Construction and expression of retroviruses encoding dual drug resistance genes in human umbilical cord blood CD34+ cells

A series of retro viral vectors encoding humanmdr1 gene alone as wetl as in combination with either humanmgmt gene or human mutantSer ³¹-dhfr gene are engineered. The resultant retroviruses are used to transduce human umbilical cord blood CD34⁺ cetls. It has been shown that expression of dual drug resistance genes in transduced cetls confers a broad range of resistance to both kinds of corresponding drugs. These data suggest a rationale for the use of such double chemoresistance gene constructs in anin vivo model in which transduced hematopoietic cetls will acquire multiple protection against the cytotoxic side effects of combination chemotherapy and may have future application in chemoprotection of normal tissues, thus killing tumor cetls more effectivety.     

δ掺杂对磁纳米结构中电子输运性质的影响

建立铁磁条调制下含有δ掺杂的磁纳米结构模型,计算不同δ掺杂位置及高度时电子的透射几率及自旋极化率,重点研究了该纳米结构中电子的自旋输运性质。结果表明,该磁纳米结构中可实现较显著的自旋极化效应,且δ掺杂的位置及高度均会对其中的电子输运性质产生影响。因此,理论上可以通过控制δ掺杂的位置及高度来获得实际需要的自旋极化强度,有助于新型自旋电子学器件的开发。     

2002-2012年中国林学基础研究热点分析——基于国家自然科学基金申请项目和资助项目关键词的研究

本文通过对2002-2012年国家自然科学基金委员会林学学科申请和资助项目的关键词进行共词分析,剖析了各关键词之间的关系,并借助对高频关键词的聚类分析和多维尺度分析,揭示了这11年来林学学科基础研究的热点及其内涵,探讨了目前被科学家忽视的重要科学问题.这一分析将为做好林学学科布局,促进学科均衡持续发展提供帮助.     

糖类遗传与生命起源

从遗传学角度探讨了糖类与生命起源，讨论了遗传学上的再认识，提出糖类在遗传学上扮演着重要、核心的角色、糖类是生命起源物质，基因是糖类衍生物。生命诞生过程可能是：先有糖类、然后有氨基酸和碱基；磷酸及其盐类既是生命物质的组成部分、也是催化剂，阳光或地热为能源，于是诞生了基因。生命体是分子相互作用、有序组合、自我调控的耗散体系。     

Fault tolerant motion planning based on joint torque limit for redundant manipulators

0 IntroductionWith the development of science and technology,manipulators have been widely utilized in some specialfields of space , deeper ocean, and nuclear materialcleanup.Becausethese workingenvironments are distant ,harsh and dangerous ,itis difficultfor peopletorepairthefailed manipulators onthe spot .Therefore ,the manipula-tors should operate normally for a long time . To meetthese requirements ,the manipulators must have not onlyhigher reliability but also fault tolerance capabilities…     

基于物体关系描述的单目语义SLAM方法

外界环境的语义感知和自身位置的准确估计是移动机器人自主导航和作业的关键。提出了一种基于单目相机的语义SLAM(simultaneous localization and mapping)方法,在轨迹估计的同时完成三维目标检测。提取物体自身语义、尺寸、颜色分布及其邻域拓扑结构等多元信息作为描述子,实现帧间物体的准确关联。在后端对相机位姿、地图点和物体路标进行联合优化,并自适应调整代价函数中各误差项的权重系数,以提高各状态变量的估计精度和鲁棒性。实验结果表明,所提出的算法在地图构建方面具有较高的精度。     

基于烟花算法的基站群协作计算卸载模型研究

车联网、AR、AI等计算密集、时延敏感型应用迅速发展,而移动设备因自身计算能力相对不足,执行此类应用任务时会因高时延而严重影响用户体验甚至无法满足用户需求。针对此问题,提出综合考虑时延与成本的多用户、多MEC (mobile edge computing)服务器的基站群协作计算卸载模型。并提出基于凸优化的改进烟花算法（improved fireworks algorithm based on convex optimization, CVX-FWA）来对模型进行求解,对用户任务进行合理的卸载与资源分配。仿真结果表明,提出的计算卸载方案有效降低了任务总时延成本值,实现计算卸载资源的整体优化配置。     

Defining G protein-coupled receptor peptide ligand expressomes and signalomes in human and mouse islets

Introduction

Islets synthesise and secrete numerous peptides, some of which are known to be important regulators of islet function and glucose homeostasis. In this study, we quantified mRNAs encoding all peptide ligands of islet G protein-coupled receptors (GPCRs) in isolated human and mouse islets and carried out in vitro islet hormone secretion studies to provide functional confirmation for the species-specific role of peptide YY (PYY) in mouse islets.

Materials and methods

GPCR peptide ligand mRNAs in human and mouse islets were quantified by quantitative real-time PCR relative to the reference genes ACTB, GAPDH, PPIA, TBP and TFRC. The pathways connecting GPCR peptide ligands with their receptors were identified by manual searches in the PubMed, IUPHAR and Ingenuity databases. Distribution of PYY protein in mouse and human islets was determined by immunohistochemistry. Insulin, glucagon and somatostatin secretion from islets was measured by radioimmunoassay.

Results

We have quantified GPCR peptide ligand mRNA expression in human and mouse islets and created specific signalomes mapping the pathways by which islet peptide ligands regulate human and mouse GPCR signalling. We also identified species-specific islet expression of several GPCR ligands. In particular, PYY mRNA levels were ~ 40,000-fold higher in mouse than human islets, suggesting a more important role of locally secreted Pyy in mouse islets. This was confirmed by IHC and functional experiments measuring insulin, glucagon and somatostatin secretion.

Discussion

The detailed human and mouse islet GPCR peptide ligand atlases will allow accurate translation of mouse islet functional studies for the identification of GPCR/peptide signalling pathways relevant for human physiology, which may lead to novel treatment modalities of diabetes and metabolic disease.

     

Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis

Atopic disease, including atopic dermatitis (eczema), allergy and asthma, has increased in frequency in recent decades and now affects approximately 20% of the population in the developed world. Twin and family studies have shown that predisposition to atopic disease is highly heritable. Although most genetic studies have focused on immunological mechanisms, a primary epithelial barrier defect has been anticipated. Filaggrin is a key protein that facilitates terminal differentiation of the epidermis and formation of the skin barrier. Here we show that two independent loss-of-function genetic variants (R510X and 2282del4) in the gene encoding filaggrin (FLG) are very strong predisposing factors for atopic dermatitis. These variants are carried by approximately 9% of people of European origin. These variants also show highly significant association with asthma occurring in the context of atopic dermatitis. This work establishes a key role for impaired skin barrier function in the development of atopic disease.     

Common variants near MC4R are associated with fat mass, weight and risk of obesity

To identify common variants influencing body mass index (BMI), we analyzed genome-wide association data from 16,876 individuals of European descent. After previously reported variants in FTO, the strongest association signal (rs17782313, P = 2.9 x 10(-6)) mapped 188 kb downstream of MC4R (melanocortin-4 receptor), mutations of which are the leading cause of monogenic severe childhood-onset obesity. We confirmed the BMI association in 60,352 adults (per-allele effect = 0.05 Z-score units; P = 2.8 x 10(-15)) and 5,988 children aged 7-11 (0.13 Z-score units; P = 1.5 x 10(-8)). In case-control analyses (n = 10,583), the odds for severe childhood obesity reached 1.30 (P = 8.0 x 10(-11)). Furthermore, we observed overtransmission of the risk allele to obese offspring in 660 families (P (pedigree disequilibrium test average; PDT-avg) = 2.4 x 10(-4)). The SNP location and patterns of phenotypic associations are consistent with effects mediated through altered MC4R function. Our findings establish that common variants near MC4R influence fat mass, weight and obesity risk at the population level and reinforce the need for large-scale data integration to identify variants influencing continuous biomedical traits.