Reinforcement learning, one of the most active research areas in artificial intelligence, is a computational approach to learning whereby an agent tries to maximize the total amount of reward it receives when interacting with a complex, uncertain environment. In Reinforcement Learning, Richard Sutton and Andrew Barto provide a clear and simple account of the key ideas and algorithms of reinforcement learning. Their discussion ranges from the history of the field's intellectual foundations to the most recent developments and applications. The only necessary mathematical background is familiarity with elementary concepts of probability. The book is divided into three parts. Part I defines the reinforcement learning problem in terms of Markov decision processes. Part II provides basic solution methods: dynamic programming, Monte Carlo methods, and temporal-difference learning. Part III presents a unified view of the solution methods and incorporates artificial neural networks, eligibility traces, and planning; the two final chapters present case studies and consider the future of reinforcement learning.

/pdf/reinforcement-learning-an-introduction-rzxgej9p17.pdf

Reinforcement Learning: An Introduction

Although genomewide RNA expression analysis has become a routine tool in biomedical research, extracting biological insight from such information remains a major challenge. Here, we describe a powerful analytical method called Gene Set Enrichment Analysis (GSEA) for interpreting gene expression data. The method derives its power by focusing on gene sets, that is, groups of genes that share common biological function, chromosomal location, or regulation. We demonstrate how GSEA yields insights into several cancer-related data sets, including leukemia and lung cancer. Notably, where single-gene analysis finds little similarity between two independent studies of patient survival in lung cancer, GSEA reveals many biological pathways in common. The GSEA method is embodied in a freely available software package, together with an initial database of 1,325 biologically defined gene sets.

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Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles

There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

http://bartellab.wi.mit.edu/publication_reprints/Bartel_Cell09.pdf

MicroRNAs: Target Recognition and Regulatory Functions

Gamma-aminobutyric acid (GABA) is an important neurotransmitter for mammals, thus biosynthesized or bio-transformed GABA is an important compound for functional foods. In this study, unique biosynthetic pathways of GABA in a novel lactic acid bacteria (LAB) strain, Lentilactobacillus curieae CCTCC M 2011381T, was discovered. L-glutamate decarboxylase (GAD) which generally catalyzes L-glutamate decarboxylation to form GABA in bacteria, is absent in this strain. Alternatively, transcriptional analysis revealed that L-glutamate played as an amino donor for the step through which succinic semialdehyde (SSA) was converted to GABA catalyzed by GABA transaminase (GABA-T). Then, the deletion and complementation of the GABA-T gene confirmed that GABA-T was the key enzyme responsible for GABA accumulation from SSA. According to residual GABA titer could be detected after the deletion of the GABA-T gene, other decarboxylases among the genome were analyzed by RT-PCR. 5-Oxopent-3-ene-1,2,5-tricarboxylate decarboxylase (HpaG) was verified possessing weaker catalytic capability for the decarboxylation of L-glutamate based on the hetero-expression of the enzyme in E. coli. Thus, GABA is produced mainly through the transamination reaction on SSA catalyzed by GABA-T and L-glutamate as the amino donor, and slightly from the decarboxylation of L-glutamate catalyzed by HpaG in L. curieae, which are distinct pathways in LAB. 

A novel γ-aminobutyric acid biosynthetic pathway in Lentilactobacillus curieae CCTCC M 2011381T

We propose a new algorithm to do posterior sampling of Kingman's coalescent, based upon the Particle Markov Chain Monte Carlo methodology. Specifically, the algorithm is an instantiation of the Particle Gibbs Sampling method, which alternately samples coalescent times conditioned on coalescent tree structures, and tree structures conditioned on coalescent times via the conditional Sequential Monte Carlo procedure. We implement our algorithm as a C++ package, and demonstrate its utility via a parameter estimation task in population genetics on both single- and multiple-locus data. The experiment results show that the proposed algorithm performs comparable to or better than several well-developed methods.

Inference in Kingman's Coalescent with Particle Markov Chain Monte Carlo Method

Abstract Context A Chinese herbal formula, Tiaopi Xiezhuo decoction (TXD), is developed from a classical Chinese prescription Sanhuang Xiexin decoction. Objective To investigate the regulatory effect of TXD on gut dysbiosis, as a treatment of constipation in patients with peritoneal dialysis (PD). Materials and methods The chemical content of TXD was assessed by high-performance liquid chromatography. A total of 29 PD patients were enrolled and treated with TXD orally (3 g crude drug/each/twice/day) for 3 months. Blood and faecal samples were collected at the beginning and end, to determine the changes in biochemical characteristics and gut microbial composition. The stool conditions were asked to be scored. Additional 30 healthy individuals were recruited as a control for the analysis of gut microbiota. Results Although having no significant effects on serum biochemical characteristics, 3-month TXD intervention improved constipation in PD patients: decreased 80% abdominal distention (p < 0.01), increased 2.6-fold sloppy stools (p < 0.05) and eliminated hard stool completely (p < 0.01). The analysis of gut microbiota showed that, compared to the healthy group, the microbial richness was reduced in PD patients. After a 3-month TXD treatment, this reduced richness was raised, and Paraprevotella clara, Lachnospiraceae bacterium 2-146FA, Phascolarctobaterium succinatutens, Lachnospiraceae bacterium 2-1-58FAA, Fusobacterium mortiferum, and Prevotella copri were accumulated in the intestinal flora. Furthermore, the bacterial species enriched by TXD correlated with the improvement of constipation. Discussion and conclusions TXD treatment may improve constipation by modulating gut dysbiosis in PD patients. These findings provide data to support the further application of TXD in the adjuvant treatment of PD.

Effects of Tiaopi Xiezhuo decoction on constipation and gut dysbiosis in patients with peritoneal dialysis

PURPOSE
To evaluate the local efficacy, safety, and long-term outcomes of combined radiofrequency ablation (RFA) and multipronged ethanol ablation (EA) in the treatment of unfavorable hepatocellular carcinoma (HCC) and to determine the prognostic factors for survival.


METHODS
Between August 2009 and December 2017, 98 patients with 110 unfavorable HCC nodules who underwent combined RFA and multipronged EA were retrospectively enrolled in the study. Unfavorable HCC was defined as a medium (3.1-5.0 cm) or large (5.1-7.0 cm) HCC nodule, a tumor located at a high-risk site, or a perivascular tumor. The treatment response, overall survival (OS), and recurrence-free survival (RFS) were analyzed. The Kaplan-Meier method and Cox proportional hazards regression model were used to evaluate the prognostic factors.


RESULTS
Complete ablation was obtained in 80.9% (89/110) of the tumors after initial treatment. Major complications were observed in 3 (3.1%) patients. The cumulative incidence of local tumor progression (LTP) was 23.5% at five years, and no variable was found to be an independent predictive factor for LTP. The five-year OS and RFS rates were 41.9% and 34.0%, respectively. Multivariate analysis showed that the serum alpha-fetoprotein level, tumor size, presence of residual tumor after ablation, and extrahepatic metastases were significant prognostic factors for OS (P = 0.023, P = 0.030, P = 0.001, and P = 0.010, respectively). Tumor type and the number of tumors were predictive factors for RFS (P = 0.029 and P = 0.001, respectively). A perivascular tumor was not an independent predictive factor for OS or RFS.


CONCLUSION
Combined RFA and multipronged EA is a safe and effective treatment for unfavorable HCC, especially for perivascular tumors.

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Long-term outcomes of combined radiofrequency ablation and multipronged ethanol ablation for the treatment of unfavorable hepatocellular carcinoma

Cardiovascular diseases remain the leading cause of death worldwide, particularly ischemic heart disease (IHD). It is also classified as incurable given the irreversible damage it causes to cardiomyocytes. Thus, myocardial tissue rejuvenation following ischemia is one of the global primary research concerns for scientists. Interestingly, the mammalian heart thrives after an injury during the embryonic or neonatal period; however, this ability disappears with increasing age. Previous studies have found that specific non-coding (nc) RNAs play a pivotal role in this process. Hence, the review herein summarizes the research on cardiomyocyte regenerative medicine in recent years and sets forth the biological functions and mechanisms of the micro (mi)RNA, long non-coding (lnc)RNA, and circular (circ)RNA in the posttranscriptional regulation of cardiomyocytes. In addition, this review summarizes the roles of ncRNAs in specific species while enumerating potential therapeutic strategies for myocardial infarction.

Xiaohui Xie

Papers

A novel γ-aminobutyric acid biosynthetic pathway in Lentilactobacillus curieae CCTCC M 2011381T

Inference in Kingman's Coalescent with Particle Markov Chain Monte Carlo Method

Effects of Tiaopi Xiezhuo decoction on constipation and gut dysbiosis in patients with peritoneal dialysis

Long-term outcomes of combined radiofrequency ablation and multipronged ethanol ablation for the treatment of unfavorable hepatocellular carcinoma

Non-coding RNAs to regulate cardiomyocyte proliferation: A new trend in therapeutic cardiac regeneration