Conformation capture technologies (e.g., Hi-C) chart physical interactions between chromatin regions on a genome-wide scale. However, the structural variability of the genome between cells poses a great challenge to interpreting ensemble-averaged Hi-C data, particularly for long-range and interchromosomal interactions. Here, we present a probabilistic approach for deconvoluting Hi-C data into a model population of distinct diploid 3D genome structures, which facilitates the detection of chromatin interactions likely to co-occur in individual cells. Our approach incorporates the stochastic nature of chromosome conformations and allows a detailed analysis of alternative chromatin structure states. For example, we predict and experimentally confirm the presence of large centromere clusters with distinct chromosome compositions varying between individual cells. The stability of these clusters varies greatly with their chromosome identities. We show that these chromosome-specific clusters can play a key role in the overall chromosome positioning in the nucleus and stabilizing specific chromatin interactions. By explicitly considering genome structural variability, our population-based method provides an important tool for revealing novel insights into the key factors shaping the spatial genome organization. (14), and single-cell (15) and in situ Hi-C (16)], close chromatin contacts can now be identified at increasing resolution, providing new insight into genome organization. These methods measure the relative frequencies of chromosome interactions averaged over a large population of cells. However, individual 3D genome structures can vary dramatically from cell to cell even within an isogenic sample, especially with respect to long-range interactions (15,17,18). This structural variability poses a great challenge to the interpretation of ensemble-averaged Hi-C data (14,(19)(20)(21)(22)(23) and prevents the direct detection of cooperative interactions co-occurring in the same cell. This problem is particularly evident for long-range (cis) and interchromosomal (trans) interactions, which are generally observed at relatively low frequencies and are therefore present only in a small subset of individual cells at any given time (3,11,15). Despite their low frequencies, long-range and interchromosome interaction patterns are not random noise. In fact, these interactions are more informative than short-range interactions in determining the global genome architectures in cells and are often functionally relevant-interactions between transcriptionally active regions are often interchromosomal in nature (14). Owing to their variable nature, long-range and trans interactions can be part of alternative, structurally different conformations, which makes their interpretation in form of consensus structures impossible. However, inferring which of the long-range interactions co-occur in the same cell from ensemble Hi-C data remains a major challenge.These challenges cannot be easily overcome even by the new single-cell Hi-C techno...
By training the deep neural network model, the hidden features in Surface Electromyography(sEMG) signals can be extracted. The motion intention of the human can be predicted by analysis of sEMG. However, the models recently proposed by researchers often have a large number of parameters. Therefore, we designed a compact Convolution Neural Network (CNN) model, which not only improves the classification accuracy but also reduces the number of parameters in the model. Our proposed model was validated on the Ninapro DB5 Dataset and the Myo Dataset. The classification accuracy of gesture recognition achieved good results.
Ru(II)-catalyzed enantioselective C−H functionalization involving an enantiodetermining C−H cleavage step remains undeveloped. Here we describe a Ru(II)-catalyzed enantioselective C−H activation/annulation of sulfoximines with αcarbonyl sulfoxonium ylides using a novel class of chiral binaphthyl monocarboxylic acids as chiral ligands, which can be easily and modularly prepared from 1,1′-binaphthyl-2,2′-dicarboxylic acid. A broad range of sulfur-stereogenic sulfoximines were prepared in high yields with excellent enantioselectivities (up to 99% yield and 99% ee) via desymmetrization, kinetic resolution, and parallel kinetic resolution. Furthermore, the resolution products can be easily transformed to chiral sulfoxides and key intermediates for kinase inhibitors.
Transition-metal-catalyzed asymmetric C–H activation
reactions
generally rely on the design of ligands with sterically bulky groups
to create a chiral environment for enantioinduction through steric
repulsion. Here we describe an Ir(III)-catalyzed asymmetric C–H
activation enabled by noncovalent interactions. A broad range of sulfur-stereogenic
sulfoximines was prepared in high yields with excellent enantioselectivities via the asymmetric C–H activation/annulation of sulfoximines
with diazo compounds. Desymmetrization, kinetic resolution, and parallel
kinetic resolution are compatible with this protocol. Detailed DFT
calculations suggested that the N–H···O hydrogen
bonding interaction between sulfoximine and the chiral carboxylic
acid ligand was crucial for the high enantiocontrol. Moreover, chiral
iridacycle intermediates were isolated, characterized, and subjected
to stoichiometric reactions. Computational and experimental studies
suggested that the C–H cleavage step was the rate- and enantio-determining
step.
We examine the problem of finite Fermi systems having a degenerate single-particle spectrum and show that the Landau approach, applied to such a system, admits the possibility of merging single-particle levels. It is demonstrated that the opportunity for this behavior is widespread in quantum many-body systems. The salient feature of the phenomenon is the occurrence of nonintegral quasiparticle occupation numbers, leading to a radical alteration of the standard quasiparticle picture. Implications of this alteration are considered for nuclear, atomic, and solid-state systems.
Background
Increasing evidence demonstrate that the gut microbiota is involved in the pathogenesis of liver diseases, and faecal microbiota transplantation is considered to be a promising new treatment option. However, there are no reports on the intestinal flora of asymptomatic HBV carriers using next-generation sequencing. This study intends to investigate the potential role of the intestinal microflora in predicting the progression of Hepatitis B patients in different non-cancerous stages.
Results
A total of 266 patients with different stages of Hepatitis B and 31 healthy controls were included in this study. Some of the subjects (217 cases) underwent 16S rRNA gene sequencing. Compared with the control group (CK), the α diversity of patients in Group A (HBV carrier) slightly increased, while that of patients in the other three groups decreased. Each group of patients, especially those in Group C (cirrhosis) and Group D (acute-on-chronic liver failure), could be separated from the CK using weighted UniFrac PCoA and ANOSIM. LEfSe revealed that 40 taxa belonging to three phyla had an LDA larger than 4. In addition to the comparison between Group B (chronic Hepatitis B) and Group C, the specific flora and potential taxonomic function were also identified. Different microbial communities were found to be highly correlated with clinical indicators and the Child-Pugh scores. Changes in the microbial community were highly related to the alternations of host metabolism, which in turn, was related to the development of Hepatitis B. Our analysis identified a total of 47 strains with potential biomarker functions at all levels except for the phylum level.
Conclusions
Faecal microbiota transplantation of some potential beneficial bacteria can change with the occurrence of disease, and HBV carriers might be the most suitable donors.
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