Charged and polar groups, through forming ion pairs, hydrogen bonds, and other less specific electrostatic interactions, impart important properties to proteins. Modulation of the charges on the ...amino acids, e.g., by pH and by phosphorylation and dephosphorylation, have significant effects such as protein denaturation and switch-like response of signal transduction networks. This review aims to present a unifying theme among the various effects of protein charges and polar groups. Simple models will be used to illustrate basic ideas about electrostatic interactions in proteins, and these ideas in turn will be used to elucidate the roles of electrostatic interactions in protein structure, folding, binding, condensation, and related biological functions. In particular, we will examine how charged side chains are spatially distributed in various types of proteins and how electrostatic interactions affect thermodynamic and kinetic properties of proteins. Our hope is to capture both important historical developments and recent experimental and theoretical advances in quantifying electrostatic contributions of proteins.
An improved feed-forward carrier phase recovery method is proposed for coherent receivers using M-ary quadrature amplitude modulation-based modulation formats. It is shown that by introducing ...multiple cascaded feed-forward carrier recovery stages, the required compute power can be significantly reduced compared to the prior art using the single-stage-based blind phase search method.
Many spatially resolved transcriptomic technologies do not have single-cell resolution but measure the average gene expression for each spot from a mixture of cells of potentially heterogeneous cell ...types. Here, we introduce a deconvolution method, conditional autoregressive-based deconvolution (CARD), that combines cell-type-specific expression information from single-cell RNA sequencing (scRNA-seq) with correlation in cell-type composition across tissue locations. Modeling spatial correlation allows us to borrow the cell-type composition information across locations, improving accuracy of deconvolution even with a mismatched scRNA-seq reference. CARD can also impute cell-type compositions and gene expression levels at unmeasured tissue locations to enable the construction of a refined spatial tissue map with a resolution arbitrarily higher than that measured in the original study and can perform deconvolution without an scRNA-seq reference. Applications to four datasets, including a pancreatic cancer dataset, identified multiple cell types and molecular markers with distinct spatial localization that define the progression, heterogeneity and compartmentalization of pancreatic cancer.
Income inequality in today’s China Xie, Yu; Zhou, Xiang
Proceedings of the National Academy of Sciences - PNAS,
05/2014, Volume:
111, Issue:
19
Journal Article
Peer reviewed
Open access
Using multiple data sources, we establish that China's income inequality since 2005 has reached very high levels, with the Gini coefficient in the range of 0.53–0.55. Analyzing comparable survey data ...collected in 2010 in China and the United States, we examine social determinants that help explain China’s high income inequality. Our results indicate that a substantial part of China’s high income inequality is due to regional disparities and the rural-urban gap. The contributions of these two structural forces are particularly strong in China, but they play a negligible role in generating the overall income inequality in the United States, where individual-level and family-level income determinants, such as family structure and race/ethnicity, play a much larger role.
Linear mixed models have attracted considerable attention recently as a powerful and effective tool for accounting for population stratification and relatedness in genetic association tests. However, ...existing methods for exact computation of standard test statistics are computationally impractical for even moderate-sized genome-wide association studies. To address this issue, several approximate methods have been proposed. Here, we present an efficient exact method, which we refer to as genome-wide efficient mixed-model association (GEMMA), that makes approximations unnecessary in many contexts. This method is approximately n times faster than the widely used exact method known as efficient mixed-model association (EMMA), where n is the sample size, making exact genome-wide association analysis computationally practical for large numbers of individuals.
Multivariate linear mixed models (mvLMMs) are powerful tools for testing associations between single-nucleotide polymorphisms and multiple correlated phenotypes while controlling for population ...stratification in genome-wide association studies. We present efficient algorithms in the genome-wide efficient mixed model association (GEMMA) software for fitting mvLMMs and computing likelihood ratio tests. These algorithms offer improved computation speed, power and P-value calibration over existing methods, and can deal with more than two phenotypes.
The functions of many proteins are regulated through allostery, whereby effector binding at a distal site changes the functional activity (e.g., substrate binding affinity or catalytic efficiency) at ...the active site. Most allosteric studies have focused on thermodynamic properties, in particular, substrate binding affinity. Changes in substrate binding affinity by allosteric effectors have generally been thought to be mediated by conformational transitions of the proteins or, alternatively, by changes in the broadness of the free energy basin of the protein conformational state without shifting the basin minimum position. When effector binding changes the free energy landscape of a protein in conformational space, the change affects not only thermodynamic properties but also dynamic properties, including the amplitudes of motions on different time scales and rates of conformational transitions. Here we assess the roles of conformational dynamics in allosteric regulation. Two cases are highlighted where NMR spectroscopy and molecular dynamics simulation have been used as complementary approaches to identify residues possibly involved in allosteric communication. Perspectives on contentious issues, for example, the relationship between picosecond–nanosecond local and microsecond–millisecond conformational exchange dynamics, are presented.
We review and study several single carrier based multi-level and multi-dimensional coding (ML-MDC) technologies recently demonstrated for spectrally-efficient 100-Gb/s transmission. These include ...16-ary PDM-QPSK, 64-ary PDM-8PSK, 64-ary PDM-8QAM as well as 256-ary PDM-16 QAM. We show that high-speed QPSK, 8PSK, 8QAM, and 16QAM can all be generated using commercially available optical modulators using only binary electrical drive signals through novel synthesis methods, and that all of these modulation formats can be detected using a universal receiver front-end and digital coherent detection. We show that the constant modulus algorithm (CMA), which is highly effective for blind polarization recovery of PDM-QPSK and PDM-8PSK signals, is much less effective for PDM-8QAM and PDM-16 QAM. We then present a recently proposed, cascaded multi-modulus algorithm for these cases. In addition to the DSP algorithms used for constellation recovery, we also describe a DSP algorithm to improve the performance of a coherent receiver using single-ended photo-detection. The system impact of ASE noise, laser phase noise, narrowband optical filtering and fiber nonlinear effects has been investigated. For high-level modulation formats using full receiver-side digital compensation, it is shown that the requirement on LO phase noise is more stringent than the signal laser. We also show that RZ pulse shaping significantly improves filter- and fiber-nonlinear tolerance. Finally we present three high-spectral-efficiency and high-speed DWDM transmission experiments implementing these ML-MDC technologies.
Aquaculture is a booming industry in the world and China is the largest producer and exporter of aquatic products. To prevent and treat diseases occurred in aquaculture, antibiotics are widely ...applied. However, the information of antibiotics used in Chinese aquaculture is still limited. Based on peer-reviewed papers, documents, reports, and even farmer surveys, this review summarized antibiotics used in Chinese aquaculture. In 2014, more than 47.4 million tonnes of farmed aquatic products were produced in mainland China. The outputs in the east and south parts of China can reach as much as 600 times higher than those in the northwest areas, which is clearly separated by the “Hu Line” – a line that marks a striking difference in the distribution of population. A total of 20 antibiotics belonging to eight categories have been reported for use, mainly via oral administration. However, only 13 antibiotics have been authorized for application in Chinese aquaculture and 12 antibiotics used are not authorized. Totally, 234 cases on antibiotic residues in Chinese aquatic products were recorded, including 24 fish species, eight crustacean species, and four mollusk species. Thirty-two antibiotics have been detected in aquatic products; quinolones and sulfonamides were the dominated residual chemicals. For specific compound, ciprofloxacin, norfloxacin, and sulfisoxazole have the highest concentrations. Except for a few cases, all residual concentrations were lower than the maximum residue limits. Through the consumption of aquatic products tainted by antibiotics, humans may acquire adverse drug reactions or antibiotic-resistant bacteria. However, the risk of antimicrobial resistance in human body, when exposed to antibiotics at sub-inhibitory concentrations, has not been exhaustively considered in the risk assessment. In addition, a national comprehensive investigation on the amount of antibiotics used in Chinese aquaculture is still needed in future studies.
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•Present the distribution of aquaculture production and density in different regions of China.•Summary the varieties and doses of antibiotics used in Chinese aquaculture.•Clarify the occurrence and residues of antibiotics in aquatic products of China.•Examine the human health risk to antibiotics via consumption of aquatic products.
The usage, residue, potential human health risk of antibiotics in Chinese aquaculture were systematically summarized.
MicroRNAs (miRNAs) are small noncoding RNAs, approximately 18–25 nucleotides in length, now recognized as one of the major regulatory gene families in eukaryotes. Recent advances have been made in ...understanding the complicated roles of miRNAs in epigenetic regulation. miRNAs, as epigenetic modulators, affect the protein levels of the target mRNAs without modifying the gene sequences. Moreover, miRNAs can also be regulated by epigenetic modifications, including DNA methylation, RNA modification, and histone modifications. The reciprocal actions of miRNAs and epigenetic pathway appear to form a miRNA-epigenetic feedback loop and have an extensive influence on gene expression proliferation. The dysregulation of the miRNA-epigenetic feedback loop interferes with the physiological and pathological processes and contributes to variety of diseases. In this review, we focus on the reciprocal interconnection of miRNAs in epigenetic regulation, with the aim of offering new insights into the epigenetic regulatory mechanism that can be used to combat diseases.