技术和价格不确定下企业研发投资决策研究

随着科学技术的迅速发展,研发(RD)活动对企业的生存与发展日益重要.本文将企业研发投资项目所承受的风险分为两种:研发前期不可对冲的技术风险,以及研发产品投入市场时因价格和需求的不确定性所承受的价格风险,而后者是可以部分对冲的.本文考虑一个以创新研发投资为主的企业,如何进行相应的投资消费问题.通过建立效用最大化模型,运用随机最优控制理论与方法得到关于指数效用函数的最优策略,同时阐述了研发投资价值及其投资/中止阈值.数值结果表明:较大的技术风险,会产生更大的信息生成价值,使得研发的总价值不减反增;风险厌恶态度对企业的研发价值以及研发/中止阈值都有较明显的影响;因研发信息生成价值的存在,使得研发/中止阈值不同于传统净现值(NPV)降为零的阈值.     

γ-Aminobutyric acid (GABA) signalling in plants

The role of γ-aminobutyric acid (GABA) as a signal in animals has been documented for over 60 years. In contrast, evidence that GABA is a signal in plants has only emerged in the last 15 years, and it was not until last year that a mechanism by which this could occur was identified—a plant ‘GABA receptor’ that inhibits anion passage through the aluminium-activated malate transporter family of proteins (ALMTs). ALMTs are multigenic, expressed in different organs and present on different membranes. We propose GABA regulation of ALMT activity could function as a signal that modulates plant growth, development, and stress response. In this review, we compare and contrast the plant ‘GABA receptor’ with mammalian GABA_A receptors in terms of their molecular identity, predicted topology, mode of action, and signalling roles. We also explore the implications of the discovery that GABA modulates anion flux in plants, its role in signal transduction for the regulation of plant physiology, and predict the possibility that there are other GABA interaction sites in the N termini of ALMT proteins through in silico evolutionary coupling analysis; we also explore the potential interactions between GABA and other signalling molecules.     

1961-2014年西安市秋淋气候特征分析

利用1961-2014年8-10月西安市7个气象站逐日降水资料,采用降水强度指数分析了西安市秋淋天气气候变化特征.结果表明,20世纪90年代是近50年来西安市秋季9~10月降水量最少的阶段.1961年以来西安市共有23 a出现秋淋多雨时段,20世纪60年代至80年代中期较多,1983年和1984年出现强秋淋;20世纪80年代中期至21世纪10年代初期,只有1992年出现了1次秋淋天气;2011年以来,秋淋呈明显上升、增强趋势.1961-2014年秋淋天气过程平均降水量呈上升趋势,偏多年份主要出现在20世纪80年代初中期和21世纪.厄尔尼诺使秋季9~10月降水量减少,与秋淋天气存在明显的负相关关系.近54年西安市秋淋没有发生显著的气候突变,存在4~6 a、10 a和24 a左右的长振荡周期.     

Granzyme B is recovered by natural killer cells via clathrin-dependent endocytosis

When they recognize a target cell, natural killer (NK) cells mount an attack to kill the target by exerting their cytotoxicity via the exocytosis of cytotoxic granules. Although the details of this process (which includes the movement of cytotoxic granules in the immune synapse and their fusion with the plasma membrane, releasing granzymes and perforin into the synaptic cleft) are relatively better understood, the post-exocytosis regulation of the process is still largely unknown. Here we show that a clathrin-dependent endocytosis stimulated by target cell occurs in NK92 cell line, which is closely correlated with granzyme B recovery. Inhibition of the endocytosis significantly attenuates the cytotoxicity of NK92 cells. The NK cell recovery of its released effector molecules, in turn, suggests that endocytosis may well play a key role in the post exocytosis regulation of immune cells.     

Mutations in NMNAT1 cause Leber congenital amaurosis and identify a new disease pathway for retinal degeneration

Leber congenital amaurosis (LCA) is a blinding retinal disease that presents within the first year after birth. Using exome sequencing, we identified mutations in the nicotinamide adenine dinucleotide (NAD) synthase gene NMNAT1 encoding nicotinamide mononucleotide adenylyltransferase 1 in eight families with LCA, including the family in which LCA was originally linked to the LCA9 locus. Notably, all individuals with NMNAT1 mutations also have macular colobomas, which are severe degenerative entities of the central retina (fovea) devoid of tissue and photoreceptors. Functional assays of the proteins encoded by the mutant alleles identified in our study showed that the mutations reduce the enzymatic activity of NMNAT1 in NAD biosynthesis and affect protein folding. Of note, recent characterization of the slow Wallerian degeneration (Wld(s)) mouse model, in which prolonged axonal survival after injury is observed, identified NMNAT1 as a neuroprotective protein when ectopically expressed. Our findings identify a new disease mechanism underlying LCA and provide the first link between endogenous NMNAT1 dysfunction and a human nervous system disorder.     

A genome-wide association study in Han Chinese identifies new susceptibility loci for ankylosing spondylitis

To identify susceptibility loci for ankylosing spondylitis, we performed a two-stage genome-wide association study in Han Chinese. In the discovery stage, we analyzed 1,356,350 autosomal SNPs in 1,837 individuals with ankylosing spondylitis and 4,231 controls; in the validation stage, we analyzed 30 suggestive SNPs in an additional 2,100 affected individuals and 3,496 controls. We identified two new susceptibility loci between EDIL3 and HAPLN1 at 5q14.3 (rs4552569; P = 8.77 × 10(-10)) and within ANO6 at 12q12 (rs17095830; P = 1.63 × 10(-8)). We also confirmed previously reported associations in Europeans within the major histocompatibility complex (MHC) region (top SNP, rs13202464; P < 5 × 10(-324)) and at 2p15 (rs10865331; P = 1.98 × 10(-8)). We show that rs13202464 within the MHC region mainly represents the risk effect of HLA-B*27 variants (including HLA-B*2704, HLA-B*2705 and HLA-B*2715) in Chinese. The two newly discovered loci implicate genes related to bone formation and cartilage development, suggesting their potential involvement in the etiology of ankylosing spondylitis.     

Frequent mutations of chromatin remodeling genes in transitional cell carcinoma of the bladder

Transitional cell carcinoma (TCC) is the most common type of bladder cancer. Here we sequenced the exomes of nine individuals with TCC and screened all the somatically mutated genes in a prevalence set of 88 additional individuals with TCC with different tumor stages and grades. In our study, we discovered a variety of genes previously unknown to be mutated in TCC. Notably, we identified genetic aberrations of the chromatin remodeling genes (UTX, MLL-MLL3, CREBBP-EP300, NCOR1, ARID1A and CHD6) in 59% of our 97 subjects with TCC. Of these genes, we showed UTX to be altered substantially more frequently in tumors of low stages and grades, highlighting its potential role in the classification and diagnosis of bladder cancer. Our results provide an overview of the genetic basis of TCC and suggest that aberration of chromatin regulation might be a hallmark of bladder cancer.     

不确定条件下纵向研发合作的投资决策研究

针对一个存在两个上游企业和两个下游企业的双层市场结构,对上下游企业实施纵向研发合作策略下的产量和利润进行了研究。并考虑了研发固有的不确定性和溢出效应的影响,从企业是否进行研发以及进行多大程度的研发两个方面,研究上下游企业实施纵向研发合作的投资决策。并在此基础上,探讨了企业研发成本分担比例和违约赔偿。