频率编码和调制原理在Hodgkin-Huxley系统上的应用

频率编码指感觉神经元在受到刺激后产生膜电位的周期变化,变化的频率往往与刺激的强度成正比.本文在Hodgkin-Huxley系统的基础上,对其微分方程进行简化;对于频率编码,给出去耦时间尺度上的微分方程系统;研究在单一参数系统下,频率编码行为的变化规律.

Differential selection in HIV-1 gp120 between subtype B and East Asian variant B'

HIV-1 evolves strongly and undergoes geographic differentiation as it spreads in diverse host populations around the world.For instance,distinct genomic backgrounds can be observed between the pandemic subtype B,prevalent in Europe and North-America,and its offspring clade B＇ in East Asia.Here we ask whether this differentiation affects the selection pressure experienced by the virus.To answer this question we evaluate selection pressure on the HIV-1 envelope protein gp120 at the level of individual codons using a simple and fast estimation method based on the ratio ka/ks of amino acid changes to synonymous changes.To validate the approach we compare results to those from a state-of-the-art mixed-effect method.The agreement is acceptable,but the analysis also demonstrates some limitations of the simpler approach.Further,we find similar distributions of codons under stabilizing and directional selection pressure in gp120 for subtypes B and B＇ with more directional selection pressure in variable loops and more stabilizing selection in the constant regions.Focusing on codons with increased ka/ks values in B＇,we show that these codons are scattered over the whole of gp120,with remarkable clusters of higher density in regions flanking the variable loops.We identify a significant statistical association of glycosylation sites and codons with increased ka/ks values.

Liver Characterization of a Cohort of Alpha-1 Antitrypsin Deficiency Patients with and without Lung Disease

Background and Aims:Alpha-1 antitrypsin deficiency(AATD)is a genetic disorder characterized by the misfolding and accumulation of the mutant variant of alpha-1 antitrypsin(AAT)within hepatocytes,which limits its access to the circulation and exposes the lungs to protease-mediated tissue damage.This results in progressive liver disease secondary to AAT polymerization and accumulation,and chronic obstructive pulmonary disease(COPD)due to deficient levels of AAT within the lungs.Our goal was to characterize the unique effects of COPD secondary to AATD on liver disease and gene expression.Methods:A subcohort of AATD individuals with COPD(n=33)and AATD individuals without COPD(n=14)were evaluated in this study from our previously reported cross-sectional cohort.We used immunohistochemistry to assess the AATD liver phenotype,and RNA sequencing to explore liver transcriptomics.We observed a distinct transcriptomic profile in liver tissues from AATD individuals with COPD compared to those without.Results:A total of 339 genes were differentially expressed.Canonical pathways related to fibrosis,extracellular matrix remodeling,collagen deposition,hepatocellular damage,and inflammation were significantly upregulated in the livers of AATD individuals with COPD.Histopathological analysis also revealed higher levels of fibrosis and hepatocellular damage in these individuals.Conclusions:Our data supports a relationship between the development of COPD and liver disease in AATD and introduces genes and pathways that may play a role in AATD liver disease when COPD is present.We believe addressing lung impairment and airway inflammation may be an approach to managing AATD-related liver disease.

i2dash:Creation of Flexible,Interactive,and Web-based Dashboards for Visualization of Omics Data

Data visualization and interactive data exploration are important aspects of illustrating complex concepts and results from analyses of omics data.A suitable visualization has to be intuitive and accessible.Web-based dashboards have become popular tools for the arrangement,consolidation,and display of such visualizations.However,the combination of automated data processing pipelines handling omics data and dynamically generated,interactive dashboards is poorly solved.Here,we present i2dash,an R package intended to encapsulate functionality for the programmatic creation of customized dashboards.It supports interactive and responsive(linked)visualizations across a set of predefined graphical layouts.i2dash addresses the needs of data analysts/software developers for a tool that is compatible and attachable to any R-based analysis pipeline,thereby fostering the separation of data visualization on one hand and data analysis tasks on the other hand.In addition,the generic design of i2dash enables the development of modular extensions for specific needs.As a proof of principle,we provide an extension of i2dash optimized for single-cell RNA sequencing analysis,supporting the creation of dashboards for the visualization needs of such experiments.Equipped with these features,i2dash is suitable for extensive use in large-scale sequencing/bioinformatics facilities.Along this line,we provide i2dash as a containerized solution,enabling a straightforward large-scale deployment and sharing of dashboards using cloud services.i2dash is freely available via the R package archive CRAN(https://CRAN.R-project.org/package=i2dash).