics) and secondary outcomes (center of pressure displacement, compliance rate) were assessed within the pre-specified endpoints. One participant did not complete the study due to pain with stimulation on the first day. One episode of autonomic dysreflexia during stimulation was recorded. Following hemodynamic normalization, the participant completed the study. Overall, spinal stimulation was well-tolerated and enabled upright sitting posture in 7 out of the 8 participants.The amount of public proteomics data is rapidly increasing but there is no standardized format to describe the sample metadata and their relationship with the dataset files in a way that fully supports their understanding or reanalysis. Here we propose to develop the transcriptomics data format MAGE-TAB into a standard representation for proteomics sample metadata. We implement MAGE-TAB-Proteomics in a crowdsourcing project to manually curate over 200 public datasets. We also describe tools and libraries to validate and submit sample metadata-related information to the PRIDE repository. We expect that these developments will improve the reproducibility and facilitate the reanalysis and integration of public proteomics datasets.Rare variants are collectively numerous and may underlie a considerable proportion of complex disease risk. However, identifying genuine rare variant associations is challenging due to small effect sizes, presence of technical artefacts, and heterogeneity in population structure. We hypothesize that rare variant burden over a large number of genes can be combined into a predictive rare variant genetic risk score (RVGRS). We propose a method (RV-EXCALIBER) that leverages summary-level data from a large public exome sequencing database (gnomAD) as controls and robustly calibrates rare variant burden to account for the aforementioned biases. A calibrated RVGRS strongly associates with coronary artery disease (CAD) in European and South Asian populations by capturing the aggregate effect of rare variants through a polygenic model of inheritance. The RVGRS identifies 1.5% of the population with substantial risk of early CAD and confers risk even when adjusting for known Mendelian CAD genes, clinical risk factors, and a common variant genetic risk score.Surface waves process the turbulent disturbances which drive dynamics in many space, astrophysical and laboratory plasma systems, with the outer boundary of Earth's magnetosphere, the magnetopause, providing an accessible environment to study them. Like waves on water, magnetopause surface waves are thought to travel in the direction of the driving solar wind, hence a paradigm in global magnetospheric dynamics of tailward propagation has been well-established. Here we show through multi-spacecraft observations, global simulations, and analytic theory that the lowest-frequency impulsively-excited magnetopause surface waves, with standing structure along the terrestrial magnetic field, propagate against the flow outside the boundary. Across a wide local time range (09-15h) the waves' Poynting flux exactly balances the flow's advective effect, leading to no net energy flux and thus stationary structure across the field also. Further down the equatorial flanks, however, advection dominates hence the waves travel downtail, seeding fluctuations at the resonant frequency which subsequently grow in amplitude via the Kelvin-Helmholtz instability and couple to magnetospheric body waves. This global response, contrary to the accepted paradigm, has implications on radiation belt, ionospheric, and auroral dynamics and potential applications to other dynamical systems.The extent of SARS-CoV-2 circulation in many African countries remains unclear, underlining the need for antibody sero-surveys to assess the cumulative attack rate. Here, we present the results of a cross-sectional sero-survey of a random sample of residents of a health district in Yaounde, Cameroon, conducted from October 14 to November 26, 2020. Among the 971 participants, the test-adjusted seroprevalence of anti-SARS-CoV-2 IgG antibodies was 29·2% (95% CI 24·3-34·1). This is about 322 times greater than the 0.09% nationwide attack rate implied by COVID-19 case counts at the time. Men, obese individuals and those living in large households were significantly more likely to be seropositive, and the majority (64·2% [58·7-69·4]) of seropositive individuals reported no symptoms. Despite the high seroprevalence, most of the population had not been infected with SARS-CoV-2, highlighting the importance of continued measures to control viral spread and quick vaccine deployment to protect the vulnerable.The intertwined processes of learning and evolution in complex environmental niches have resulted in a remarkable diversity of morphological forms. Moreover, many aspects of animal intelligence are deeply embodied in these evolved morphologies. However, the principles governing relations between environmental complexity, evolved morphology, and the learnability of intelligent control, remain elusive, because performing large-scale in silico experiments on evolution and learning is challenging. Here, we introduce Deep Evolutionary Reinforcement Learning (DERL) a computational framework which can evolve diverse agent morphologies to learn challenging locomotion and manipulation tasks in complex environments. Leveraging DERL we demonstrate several relations between environmental complexity, morphological intelligence and the learnability of control. First, environmental complexity fosters the evolution of morphological intelligence as quantified by the ability of a morphology to facilitate the learning of novel tasks. Second, we demonstrate a morphological Baldwin effect i.e., in our simulations evolution rapidly selects morphologies that learn faster, thereby enabling behaviors learned late in the lifetime of early ancestors to be expressed early in the descendants lifetime. Third, we suggest a mechanistic basis for the above relationships through the evolution of morphologies that are more physically stable and energy efficient, and can therefore facilitate learning and control.Feature selection (marker gene selection) is widely believed to improve clustering accuracy, and is thus a key component of single cell clustering pipelines. Existing feature selection methods perform inconsistently across datasets, occasionally even resulting in poorer clustering accuracy than without feature selection. Moreover, existing methods ignore information contained in gene-gene correlations. Here, we introduce DUBStepR (Determining the Underlying Basis using Stepwise Regression), a feature selection algorithm that leverages gene-gene correlations with a novel measure of inhomogeneity in feature space, termed the Density Index (DI). Despite selecting a relatively small number of genes, DUBStepR substantially outperformed existing single-cell feature selection methods across diverse clustering benchmarks. Additionally, DUBStepR was the only method to robustly deconvolve T and NK heterogeneity by identifying disease-associated common and rare cell types and subtypes in PBMCs from rheumatoid arthritis patients.
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