Analysis of Gene Coexpression by B-Spline Based CoD Estimation

The gene coexpression study has emerged as a novel holistic approach for microarray data analysis. Different indices have been used in exploring coexpression relationship, but each is associated with certain pitfalls. The Pearson's correlation coefficient, for example, is not capable of uncovering nonlinear pattern and directionality of coexpression. Mutual information can detect nonlinearity but fails to show directionality. The coefficient of determination (CoD) is unique in exploring different patterns of gene coexpression, but so far only applied to discrete data and the conversion of continuous microarray data to the discrete format could lead to information loss. Here, we proposed an effective algorithm, CoexPro, for gene coexpression analysis. The new algorithm is based on B-spline approximation of coexpression between a pair of genes, followed by CoD estimation. The algorithm was justified by simulation studies and by functional semantic similarity analysis. The proposed algorithm is capable of uncovering both linear and a specific class of nonlinear relationships from continuous microarray data. It can also provide suggestions for possible directionality of coexpression to the researchers. The new algorithm presents a novel model for gene coexpression and will be a valuable tool for a variety of gene expression and network studies. The application of the algorithm was demonstrated by an analysis on ligand-receptor coexpression in cancerous and noncancerous cells. The software implementing the algorithm is available upon request to the authors

Quantum speed limit for complex dynamics

Quantum speed limit focuses on the minimum time scale for a fixed mission and hence is important in quantum information where fast dynamics is usually beneficial. Recently an operational definition of quantum speed limit (OQSL) was proposed, which reveals the intrinsic minimum time for time-independent Hamiltonians. However, a general method to evaluate the OQSL for time-dependent Hamiltonians, especially when noises are involved, is still in lack. Hereby we provide the expression of OQSL for a certain type of time-dependent Hamiltonians and propose a three-step (classification-regression-calibration) methodology based on machine learning for the evaluation of OQSL in complex dynamics.Comment: 24 pages, 14 figures, 1 tabl

Transcriptome coexpression map of human embryonic stem cells

BACKGROUND: Human embryonic stem (ES) cells hold great promise for medicine and science. The transcriptome of human ES cells has been studied in detail in recent years. However, no systematic analysis has yet addressed whether gene expression in human ES cells may be regulated in chromosomal domains, and no chromosomal domains of coexpression have been identified. RESULTS: We report the first transcriptome coexpression map of the human ES cell and the earliest stage of ES differentiation, the embryoid body (EB), for the analysis of how transcriptional regulation interacts with genomic structure during ES self-renewal and differentiation. We determined the gene expression profiles from multiple ES and EB samples and identified chromosomal domains showing coexpression of adjacent genes on the genome. The coexpression domains were not random, with significant enrichment in chromosomes 8, 11, 16, 17, 19, and Y in the ES state, and 6, 11, 17, 19 and 20 in the EB state. The domains were significantly associated with Giemsa-negative bands in EB, yet showed little correlation with known cytogenetic structures in ES cells. Different patterns of coexpression were revealed by comparative transcriptome mapping between ES and EB. CONCLUSION: The findings and methods reported in this investigation advance our understanding of how genome organization affects gene expression in human ES cells and help to identify new mechanisms and pathways controlling ES self-renewal or differentiation

High speed self-testing quantum random number generation without detection loophole

Quantum mechanics provides means of generating genuine randomness that is impossible with deterministic classical processes. Remarkably, the unpredictability of randomness can be certified in a self-testing manner that is independent of implementation devices. Here, we present an experimental demonstration of self-testing quantum random number generation based on an detection-loophole free Bell test with entangled photons. In the randomness analysis, without the assumption of independent identical distribution, we consider the worst case scenario that the adversary launches the most powerful attacks against quantum adversary. After considering statistical fluctuations and applying an 80 Gb $\times$ 45.6 Mb Toeplitz matrix hashing, we achieve a final random bit rate of 114 bits/s, with a failure probability less than $10^{-5}$. Such self-testing random number generators mark a critical step towards realistic applications in cryptography and fundamental physics tests.Comment: 34 pages, 10 figure

TBHQ Alleviated Endoplasmic Reticulum Stress-Apoptosis and Oxidative Stress by PERK-Nrf2 Crosstalk in Methamphetamine-Induced Chronic Pulmonary Toxicity

Methamphetamine (MA) leads to cardiac and pulmonary toxicity expressed as increases in inflammatory responses and oxidative stress. However, some interactions may exist between oxidative stress and endoplasmic reticulum stress (ERS). The current study is designed to investigate if both oxidative stress and ERS are involved in MA-induced chronic pulmonary toxicity and if antioxidant tertiary butylhydroquinone (TBHQ) alleviated ERS-apoptosis and oxidative stress by PERK-Nrf2 crosstalk. In this study, the rats were randomly divided into control group, MA-treated group (MA), and MA plus TBHQ-treated group (MA + TBHQ). Chronic exposure to MA resulted in slower growth of weight and pulmonary toxicity of the rats by increasing the pulmonary arterial pressure, promoting the hypertrophy of right ventricle and the remodeling of pulmonary arteries. MA inhibited the Nrf2-mediated antioxidative stress by downregulation of Nrf2, GCS, and HO-1 and upregulation of SOD2. MA increased GRP78 to induce ERS. Overexpression and phosphorylation of PERK rapidly phosphorylated eIF2α, increased ATF4, CHOP, bax, caspase 3, and caspase 12, and decreased bcl-2. These changes can be reversed by antioxidant TBHQ through upregulating expression of Nrf2. The above results indicated that TBHQ can alleviate MA-induced oxidative stress which can accelerate ERS to initiate PERK-dependent apoptosis and that PERK/Nrf2 is likely to be the key crosstalk between oxidative stress and ERS in MA-induced chronic pulmonary toxicity

Oncologic Outcomes of Asian Men with Clinically Localized Prostate Cancer after Extraperitoneal Laparoscopic Radical Prostatectomy: A Single-Institution Experience

Purpose. To evaluate the midterm oncologic results of extraperitoneal laparoscopic radical prostatectomy (EPLRP) for Asian men with localized prostate cancer. Methods. Between 2004 and 2009, 218 men underwent EPLRP at an Asian tertiary hospital. The mean preoperative prostate-specific antigen (PSA) was 15.5 ng/ml and mean Gleason score was 6.6. Stage distributions were cT1a-b in 21 cases, cT1c in 139, cT2 in 48 and cT3 in 10. Disease recurrence was defined as PSA ≥ 0.2 ng/mL in 2 consecutive measurements or initiation of secondary therapy. Results. Postoperative pathological stage was pT2a-b in 33 patients, pT2cN0 in 10, pT3a in 27, pT3b in 36, pT4 in 9 and pN1 in 10. Positive surgical margins occurred in 14.6% and 48.6% for pT2 and pT3 diseases, respectively (P < .001). The overall PSA recurrence-free survival at 3 and 5 years was 82.1% and 74.5%. By the pathological stages, 3-year recurrence-free survival was 92.4% (pT2), 81.1% (pT3a), 62.6% (pT3b-4) and 55.6% (pN1), respectively (P < .001). Conclusions. EPLRP is curative even for some locally advanced prostate cancers in a midterm follow-up. Even at an Asian center of low volume of radical prostatectomy EPLRP still provides oncologic outcomes similar to that of high volume centers

Expression profile analysis to identify potential gene changes induced by dexamethasone in the trabecular meshwork

AIM: To investigate potential gene changes in trabecular meshwork (TM) induced by dexamethasone (DEX) in steroid-induced glaucoma (SIG). METHODS: The expression data of 24 cases from a public functional genomics data were sorted to identify the mechanisms of action of DEX on the TM. The relationships of the differentially expressed genes (DEGs) were enriched using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. In addition, the hub genes were screened by the Search Tool for the Retrieval of Interacting Genes Database (STRING) and Cytoscape tools. Finally, human TM cells (HTMCs) were treated with DEX to preliminarily explore the function of hub genes. RESULTS: Totally 47 DEGs, including 21 downregulated and 26 upregulated genes were identified. The primary enriched results of the DEGs consisted of inflammatory response, extracellular matrix (ECM), negative regulation of cell proliferation, TNF signalling pathway and the regulation of tryptophan channels by inflammatory mediators. Subsequently, pro-melanin-enriched hormone (PMCH) and Bradykinin B1 receptor (BDKRB1) were screened as hub genes. It is verified in GSE37474 data set. Western blot and quantitative real-time polymerase chain reaction (qPCR) results showed that protein and RNA expression levels of BDKRB1 were significantly decreased after DEX treatment, while PMCH was not significantly changed. CONCLUSION: BDKRB1 may be a key gene involved in SIG onset, providing a suitable therapeutic target for improving the prognosis of SIG patients