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Selected AbstractsG-protein coupled receptors: SAR analyses of neurotransmitters and antagonistsJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 3 2004C. L. Kuo MS Summary Background:, From the deductive point of view, neurotransmitter receptors can be divided into categories such as cholinergic (muscarinic, nicotinic), adrenergic (, - and , -), dopaminergic, serotoninergic (5-HT1,5-HT5), and histaminergic (H1 and H2). Selective agonists and antagonists of each receptor subtype can have specific useful therapeutic applications. For understanding the molecular mechanisms of action, an inductive method of analysis is useful. Objective:, The aim of the present study is to examine the structure,activity relationships of agents acting on G-protein coupled receptors. Method:, Representative sets of G-PCR agonists and antagonists were identified from the literature and Medline [P.M. Walsh (2003) Physicians' desk reference; M.J. O'Neil (2001) The Merck index]. The molecular weight (MW), calculated logarithm of octanol/water partition coefficient (C log P) and molar refraction (CMR), dipole moment (DM), Elumo (the energy of the lowest unoccupied molecular orbital, a measure of the electron affinity of a molecule and its reactivity as an electrophile), Ehomo (the energy of the highest occupied molecular orbital, related to the ionization potential of a molecule, and its reactivity as a nucleophile), and the total number of hydrogen bonds (Hb) (donors and receptors), were chosen as molecular descriptors for SAR analyses. Results:, The data suggest that not only do neurotransmitters share common structural features but their receptors belong to the same ensemble of G-protein coupled receptor with seven to eight transmembrane domains with their resultant dipoles in an antiparallel configuration. Moreover, the analysis indicates that the receptor exists in a dynamic equilibrium between the closed state and the open state. The energy needed to open the closed state is provided by the hydrolysis of GTP. A composite 3-D parameter frame setting of all the neurotransmitter agonists and antagonists are presented using MW, Hb and , as independent variables. Conclusion:, It appears that all neurotransmitters examined in this study operate by a similar mechanism with the G-protein coupled receptors. [source] Small-scale variability in surface moisture on a fine-grained beach: implications for modeling aeolian transportEARTH SURFACE PROCESSES AND LANDFORMS, Issue 10 2009Brandon L. Edwards Abstract Small-scale variations in surface moisture content were measured on a fine-grained beach using a Delta-T Theta probe. The resulting data set was used to examine the implications of small-scale variability for estimating aeolian transport potential. Surface moisture measurements were collected on a 40 cm × 40 cm grid at 10 cm intervals, providing a total of 25 measurements for each grid data set. A total of 44 grid data sets were obtained from a representative set of beach sub-environments. Measured moisture contents ranged from about 0% (dry) to 25% (saturated), by weight. The moisture content range within a grid data set was found to vary from less than 1% to almost 15%. The magnitude of within-grid variability varied consistently with the mean moisture content of the grid sets, following an approximately normal distribution. Both very wet and very dry grid data sets exhibited little internal variability in moisture content, while intermediate moisture contents were associated with higher levels of variability. Thus, at intermediate moisture contents it was apparent that some portions of the beach surface could be dry enough to allow aeolian transport (i.e. moisture content is below the critical threshold), while adjacent portions are too wet for transport to occur. To examine the implications of this finding, cumulative distribution functions were calculated to model the relative proportions of beach surface area expected to be above or below specified threshold moisture levels (4%, 7%, and 14%). It was found that the implicit inclusion of small-scale variability in surface moisture levels typically resulted in changes of less than 1% in the beach area available for transport, suggesting that this parameter can be ignored at larger spatial scales. Copyright © 2009 John Wiley & Sons, Ltd. [source] Seismic design of bridges accounting for spatial variability of ground motionEARTHQUAKE ENGINEERING AND STRUCTURAL DYNAMICS, Issue 4-5 2005A. Lupoi Abstract The effects of the spatial variability of the ground motion on the response of bridge structures are investigated in this study. Following a well-established convention, the phenomenon is represented as the combined effect of three causes: the loss of coherence of the motion with distance, the wave-passage, and the local site conditions. Since the nature and amount of non-synchronism vary within ample limits a statistical approach is adopted. A parametric study is carried out on a representative set of bridges subjected to carefully selected combinations of the factors inducing spatial variability. The investigation has shown that the phenomenon affects the response considerably and, hence, the level of protection of these structures. It is observed that for all bridge types considered, the ductility demands at the base of the piers in the presence of spatial variability increase in the majority of cases. Further, for a given bridge type, the probabilities of failure vary by more than one order of magnitude depending on the combination of the parameters. Attention has been focused on a parameter representing the ratio between the maximum curvature ductility demand and the same quantity for the case of fully synchronous motion. This parameter has been used to correct the conventional synchronous design procedure by increasing the available ductility. The re-analysis of all the cases with a modified ductility capacity shows that the procedure is effective in reducing the fragilities to the values corresponding to synchronous input. Copyright © 2005 John Wiley & Sons, Ltd. [source] Lipopolysaccharide is a frequent and significant contaminant in microglia-activating factorsGLIA, Issue 1 2008Jonathan R. Weinstein Abstract Lipopolysaccharide (LPS/endotoxin) is a potent immunologic stimulant. Many commercial-grade reagents used in research are not screened for LPS contamination. LPS induces a wide spectrum of proinflammatory responses in microglia, the immune cells of the brain. Recent studies have demonstrated that a broad range of endogenous factors including plasma-derived proteins and bioactive phospholipids can also activate microglia. However, few of these studies have reported either the LPS levels found in the preparations used or the effect of LPS inhibitors such as polymyxin B (PMX) on factor-induced responses. Here, we used the Limulus amoebocyte lysate assay to screen a broad range of commercial- and pharmaceutical-grade proteins, peptides, lipids, and inhibitors commonly used in microglia research for contamination with LPS. We then characterized the ability of PMX to alter a representative set of factor-induced microglial activation parameters including surface antigen expression, metabolic activity/proliferation, and NO/cytokine/chemokine release in both the N9 microglial cell line and primary microglia. Significant levels of LPS contamination were detected in a number of commercial-grade plasma/serum- and nonplasma/serum-derived proteins, phospholipids, and synthetic peptide preparations, but not in pharmaceutical-grade recombinant proteins or pharmacological inhibitors. PMX had a significant inhibitory effect on the microglia-activating potential of a number of commercial-, but not pharmaceutical-grade, protein preparations. Novel PMX-resistant responses to ,2 -macroglobulin and albumin were incidentally observed. Our results indicate that LPS is a frequent and significant contaminant in commercial-grade preparations of previously reported microglia-activating factors. Careful attention to LPS levels and appropriate controls are necessary for future studies in the neuroinflammation field. © 2007 Wiley-Liss, Inc. [source] A large carbon pool and small sink in boreal Holocene lake sedimentsGLOBAL CHANGE BIOLOGY, Issue 10 2004Pirkko Kortelainen Abstract Model-based estimates suggest that lake sediments may be a significant, long-term sink for organic carbon (C) at regional to global scales. These models have used various approaches to predict sediment storage at broad scales from very limited data sets. Here, we report a large-scale direct assessment of the standing stock and sedimentation rate of C for a representative set of lakes in Finland. The 122 lakes were selected from the statistically selected Nordic Lake Survey database, they cover the entire country and the water quality represents the average lake water quality in Finland. Unlike all prior estimates, these data use sediment cores that comprise the entire sediment record. The data show that within Finland, aquatic ecosystems contain the second largest areal C stocks (19 kg C m,2) after peatlands (72 kg C m,2), and exceed by significant amounts stocks in the forest soil (uppermost 75cm; 7.2 kg C m,2) and woody biomass (3.4 kg C m,2). Kauppi et al. (1997). The Finnish estimate extrapolated over the boreal region gives a total C pool in lakes 19,27 Pg C, significantly lower than the previous model-based estimates. [source] Analysis of microstructure development in shearbands by energy relaxation of incremental stress potentials: Large-strain theory for standard dissipative solidsINTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN ENGINEERING, Issue 1 2003Christian Miehe Abstract We propose a fundamentally new approach to the treatment of shearband localizations in strain softening elastic,plastic solids at finite strains based on energy minimization principles associated with microstructure developments. The point of departure is a general internal variable formulation that determines the finite inelastic response as a standard dissipative medium. Consistent with this type of inelasticity we consider an incremental variational formulation of the local constitutive response where a quasi-hyperelastic stress potential is obtained from a local constitutive minimization problem with respect to the internal variables. The existence of this variational formulation allows the definition of the material stability of an inelastic solid based on weak convexity conditions of the incremental stress potential in analogy to treatments of finite elasticity. Furthermore, localization phenomena are interpreted as microstructure developments on multiple scales associated with non-convex incremental stress potentials in analogy to elastic phase decomposition problems. These microstructures can be resolved by the relaxation of non-convex energy functionals based on a convexification of the stress potential. The relaxed problem provides a well-posed formulation for a mesh-objective analysis of localizations as close as possible to the non-convex original problem. Based on an approximated rank-one convexification of the incremental stress potential we develop a computational two-scale procedure for a mesh-objective treatment of localization problems at finite strains. It constitutes a local minimization problem for a relaxed incremental stress potential with just one scalar variable representing the intensity of the microshearing of a rank-one laminate aligned to the shear band. This problem is sufficiently robust with regard to applications to large-scale inhomogeneous deformation processes of elastic,plastic solids. The performance of the proposed energy relaxation method is demonstrated for a representative set of numerical simulations of straight and curved shear bands which report on the mesh independence of the results. Copyright © 2003 John Wiley & Sons, Ltd. [source] Elastoplastic dynamic analysis with hybrid stress elementsINTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN ENGINEERING, Issue 3 2002J. A. Teixeira de Freitas Abstract The stress model of the hybrid finite element formulation is applied to the solution of dynamic elastoplastic structural problems. The stress field is approximated in the domain of the elements and the displacements on its boundary. The displacement, velocity and acceleration approximations in the domain of the element are implicit, in the sense that they result from a combination of the stress estimate with the time integration procedure that ensures that the equilibrium condition is locally satisfied. The finite elements are subdivided in plastic cells where a gradient dependent model is implemented using a hybrid formulation based on the approximation of the plastic parameter and the plastic radiation fields in the domain and on the boundary of the plastic cells, respectively. Generalized variables associated with orthogonal and naturally hierarchical bases are used. The resulting solving systems are symmetric, sparse, p -adaptive and well suited to parallel processing. The performance of the element is assessed using a representative set of testing problems. Copyright © 2001 John Wiley & Sons, Ltd. [source] Method of fundamental solutions for partial-slip fibrous filtration flowsINTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN FLUIDS, Issue 3 2009Shunliu Zhao Abstract In this study a Stokeslet-based method of fundamental solutions (MFS) for two-dimensional low Reynolds number partial-slip flows has been developed. First, the flow past an infinitely long cylinder is selected as a benchmark. The numerical accuracy is investigated in terms of the location and the number of the Stokeslets. The benchmark study shows that the numerical accuracy increases when the Stokeslets are submerged deeper beneath the cylinder surface, as long as the formed linear system remains numerically solvable. The maximum submergence depth increases with the decrease in the number of Stokeslets. As a result, the numerical accuracy does not deteriorate with the dramatic decrease in the number of Stokeslets. A relatively small number of Stokeslets with a substantial submergence depth is thus chosen for modeling fibrous filtration flows. The developed methodology is further examined by application to Taylor,Couette flows. A good agreement between the numerical and analytical results is observed for no-slip and partial-slip boundary conditions. Next, the flow about a representative set of infinitely long cylindrical fibers confined between two planar walls is considered to represent the fibrous filter flow. The obtained flowfield and pressure drop agree very well with the experimental data for this setup of fibers. The developed MFS with submerged Stokeslets is then applied to partial-slip flows about fibers to investigate the slip effect at fiber,fluid interface on the pressure drop. The numerical results compare qualitatively with the analytical solution available for the limit case of infinite number of fibers. Copyright © 2008 John Wiley & Sons, Ltd. [source] Color reduction for complex document imagesINTERNATIONAL JOURNAL OF IMAGING SYSTEMS AND TECHNOLOGY, Issue 1 2009Nikos Nikolaou Abstract A new technique for color reduction of complex document images is presented in this article. It reduces significantly the number of colors of the document image (less than 15 colors in most of the cases) so as to have solid characters and uniform local backgrounds. Therefore, this technique can be used as a preprocessing step by text information extraction applications. Specifically, using the edge map of the document image, a representative set of samples is chosen that constructs a 3D color histogram. Based on these samples in the 3D color space, a relatively large number of colors (usually no more than 100 colors) are obtained by using a simple clustering procedure. The final colors are obtained by applying a mean-shift based procedure. Also, an edge preserving smoothing filter is used as a preprocessing stage that enhances significantly the quality of the initial image. Experimental results prove the method's capability of producing correctly segmented complex color documents where the character elements can be easily extracted as connected components. © 2009 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 19, 14,26, 2009 [source] Rapid detection of bordetella pertussis by real-time PCR using SYBR green I and a LightCycler instrumentJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 5 2004S. K. Poddar Abstract A polymerase chain reaction (PCR) assay in real-time for detection of B. pertussis using SYBR green I as the reporter fluorophore and LightCycler instrument (a thermocycler coupled to a fluorescence detection device) was established and evaluated. The amplified amplicon using series diluted control prototype strain (ATCC strain #9797) of B. pertussis was analyzed for the fluorescent melting profile, and melting temperature (Tm) was determined. When examined, amplicons using a representative set of clinical isolates of B. pertussis were found to have the same Tm value (86 ± 0.5°C, the specificity parameter of detection) as the control prototype strain as expected. Amplified product was also analyzed and detected by agarose gel electrophoresis. The detection limit by fluorescent profile and Tm analysis was 10-fold better than that detected by agarose gel analysis. J. Clin. Lab. Anal. 18:265,270, 2004. © 2004 Wiley-Liss, Inc. [source] Insights on protein-DNA recognition by coarse grain modellingJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 15 2008P. Poulain Abstract Coarse grain modelling of macromolecules is a new approach, potentially well adapted to answer numerous issues, ranging from physics to biology. We propose here an original DNA coarse grain model specifically dedicated to protein-DNA docking, a crucial, but still largely unresolved, question in molecular biology. Using a representative set of protein-DNA complexes, we first show that our model is able to predict the interaction surface between the macromolecular partners taken in their bound form. In a second part, the impact of the DNA sequence and electrostatics, together with the DNA and protein conformations on docking is investigated. Our results strongly suggest that the overall DNA structure mainly contributes in discriminating the interaction site on cognate proteins. Direct electrostatic interactions between phosphate groups and amino acid side chains strengthen the binding. Overall, this work demonstrates that coarse grain modeling can reveal itself a precious auxiliary for a general and complete description and understanding of protein-DNA association mechanisms. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2008 [source] Global physicochemical properties as activity discriminants for the mGluR1 subtype of metabotropic glutamate receptorsJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 16 2001Marta Filizola Abstract Metabotropic glutamate receptors (mGluRs) are important as candidate therapeutic targets for many neurological disorders. In the present work, the focus has been on the mGluR1 subtype, where agonists have a proconvulsant profile while antagonists exert anticonvulsant activity. Identification of molecular determinants for the inhibition of mGluR1 provides a new avenue for the discovery and development of novel anticonvulsant drugs. Spatial configuration of key groups alone cannot explain activation selectivity at this specific receptor subtype. In fact, all known agonists and antagonists acting at mGluR1 can accommodate the same critical moieties in a similar geometric arrangement that corresponds to the extended conformation of glutamate. Therefore, other factors must account for the differences in activation. This study presents the results of an analysis of a large suite of steric, topological, electrostatic, and thermodynamic molecular properties calculated for a representative set of potent mGluR1 agonists and antagonists. Global steric parameters and the total nonpolar area provide discrimination between the mGluR1 agonists and antagonists considered in the present work. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 2018,2027, 2001 [source] Target rocks, impact glasses, and melt rocks from the Lonar impact crater, India: Petrography and geochemistryMETEORITICS & PLANETARY SCIENCE, Issue 9-10 2005Shiloh Osae A representative set of target basalts, including the basalt flows excavated by the crater, and a variety of impact breccias and impact glasses, were analyzed for their major and trace element compositions. Impact glasses and breccias were found inside and outside the crater rim in a variety of morphological forms and shapes. Comparable geochemical patterns of immobile elements (e.g., REEs) for glass, melt rock and basalt indicates minimal fractionation between the target rocks and the impactites. We found only little indication of post-impact hydrothermal alteration in terms of volatile trace element changes. No clear indication of an extraterrestrial component was found in any of our breccias and impact glasses, indicating either a low level of contamination, or a non-chondritic or otherwise iridium-poor impactor. [source] The Impact of Diagnostic Feedback to Teachers on Student Learning: Experimental Evidence from India,THE ECONOMIC JOURNAL, Issue 546 2010Karthik Muralidharan We present experimental evidence on the impact of a programme that provided low-stakes diagnostic tests and feedback to teachers, and low-stakes monitoring of classroom processes across a representative set of schools in the Indian state of Andhra Pradesh. We find teachers in treatment schools exerting more effort when observed in the classroom but students in these schools do no better on independently-administered tests than students in schools that did not receive the programme. This suggests that though teachers in the programme schools worked harder while being observed, there was no impact of the feedback and monitoring on student learning outcomes. [source] Recent developments in effector biology of filamentous plant pathogensCELLULAR MICROBIOLOGY, Issue 6 2010Ricardo Oliva Summary Filamentous pathogens, such as plant pathogenic fungi and oomycetes, secrete an arsenal of effector molecules that modulate host innate immunity and enable parasitic infection. It is now well accepted that these effectors are key pathogenicity determinants that enable parasitic infection. In this review, we report on the most interesting features of a representative set of filamentous pathogen effectors and highlight recent findings. We also list and describe all the linear motifs reported to date in filamentous pathogen effector proteins. Some of these motifs appear to define domains that mediate translocation inside host cells. [source] Nestedness, SLOSS and conservation networks of boreal herb-rich forestsAPPLIED VEGETATION SCIENCE, Issue 3 2009Päivi J. Hokkanen Abstract Question: Herb-rich patches are biodiversity hotspots for vascular plants in boreal forests. We ask: Do species occurrences on herb-rich patches show a non-random, nested structure?; Does patch size relate to richness of edaphically demanding and red-listed species?; Does a set of small patches support more edaphically demanding and red-listed species than a few large patches of the equal area? Location: Eastern Finland (63°04,N, 29°52,E), boreal vegetation zone. Data: Vegetation mapping of 90 herb-rich sites, varying from 0.05 to 6.93 ha in size and belonging to six different, predetermined forest site types. Results: Using the RANDNEST procedure, only one site type showed a significantly nested pattern, and patch area was not related to "nestedness" in any of the site types. The number of edaphically demanding and red-listed plant species was positively correlated with a patch size in three forest site types. In all site types, a set of small patches had more edaphically demanding and red-listed species than did a few large patches of the equal total area. Conclusions: For conservation, it is essential to protect representative sets of different herb-rich forest site types because flora varies between the site types. Within herb-rich forest site types, several small areas may support representative species composition. However, successful conservation requires thorough species inventories, because of the high level of heterogeneity between the herb-rich patches. [source] |