A Holistic Evolutionary and 3D Pharmacophore Modelling Study Provides Insights into the Metabolism,Function, and Substrate Selectivity of the Human Monocarboxylate Transporter 4 (hMCT4)

Monocarboxylate transporters (MCTs) are of great research interest for their role in cancer cell metabolism and their potential ability to transport pharmacologically relevant compounds across the membrane. Each member of the MCT family could potentially provide novel therapeutic approaches to various diseases. The major differences among MCTs are related to each of their specific metabolic roles, their relative substrate and inhibitor affinities, the regulation of their expression, their intracellular localization, and their tissue distribution. MCT4 is the main mediator for the efflux of L-lactate produced in the cell. Thus, MCT4 maintains the glycolytic phenotype of the cancer cell by supplying the molecular resources for tumor cell proliferation and promotes the acidification of the extracellular microenvironment from the co-transport of protons. A promising therapeutic strategy in anti-cancer drug design is the selective inhibition of MCT4 for the glycolytic suppression of solid tumors. A small number of studies indicate molecules for dual inhibition of MCT1 and MCT4; however, no selective inhibitor with high-affinity for MCT4 has been identified. In this study, we attempt to approach the structural characteristics of MCT4 through an in silico pipeline for molecular modelling and pharmacophore elucidation towards the identification of specific inhibitors as a novel anti-cancer strategy.     

Novel Cell Permeable Polymers of N-Substituted L-2,3-Diaminopropionic Acid (DAPEGs) and Cellular Consequences of Their Interactions with Nucleic Acids

The present study aimed to synthesize novel polycationic polymers composed of N-substituted L-2,3-diaminopropionic acid residues (DAPEGs) and investigate their cell permeability, cytotoxicity, and DNA-binding ability. The most efficient cell membrane-penetrating compounds (O2Oc-Dap(GO2)_n-O2Oc-NH₂, where n = 4, 6, and 8) showed dsDNA binding with a binding constant in the micromolar range (0.3, 3.4, and 0.19 µM, respectively) and were not cytotoxic to HB2 and MDA-MB-231 cells. Selected compounds used in the transfection of a GFP plasmid showed high transfection efficacy and minimal cytotoxicity. Their interaction with plasmid DNA and the increasing length of the main chain of tested compounds strongly influenced the organization and shape of the flower-like nanostructures formed, which were unique for 5/6-FAM-O2Oc-[Dap(GO2)]₈-O2Oc-NH₂ and typical for large proteins.     

冷轧带钢板形测控技术的发展状况和关键问题

 冷轧带钢属于高端精品钢材,板形在线检测与控制是冷轧带钢的高端核心关键技术。自主创新研制板形测控系统是实现中国钢铁工业发展升级、建设钢铁强国的重大需求。目前,板形测控技术市场国外占据优势,国产系统正在代替进口,扩大应用规模,推进技术完善。研制先进的板形测控系统需要解决的关键技术有高精度高质量的板形仪、功能完备强大的控制手段和方法、高精度高速度的数学模型。板形仪主要有接触式和非接触式两大类,接触式板形仪通过测量带钢张力的横向分布反映板形,非接触式板形仪通过测量带钢浪形反映板形。接触式板形仪可靠耐用精度高,应用广泛,发展趋势为整辊式板形检测辊、无线式信号传输装置、板形数据的精确处理。板形控制数学模型的主要类型,按建模的原理和方法可分为机理模型和智能模型;按模型的性质和作用可分为分析模型和控制模型;按板形的表示方法可分为多点控制模型和分量控制模型。板形控制模型的发展趋势为机理与智能协同建模、动态模拟预报和动态解耦控制、多种手段和方法的协同优化。进一步提高板形测控技术水平需要突破3项关键问题,即整辊式板形仪通道耦合与解耦的机理模型、板形控制的动态模拟和动态解耦模型、板形控制的高精度智能建模方法。     

Photoelastic Studies on Rubber-to-Rubber Joints

Photoelasticity is a method which yields information on the principal stress difference and orientation in a composite structure. Various problems associated with this technique, especially those concerning the fundamental relationship between the fringe order and the stress, have yet to be investigated. A few studies of this relationship in a universal stress state have been presented, particularly in the field of rubber-to-metal and rubber-to-fabric composites, but no evaluations have so far been made in the field of rubber-to-rubber joints. Applying the photoelastic method, we report our observations on the stress distribution in a natural rubber to natural rubber joint subjected to uniaxial tension. A comparison between the results of experimental photoelastic studies and the corresponding computer modelling has been illustrated. The theoretical displacement pattern of the angular joints of bi-rubber part has also been highlighted.     

Current problems in the modelling of chemical reactors

Modelling of chemical reactors is reviewed with an emphasis on process development and scale-up. A distinction is made between modelling of chemical kinetics, of rate processes in volume elements and of whole reactors. Examples are mainly taken from papers presented at the Sixth International Symposium on Chemical Reaction Engineering. Special attention is given to the modelling of single phase reactors, fixed beds, trickle beds, fluid beds, and gas bubble reactors.     

双甲脒分析方法的国际协作研究

结合参加双甲脒分析方法的国际协作研究，对国际分析方法协作研究的一般程序做了介绍，反映了国际同行们的分析水平。对国内同行了解和掌握国际协作研究的程序，及国内分析方法标准的协作实验验证也有所裨益。     

Developing human factors/ergonomics as a design discipline

This paper deals with internal challenges that the human factors/ergonomics (HFE) research faces when wishing to strengthen its contribution to development of work systems. Three established characteristics of high-quality HFE, i.e., HFE takes a systems approach, HFE is design-driven, and HFE focuses on two closely related outcomes, performance and well-being, are taken as a starting point of a methodological discussion, in which conceptual innovations, e.g. adopting the technology-in-use perspective, are proposed to support development of HFE towards the high-quality aims. The feasibility of the proposed conceptual choices is demonstrated by introducing a naturalistic HFE analysis approach including four HFE functions. The gained experience of the use of this approach in a number of complex work domains allows the conclusion that becoming design-driven appears as that most difficult quality target for HFE to reach. Creating an own design discipline identity in a multi-voiced collaboration is the key internal challenge for human factors/ergonomics.     

Development of a system‐based water balance model to assess interrelated physical and anthropogenic constraints in lake and reservoir watersheds,applied to Coeur d'Alene Lake,Idaho, USA

This study presents a methodology for the development of a water balance model that uses publicly available data in a manner useful to water scientists and managers who manage complex lake and reservoir watersheds. The approach was applied to Coeur d'Alene Lake, a naturally occurring lake that is controlled by a dam located on its outlet (Spokane River) in North Idaho, USA. As in many other areas, the region surrounding Coeur d'Alene Lake has experienced high rates of population growth in recent years, and there is concern that, as consumptive water use increases, the lake will eventually not be able to be managed to simultaneously maintain the federally mandated minimum flow requirements in the Spokane River and also maintain the target summertime elevation of 2128 feet (648.6 m) for recreation and hydropower purposes. The complexity caused by the competing uses at Coeur d'Alene Lake makes it an excellent case study for similarly characterized watersheds. Both a natural flow model and regulated elevation model were developed, and sensitivity analysis was conducted on both models to evaluate which lake processes have the greatest effects on lake elevation, thereby requiring the most attention. A ‘low‐flow’ scenario was modelled to demonstrate the usefulness of the model and to inform Coeur d'Alene Lake regional stakeholders regarding the interrelationship between current water policy and the lake's physical behaviour under stressed conditions that could result from climate change. Model result indicates that, while lake elevation may be maintained at the summertime elevation of 2128 feet (648.6 m) under a low‐flow scenario, the outflows in the Spokane River start to approach the minimum flow requirements in the month of August. The developed approach is useful where publicly available data exist and allows for economic, yet rigorous, water resources systems evaluation without requiring significant field data collection.