Vitamin D Compounds PRI-2191 and PRI-2205 Enhance Anastrozole Activity in Human Breast Cancer Models

1,25-Dihydroxycholecalciferol, the hormonally active vitamin D₃ metabolite, is known to exhibit therapeutic effects against breast cancer, mainly by lowering the expression of estrogen receptors and aromatase activity. Previously, the safety of the vitamin D active metabolite (24R)-1,24-dihydroxycholecalciferol (PRI-2191) and 1,25(OH)₂D₃ analog PRI-2205 was tested, and the in vitro activity of these analogs against different cancer cell lines was studied. We determined the effect of the two vitamin D compounds on anastrozole (An) activity against breast cancer based on antiproliferative activity, ELISA, flow cytometry, enzyme inhibition potency, PCR, and xenograft study. Both the vitamin D active metabolite and synthetic analog regulated the growth of not only estrogen receptor-positive cells (T47D and MCF-7, in vitro and in vivo), but also hormone-independent cancer cells such as SKBR-3 (HER-2-positive) and MDA-MB-231 (triple-negative), despite their relatively low VDR expression. Combined with An, PRI-2191 and PRI-2205 significantly inhibited the tumor growth of MCF-7 cells. Potentiation of the antitumor activity in combined treatment of MCF-7 tumor-bearing mice is related to the reduced activity of aromatase by both An (enzyme inhibition) and vitamin D compounds (switched off/decreased aromatase gene expression, decreased expression of other genes related to estrogen signaling) and by regulation of the expression of the estrogen receptor ERα and VDR.     

IGCT 综合型电荷控制 模型的建立和仿真

以电荷控制方程而建立的IGCT综合型电荷控制模型，经关键性的关断电流和关断电压进行了仿真分析，所得结果与实际结果吻合。因此该模型是有效的，可用于IGCT的开关特性分析和集成门极电路设计。     

海南省水资源配置决策的层次分析模型研究

海南省特殊的地理位置决定了其水资源配置问题的独特性,在水资源配置方案中,呈现出多阶段、多层次、多目标、多决策主体的特点,使得水资源配置模型难以确定并给决策带来了很大的风险性。本文研究了适合于海南省水资源优化配置所需的评比指标,对层次分析法加以改进,结合海南省水资源配置问题的决策要求,用改进后的层次分析法进行评价指标优化计算,最终得出了较为满意的结果。     

Retrospective adaptive prefetching for interactive Web GIS applications

A major task of a Web GIS (Geographic Information Systems) system is to transfer map data to client applications over the Internet, which may be too costly. To improve this inefficient process, various solutions are available. Caching the responses of the requests on the client side is the most commonly implemented solution. However, this method may not be adequate by itself. Besides caching the responses, predicting the next possible requests from a client and updating the cache with responses for those requests together provide a remarkable performance improvement. This procedure is called “prefetching” and makes caching mechanisms more effective and efficient. This paper proposes an efficient prefetching algorithm called Retrospective Adaptive Prefetch (RAP), which is constructed over a heuristic method that considers the former actions of a given user. The algorithm reduces the user-perceived response time and improves user navigation efficiency. Additionally, it adjusts the cache size automatically, based on the memory size of the client’s machine. RAP is compared with four other prefetching algorithms. The experiments show that RAP provides better performance enhancements than the other methods.     

The Effect of Hypoxia on the Expression of CXC Chemokines and CXC Chemokine Receptors—A Review of Literature

Hypoxia is an integral component of the tumor microenvironment. Either as chronic or cycling hypoxia, it exerts a similar effect on cancer processes by activating hypoxia-inducible factor-1 (HIF-1) and nuclear factor (NF-κB), with cycling hypoxia showing a stronger proinflammatory influence. One of the systems affected by hypoxia is the CXC chemokine system. This paper reviews all available information on hypoxia-induced changes in the expression of all CXC chemokines (CXCL1, CXCL2, CXCL3, CXCL4, CXCL5, CXCL6, CXCL7, CXCL8 (IL-8), CXCL9, CXCL10, CXCL11, CXCL12 (SDF-1), CXCL13, CXCL14, CXCL15, CXCL16, CXCL17) as well as CXC chemokine receptors—CXCR1, CXCR2, CXCR3, CXCR4, CXCR5, CXCR6, CXCR7 and CXCR8. First, we present basic information on the effect of these chemoattractant cytokines on cancer processes. We then discuss the effect of hypoxia-induced changes on CXC chemokine expression on the angiogenesis, lymphangiogenesis and recruitment of various cells to the tumor niche, including myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), tumor-associated neutrophils (TANs), regulatory T cells (T_regs) and tumor-infiltrating lymphocytes (TILs). Finally, the review summarizes data on the use of drugs targeting the CXC chemokine system in cancer therapies.     

Poly(chitosan-ester-ether-urethane) Hydrogels as Highly Controlled Genistein Release Systems

Polymeric hydrogels play an increasingly important role in medicine, pharmacy and cosmetology. They appear to be one of the most promising groups of biomaterials due to their favorable physicochemical properties and biocompatibility. The objective of the presented study was to synthesize new poly(chitosan-ester-ether-urethane) hydrogels and to study the kinetic release of genistein (GEN) from these biomaterials. In view of the above, six non-toxic hydrogels were synthesized via the Ring-Opening Polymerization (ROP) and polyaddition processes. The poly(ester-ether) components of the hydrogels have been produced in the presence of the enzyme as a biocatalyst. In some cases, the in vitro release rate of GEN from the obtained hydrogels was characterized by near-zero-order kinetics, without “burst release” and with non-Fickian transport. It is important to note that developed hydrogels have been shown to possess the desired safety profile due to lack of cytotoxicity to skin cells (keratinocytes and fibroblasts). Taking into account the non-toxicity of hydrogels and the relatively highly controlled release profile of GEN, these results may provide fresh insight into polymeric hydrogels as an effective dermatological and/or cosmetological tool.     

Maximization of total surface area of Pt-SnO<Subscript>2</Subscript>/Al<Subscript>2</Subscript>O<Subscript>3</Subscript> catalyst by the Taguchi method

The maximization of the total surface area of Pt-SnO₂/Al₂O₃ catalyst was studied by using the Taguchi method of experimental design. The catalysts were prepared by sol-gel method. The effects of HNO₃, H₂O and aluminum nitrate concentrations and the stirring rate on the total surface area were studied at three levels of each. L₉ orthogonal array leading nine experiments was used in the experimental design. The parameter levels that give maximum total surface area were determined and experimentally verified. In the range of conditions studied it was found that, medium levels of HNO₃ and H₂O concentration and lower levels of aluminum nitrate concentration and stirring rate maximize the total surface area.     

HamleDT: Harmonized multi-language dependency treebank

We present HamleDT—a HArmonized Multi-LanguagE Dependency Treebank. HamleDT is a compilation of existing dependency treebanks (or dependency conversions of other treebanks), transformed so that they all conform to the same annotation style. In the present article, we provide a thorough investigation and discussion of a number of phenomena that are comparable across languages, though their annotation in treebanks often differs. We claim that transformation procedures can be designed to automatically identify most such phenomena and convert them to a unified annotation style. This unification is beneficial both to comparative corpus linguistics and to machine learning of syntactic parsing.     

One-Way Functions Using Algorithmic and Classical Information Theories

We prove several results relating injective one-way functions, time-bounded conditional Kolmogorov complexity, and time-bounded conditional entropy. First we establish a connection between injective, strong and weak one-way functions and the expected value of the polynomial time-bounded Kolmogorov complexity, denoted here by?E(K ^t (x|f(x))). These results are in both directions. More precisely, conditions on?E(K ^t (x|f(x))) that imply that?f is a weak one-way function, and properties of?E(K ^t (x|f(x))) that are implied by the fact that?f is a strong one-way function. In particular, we prove a separation result: based on the concept of time-bounded Kolmogorov complexity, we find an interval in which every function?f is a necessarily weak but not a strong one-way function. Then we propose an individual approach to injective one-way functions based on Kolmogorov complexity, defining Kolmogorov one-way functions and prove some relationships between the new proposal and the classical definition of one-way functions, showing that a Kolmogorov one-way function is also a deterministic one-way function. A relationship between Kolmogorov one-way functions and the conjecture of polynomial time symmetry of information is also proved. Finally, we relate?E(K ^t (x|f(x))) and two forms of time-bounded entropy, the unpredictable entropy?H ^unp, in which ??one-wayness?? of a function can be easily expressed, and the Yao⁺ entropy, a measure based on compression/decompression schema in which only the decompressor is restricted to be time-bounded.     

A general topology-based framework for adaptive insertion of cohesive elements in finite element meshes

Large-scale simulation of separation phenomena in solids such as fracture, branching, and fragmentation requires a scalable data structure representation of the evolving model. Modeling of such phenomena can be successfully accomplished by means of cohesive models of fracture, which are versatile and effective tools for computational analysis. A common approach to insert cohesive elements in finite element meshes consists of adding discrete special interfaces (cohesive elements) between bulk elements. The insertion of cohesive elements along bulk element interfaces for fragmentation simulation imposes changes in the topology of the mesh. This paper presents a unified topology-based framework for supporting adaptive fragmentation simulations, being able to handle two- and three-dimensional models, with finite elements of any order. We represent the finite element model using a compact and “complete” topological data structure, which is capable of retrieving all adjacency relationships needed for the simulation. Moreover, we introduce a new topology-based algorithm that systematically classifies fractured facets (i.e., facets along which fracture has occurred). The algorithm follows a set of procedures that consistently perform all the topological changes needed to update the model. The proposed topology-based framework is general and ensures that the model representation remains always valid during fragmentation, even when very complex crack patterns are involved. The framework correctness and efficiency are illustrated by arbitrary insertion of cohesive elements in various finite element meshes of self-similar geometries, including both two- and three-dimensional models. These computational tests clearly show linear scaling in time, which is a key feature of the present data-structure representation. The effectiveness of the proposed approach is also demonstrated by dynamic fracture analysis through finite element simulations of actual engineering problems.