Using Generic Structures in System Dynamics Model Building: Reflection from Modeling for Indian Shrimp Industry

The paper focused on how a system dynamics modeler could reduce model development and testing time by using “Generic Structures” as an interim benchmark between causal loop diagram and stock flow diagram. Using generic structures as a benchmark could prevent the modeler from including redundant structures to the model and getting affected by personal biases that in turn could reduce repetitive amendments to the model during model testing. Indian Shrimp Industry, during 1990–2010, sequentially showed an early growth, a hasty decline, a combative rejuvenation, and an inexorable re-decline behavior in terms of the annual shrimp production and production capacity. Average Yield continuously fluctuated throughout the Industry’s life cycle during 1990–2010. Breaking such progressive behavior into temporal units, we found that the unit behaviors resemble with the behaviors of generic structures like, exponential growth, goal-seeking, S-shaped growth, limits to success, and overshoot-and-collapse. We, using the related generic structures as the interim benchmarks, illustrated a step-by-step modeling exercise for studying the dynamic behavior of Indian Shrimp Industry during 1990–2010. The paper concluded that using generic structures as the benchmark during system dynamics modeling improved the efficiency and the effectiveness of model building due to reduction in model building and testing time.     

中国公路沥青路面水损害气候影响分区方案

为了了解中国气候条件对沥青路面水损害的影响情况,对沥青路面水损害研究成果进行了回顾与分析,认为影响沥青路面水损害的主要气候因素为:降水、高温以及冻融循环过程.降水与高温过程组合以及降水与冻融循环过程组合是影响沥青路面水损害的两个主要气候过程.针对这两个主要气候过程,构建了降水气温指数和降水冰冻指数,用于评价上述气候过程对沥青路面水损害的影响.分析结果表明:利用降水气温指数和降水冰冻指数划分中国公路沥青路面水损害气候影响分区是合理可行的;根据各个气候指数的工程意义和等概率原则,确定了分区界限,拟定了包含14个区的分区方案.     

Genome-wide association study identifies a susceptibility locus for HCV-induced hepatocellular carcinoma

To identify the genetic susceptibility factor(s) for hepatitis C virus-induced hepatocellular carcinoma (HCV-induced HCC), we conducted a genome-wide association study using 432,703 autosomal SNPs in 721 individuals with HCV-induced HCC (cases) and 2,890 HCV-negative controls of Japanese origin. Eight SNPs that showed possible association (P < 1 × 10(-5)) in the genome-wide association study were further genotyped in 673 cases and 2,596 controls. We found a previously unidentified locus in the 5' flanking region of MICA on 6p21.33 (rs2596542, P(combined) = 4.21 × 10(-13), odds ratio = 1.39) to be strongly associated with HCV-induced HCC. Subsequent analyses using individuals with chronic hepatitis C (CHC) indicated that this SNP is not associated with CHC susceptibility (P = 0.61) but is significantly associated with progression from CHC to HCC (P = 3.13 × 10(-8)). We also found that the risk allele of rs2596542 was associated with lower soluble MICA protein levels in individuals with HCV-induced HCC (P = 1.38 × 10(-13)).     

Biology-inspired synthesis of compound libraries

Biologically active small molecules represent the basis for chemical biology applications in which small molecules are used as chemical tools to probe biological processes. In this report, we review two approaches to design and synthesize compound libraries for biological screenings, i.e., diversity-oriented synthesis (DOS) and biology-oriented synthesis (BIOS). Received 23 October 2007; received after revision 26 November 2007; accepted 28 November 2007     

Role of a novel photopigment,melanopsin, in behavioral adaptation to light

Adaptation to changes in the ambient light is of critical importance to life. In mammals, three principal photoadaptation mechanisms depend on ocular photoreception and exhibit spectral sensitivity suggestive of the opsin class of photopigment(s). These include rapid adaptation of the visual system to the ambient light by pupil constriction, direct modulation of neuroendocrine function and entrainment of the circadian clock to the day:night cycle. Surprisingly, these processes can largely function independent of classical rod/cone photoreceptors, suggesting a novel opsin-based signaling mechanism. They appear to involve a recently discovered network of intrinsically photosensitive retinal ganglion cells that make direct or indirect axonal connections to brain centers regulating photoadaptive behaviors. The discovery of a novel opsin, melanopsin, in these cells has offered an exciting entry point to explore, at the molecular level, how mammals adapt to their light environment. There is now genetic proof of a principal role for melanopsin in all three major photoadaptation processes.     

A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci

We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10?12) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10?11) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10??) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10?11) and a tag SNP for NAT2 acetylation status (P = 4 × 10?11), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis.     

The mesenchymoangioblast,mesodermal precursor for mesenchymal and endothelial cells

Mesenchymoangioblast (MB) is the earliest precursor for endothelial and mesenchymal cells originating from APLNR⁺PDGFRα⁺KDR⁺ mesoderm in human pluripotent stem cell cultures. MBs are identified based on their capacity to form FGF2-dependent compact spheroid colonies in a serum-free semisolid medium. MBs colonies are composed of PDGFRβ⁺CD271⁺EMCN⁺DLK1⁺CD73^? primitive mesenchymal cells which are generated through endothelial/angioblastic intermediates (cores) formed during first 3–4 days of clonogenic cultures. MB-derived primitive mesenchymal cells have potential to differentiate into mesenchymal stromal/stem cells (MSCs), pericytes, and smooth muscle cells. In this review, we summarize the specification and developmental potential of MBs, emphasize features that distinguish MBs from other mesenchymal progenitors described in the literature and discuss the value of these findings for identifying molecular pathways leading to MSC and vasculogenic cell specification, and developing cellular therapies using MB-derived progeny.