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Sample records for causap csar pedrocchi

  1. Application of the docking program SOL for CSAR benchmark.

    PubMed

    Sulimov, Alexey V; Kutov, Danil C; Oferkin, Igor V; Katkova, Ekaterina V; Sulimov, Vladimir B

    2013-08-26

    This paper is devoted to results obtained by the docking program SOL and the post-processing program DISCORE at the CSAR benchmark. SOL and DISCORE programs are described. SOL is the original docking program developed on the basis of the genetic algorithm, MMFF94 force field, rigid protein, precalculated energy grid including desolvation in the frame of simplified GB model, vdW, and electrostatic interactions and taking into account the ligand internal strain energy. An important SOL feature is the single- or multi-processor performance for up to hundreds of CPUs. DISCORE improves the binding energy scoring by the local energy optimization of the ligand docked pose and a simple linear regression on the base of available experimental data. The docking program SOL has demonstrated a good ability for correct ligand positioning in the active sites of the tested proteins in most cases of CSAR exercises. SOL and DISCORE have not demonstrated very exciting results on the protein-ligand binding free energy estimation. Nevertheless, for some target proteins, SOL and DISCORE were among the first in prediction of inhibition activity. Ways to improve SOL and DISCORE are discussed.

  2. CSAR 2014: A Benchmark Exercise Using Unpublished Data from Pharma.

    PubMed

    Carlson, Heather A; Smith, Richard D; Damm-Ganamet, Kelly L; Stuckey, Jeanne A; Ahmed, Aqeel; Convery, Maire A; Somers, Donald O; Kranz, Michael; Elkins, Patricia A; Cui, Guanglei; Peishoff, Catherine E; Lambert, Millard H; Dunbar, James B

    2016-06-27

    The 2014 CSAR Benchmark Exercise was the last community-wide exercise that was conducted by the group at the University of Michigan, Ann Arbor. For this event, GlaxoSmithKline (GSK) donated unpublished crystal structures and affinity data from in-house projects. Three targets were used: tRNA (m1G37) methyltransferase (TrmD), Spleen Tyrosine Kinase (SYK), and Factor Xa (FXa). A particularly strong feature of the GSK data is its large size, which lends greater statistical significance to comparisons between different methods. In Phase 1 of the CSAR 2014 Exercise, participants were given several protein-ligand complexes and asked to identify the one near-native pose from among 200 decoys provided by CSAR. Though decoys were requested by the community, we found that they complicated our analysis. We could not discern whether poor predictions were failures of the chosen method or an incompatibility between the participant's method and the setup protocol we used. This problem is inherent to decoys, and we strongly advise against their use. In Phase 2, participants had to dock and rank/score a set of small molecules given only the SMILES strings of the ligands and a protein structure with a different ligand bound. Overall, docking was a success for most participants, much better in Phase 2 than in Phase 1. However, scoring was a greater challenge. No particular approach to docking and scoring had an edge, and successful methods included empirical, knowledge-based, machine-learning, shape-fitting, and even those with solvation and entropy terms. Several groups were successful in ranking TrmD and/or SYK, but ranking FXa ligands was intractable for all participants. Methods that were able to dock well across all submitted systems include MDock,1 Glide-XP,2 PLANTS,3 Wilma,4 Gold,5 SMINA,6 Glide-XP2/PELE,7 FlexX,8 and MedusaDock.9 In fact, the submission based on Glide-XP2/PELE7 cross-docked all ligands to many crystal structures, and it was particularly impressive to see

  3. Lessons learned in empirical scoring with smina from the CSAR 2011 benchmarking exercise.

    PubMed

    Koes, David Ryan; Baumgartner, Matthew P; Camacho, Carlos J

    2013-08-26

    We describe a general methodology for designing an empirical scoring function and provide smina, a version of AutoDock Vina specially optimized to support high-throughput scoring and user-specified custom scoring functions. Using our general method, the unique capabilities of smina, a set of default interaction terms from AutoDock Vina, and the CSAR (Community Structure-Activity Resource) 2010 data set, we created a custom scoring function and evaluated it in the context of the CSAR 2011 benchmarking exercise. We find that our custom scoring function does a better job sampling low RMSD poses when crossdocking compared to the default AutoDock Vina scoring function. The design and application of our method and scoring function reveal several insights into possible improvements and the remaining challenges when scoring and ranking putative ligands. PMID:23379370

  4. CSAR Data Set Release 2012: Ligands, Affinities, Complexes, and Docking Decoys

    PubMed Central

    2013-01-01

    A major goal in drug design is the improvement of computational methods for docking and scoring. The Community Structure Activity Resource (CSAR) has collected several data sets from industry and added in-house data sets that may be used for this purpose (www.csardock.org). CSAR has currently obtained data from Abbott, GlaxoSmithKline, and Vertex and is working on obtaining data from several others. Combined with our in-house projects, we are providing a data set consisting of 6 protein targets, 647 compounds with biological affinities, and 82 crystal structures. Multiple congeneric series are available for several targets with a few representative crystal structures of each of the series. These series generally contain a few inactive compounds, usually not available in the literature, to provide an upper bound to the affinity range. The affinity ranges are typically 3–4 orders of magnitude per series. For our in-house projects, we have had compounds synthesized for biological testing. Affinities were measured by Thermofluor, Octet RED, and isothermal titration calorimetry for the most soluble. This allows the direct comparison of the biological affinities for those compounds, providing a measure of the variance in the experimental affinity. It appears that there can be considerable variance in the absolute value of the affinity, making the prediction of the absolute value ill-defined. However, the relative rankings within the methods are much better, and this fits with the observation that predicting relative ranking is a more tractable problem computationally. For those in-house compounds, we also have measured the following physical properties: logD, logP, thermodynamic solubility, and pKa. This data set also provides a substantial decoy set for each target consisting of diverse conformations covering the entire active site for all of the 58 CSAR-quality crystal structures. The CSAR data sets (CSAR-NRC HiQ and the 2012 release) provide substantial, publically

  5. Blind Pose Prediction, Scoring, and Affinity Ranking of the CSAR 2014 Dataset.

    PubMed

    Martiny, Virginie Y; Martz, François; Selwa, Edithe; Iorga, Bogdan I

    2016-06-27

    The 2014 CSAR Benchmark Exercise was focused on three protein targets: coagulation factor Xa, spleen tyrosine kinase, and bacterial tRNA methyltransferase. Our protocol involved a preliminary analysis of the structural information available in the Protein Data Bank for the protein targets, which allowed the identification of the most appropriate docking software and scoring functions to be used for the rescoring of several docking conformations datasets, as well as for pose prediction and affinity ranking. The two key points of this study were (i) the prior evaluation of molecular modeling tools that are most adapted for each target and (ii) the increased search efficiency during the docking process to better explore the conformational space of big and flexible ligands.

  6. CSAR Benchmark Exercise of 2010: Selection of the Protein–Ligand Complexes

    PubMed Central

    2011-01-01

    A major goal in drug design is the improvement of computational methods for docking and scoring. The Community Structure Activity Resource (CSAR) aims to collect available data from industry and academia which may be used for this purpose (www.csardock.org). Also, CSAR is charged with organizing community-wide exercises based on the collected data. The first of these exercises was aimed to gauge the overall state of docking and scoring, using a large and diverse data set of protein–ligand complexes. Participants were asked to calculate the affinity of the complexes as provided and then recalculate with changes which may improve their specific method. This first data set was selected from existing PDB entries which had binding data (Kd or Ki) in Binding MOAD, augmented with entries from PDBbind. The final data set contains 343 diverse protein–ligand complexes and spans 14 pKd. Sixteen proteins have three or more complexes in the data set, from which a user could start an inspection of congeneric series. Inherent experimental error limits the possible correlation between scores and measured affinity; R2 is limited to ∼0.9 when fitting to the data set without over parametrizing. R2 is limited to ∼0.8 when scoring the data set with a method trained on outside data. The details of how the data set was initially selected, and the process by which it matured to better fit the needs of the community are presented. Many groups generously participated in improving the data set, and this underscores the value of a supportive, collaborative effort in moving our field forward. PMID:21728306

  7. Implementation of a segmentation method for agricultural fields in aerial sequences of images based on CSAR model

    NASA Astrophysics Data System (ADS)

    Chen, Haijun; Houkes, Zweitze

    1998-09-01

    In this paper, a segmentation method for agricultural fields in aerial sequences of images based on the Circular Symmetri Auto-Regressive (CSAR) model is presented. The image sequences assumed to be acquired by a video camera (RGB-CCD system) from an aeroplane, which moves linearly over the scene. The objects in the scenes being considered in this paper, are agricultural fields. The classes of agricultural fields to be distinguished are determined by the type of crop, e.g. potatoes sugar beet, wheat, etc. In order to recognize and classify these fields from aerial sequence of images, a reliable segmentatio is required. Here texture features are used for segmentation. The implementation of segmentation for agricultural fields in aerial sequences of images is based on CSAR model in texture analysis. By comparing the estimated parameters of CSAR model from different area in an image, the characteristics and the class of a texture may be determined. The paper describes the segmentation method and its evaluation through experiments. Based on segmentation results, classification for surface texture of vegetation from aerial sequences of images is realized.

  8. One-electron pseudopotential investigation of CsAr van der Waals system including the spin-orbit interaction.

    PubMed

    Dhiflaoui, J; Berriche, H

    2010-07-01

    The potential energy curves of the ground state and many excited states of the CsAr van der Waals system have been determined using [Cs(+)] and [Ar] core pseudopotentials and by considering core polarization operators on both atoms. This has permitted to reduce the number of active electrons of the CsAr system to only one electron, i.e., the valence electron, which led to use of large basis sets for Cs and Ar atoms. In this context, the potential energy curves of the ground state and many excited states are performed at the self consistent field (SCF) level. Spin-orbit interaction is also considered within a semiempirical scheme for the states dissociating into Cs(6p) and Cs(5d). The core-core interactions for Cs(+)Ar is included using the coupled cluster simple and double excitation (CCSD) accurate potential of Hickling et al. (Hickling, H.; Viehland, L.; Shepherd, D.; Soldan, P.; Lee, E.; Wright, T. Phys. Chem. Chem. Phys. 2004, 6, 4233). In addition, the spectroscopic constants of these states are derived and compared with the available theoretical and experimental works. Such comparison has shown a very good agreement for the ground and the first excited states. However, the spectroscopic data for the higher excited states are presented for the first time.

  9. Incorporating specificity into optimization: evaluation of SPA using CSAR 2014 and CASF 2013 benchmarks.

    PubMed

    Yan, Zhiqiang; Wang, Jin

    2016-03-01

    Scoring functions of protein-ligand interactions are widely used in computationally docking software and structure-based drug discovery. Accurate prediction of the binding energy between the protein and the ligand is the main task of the scoring function. The accuracy of a scoring function is normally evaluated by testing it on the benchmarks of protein-ligand complexes. In this work, we report the evaluation analysis of an improved version of scoring function SPecificity and Affinity (SPA). By testing on two independent benchmarks Community Structure-Activity Resource (CSAR) 2014 and Comparative Assessment of Scoring Functions (CASF) 2013, the assessment shows that SPA is relatively more accurate than other compared scoring functions in predicting the interactions between the protein and the ligand. We conclude that the inclusion of the specificity in the optimization can effectively suppress the competitive state on the funnel-like binding energy landscape, and make SPA more accurate in identifying the "native" conformation and scoring the binding decoys. The evaluation of SPA highlights the importance of binding specificity in improving the accuracy of the scoring functions.

  10. Study of the new CSAR62 positive tone electron-beam resist at 40 keV electron energy

    NASA Astrophysics Data System (ADS)

    Andok, R.; Bencurova, A.; Vutova, K.; Koleva, E.; Nemec, P.; Hrkut, P.; Kostic, I.; Mladenov, G.

    2016-03-01

    One of the few "top-down" methods for nano-device fabrication is the electron-beam lithography, which allows flexible patterning of various structures with a nanoscale resolution down to less than 10 nm. Thinner, more etching durable, and more sensitive e-beam resists are required for the better control, linearity, and uniformity of critical dimensions of structures for nano-device fabrication. Within the last decade, researchers have made significant efforts to improve the resolution of the nanoscale e-beam lithography. The resist material properties are an important factor governing the resolution. Only the e-beam resist ZEP 520 of the Japanese manufacturer ZEON is characterized by relatively good properties and thus meets most users' expectations. This paper deals with the investigation and simulation of the characteristics of the new less-expensive AR-P 6200 (CSAR 62) positive e-beam resist (available since May 2013, manufactured by Allresist GmbH company).

  11. Integrated imaging experiment with C-SAR and other geological image data across the Nelson Front, Northern Manitoba

    NASA Technical Reports Server (NTRS)

    Rao, G. S. K.; Won, J. S.; Moon, W. M.; Slaney, V. R.; Graham, D. F.; Lowman, P. D.

    1990-01-01

    This paper presents preliminary results from the integration of geophysical and geological data sets using Bayesian statistical analysis with the purpose of mapping the Churchill-Superior Boundary zone. In the Wabowden area the contribution of each rock type to the aeromagnetic anomaly is judged by convolving the aeromagnetic anomaly value with the average magnetic susceptibility. The 'a posteriori' probabilities of significant patterns in the new data are then computed. The highest 'a posteriori' probability occurs along a narrow corridor whose trend coincides remarkably with the location of the Churchill-Superior Boundary Zone. In the Wekusko Lake area, C-SAR and TM data were integrated using an image analysis system. Here the emphasis is on mapping of geological structures.

  12. CSAR Benchmark Exercise 2011–2012: Evaluation of Results from Docking and Relative Ranking of Blinded Congeneric Series

    PubMed Central

    2013-01-01

    The Community Structure–Activity Resource (CSAR) recently held its first blinded exercise based on data provided by Abbott, Vertex, and colleagues at the University of Michigan, Ann Arbor. A total of 20 research groups submitted results for the benchmark exercise where the goal was to compare different improvements for pose prediction, enrichment, and relative ranking of congeneric series of compounds. The exercise was built around blinded high-quality experimental data from four protein targets: LpxC, Urokinase, Chk1, and Erk2. Pose prediction proved to be the most straightforward task, and most methods were able to successfully reproduce binding poses when the crystal structure employed was co-crystallized with a ligand from the same chemical series. Multiple evaluation metrics were examined, and we found that RMSD and native contact metrics together provide a robust evaluation of the predicted poses. It was notable that most scoring functions underpredicted contacts between the hetero atoms (i.e., N, O, S, etc.) of the protein and ligand. Relative ranking was found to be the most difficult area for the methods, but many of the scoring functions were able to properly identify Urokinase actives from the inactives in the series. Lastly, we found that minimizing the protein and correcting histidine tautomeric states positively trended with low RMSD for pose prediction but minimizing the ligand negatively trended. Pregenerated ligand conformations performed better than those that were generated on the fly. Optimizing docking parameters and pretraining with the native ligand had a positive effect on the docking performance as did using restraints, substructure fitting, and shape fitting. Lastly, for both sampling and ranking scoring functions, the use of the empirical scoring function appeared to trend positively with the RMSD. Here, by combining the results of many methods, we hope to provide a statistically relevant evaluation and elucidate specific shortcomings

  13. Addendum 6 to CSAR 79-038 out-of-hood plutonium storage (burial box)

    SciTech Connect

    Chiao, T.

    1995-06-14

    The Addendum considered an increase in the limit of fissile material in a stacked container array to 500 grams. In other words, the sum of fissile material in an array of containers is limited to 500 grams, regardless of whether the containers are stacked or not. The results of this evaluation indicates that with the modification of the fissile limits described, the system of a container array will stay sub-critical.

  14. Addendum 3 to CSAR 80-027, Use of calorimeter 109B for fissile material measurement

    SciTech Connect

    Chiao, T.

    1994-12-05

    This modification to the Plutonium Finishing Plant (PFP) calorimeter system involves removing current calorimeter No. 3 from the water bath and replacing it with a calorimeter that can accommodate larger diameter items (an oversize can). The inside diameters of both the sample and the reference cells will be increased to 5.835 inches at the top opening and to 5.22 inches at the bottom, the 8 inch high measurement zone. This Addendum 3 to Criticality Safety Analysis Report 80-027 examines criticality safety during the use of the modified calorimeter (Calorimeter 109B) with enlarged cell tube diameters to assure that an adequate margin of subcriticality is maintained for all normal and contingency conditions.

  15. CSAR 79-034 ADDENDUM 2, storing the man-basket in the process cell in 236-Z Building, Plutonium Finishing Plant/Plutonium Reclamation Facility

    SciTech Connect

    Chiao, T.

    1994-10-25

    The man-basket is stored in the Plutonium Reclamation Facility canyon area and this addendum reports on a technical evaluation for the storage inside the canyon to ensure consistency with the requirements of the Nuclear Criticality Safety Manual, WHC-CM-4-29.

  16. Stresses and Strains

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Computerized Structural Analysis and Research Corporation (CSAR) flagship product is CSA/NASTRAN, a Finite Element Analysis program for structural, thermal, aeroelastic and acoustic analysis. CSAR's first products were software products for performing structural optimization in conjuction wtih MSC/NASTRAN. In 1984, CSAR released the first version of CSA/NASTRAN, then merely an enhanced version of COSMIC NASTRAN. In 1988, CSAR purchased the source code outright and released the first "independent" version of CSA/NASTRAN.

  17. Cardiac sympathetic afferent reflex and its implications for sympathetic activation in chronic heart failure and hypertension.

    PubMed

    Chen, W-W; Xiong, X-Q; Chen, Q; Li, Y-H; Kang, Y-M; Zhu, G-Q

    2015-04-01

    Persistent excessive sympathetic activation greatly contributes to the pathogenesis of chronic heart failure (CHF) and hypertension. Cardiac sympathetic afferent reflex (CSAR) is a sympathoexcitatory reflex with positive feedback characteristics. Humoral factors such as bradykinin, adenosine and reactive oxygen species produced in myocardium due to myocardial ischaemia stimulate cardiac sympathetic afferents and thereby reflexly increase sympathetic activity and blood pressure. The CSAR is enhanced in myocardial ischaemia, CHF and hypertension. The enhanced CSAR at least partially contributes to the sympathetic activation and pathogenesis of these diseases. Nucleus of the solitary tract (NTS), hypothalamic paraventricular nucleus (PVN) and rostral ventrolateral medulla are the most important central sites involved in the modulation and integration of the CSAR. Angiotensin II, AT1 receptors and NAD(P)H oxidase-derived superoxide anions pathway in the PVN are mainly responsible for the enhanced CSAR in CHF and hypertension. Central angiotensin-(1-7), nitric oxide, endothelin, intermedin, hydrogen peroxide and several other signal molecules are involved in regulating CSAR. Blockade of the CSAR shows beneficial effects in CHF and hypertension. This review focuses on the anatomical and physiological basis of the CSAR, the interaction of CSAR with baroreflex and chemoreflex, and the role of enhanced CSAR in the pathogenesis of CHF and hypertension.

  18. Breast tumor detection using UWB circular-SAR tomographic microwave imaging.

    PubMed

    Oloumi, Daniel; Boulanger, Pierre; Kordzadeh, Atefeh; Rambabu, Karumudi

    2015-01-01

    This paper describes the possibility of detecting tumors in human breast using ultra-wideband (UWB) circular synthetic aperture radar (CSAR). CSAR is a subset of SAR which is a radar imaging technique using a circular data acquisition pattern. Tomographic image reconstruction is done using a time domain global back projection technique adapted to CSAR. Experiments are conducted on a breast phantoms made of pork fat emulating normal and cancerous conditions. Preliminary experimental results show that microwave imaging of a breast phantom using UWB-CSAR is a simple and low-cost method, efficiently capable of detecting the presence of tumors.

  19. Angiotensin-(1-7) enhances the effects of angiotensin II on the cardiac sympathetic afferent reflex and sympathetic activity in rostral ventrolateral medulla in renovascular hypertensive rats.

    PubMed

    Li, Peng; Zhang, Feng; Sun, Hai-Jian; Zhang, Feng; Han, Ying

    2015-11-01

    Excessive sympathetic activity propels the pathogenesis and progression of organ damage in hypertension. Enhanced cardiac sympathetic afferent reflex (CSAR) is involved in sympathetic activation in hypertension. Given the important role of the renin-angiotensin (Ang) system in regulating sympathetic outflow and cardiovascular activity, the present study aimed to investigate the roles of Ang-(1-7) in Ang II-induced CSAR and the sympathetic activation responses in the rostral ventrolateral medulla (RVLM) of hypertensive rats. The two-kidney one-clip (2K1C) method was used to induce renovascular hypertension. Responses of renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) to epicardial application of capsaicin were used to evaluate the CSAR in sinoaortic-denervated and cervical-vagotomized rats with anesthesia. Both Ang II and Ang-(1-7) in the RVLM caused greater increases in RSNA and MAP in 2K1C rats than in sham-operated (sham) rats and enhanced CSAR independently. RVLM pretreatment with Ang-(1-7) dose dependently augmented the effects of Ang II on RSNA, MAP, and CSAR in 2K1C rats. Mas receptor antagonist A-779 in the RVLM exhibited more powerful inhibitory effects on RSNA, MAP, and CSAR than the Ang II type 1 (AT1) receptor antagonist losartan. The expression of both the AT1 receptor and Mas receptor proteins in the RVLM increased, but neither the Ang II nor Ang-(1-7) levels in the RVLM changed significantly in the 2K1C rats compared with the sham rats. These results indicate that Ang-(1-7) in the RVLM enhances the CSAR and sympathetic output not only by itself but also through enhancing the effects of Ang II in renovascular hypertensive rats. Both endogenous Ang-(1-7) and Ang II in the RVLM contribute to the enhanced CSAR and sympathetic activation in renovascular hypertension.

  20. Interaction between cardiac sympathetic afferent reflex and chemoreflex is mediated by the NTS AT1 receptors in heart failure.

    PubMed

    Wang, Wei-Zhong; Gao, Lie; Wang, Han-Jun; Zucker, Irving H; Wang, Wei

    2008-09-01

    Several sympathoexcitatory reflexes, such as the cardiac sympathetic afferent reflex (CSAR) and arterial chemoreflex, are significantly augmented and contribute to elevated sympathetic outflow in chronic heart failure (CHF). This study was undertaken to investigate the interaction between the CSAR and the chemoreflex in CHF and to further identify the involvement of angiotensin II type 1 receptors (AT1Rs) in the nucleus of the tractus solitarius (NTS) in this interaction. CHF was induced in rats by coronary ligation. Acute experiments were performed in anesthetized rats. The chemoreflex-induced increase in cardiovascular responses was significantly greater in CHF than in sham-operated rats after either chemical or electrical activation of the CSAR. The inhibition of the CSAR by epicardial lidocaine reduced the chemoreflex-induced effects in CHF rats but not in sham-operated rats. Bilateral NTS injection of the AT1R antagonist losartan (10 and 100 pmol) dose-dependently decreased basal sympathetic nerve activity in CHF but not in sham-operated rats. This procedure also abolished the CSAR-induced enhancement of the chemoreflex. The discharge and chemosensitivity of NTS chemosensitive neurons were significantly increased following the stimulation of the CSAR in sham-operated and CHF rats, whereas CSAR inhibition by epicardial lidocaine significantly attenuated chemosensitivity of NTS neurons in CHF but not in sham-operated rats. Finally, the protein expression of AT1R in the NTS was significantly higher in CHF than in sham-operated rats. These results demonstrate that the enhanced cardiac sympathetic afferent input contributes to an excitatory effect of chemoreflex function in CHF, which is mediated by an NTS-AT1R-dependent mechanism.

  1. Assessing the Written Communication Skills of Medical School Graduates

    ERIC Educational Resources Information Center

    Boulet, John R.; Rebbecchi, Thomas A.; Denton, Elizabeth C.; McKinley, Danette W.; Whelan, Gerald P.

    2004-01-01

    The ECFMG[R] Clinical Skills Assessment (CSA[R]) was developed to evaluate whether graduates of international medical schools (IMGs) are ready to enter graduate training programs in the United States. The patient note (PN) exercise, conducted after a 15-minute interview with a standardized patient (SP), is specifically used to assess a candidate's…

  2. Investigating Gender-Related Construct-Irrelevant Components of Scores on the Written Assessment Exercise of a High-Stakes Certification Assessment

    ERIC Educational Resources Information Center

    Boulet, John R.; McKinley, Danette W.

    2005-01-01

    The ECFMG[R] Clinical Skills Assessment (CSA[R]) was developed to evaluate whether graduates of international medical schools (IMGs) are ready to enter graduate training programs in the United States. The patient note (PN) exercise is specifically used to assess a candidate's ability to summarize and synthesize the data collected in a simulated…

  3. GOTCHA experience report: three-dimensional SAR imaging with complete circular apertures

    NASA Astrophysics Data System (ADS)

    Ertin, Emre; Austin, Christian D.; Sharma, Samir; Moses, Randolph L.; Potter, Lee C.

    2007-04-01

    We study circular synthetic aperture radar (CSAR) systems collecting radar backscatter measurements over a complete circular aperture of 360 degrees. This study is motivated by the GOTCHA CSAR data collection experiment conducted by the Air Force Research Laboratory (AFRL). Circular SAR provides wide-angle information about the anisotropic reflectivity of the scattering centers in the scene, and also provides three dimensional information about the location of the scattering centers due to a non planar collection geometry. Three dimensional imaging results with single pass circular SAR data reveals that the 3D resolution of the system is poor due to the limited persistence of the reflectors in the scene. We present results on polarimetric processing of CSAR data and illustrate reasoning of three dimensional shape from multi-view layover using prior information about target scattering mechanisms. Next, we discuss processing of multipass (CSAR) data and present volumetric imaging results with IFSAR and three dimensional backprojection techniques on the GOTCHA data set. We observe that the volumetric imaging with GOTCHA data is degraded by aliasing and high sidelobes due to nonlinear flightpaths and sparse and unequal sampling in elevation. We conclude with a model based technique that resolves target features and enhances the volumetric imagery by extrapolating the phase history data using the estimated model.

  4. Cardiac Sympathetic Afferent Denervation Attenuates Cardiac Remodeling and Improves Cardiovascular Dysfunction in Rats with Heart Failure

    PubMed Central

    Wang, Han-Jun; Wang, Wei; Cornish, Kurtis G.; Rozanski, George J.; Zucker, Irving H.

    2014-01-01

    The enhanced cardiac sympathetic afferent reflex (CSAR) contributes to the exaggerated sympatho-excitation in chronic heart failure (CHF). Increased sympatho-excitation is positively related to mortality in CHF patients. However, the potential beneficial effects of chronic CSAR deletion on cardiac and autonomic function in CHF have not been previously explored. Here we determined the effects of chronic CSAR deletion on cardiac remodeling and autonomic dysfunction in CHF. In order to selectively delete the transient receptor potential vanilloid 1 receptor (TRPV1) -expressing CSAR afferents, epicardial application of resiniferatoxin (RTX, 50 μg/ml), an ultrapotent analogue of capsaicin, was performed during myocardium infarction (MI) surgery in rats. This procedure largely abolished the enhanced CSAR, prevented the exaggerated renal and cardiac sympathetic nerve activity and improved baroreflex sensitivity in CHF rats. Most importantly, we found that epicardial application of RTX largely prevented the elevated LVEDP, lung edema and cardiac hypertrophy, partially reduced left ventricular dimensions in the failing heart and increased cardiac contractile reserve in response to β-adrenergic receptor stimulation with isoproterenol in CHF rats. Molecular evidence showed that RTX attenuated cardiac fibrosis and apoptosis and reduced expression of fibrotic markers and TGF β-receptor I in CHF rats. Pressure - volume loop analysis showed that RTX reduced the end diastolic pressure volume relations in CHF rats indicating improved cardiac compliance. In summary, cardiac sympathetic afferent deletion exhibits protective effects against deleterious cardiac remodeling and autonomic dysfunction in CHF. These data suggest a potential new paradigm and therapeutic potential in the management of CHF. PMID:24980663

  5. Physical states and finite-size effects in Kitaev's honeycomb model: Bond disorder, spin excitations, and NMR line shape

    NASA Astrophysics Data System (ADS)

    Zschocke, Fabian; Vojta, Matthias

    2015-07-01

    Kitaev's compass model on the honeycomb lattice realizes a spin liquid whose emergent excitations are dispersive Majorana fermions and static Z2 gauge fluxes. We discuss the proper selection of physical states for finite-size simulations in the Majorana representation, based on a recent paper by F. L. Pedrocchi, S. Chesi, and D. Loss [Phys. Rev. B 84, 165414 (2011), 10.1103/PhysRevB.84.165414]. Certain physical observables acquire large finite-size effects, in particular if the ground state is not fermion-free, which we prove to generally apply to the system in the gapless phase and with periodic boundary conditions. To illustrate our findings, we compute the static and dynamic spin susceptibilities for finite-size systems. Specifically, we consider random-bond disorder (which preserves the solubility of the model), calculate the distribution of local flux gaps, and extract the NMR line shape. We also predict a transition to a random-flux state with increasing disorder.

  6. DOCUMENTATION OF NATIONAL WEATHER CONDITIONS AFFECTING LONG-TERM DEGRADATION OF COMMERCIAL SPENT NUCLEAR FUEL AND DOE SPENT NUCLEAR FUEL AND HIGH-LEVEL WASTE

    SciTech Connect

    W. L. Poe, Jr.; P.F. Wise

    1998-11-01

    The U.S. Department of Energy (DOE) is preparing a proposal to construct, operate 2nd monitor, and eventually close a repository at Yucca Mountain in Nye County, Nevada, for the geologic disposal of spent nuclear fuel (SNF) and high-level radioactive waste (HLW). As part of this effort, DOE has prepared a viability assessment and an assessment of potential consequences that may exist if the repository is not constructed. The assessment of potential consequences if the repository is not constructed assumes that all SNF and HLW would be left at the generator sites. These include 72 commercial generator sites (three commercial facility pairs--Salem and Hope Creek, Fitzpatrick and Nine Mile Point, and Dresden and Morris--would share common storage due to their close proximity to each other) and five DOE sites across the country. DOE analyzed the environmental consequences of the effects of the continued storage of these materials at these sites in a report titled Continued Storage Analysis Report (CSAR; Reference 1 ) . The CSAR analysis includes a discussion of the degradation of these materials when exposed to the environment. This document describes the environmental parameters that influence the degradation analyzed in the CSAR. These include temperature, relative humidity, precipitation chemistry (pH and chemical composition), annual precipitation rates, annual number of rain-days, and annual freeze/thaw cycles. The document also tabulates weather conditions for each storage site, evaluates the degradation of concrete storage modules and vaults in different regions of the country, and provides a thermal analysis of commercial SNF in storage.

  7. Design definition study of a lift/cruise fan technology V/STOL aircraft. Volume 1: Navy operational aircraft

    NASA Technical Reports Server (NTRS)

    1975-01-01

    Aircraft were designed and sized to meet Navy mission requirements. Five missions were established for evaluation: anti-submarine warfare (ASW), surface attack (SA), combat search and rescue (CSAR), surveillance (SURV), and vertical on-board delivery (VOD). All missions were performed with a short takeoff and a vertical landing. The aircraft were defined using existing J97-GE gas generators or reasonable growth derivatives in conjunction with turbotip fans reflecting LF460 type technology. The multipurpose aircraft configuration established for U.S. Navy missions utilizes the turbotip driven lift/cruise fan concept for V/STOL aircraft.

  8. Identification and catalytic residues of the arsenite methyltransferase from a sulfate-reducing bacterium, Clostridium sp. BXM.

    PubMed

    Wang, Pei-Pei; Bao, Peng; Sun, Guo-Xin

    2015-01-01

    Arsenic methylation is an important process frequently occurring in anaerobic environments. Anaerobic microorganisms have been implicated as the major contributors for As methylation. However, very little information is available regarding the enzymatic mechanism of As methylation by anaerobes. In this study, one novel sulfate-reducing bacterium isolate, Clostridium sp. BXM, which was isolated from a paddy soil in our laboratory, was demonstrated to have the ability of methylating As. One putative arsenite S-Adenosyl-Methionine methyltransferase (ArsM) gene, CsarsM was cloned from Clostridium sp. BXM. Heterologous expression of CsarsM conferred As resistance and the ability of methylating As to an As-sensitive strain of Escherichia coli. Purified methyltransferase CsArsM catalyzed the formation of methylated products from arsenite, further confirming its function of As methylation. Site-directed mutagenesis studies demonstrated that three conserved cysteine residues at positions 65, 153 and 203 in CsArsM are necessary for arsenite methylation, but only Cysteine 153 and Cysteine 203 are required for the methylation of monomethylarsenic to dimethylarsenic. These results provided the characterization of arsenic methyltransferase from anaerobic sulfate-reducing bacterium. Given that sulfate-reducing bacteria are ubiquitous in various wetlands including paddy soils, enzymatic methylation mediated by these anaerobes is proposed to contribute to the arsenic biogeochemical cycling. PMID:25790486

  9. Analysis of containment performance and radiological consequences under severe accident conditions for the Advanced Neutron Source Reactor at the Oak Ridge National Laboratory

    SciTech Connect

    Kim, S.H.; Taleyarkhan, R.P.

    1994-01-01

    A severe accident study was conducted to evaluate conservatively scoped source terms and radiological consequences to support the Advanced Neutron Source (ANS) Conceptual Safety Analysis Report (CSAR). Three different types of severe accident scenarios were postulated with a view of evaluating conservatively scoped source terms. The first scenario evaluates maximum possible steaming loads and associated radionuclide transport, whereas the next scenario is geared towards evaluating conservative containment loads from releases of radionuclide vapors and aerosols with associated generation of combustible gases. The third scenario follows the prescriptions given by the 10 CFR 100 guidelines. It was included in the CSAR for demonstrating site-suitability characteristics of the ANS. Various containment configurations are considered for the study of thermal-hydraulic and radiological behaviors of the ANS containment. Severe accident mitigative design features such as the use of rupture disks were accounted for. This report describes the postulated severe accident scenarios, methodology for analysis, modeling assumptions, modeling of several severe accident phenomena, and evaluation of the resulting source term and radiological consequences.

  10. Standard review plan for reviewing safety analysis reports for dry metallic spent fuel storage casks

    SciTech Connect

    Not Available

    1988-01-01

    The Cask Standard Review Plan (CSRP) has been prepared as guidance to be used in the review of Cask Safety Analysis Reports (CSARs) for storage packages. The principal purpose of the CSRP is to assure the quality and uniformity of storage cask reviews and to present a well-defined base from which to evaluate proposed changes in the scope and requirements of reviews. The CSRP also sets forth solutions and approaches determined to be acceptable in the past by the NRC staff in dealing with a specific safety issue or safety-related design area. These solutions and approaches are presented in this form so that reviewers can take consistent and well-understood positions as the same safety issues arise in future cases. An applicant submitting a CSAR does not have to follow the solutions or approaches presented in the CSRP. However, applicants should recognize that the NRC staff has spent substantial time and effort in reviewing and developing their positions for the issues. A corresponding amount of time and effort will probably be required to review and accept new or different solutions and approaches.

  11. Safety review of the design, operation, and radiation sections of the General Electric Morris Operation Consolidated Safety Analysis Report

    SciTech Connect

    McBride, J.P.

    1981-01-30

    A safety review was made of Sections 4 through 9 of the Consolidated Safety Analysis Report (CSAR) for the GE Morris Operation spent-fuel storage facility. The sections reviewed include Design Criteria and Compliance, Facility Design and Description, Radiation Protection, Accident Analysis, and Conduct of Operations. The safety review was performed in accordance with the Code of Federal Regulations, Title 10, Part 72, ''Licensing Requirements for the Storage of Spent Fuel in an Independent Spent Fuel Storage Installation'' and contains independent estimations of source terms and dose-commitments from postulated accidents in the storage facility and a structural analysis of the Morris Operation cranes as an appendix. The review confirms that the features of the facility as described in Sections 4 through 9 of the CSAR fulfilled the safety requirements of 10 CFR 72, and it is concluded that spent-fuel handling and storage at the Morris Operation do not present significant risks to public health and safety. 15 refs., 3 tabs.

  12. Heterogeneous propellant internal ballistics: criticism and regeneration

    NASA Astrophysics Data System (ADS)

    Glick, R. L.

    2011-10-01

    Although heterogeneous propellant and its innately nondeterministic, chemically discrete morphology dominates applications, ballisticcharacterization deterministic time-mean burning rate and acoustic admittance measures' absence of explicit, nondeterministic information requires homogeneous propellant with a smooth, uniformly regressing burning surface: inadequate boundary conditions for heterogeneous propellant grained applications. The past age overcame this dichotomy with one-dimensional (1D) models and empirical knowledge from numerous, adequately supported motor developments and supplementary experiments. However, current cost and risk constraints inhibit this approach. Moreover, its fundamental science approach is more sensitive to incomplete boundary condition information (garbage-in still equals garbage-out) and more is expected. This work critiques this situation and sketches a path forward based on enhanced ballistic and motor characterizations in the workplace and approximate model and apparatus developments mentored by CSAR DNS capabilities (or equivalent).

  13. Hyperfine relaxation of an optically pumped cesium vapor

    SciTech Connect

    Tornos, J.; Amare, J.C.

    1986-07-01

    The relaxation of hyperfine orientation indirectly induced by optical pumping with a sigma-polarized D/sub 1/-light in a cesium vapor in the presence of Ar is experimentally studied. The detection technique ensures the absence of quadrupole relaxation contributions in the relaxation signals. The results from the dependences of the hyperfine relaxation rate on the temperature and argon pressure are: diffusion coefficient of Cs in Ar, D/sub 0/ = 0.101 +- 0.010 cm/sup 2/s/sup -1/ at 0/sup 0/C and 760 Torr; relaxation cross section by Cs-Ar collisions, sigma/sub c/ = (104 +- 5) x 10/sup -23/ cm/sup 2/; relaxation cross section by Cs-Cs (spin exchange) collisions, sigma/sub e//sub x/ = (1.63 +- 0.13) x 10/sup -14/ cm/sup 2/.

  14. [Structural analyses of unknown red dyes detected in dried strawberry].

    PubMed

    Shindo, Tetsuya; Sadamasu, Yuki; Suzuki, Keiko; Tanaka, Yasukazu; Togawa, Akiko; Nakajima, Junichi; Nakazato, Mitsuo; Uematsu, Yoko

    2012-01-01

    We examined two unknown red dyes (designated as red dyes "A" and "B") from a dried strawberry package with a label that indicated the presence of food red No. 40 (R40). Red dye "A" was identified as trisodium 3-hydroxy-4-[(2'-methoxy-5'-methyl-4'-sulfonatophenyl)azo]-2,7-naphthalenedisulfonate (CSA-R) by HPLC, UV-VIS spectra and MS spectra. This compound is one of the four reported subsidiary colors of R40. Detailed analyses of red dye "B" by MS and NMR demonstrated that its structure was disodium 3-hydroxy-4-[(2'-methoxy-5'-methyl-4'-sulfonatophenyl)azo]-2-naphthalenesulfonate. Red dye "B" is a structural isomer of R40, that has not been reported previously. Our results suggest that the two minor red dyes were subsidiary colors contained in R40, which had been added to the dried strawberries.

  15. Toward a physical interpretation of substituent effects: the case of fluorine and trifluoromethyl groups.

    PubMed

    Siodła, Tomasz; Ozimiński, Wojciech P; Hoffmann, Marcin; Koroniak, Henryk; Krygowski, Tadeusz M

    2014-08-15

    The application of ab initio and DFT computational methods at six different levels of theory (MP2/cc-pVDZ, MP2/aug-cc-pVTZ, B3LYP/cc-pVDZ, B3LYP/aug-cc-pVTZ, M06/cc-pVDZ, and M06/aug-cc-pVTZ) to meta- and para-substituted fluoro- and trifluoromethylbenzene derivatives and to 1-fluoro- and 1-trifluoromethyl-2-substituted trans-ethenes allowed the study of changes in the electronic and geometric properties of F- and CF3-substituted systems under the impact of other substituents (BeH, BF2, BH2, Br, CFO, CHO, Cl, CN, F, Li, NH2, NMe2, NO, NO2, OH, H, CF3, and CH3). Various parameters of these systems have been investigated, including homodesmotic reactions in terms of the substituent effect stabilization energy (SESE), the π and σ electron donor-acceptor indexes (pEDA and sEDA, respectively), the charge on the substituent active region (cSAR, known earlier as qSAR), and bond lengths, which have been regressed against Hammett constants, resulting mostly in an accurate correspondence except in the case of p-fluorobenzene derivatives. Moreover, changes in the characteristics of the ability of the substituent to attract or donate electrons under the impact of the kind of moiety to which the substituent is attached have been considered as the indirect substituent effect and investigated by means of the cSAR model. Regressions of cSAR(X) versus cSAR(Y) for any systems X and Y allow final results to be obtained on the same scale of magnitude. PMID:25046196

  16. Activation of afferent renal nerves modulates RVLM-projecting PVN neurons.

    PubMed

    Xu, Bo; Zheng, Hong; Liu, Xuefei; Patel, Kaushik P

    2015-05-01

    Renal denervation for the treatment of hypertension has proven to be successful; however, the underlying mechanism/s are not entirely clear. To determine if preautonomic neurons in the paraventricular nucleus (PVN) respond to afferent renal nerve (ARN) stimulation, extracellular single-unit recording was used to investigate the contribution of the rostral ventrolateral medulla (RVLM)-projecting PVN (PVN-RVLM) neurons to the response elicited during stimulation of ARN. In 109 spontaneously active neurons recorded in the PVN of anesthetized rats, 25 units were antidromically activated from the RVLM. Among these PVN-RVLM neurons, 84% (21/25) were activated by ARN stimulation. The baseline discharge rate was significantly higher in these neurons than those PVN-RVLM neurons not activated by ARN stimulation (16%, 4/25). The responsiveness of these neurons to baroreflex activation induced by phenylephrine and activation of cardiac sympathetic afferent reflex (CSAR) was also examined. Almost all of the PVN neurons that responded to ARN stimulation were sensitive to baroreflex (95%) and CSAR (100%). The discharge characteristics for nonevoked neurons (not activated by RVLM antidromic stimulation) showed that 23% of these PVN neurons responded to ARN stimulation. All the PVN neurons that responded to ARN stimulation were activated by N-methyl-D-aspartate, and these responses were attenuated by the glutamate receptor blocker AP5. These experiments demonstrated that sensory information originating in the kidney is integrated at the level of preautonomic neurons within the PVN, providing a novel mechanistic insight for use of renal denervation in the modulation of sympathetic outflow in disease states such as hypertension and heart failure.

  17. REGIONAL BINNING FOR CONTINUED STORAGE OF SPENT NUCLEAR FUEL AND HIGH-LEVEL WASTES

    SciTech Connect

    W. Lee Poe, Jr

    1998-10-01

    In the Continued Storage Analysis Report (CSAR) (Reference 1), DOE decided to analyze the environmental consequences of continuing to store the commercial spent nuclear fuel (SNF) at 72 commercial nuclear power sites and DOE-owned spent nuclear fuel and high-level waste at five Department of Energy sites by region rather than by individual site. This analysis assumes that three commercial facilities pairs--Salem and Hope Creek, Fitzpatrick and Nine-Mile Point, and Dresden and Moms--share common storage due to their proximity to each other. The five regions selected for this analysis are shown on Figure 1. Regions 1, 2, and 3 are the same as those used by the Nuclear Regulatory Commission in their regulatory oversight of commercial power reactors. NRC Region 4 was subdivided into two regions to more appropriately define the two different climates that exist in NRC Region 4. A single hypothetical site in each region was assumed to store all the SNF and HLW in that region. Such a site does not exist and has no geographic location but is a mathematical construct for analytical purposes. To ensure that the calculated results for the regional analyses reflect appropriate inventory, facility and material degradation, and radionuclide transport, the waste inventories, engineered barriers, and environmental conditions for the hypothetical sites were developed from data for each of the existing sites within the given region. Weighting criteria to account for the amount and types of SNF and HLW at each site were used in the development of the environmental data for the regional site, such that the results of the analyses for the hypothetical site were representative of the sum of the results of each actual site if they had been modeled independently. This report defines the actual site data used in development of this hypothetical site, shows how the individual site data was weighted to develop the regional site, and provides the weighted data used in the CSAR analysis. It is

  18. Three-dimensional landing zone ladar

    NASA Astrophysics Data System (ADS)

    Savage, James; Goodrich, Shawn; Burns, H. N.

    2016-05-01

    Three-Dimensional Landing Zone (3D-LZ) refers to a series of Air Force Research Laboratory (AFRL) programs to develop high-resolution, imaging ladar to address helicopter approach and landing in degraded visual environments with emphasis on brownout; cable warning and obstacle avoidance; and controlled flight into terrain. Initial efforts adapted ladar systems built for munition seekers, and success led to a the 3D-LZ Joint Capability Technology Demonstration (JCTD) , a 27-month program to develop and demonstrate a ladar subsystem that could be housed with the AN/AAQ-29 FLIR turret flown on US Air Force Combat Search and Rescue (CSAR) HH-60G Pave Hawk helicopters. Following the JCTD flight demonstration, further development focused on reducing size, weight, and power while continuing to refine the real-time geo-referencing, dust rejection, obstacle and cable avoidance, and Helicopter Terrain Awareness and Warning (HTAWS) capability demonstrated under the JCTD. This paper summarizes significant ladar technology development milestones to date, individual LADAR technologies within 3D-LZ, and results of the flight testing.

  19. M.Y.S.P.A.C.E. : Multinational Youth Studying Practical Applications of Climatic Events

    NASA Astrophysics Data System (ADS)

    Mckay, M.; Arvedson, J. P.; Arvedson, P.

    2014-12-01

    M.Y. S.P.A.C.E. (Multinational Youth Studying Practical Applications of Climatic Events) is an international collaboration of high school students engaged in self-selected research projects on the local impact of global environmental issues. Students work with their own, trained, Teacher Leaders at their school sites using both locally generated and satellite-based remote-sensing data with support from the National Oceanic and Atmospheric Administration (NOAA) and the National Aeronautics and Space Administration (NASA). Teams from each school meet at the annual Satellites & Education Conference to discover global trends in their collective data and present their findings. Students learn and practice techniques of scientific investigation; methods of data processing, analysis and interpretation; leadership; and effective communication. They work with NOAA and NASA scientists and engineers, experience university campus life, and can apply for special internships at selected university research centers such as the Center for Energy and Sustainability (CE&S), the Center for Spatial Analysis and Remote Sensing (CSARS), and graduate research opportunities in Geosciences and Environment. The M.Y. S.P.A.C.E. Program is an initiative of the Satellites & Education Conference, which is produced by the non-profit Satellite Educators Association. It is administered from the campus of California State University, Los Angeles. NOAA, NASA, and the NOAA-CREST West grant support the program. It is aligned with NOAA goals of building excitement about careers in science, math, engineering and technology.

  20. A New Scoring Function for Molecular Docking Based on AutoDock and AutoDock Vina.

    PubMed

    Tanchuk, Vsevolod Yu; Tanin, Volodymyr O; Vovk, Andriy I; Poda, Gennady

    2015-01-01

    Molecular docking of small molecules in the protein binding sites is the most widely used computational technique in modern structure-based drug discovery. Although accurate prediction of binding modes of small molecules can be achieved in most cases, estimation of their binding affinities remains mediocre at best. As an attempt to improve the correlation between the inhibitory constants, pKi, and scoring, we created a new, hybrid scoring function. The new function is a linear combination of the terms of the scoring functions of AutoDock and AutoDock Vina. It was trained on 2,412 protein-ligand complexes from the PDBbind database (www.pdbbind.org.cn, version 2012) and validated on a set of 313 complexes released in the 2013 version as a test set. The new function was included in a modified version of AutoDock. The hybrid scoring function showed a statistically significant improvement in both training and test sets in terms of correlation with and root mean square and mean absolute errors in prediction of pKi values. It was also tested on the CSAR 2014 Benchmark Exercise dataset (team T) and produced reasonably good results.

  1. Model-based recognition and classification for surface texture of vegetation from an aerial sequence of images

    NASA Astrophysics Data System (ADS)

    Chen, Haijun; Houkes, Zweitze

    1997-12-01

    In this paper, a model based recognition and classification method for surface texture of vegetation from aerial sequence of images is presented. The image sequences are assumed to be acquired by a video camera (RGB-CCD system) from an aeroplane, which moves linearly over the scene. The objects in the scenes being considered in this paper, are agricultural fields. The classes of agricultural fields to be distinguished are determined by the type of crop, e.g. potatoes, sugar beet, what, etc. In order to recognize and classify these fields from aerial sequence of images, a common approach is in the use of surface texture. Here the circular symmetric auto- regressive (CSAR) random model is used for texture analysis. By manipulating the estimated value against its real value, the characteristics of a texture image may be determined. A hypothesize-and verify algorithm is used for model recognition. Based on all kinds of models, classification for surface texture of vegetation from aerial sequences of images is realized.

  2. Multiphysics Application Coupling Toolkit

    SciTech Connect

    Campbell, Michael T.

    2013-12-02

    This particular consortium implementation of the software integration infrastructure will, in large part, refactor portions of the Rocstar multiphysics infrastructure. Development of this infrastructure originated at the University of Illinois DOE ASCI Center for Simulation of Advanced Rockets (CSAR) to support the center's massively parallel multiphysics simulation application, Rocstar, and has continued at IllinoisRocstar, a small company formed near the end of the University-based program. IllinoisRocstar is now licensing these new developments as free, open source, in hopes to help improve their own and others' access to infrastructure which can be readily utilized in developing coupled or composite software systems; with particular attention to more rapid production and utilization of multiphysics applications in the HPC environment. There are two major pieces to the consortium implementation, the Application Component Toolkit (ACT), and the Multiphysics Application Coupling Toolkit (MPACT). The current development focus is the ACT, which is (will be) the substrate for MPACT. The ACT itself is built up from the components described in the technical approach. In particular, the ACT has the following major components: 1.The Component Object Manager (COM): The COM package provides encapsulation of user applications, and their data. COM also provides the inter-component function call mechanism. 2.The System Integration Manager (SIM): The SIM package provides constructs and mechanisms for orchestrating composite systems of multiply integrated pieces.

  3. Multiphysics Application Coupling Toolkit

    2013-12-02

    This particular consortium implementation of the software integration infrastructure will, in large part, refactor portions of the Rocstar multiphysics infrastructure. Development of this infrastructure originated at the University of Illinois DOE ASCI Center for Simulation of Advanced Rockets (CSAR) to support the center's massively parallel multiphysics simulation application, Rocstar, and has continued at IllinoisRocstar, a small company formed near the end of the University-based program. IllinoisRocstar is now licensing these new developments as free, openmore » source, in hopes to help improve their own and others' access to infrastructure which can be readily utilized in developing coupled or composite software systems; with particular attention to more rapid production and utilization of multiphysics applications in the HPC environment. There are two major pieces to the consortium implementation, the Application Component Toolkit (ACT), and the Multiphysics Application Coupling Toolkit (MPACT). The current development focus is the ACT, which is (will be) the substrate for MPACT. The ACT itself is built up from the components described in the technical approach. In particular, the ACT has the following major components: 1.The Component Object Manager (COM): The COM package provides encapsulation of user applications, and their data. COM also provides the inter-component function call mechanism. 2.The System Integration Manager (SIM): The SIM package provides constructs and mechanisms for orchestrating composite systems of multiply integrated pieces.« less

  4. Systemic treatment with telmisartan improves femur fracture healing in mice.

    PubMed

    Zhao, Xiong; Wang, Jia-xing; Feng, Ya-fei; Wu, Zi-xiang; Zhang, Yang; Shi, Lei; Tan, Quan-chang; Yan, Ya-bo; Lei, Wei

    2014-01-01

    Recent clinical studies indicated that angiotensin receptor blockers (ARBs) would decrease the risk of bone fractures in the elderly populations. There is little known about the role of the ARBs in the process of fracture healing. The purpose of the present study was to verify the hypothesis that systemic treatment with telmisartan has the ability to promote fracture healing. In this study, femur fractures were produced in 96 mature male BALB/c mice. Animals were treated with the ARBs telmisartan or vehicle. Fracture healing was analysed after 2, 5 and 10 weeks postoperatively using X-ray, biomechanical testing, histomorphometry, immunohistochemistry and micro-computed tomography (micro-CT). Radiological analysis showed the diameter of the callus in the telmisartan treated animals was significantly increased when compared with that of vehicle treated controls after two weeks of fracture healing. The radiologically observed promotion of callus formation was confirmed by histomorphometric analyses, which revealed a significantly increased amount of bone formation when compared with vehicle-treated controls. Biomechanical testing further showed a significantly greater peak torque at failure, and a higher torsional stiffness in telmisartan-treated animals compared with controls. There was an increased fraction of PCNA-positive cells and VEGF-positive cells in telmisartan-treated group compared with vehicle-treated controls. From the three-dimensional reconstruction of the bony callus, telmisartan-treated group significantly increased the values of BV/TV by 21.7% and CsAr by 26.0% compared to the vehicle-treated controls at 5 weeks post-fracture. In summary, we demonstrate in the current study that telmisartan could promote fracture healing in a mice model via increasing mechanical strength and improving microstructure. The most mechanism is probably by an increase of cell proliferation and neovascularization associated with a decreased VEGF expression in hypertrophic

  5. Benchmarking the QUAD4/TRIA3 element

    NASA Astrophysics Data System (ADS)

    Pitrof, Stephen M.; Venkayya, Vipperla B.

    1993-09-01

    The QUAD4 and TRIA3 elements are the primary plate/shell elements in NASTRAN. These elements enable the user to analyze thin plate/shell structures for membrane, bending and shear phenomena. They are also very new elements in the NASTRAN library. These elements are extremely versatile and constitute a substantially enhanced analysis capability in NASTRAN. However, with the versatility comes the burden of understanding a myriad of modeling implications and their effect on accuracy and analysis quality. The validity of many aspects of these elements were established through a series of benchmark problem results and comparison with those available in the literature and obtained from other programs like MSC/NASTRAN and CSAR/NASTRAN. Never-the-less such a comparison is never complete because of the new and creative use of these elements in complex modeling situations. One of the important features of QUAD4 and TRIA3 elements is the offset capability which allows the midsurface of the plate to be noncoincident with the surface of the grid points. None of the previous elements, with the exception of bar (beam), has this capability. The offset capability played a crucial role in the design of QUAD4 and TRIA3 elements. It allowed modeling layered composites, laminated plates and sandwich plates with the metal and composite face sheets. Even though the basic implementation of the offset capability is found to be sound in the previous applications, there is some uncertainty in relatively simple applications. The main purpose of this paper is to test the integrity of the offset capability and provide guidelines for its effective use. For the purpose of simplicity, references in this paper to the QUAD4 element will also include the TRIA3 element.

  6. Systemic Treatment with Telmisartan Improves Femur Fracture Healing in Mice

    PubMed Central

    Wu, Zi-xiang; Zhang, Yang; Shi, Lei; Tan, Quan-chang; Yan, Ya-bo; Lei, Wei

    2014-01-01

    Recent clinical studies indicated that angiotensin receptor blockers (ARBs) would decrease the risk of bone fractures in the elderly populations. There is little known about the role of the ARBs in the process of fracture healing. The purpose of the present study was to verify the hypothesis that systemic treatment with telmisartan has the ability to promote fracture healing. In this study, femur fractures were produced in 96 mature male BALB/c mice. Animals were treated with the ARBs telmisartan or vehicle. Fracture healing was analysed after 2, 5 and 10 weeks postoperatively using X-ray, biomechanical testing, histomorphometry, immunohistochemistry and micro-computed tomography (micro-CT). Radiological analysis showed the diameter of the callus in the telmisartan treated animals was significantly increased when compared with that of vehicle treated controls after two weeks of fracture healing. The radiologically observed promotion of callus formation was confirmed by histomorphometric analyses, which revealed a significantly increased amount of bone formation when compared with vehicle-treated controls. Biomechanical testing further showed a significantly greater peak torque at failure, and a higher torsional stiffness in telmisartan-treated animals compared with controls. There was an increased fraction of PCNA-positive cells and VEGF-positive cells in telmisartan-treated group compared with vehicle-treated controls. From the three-dimensional reconstruction of the bony callus, telmisartan-treated group significantly increased the values of BV/TV by 21.7% and CsAr by 26.0% compared to the vehicle-treated controls at 5 weeks post-fracture. In summary, we demonstrate in the current study that telmisartan could promote fracture healing in a mice model via increasing mechanical strength and improving microstructure. The most mechanism is probably by an increase of cell proliferation and neovascularization associated with a decreased VEGF expression in hypertrophic

  7. Substituent effects in 1-nitro-4-substituted bicyclo[2.2.2]octane derivatives: inductive or field effects?

    PubMed

    Krygowski, Tadeusz M; Oziminski, Wojciech P

    2014-08-01

    Interactions between the NO2 group and 13 different substituents (BF2, BH2, CF3, CH3, CHO, CN, F, NH2, NMe2, NO2, NO, OH, OMe) were investigated computationally for bicyclo[2.2.2]octane (BCO) and benzene substituted at 1,4 and 1,3 positions in the ring. Three methods were employed to estimate the character and strength of the substituent effect: substituent effect stabilization energy (SESE), sigma/pi electron donor acceptor index (sEDA/pEDA) and substituent active region (cSAR) parameter. For the first time the sEDA/pEDA parameters were calculated not for the ring but for the NO2 group. All calculations were performed at the B3LYP/6-31G(d,p) level of theory. For 1,4 derivatives, a direct comparison of slopes of linear regressions between BCO and benzene reveals a much better transmission of the substituent effect in the latter. The ratio of slopes (benzene over BCO) is always larger than 4. It follows that the resonance effects, which are absent in the BCO, dominate in this case. For 1,3 derivatives, because of much lower correlation coefficients, estimated standard deviations (ESD) were used to calculate the ratio instead of the slopes. For these systems the ratio is much closer to the unity, which indicates that only the sigma/through space effects are present and they are of similar magnitude in benzene and BCO. It follows from natural population analysis (NPA) charges that the substituent effect in the studied systems is due mainly to through-space interactions.

  8. Benchmarking the QUAD4/TRIA3 element

    NASA Technical Reports Server (NTRS)

    Pitrof, Stephen M.; Venkayya, Vipperla B.

    1993-01-01

    The QUAD4 and TRIA3 elements are the primary plate/shell elements in NASTRAN. These elements enable the user to analyze thin plate/shell structures for membrane, bending and shear phenomena. They are also very new elements in the NASTRAN library. These elements are extremely versatile and constitute a substantially enhanced analysis capability in NASTRAN. However, with the versatility comes the burden of understanding a myriad of modeling implications and their effect on accuracy and analysis quality. The validity of many aspects of these elements were established through a series of benchmark problem results and comparison with those available in the literature and obtained from other programs like MSC/NASTRAN and CSAR/NASTRAN. Never-the-less such a comparison is never complete because of the new and creative use of these elements in complex modeling situations. One of the important features of QUAD4 and TRIA3 elements is the offset capability which allows the midsurface of the plate to be noncoincident with the surface of the grid points. None of the previous elements, with the exception of bar (beam), has this capability. The offset capability played a crucial role in the design of QUAD4 and TRIA3 elements. It allowed modeling layered composites, laminated plates and sandwich plates with the metal and composite face sheets. Even though the basic implementation of the offset capability is found to be sound in the previous applications, there is some uncertainty in relatively simple applications. The main purpose of this paper is to test the integrity of the offset capability and provide guidelines for its effective use. For the purpose of simplicity, references in this paper to the QUAD4 element will also include the TRIA3 element.

  9. Synthesis and Preclinical Evaluation of Sulfonamido-based [11C-Carbonyl]-Carbamates and Ureas for Imaging Monoacylglycerol Lipase

    PubMed Central

    Wang, Lu; Mori, Wakana; Cheng, Ran; Yui, Joji; Hatori, Akiko; Ma, Longle; Zhang, Yiding; Rotstein, Benjamin H.; Fujinaga, Masayuki; Shimoda, Yoko; Yamasaki, Tomoteru; Xie, Lin; Nagai, Yuji; Minamimoto, Takafumi; Higuchi, Makoto; Vasdev, Neil; Zhang, Ming-Rong; Liang, Steven H.

    2016-01-01

    Monoacylglycerol lipase (MAGL) is a 33 kDa member of the serine hydrolase superfamily that preferentially degrades 2-arachidonoylglycerol (2-AG) to arachidonic acid in the endocannabinoid system. Inhibition of MAGL is not only of interest for probing the cannabinoid pathway but also as a therapeutic and diagnostic target for neuroinflammation. Limited attempts have been made to image MAGL in vivo and a suitable PET ligand for this target has yet to be identified and is urgently sought to guide small molecule drug development in this pathway. Herein we synthesized and evaluated the physiochemical properties of an array of eleven sulfonamido-based carbamates and ureas with a series of terminal aryl moieties, linkers and leaving groups. The most potent compounds were a novel MAGL inhibitor, N-((1-(1H-1,2,4-triazole-1-carbonyl)piperidin-4-yl) methyl)-4-chlorobenzenesulfonamide (TZPU; IC50 = 35.9 nM), and the known inhibitor 1,1,1,3,3,3-hexafluoropropan-2-yl 4-(((4-chlorophenyl)sulfonamido) methyl)piperidine-1-carboxylate (SAR127303; IC50 = 39.3 nM), which were also shown to be selective for MAGL over fatty acid amide hydrolase (FAAH), and cannabinoid receptors (CB1 & CB2). Both of these compounds were radiolabeled with carbon-11 via [11C]COCl2, followed by comprehensive ex vivo biodistribution and in vivo PET imaging studies in normal rats to determine their brain permeability, specificity, clearance and metabolism. Whereas TZPU did not show adequate specificity to warrant further evaluation, [11C]SAR127303 was advanced for preliminary PET neuroimaging studies in nonhuman primate. The tracer showed good brain permeability (ca. 1 SUV) and heterogeneous regional brain distribution which is consistent with the distribution of MAGL. PMID:27279908

  10. The L1495-B218 filaments in Taurus seen in NH3 & CCS and Dynamical Stability of Filaments and Dense Cores

    NASA Astrophysics Data System (ADS)

    Seo, Youngmin

    2016-01-01

    We present deep NH3 map of L1495-B218 filaments and the dense cores embedded within the filaments in Taurus. The L1495-B218 filaments form an interconnected, nearby, large complex extending 8 pc. We observed the filaments in NH3 (1,1) & (2,2) and CCS 21-10 with spectral resolution of 0.038 km/s and spatial resolution of 31". The CSAR algorithm, which is a hybrid of seeded-watershed and binary dendrogram algorithm, identifies 39 leaves and 16 branches in NH3 (1,1). Applying a virial analysis for the 39 NH3 leaves, we find only 9 out of 39 leaves are gravitationally bound, and 12 out of 30 gravitationally unbound leaves are pressure-confined. Our analysis suggests that a dense core may form as a pressure-confined structure, evolve to a gravitationally bound core, and then undergo collapse to form a protostar (Seo et al. 2015).We also present more realistic dynamic stability conditions for dense cores with converging motions and under the influence of radiation pressure. The critical Bonnor-Ebert sphere and the isothermal cylinder have been widely used to test stability of dense cores and filaments; however, these assume a quiescent environment while actual star forming regions are turbulent and illuminated by radiation. In a new analysis of stability conditions we account for converging motions which have been modeled toward starless cores (Seo et al. 2011) and the effect of radiation fields into account. We find that the critical size of a dense core having a homologous converging motion with its peak speed being the sound speed is roughly half of the critical size of the Bonnor-Ebert sphere (Seo et al. 2013). We also find that the critical mass/line density of a dense core/filament irradiated by radiation are considerably smaller than that of the Bonnor-Ebert sphere/isothermal cylinder when the radiation pressure is stronger than the central gas pressure of dense core/isothermal cylinder. For inner Galactic regions and regions near OB associations, the critical

  11. istar: a web platform for large-scale protein-ligand docking.

    PubMed

    Li, Hongjian; Leung, Kwong-Sak; Ballester, Pedro J; Wong, Man-Hon

    2014-01-01

    Protein-ligand docking is a key computational method in the design of starting points for the drug discovery process. We are motivated by the desire to automate large-scale docking using our popular docking engine idock and thus have developed a publicly-accessible web platform called istar. Without tedious software installation, users can submit jobs using our website. Our istar website supports 1) filtering ligands by desired molecular properties and previewing the number of ligands to dock, 2) monitoring job progress in real time, and 3) visualizing ligand conformations and outputting free energy and ligand efficiency predicted by idock, binding affinity predicted by RF-Score, putative hydrogen bonds, and supplier information for easy purchase, three useful features commonly lacked on other online docking platforms like DOCK Blaster or iScreen. We have collected 17,224,424 ligands from the All Clean subset of the ZINC database, and revamped our docking engine idock to version 2.0, further improving docking speed and accuracy, and integrating RF-Score as an alternative rescoring function. To compare idock 2.0 with the state-of-the-art AutoDock Vina 1.1.2, we have carried out a rescoring benchmark and a redocking benchmark on the 2,897 and 343 protein-ligand complexes of PDBbind v2012 refined set and CSAR NRC HiQ Set 24Sept2010 respectively, and an execution time benchmark on 12 diverse proteins and 3,000 ligands of different molecular weight. Results show that, under various scenarios, idock achieves comparable success rates while outperforming AutoDock Vina in terms of docking speed by at least 8.69 times and at most 37.51 times. When evaluated on the PDBbind v2012 core set, our istar platform combining with RF-Score manages to reproduce Pearson's correlation coefficient and Spearman's correlation coefficient of as high as 0.855 and 0.859 respectively between the experimental binding affinity and the predicted binding affinity of the docked conformation. istar

  12. Sentinel-1 Mission Overview and Implementation Status

    NASA Astrophysics Data System (ADS)

    Davidson, M.; Attema, E.; Snoeij, P.; Levrini, G.

    2009-04-01

    Sentinel-1 is an imaging radar mission at C-band consisting of a constellation of two satellites aimed at providing continuity of all-weather day-and-night supply of imagery for user services. Special emphasis is placed on services identified in ESA's GMES service elements program and on projects funded by the European Union Framework Programmes. Three priorities (fast-track services) for the mission have been identified by user consultation working groups of the European Union: Marine Core Services, Land Monitoring and Emergency Services. These cover applications such as: - Monitoring sea ice zones and the arctic environment - Surveillance of marine environment - Monitoring land surface motion risks - Mapping of land surfaces: forest, water and soil, agriculture - Mapping in support of humanitarian aid in crisis situations. The Sentinel 1 space segment will be designed and built by an industrial consortium with Thales Alenia Space Italia as prime contractor and EADS Astrium GmbH as C-SAR instrument responsible. Data products from current and previous ESA missions including ERS-1, ERS-2 and Envisat missions form the basis for many of the pilot GMES services. Consequently Sentinel-1 data maintain data quality levels of the Agency‘s previous SAR missions in terms of spatial resolution, sensitivity, accuracy, polarization and wavelength. Nonetheless, the Sentinel-1 synthetic aperture radar (SAR) constellation represents a completely new approach to SAR mission design by ESA in direct response to the operational needs for SAR data expressed under the EU-ESA Global Monitoring for Environment and Security (GMES) programme. The Sentinel-1 constellation is expected to provide near daily coverage over Europe and Canada, global coverage all independent of weather with delivery of radar data within 1 hour of acquisition - all vast improvements with respect to the existing SAR systems. The continuity of C-band SAR data combined with the greatly improved data provision is