Generalized Multivariate Gumbel Distributions——Dependence,Aging Properties and Applications

This paper introduces a generalized multivariate Gumbel (GMG) distribution using a survival copula. Various dependence properties of the GMG distribution and some analytical properties of the generators of the GMG distribution are studied. Furthermore, the authors also investigate the dependence behavior of the residual lifetime vector of the GMG distribution. As an illustration, the GMG distribution is applied to fit a real data set.     

A two-dimensional improvement for Farr-Gao algorithm

Farr-Gao algorithm is a state-of-the-art algorithm for reduced Gröbner bases of vanishing ideals of finite points, which has been implemented in Maple as a build-in command. This paper presents a two-dimensional improvement for it that employs a preprocessing strategy for computing reduced Gröbner bases associated with tower subsets of given point sets. Experimental results show that the preprocessed Farr-Gao algorithm is more efficient than the classical one.     

The complexity and on-line algorithm for automated storage and retrieval system with stacker cranes on one rail

This paper considers an on-line scheduling and routing problem concerning the automated storage and retrieval system from tobacco industry. In this problem, stacker cranes run on one common rail between two racks. Multiple input/output-points are located at the bottom of the racks. The stacker cranes transport bins between the input/output-points and cells on the racks to complete requests generated over time. Each request should be accomplished within its response time. The objective is to minimize the time by which all the generated requests are completed. Under a given physical layout, the authors study the complexity of the problem and design on-line algorithms for both one-stacker-crane model and two-stacker-crane model. The algorithms are validated by instances and numerical simulations.     

Developing anti-neoplastic biotherapeutics against eIF4F

Biotherapeutics have revolutionized modern medicine by providing medicines that would not have been possible with small molecules. With respect to cancer therapies, this represents the current sector of the pharmaceutical industry having the largest therapeutic impact, as exemplified by the development of recombinant antibodies and cell-based therapies. In cancer, one of the most common regulatory alterations is the perturbation of translational control. Among these, changes in eukaryotic initiation factor 4F (eIF4F) are associated with tumor initiation, progression, and drug resistance in a number of settings. This, coupled with the fact that systemic suppression of eIF4F appears well tolerated, indicates that therapeutic agents targeting eIF4F hold much therapeutic potential. Here, we discuss opportunities offered by biologicals for this purpose.     

基于RSM和FEM的辊锻件长度控制技术

以某钩尾框精密辊锻工艺为研究对象,首次应用响应面法(RSM)和有限元数值模拟法(FEM)对精密辊锻件的长度控制问题进行了研究.首先以满足辊锻件长度和降低轧辊最大扭矩为目标,采用FORGE3有限元软件建立了RSM与FEM相结合的二阶分析模型,研究了轧辊间隙、摩擦因子、轧辊转速和坯料温度对辊锻件的长度和轧辊最大扭矩的显著性和影响规律;其次采用优化后的工艺参数对该辊锻工艺进行了再模拟,提出了辊锻件长度的调试原则,利用该原则和点的反追踪技术对辊锻模具进行了再设计,同时分析了设计、模拟和生产辊锻件的长度和辊锻过程的功率耗散和分布.研究结果表明:应用RSM和FEM可准确有效地掌握精密辊锻件的长度控制技术.     

Disruption of calcitonin gene-related peptide signaling accelerates muscle denervation and dampens cytotoxic neuroinflammation in SOD1 mutant mice

Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease. Neuronal vacuolization and glial activation are pathologic hallmarks in the superoxide dismutase 1 (SOD1) mouse model of ALS. Previously, we found the neuropeptide calcitonin gene-related peptide (CGRP) associated with vacuolization and astrogliosis in the spinal cord of these mice. We now show that CGRP abundance positively correlated with the severity of astrogliosis, but not vacuolization, in several motor and non-motor areas throughout the brain. SOD1 mice harboring a genetic depletion of the βCGRP isoform showed reduced CGRP immunoreactivity associated with vacuolization, while motor functions, body weight, survival, and astrogliosis were not altered. When CGRP signaling was completely disrupted through genetic depletion of the CGRP receptor component, receptor activity-modifying protein 1 (RAMP1), hind limb muscle denervation, and loss of muscle performance were accelerated, while body weight and survival were not affected. Dampened neuroinflammation, i.e., reduced levels of astrogliosis in the brain stem already in the pre-symptomatic disease stage, and reduced microgliosis and lymphocyte infiltrations during the late disease phase were additional neuropathology features in these mice. On the molecular level, mRNA expression levels of brain-derived neurotrophic factor (BDNF) and those of the anti-inflammatory cytokine interleukin 6 (IL-6) were elevated, while those of several pro-inflammatory cytokines found reduced in the brain stem of RAMP1-deficient SOD1 mice at disease end stage. Our results thus identify an important, possibly dual role of CGRP in ALS pathogenesis.     

Liquidity dynamics around intraday price jumps in Chinese stock market

Using 4128 single jumps detected from high frequency data of 220 individual stocks in SZ300P index, this paper investigates the liquidity dynamics around price jumps in Chinese market. Some interesting empirical results are obtained and the corresponding explanations are given. The frequency of positive jumps is quite higher than that of negative jumps. The trading volumes and average trade sizes are all in a high level around positive jumps. The relatively low liquidities around negative jumps show that negative jumps may be generated and enlarged by poor liquidity provision. The price reversal after price jumps is significant, and price reversal lasts longer after positive jumps. Moreover, the size and direction of jumps are significantly correlated with the returns and trades in the post-jump trading time. These findings are believed to be associated with the high proportion of retail investors and their herding behavior for price trend chasing.     

辅助数据缺失环境下结构化自适应目标检测器

杂波背景非均匀导致经典自适应检测方法性能下降,为改善辅助数据缺失环境下的目标检测性能,研究了雷达目标结构化自适应检测方法。利用杂波协方差矩阵斜对称特征,设计了结构化广义似然比检验自适应检测器,提高了杂波谱结构化信息和待检测单元杂波信息的利用率;进一步推导了检测器的实数域表达式。仿真分析表明,所提检测器具有恒虚警率特性,其检测性能对不同杂波相关性具有很好的鲁棒性。在辅助数据缺失环境下,所提检测器性能优于现有典型非结构化和结构化检测器,且这种优势随着辅助数据缺失程度的增大而加大。     

ATP-induced Ca<Superscript>2+</Superscript>-signalling mechanisms in the regulation of mesenchymal stem cell migration

The ability of cells to migrate to the destined tissues or lesions is crucial for physiological processes from tissue morphogenesis, homeostasis and immune responses, and also for stem cell-based regenerative medicines. Cytosolic Ca²⁺ is a primary second messenger in the control and regulation of a wide range of cell functions including cell migration. Extracellular ATP, together with the cognate receptors on the cell surface, ligand-gated ion channel P2X receptors and a subset of G-protein-coupled P2Y receptors, represents common autocrine and/or paracrine Ca²⁺ signalling mechanisms. The P2X receptor ion channels mediate extracellular Ca²⁺ influx, whereas stimulation of the P2Y receptors triggers intracellular Ca²⁺ release from the endoplasmic reticulum (ER), and activation of both type of receptors thus can elevate the cytosolic Ca²⁺ concentration ([Ca²⁺]_c), albeit with different kinetics and capacity. Reduction in the ER Ca²⁺ level following the P2Y receptor activation can further induce store-operated Ca²⁺ entry as a distinct Ca²⁺ influx pathway that contributes in ATP-induced increase in the [Ca²⁺]_c. Mesenchymal stem cells (MSC) are a group of multipotent stem cells that grow from adult tissues and hold promising applications in tissue engineering and cell-based therapies treating a great and diverse number of diseases. There is increasing evidence to show constitutive or evoked ATP release from stem cells themselves or mature cells in the close vicinity. In this review, we discuss the mechanisms for ATP release and clearance, the receptors and ion channels participating in ATP-induced Ca²⁺ signalling and the roles of such signalling mechanisms in mediating ATP-induced regulation of MSC migration.     

Intracellular localization of DR5 and related regulatory pathways as a mechanism of resistance to TRAIL in cancer

TNF-related apoptosis-inducing ligand (TRAIL) is a prominent cytokine capable of inducing apoptosis. It can bind to five different cognate receptors, through which diverse intracellular pathways can be activated. TRAIL’s ability to preferentially kill transformed cells makes it a promising potential weapon for targeted tumor therapy. However, recognition of several resistance mechanisms to TRAIL-induced apoptosis has indicated that a thorough understanding of the details of TRAIL biology is still essential before this weapon can be confidently unleashed. Critical to this aim is revealing the functions and regulation mechanisms of TRAIL’s potent death receptor DR5. Although expression and signaling mechanisms of DR5 have been extensively studied, other aspects, such as its subcellular localization, non-signaling functions, and regulation of its membrane transport, have only recently attracted attention. Here, we discuss different aspects of TRAIL/DR5 biology, with a particular emphasis on the factors that seem to influence the cell surface expression pattern of DR5, along with factors that lead to its nuclear localization. Disturbance of this balance apparently affects the sensitivity of cancer cells to TRAIL-mediated apoptosis, thus constituting an eligible target for potential new therapeutic agents.