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Turbulence is a complex and chaotic state of fluid motion. Atmospheric turbulence within the Earth’s atmosphere poses fundamental challenges for applications such as remote sensing, free-space optical communications and astronomical observation due to its rapid evolution across temporal and spatial scales. Conventional methods for studying atmospheric turbulence face hurdles in capturing the wide-field distribution of turbulence due to its transparency and anisoplanatism. Here we develop a light-field-based plug-and-play wide-field wavefront sensor (WWS), facilitating the direct observation of atmospheric turbulence over 1,100 arcsec at 30 Hz. The experimental measurements agreed with the von Kármán turbulence model, further verified using a differential image motion monitor. Attached to an 80 cm telescope, our WWS enables clear turbulence profiling of three layers below an altitude of 750 m and high-resolution aberration-corrected imaging without additional deformable mirrors. The WWS also enables prediction of the evolution of turbulence dynamics within 33 ms using a convolutional recurrent neural network with wide-field measurements, leading to more accurate pre-compensation of turbulence-induced errors during free-space optical communication. Wide-field sensing of dynamic turbulence wavefronts provides new opportunities for studying the evolution of turbulence in the broad field of atmospheric optics.

The fast charging problem of lithium-ion batteries with minimum charging time while limiting battery degradation is receiving increasing attention and is a critical challenge to battery community. Difficulties in this optimization lie in that: 1) the parameter space of charging strategies is high dimensional, while the budget of the experimental cost is often limited; 2) the evaluation of charging strategies' performance is expensive; and 3) the degradation process of the battery is strongly nonlinear, and multiple degradation mechanisms occur simultaneously leading to difficulties for establishing accurate first-principle models. Current methods to address these difficulties are mainly electrochemical-model-based optimization and grid search, which are rarely adaptive to battery degradation and/or are of low sample efficiency. In this article, we propose an adaptive model-based reinforcement learning (RL) approach for fast-charging optimization while limiting battery degradation, in which a probabilistic surrogate model of differential Gaussian process (GP) is adopted to adaptively describe the degradation of cells. The effectiveness of the proposed approach is demonstrated on PETLION, a high-performance porous-electrode-theory-based battery simulator. The results show that 1) compared with the model-free RL method, the proposed adaptive GP-based RL approach possesses superior charging performance and high sample efficiency and 2) the proposed method performs well in the handling of degradation constraints on voltage and temperature for dynamically aging batteries with its adaptability to the variations of environment.

The immune response to SARS-CoV-2 antigen after infection or vaccination is defined by the durable production of antibodies and T cells. Population-based monitoring typically focuses on antibody titer, but there is a need for improved characterization and quantification of T cell responses. Here, we used multimodal sequencing technologies to perform a longitudinal analysis of circulating human leukocytes collected before and after immunization with the mRNA vaccine BNT162b2. Our data indicated distinct subpopulations of CD8+T cells, which reliably appeared 28 days after prime vaccination. Using a suite of cross-modality integration tools, we defined their transcriptome, accessible chromatin landscape and immunophenotype, and we identified unique biomarkers within each modality. We further showed that this vaccine-induced population was SARS-CoV-2 antigen-specific and capable of rapid clonal expansion. Moreover, we identified these CD8+T cell populations in scRNA-seq datasets from COVID-19 patients and found that their relative frequency and differentiation outcomes were predictive of subsequent clinical outcomes.

Pooled CRISPR screens coupled with single-cell RNA-sequencing have enabled systematic interrogation of gene function and regulatory networks. Here, we introduce Cas13 RNA Perturb-seq (CaRPool-seq), which leverages the RNA-targeting CRISPR–Cas13d system and enables efficient combinatorial perturbations alongside multimodal single-cell profiling. CaRPool-seq encodes multiple perturbations on a cleavable CRISPR array that is associated with a detectable barcode sequence, allowing for the simultaneous targeting of multiple genes. We compared CaRPool-seq to existing Cas9-based methods, highlighting its unique strength to efficiently profile combinatorially perturbed cells. Finally, we apply CaRPool-seq to perform multiplexed combinatorial perturbations of myeloid differentiation regulators in an acute myeloid leukemia (AML) model system and identify extensive interactions between different chromatin regulators that can enhance or suppress AML differentiation phenotypes.

OBJECTIVE--Pertussis toxin uncoupling-based studies have shown that Gαi and Gαo can inhibit insulin secretion in pancreatic β-cells. Yet it is unclear whether Gαi and Gαo operate through identical mechanisms and how these G-protein-mediated signals inhibit insulin secretion in vivo. Our objective is to examine whether/how Gαo regulates islet development and insulin secretion in β-cells. RESEARCH DESIGN AND METHODS--Immunoassays were used to analyze the Gαo expression in mouse pancreatic cells. Gαo was specifically inactivated in pancreatic progenitor cells by pancreatic cell-specific gene deletion. Hormone expression and insulin secretion in response to different stimuli were assayed in vivo and in vitro. Electron microscope and total internal reflection fluorescence-based assays were used to evaluate how Gαo regulates insulin vesicle docking and secretion in response to glucose stimulation. RESULTS--Islet cells differentiate properly in [Gαo.sup.-/-] mutant mice. Gαo inactivation significantly enhances insulin secretion both in vivo and in isolation. Gαo nullizygous β-cells contain an increased number of insulin granules docked on the cell plasma membrane, although the total number of vesicles per β-cell remains unchanged. CONCLUSIONS--Gαo is not required for endocrine islet cell differentiation, but it regulates the number of insulin vesicles docked on the β-cell membrane. Diabetes 59:2522-2529, 2010, Nutritional signals, including glucose and amino acids, are the major inducers for insulin secretion in pancreatic β-cells. Upon glucose entry into β-cells, glucokinase initiates glucose metabolism to increase the cytosolic [...]

Two-dimensional layered-like materials are attracted extensive attention to be the potential cathode materials for magnesium ion batteries because of the wide layer distances and high capacities. Whereas such strong interaction between bivalent Mg2+and layered cathode materials is prone to cause the slow diffusion kinetics, and irreversible electrochemical reaction, finally bringing about the low specific capacity and inferior rate capability. Meanwhile, limited by the inherent crystal structure of MoSe2and unsuitable electrolyte, the magnesium storage properties are not ideal. Herein, the low-crystalline 1T/2H-MoSe2heterostructure (LC-MoSe2) is synthesized via one-step hydrothermal method. Such low-crystalline feature of LC-MoSe2and MgCl+in the electrolyte significantly decrease the Mg2+diffusion barrier, and largely promote the Mg2+diffusion kinetics. The rich heterogeneous interfaces in the 1T/2H-MoSe2boost the electron/ion transfer kinetics and endow plentiful active sites for the Mg2+storage. As expected, the LC-MoSe2exhibits a high discharge capacity (257.4 mAh g−1/0.5 A g−1/200 cycles) and stable long-span cyclic life of 2000/1000 loops even at 2/5 A g−1, distinctly transcending those of relatively high-crystalline MoSe2(HC-MoSe2). Such electrode can also surprisingly cycle at an ultra-high rate of 10 A g−1. Meanwhile, the charge transfer/ion diffusion kinetics along with charge storage mechanism of LC-MoSe2are carried out by various kinetics strategies from experimental and theoretical aspects. The reaction mechanism has also been discussed by some ex-situ characterization techniques. The remarkable Mg2+storage properties of LC-MoSe2cathode materials provide new ideas for the long-run development of MIBs.

The mutualistic relationship of gut-resident microbiota and the host immune system promotes homeostasis that ensures maintenance of the microbial community and of a largely non-aggressive immune cell compartment1,2. The consequences of disturbing this balance include proximal inflammatory conditions, such as Crohn’s disease, and systemic illnesses. This equilibrium is achieved in part through the induction of both effector and suppressor arms of the adaptive immune system. Helicobacterspecies induce T regulatory (Treg) and T follicular helper (TFH) cells under homeostatic conditions, but induce inflammatory T helper 17 (TH17) cells when induced Treg(iTreg) cells are compromised3,4. How Helicobacterand other gut bacteria direct T cells to adopt distinct functions remains poorly understood. Here we investigated the cells and molecular components required for iTregcell differentiation. We found that antigen presentation by cells expressing RORγt, rather than by classical dendritic cells, was required and sufficient for induction of Tregcells. These RORγt+cells—probably type 3 innate lymphoid cells and/or Janus cells5—require the antigen-presentation machinery, the chemokine receptor CCR7 and the TGFβ activator αvintegrin. In the absence of any of these factors, there was expansion of pathogenic TH17 cells instead of iTregcells, induced by CCR7-independent antigen-presenting cells. Thus, intestinal commensal microbes and their products target multiple antigen-presenting cells with pre-determined features suited to directing appropriate T cell differentiation programmes, rather than a common antigen-presenting cell that they endow with appropriate functions.

The expression of inhibitory immune checkpoint molecules, such as programmed death-ligand (PD-L)1, is frequently observed in human cancers and can lead to the suppression of T cell–mediated immune responses. Here, we apply expanded CRISPR-compatible (EC)CITE-seq, a technology that combines pooled CRISPR screens with single-cell mRNA and surface protein measurements, to explore the molecular networks that regulate PD-L1 expression. We also develop a computational framework, mixscape, that substantially improves the signal-to-noise ratio in single-cell perturbation screens by identifying and removing confounding sources of variation. Applying these tools, we identify and validate regulators of PD-L1 and leverage our multimodal data to identify both transcriptional and post-transcriptional modes of regulation. Specifically, we discover that the Kelch-like protein KEAP1 and the transcriptional activator NRF2 mediate the upregulation of PD-L1 after interferon (IFN)-γ stimulation. Our results identify a new mechanism for the regulation of immune checkpoints and present a powerful analytical framework for the analysis of multimodal single-cell perturbation screens.

•Whole-genome sequencing of Mycobacterium tuberculosis(MTB) isolates.•21 isolates (72.4%) were multidrug-resistant (MDR) and 1 (3.4%) was extensively-drug resistant (XDR-TB).•The most common mutations observed for isoniazid and rifampicin resistance were katG(S315T) and rpoB(S450L), respectively.•The most common mutations observed for ofloxacin and kanamycin resistance were gyrA(A90V) and rrs(A1401G), respectively.•The isolates belonged mainly to lineages 2 and 3, with most MDR-TB among lineage 2 isolates.

A DNA microarray can measure the expression of thousands of genes simultaneously, and this enables us to study the molecular pathways underlying Age-related Macular Degeneration. Previous studies have not determined which genes are responsible for the process of AMD. The authors address this deficiency by applying modern data mining and machine learning feature selection algorithms to the AMD microarray dataset. In this paper four methods are utilized to perform feature selection: Naïve Bayes, Random Forest, Random Lasso, and Ensemble Feature Selection. Functional Annotation of 20 final selected genes suggests that most of them are responsible for signal transduction in an individual cell or between cells. The top seven genes, five protein-coding genes and two non-coding RNAs, are explored from their signaling pathways, functional interactions and associations with retinal pigment epithelium cells. The authors conclude that Pten/PI3K/Akt pathway, NF-kappaB pathway, JNK cascade, Non-canonical Wnt Pathway, and two biological processes of cilia are likely to play important roles in AMD pathogenesis.

ATR (ataxia telangiectasia-mutated and Rad3-related) protein kinase and ATRIP (ATR-interacting protein) form a complex and play a critical role in response to replication stress and DNA damage. Here, we determined the cryo-electron microscopy (EM) structure of the human ATR-ATRIP complex at 4.7 Å resolution and built an atomic model of the C-terminal catalytic core of ATR (residues 1 521-2 644) at 3.9 Å resolution. The complex adopts a hollow “heart” shape, consisting of two ATR monomers in distinct conformations. The EM map for ATRIP reveals 14 HEAT repeats in an extended “S” shape. The conformational flexibility of ATR allows ATRIP to properly lock the N-termini of the two ATR monomers to favor ATR-ATRIP complex formation and functional diversity. The isolated “head-head” and “tail-tail” each adopts a pseudo 2-fold symmetry. The catalytic pockets face outward and substrate access is not restricted by inhibitory elements. Our studies provide a structural basis for understanding the assembly of the ATR-ATRIP complex and a framework for characterizing ATR-mediated DNA repair pathways.

Sodium-ion batteries (SIBs) are attracting worldwide attention due to their multiple merits including abundant reserve and safety. However, industrialization is challenged by the scarcity of high-performance carbon anodes with high specific capacities. Here, we report the metal-assisted microcrystalline structure regulation of carbon materials to achieve high-capacity sodium storage. Systematic investigations of in situthermal-treatment X-ray diffraction and multiple spectroscopies uncover the regulation mechanism of constructing steric hindrance (C–O–C bonds) to restrain the aromatic polycondensation reaction. The carbon precursor of polycyclic aromatic hydrocarbon-type pitch contributes to a high carbon yield rate (40%) compared with those of resin and biomass precursors. The as-synthesized carbon materials deliver high capacities of up to 390 mAh g–1, surpassing many reported carbon anodes for SIBs. Through correlating specific capacity with ID/IGvalues in Raman spectra and theoretical calculation of carbon materials regulated by different metal elements (Mn, Nb, Ce, Cr, and V), we identify and propose the binding energy as the descriptor for characterizing the capability of regulating the carbon microcrystalline structure to promote sodium storage. This work provides a universal method for regulating the carbon structure, which may lead to the controlled design and fabrication of carbon materials for energy storage and conversion and beyond.