Cell-Free Seminal mRNA and MicroRNA Exist in Different Forms

BACKGROUND: The great interest in cell-free mRNA, microRNA (miRNA) as molecular biomarkers for clinical applications, and as 'signaling' molecules for intercellular communication highlights the need to reveal their physical nature. Here this issue was explored in human cell-free seminal mRNA (cfs-mRNA) and miRNA (cfs-miRNA). METHODOLOGY/PRINCIPAL FINDINGS: Selected male reproductive organ-specific mRNAs, miRNAs, and piRNAs were quantified by quantitative real-time PCR in all experiments. While the stability of cfs-miRNA assessed by time-course analysis (up to 24 h at room temperature) was similar with cfs-mRNA, the reductive changes between cfs-miRNA and cfs-mRNA after filtration and Triton X-100 treatment on seminal plasma were very different, implying their different physical nature. Seminal microvesicles (SMVs) were then recovered and proportions of cfs-mRNA and cfs-miRNA within SMVs were quantified. The amounts of SMVs- sequestered cfs-mRNAs almost were the same as total cfs-mRNA, and were highly variable depending on the different sizes of SMVs. But most of cfs-miRNA was independent of SMVs and existed in the supernatant. The possible form of cfs-miRNA in the supernatant was further explored by filtration and protease K digestion. It passed through the 0.10-µm pore, but was degraded dramatically after intense protease K digestion. CONCLUSIONS/SIGNIFICANCE: The predominant cfs-mRNA is contained in SMVs, while most cfs-miRNA is bound with protein complexes. Our data explained the stability of extracellular RNAs in human semen, and shed light on their origins and potential functions in male reproduction, and strategy of developing them as biomarkers of male reproductive system

Sequence Design for Cognitive CDMA Communications under Arbitrary Spectrum Hole Constraint

To support interference-free quasi-synchronous code-division multiple-access (QS-CDMA) communication with low spectral density profile in a cognitive radio (CR) network, it is desirable to design a set of CDMA spreading sequences with zero-correlation zone (ZCZ) property. However, traditional ZCZ sequences (which assume the availability of the entire spectral band) cannot be used because their orthogonality will be destroyed by the spectrum hole constraint in a CR channel. To date, analytical construction of ZCZ CR sequences remains open. Taking advantage of the Kronecker sequence property, a novel family of sequences (called "quasi-ZCZ" CR sequences) which displays zero cross-correlation and near-zero auto-correlation zone property under arbitrary spectrum hole constraint is presented in this paper. Furthermore, a novel algorithm is proposed to jointly optimize the peak-to-average power ratio (PAPR) and the periodic auto-correlations of the proposed quasi-ZCZ CR sequences. Simulations show that they give rise to single-user bit-error-rate performance in CR-CDMA systems which outperform traditional non-contiguous multicarrier CDMA and transform domain communication systems; they also lead to CR-CDMA systems which are more resilient than non-contiguous OFDM systems to spectrum sensing mismatch, due to the wideband spreading.Comment: 13 pages,10 figures,Accepted by IEEE Journal on Selected Areas in Communications (JSAC)--Special Issue:Cognitive Radio Nov, 201

Policy assessments for the carbon emission flows and sustainability of Bitcoin blockchain operation in China

The growing energy consumption and associated carbon emission of Bitcoin mining could potentially undermine global sustainable efforts. By investigating carbon emission flows of Bitcoin blockchain operation in China with a simulation-based Bitcoin blockchain carbon emission model, we find that without any policy interventions, the annual energy consumption of the Bitcoin blockchain in China is expected to peak in 2024 at 296.59 Twh and generate 130.50 million metric tons of carbon emission correspondingly. Internationally, this emission output would exceed the total annualized greenhouse gas emission output of the Czech Republic and Qatar. Domestically, it ranks in the top 10 among 182 cities and 42 industrial sectors in China. In this work, we show that moving away from the current punitive carbon tax policy to a site regulation policy which induces changes in the energy consumption structure of the mining activities is more effective in limiting carbon emission of Bitcoin blockchain operation

Robust normalization and guaranteed cost control for a class of uncertain singular Markovian jump systems via hybrid impulsive control

This paper investigates the problem of robust normalization and guaranteed cost control for a class of uncertain singular Markovian jump systems. The uncertainties exhibit in both system matrices and transition rate matrix of the Markovian chain. A new impulsive and proportional-derivative control strategy is presented, where the derivative gain is to make the closed-loop system of the singular plant to be a normal one, and the impulsive control part is to make the value of the Lyapunov function does not increase at each time instant of the Markovian switching. A linearization approach via congruence transformations is proposed to solve the controller design problem. The cost function is minimized via solving an optimization problem under the designed control scheme. Finally, three examples (two numerical examples and an RC pulse divider circuit example) are provided to illustrate the effectiveness and applicability of the proposed methods

The SNP rs961253 in 20p12.3 Is Associated with Colorectal Cancer Risk: A Case-Control Study and a Meta-Analysis of the Published Literature

Background: Colorectal cancer (CRC) is the third common cancer and the fourth leading cause of cancer death worldwide. A single nucleotide polymorphism (SNP), rs961253 located in 20p12, was firstly described to be associated with the increased risk of CRC in a genome-wide association study; however, more recent replication studies yielded controversial results. Methodology/Principal Findings: A hospital-based case-control study in a Chinese population was firstly performed, and then a meta-analysis combining the current and previously published studies were conducted to explore the real effect of rs961253 in CRC susceptibility. In the Chinese population including 641 cases and 1037 controls, per-A-allele conferred an OR of 1.60 (95 % CI = 1.26–2.02) under additive model. In the meta-analysis including 29859 cases and 29696 controls, per-Aallele have an OR of 1.13 (95 % CI = 1.09–1.18) under a random-effects model due to heterogeneity (P = 0.019). Nevertheless, the heterogeneity can be totally explained by ethnicity, with the tau 2 reduced to 0 after including ethnicity in metaregression model. In stratified analysis by ethnicity, per-A-allele had ORs of 1.34 (95 % CI = 1.20–1.50) and 1.11 (95% CI = 1.08–1.14) for Asian and European, respectively, without heterogeneity. Modest influence of each study was observed on overall estimate in sensitive analysis, and evident tendency to significant association was seen in cumulative analysis over time, together indicating the robust stability of the current results

Recent Advances in Hypertrophic Cardiomyopathy: A System Review

Hypertrophic cardiomyopathy (HCM) is a common genetic cardiovascular disease present in 1 in 500 of the general population, leading to the most frequent cause of sudden death in young people (including trained athletes), heart failure, and stroke. HCM is an autosomal dominant inheritance, which is associated with a large number of mutations in genes encoding proteins of the cardiac sarcomere. Over the last 20 years, the recognition, diagnosis, and treatment of HCM have been improved dramatically. And moreover, recent advancement in genomic medicine, the growing amount of data from genotype-phenotype correlation studies, and new pathways for HCM help the progress in understanding the diagnosis, mechanism, and treatment of HCM. In this chapter, we aim to outline the symptoms, complications, and diagnosis of HCM; update pathogenic variants (including miRNAs); review the treatment of HCM; and discuss current treatment and efforts to study HCM using induced pluripotent stem cell–derived cardiomyocytes and gene editing technologies. The authors ultimately hope that this chapter will stimulate further research, drive novel discoveries, and contribute to the precision medicine in diagnosis and therapy for HCM