Extracellular Vesicles: Messengers of p53 in Tumor–Stroma Communication and Cancer Metastasis

Tumor progression to a metastatic and ultimately lethal stage relies on a tumor-supporting microenvironment that is generated by reciprocal communication between tumor and stromal host cells. The tumor–stroma crosstalk is instructed by the genetic alterations of the tumor cells—the most frequent being mutations in the gene Tumor protein p53 (TP53) that are clinically correlated with metastasis, drug resistance and poor patient survival. The crucial mediators of tumor–stroma communication are tumor-derived extracellular vesicles (EVs), in particular exosomes, which operate both locally within the primary tumor and in distant organs, at pre-metastatic niches as the future sites of metastasis. Here, we review how wild-type and mutant p53 proteins control the secretion, size, and especially the RNA and protein cargo of tumor-derived EVs. We highlight how EVs extend the cell-autonomous tumor suppressive activity of wild-type p53 into the tumor microenvironment (TME), and how mutant p53 proteins switch EVs into oncogenic messengers that reprogram tumor–host communication within the entire organism so as to promote metastatic tumor cell dissemination.     

Phase diagram of the Li2SO4–Na2SO4 system

The thermal analysis and X-ray powder diffraction studies of the Li₂SO₄–Na₂SO₄ system, including the high-temperature X-ray diffraction technique, have elucidated four phases of variable composition: three solid solutions based on the α-Li₂SO₄, α-Na₂SO₄, and α-LiNaSO₄ high-temperature polymorphs, and a low-temperature β-LiNaSO₄ phase. α-Na₂SO₄-Base solid solution disintegrates into two phases via a monotectoid phase transformation. It is quite probable that the monotectoid process is related to the conversion of the second-order phase transition to the first-order phase transition.     

基于变异测试的错误定位研究进展

随着软件规模和复杂度的不断提高，软件的质量问题成为了关注的焦点，如何高效地找出软件中的错误成为一个亟需解决的问题。错误定位是软件质量保证的重要途径之一，近年来已经成为软件工程中一个非常重要的研究课题。基于变异测试的错误定位通过比较原程序和对应变异体的差异来计算每条语句的怀疑度，再由怀疑度大小进行排序，程序员根据排序逐个检查找出错误语句。汇总近7年（2012-2018）国内外的基于变异测试的错误定位技术的研究成果，介绍了错误定位的基本方法，介绍基于变异测试的错误定位思想，从变异算子、变异体及等价变异体3个方面对已有的研究工作进行分类归纳和总结，探讨了基于变异测试的错误定位未来可能的研究方向、机遇和挑战。     

A practical assessment of risk-averse approaches in production lot-sizing problems

ABSTRACT

This paper presents an empirical assessment of four state-of-the-art risk-averse approaches to deal with the capacitated lot-sizing problem under stochastic demand. We analyse two mean-risk models based on the semideviation and on the conditional value-at-risk risk measures, and alternate first and second-order stochastic dominance approaches. The extensive computational experiments based on different instances characteristics and on a case-study suggest that CVaR exhibits a good trade-off between risk and performance, followed by the semideviation and first-order stochastic dominance approach. For all approaches, enforcing risk-aversion helps to reduce the cost-standard deviation substantially, which is usually accomplished via increasing production rates. Overall, we can say that very risk-averse decision-makers would be willing to pay an increased price to have a much less risky solution given by CVaR. In less risk-averse settings, though, semideviation and first-order stochastic dominance can be appealing alternatives to provide significantly more stable production planning costs with a marginal increase of the expected costs.     

Design and Synthesis of Novel Chromophore with Multi-Carboxyl Groups

In order to explore the application of organic conjugated small molecules in bioimaging, a novel functional chromophore with A-π-D-π-A structure (Cr-3) was synthesized through Knoevenagel condensation reaction, consisting of carbazole unit as electron donor and cyanoacetic acid as electron acceptor groups. To improve the water solubility of this conjugated molecule, three carboxyl groups were introduced to chromophore Cr-3. Compared to the traditional D-π-A chromophores, chromophore Cr-3 showed the great improvement in water with the solubility of 2000 ppm. Also, the thermal stability of chromophore Cr-3 was also studied. The thermal decomposition temperature (Td) of Cr-3 was approximately 180°C, which was attributed to the dehydration of the carboxyl groups. Though the second harmonic generation (SHG) effect was not very high, it is large enough for the detection of SHG signal in water solution (0.28 pm/V).     

Maximizing Convergence Speed for Second Order Consensus in Leaderless Multi-Agent Systems

The paper deals with the consensus problem in a leaderless network of agents that have to reach a common velocity while forming a uniformly spaced string. Moreover, the final common velocity (reference velocity) is determined by the agents in a distributed and leaderless way. Then, the consensus protocol parameters are optimized for networks characterized by a communication topology described by a class of directed graphs having a directed spanning tree, in order to maximize the convergence rate and avoid oscillations. The advantages of the optimized consensus protocol are enlightened by some simulation results and comparison with a protocol proposed in the related literature. The presented protocol can be applied to coordinate agents such as mobile robots, automated guided vehicles (AGVs) and autonomous vehicles that have to move with the same velocity and a common inter-space gap.      

Rice PIN Auxin Efflux Carriers Modulate the Nitrogen Response in a Changing Nitrogen Growth Environment

Auxins play an essential role in regulating plant growth and adaptation to abiotic stresses, such as nutrient stress. Our current understanding of auxins is based almost entirely on the results of research on the eudicot Arabidopsis thaliana, however, the role of the rice PIN-FORMED (PIN) auxin efflux carriers in the regulation of the ammonium-dependent response remains elusive. Here, we analyzed the expression patterns in various organs/tissues and the ammonium-dependent response of rice PIN-family genes (OsPIN genes) via qRT–PCR, and attempted to elucidate the relationship between nitrogen (N) utilization and auxin transporters. To investigate auxin distribution under ammonium-dependent response after N deficiency in rice roots, we used DR5::VENUS reporter lines that retained a highly active synthetic auxin response. Subsequently, we confirmed that ammonium supplementation reduced the DR5::VENUS signal compared with that observed in the N-deficient condition. These results are consistent with the decreased expression patterns of almost all OsPIN genes in the presence of the ammonium-dependent response to N deficiency. Furthermore, the ospin1b mutant showed an insensitive phenotype in the ammonium-dependent response to N deficiency and disturbances in the regulation of several N-assimilation genes. These molecular and physiological findings suggest that auxin is involved in the ammonium assimilation process of rice, which is a model crop plant.     

二阶效应的荷载判别式

结构设计过程中各种判断二阶效应的理论公式都比较复杂和繁琐。以单层钢框架为例,从放大系数与稳定系数之间的关系出发,推导出的二阶效应荷载判别公式形式简单,概念清楚,应用方便。     

初始几何缺陷对钢框架柱性能的影响(Ⅱ):参数分析

在钢框架二阶弹性分析中,结构整体初始几何缺陷和构件的初始几何缺陷是实际存在的,其影响不可忽略。通过平面子结构理论模型进行参数分析,结果证明,对于弱支撑钢框架柱,结构的整体几何缺陷和构件几何缺陷对弯矩的影响均可以等效为作用于楼层处的假想水平力,假想水平力是作用于该楼层的竖向荷载的函数。     

半刚性钢框架优化设计研究

推导了考虑连接柔性和几何非线性的局部坐标下的单元刚度矩阵,并对半刚性连接单元的固端力进行了修正;其次,采用增量加载法,给出了考虑连接柔性、框架的几何非线性和单元内力与连接之间耦合效应的半刚性钢框架结构分析计算机流程;按照GB50017-2003《钢结构设计规范》和实际施工的要求,建立了考虑构件和连接最小费用问题的半刚性钢框架优化数学模型;然后,在遗传算法和半刚性钢框架结构分析流程的基础上,给出了半刚性钢框架优化设计步骤;根据算例,对半刚性钢框架优化设计做了初步的探讨。