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Selected AbstractsOrganic dyes as small molecule protein,protein interaction inhibitors for the CD40,CD154 costimulatory interactionJOURNAL OF MOLECULAR RECOGNITION, Issue 1 2010Peter Buchwald Abstract It is becoming increasingly clear that small molecules can often act as effective protein,protein interaction (PPI) inhibitors, an area of increasing interest for its many possible therapeutic applications. We have identified several organic dyes and related small molecules that (i) concentration-dependently inhibit the important CD40,CD154 costimulatory interaction with activities in the low micromolar (µM) range, (ii) show selectivity toward this particular PPI, (iii) seem to bind on the surface of CD154, and (iv) concentration-dependently inhibit the CD154-induced B cell proliferation. They were identified through an iterative activity screening/structural similarity search procedure starting with suramin as lead, and the best smaller compounds, the main focus of the present work, achieved an almost 3-fold increase in ligand efficiency (,G0/nonhydrogen atom,=,0.8,kJ/NnHa) approaching the average of known promising small-molecule PPI inhibitors (,1.0,kJ/NnHa). Since CD154 is a member of the tumor necrosis factor (TNF) superfamily of cell surface interaction molecules, inhibitory activities on the TNF-R1,TNF- , interactions were also determined to test for specificity, and the compounds selected here all showed more than 30-fold selectivity toward the CD40,CD154 interaction. Because of their easy availability in various structural scaffolds and because of their good protein-binding ability, often explored for tissue-specific staining and other purposes, such organic dyes can provide a valuable addition to the chemical space searched to identify small molecule PPI inhibitors in general. Copyright © 2009 John Wiley & Sons, Ltd. [source] A General Misspecification Test for Spatial Regression Models: Dependence, Heterogeneity, and NonlinearityJOURNAL OF REGIONAL SCIENCE, Issue 2 2001Thomas De Graaff There is an increasing awareness of the potentials of nonlinear modeling in regional science. This can be explained partly by the recognition of the limitations of conventional equilibrium models in complex situations, and also by the easy availability and accessibility of sophisticated computational techniques. Among the class of nonlinear models, dynamic variants based on, for example, chaos theory stand out as an interesting approach. However, the operational significance of such approaches is still rather limited and a rigorous statistical-econometric treatment of nonlinear dynamic modeling experiments is lacking. Against this background this paper is concerned with a methodological and empirical analysis of a general misspecification test for spatial regression models that is expected to have power against nonlinearity, spatial dependence, and heteroskedasticity. The paper seeks to break new research ground by linking the classical diagnostic tools developed in spatial econometrics to a misspecification test derived directly from chaos theory,the BDS test, developed by Brock, Dechert, and Scheinkman (1987). A spatial variant of the BDS test is introduced and applied in the context of two examples of spatial process models, one of which is concerned with the spatial distribution of regional investments in The Netherlands, the other with spatial crime patterns in Columbus, Ohio. [source] Water Resources Modeling of the Ganges-Brahmaputra-Meghna River Basins Using Satellite Remote Sensing Data,JOURNAL OF THE AMERICAN WATER RESOURCES ASSOCIATION, Issue 6 2009Bushra Nishat Nishat, Bushra and S.M. Mahbubur Rahman, 2009. Water Resources Modeling of the Ganges-Brahmaputra-Meghna River Basins Using Satellite Remote Sensing Data. Journal of the American Water Resources Association (JAWRA) 45(6):1313-1327. Abstract:, Large-scale water resources modeling can provide useful insights on future water availability scenarios for downstream nations in anticipation of proposed upstream water resources projects in large international river basins (IRBs). However, model set up can be challenging due to the large amounts of data requirement on both static states (soils, vegetation, topography, drainage network, etc.) and dynamic variables (rainfall, streamflow, soil moisture, evapotranspiration, etc.) over the basin from multiple nations and data collection agencies. Under such circumstances, satellite remote sensing provides a more pragmatic and convenient alternative because of the vantage of space and easy availability from a single data platform. In this paper, we demonstrate a modeling effort to set up a water resources management model, MIKE BASIN, over the Ganges, Brahmaputra, and Meghna (GBM) river basins. The model is set up with the objective of providing Bangladesh, the lowermost riparian nation in the GBM basins, a framework for assessing proposed water diversion scenarios in the upstream transboundary regions of India and deriving quantitative impacts on water availability. Using an array of satellite remote sensing data on topography, vegetation, and rainfall from the transboundary regions, we demonstrate that it is possible to calibrate MIKE BASIN to a satisfactory level and predict streamflow in the Ganges and Brahmaputra rivers at the entry points of Bangladesh at relevant scales of water resources management. Simulated runoff for the Ganges and Brahmaputra rivers follow the trends in the rated discharge for the calibration period. However, monthly flow volume differs from the actual rated flow by (,) 8% to (+) 20% in the Ganges basin, by (,) 15 to (+) 12% in the Brahmaputra basin, and by (,) 15 to (+) 19% in the Meghna basin. Our large-scale modeling initiative is generic enough for other downstream nations in IRBs to adopt for their own modeling needs. [source] Wear and microstructural characteristics of spray atomized zircon sand reinforced LM13 alloy.MATERIALWISSENSCHAFT UND WERKSTOFFTECHNIK, Issue 7 2010Verschleiß- und Gefügecharakteristik von sprühkompaktierter mit Zirkoniumsand verstärkter LM13 Legierung Verbundwerkstoff; Aluminiummatrix; Sprühkompaktieren; Verschleißverhalten Abstract The requirement of the high performance light weight materials demands the development of varieties of materials within the economical range to get it commercialized. Light weight aluminium alloys are used in several structural applications like automotive, aerospace, defense industry and other fields of engineering. The ceramic particle reinforced aluminium metal matrix composites (AMCs) have emerged as a suitable candidate for commercial applications. A variety of processing routes have been adopted to manufacture AMCs. In the present work LM13 alloy reinforced with zircon sand is formed via spray forming. During experimentation a self prepared convergent-divergent nozzle is used for inert gas atomization of the melt which is subsequently deposited on copper substrate placed vertically below the atomizer. The zircon sand particles are injected in the atomization zone by external injectors aligned perpendicular to the gas atomization axis. Zircon sand has been found to have new promising economical commercial candidate due to its easy availability and good mechanical properties like high hardness, high modulus of elasticity and good thermal stability. The microhardness of cast alloy and spray formed composite shows that the spray formed zircon sand reinforced composite has higher hardness. Also the lower wear rate has been observed in case of the zircon sand reinforced AMC as compared to LM13 alloy. This behaviour is further analyzed in light of microstructural features of the spray deposited composite using optical and scanning electron microscope (SEM). A comparative study of this material (LM13/Zircon sand) with the parent alloy (LM13) is presented in this work. [source] Microvascular Angiogenesis and Apoptosis in the Survival of Free Fat Grafts ,THE LARYNGOSCOPE, Issue 8 2000Toshiro Nishimura MD Abstract Objectives/Hypothesis Autologous fat is an ideal material for augmentation in plastic surgery because of its minimal tissue reaction and easy availability, but its long-term graft survival is somewhat unpredictable. This study was conducted to determine how fat grafts get their vascular supply from the recipient bed and why they keep reducing in volume and weight. Study Design Experimental study using animal models. Methods The expression of vascular endothelial growth factor (VEGF) in grafted fat tissue was examined by using immunohistochemical staining, and apoptotic cell death in the grafted fat was studied by using terminal deoxynucleotidyl transferase (TdT),mediated deoxy-uridine triphosphate (dUTP)-biotin nick end-labeling method. Twenty-five Wistar rats were used as models of free fat grafts. Fat tissue taken from inguinal fat pads was grafted to the back skin with an 18-gauge needle injection. Results The weight of the injected fat was significantly reduced on the 180th day compared with the original weight (32% ± 10%). VEGF+ cells were observed in fibrous connective tissue of the grafts on days 7 and 30 but not after day 90. Apoptotic cells were also observed on days 7 and 30. Conclusions Angiogenic factors including VEGF started to revascularize the graft around day 7, and the extent of the vasculature was not reduced after the revascularization. In addition to necrosis in the graft's early stages, apoptosis induced by many factors in the graft's environment is also, at least in part, a cause of long-term volume reduction of the fat graft. Thus clinical application of angiogenic factors such as VEGF to fat grafts and control of apoptosis may contribute to improvements in fat-grafting techniques. [source] Amino Acid Ligand Chirality for Enantioselective SynthesesCHEMISTRY & BIODIVERSITY, Issue 6 2010Károly Micskei Abstract Amino acids are attractive sources of chirality in stoichiometric or catalytic transition metal/organic chemistry. In spite of easy availability and other advantages, the application of these ligands is hindered by several problems. Now, at the dawn of emerging d- amino acid biochemistry, efforts in this direction are becoming increasingly important. The results of research on application of amino acid ligands for transition-metal reagents in organic syntheses are reviewed in the present work. [source] | ||||||||||