DACFL: Dynamic Average Consensus Based Federated Learning in Decentralized Topology

Federated learning (FL) is a burgeoning distributed machine learning framework where a central parameter server (PS) coordinates many local users to train a globally consistent model. Conventional federated learning inevitably relies on a centralized topology with a PS. As a result, it will paralyze once the PS fails. To alleviate such a single point failure, especially on the PS, some existing work has provided decentralized FL (DFL) implementations like CDSGD and D-PSGD to facilitate FL in a decentralized topology. However, there are still some problems with these methods, e.g., significant divergence between users' final models in CDSGD and a network-wide model average necessity in D-PSGD. In order to solve these deficiency, this paper devises a new DFL implementation coined as DACFL, where each user trains its model using its own training data and exchanges the intermediate models with its neighbors through a symmetric and doubly stochastic matrix. The DACFL treats the progress of each user's local training as a discrete-time process and employs a first order dynamic average consensus (FODAC) method to track the \textit{average model} in the absence of the PS. In this paper, we also provide a theoretical convergence analysis of DACFL on the premise of i.i.d data to strengthen its rationality. The experimental results on MNIST, Fashion-MNIST and CIFAR-10 validate the feasibility of our solution in both time-invariant and time-varying network topologies, and declare that DACFL outperforms D-PSGD and CDSGD in most cases

Soluble inflammatory mediators induce transcriptional re-organization that is independent of dna methylation changes in cultured human chorionic villous trophoblasts.

The studies proposed here were undertaken to test the hypothesis that, under specific circumstances (e.g., a strong enough inflammatory stimulus), genes that are repressed at the maternal-fetal interface via DNA methylation might be de-methylated, allowing either a maternal immune response to the semi-allogenic fetus or the onset of early labor. Chorionic trophoblasts (CT) were isolated from fetal membranes, followed by incubation with medium from LPS-activated PBMC or resting PBMC medium for 2 h. RNA and DNA were isolated from the cells for RNA-seq and DNA methylation studies. Two hrs after being exposed to conditioned medium from LPS-activated PBMC, CT showed differential expression of 114 genes, all but 2 of which showed higher expression in the stimulated cells than is the unstimulated cells. We also identified 318 differentially methylated regions (DMRs) that associated with 306 genes (155 protein coding genes) in the two groups, but the observed methylation changes had negligible impact on the observed transcriptional changes in CT. CT display complex patterns of transcription in response to inflammation. DNA methylation does not appear to be an important regulator of the observed transcriptional changes

Attenuation of oxidative stress in HEK 293 cells by the TCM constituents schisanhenol, baicalein, resveratrol or crocetin and two defined mixtures

PURPOSE: Our working hypothesis is that single bioactive phytochemicals with antioxidant properties that are important constituents of Traditional Chinese Medicine (TCM) and their defined mixtures have potential as chemoprotective agents for chronic conditions characterized by oxidative and nitrosative stress, including Alzheimer’s. Here we evaluate the ability of baicalein, crocetin, trans-resveratrol or schisanhenol and two defined mixtures of these TCM phytochemicals to attenuate the toxicity resulting from exposure to cell permeant t-butyl hydroperoxide (tBPH) in wild-type and bioengineered (to express choline acetyltransferase) HEK 293 cells. METHODS: Endpoints of tBHP-initiated oxidative and nitrosative stress in both types of HEK 293 cells and its attenuation by TCM constituents and mixtures included cytotoxicity (LDH release); depletion of intracellular glutathione (GSH); formation of S-glutathionylated proteins; oxidative changes to the disulfide proteome; and real-time changes in intracellular redox status. RESULTS: At low µM concentrations, each of the TCM constituents and mixtures effectively attenuated intracellular toxicity due to exposure of HEK 293 cells to 50 or 250 µM tBHP for 30 min to 3 h. Confocal microscopy of HEK 293 cells transfected with mutated green fluorescent protein (roGFP2) showed effective attenuation of tBHP oxidation by baicalein in real time. Three redox-regulated proteins prominent in the disulfide proteome of HEK 293 cells were identified by MALDI-TOF mass spectrometry. CONCLUSIONS: We conclude that single TCM chemicals and their simple mixtures have potential for use in adjunct chemoprotective therapy. Advantages of mixtures compared to single TCM constituents include the ability to combine compounds with varying molecular mechanisms of cytoprotection for enhanced biological activity; and to combine chemicals with complementary pharmacokinetic properties to increase half-life and prolong activity in vivo

Pycallingcards: An integrated environment for visualizing, analyzing, and interpreting Calling Cards data

MOTIVATION: Unraveling the transcriptional programs that control how cells divide, differentiate, and respond to their environments requires a precise understanding of transcription factors\u27 (TFs) DNA-binding activities. Calling cards (CC) technology uses transposons to capture transient TF binding events at one instant in time and then read them out at a later time. This methodology can also be used to simultaneously measure TF binding and mRNA expression from single-cell CC and to record and integrate TF binding events across time in any cell type of interest without the need for purification. Despite these advantages, there has been a lack of dedicated bioinformatics tools for the detailed analysis of CC data. RESULTS: We introduce Pycallingcards, a comprehensive Python module specifically designed for the analysis of single-cell and bulk CC data across multiple species. Pycallingcards introduces two innovative peak callers, CCcaller and MACCs, enhancing the accuracy and speed of pinpointing TF binding sites from CC data. Pycallingcards offers a fully integrated environment for data visualization, motif finding, and comparative analysis with RNA-seq and ChIP-seq datasets. To illustrate its practical application, we have reanalyzed previously published mouse cortex and glioblastoma datasets. This analysis revealed novel cell-type-specific binding sites and potential sex-linked TF regulators, furthering our understanding of TF binding and gene expression relationships. Thus, Pycallingcards, with its user-friendly design and seamless interface with the Python data science ecosystem, stands as a critical tool for advancing the analysis of TF functions via CC data. AVAILABILITY AND IMPLEMENTATION: Pycallingcards can be accessed on the GitHub repository: https://github.com/The-Mitra-Lab/pycallingcards

Comparing genomic and epigenomic features across species using the WashU Comparative Epigenome Browser

Genome browsers have become an intuitive and critical tool to visualize and analyze genomic features and data. Conventional genome browsers display data/annotations on a single reference genome/assembly; there are also genomic alignment viewer/browsers that help users visualize alignment, mismatch, and rearrangement between syntenic regions. However, there is a growing need for a comparative epigenome browser that can display genomic and epigenomic data sets across different species and enable users to compare them between syntenic regions. Here, we present the WashU Comparative Epigenome Browser. It allows users to load functional genomic data sets/annotations mapped to different genomes and display them over syntenic regions simultaneously. The browser also displays genetic differences between the genomes from single-nucleotide variants (SNVs) to structural variants (SVs) to visualize the association between epigenomic differences and genetic differences. Instead of anchoring all data sets to the reference genome coordinates, it creates independent coordinates of different genome assemblies to faithfully present features and data mapped to different genomes. It uses a simple, intuitive genome-align track to illustrate the syntenic relationship between different species. It extends the widely used WashU Epigenome Browser infrastructure and can be expanded to support multiple species. This new browser function will greatly facilitate comparative genomic/epigenomic research, as well as support the recent growing needs to directly compare and benchmark the T2T CHM13 assembly and other human genome assemblies

Neglschisandrins E–F: Two New Lignans and Related Cytotoxic Lignans from Schisandra neglecta

Phytochemical investigation of an ethanolic extract of stems of Schisandra neglecta led to the isolation and identification of two new dibenzocyclooctadiene lignans, designated neglschisandrins E ( 1) and F ( 2), and thirteen known lignans. All structures and stereochemistries were determined by spectroscopic methods, including 2D-NMR techniques. The isolates were evaluated for in vitro cytotoxic activity. Among them, compounds 2– 6 exhibited moderate to weak cytotoxicity against the human colorectal carcinoma HCT-8 cell line with EC 50 values of 7.33~19.8 μg/mL. In addition, compounds 2– 4 also exhibited marginal cytotoxicity against the human lung carcinoma A549 cell line with EC 50 values of 11.8~15.0 μg/mL

WashU Epigenome Browser update 2022

WashU Epigenome Browser (https://epigenomegateway.wustl.edu/browser/) is a web-based genomic data exploration tool that provides visualization, integration, and analysis of epigenomic datasets. The newly renovated user interface and functions have enabled researchers to engage with the browser and genomic data more efficiently and effectively since 2018. Here, we introduce a new integrated panel design in the browser that allows users to interact with 1D (genomic features), 2D (such as Hi-C), 3D (genome structure), and 4D (time series) data in a single web page. The browser can display three-dimensional chromatin structures with the 3D viewer module. The 4D tracks, called \u27Dynamic\u27 tracks, animatedly display time-series data, allowing for a more striking visual impact to identify the gene or genomic region candidates as a function of time. Genomic data, such as annotation features, numerical values, and chromatin interaction data can all be viewed in the dynamic track mode. Imaging data from microscopy experiments can also be displayed in the browser. In addition to software development, we continue to service and expand the data hubs we host for large consortia including 4DN, Roadmap Epigenomics, TaRGET and ENCODE, among others. Our growing user/developer community developed additional track types as plugins, such as qBed and dynseq tracks, which extend the utility of the browser. The browser serves as a foundation for additional genomics platforms including the WashU Virus Genome Browser (for COVID-19 research) and the Comparative Genome Browser. The WashU Epigenome Browser can also be accessed freely through Amazon Web Services at https://epigenomegateway.org/

Epigenetic dynamics shaping melanophore and iridophore cell fate in zebrafish

BACKGROUND: Zebrafish pigment cell differentiation provides an attractive model for studying cell fate progression as a neural crest progenitor engenders diverse cell types, including two morphologically distinct pigment cells: black melanophores and reflective iridophores. Nontrivial classical genetic and transcriptomic approaches have revealed essential molecular mechanisms and gene regulatory circuits that drive neural crest-derived cell fate decisions. However, how the epigenetic landscape contributes to pigment cell differentiation, especially in the context of iridophore cell fate, is poorly understood. RESULTS: We chart the global changes in the epigenetic landscape, including DNA methylation and chromatin accessibility, during neural crest differentiation into melanophores and iridophores to identify epigenetic determinants shaping cell type-specific gene expression. Motif enrichment in the epigenetically dynamic regions reveals putative transcription factors that might be responsible for driving pigment cell identity. Through this effort, in the relatively uncharacterized iridophores, we validate alx4a as a necessary and sufficient transcription factor for iridophore differentiation and present evidence on alx4a\u27s potential regulatory role in guanine synthesis pathway. CONCLUSIONS: Pigment cell fate is marked by substantial DNA demethylation events coupled with dynamic chromatin accessibility to potentiate gene regulation through cis-regulatory control. Here, we provide a multi-omic resource for neural crest differentiation into melanophores and iridophores. This work led to the discovery and validation of iridophore-specific alx4a transcription factor

http://lcgdbzz.org/qk_content.asp?id=8833

ObjectiveTo investigate the clinical features and diagnosis and treatment of acute fatty liver of pregnancy (AFLP). Methods A retrospective analysis was performed for the clinical data of 12 patients with AFLP who were diagnosed and treated in Department of Infectious Diseases, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, from April 2012 to March 2017, including general data, clinical manifestations, laboratory markers, imaging examinations, treatment, and prognosis. ResultsAll 12 patients developed AFLP in late pregnancy, and major clinical manifestations included gastrointestinal symptoms, liver failure, jaundice, and coagulation disorder. All patients were given multimodality therapy to protect the liver, improve coagulation, and reduce infection, 11 patients underwent cesarean section, 6 underwent blood filtration, 5 underwent plasma exchange. One patient died, resulting in a mortality rate of 83%, 5 perinatal infants died, resulting in a mortality rate of 357%. ConclusionIn patients with AFLP, early diagnosis, timely termination of pregnancy, maximum symptomatic/supportive treatment, and control of infection, as well as the artificial liver support system, is the key to improving the prognosis of mothers and infants

Simultaneous determination of six steroidal saponins and one ecdysone in Asparagus filicinus using high performance liquid chromatography coupled with evaporative light scattering detection

A high-performance liquid chromatography coupled with an evaporative light scattering detector (HPLC–ELSD) has been developed to evaluate the quality of Asparagus filicinus through a simultaneous determination of six steroidal saponins and one ecdysone, including aspafiliosides A, B, C, E, G, filiasparoside A and 20-hydroxyecdysone. With a C18 analytical column, the seven analytes were separated efficiently using acetonitrile–water as the mobile phase in a gradient program. The method limits of detection ranged 0.125–0.225 μg, and the method limits of quantitation ranged 0.408–0.720 μg, respectively. The intra- and inter-day precisions of the method were evaluated and were all less than 3%. All the recoveries for the spiked analytes ranged 95.16%–100.61%. The proposed method was successfully applied to quantify the seven components in thirteen samples from different localities in China