Impaired Flush Response to Niacin Skin Patch Among Schizophrenia Patients and Their Nonpsychotic Relatives: The Effect of Genetic Loading

We previously reported familial aggregation in flush response to niacin skin patch among schizophrenia patients and their nonpsychotic relatives. However, little is known about whether this abnormal skin response is associated with genetic loading for schizophrenia. This study compared the niacin flush response in subjects from families with only one member affected with schizophrenia (simplex families) with those from families having a sib-pair with schizophrenia (multiplex families). Subjects were patients with schizophrenia and their nonpsychotic first-degree relatives from simplex families (176 probands, 260 parents, and 80 siblings) and multiplex families (311 probands, 180 parents, and 52 siblings) as well as 94 healthy controls. Niacin patches of 3 concentrations (0.001M, 0.01M, and 0.1M) were applied to forearm skin, and the flush response was rated at 5, 10, and 15 minutes, respectively, with a 4-point scale. More attenuated flush response to topical niacin was shown in schizophrenia probands and their relatives from multiplex families than in their counterparts from simplex families, and the differentiation was better revealed using 0.1M concentration of niacin than 0.01M or 0.001M. For the highest concentration of 0.1M and the longest time lag of 15 minutes, a subgroup of probands (23%), parents (27%), and siblings (19%) still exhibited nonflush response. Flush response to niacin skin patch is more impaired in schizophrenia patients and their relatives from families with higher genetic loading for schizophrenia, and this finding has implications for future genetic dissection of schizophrenia

Broad targeting of resistance to apoptosis in cancer

Apoptosis or programmed cell death is natural way of removing aged cells from the body. Most of the anti-cancer therapies trigger apoptosis induction and related cell death networks to eliminate malignant cells. However, in cancer, de-regulated apoptotic signaling, particularly the activation of an anti-apoptotic systems, allows cancer cells to escape this program leading to uncontrolled proliferation resulting in tumor survival, therapeutic resistance and recurrence of cancer. This resistance is a complicated phenomenon that emanates from the interactions of various molecules and signaling pathways. In this comprehensive review we discuss the various factors contributing to apoptosis resistance in cancers. The key resistance targets that are discussed include (1) Bcl-2 and Mcl-1 proteins; (2) autophagy processes; (3) necrosis and necroptosis; (4) heat shock protein signaling; (5) the proteasome pathway; (6) epigenetic mechanisms; and (7) aberrant nuclear export signaling. The shortcomings of current therapeutic modalities are highlighted and a broad spectrum strategy using approaches including (a) gossypol; (b) epigallocatechin-3-gallate; (c) UMI-77 (d) triptolide and (e) selinexor that can be used to overcome cell death resistance is presented. This review provides a roadmap for the design of successful anti-cancer strategies that overcome resistance to apoptosis for better therapeutic outcome in patients with cancer

Enabling Cyber Physical Systems with Wireless Sensor Networking Technologies

[[abstract]]Over the last few years, we have witnessed a growing interest in Cyber Physical Systems (CPSs) that rely on a strong synergy between computational and physical components. CPSs are expected to have a tremendous impact on many critical sectors (such as energy, manufacturing, healthcare, transportation, aerospace, etc) of the economy. CPSs have the ability to transform the way human-to-human, human-toobject, and object-to-object interactions take place in the physical and virtual worlds. The increasing pervasiveness of Wireless Sensor Networking (WSN) technologies in many applications make them an important component of emerging CPS designs. We present some of the most important design requirements of CPS architectures. We discuss key sensor network characteristics that can be leveraged in CPS designs. In addition, we also review a few well-known CPS application domains that depend on WSNs in their design architectures and implementations. Finally, we present some of the challenges that still need to be addressed to enable seamless integration of WSN with CPS designs.[[incitationindex]]SCI[[booktype]]紙

Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels

Large-scale meta-analyses of genome-wide association studies (GWAS) have identified >175 loci associated with fasting cholesterol levels, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). With differences in linkage disequilibrium (LD) structure and allele frequencies between ancestry groups, studies in additional large samples may detect new associations. We conducted staged GWAS meta-analyses in up to 69,414 East Asian individuals from 24 studies with participants from Japan, the Philippines, Korea, China, Singapore, and Taiwan. These meta-analyses identified (P < 5 × 10-8) three novel loci associated with HDL-C near CD163-APOBEC1 (P = 7.4 × 10-9), NCOA2 (P = 1.6 × 10-8), and NID2-PTGDR (P = 4.2 × 10-8), and one novel locus associated with TG near WDR11-FGFR2 (P = 2.7 × 10-10). Conditional analyses identified a second signal near CD163-APOBEC1. We then combined results from the East Asian meta-analysis with association results from up to 187,365 European individuals from the Global Lipids Genetics Consortium in a trans-ancestry meta-analysis. This analysis identified (log10Bayes Factor ≥6.1) eight additional novel lipid loci. Among the twelve total loci identified, the index variants at eight loci have demonstrated at least nominal significance with other metabolic traits in prior studies, and two loci exhibited coincident eQTLs (P < 1 × 10-5) in subcutaneous adipose tissue for BPTF and PDGFC. Taken together, these analyses identified multiple novel lipid loci, providing new potential therapeutic targets

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Meta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index

Recent genetic association studies have identified 55 genetic loci associated with obesity or body mass index (BMI). The vast majority, 51 loci, however, were identified in European-ancestry populations. We conducted a meta-analysis of associations between BMI and ∼2.5 million genotyped or imputed single nucleotide polymorphisms among 86 757 individuals of Asian ancestry, followed by in silico and de novo replication among 7488–47 352 additional Asian-ancestry individuals. We identified four novel BMI-associated loci near the KCNQ1 (rs2237892, P = 9.29 × 10−13), ALDH2/MYL2 (rs671, P = 3.40 × 10−11; rs12229654, P = 4.56 × 10−9), ITIH4 (rs2535633, P = 1.77 × 10−10) and NT5C2 (rs11191580, P = 3.83 × 10−8) genes. The association of BMI with rs2237892, rs671 and rs12229654 was significantly stronger among men than among women. Of the 51 BMI-associated loci initially identified in European-ancestry populations, we confirmed eight loci at the genome-wide significance level (P < 5.0 × 10−8) and an additional 14 at P < 1.0 × 10−3 with the same direction of effect as reported previously. Findings from this analysis expand our knowledge of the genetic basis of obesity

[[alternative]]設計及製作一個使用者交談式之平行程式環境

[[abstract]]在這篇文章中，一個利用現代編譯技巧所發展成的平行程式環境將被提出；其名為UPPER。可於數百個甚或數千個處理器上平行執行程式的平行機器提供了比單一處理器更強大的處理能力；然而，要以人為的方式在平行機器上設計平行程式卻是相當困難而且易出錯的。由於這些問題的存在，許多幫助程式設計者將循序程式轉換成平行程式亦或直接設計平行程式的工具已經發展多年了。本篇文章中所提出的平行程式環境亦是基於相同的目的。在這個環境中，主要組件包含了平行化編譯器系統及標的機器模擬器。平行化編譯器系統主要在設計並製作新的及現存的編譯技巧。模擬器則可模擬平行程式在標的機器上執行的情形並將模擬後的效能資料以圖表的方式展示出來。經由此系統所產生的資訊，使用者或程式設計者可藉由此整合環境很容易的設計亦或直接撰寫平行程式。透過此環境的幫助，程式設計者可以輕鬆的將循序程式轉換成有效率的平行程式，免去直接設計平行程式的困擾。 A state-of-the-art parallel programming environment called UPPER (User-interactive Parallel Pro-gramming EnviRonment) is presented in this paper. Parallel machines which execute programs concurrentlyon hundreds or thousands of processors provide far more computational power than does a uniprocessor.However. designing parallel programs on parallel machines manually is very difficult and error-prone.Due to these problems, many tools which help programmers translate sequential programs into parallelizedprograms or even help them design parallel programs have been developed. The proposed environmentalso has the same purpose. The major components of this environment include a parallelizing compilersystem and simulators of the given target machines. The parallelizing compiler system introduces newand existing techniques for compiler-time analysis, and the simulator can simulate execution of thetranslated parallelized program on the target machine and show the simulated performance reports. Thisintegrated environment attempts to provide convenience for users or programmers who can easily designor write their desirable parallel programs based on a variety of assertions and information generated bythis environment. Using our environment, programmers can avoid the necessity of designing parallelprograms and can obtain efficient parallelized programs from sequential programs easily.[[incitationindex]]EI[[booktype]]紙

Mobile Charging Strategy for Wireless Rechargeable Sensor Networks

In a wireless sensor network, the sensing and data transmission for sensors will cause energy depletion, which will lead to the inability to complete the tasks. To solve this problem, wireless rechargeable sensor networks (WRSNs) have been developed to extend the lifetime of the entire network. In WRSNs, a mobile charging robot (MR) is responsible for wireless charging each sensor battery and collecting sensory data from the sensor simultaneously. Thereby, MR needs to traverse along a designed path for all sensors in the WRSNs. In this paper, dual-side charging strategies are proposed for MR traversal planning, which minimize the MR traversal path length, energy consumption, and completion time. Based on MR dual-side charging, neighboring sensors in both sides of a designated path can be wirelessly charged by MR and sensory data sent to MR simultaneously. The constructed path is based on the power diagram according to the remaining power of sensors and distances among sensors in a WRSN. While the power diagram is built, charging strategies with dual-side charging capability are determined accordingly. In addition, a clustering-based approach is proposed to improve minimizing MR moving total distance, saving charging energy and total completion time in a round. Moreover, integrated strategies that apply a clustering-based approach on the dual-side charging strategies are presented in WRSNs. The simulation results show that, no matter with or without clustering, the performances of proposed strategies outperform the baseline strategies in three respects, energy saving, total distance reduced, and completion time reduced for MR in WSRNs

Design and Implementation of a User-interactive Parallel Programming Environment

[[notice]]本書目待補