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Sample records for activity relationships sar

  1. THE PRACTICE OF STRUCTURE ACTIVITY RELATIONSHIPS (SAR) IN TOXICOLOGY

    EPA Science Inventory

    Both qualitative and quantitative modeling methods relating chemical structure to biological activity, called structure-activity relationship analyses or SAR, are applied to the prediction and characterization of chemical toxicity. This minireview will discuss some generic issue...

  2. Synthesis, Structure-Activity Relationships (SAR) and in Silico Studies of Coumarin Derivatives with Antifungal Activity

    PubMed Central

    de Araújo, Rodrigo S. A.; Guerra, Felipe Q. S.; de O. Lima, Edeltrudes; de Simone, Carlos A.; Tavares, Josean F.; Scotti, Luciana; Scotti, Marcus T.; de Aquino, Thiago M.; de Moura, Ricardo O.; Mendonça, Francisco J. B.; Barbosa-Filho, José M.

    2013-01-01

    The increased incidence of opportunistic fungal infections, associated with greater resistance to the antifungal drugs currently in use has highlighted the need for new solutions. In this study twenty four coumarin derivatives were screened in vitro for antifungal activity against strains of Aspergillus. Some of the compounds exhibited significant antifungal activity with MICs values ranging between 16 and 32 μg/mL. The structure-activity relationships (SAR) study demonstrated that O-substitutions are essential for antifungal activity. It also showed that the presence of a short aliphatic chain and/or electron withdrawing groups (NO2 and/or acetate) favor activity. These findings were confirmed using density functional theory (DFT), when calculating the LUMO density. In Principal Component Analysis (PCA), two significant principal components (PCs) explained more than 60% of the total variance. The best Partial Least Squares Regression (PLS) model showed an r2 of 0.86 and q2cv of 0.64 corroborating the SAR observations as well as demonstrating a greater probe N1 interaction for active compounds. Descriptors generated by TIP correlogram demonstrated the importance of the molecular shape for antifungal activity. PMID:23306152

  3. Quantitative structure-activity/ecotoxicity relationships (QSAR/QEcoSAR) of a series of phosphonates.

    PubMed

    Petrescu, Alina-Maria; Putz, Mihai V; Ilia, Gheorghe

    2015-11-01

    In this paper the structure-toxicity relationship studies were performed for a series of 60 phosphonates. The toxicity of the compounds was determined by two ways: by quantifying the measured toxicity values, Mlog(1/MRIC50) collected by literature, for rodents species; second by using EcoSAR software version 1.11, for calculating the toxicity for fish species, considered as dependent variables and they were related to structural features obtained by molecular and quantum mechanics calculations. The QSAR/QEcoSAR was validated by multiple linear regression (MLR), although the purpose of this work was not to validate the model proposed, but rather to test the influence of structural parameters of the proposed model QSAR/QEcoSAR. The obtained models showed that the toxicity of phosphonates was influenced by steric and molecular geometry which cause inhibition of cholinesterase activity.

  4. Quantitative structure-activity relationships of selective antagonists of glucagon receptor using QuaSAR descriptors.

    PubMed

    Manoj Kumar, Palanivelu; Karthikeyan, Chandrabose; Hari Narayana Moorthy, Narayana Subbiah; Trivedi, Piyush

    2006-11-01

    In the present paper, quantitative structure activity relationship (QSAR) approach was applied to understand the affinity and selectivity of a novel series of triaryl imidazole derivatives towards glucagon receptor. Statistically significant and highly predictive QSARs were derived for glucagon receptor inhibition by triaryl imidazoles using QuaSAR descriptors of molecular operating environment (MOE) employing computer-assisted multiple regression procedure. The generated QSAR models revealed that factors related to hydrophobicity, molecular shape and geometry predominantly influences glucagon receptor binding affinity of the triaryl imidazoles indicating the relevance of shape specific steric interactions between the molecule and the receptor. Further, QSAR models formulated for selective inhibition of glucagon receptor over p38 mitogen activated protein (MAP) kinase of the compounds in the series highlights that the same structural features, which influence the glucagon receptor affinity, also contribute to their selective inhibition.

  5. Structure-activity relationship (SAR) analysis of a family of steroids acutely controlling steroidogenesis.

    PubMed

    Midzak, Andrew; Rammouz, Georges; Papadopoulos, Vassilios

    2012-11-01

    Steroids metabolically derive from lipid cholesterol, and vertebrate steroids additionally derive from the steroid pregnenolone. Pregnenolone is derived from cholesterol by hydrolytic cleavage of the aliphatic tail by mitochondrial cytochrome P450 enzyme CYP11A1, located in the inner mitochondrial membrane. Delivery of cholesterol to CYP11A1 comprises the principal control step of steroidogenesis, and requires a series of proteins spanning the mitochondrial double membranes. A critical member of this cholesterol translocation machinery is the integral outer mitochondrial membrane translocator protein (18kDa, TSPO), a high-affinity drug- and cholesterol-binding protein. The cholesterol-binding site of TSPO consists of a phylogenetically conserved cholesterol recognition/interaction amino acid consensus (CRAC). Previous studies from our group identified 5-androsten-3β,17,19-triol (19-Atriol) as drug ligand for the TSPO CRAC motif inhibiting cholesterol binding to CRAC domain and steroidogenesis. To further understand 19-Atriol's mechanism of action as well as the molecular recognition by the TSPO CRAC motif, we undertook structure-activity relationship (SAR) analysis of the 19-Atriol molecule with a variety of substituted steroids oxygenated at positions around the steroid backbone. We found that in addition to steroids hydroxylated at carbon C19, hydroxylations at C4, C7, and C11 contributed to inhibition of cAMP-mediated steroidogenesis in a minimal steroidogenic cell model. However, only substituted steroids with C19 hydroxylations exhibited specificity to TSPO, its CRAC motif, and mitochondrial cholesterol transport, as the C4, C7, and C11 hydroxylated steroids inhibited the metabolic transformation of cholesterol by CYP11A1. We thus provide new insights into structure-activity relationships of steroids inhibiting mitochondrial cholesterol transport and steroidogenic cholesterol metabolic enzymes.

  6. Synthesis, insecticidal activity, and structure-activity relationship (SAR) of anthranilic diamides analogs containing oxadiazole rings.

    PubMed

    Li, Yuhao; Zhu, Hongjun; Chen, Kai; Liu, Rui; Khallaf, Abdalla; Zhang, Xiangning; Ni, Jueping

    2013-06-28

    A series of anthranilic diamides analogs (3–11, 16–24) containing 1,2,4- or 1,3,4-oxadiazole rings were synthesized and characterized by (1)H NMR, MS and elemental analyses. The structure of 3-bromo-N-(2-(3-(4-bromophenyl)-1,2,4-oxadiazol-5-yl)-4-chloro-6-methylphenyl)-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxamide (18, CCDC-) was determined by X-ray diffraction crystallography. The insecticidal activities against Plutella xylostella and Spodoptera exigua were evaluated. The results showed that most of title compounds displayed good larvicidal activities against P. xylostella, especially compound 3-bromo-N-(4-chloro-2-methyl-6-(5-(methylthio)-1,3,4-oxadiazol-2-yl)phenyl)-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxamide (6), which displayed 71.43% activity against P. xylostella at 0.4 μg mL(-1) and 33.33% against S. exigua at 1 μg mL(-1). The structure-activity relationship showed that compounds decorated with a 1,3,4-oxadiazole were more potent than compounds decorated with a 1,2,4-oxadiazole, and different substituents attached to the oxadiazole ring also affected the insecticidal activity. This work provides some hints for further structure modification and the enhancement of insecticidal activity.

  7. Synthesis, insecticidal activity, and structure-activity relationship (SAR) of anthranilic diamides analogs containing oxadiazole rings.

    PubMed

    Li, Yuhao; Zhu, Hongjun; Chen, Kai; Liu, Rui; Khallaf, Abdalla; Zhang, Xiangning; Ni, Jueping

    2013-06-28

    A series of anthranilic diamides analogs (3–11, 16–24) containing 1,2,4- or 1,3,4-oxadiazole rings were synthesized and characterized by (1)H NMR, MS and elemental analyses. The structure of 3-bromo-N-(2-(3-(4-bromophenyl)-1,2,4-oxadiazol-5-yl)-4-chloro-6-methylphenyl)-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxamide (18, CCDC-) was determined by X-ray diffraction crystallography. The insecticidal activities against Plutella xylostella and Spodoptera exigua were evaluated. The results showed that most of title compounds displayed good larvicidal activities against P. xylostella, especially compound 3-bromo-N-(4-chloro-2-methyl-6-(5-(methylthio)-1,3,4-oxadiazol-2-yl)phenyl)-1-(3-chloropyridin-2-yl)-1H-pyrazole-5-carboxamide (6), which displayed 71.43% activity against P. xylostella at 0.4 μg mL(-1) and 33.33% against S. exigua at 1 μg mL(-1). The structure-activity relationship showed that compounds decorated with a 1,3,4-oxadiazole were more potent than compounds decorated with a 1,2,4-oxadiazole, and different substituents attached to the oxadiazole ring also affected the insecticidal activity. This work provides some hints for further structure modification and the enhancement of insecticidal activity. PMID:23657615

  8. Oximes: inhibitors of human recombinant acetylcholinesterase. A structure-activity relationship (SAR) study.

    PubMed

    Sepsova, Vendula; Karasova, Jana Zdarova; Korabecny, Jan; Dolezal, Rafael; Zemek, Filip; Bennion, Brian J; Kuca, Kamil

    2013-08-16

    Acetylcholinesterase (AChE) reactivators were developed for the treatment of organophosphate intoxication. Standard care involves the use of anticonvulsants (e.g., diazepam), parasympatolytics (e.g., atropine) and oximes that restore AChE activity. However, oximes also bind to the active site of AChE, simultaneously acting as reversible inhibitors. The goal of the present study is to determine how oxime structure influences the inhibition of human recombinant AChE (hrAChE). Therefore, 24 structurally different oximes were tested and the results compared to the previous eel AChE (EeAChE) experiments. Structural factors that were tested included the number of pyridinium rings, the length and structural features of the linker, and the number and position of the oxime group on the pyridinium ring.

  9. Thinking in Terms of Structure-Activity-Relationships (T-SAR): A Tool to Better Understand Nanofiltration Membranes

    PubMed Central

    Fernández, José F.; Jastorff, Bernd; Störmann, Reinhold; Stolte, Stefan; Thöming, Jorg

    2011-01-01

    A frontier to be conquered in the field of membrane technology is related to the very limited scientific base for the rational and task-specific design of membranes. This is especially true for nanofiltration membranes with properties that are based on several solute-membrane interaction mechanisms. “Thinking in terms of Structure-Activity-Relationships” (T-SAR) is a methodology which applies a systematic analysis of a chemical entity based on its structural formula. However, the analysis become more complex with increasing size of the molecules considered. In this study, T-SAR was combined with classical membrane characterization methods, resulting in a new methodology which allowed us not only to explain membrane characteristics, but also provides evidence for the importance of the chemical structure for separation performance. We demonstrate an application of the combined approach and its potential to discover stereochemistry, molecular interaction potentials, and reactivity of two FilmTec nanofiltration membranes (NF-90 and NF-270). Based on these results, it was possible to predict both properties and performance in the recovery of hydrophobic ionic liquids from aqueous solution. PMID:24957730

  10. Fragrances and other materials in deodorants: search for potentially sensitizing molecules using combined GC-MS and structure activity relationship (SAR) analysis.

    PubMed

    Rastogi, S C; Lepoittevin, J P; Johansen, J D; Frosch, P J; Menné, T; Bruze, M; Dreier, B; Andersen, K E; White, I R

    1998-12-01

    Deodorants are one of the most frequently-used types of cosmetics and are a source of allergic contact dermatitis. Therefore, a gas chromatography - mass spectrometric analysis of 71 deodorants was performed for identification of fragrance and non-fragrance materials present in marketed deodorants. Futhermore, the sensitizing potential of these molecules was evaluated using structure activity relationships (SARs) analysis. This was based on the presence of 1 or more chemically reactive site(s), in the chemical structure, associated with sensitizing potential. Among the many different substances used to formulate cosmetic products (over 3500), 226 chemicals were identified in a sample of 71 deodorants. 84 molecules were found to contain at least 1 structural alert, and 70 to belong to, or be susceptible to being metabolized into, the chemical group of aldehydes, ketones and alpha,beta-unsaturated aldehydes, ketone or esters. The combination of GC-MS and SARs analysis could be helpful in the selection of substances for supplementary investigations regarding sensitizing properties. Thus, it may be a valuable tool in the management of contact allergy to deodorants and for producing new deodorants with decreased propensity to cause contact allergy.

  11. Benzoic acid derivatives with improved antifungal activity: Design, synthesis, structure-activity relationship (SAR) and CYP53 docking studies.

    PubMed

    Berne, Sabina; Kovačič, Lidija; Sova, Matej; Kraševec, Nada; Gobec, Stanislav; Križaj, Igor; Komel, Radovan

    2015-08-01

    Previously, we identified CYP53 as a fungal-specific target of natural phenolic antifungal compounds and discovered several inhibitors with antifungal properties. In this study, we performed similarity-based virtual screening and synthesis to obtain benzoic acid-derived compounds and assessed their antifungal activity against Cochliobolus lunatus, Aspergillus niger and Pleurotus ostreatus. In addition, we generated structural models of CYP53 enzyme and used them in docking trials with 40 selected compounds. Finally, we explored CYP53-ligand interactions and identified structural elements conferring increased antifungal activity to facilitate the development of potential new antifungal agents that specifically target CYP53 enzymes of animal and plant pathogenic fungi. PMID:26154240

  12. Mode of action and the assessment of chemical hazards in the presence of limited data: use of structure-activity relationships (SAR) under TSCA, Section 5.

    PubMed Central

    Auer, C M; Nabholz, J V; Baetcke, K P

    1990-01-01

    Section 5 of the Toxic Substances Control Act (TSCA) requires that manufacturers and importers of new chemicals must submit a Premanufacture Notification (PMN) to the U.S. Environmental Protection Agency 90 days before they intend to commence manufacture or import. Certain information such as chemical identity, uses, etc., must be included in the notification. The submission of test data on the new substance, however, is not required, although any available health and environmental information must be provided. Nonetheless, over half of all PMNs submitted to the agency do not contain any test data; because PMN chemicals are new, no test data is generally available in the scientific literature. Given this situation, EPA has had to develop techniques for hazard assessment that can be used in the presence of limited test data. EPA's approach has been termed "structure-activity relationships" (SAR) and involves three major components: the first is critical evaluation and interpretation of available toxicity data on the chemical; the second component involves evaluation of test data available on analogous substances and/or potential metabolites; and the third component involves the use of mathematical expressions for biological activity known as "quantitative structure-activity relationships" (QSARs). At present, the use of QSARs is limited to estimating physical chemical properties, environmental toxicity, and bioconcentration factors. An important overarching element in EPA's approach is the experience and judgment of scientific assessors in interpreting and integrating the available data and information. Examples are provided that illustrate EPA's approach to hazard assessment for PMN chemicals. PMID:2269224

  13. Binding interaction of quercetin-3-beta-galactoside and its synthetic derivatives with SARS-CoV 3CL(pro): structure-activity relationship studies reveal salient pharmacophore features.

    PubMed

    Chen, Lili; Li, Jian; Luo, Cheng; Liu, Hong; Xu, Weijun; Chen, Gang; Liew, Oi Wah; Zhu, Weiliang; Puah, Chum Mok; Shen, Xu; Jiang, Hualiang

    2006-12-15

    The 3C-like protease (3CL(pro)) of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is one of the most promising targets for discovery of drugs against SARS, because of its critical role in the viral life cycle. In this study, a natural compound called quercetin-3-beta-galactoside was identified as an inhibitor of the protease by molecular docking, SPR/FRET-based bioassays, and mutagenesis studies. Both molecular modeling and Q189A mutation revealed that Gln189 plays a key role in the binding. Furthermore, experimental evidence showed that the secondary structure and enzymatic activity of SARS-CoV 3CL(pro) were not affected by the Q189A mutation. With the help of molecular modeling, eight new derivatives of the natural product were designed and synthesized. Bioassay results reveal salient features of the structure-activity relationship of the new compounds: (1) removal of the 7-hydroxy group of the quercetin moiety decreases the bioactivity of the derivatives; (2) acetoxylation of the sugar moiety abolishes inhibitor action; (3) introduction of a large sugar substituent on 7-hydroxy of quercetin can be tolerated; (4) replacement of the galactose moiety with other sugars does not affect inhibitor potency. This study not only reveals a new class of compounds as potential drug leads against the SARS virus, but also provides a solid understanding of the mechanism of inhibition against the target enzyme.

  14. From Sphingosine Kinase to Dihydroceramide Desaturase: A Structure-Activity Relationship (SAR) Study of the Enzyme Inhibitory and Anticancer Activity of 4-((4-(4-Chlorophenyl)thiazol-2-yl)amino)phenol (SKI-II).

    PubMed

    Aurelio, Luigi; Scullino, Carmen V; Pitman, Melissa R; Sexton, Anna; Oliver, Victoria; Davies, Lorena; Rebello, Richard J; Furic, Luc; Creek, Darren J; Pitson, Stuart M; Flynn, Bernard L

    2016-02-11

    The sphingosine kinase (SK) inhibitor, SKI-II, has been employed extensively in biological investigations of the role of SK1 and SK2 in disease and has demonstrated impressive anticancer activity in vitro and in vivo. However, interpretations of results using this pharmacological agent are complicated by several factors: poor SK1/2 selectivity, additional activity as an inducer of SK1-degradation, and off-target effects, including its recently identified capacity to inhibit dihydroceramide desaturase-1 (Des1). In this study, we have delineated the structure-activity relationship (SAR) for these different targets and correlated them to that required for anticancer activity and determined that Des1 inhibition is primarily responsible for the antiproliferative effects of SKI-II and its analogues. In the course of these efforts, a series of novel SK1, SK2, and Des1 inhibitors have been generated, including compounds with significantly greater anticancer activity.

  15. SAR and QSAR of the antioxidant activity of flavonoids.

    PubMed

    Amić, Dragan; Davidović-Amić, Dusanka; Beslo, Drago; Rastija, Vesna; Lucić, Bono; Trinajstić, Nenad

    2007-01-01

    Flavonoids are a group of naturally occurring phytochemicals abundantly present in fruits, vegetables, and beverages such as wine and tea. In the past two decades, flavonoids have gained enormous interest because of their beneficial health effects such as anti-inflammatory, cardio-protective and anticancer activities. These findings have contributed to the dramatic increase in the consumption and use of dietary supplements containing high concentrations of plant flavonoids. The pharmacological effect of flavonoids is mainly due to their antioxidant activity and their inhibition of certain enzymes. In spite of abundant data, structural requirements and mechanisms underlying these effects have not been fully understood. This review presents the current knowledge about structure-activity relationships (SARs) and quantitative structure-activity relationships (QSARs) of the antioxidant activity of flavonoids. SAR and QSAR can provide useful tools for revealing the nature of flavonoid antioxidant action. They may also help in the design of new and efficient flavonoids, which could be used as potential therapeutic agents.

  16. (Z)-1-aryl-3-arylamino-2-propen-1-ones, highly active stimulators of tubulin polymerization: synthesis, structure-activity relationship (SAR), tubulin polymerization, and cell growth inhibition studies.

    PubMed

    Reddy, M V Ramana; Akula, Balaiah; Cosenza, Stephen C; Lee, Clement M; Mallireddigari, Muralidhar R; Pallela, Venkat R; Subbaiah, D R C Venkata; Udofa, Andrew; Reddy, E Premkumar

    2012-06-14

    Tubulin, the major structural component of microtubules, is a target for the development of anticancer agents. A series of (Z)-1-aryl-3-arylamino-2-propen-1-one (10) were synthesized and evaluated for antiproliferative activity in cell-based assay. The most active compound (Z)-1-(2-bromo-3,4,5-trimethoxyphenyl)-3-(3-hydroxy-4-methoxyphenylamino)prop-2-en-1-one (10ae) was tested in 20 tumor cell lines including multidrug resistant phenotype and was found to induce apoptosis in all these cell lines with similar GI(50) values. Flow cytometry studies showed that 10ae arrested the cells in G2/M phase of cell cycle. In addition to G2/M block, these compounds caused microtubule stabilization like paclitaxel and induced apoptosis via activation of the caspase family. The observations made in this investigation demonstrate that (Z)-1-Aryl-3-arylamino-2-propen-1-one (10) represents a new class of microtubule-stabilizing agents.

  17. (Z)-1-Aryl-3-arylamino-2-propen-1-ones, Highly Active Stimulators of Tubulin Polymerization: Synthesis, Structure Activity Relationship (SAR), Tubulin Polymerization and Cell Growth Inhibition Studies

    PubMed Central

    Reddy, M.V. Ramana; Akula, Balaiah; Cosenza, Stephen C; Lee, Clement M; Mallireddigari, Muralidhar R; Pallela, Venkat R; Subbaiah, DRC Venkata; Udofa, Andrew; Reddy, E. Premkumar

    2012-01-01

    Tubulin, the major structural component of microtubules, is a target for the development of anticancer agents. A series of (Z)-1-Aryl-3-arylamino-2-propen-1-one (10) were synthesized and evaluated for anti-proliferative activity in cell based assay. The most active compound (Z)-1-(2- bromo-3,4,5-trimethoxyphenyl)-3-(3-hydroxy-4-methoxyphenylamino)-prop-2-en-1-one (10ae) was tested in 20 tumor cell lines including multidrug resistant phenotype and was found to induce apoptosis in all these cell lines with similar GI50 values. Flow cytometry studies showed that 10ae arrested the cells in G2/M phase of cell cycle. In addition to G2/M block, these compounds caused microtubule stabilization like paclitaxel and induced apoptosis via activation of the caspase family. The observations made in this investigation demonstrate that (Z)-1-Aryl-3- arylamino-2-propen-1-one (10) represents a new class of microtubule – stabilizing agents. PMID:22587519

  18. Extraction of SAR information from activity cliff clusters via matching molecular series.

    PubMed

    Dimova, Dilyana; Bajorath, Jürgen

    2014-11-24

    The vast majority of activity cliffs that occur is sets of bioactive compounds are formed in a coordinated manner. This means that multiple and overlapping cliffs are formed by groups of structural analogs with varying activity. In network representations, coordinated activity cliffs emerge as clusters of varying size and topology. Activity cliff clusters are typically rich in structure-activity relationship (SAR) information but often difficult to analyze from a medicinal chemistry viewpoint. A key question is how to best access SAR information contained in activity cliff clusters without the need to evaluate many different clusters individually. Herein, we introduce a methodology for the systematic extraction of SAR information from activity cliff clusters that utilizes the concept of matching molecular series (MMS). Sequences of activity cliff-forming compounds are isolated from clusters that follow a activity gradient and series spanning large activity differences are preferentially selected. In addition to its systematic nature, an attractive feature of the approach is that SAR information associated with extracted series is readily interpretable. We show that MMS are abundant in activity cliff clusters from the current spectrum of bioactive compounds and that many MMS share compounds. The resulting pairs of connected MMS contain compounds with closely related structural cores and alternative substitution sites that reveal SAR determinants and preferred substituents.

  19. Seasonal dynamics of active SAR11 ecotypes in the oligotrophic Northwest Mediterranean Sea

    PubMed Central

    Salter, Ian; Galand, Pierre E; Fagervold, Sonja K; Lebaron, Philippe; Obernosterer, Ingrid; Oliver, Matthew J; Suzuki, Marcelino T; Tricoire, Cyrielle

    2015-01-01

    A seven-year oceanographic time series in NW Mediterranean surface waters was combined with pyrosequencing of ribosomal RNA (16S rRNA) and ribosomal RNA gene copies (16S rDNA) to examine the environmental controls on SAR11 ecotype dynamics and potential activity. SAR11 diversity exhibited pronounced seasonal cycles remarkably similar to total bacterial diversity. The timing of diversity maxima was similar across narrow and broad phylogenetic clades and strongly associated with deep winter mixing. Diversity minima were associated with periods of stratification that were low in nutrients and phytoplankton biomass and characterised by intense phosphate limitation (turnover time<5 h). We propose a conceptual framework in which physical mixing of the water column periodically resets SAR11 communities to a high diversity state and the seasonal evolution of phosphate limitation competitively excludes deeper-dwelling ecotypes to promote low diversity states dominated (>80%) by SAR11 Ia. A partial least squares (PLS) regression model was developed that could reliably predict sequence abundances of SAR11 ecotypes (Q2=0.70) from measured environmental variables, of which mixed layer depth was quantitatively the most important. Comparison of clade-level SAR11 rRNA:rDNA signals with leucine incorporation enabled us to partially validate the use of these ratios as an in-situ activity measure. However, temporal trends in the activity of SAR11 ecotypes and their relationship to environmental variables were unclear. The strong and predictable temporal patterns observed in SAR11 sequence abundance was not linked to metabolic activity of different ecotypes at the phylogenetic and temporal resolution of our study. PMID:25238399

  20. ICAO's anti-SARS airport activities.

    PubMed

    Finkelstein, Silvio; Curdt-Christiansen, Claus M

    2003-11-01

    To prevent SARS from spreading through air travel and in order to rebuild the confidence of the traveling public in the safety of air travel, ICAO has set up an "Anti-SARS Airport Evaluation Project." The first phase of this project was to develop a set of protective measures for international airports in affected areas to adopt and implement and then to send out, on the request of Contracting States, a team of inspectors to evaluate and assess airports and issue a "statement of evaluation" that the airport inspected complies with the ICAO anti-SARS protective measures. In cooperation with the World Health Organization (WHO), the first part of phase 1 was completed in early June this year, and the second part of phase 1 followed soon after. By mid-July, five international airports in Southeast Asia had been inspected and found to be in full compliance with the ICAO anti-SARS protective measures. The success of this ICAO project is believed to have contributed significantly to the recovery of international air travel and related industries now taking place. Phase 2 of the project is now being developed. It is aimed at preventing a resurgence of SARS, but it also contains elements to make the methodology developed applicable to future outbreaks of any other communicable disease in which the mode of transmission could involve aviation and/or the need to prevent the spread of the disease by air travel.

  1. THE USE OF STRUCTURE-ACTIVITY RELATIONSHIPS IN INTEGRATING THE CHEMISTRY AND TOXICOLOGY OF ENDOCRINE DISRUPTING CHEMICALS

    EPA Science Inventory

    Structure activity relationships (SARs) are based on the principle that structurally similar chemicals should have similar biological activity. SARs relate specifically-defined toxicological activity of chemicals to their molecular structure and physico-chemical properties. To de...

  2. STRUCTURE-ACTIVITY RELATIONSHIP STUIDES AND THEIR ROLE IN PREDICTING AND INVESTIGATING CHEMICAL TOXICITY

    EPA Science Inventory

    Structure-Activity Relationship Studies and their Role in Predicting and Investigating Chemical Toxicity

    Structure-activity relationships (SAR) represent attempts to generalize chemical information relative to biological activity for the twin purposes of generating insigh...

  3. Naturally occurring plant isoquinoline N-oxide alkaloids: their pharmacological and SAR activities.

    PubMed

    Dembitsky, Valery M; Gloriozova, Tatyana A; Poroikov, Vladimir V

    2015-01-15

    The present review describes research on novel natural isoquinoline alkaloids and their N-oxides isolated from different plant species. More than 200 biological active compounds have shown confirmed antimicrobial, antibacterial, antitumor, and other activities. The structures, origins, and reported biological activities of a selection of isoquinoline N-oxides alkaloids are reviewed. With the computer program PASS some additional SAR (structure-activity relationship) activities are also predicted, which point toward new possible applications of these compounds. This review emphasizes the role of isoquinoline N-oxides alkaloids as an important source of leads for drug discovery.

  4. 76 FR 20822 - Proposed Information Collection (Servicer's Staff Appraisal Reviewer (SAR) Application) Activity...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-13

    ... approval as Staff Appraisal Reviewer (SAR). Servicers SAR's will have the authority to review real estate... AFFAIRS Proposed Information Collection (Servicer's Staff Appraisal Reviewer (SAR) Application) Activity... needed to nominate servicer appraisal employee as a staff appraisal reviewer. DATES: Written comments...

  5. 76 FR 27387 - Agency Information Collection Activity (Lenders Staff Appraisal Reviewer (SAR) Application) Under...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-11

    ... approved, SARs will have the authority to review real estate appraisals and to issue notices of values on... AFFAIRS Agency Information Collection Activity (Lenders Staff Appraisal Reviewer (SAR) Application) Under....'' Title: Lenders Staff Appraisal Reviewer (SAR) Application, VA Form 26-0785. OMB Control Number:...

  6. 76 FR 35949 - Agency Information Collection Activity (Servicer's Staff Appraisal Reviewer (SAR) Application...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-20

    ...). Servicers SAR's will have the authority to review real estate appraisals and to issue liquidation notices of... AFFAIRS Agency Information Collection Activity (Servicer's Staff Appraisal Reviewer (SAR) Application....'' SUPPLEMENTARY INFORMATION: ] Title: Servicer's Staff Appraisal Reviewer (SAR) Application, VA Form 26-0829....

  7. Investigating earthquake scaling relationships from a 15 year archive of InSAR-derived earthquake models

    NASA Astrophysics Data System (ADS)

    Funning, G. J.; Ferreira, A. M.; Parsons, B. E.

    2008-12-01

    In the 15 years since the first InSAR study of the 1992 Landers earthquake, the first event to be studied using InSAR, over 50 events have been studied wholly or jointly using InSAR. This constitutes a rich archive of published studies that can be mined for information on earthquake phenomenology. Empirical earthquake scaling relationships, as can be inferred from estimates of fault dimensions, slip and moment for multiple earthquakes, are extensively used in seismic hazard forecasting, and also constitute a means of placing constraints on the bulk mechanical behaviour of the seismogenic upper crust. As a source of such data, studies that utilise information from InSAR have an advantage over seismic methods in that in many cases, a key parameter, the fault length, can be measured directly from the observations. In addition, in cases of good interferogram coherence, the high spatial density of surface deformation observations that InSAR affords can place tight constraints on fault width and other important parameters. We present here a preliminary survey of earthquake scaling relationships as supported by the existing archive of InSAR earthquake studies. We find that for events with Mw > 6, the data support moment scaling with the square of fault length, in keeping with the studies of Scholz and others, and imply proportionality between fault average slip and fault length. There are currently too few datapoints for great earthquakes (Mw > 8) to assess any proposed change in scaling for such events. Scatterplots of average slip versus fault length show two broad fields -- an area of high slip-to-length ratios (> 2 × 10-5) which are predominantly associated with faults with low long-term slip rates, predominantly from intraplate settings, and an area of lower slip-to-length ratios (< 2 × 10-5) which typically are larger events from faults with higher long-term slip rates (e.g. the North Anatolian and Kunlun faults, and the Peru-Chile subduction zone). In addition

  8. Structural interpretation of activity cliffs revealed by systematic analysis of structure-activity relationships in analog series.

    PubMed

    Sisay, Mihiret T; Peltason, Lisa; Bajorath, Jürgen

    2009-10-01

    Discontinuity in structure-activity relationships (SARs) is caused by so-called activity cliffs and represents one of the major caveats in SAR modeling and lead optimization. At activity cliffs, small structural modifications of compounds lead to substantial differences in potency that are essentially unpredictable using quantitative structure-activity relationship (QSAR) methods. In order to better understand SAR discontinuity at the molecular level of detail, we have analyzed different compound series in combinatorial analog graphs and determined substitution patterns that introduce activity cliffs of varying magnitude. So identified SAR determinants were then analyzed on the basis of complex crystal structures to enable a structural interpretation of SAR discontinuity and underlying activity cliffs. In some instances, SAR discontinuity detected within analog series could be well rationalized on the basis of structural data, whereas in others a structural explanation was not possible. This reflects the intrinsic complexity of small molecule SARs and suggests that the analysis of short-range receptor-ligand interactions seen in X-ray structures is insufficient to comprehensively account for SAR discontinuity. However, in other cases, SAR information extracted from ligands was incomplete but could be deduced taking X-ray data into account. Thus, taken together, these findings illustrate the complementarity of ligand-based SAR analysis and structural information. PMID:19761254

  9. Systematic assessment of coordinated activity cliffs formed by kinase inhibitors and detailed characterization of activity cliff clusters and associated SAR information.

    PubMed

    Dimova, Dilyana; Stumpfe, Dagmar; Bajorath, Jürgen

    2015-01-27

    From currently available kinase inhibitors and their activity data, clusters of coordinated activity cliffs were systematically derived and subjected to cluster index and index map analysis. Type I-like inhibitors with well-defined IC50 measurements were found to provide a large knowledge base of activity cliff clusters for 266 targets from nine kinase groups. On the basis of index map analysis, these clusters were systematically organized according to structural similarity of inhibitors and activity cliff diversity and prioritized for structure-activity relationship (SAR) analysis. From prioritized clusters, interpretable SAR information can be extracted. It is also shown that activity cliff clusters formed by ATP site-directed inhibitors often represent local SAR environments of rather different complexity and interpretability. In addition, activity cliff clusters including promiscuous kinase inhibitors have been determined. Only a small subset of inhibitors was found to change activity cliff roles in different clusters. The activity cliff clusters described herein and their index map organization substantially enrich SAR information associated with kinase inhibitors in compound subsets of limited size. The cluster and index map information is made available upon request to provide opportunities for further SAR exploration. On the basis of our analysis and the data provided, activity cliff clusters and corresponding inhibitor series for kinase targets of interest can be readily selected.

  10. Relationships between autofocus methods for SAR and self-survey techniques for SONAR. [Synthetic Aperture Radar (SAR)

    SciTech Connect

    Wahl, D.E.; Jakowatz, C.V. Jr.; Ghiglia, D.C.; Eichel, P.H.

    1991-01-01

    Autofocus methods in SAR and self-survey techniques in SONAR have a common mathematical basis in that they both involve estimation and correction of phase errors introduced by sensor position uncertainties. Time delay estimation and correlation methods have been shown to be effective in solving the self-survey problem for towed SONAR arrays. Since it can be shown that platform motion errors introduce similar time-delay estimation problems in SAR imaging, the question arises as to whether such techniques could be effectively employed for autofocus of SAR imagery. With a simple mathematical model for motion errors in SAR, we will show why such correlation/time-delay techniques are not nearly as effective as established SAR autofocus algorithms such as phase gradient autofocus or sub-aperture based methods. This analysis forms an important bridge between signal processing methodologies for SAR and SONAR. 5 refs., 4 figs.

  11. The Seamless SAR Archive (SSARA) Project and Other SAR Activities at UNAVCO

    NASA Astrophysics Data System (ADS)

    Baker, S.; Crosby, C. J.; Meertens, C. M.; Fielding, E. J.; Bryson, G.; Buechler, B.; Nicoll, J.; Baru, C.

    2014-12-01

    The seamless synthetic aperture radar archive (SSARA) implements a seamless distributed access system for SAR data and derived data products (i.e. interferograms). SSARA provides a unified application programming interface (API) for SAR data search and results at the Alaska Satellite Facility and UNAVCO (WInSAR and EarthScope data archives) through the use of simple web services. A federated query service was developed using the unified APIs, providing users a single search interface for both archives. Interest from the international community has prompted an effort to incorporate ESA's Virtual Archive 4 Geohazard Supersites and Natural Laboratories (GSNL) collections and other archives into the federated query service. SSARA also provides Digital Elevation Model access for topographic correction via a simple web service through OpenTopography and tropospheric correction products through JPL's OSCAR service. Additionally, UNAVCO provides data storage capabilities for WInSAR PIs with approved TerraSAR-X and ALOS-2 proposals which allows easier distribution to US collaborators on associated proposals and facilitates data access through the SSARA web services. Further work is underway to incorporate federated data discovery for GSNL across SAR, GPS, and seismic datasets provided by web services from SSARA, GSAC, and COOPEUS.

  12. Relationship of SARS-CoV to other pathogenic RNA viruses explored by tetranucleotide usage profiling

    PubMed Central

    Yap, Yee Leng; Zhang, Xue Wu; Danchin, Antoine

    2003-01-01

    Background The exact origin of the cause of the Severe Acute Respiratory Syndrome (SARS) is still an open question. The genomic sequence relationship of SARS-CoV with 30 different single-stranded RNA (ssRNA) viruses of various families was studied using two non-standard approaches. Both approaches began with the vectorial profiling of the tetra-nucleotide usage pattern V for each virus. In approach one, a distance measure of a vector V, based on correlation coefficient was devised to construct a relationship tree by the neighbor-joining algorithm. In approach two, a multivariate factor analysis was performed to derive the embedded tetra-nucleotide usage patterns. These patterns were subsequently used to classify the selected viruses. Results Both approaches yielded relationship outcomes that are consistent with the known virus classification. They also indicated that the genome of RNA viruses from the same family conform to a specific pattern of word usage. Based on the correlation of the overall tetra-nucleotide usage patterns, the Transmissible Gastroenteritis Virus (TGV) and the Feline CoronaVirus (FCoV) are closest to SARS-CoV. Surprisingly also, the RNA viruses that do not go through a DNA stage displayed a remarkable discrimination against the CpG and UpA di-nucleotide (z = -77.31, -52.48 respectively) and selection for UpG and CpA (z = 65.79,49.99 respectively). Potential factors influencing these biases are discussed. Conclusion The study of genomic word usage is a powerful method to classify RNA viruses. The congruence of the relationship outcomes with the known classification indicates that there exist phylogenetic signals in the tetra-nucleotide usage patterns, that is most prominent in the replicase open reading frames. PMID:14499005

  13. Follow-up: Prospective compound design using the 'SAR Matrix' method and matrix-derived conditional probabilities of activity.

    PubMed

    Gupta-Ostermann, Disha; Hirose, Yoichiro; Odagami, Takenao; Kouji, Hiroyuki; Bajorath, Jürgen

    2015-01-01

    In a previous Method Article, we have presented the 'Structure-Activity Relationship (SAR) Matrix' (SARM) approach. The SARM methodology is designed to systematically extract structurally related compound series from screening or chemical optimization data and organize these series and associated SAR information in matrices reminiscent of R-group tables. SARM calculations also yield many virtual candidate compounds that form a "chemical space envelope" around related series. To further extend the SARM approach, different methods are developed to predict the activity of virtual compounds. In this follow-up contribution, we describe an activity prediction method that derives conditional probabilities of activity from SARMs and report representative results of first prospective applications of this approach. PMID:25949808

  14. SAR studies directed toward the pyridine moiety of the sap-feeding insecticide sulfoxaflor (Isoclast™ active).

    PubMed

    Loso, Michael R; Benko, Zoltan; Buysse, Ann; Johnson, Timothy C; Nugent, Benjamin M; Rogers, Richard B; Sparks, Thomas C; Wang, Nick X; Watson, Gerald B; Zhu, Yuanming

    2016-02-01

    Sap-feeding insect pests constitute a major insect pest complex that includes a range of aphids, whiteflies, planthoppers and other insect species. Sulfoxaflor (Isoclast™ active), a new sulfoximine class insecticide, targets sap-feeding insect pests including those resistant to many other classes of insecticides. A structure activity relationship (SAR) investigation of the sulfoximine insecticides revealed the importance of a 3-pyridyl ring and a methyl substituent on the methylene bridge linking the pyridine and the sulfoximine moiety to achieving strong Myzus persicae activity. A more in depth QSAR investigation of pyridine ring substituents revealed a strong correlation with the calculated logoctanol/water partition coefficient (SlogP). Model development resulted in a highly predictive model for a set of 18 sulfoximines including sulfoxaflor. The model is consistent with and helps explain the highly optimized pyridine substitution pattern for sulfoxaflor.

  15. Methods of InSAR atmosphere correction for volcano activity monitoring

    USGS Publications Warehouse

    Gong, W.; Meyer, F.; Webley, P.W.; Lu, Zhiming

    2011-01-01

    When a Synthetic Aperture Radar (SAR) signal propagates through the atmosphere on its path to and from the sensor, it is inevitably affected by atmospheric effects. In particular, the applicability and accuracy of Interferometric SAR (InSAR) techniques for volcano monitoring is limited by atmospheric path delays. Therefore, atmospheric correction of interferograms is required to improve the performance of InSAR for detecting volcanic activity, especially in order to advance its ability to detect subtle pre-eruptive changes in deformation dynamics. In this paper, we focus on InSAR tropospheric mitigation methods and their performance in volcano deformation monitoring. Our study areas include Okmok volcano and Unimak Island located in the eastern Aleutians, AK. We explore two methods to mitigate atmospheric artifacts, namely the numerical weather model simulation and the atmospheric filtering using Persistent Scatterer processing. We investigate the capability of the proposed methods, and investigate their limitations and advantages when applied to determine volcanic processes. ?? 2011 IEEE.

  16. Use of SAR data to study active volcanoes in Alaska

    USGS Publications Warehouse

    Dean, K.G.; Engle, K.; Lu, Zhiming; Eichelberger, J.; Neal, T.; Doukas, M.

    1996-01-01

    Synthetic Aperture Radar (SAR) data of Westdahl, Veniaminof, and Novarupta volcanoes in the Aleutian Arc of Alaska were analyzed to investigate recent surface volcanic processes. These studies support ongoing monitoring and research by the Alaska Volcano Observatory (AVO) in the North Pacific Ocean Region. Landforms and possible crustal deformation before, during, or after eruptions were detected and analyzed using data from the European Remote Sensing Satellites (ERS), Japanese Earth Resources Satellite (JERS) and the U. S. Seasat platforms. Field observations collected by scientists from the AVO were used to verify the results from the analysis of SAR data.

  17. Use of SAR data to study active volcanoes in Alaska

    USGS Publications Warehouse

    Dean, K.G.; Engle, K.; Lu, Zhiming; Eichelberger, J.; Near, T.; Doukas, M.

    1996-01-01

    Synthetic Aperture Radar (SAR) data of the Westdahl, Veniaminof, and Novarupta volcanoes in the Aleutian Arc of Alaska were analysed to investigate recent surface volcanic processes. These studies support ongoing monitoring and research by the Alaska Volcano Observatory (AVO) in the North Pacific Ocean Region. Landforms and possible crustal deformation before, during, or after eruptions were detected and analysed using data from the European Remote Sensing Satellites (ERS), the Japanese Earth Resources Satellite (JERS) and the US Seasat platforms. Field observations collected by scientists from the AVO were used to verify the results from the analysis of SAR data.

  18. Assessing sinkhole activity in the Ebro Valley mantled evaporite karst using advanced DInSAR

    NASA Astrophysics Data System (ADS)

    Galve, Jorge Pedro; Castañeda, Carmen; Gutiérrez, Francisco; Herrera, Gerardo

    2015-01-01

    Sinkholes in karst areas may cause subsidence damage in transportation infrastructures, demolition of buildings and even the loss of human lives when they occur in a catastrophic way. Differential Interferometry (DInSAR) is a promising technology for detecting and characterizing sinkholes, as well as for reducing the associated risk when combined with other sources of data such as a sinkhole inventory. In this work, the usefulness of InSAR techniques and data for sinkhole risk management has been analyzed through the comparison of three DInSAR-derived velocity maps with a comprehensive sinkhole inventory in the Ebro Valley, NE Spain. The DInSAR maps have contributed to improve the sinkhole inventory in different ways: (1) detection of non-inventoried sinkholes; (2) revision of sinkhole areas previously classified as inactive as active; and (3) refinement of underestimated sinkhole boundaries. The obtained results suggest that DInSAR products are suitable for analyzing active dissolution-induced subsidence. The application of these techniques may help in recognizing and better characterizing previously unknown karst subsidence problems and in preventing personal and property losses. However, the analysis reveals that the available DInSAR maps combined overlook about 70% of the previously mapped active sinkholes mainly due to decorrelation.

  19. Validation of an active transponder for KOMPSAT-5 SAR image calibration

    NASA Astrophysics Data System (ADS)

    Park, Durk Jong; Yeom, Kyung Whan; Ahn, Sang Il; Lim, Hyo Suk

    2014-10-01

    This paper describes the development and validation of a transportable active transponder designed for the image calibration of Korea Multi-Purpose Satellite-5 (KOMPSAT-5) with a synthetic aperture radar (SAR). Ground targets are essential in SAR image calibration. The environment for the deployment of ground targets for SAR image calibration should provide uniformity and minimum interference. The Amazon or deserts are regarded as desirable environments. However, such environments for SAR image calibration are difficult to find in Korea. Thus, it will be advantageous to have an active transponder whose performance will not be severely limited by the absence of such uniform environment. We have therefore developed an active transponder which has an adjustable internal delay and into which the orbit data of an arbitrary satellite can be loaded. The stored obit data with the aid of an internal global positioning system (GPS) receiver and gyroscope enables the active transponder to point to a selected satellite. In addition, a virtual deployment of the active transponder is possible due to its adjustable internal delay. Thus, the developed active transponder can be deployed at any place without environmental constraint. The performance of the developed active transponder is validated using the satellite TerraSAR-X, which is already in operation. The test results show that the active transponder is successfully compliant with the requirements for KOMPSAT-5 image calibration.

  20. Interseismic strain accumulation across an active thrust system: an InSAR case study in the Himalaya

    NASA Astrophysics Data System (ADS)

    Grandin, R.; Doin, M.; Ducret, G.; Bollinger, L.; Pinel-Puysségur, B.; Lasserre, C.; Jolivet, R.

    2011-12-01

    The major active thrust system underlying the Himalayan range produces recurrent large earthquakes, posing a significant threat to the densely populated Indo-Gangetic basin. Measuring the interseismic deformation associated with this fault system could provide important constraints on the geometry of the locked faults that are bound to rupture in future great earthquakes. This has so far been considered out of reach of InSAR techniques, due to decorrelation, prominent topographic features, and unfavourable climatic conditions. However, preliminary tests carried out with the archived ASAR data provided by ESA's ENVISAT satellite since 2002 have shown that recent advances in InSAR processing may now allow geodesists to tackle most of these perturbations. In this context, applying these advanced techniques to the case of the Himalayas is both a challenging and necessary task. We will present the methodology and the first results of an InSAR study of interseismic strain accumulation across the Himalayas. Small-baseline processing of ENVISAT data using a combination of ROI_PAC software, NSBAS processing chain and MulSAR technique yields a sufficient number of coherent interferograms to compute a preliminary average velocity map of interseismic uplift. Time-space variations of stratified tropospheric delay observed in these interferogrames are mitigated using a prediction deduced from outputs of the ECMWF global meteorological reanalysis ERA-Interim. Finally, a correction of DEM errors from the wrapped InSAR data set further improves the coherence of interferograms with a large perpendicular baseline. Comparison of the InSAR LOS velocity maps with microseismic activity detected near the transition zone at the base of the seismogenic portion of the Main Himalayan Thrust is expected to provide constraints on the process of elastic strain accumulation during the interseismic period. This will help in understanding the interaction between the construction of topography

  1. Application of Satellite SAR Imagery in Mapping the Active Layer of Arctic Permafrost

    NASA Technical Reports Server (NTRS)

    Li, Shu-Sun; Romanovsky, V.; Lovick, Joe; Wang, Z.; Peterson, Rorik

    2003-01-01

    A method of mapping the active layer of Arctic permafrost using a combination of conventional synthetic aperture radar (SAR) backscatter and more sophisticated interferometric SAR (INSAR) techniques is proposed. The proposed research is based on the sensitivity of radar backscatter to the freeze and thaw status of the surface soil, and the sensitivity of INSAR techniques to centimeter- to sub-centimeter-level surface differential deformation. The former capability of SAR is investigated for deriving the timing and duration of the thaw period for surface soil of the active layer over permafrost. The latter is investigated for the feasibility of quantitative measurement of frost heaving and thaw settlement of the active layer during the freezing and thawing processes. The resulting knowledge contributes to remote sensing mapping of the active layer dynamics and Arctic land surface hydrology.

  2. Method for the evaluation of structure-activity relationship information associated with coordinated activity cliffs.

    PubMed

    Dimova, Dilyana; Stumpfe, Dagmar; Bajorath, Jürgen

    2014-08-14

    Activity cliffs are generally defined as pairs of active compounds having a large difference in potency. Although this definition of activity cliffs focuses on compound pairs, the vast majority of cliffs are formed in a coordinated manner. This means that multiple highly and weakly potent compounds form series of activity cliffs, which often overlap. In activity cliff networks, coordinated cliffs emerge as disjoint activity cliff clusters. Recently, we have identified all cliff clusters from current bioactive compounds and analyzed their topologies. For structure-activity relationship (SAR) analysis, activity cliff clusters are of high interest, since they contain more SAR information than cliffs that are individually considered. For medicinal chemistry applications, a key question becomes how to best extract SAR information from activity cliff clusters. This represents a challenging problem, given the complexity of many activity cliff configurations. Herein we introduce a generally applicable methodology to organize activity cliff clusters on the basis of structural relationships, prioritize clusters, and systematically extract SAR information from them. PMID:25014781

  3. Identification of natural compounds with antiviral activities against SARS-associated coronavirus.

    PubMed

    Li, Shi-You; Chen, Cong; Zhang, Hai-Qing; Guo, Hai-Yan; Wang, Hui; Wang, Lin; Zhang, Xiang; Hua, Shi-Neng; Yu, Jun; Xiao, Pei-Gen; Li, Rong-Song; Tan, Xuehai

    2005-07-01

    More than 200 Chinese medicinal herb extracts were screened for antiviral activities against Severe Acute Respiratory Syndrome-associated coronavirus (SARS-CoV) using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt (MTS) assay for virus-induced cytopathic effect (CPE). Four of these extracts showed moderate to potent antiviral activities against SARS-CoV with 50% effective concentration (EC50) ranging from 2.4 +/- 0.2 to 88.2 +/- 7.7 microg/ml. Out of the four, Lycoris radiata was most potent. To identify the active component, L. radiata extract was subjected to further fractionation, purification, and CPE/MTS assays. This process led to the identification of a single substance lycorine as an anti-SARS-CoV component with an EC50 value of 15.7 +/- 1.2 nM. This compound has a CC50 value of 14980.0 +/- 912.0 nM in cytotoxicity assay and a selective index (SI) greater than 900. The results suggested that four herbal extracts and the compound lycorine are candidates for the development of new anti-SARS-CoV drugs in the treatment of SARS. PMID:15885816

  4. 76 FR 8847 - Proposed Information Collection (Lenders Staff Appraisal Reviewer (SAR) Application) Activity...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-15

    ...'s will have the authority to review real estate appraisals and to issue notices of values on behalf... AFFAIRS Proposed Information Collection (Lenders Staff Appraisal Reviewer (SAR) Application) Activity... solicits comments information needed to certify a lender's nominee as a VA Staff Appraisal Reviewer....

  5. SARS-CoV proteins decrease levels and activity of human ENaC via activation of distinct PKC isoforms

    PubMed Central

    Ji, Hong-Long; Song, Weifeng; Gao, Zhiqian; Su, Xue-Feng; Nie, Hong-Guang; Jiang, Yi; Peng, Ji-Bin; He, Yu-Xian; Liao, Ying; Zhou, Yong-Jian; Tousson, Albert; Matalon, Sadis

    2009-01-01

    Among the multiple organ disorders caused by the severe acute respiratory syndrome coronavirus (SARS-CoV), acute lung failure following atypical pneumonia is the most serious and often fatal event. We hypothesized that two of the hydrophilic structural coronoviral proteins (S and E) would regulate alveolar fluid clearance by decreasing the cell surface expression and activity of amiloride-sensitive epithelial sodium (Na+) channels (ENaC), the rate-limiting protein in transepithelial Na+ vectorial transport across distal lung epithelial cells. Coexpression of either S or E protein with human α-, β-, and γ-ENaC in Xenopus oocytes led to significant decreases of both amiloride-sensitive Na+ currents and γ-ENaC protein levels at their plasma membranes. S and E proteins decreased the rate of ENaC exocytosis and either had no effect (S) or decreased (E) rates of endocytosis. No direct interactions among SARS-CoV E protein with either α- or γ-ENaC were indentified. Instead, the downregulation of ENaC activity by SARS proteins was partially or completely restored by administration of inhibitors of PKCα/β1 and PKCζ. Consistent with the whole cell data, expression of S and E proteins decreased ENaC single-channel activity in oocytes, and these effects were partially abrogated by PKCα/β1 inhibitors. Finally, transfection of human airway epithelial (H441) cells with SARS E protein decreased whole cell amiloride-sensitive currents. These findings indicate that lung edema in SARS infection may be due at least in part to activation of PKC by SARS proteins, leading to decreasing levels and activity of ENaC at the apical surfaces of lung epithelial cells. PMID:19112100

  6. Different host cell proteases activate the SARS-coronavirus spike-protein for cell-cell and virus-cell fusion

    SciTech Connect

    Simmons, Graham; Bertram, Stephanie; Glowacka, Ilona; Steffen, Imke; Chaipan, Chawaree; Agudelo, Juliet; Lu Kai; Rennekamp, Andrew J.; Hofmann, Heike; Bates, Paul; Poehlmann, Stefan

    2011-05-10

    Severe acute respiratory syndrome coronavirus (SARS-CoV) poses a considerable threat to human health. Activation of the viral spike (S)-protein by host cell proteases is essential for viral infectivity. However, the cleavage sites in SARS-S and the protease(s) activating SARS-S are incompletely defined. We found that R667 was dispensable for SARS-S-driven virus-cell fusion and for SARS-S-activation by trypsin and cathepsin L in a virus-virus fusion assay. Mutation T760R, which optimizes the minimal furin consensus motif 758-RXXR-762, and furin overexpression augmented SARS-S activity, but did not result in detectable SARS-S cleavage. Finally, SARS-S-driven cell-cell fusion was independent of cathepsin L, a protease essential for virus-cell fusion. Instead, a so far unknown leupeptin-sensitive host cell protease activated cellular SARS-S for fusion with target cells expressing high levels of ACE2. Thus, different host cell proteases activate SARS-S for virus-cell and cell-cell fusion and SARS-S cleavage at R667 and 758-RXXR-762 can be dispensable for SARS-S activation.

  7. A Survey of Landslide Activity in the Columbia River Gorge from InSAR

    NASA Astrophysics Data System (ADS)

    Tong, X.; Schmidt, D. A.

    2015-12-01

    The Columbia River Gorge contains several large landslide complexes that have exhibited historical movement, both catastrophic and slow moving. Monitoring the kinematics of active movement helps to characterize the ongoing natural hazard. In this study, we document the status of several large landslide complexes along the Columbia River Gorge. We use synthetic aperture radar (SAR) data from multiple satellites (ERS, ENVISAT and ALOS) to reveal the spatial-temporal movement of slow-moving landslides over two decades, 1992-2011. To increase the spatial extent of the signal we developed a new InSAR time-series method based on pixel coherence and derived the time series of the landslides. We also investigate the ability of Persistent Scatterer InSAR to better illuminate active movement. While many historical landslide complexes show minimal or non-existent movement, we measure significant creep on the Redbluff landslide, which is part of the Cascade Landslide Complex near the Bonneville Dam. The InSAR time-series data reveal approximately 25 cm of line-of-sight movement from 5 years of ALOS observations, which translates into greater than 60 cm of downslope movement. The Redbluff landslide is seasonally activated, with accelerated movement observed during the early winter of each year. However, the amplitude of the seasonal signal is variable from year-to-year. To assess the triggering mechanisms, we compared the deformation time series data with local precipitation data. The deformation correlates well with precipitation, implying the slow movement is controlled by rainfall that infiltrates to the base of the slide. A preliminary comparison with the bare earth 2m-resolution digital elevation model from LiDAR reveals that the overall deformation pattern and the active perimeter is highly correlated with the morphology of the landslide.

  8. Development of structure-activity relationship for metal oxide nanoparticles

    NASA Astrophysics Data System (ADS)

    Liu, Rong; Zhang, Hai Yuan; Ji, Zhao Xia; Rallo, Robert; Xia, Tian; Chang, Chong Hyun; Nel, Andre; Cohen, Yoram

    2013-05-01

    Nanomaterial structure-activity relationships (nano-SARs) for metal oxide nanoparticles (NPs) toxicity were investigated using metrics based on dose-response analysis and consensus self-organizing map clustering. The NP cellular toxicity dataset included toxicity profiles consisting of seven different assays for human bronchial epithelial (BEAS-2B) and murine myeloid (RAW 264.7) cells, over a concentration range of 0.39-100 mg L-1 and exposure time up to 24 h, for twenty-four different metal oxide NPs. Various nano-SAR building models were evaluated, based on an initial pool of thirty NP descriptors. The conduction band energy and ionic index (often correlated with the hydration enthalpy) were identified as suitable NP descriptors that are consistent with suggested toxicity mechanisms for metal oxide NPs and metal ions. The best performing nano-SAR with the above two descriptors, built with support vector machine (SVM) model and of validated robustness, had a balanced classification accuracy of ~94%. An applicability domain for the present data was established with a reasonable confidence level of 80%. Given the potential role of nano-SARs in decision making, regarding the environmental impact of NPs, the class probabilities provided by the SVM nano-SAR enabled the construction of decision boundaries with respect to toxicity classification under different acceptance levels of false negative relative to false positive predictions.Nanomaterial structure-activity relationships (nano-SARs) for metal oxide nanoparticles (NPs) toxicity were investigated using metrics based on dose-response analysis and consensus self-organizing map clustering. The NP cellular toxicity dataset included toxicity profiles consisting of seven different assays for human bronchial epithelial (BEAS-2B) and murine myeloid (RAW 264.7) cells, over a concentration range of 0.39-100 mg L-1 and exposure time up to 24 h, for twenty-four different metal oxide NPs. Various nano-SAR building models were

  9. Hit Expansion from Screening Data Based upon Conditional Probabilities of Activity Derived from SAR Matrices.

    PubMed

    Gupta-Ostermann, Disha; Balfer, Jenny; Bajorath, Jürgen

    2015-02-01

    A new methodology for activity prediction of compounds from SAR matrices is introduced that is based upon conditional probabilities of activity. The approach has low computational complexity, is primarily designed for hit expansion from biological screening data, and accurately predicts both active and inactive compounds. Its performance is comparable to state-of-the-art machine learning methods such as support vector machines or Bayesian classification. Matrix-based activity prediction of virtual compounds further extends the spectrum of computational methods for compound design.

  10. Hit Expansion from Screening Data Based upon Conditional Probabilities of Activity Derived from SAR Matrices.

    PubMed

    Gupta-Ostermann, Disha; Balfer, Jenny; Bajorath, Jürgen

    2015-02-01

    A new methodology for activity prediction of compounds from SAR matrices is introduced that is based upon conditional probabilities of activity. The approach has low computational complexity, is primarily designed for hit expansion from biological screening data, and accurately predicts both active and inactive compounds. Its performance is comparable to state-of-the-art machine learning methods such as support vector machines or Bayesian classification. Matrix-based activity prediction of virtual compounds further extends the spectrum of computational methods for compound design. PMID:27490036

  11. Mutation of Asn28 Disrupts the Dimerization and Enzymatic Activity of SARS 3CL

    SciTech Connect

    Barrila, J.; Gabelli, S; Bacha, U; Amzel, M; Freire, E

    2010-01-01

    Coronaviruses are responsible for a significant proportion of annual respiratory and enteric infections in humans and other mammals. The most prominent of these viruses is the severe acute respiratory syndrome coronavirus (SARS-CoV) which causes acute respiratory and gastrointestinal infection in humans. The coronavirus main protease, 3CL{sup pro}, is a key target for broad-spectrum antiviral development because of its critical role in viral maturation and high degree of structural conservation among coronaviruses. Dimerization is an indispensable requirement for the function of SARS 3CL{sup pro} and is regulated through mechanisms involving both direct and long-range interactions in the enzyme. While many of the binding interactions at the dimerization interface have been extensively studied, those that are important for long-range control are not well-understood. Characterization of these dimerization mechanisms is important for the structure-based design of new treatments targeting coronavirus-based infections. Here we report that Asn28, a residue 11 {angstrom} from the closest residue in the opposing monomer, is essential for the enzymatic activity and dimerization of SARS 3CLpro. Mutation of this residue to alanine almost completely inactivates the enzyme and results in a 19.2-fold decrease in the dimerization K{sub d}. The crystallographic structure of the N28A mutant determined at 2.35 {angstrom} resolution reveals the critical role of Asn28 in maintaining the structural integrity of the active site and in orienting key residues involved in binding at the dimer interface and substrate catalysis. These findings provide deeper insight into complex mechanisms regulating the activity and dimerization of SARS 3CL{sup pro}.

  12. The variety of subaerial active salt deformations in the Kuqa fold-thrust belt (China) constrained by InSAR

    NASA Astrophysics Data System (ADS)

    Colón, Cindy; Webb, A. Alexander G.; Lasserre, Cécile; Doin, Marie-Pierre; Renard, François; Lohman, Rowena; Li, Jianghai; Baudoin, Patrick F.

    2016-09-01

    Surface salt bodies in the western Kuqa fold-thrust belt of northwestern China allow study of subaerial salt kinematics and its possible correlations with weather variations. Ephemeral subaerial salt exposure during the evolution of a salt structure can greatly impact the subsequent development and deformation of its tectonic setting. Here, we present a quantitative time-lapse survey of surface salt deformation measured from interferometric synthetic aperture radar (InSAR) using Envisat radar imagery acquired between 2003 and 2010. Time series analysis and inspection of individual interferograms confirm that the majority of the salt bodies in western Kuqa are active, with significant InSAR observable displacements at 3 of 4 structures studied in the region. Subaerial salt motion toward and away from the satellite at rates up to 5 mm/yr with respect to local references. Rainfall measurements from the Tropical Rainfall Measuring Mission (TRMM) and temperature from a local weather station are used to test the relationship between seasonality and surface salt motion. We observe decoupling between surface salt motion and seasonality and interpret these observations to indicate that regional and local structural regimes exert primary control on surface salt displacement rates.

  13. Synthesis and SAR study of modulators inhibiting tRXRα-dependent AKT activation

    PubMed Central

    Wang, Zhi-Gang; Chen, Liqun; Chen, Jiebo; Zheng, Jian-Feng; Gao, Weiwei; Zeng, Zhiping; Zhou, Hu; Zhang, Xiao-kun; Huang, Pei-Qiang; Su, Ying

    2013-01-01

    RXRα represents an intriguing and unique target for pharmacologic interventions. We recently showed that Sulindac and a designed analog could bind to RXRα and modulate its biological activity, including inhibition of the interaction of an N-terminally truncated RXRα (tRXRα) with the p85α regulatory subunit of phosphatidylinositol-3-OH kinase (PI3K). Here we report the synthesis, testing and SAR of a series of novel analogs of Sulindac as potential modulators for inhibiting tRXRα-dependent AKT activation. A new compound 30 was identified to have improved biological activity. PMID:23434637

  14. Railway deformation detected by DInSAR over active sinkholes in the Ebro Valley evaporite karst, Spain

    NASA Astrophysics Data System (ADS)

    Galve, J. P.; Castañeda, C.; Gutiérrez, F.

    2015-11-01

    Subsidence was measured for the first time on railway tracks in the central sector of Ebro Valley (NE Spain) using Differential Synthetic Aperture Radar Interferometry (DInSAR) techniques. This area is affected by evaporite karst and the analysed railway corridors traverse active sinkholes that produce deformations in these infrastructures. One of the railway tracks affected by slight settlements is the Madrid-Barcelona high-speed line, a form of transport infrastructure highly vulnerable to ground deformation processes. Our analysis based on DInSAR measurements and geomorphological surveys indicates that this line shows dissolution-induced subsidence and compaction of anthropogenic deposits (infills and embankments). Significant sinkhole-related subsidence was also measured by DInSAR techniques on the Castejón-Zaragoza conventional railway line. This study demonstrates that DInSAR velocity maps, coupled with detailed geomorphological surveys, may help in the identification of the railway track sections that are affected by active subsidence.

  15. Synthesis and antibacterial activity of sulfonamides. SAR and DFT studies

    NASA Astrophysics Data System (ADS)

    Boufas, Wahida; Dupont, Nathalie; Berredjem, Malika; Berrezag, Kamel; Becheker, Imène; Berredjem, Hajira; Aouf, Nour-Eddine

    2014-09-01

    A series of substituted sulfonamide derivatives were synthesized from chlorosulfonyl isocyanate (CSI) in tree steps (carbamoylation, sulfamoylation and deprotection). Antibacterial activity in vitro of some newly formed compounds investigated against clinical strains Gram-positive and Gram-negative: Escherichia coli and Staphylococcus aureus applying the method of dilution and minimal inhibition concentration (MIC) methods. These compounds have significant bacteriostatic activity with totalities of bacterial strains used. DFT calculations with B3LYP/6-31G(d) level have been used to analyze the electronic and geometric characteristics deduced for the stable structure of three compounds presenting conjugation between a nitrogen atom N through its lone pair and an aromatic ring next to it. The principal quantum chemical descriptors have been correlated with the antibacterial activity.

  16. Interseismic deformations along Ecuador active fault systems: Contribution of space-borne SAR Interferometry

    NASA Astrophysics Data System (ADS)

    Champenois, J.; Audin, L.; Baize, S.; Nocquet, J.; Alvarado, A.

    2013-05-01

    Located in the Northern Andes along the active subduction zone of the Nazca plate beneath the South American continent, Ecuador is highly exposed to seismic hazard. Up to now, numerous multidisciplinary studies for the last ten years focused on the seismicity related to the subduction, whereas few investigations concentrated on the crustal seismicity in the upper plate (through few strong events like the 1797 Riobamba earthquake, ML 8.3, 12.000 deaths). The faults that are responsible of these earthquakes are poorly known in term of slip rate and in some cases are even not identified yet. To address this issue and compare the interseismic data to the geomorphological long term signature of active faulting we propose to use multi-temporal Synthetic Aperture Radar Interferometry (InSAR) methods.Using these cost-effective techniques, we are able to investigate surface interseismic deformation with an unprecedented spatial density of measurements (highly superior to Global Positioning System network density). This study presents preliminary results of tectonic surface deformation using ERS (1993-2000) and Envisat (2002-2010) SAR data in the Inter Andean Valley and along the eastern border of the North Andean Block, where is accommodated the relative displacement between the North Andean Block and South America plate (~ 8 mm/yr). We generated average velocity maps and consistent time-series of displacements with values measured along the line of sight of the radar. Resulting maps of ground displacements are calibrated by GPS data in order to provide a homogeneous database. These preliminary results show large scale deformation localized on some major fault systems in the Inter Andean Valley (from Quito to north of Cuenca) and allow an updating of the active faults map. Moreover, these InSAR results permit detecting and quantifying ground deformation due to volcanic unrest.

  17. Induced resistance in tomato by SAR activators during predisposing salinity stress

    PubMed Central

    Pye, Matthew F.; Hakuno, Fumiaki; MacDonald, James D.; Bostock, Richard M.

    2013-01-01

    Plant activators are chemicals that induce disease resistance. The phytohormone salicylic acid (SA) is a crucial signal for systemic acquired resistance (SAR), and SA-mediated resistance is a target of several commercial plant activators, including Actigard (1,2,3-benzothiadiazole-7-thiocarboxylic acid-S-methyl-ester, BTH) and Tiadinil [N-(3-chloro-4-methylphenyl)-4-methyl-1,2,3-thiadiazole-5-carboxamide, TDL]. BTH and TDL were examined for their impact on abscisic acid (ABA)-mediated, salt-induced disease predisposition in tomato seedlings. A brief episode of salt stress to roots significantly increased the severity of disease caused by Pseudomonas syringae pv. tomato (Pst) and Phytophthora capsici relative to non-stressed plants. Root treatment with TDL induced resistance to Pst in leaves and provided protection in both non-stressed and salt-stressed seedlings in wild-type and highly susceptible NahG plants. Non-stressed and salt-stressed ABA-deficient sitiens mutants were highly resistant to Pst. Neither TDL nor BTH induced resistance to root infection by Phytophthora capsici, nor did they moderate the salt-induced increment in disease severity. Root treatment with these plant activators increased the levels of ABA in roots and shoots similar to levels observed in salt-stressed plants. The results indicate that SAR activators can protect tomato plants from bacterial speck disease under predisposing salt stress, and suggest that some SA-mediated defense responses function sufficiently in plants with elevated levels of ABA. PMID:23653630

  18. (Q)SAR: A Tool for the Toxicologist.

    PubMed

    Steinbach, Thomas; Gad-McDonald, Samantha; Kruhlak, Naomi; Powley, Mark; Greene, Nigel

    2015-01-01

    A continuing education (CE) course at the 2014 American College of Toxicology annual meeting covered the topic of (Quantitative) Structure-Activity Relationships [(Q)SAR]. The (Q)SAR methodologies use predictive computer modeling based on predefined rules to describe the relationship between chemical structure and a chemical's associated biological activity or statistical tools to find correlations between biologic activity and the molecular structure or properties of a compound. The (Q)SAR has applications in risk assessment, drug discovery, and regulatory decision making. Pressure within industry to reduce the cost of drug development and societal pressure for government regulatory agencies to produce more accurate and timely risk assessment of drugs and chemicals have necessitated the use of (Q)SAR. Producing a high-quality (Q)SAR model depends on many factors including the choice of statistical methods and descriptors, but first and foremost the quality of the data input into the model. Understanding how a (Q)SAR model is developed and applied is critical to the successful use of such a tool. The CE session covered the basic principles of (Q)SAR, practical applications of these computational models in toxicology, how regulatory agencies use and interpret (Q)SAR models, and potential pitfalls of using them.

  19. Faults Activities And Crustal Deformation near Hualien City, eastern Taiwan Analysed By Persistent Scatterer InSAR

    NASA Astrophysics Data System (ADS)

    Lu, C.; Lin, M.; Yen, J.; Chang, C.

    2008-12-01

    Hualien is located in eastern part of Taiwan, and is the collision boundary in the northern of Huatung Longitudinal Valley between the Philippine Sea tectonic plate and Eurasian tectonic plate(Biq, 1981; Barrier and Angelier, 1986). There are several active faults, such as Milun fault, Beipu fault and Minyi fault, pass through the Hualien city, and create many crustal deformation. According to previous researches (Hsu, 1956; Lin, 1962; Yu, 1997) we know Milun fault is a thrust and left lateral fault, and the fault plane incline to east. Minyi fault also is a left lateral and a slight reverse fault, but it's fault plane incline to west. (Chang, 1994; Yu, 1997) We applied the Persistent Scatterer Interferometric Synthetic Aperture Radar (PSInSAR, Hooper, 2007) to observe temporally-variable processes of Hualien city between 2004 to 2008. At the same time, precise leveling and GPS data were taken for the auxiliary data to verify the deformation rate and pattern in this area. In the Hualien city area, our observation showed that the active faults separate this area into several distinct blocks. Most of the blocks moved slowly, but the hanging wall of the Milun fault decreases 5- 8mm in line of sight (LOS) direction between 15 May 2004 to 24 Feb 2007, then increases 3-6mm in LOS between 1 Dec 2007 to 5 Jan 2008. The deformation reversed its direction in 2007. The western surface of Hualien City displays continuous deformation about 1.5-2mm/yr , which spread along the Beipu fault. Our preliminary investigation indicated that between late 2004 and middle 2005 there had been an abrupt increase in seismicity, which coincided with PSInSAR observation of a large displacement. The distribution of shallow source earthquakes correlate with the area with large deformation. Our following works include continuing observation of the Hualien City, and decipher the relationship between earthquakes and surface deformation, and model the fault action in Hualien City with time series.

  20. Automated Structure-Activity Relationship Mining: Connecting Chemical Structure to Biological Profiles.

    PubMed

    Wawer, Mathias J; Jaramillo, David E; Dančík, Vlado; Fass, Daniel M; Haggarty, Stephen J; Shamji, Alykhan F; Wagner, Bridget K; Schreiber, Stuart L; Clemons, Paul A

    2014-06-01

    Understanding the structure-activity relationships (SARs) of small molecules is important for developing probes and novel therapeutic agents in chemical biology and drug discovery. Increasingly, multiplexed small-molecule profiling assays allow simultaneous measurement of many biological response parameters for the same compound (e.g., expression levels for many genes or binding constants against many proteins). Although such methods promise to capture SARs with high granularity, few computational methods are available to support SAR analyses of high-dimensional compound activity profiles. Many of these methods are not generally applicable or reduce the activity space to scalar summary statistics before establishing SARs. In this article, we present a versatile computational method that automatically extracts interpretable SAR rules from high-dimensional profiling data. The rules connect chemical structural features of compounds to patterns in their biological activity profiles. We applied our method to data from novel cell-based gene-expression and imaging assays collected on more than 30,000 small molecules. Based on the rules identified for this data set, we prioritized groups of compounds for further study, including a novel set of putative histone deacetylase inhibitors.

  1. Active anthropogenic and surface salt deformation measured by InSAR, northwestern China

    NASA Astrophysics Data System (ADS)

    Colon, C.; Webb, A. G.; Lasserre, C.; Doin, M. P.

    2014-12-01

    Despite the global occurrence of salt, very few salt bodies outcrop and are presently preserved at the surface. Because of this much of our knowledge on salt structures is sourced from subsurface imaging and modeling and less from field based studies. Using interferometry of synthetic aperture radar (InSAR) we monitor surface displacements across four surface salt outcrops in the western margin of the Kuqa fold-thrust belt of Xinjiang Province, China. An InSAR time series was constructed from 40 Envisat ASAR C-band images between June 2003 and October 2010. Interferometric processing was completed using the New Small Baseline Algorithm Subset (NSBAS). These poorly studied salt structures provide a fresh opportunity to study how salt behaves on the surface. The salt bodies outcrop along an active intracontinental thrust system between the Tian Shan and Tarim basin to the south. The four surface namakiers (salt glaciers) were analyzed in this study include: the Quele, Awate, Bozidun, and an unnamed structure referred to as the Western namakier. The ~35 km long Quele namakier is a line-sourced structure advancing along the Quele salt thrust. The other three namakiers range between ~1-3 km long and are point-sourced structures. The namakiers studied display non-steady deformation with rates of displacement varying between uplifts of up to +4 cm/yr and subsidence rates of -4 cm/yr. Additionally, the Kuqa fold-thrust belt hosts a number of hydrocarbon fields and InSAR measurements detect significant anthropogenic deformation associated with hydrocarbon extraction and fluid injection.

  2. Benzothiophene inhibitors of MK2. Part 1: structure-activity relationships, assessments of selectivity and cellular potency.

    PubMed

    Anderson, David R; Meyers, Marvin J; Kurumbail, Ravi G; Caspers, Nicole; Poda, Gennadiy I; Long, Scott A; Pierce, Betsy S; Mahoney, Matthew W; Mourey, Robert J

    2009-08-15

    Identification of potent benzothiophene inhibitors of mitogen activated protein kinase-activated protein kinase 2 (MK2), structure-activity relationship (SAR) studies, selectivity assessments against CDK2, cellular potency and mechanism of action are presented. Crystallographic data provide a rationale for the observed MK2 potency as well as selectivity over CDK2 for this class of inhibitors.

  3. In Vivo Structure-Activity Relationship Studies Support Allosteric Targeting of a Dual Specificity Phosphatase

    PubMed Central

    Korotchenko, Vasiliy N.; Saydmohammed, Manush; Vollmer, Laura L.; Bakan, Ahmet; Sheetz, Kyle; Debiec, Karl T.; Greene, Kristina A.; Agliori, Christine S.; Bahar, Ivet; Day, Billy W.; Vogt, Andreas; Tsang, Michael

    2014-01-01

    Dual specificity phosphatase 6 (DUSP6) functions as a feedback attenuator of Fibroblast Growth Factor signaling during development. In vitro high throughput chemical screening attempts to discover DUSP6 inhibitors have yielded limited success. Yet, in vivo whole organism screens using zebrafish identified 1 (BCI) as an allosteric inhibitor of DUSP6. Here we designed and synthesized a panel of analogs to define structure-activity relationship (SAR) of DUSP6 inhibition. In vivo, high-content analysis in transgenic zebrafish coupled with cell-based chemical complementation assays identified structural features of the 1 pharmacophore that were essential for biological activity. In vitro assays of DUSP hyperactivation corroborated the results from in vivo and cellular SAR. The results reinforce the notion that DUSPs are druggable through allosteric mechanisms, and illustrate the utility of zebrafish as a model organism for in vivo SAR analyses. PMID:24909879

  4. Structure-Activity Relationship of Azaindole-Based Glucokinase Activators.

    PubMed

    Paczal, Attila; Bálint, Balázs; Wéber, Csaba; Szabó, Zoltán B; Ondi, Levente; Theret, Isabelle; De Ceuninck, Frédéric; Bernard, Catherine; Ktorza, Alain; Perron-Sierra, Francoise; Kotschy, András

    2016-01-28

    7-Azaindole has been identified as a novel bidentate anchor point for allosteric glucokinase activators. A systematic investigation around three principal parts of the new small molecule glucokinase activators led to a robust SAR in agreement with structural data that also helped to assess the conformational flexibility of the allosteric activation site. The increase in glucose uptake resulting from glucokinase activation in hepatocytes in vitro translated into the efficient lowering of glucose levels in vivo with the best compounds. PMID:26685731

  5. Adaptive InSAR combined with surveying techniques for an improved characterisation of active landslides (El Portalet)

    NASA Astrophysics Data System (ADS)

    Duro, Javier; Albiol, David; Sánchez, Francisco; Herrera, Gerardo; García Davalillo, Juan Carlos; Fernandez Merodo, Jose Antonio; Allasia, Paolo; Lollino, Piernicola; Manconi, Andrea

    2014-05-01

    InSAR and the Persistent Scatterer Interferometry (PSI) are well established techniques for monitoring urban and rural areas. Besides the large number of available SAR data in the past, the current and forthcoming space-borne SAR sensors offer the possibility of selecting the optimal acquisition configuration (wavelength, resolution, incidence angle, etc.) for each application. However, optimal data takes are not always possible and/or the processing area is difficult to analyse under an InSAR point of view. In such situations, additional and adaptive InSAR developments combined with other surveying techniques provide consistent solutions that meet the requirements of different application cases This work presents an advanced InSAR processing adapted for an active slow deformation landslide in a mountainous area. The presentation will show the benefits of applying advanced and adaptive filtering strategies for improving the InSAR quality in highly decorrelated environments. The availability of Artificial Corner Reflectors over the area of interest enables to tune the filtering procedure and thus maximize the detection and exploitation of natural targets (bare soil, roads, rocks) as measurement points while preserving the phase characteristics over individual and punctual targets (building corners, poles). The new results will be evaluated in terms of final density and quality of measurement points that can be retrieved. The results will show that a very high density of measurements improves the detection of the deformation gradients and its perimeters resulting in a more accurate characterization of the landslide area. The area of study is El Portalet, an active slow deformation landslide area in Central Spanish Pyrenees. During many years the slope of interest has been monitored with several surveying techniques like DGPS, extensometers, inclinometers, GB-SAR and InSAR jointly with an extensive geological interpretation. Currently, in the frame of the FP7 Project

  6. Structure-activity relationships derived by machine learning: the use of atoms and their bond connectivities to predict mutagenicity by inductive logic programming.

    PubMed Central

    King, R D; Muggleton, S H; Srinivasan, A; Sternberg, M J

    1996-01-01

    We present a general approach to forming structure-activity relationships (SARs). This approach is based on representing chemical structure by atoms and their bond connectivities in combination with the inductive logic programming (ILP) algorithm PROGOL. Existing SAR methods describe chemical structure by using attributes which are general properties of an object. It is not possible to map chemical structure directly to attribute-based descriptions, as such descriptions have no internal organization. A more natural and general way to describe chemical structure is to use a relational description, where the internal construction of the description maps that of the object described. Our atom and bond connectivities representation is a relational description. ILP algorithms can form SARs with relational descriptions. We have tested the relational approach by investigating the SARs of 230 aromatic and heteroaromatic nitro compounds. These compounds had been split previously into two subsets, 188 compounds that were amenable to regression and 42 that were not. For the 188 compounds, a SAR was found that was as accurate as the best statistical or neural network-generated SARs. The PROGOL SAR has the advantages that it did not need the use of any indicator variables handcrafted by an expert, and the generated rules were easily comprehensible. For the 42 compounds, PROGOL formed a SAR that was significantly (P < 0.025) more accurate than linear regression, quadratic regression, and back-propagation. This SAR is based on an automatically generated structural alert for mutagenicity. PMID:8552655

  7. Heteroannelated and 7-deoxygenated goniofufurone mimics with antitumour activity: design, synthesis and preliminary SAR studies.

    PubMed

    Popsavin, Velimir; Francuz, Jovana; Srećo Zelenović, Bojana; Benedeković, Goran; Popsavin, Mirjana; Kojić, Vesna; Bogdanović, Gordana

    2013-10-15

    Cytotoxic (+)-goniofufurone mimic such as benzoxepane 2 was preferentially formed after the treatment of 7-O-benzoyl-5-O-benzyl (+)-goniofufurone derivative 6 with titanium(IV) fluoride. However, the corresponding 7-epimer 5 (derivative of 7-epi-goniofufurone) under the similar reaction conditions gave mainly 7-deoxy derivative 7 as a result of an unexpected 1,5-hydride shift. Extension of this methodology to the enantiomer ent-6 provided cytotoxic (-)-goniofufurone mimics ent-2 and ent-7. Synthesized compounds showed diverse growth inhibitory effects against selected tumour cell lines, but were devoid of any significant toxicity towards the normal foetal lung fibroblasts (MRC-5). A SAR study reveals the structural features of these lactones that are beneficial for their antiproliferative activity, such as presence of an additional oxepane ring, the absolute stereochemistry and the presence of a deoxy function at the C-7 position. PMID:24021462

  8. Railway deformation detected by DInSAR over active sinkholes in the Ebro Valley evaporite karst, Spain

    NASA Astrophysics Data System (ADS)

    Galve, J. P.; Castañeda, C.; Gutiérrez, F.

    2015-06-01

    Previously not measured subsidence on railway tracks was detected using DInSAR displacement maps produced for the central sector of Ebro Valley (NE Spain). This area is affected by evaporite karst and the analyzed railway corridors traverse active sinkholes that produce deformations in these infrastructures. One of the railway tracks affected by slight settlements corresponds to the Madrid-Barcelona high-speed line, a transport infrastructure highly vulnerable to ground deformation processes. Our analysis based on DInSAR measurements and geomorphological surveys indicate that this line show dissolution-induced subsidence and compaction of anthropogenic deposits (infills and embankments). By using DInSAR techniques, it was also measured the significant subsidence related to the activity of sinkholes in the Castejón-Zaragoza conventional railway line. Thus, this study demonstrate that DInSAR velocity maps coupled with detailed geomorphological surveys may help in the identification of the sectors of railway tracks that may compromise the safety of travellers.

  9. Structure activity relationship, cytotoxicity and evaluation of antioxidant activity of curcumin derivatives.

    PubMed

    Sahu, Pramod K; Sahu, Praveen K; Sahu, Puran L; Agarwal, Dau D

    2016-02-15

    Series of curcumin derivatives/analogues were designed and efficient method for synthesis thereof is described. All the synthesized compounds have been screened for their cytotoxicity and evaluated their antioxidant activity. Cytotoxicity effect has been evaluated against three cell lines Hep-G2, HCT-116 and QG-56 by MTT assay method. Structure activity relationship has revealed that particularly, compound 3c, (IC50 value 6.25 μM) has shown better cytotoxicity effect against three cell lines. According to results of SAR study, it was found that 4H-pyrimido[2,1-b]benzothiazole derivatives (2e and 2f), pyrazoles (3a, 3b, 3c and 3d) benzylidenes (4d) exhibited better antioxidant activity than curcumin. A correlation of structure and activities relationship of these compounds with respect to drug score profiles and other physico-chemical properties of drugs are described and verified experimentally. PMID:26810315

  10. The First Structure–Activity Relationship Studies for Designer Receptors Exclusively Activated by Designer Drugs

    PubMed Central

    2016-01-01

    Over the past decade, two independent technologies have emerged and been widely adopted by the neuroscience community for remotely controlling neuronal activity: optogenetics which utilize engineered channelrhodopsin and other opsins, and chemogenetics which utilize engineered G protein-coupled receptors (Designer Receptors Exclusively Activated by Designer Drugs (DREADDs)) and other orthologous ligand–receptor pairs. Using directed molecular evolution, two types of DREADDs derived from human muscarinic acetylcholine receptors have been developed: hM3Dq which activates neuronal firing, and hM4Di which inhibits neuronal firing. Importantly, these DREADDs were not activated by the native ligand acetylcholine (ACh), but selectively activated by clozapine N-oxide (CNO), a pharmacologically inert ligand. CNO has been used extensively in rodent models to activate DREADDs, and although CNO is not subject to significant metabolic transformation in mice, a small fraction of CNO is apparently metabolized to clozapine in humans and guinea pigs, lessening the translational potential of DREADDs. To effectively translate the DREADD technology, the next generation of DREADD agonists are needed and a thorough understanding of structure–activity relationships (SARs) of DREADDs is required for developing such ligands. We therefore conducted the first SAR studies of hM3Dq. We explored multiple regions of the scaffold represented by CNO, identified interesting SAR trends, and discovered several compounds that are very potent hM3Dq agonists but do not activate the native human M3 receptor (hM3). We also discovered that the approved drug perlapine is a novel hM3Dq agonist with >10 000-fold selectivity for hM3Dq over hM3. PMID:25587888

  11. AI AND SAR APPROACHES FOR PREDICTING CHEMICAL CARCINOGENICITY: SURVEY AND STATUS REPORT

    EPA Science Inventory

    A wide variety of artificial intelligence (AI) and structure-activity relationship (SAR approaches have been applied to tackling the general problem of predicting rodent chemical carcinogenicity. Given the diversity of chemical structures and mechanisms relative to this endpoin...

  12. TOWARDS REFINED USE OF TOXICITY DATA IN STATISTICALLY BASED SAR MODELS FOR DEVELOPMENTAL TOXICITY.

    EPA Science Inventory

    In 2003, an International Life Sciences Institute (ILSI) Working Group examined the potential of statistically based structure-activity relationship (SAR) models for use in screening environmental contaminants for possible developmental toxicants.

  13. Structure-Activity Relationships in Nitro-Aromatic Compounds

    NASA Astrophysics Data System (ADS)

    Vogt, R. A.; Rahman, S.; Crespo-Hernández, C. E.

    Many nitro-aromatic compounds show mutagenic and carcinogenic properties, posing a potential human health risk. Despite this potential health hazard, nitro-aromatic compounds continue to be emitted into ambient air from municipal incinerators, motor vehicles, and industrial power plants. As a result, understanding the structural and electronic factors that influence mutagenicity in nitro-aromatic compounds has been a long standing objective. Progress toward this goal has accelerated over the years, in large part due to the synergistic efforts among toxicology, computational chemistry, and statistical modeling of toxicological data. The concerted influence of several structural and electronic factors in nitro-aromatic compounds makes the development of structure-activity relationships (SARs) a paramount challenge. Mathematical models that include a regression analysis show promise in predicting the mutagenic activity of nitro-aromatic compounds as well as in prioritizing compounds for which experimental data should be pursued. A major challenge of the structure-activity models developed thus far is their failure to apply beyond a subset of nitro-aromatic compounds. Most quantitative structure-activity relationship papers point to statistics as the most important confirmation of the validity of a model. However, the experimental evidence shows the importance of the chemical knowledge in the process of generating models with reasonable applicability. This chapter will concisely summarize the structural and electronic factors that influence the mutagenicity in nitro-aromatic compounds and the recent efforts to use quantitative structure-activity relationships to predict those physicochemical properties.

  14. InSAR measurements around active faults: creeping Philippine Fault and un-creeping Alpine Fault

    NASA Astrophysics Data System (ADS)

    Fukushima, Y.

    2013-12-01

    Recently, interferometric synthetic aperture radar (InSAR) time-series analyses have been frequently applied to measure the time-series of small and quasi-steady displacements in wide areas. Large efforts in the methodological developments have been made to pursue higher temporal and spatial resolutions by using frequently acquired SAR images and detecting more pixels that exhibit phase stability. While such a high resolution is indispensable for tracking displacements of man-made and other small-scale structures, it is not necessarily needed and can be unnecessarily computer-intensive for measuring the crustal deformation associated with active faults and volcanic activities. I apply a simple and efficient method to measure the deformation around the Alpine Fault in the South Island of New Zealand, and the Philippine Fault in the Leyte Island. I use a small-baseline subset (SBAS) analysis approach (Berardino, et al., 2002). Generally, the more we average the pixel values, the more coherent the signals are. Considering that, for the deformation around active faults, the spatial resolution can be as coarse as a few hundred meters, we can severely 'multi-look' the interferograms. The two applied cases in this study benefited from this approach; I could obtain the mean velocity maps on practically the entire area without discarding decorrelated areas. The signals could have been only partially obtained by standard persistent scatterer or single-look small-baseline approaches that are much more computer-intensive. In order to further increase the signal detection capability, it is sometimes effective to introduce a processing algorithm adapted to the signal of interest. In an InSAR time-series processing, one usually needs to set the reference point because interferograms are all relative measurements. It is difficult, however, to fix the reference point when one aims to measure long-wavelength deformation signals that span the whole analysis area. This problem can be

  15. Preliminary results of ESA Category-1 Project 5834 "Application of DInSAR technique to areas of active ground deformations"

    NASA Astrophysics Data System (ADS)

    Massa, B.; D'Auria, L.

    2009-04-01

    We have established a processing chain of Synthetic Aperture Radar (SAR) data for identification and parametrisation of deformation sources in areas of active ground deformation (e.g. seismogenic areas, volcanic districts). SAR data from European Space Agency (ESA) satellites ERS-2 and ENVISAT are used. SAR and InSAR data processing LEVEL 0 SAR data are focussed to Single Look Complex (SLC) through ROI_PAC (Copyright 2002-2008, Caltech/Jet Propulsion Laboratory). We perform an advanced data processing using Doris (Kampes and Usai, 1999) a single program that can do most common steps of the interferometric radar processing starting from SLC data to generation of interferometric products and geocoding. Unwrapping of interferometric phase is performed using the public domain software snaphu (Chen and Zebker, 2001). Modeling of deformation sources We propose a novel inversion approach base on non-linear inversion. The forward modeling is provided by the semi-analytic deformation model for point sources and finite faults. The parameters of the fault (center position, width, height, rake and seismic moment) are inverted using a combination of non-linear optimization algorithms (as Monte-Carlo, Nelder&Mead Simplex and Simulated Annealing). The misfit function defined for the optimization is based on the L2 norm of the error weighted by the coherence of the considered spatial point. Test datasets To test our modeling procedure we chose three different study areas, refer to mainly strike-slip seismogenic sources with different orientation to respect satellite Line Of Sight (LOS): December 26 2003 Iranian earthquake (Bam e.), data from both ascending and descending passes of ENVISAT ASAR narrow swath IS2 (RAW and SLCs); August 17 1999 Turkey earthquake (Izmit e.), data from both ascending and descending passes of ERS-2 AMI SAR (SLCs); June 17-21 2000 Iceland earthquakes, data from both ascending and descending passes of ERS-2 AMI SAR (SLCs). Tests carried over real

  16. Design, synthesis, and structure-activity relationship studies of benzothiazole derivatives as antifungal agents.

    PubMed

    Zhao, Shizhen; Zhao, Liyu; Zhang, Xiangqian; Liu, Chunchi; Hao, Chenzhou; Xie, Honglei; Sun, Bin; Zhao, Dongmei; Cheng, Maosheng

    2016-11-10

    A series of compounds with benzothiazole and amide-imidazole scaffolds were designed and synthesized to combat the increasing incidence of drug-resistant fungal infections. The antifungal activity of these compounds was evaluated in vitro, and their structure-activity relationships (SARs) were evaluated. The synthesized compounds showed excellent inhibitory activity against Candida albicans and Cryptococcus neoformans. The most potent compounds 14o, 14p, and 14r exhibited potent activity, with minimum inhibitory concentration (MIC) values in the range of 0.125-2 μg/mL. Preliminary mechanism studies revealed that the compound 14p might act by inhibiting the CYP51 of Candida albicans. The SARs and binding mode established in this study are useful for further lead optimization. PMID:27494168

  17. Recognition of Lys48-Linked Di-ubiquitin and Deubiquitinating Activities of the SARS Coronavirus Papain-like Protease.

    PubMed

    Békés, Miklós; van der Heden van Noort, Gerbrand J; Ekkebus, Reggy; Ovaa, Huib; Huang, Tony T; Lima, Christopher D

    2016-05-19

    Deubiquitinating enzymes (DUBs) recognize and cleave linkage-specific polyubiquitin (polyUb) chains, but mechanisms underlying specificity remain elusive in many cases. The severe acute respiratory syndrome (SARS) coronavirus papain-like protease (PLpro) is a DUB that cleaves ISG15, a two-domain Ub-like protein, and Lys48-linked polyUb chains, releasing diUb(Lys48) products. To elucidate this specificity, we report the 2.85 Å crystal structure of SARS PLpro bound to a diUb(Lys48) activity-based probe. SARS PLpro binds diUb(Lys48) in an extended conformation via two contact sites, S1 and S2, which are proximal and distal to the active site, respectively. We show that specificity for polyUb(Lys48) chains is predicated on contacts in the S2 site and enhanced by an S1-S1' preference for a Lys48 linkage across the active site. In contrast, ISG15 specificity is dominated by contacts in the S1 site. Determinants revealed for polyUb(Lys48) specificity should prove useful in understanding PLpro deubiquitinating activities in coronavirus infections. PMID:27203180

  18. Cytotoxic Activities, SAR and Anti-Invasion Effects of Butylphthalide Derivatives on Human Hepatocellular Carcinoma SMMC7721 Cells.

    PubMed

    Hu, Yihan; Bi, Xiaoxu; Zhao, Pu; Zheng, Huachuan; Huang, Xueshi

    2015-01-01

    A series of butylphthalide derivatives (BPDs) 1-8 were isolated from the extract of the dried rhizome of Ligusticum chuanxiong Hort. (Umbelliferae). The cytotoxic activities of BPDs 1-8 were evaluated using a panel of human cancer cell lines. In addition, the SAR analysis and potential anti-invasion activities were investigated. The sp² carbons at C-7 and C-7a appeared to be essential for the cytotoxic activities of BPDs. BPDs 5 and 6 remarkably inhibited the migration and invasion of cancer cells. The anti-invasion activity of dimer 6 was demonstrated to be significantly higher than monomer 5. PMID:26569212

  19. Remotely Sensed Active Layer Thickness (ReSALT) from InSAR data near Toolik Lake in Northern Alaska

    NASA Astrophysics Data System (ADS)

    Chen, A. C.; Liu, L.; Schaefer, K. M.; Parsekian, A.; Jafarov, E. E.; Zebker, H. A.; Zhang, T.

    2014-12-01

    Toolik Field Station is built on spatially continuous permafrost on the north slope of Alaska. Seasonal surface subsidence and uplift occurs in permafrost regions due to thaw settlement and frost heave as the active layer thaws and refreezes. Using L-band (23.6 cm wavelength) InSAR data from ALOS-PALSAR acquired between 2006 and 2010, we use a small-baseline subset (SBAS) method to estimate seasonal surface subsidence and retrieve fine-resolution maps of active layer thickness (ALT) for a ~25x25 km area surrounding Toolik Field Station (located at 68.63°N, -149.60°E). We compare these remotely sensed ALT (ReSALT) results with in situ data from: 1) the Circumpolar Active Layer Monitoring (CALM) network showing mean ALT of ~40-50 cm in the region surrounding Toolik Field Station, corresponding to seasonal subsidence of 1 to 2 cm, and 2) mechanical probing measurements of ALT, obtained during field work in the study area in August 2014. We also solve for secular subsidence trends from the InSAR data. The trends are close to zero in most places, but larger subsidence trends in some isolated areas could be due to thermokarst processes (long-term thawing of ice-rich permafrost). We note, however, that downslope motion due to gelifluction cannot be separated from vertical thermokarst-related deformation without incorporating InSAR measurements from multiple look angles. Two key limitations to our method are the spatial variability of volumetric soil moisture content and the accuracy of the DEM needed to correct for topographic effects. We investigate the use of bulk volumetric water content inferred from ground-penetrating radar (GPR) data to improve the ReSALT retrieval algorithm. We also quantify the effect of DEM accuracy on ReSALT uncertainties, leads to requirements for DEM accuracy in InSAR-based ALT retrieval.

  20. New evidence for active tectonics at the boundary of the Kashi Depression, China, from time series InSAR observations

    NASA Astrophysics Data System (ADS)

    He, Ping; Wen, Yangmao; Xu, Caijun; Liu, Yang; Fok, H. S.

    2015-06-01

    Kashi Depression is one of the most complex active tectonic areas in the southern flank of Tianshan, China. Due to the lack of ground observations, the boundary of basin mountain transition zone and the interseismic activity of the Tianshan have not been clearly determined. In this study, 48 Envisat Advanced Synthetic Aperture Radar (ASAR) imagery acquired from 2003 to 2010 are used to construct interferograms for measuring high-resolution interseismic deformation in the Kashi Depression area. A global atmospheric model ERA-Interim provided by the European Center for Medium Range Weather Forecast (ECMWF) and a global network orbital correction are applied to remove atmospheric effect, and the long-wavelength orbital errors, respectively, for the interferograms. Interferometric SAR time series with Atmospheric Estimation Model (InSAR TS + AEM) are then used to obtain a deformation rate map for the Kashi Depression area. The InSAR rate map indicates that the north part of South Atushi Fault has ~ 3 mm/year uplift relative to that of the south part. This result manifests the main tectonic deformation potentially occurs along the Southern Atushi Fault. Based on a simple edge dislocation model, the dip angle of 31 ± 0.6°, slip rate of 2.3 ± 0.1 mm/year, and locking depth of 10.6 ± 0.4 km for the Southern Atushi Fault between Tianshan Orogenic Belt and the Kashi Depression are obtained. This modeling result shows in good agreement with the InSAR derived rates. Our results show that the Southern Atushi Fault is the main active fault in block boundary region between the south of Tianshan and the Tarim Basin.

  1. sarU, a sarA homolog, is repressed by SarT and regulates virulence genes in Staphylococcus aureus.

    PubMed

    Manna, Adhar C; Cheung, Ambrose L

    2003-01-01

    In searching the Staphylococcus aureus genome, we previously identified sarT, a homolog of sarA, which encodes a repressor for alpha-hemolysin synthesis. Adjacent but transcribed divergently to sarT is sarU, which encodes a 247-residue polypeptide, almost twice the length of SarA. Sequence alignment disclosed that SarU, like SarS, which is another SarA homolog, could be envisioned as a molecule with two halves, with each half being homologous to SarA. SarU, as a member of the SarA family proteins, disclosed conservation of basic residues within the helix-turn-helix motif and within the beta hairpin loop, two putative DNA binding domains within this protein family. The transcription of sarU is increased in a sarT mutant. Gel shift and transcriptional fusion studies revealed that SarT can bind to the sarU promoter region, probably acting as a repressor for sarU transcription. The expression of RNAII and RNAIII of agr is decreased in a sarU mutant. As RNAIII expression is up-regulated in a sarT mutant, we hypothesize that sarT may down regulate agr RNAIII expression by repressing sarU, a positive activator of agr expression. We propose that, in addition to the quorum sensing effect of the autoinducing peptide of agr, the sarT-sarU pathway may represent a secondary amplification loop whereby the expression of agr (e.g., those found in vivo) might repress sarT, leading to increased expression of sarU. Elevated sarU expression would result in additional amplification of the original agr signal.

  2. Crystal structure of the SarS protein from Staphylococcus aureus.

    PubMed

    Li, Ronggui; Manna, Adhar C; Dai, Shaodong; Cheung, Ambrose L; Zhang, Gongyi

    2003-07-01

    The expression of virulence determinants in Staphylococcus aureus is controlled by global regulatory loci (e.g., sarA and agr). One of these determinants, protein A (spa), is activated by sarS, which encodes a 250-residue DNA-binding protein. Genetic analysis indicated that the agr locus likely mediates spa repression by suppressing the transcription of sarS. Contrary to SarA and SarR, which require homodimer formation for proper function, SarS is unusual within the SarA protein family in that it contains two homologous halves, with each half sharing sequence similarity to SarA and SarR. Here we report the 2.2 A resolution X-ray crystal structure of the SarS protein. SarS has folds similar to those of SarR and, quite plausibly, the native SarA structure. Two typical winged-helix DNA-binding domains are connected by a well-ordered loop. The interactions between the two domains are extensive and conserved. The putative DNA-binding surface is highly positively charged. In contrast, negatively charged patches are located opposite to the DNA-binding surface. Furthermore, sequence alignment and structural comparison revealed that MarR has folds similar to those of SarR and SarS. Members of the MarR protein family have previously been implicated in the negative regulation of an efflux pump involved in multiple antibiotic resistance in many gram-negative species. We propose that MarR also belongs to the winged-helix protein family and has a similar mode of DNA binding as SarR and SarS and possibly the entire SarA protein family member. Based on the structural differences of SarR, SarS, and MarR, we further classified these winged-helix proteins to three subfamilies, SarA, SarS, and MarR. Finally, a possible transcription regulation mechanism is proposed.

  3. Observing ground surface change series at active volcanoes in Indonesia using backscattering intensity of SAR data

    NASA Astrophysics Data System (ADS)

    Saepuloh, Asep; Trianaputri, Mila Olivia

    2015-04-01

    Indonesia contains 27 active volcanoes passing the West through the East part. Therefore, Indonesia is the most hazard front due to the volcanic activities. To obtain the new precursory signals leading to the eruptions, we applied remote sensing technique to observe ground surface change series at the summit of Sinabung and Kelud volcanoes. Sinabung volcano is located at Karo Region, North Sumatra Province. This volcano is a strato volcano type which is re-activated in August 2010. The eruption continues to the later years by ejecting volcanic products such as lava, pyroclastic flow, and ash fall deposits. This study is targeted to observe ground surface change series at the summit of Sinabung volcano since 2007 to 2011. In addition, we also compared the summit ground surface changes after the eruptions of Kelud volcano in 2007. Kelud volcano is also strato volcano type which is located at East Java, Indonesia. The Synthetic Aperture Radar (SAR) remotely sensed technology makes possible to observe rapidly a wide ground surface changes related to ground surface roughness. Detection series were performed by extracting the backscattering intensity of the Phased Array type L-band Synthetic Aperture Radar (PALSAR) onboard the Advanced Land Observing Satellite (ALOS). The intensity values were then calculated using a Normalized Radar Cross-Section (NRCS). Based on surface roughness criterion at the summit of Sinabung volcano, we could observe the ground surface changes prior to the early eruption in August 2010. The continuous increment of NRCS values showed clearly at window size 3×3 pixel of the summit of Sinabung volcano. The same phenomenon was also detected at the summit of Kelud volcano after the 2007 eruptions. The detected ground surface changes were validated using optical Landsat-8, backscattering intensity ratio for volcanic products detection, and radial component of a tilt-meter data.

  4. Design, structure activity relationship, cytotoxicity and evaluation of antioxidant activity of curcumin derivatives/analogues.

    PubMed

    Sahu, Pramod K

    2016-10-01

    New fourteen 3,4-dihydropyrimidine derivatives/analogues of curcumin (2a-2n) were designed, synthesized and biologically evaluated for their cytotoxicity and antioxidant activity. Cytotoxicity effect has been evaluated against three cell lines HeLa, HCT-116 and QG-56 by MTT assay method. From SAR study, it has been revealed that particularly, compound 2e and 2j (IC50 value 12.5 μM) have shown better cytotoxicity effect against three cell lines. According to results of SAR study, it was found that 3,4-dihydropyrimidines of curcumin, 2c, 2d, 2j and 2n exhibited better antioxidant activity than curcumin. A correlation of structure and activities relationship of these compounds with respect to drug score profiles and other physico-chemical properties of drugs are described and verified experimentally. Therefore, we conclude that physico-chemical analyses may prove structural features of curcumin analogues with their promising combined cytotoxicity/antioxidant activity and it is also concluded from virtual and practical screening that the compounds were varied to possess a broad range of lipophilic character, revealed by Log P values. PMID:27318975

  5. Application of cultured human mast cells (CHMC) for the design and structure-activity relationship of IgE-mediated mast cell activation inhibitors.

    PubMed

    Argade, Ankush; Bhamidipati, Somasekhar; Li, Hui; Carroll, David; Clough, Jeffrey; Keim, Holger; Sylvain, Catherine; Rossi, Alexander B; Coquilla, Christina; Issakani, Sarkiz D; Masuda, Esteban S; Payan, Donald G; Singh, Rajinder

    2015-01-01

    Here we report the optimization of small molecule inhibitors of human mast cell degranulation via anti-IgE-mediated tryptase release following cross-linking and activation of IgE-loaded FcεR1 receptors. The compounds are selective upstream inhibitors of FcεR1-dependent human mast cell degranulation and proved to be devoid of activity in downstream ionomycin mediated degranulation. Structure-activity relationship (SAR) leading to compound 26 is outlined.

  6. Measuring active deformation of the Yakima fold and thrust belt using GPS and InSAR

    NASA Astrophysics Data System (ADS)

    Schmalzle, G. M.; Baker, M. S.; McCaffrey, R.; King, R. W.; Osmanoglu, B.

    2011-12-01

    The Yakima fold-thrust belt (YFTB; also known as Yakima Fold Belt), forming the distinct geomorphology of northernmost Oregon and south-central Washington, is one of the few actively deforming fold and thrust belts in the conterminous United States. Although controversial, currently available data suggest that the YFTB is "thick-skinned", i.e., its faults penetrate the seismogenic layer, allowing for large (~M7) earthquakes. The YFTB is bisected by the Olympic-Wallowa Lineament (OWL) that runs from eastern Washington into the highly populated Puget Sound. Together, the YFTB and OWL make up the boundary between the clockwise rotating Oregon block and eastern Washington, which is largely moving with the North American plate. Paleomagnetic data suggest that Oregon has been rotating at its present (GPS-derived) rate for more than 15 million years with the predicted consequence of a long history of shortening across the YFTB. GPS data obtained over the past ~20 years indicate a NE-directed shortening strain rate of about 9 x 10^-9 /yr, but how this strain is partitioned across the YFTB is unclear due to the sparse locations of GPS sites. We use Global Positioning System (GPS) and Interferometric Synthetic Aperture Radar (InSAR) data to examine the degree to which strain rates are localized or distributed within this continental thrust belt, shedding light on the controversy regarding the behavior of the continental lithosphere under contraction. These data are compared to local seismicity, gravity surveys, recent high-resolution aeromagnetic work and paleoseismic studies.

  7. Conformational Flexibility of a Short Loop near the Active Site of the SARS-3CLpro is Essential to Maintain Catalytic Activity

    NASA Astrophysics Data System (ADS)

    Li, Chunmei; Teng, Xin; Qi, Yifei; Tang, Bo; Shi, Hailing; Ma, Xiaomin; Lai, Luhua

    2016-02-01

    The SARS 3C-like proteinase (SARS-3CLpro), which is the main proteinase of the SARS coronavirus, is essential to the virus life cycle. This enzyme has been shown to be active as a dimer in which only one protomer is active. However, it remains unknown how the dimer structure maintains an active monomer conformation. It has been observed that the Ser139-Leu141 loop forms a short 310-helix that disrupts the catalytic machinery in the inactive monomer structure. We have tried to disrupt this helical conformation by mutating L141 to T in the stable inactive monomer G11A/R298A/Q299A. The resulting tetra-mutant G11A/L141T/R298A/Q299A is indeed enzymatically active as a monomer. Molecular dynamics simulations revealed that the L141T mutation disrupts the 310-helix and helps to stabilize the active conformation. The coil-310-helix conformational transition of the Ser139-Leu141 loop serves as an enzyme activity switch. Our study therefore indicates that the dimer structure can stabilize the active conformation but is not a required structure in the evolution of the active enzyme, which can also arise through simple mutations.

  8. SARS Basics

    MedlinePlus

    ... waiting room or office. Top of Page CDC’s response to SARS during the 2003 outbreak CDC worked ... Center to provide round-the-clock coordination and response. Committed more than 800 medical experts and support ...

  9. Strong Nonadditivity as a Key Structure–Activity Relationship Feature: Distinguishing Structural Changes from Assay Artifacts

    PubMed Central

    2015-01-01

    Nonadditivity in protein–ligand affinity data represents highly instructive structure–activity relationship (SAR) features that indicate structural changes and have the potential to guide rational drug design. At the same time, nonadditivity is a challenge for both basic SAR analysis as well as many ligand-based data analysis techniques such as Free-Wilson Analysis and Matched Molecular Pair analysis, since linear substituent contribution models inherently assume additivity and thus do not work in such cases. While structural causes for nonadditivity have been analyzed anecdotally, no systematic approaches to interpret and use nonadditivity prospectively have been developed yet. In this contribution, we lay the statistical framework for systematic analysis of nonadditivity in a SAR series. First, we develop a general metric to quantify nonadditivity. Then, we demonstrate the non-negligible impact of experimental uncertainty that creates apparent nonadditivity, and we introduce techniques to handle experimental uncertainty. Finally, we analyze public SAR data sets for strong nonadditivity and use recourse to the original publications and available X-ray structures to find structural explanations for the nonadditivity observed. We find that all cases of strong nonadditivity (ΔΔpKi and ΔΔpIC50 > 2.0 log units) with sufficient structural information to generate reasonable hypothesis involve changes in binding mode. With the appropriate statistical basis, nonadditivity analysis offers a variety of new attempts for various areas in computer-aided drug design, including the validation of scoring functions and free energy perturbation approaches, binding pocket classification, and novel features in SAR analysis tools. PMID:25760829

  10. Review of bats and SARS.

    PubMed

    Wang, Lin-Fa; Shi, Zhengli; Zhang, Shuyi; Field, Hume; Daszak, Peter; Eaton, Bryan T

    2006-12-01

    Bats have been identified as a natural reservoir for an increasing number of emerging zoonotic viruses, including henipaviruses and variants of rabies viruses. Recently, we and another group independently identified several horseshoe bat species (genus Rhinolophus) as the reservoir host for a large number of viruses that have a close genetic relationship with the coronavirus associated with severe acute respiratory syndrome (SARS). Our current research focused on the identification of the reservoir species for the progenitor virus of the SARS coronaviruses responsible for outbreaks during 2002-2003 and 2003-2004. In addition to SARS-like coronaviruses, many other novel bat coronaviruses, which belong to groups 1 and 2 of the 3 existing coronavirus groups, have been detected by PCR. The discovery of bat SARS-like coronaviruses and the great genetic diversity of coronaviruses in bats have shed new light on the origin and transmission of SARS coronaviruses.

  11. Review of Bats and SARS

    PubMed Central

    Shi, Zhengli; Zhang, Shuyi; Field, Hume; Daszak, Peter; Eaton, Bryan T.

    2006-01-01

    Bats have been identified as a natural reservoir for an increasing number of emerging zoonotic viruses, including henipaviruses and variants of rabies viruses. Recently, we and another group independently identified several horseshoe bat species (genus Rhinolophus) as the reservoir host for a large number of viruses that have a close genetic relationship with the coronavirus associated with severe acute respiratory syndrome (SARS). Our current research focused on the identification of the reservoir species for the progenitor virus of the SARS coronaviruses responsible for outbreaks during 2002–2003 and 2003–2004. In addition to SARS-like coronaviruses, many other novel bat coronaviruses, which belong to groups 1 and 2 of the 3 existing coronavirus groups, have been detected by PCR. The discovery of bat SARS-like coronaviruses and the great genetic diversity of coronaviruses in bats have shed new light on the origin and transmission of SARS coronaviruses. PMID:17326933

  12. Design, synthesis, and SAR of embelin analogues as the inhibitors of PAI-1 (plasminogen activator inhibitor-1).

    PubMed

    Chen, Fanglei; Zhang, Guiping; Hong, Zebin; Lin, Zhonghui; Lei, Min; Huang, Mingdong; Hu, Lihong

    2014-05-15

    The natural product embelin was found to have PAI-1 inhibitory activity with the IC50 value of 4.94μM. Based on the structure of embelin, a series of analogues were designed, synthesized, and evaluated for their ability to inhibit PAI-1. The SAR study on these compounds disclosed that the inhibitory potency largely depended on the hydroxyl groups at C2 and C5, and the length of the alkyl chains at C3 and C6. Compound 11 displayed the best PAI-1 inhibitory potency with the IC50 value of 0.18μM.

  13. Intracellular localization of the SARS coronavirus protein 9b: evidence of active export from the nucleus.

    PubMed

    Moshynskyy, Igor; Viswanathan, Sathiyanarayanan; Vasilenko, Natalia; Lobanov, Vladislav; Petric, Martin; Babiuk, Lorne A; Zakhartchouk, Alexander N

    2007-07-01

    Open reading frame 9b (ORF 9b) encodes a 98 amino acid group-specific protein of severe acute respiratory syndrome (SARS) coronavirus (CoV). It has no homology with known proteins and its function in SARS CoV replication has not been determined. The N-terminal part of the 9b protein was used to raise polyclonal antibodies in rabbits, and these antibodies could detect 9b protein in infected cells. We analyzed the sub-cellular localization of recombinant 9b protein using fluorescence microscopy of live transfected cells and indirect immunofluorescence of transfected fixed cells. Our findings indicate that the 9b protein is exported outside of a cell nucleus and localizes to the endoplasmic reticulum. Our data also suggest that the 46-LRLGSQLSL-54 amino acid sequence of 9b functions as a nuclear export signal (NES).

  14. The mammalian guanine nucleotide exchange factor mSec12 is essential for activation of the Sar1 GTPase directing endoplasmic reticulum export.

    PubMed

    Weissman, J T; Plutner, H; Balch, W E

    2001-07-01

    The Sar1 GTPase is an essential component of COPII vesicle coats involved in export of cargo from the endoplasmic reticulum of mammalian cells. To begin to elucidate its mechanism of action, we now report the identity of the mammalian homolog to the yeast Sec12 guanine nucleotide exchange factor (18% identity) that promotes Sar1 activation. Mammalian Sec12 (mSec12) is a type II transmembrane protein with a large cytosolic domain, a fragment of which has previously been reported as the transcription factor prolactin regulatory element binding protein (PREB). mSec12 promotes efficient guanine nucleotide exchange on Sar1, but not Arf1 or Rab GTPases. mSec12 is localized to the endoplasmic reticulum and an antibody to the cytosolic domain of mSec12 potently inhibits Sar1 recruitment and the formation of COPII vesicles in vitro. The dominant negative GDP-restricted mutant Sar1[T39N] is shown to be a potent inhibitor of mSec12 activity, consistent with its role in preventing COPII vesicle formation in vitro and during transient expression in vivo. We propose that mSec12 is an evolutionarily distant guanine nucleotide exchange factor directing Sar1 GTPase activation in mammalian cells. Its divergence from yeast Sec12p may reflect the specialized needs of the mammalian endoplasmic reticulum involving the formation of Sar1-dependent transitional elements (Aridor M, et al. J Cell Biol 2001;152:213-229) and selection of cargo into prebudding complexes.

  15. Synthesis and structure-activity relationships of potent 4-fluoro-2-cyanopyrrolidine dipeptidyl peptidase IV inhibitors.

    PubMed

    Fukushima, Hiroshi; Hiratate, Akira; Takahashi, Masato; Mikami, Ayako; Saito-Hori, Masako; Munetomo, Eiji; Kitano, Kiyokazu; Chonan, Sumi; Saito, Hidetaka; Suzuki, Akio; Takaoka, Yuji; Yamamoto, Koji

    2008-04-01

    Dipeptidyl peptidase IV (DPP-IV) inhibitors are promising antidiabetic drugs, and several drugs are in the developmental stage. We previously reported that the introduction of fluorine to the 4-position of 2-cyanopyrrolidine enhanced the DPP-IV inhibitory effect. In the present report, we examined the structure-activity relationship (SAR) of 2-cyano-4-fluoropyrrolidine with N-substituted glycine at the 1-position. We report the identification of a potent and stable DPP-IV inhibitor (TS-021) with a long-term persistent plasma drug concentration and a potent antihyperglycemic activity.

  16. Virulence Factor-activity Relationships: Workshop Summary

    EPA Science Inventory

    The concept or notion of virulence factor–activity relationships (VFAR) is an approach for identifying an analogous process to the use of qualitative structure–activity relationships (QSAR) for identifying new microbial contaminants. In QSAR, it is hypothesized that, for new chem...

  17. Synthesis, biological activities, and quantitative structure-activity relationship (QSAR) study of novel camptothecin analogues.

    PubMed

    Wu, Dan; Zhang, Shao-Yong; Liu, Ying-Qian; Wu, Xiao-Bing; Zhu, Gao-Xiang; Zhang, Yan; Wei, Wei; Liu, Huan-Xiang; Chen, An-Liang

    2015-05-13

    In continuation of our program aimed at the development of natural product-based pesticidal agents, three series of novel camptothecin derivatives were designed, synthesized, and evaluated for their biological activities against T. Cinnabarinus, B. brassicae, and B. xylophilus. All of the derivatives showed good-to-excellent activity against three insect species tested, with LC50 values ranging from 0.00761 to 0.35496 mmol/L. Remarkably, all of the compounds were more potent than CPT against T. Cinnabarinus, and compounds 4d and 4c displayed superior activity (LC50 0.00761 mmol/L and 0.00942 mmol/L, respectively) compared with CPT (LC50 0.19719 mmol/L) against T. Cinnabarinus. Based on the observed bioactivities, preliminary structure-activity relationship (SAR) correlations were also discussed. Furthermore, a three-dimensional quantitative structure-activity relationship (3D-QSAR) model using comparative molecular field analysis (CoMFA) was built. The model gave statistically significant results with the cross-validated q2 values of 0.580 and correlation coefficient r2 of 0.991 and  of 0.993. The QSAR analysis indicated that the size of the substituents play an important in the activity of 7-modified camptothecin derivatives. These findings will pave the way for further design, structural optimization, and development of camptothecin-derived compounds as pesticidal agents.

  18. Structure-Activity Relationship Studies and Biological Characterization of Human NAD+-dependent 15-Hydroxyprostaglandin Dehydrogenase Inhibitors

    PubMed Central

    Duveau, Damien Y.; Yasgar, Adam; Wang, Yuhong; Hu, Xin; Kouznetsova, Jennifer; Brimacombe, Kyle R.; Jadhav, Ajit; Simeonov, Anton; Thomas, Craig J.; Maloney, David J.

    2014-01-01

    The structure-activity relationship (SAR) study of two chemotypes identified as inhibitors of the human NAD+-dependent 15-hydroxyprostaglandin dehydrogenase (HPGD, 15-PGDH) was conducted. Top compounds from both series displayed potent inhibition (IC50 <50 nM), demonstrate excellent selectivity towards HPGD and potently induce PGE2 production in A549 lung cancer and LNCaP prostate cancer cells. PMID:24360556

  19. Structure-activity relationship studies and biological characterization of human NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase inhibitors.

    PubMed

    Duveau, Damien Y; Yasgar, Adam; Wang, Yuhong; Hu, Xin; Kouznetsova, Jennifer; Brimacombe, Kyle R; Jadhav, Ajit; Simeonov, Anton; Thomas, Craig J; Maloney, David J

    2014-01-15

    The structure-activity relationship (SAR) study of two chemotypes identified as inhibitors of the human NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase (HPGD, 15-PGDH) was conducted. Top compounds from both series displayed potent inhibition (IC50 <50 nM), demonstrate excellent selectivity towards HPGD and potently induce PGE2 production in A549 lung cancer and LNCaP prostate cancer cells. PMID:24360556

  20. Synthesis and Biological Evaluation of 14-(Aminoalkyl-aminomethyl)aromathecins as Topoisomerase I Inhibitors: Investigating the Hypothesis of Shared Structure-Activity Relationships

    PubMed Central

    Cinelli, Maris A.; Cordero, Brenda; Dexheimer, Thomas S.; Pommier, Yves; Cushman, Mark

    2009-01-01

    The aromathecin topoisomerase I (top1) inhibitors offer promising scaffolds for the development of novel cancer chemotherapeutics. They are “composites” of the camptothecin and indenoisoquinoline top1 inhibitors. Interestingly, some structure-activity-relationship (SAR) overlap between the aromathecins and the indenoisoquinolines has been observed. For both classes, placement of certain polar groups in similar regions of the heteroaromatic system improves top1 inhibitory and antiproliferative activities. A series of water-soluble aromathecins substituted at position 14 with diaminoalkanes of various lengths has been prepared. These compounds all possess similar antiproliferative potency, but a general trend is observed: aromathecins with longer diaminoalkane substituents (> 6 carbons) possess lower anti-top1 activity than their smaller counterparts (2–4 carbons), presumably as a result of unfavorable hydrophobic interactions. This trend is also noted with the indenoisoquinolines, revealing additional SAR overlap that supports the hypothesis that there is a “universal” top1 inhibitor SAR. PMID:19783447

  1. Modeling chemical interaction profiles: I. Spectral data-activity relationship and structure-activity relationship models for inhibitors and non-inhibitors of cytochrome P450 CYP3A4 and CYP2D6 isozymes.

    PubMed

    McPhail, Brooks; Tie, Yunfeng; Hong, Huixiao; Pearce, Bruce A; Schnackenberg, Laura K; Ge, Weigong; Valerio, Luis G; Fuscoe, James C; Tong, Weida; Buzatu, Dan A; Wilkes, Jon G; Fowler, Bruce A; Demchuk, Eugene; Beger, Richard D

    2012-03-15

    An interagency collaboration was established to model chemical interactions that may cause adverse health effects when an exposure to a mixture of chemicals occurs. Many of these chemicals--drugs, pesticides, and environmental pollutants--interact at the level of metabolic biotransformations mediated by cytochrome P450 (CYP) enzymes. In the present work, spectral data-activity relationship (SDAR) and structure-activity relationship (SAR) approaches were used to develop machine-learning classifiers of inhibitors and non-inhibitors of the CYP3A4 and CYP2D6 isozymes. The models were built upon 602 reference pharmaceutical compounds whose interactions have been deduced from clinical data, and 100 additional chemicals that were used to evaluate model performance in an external validation (EV) test. SDAR is an innovative modeling approach that relies on discriminant analysis applied to binned nuclear magnetic resonance (NMR) spectral descriptors. In the present work, both 1D ¹³C and 1D ¹⁵N-NMR spectra were used together in a novel implementation of the SDAR technique. It was found that increasing the binning size of 1D ¹³C-NMR and ¹⁵N-NMR spectra caused an increase in the tenfold cross-validation (CV) performance in terms of both the rate of correct classification and sensitivity. The results of SDAR modeling were verified using SAR. For SAR modeling, a decision forest approach involving from 6 to 17 Mold2 descriptors in a tree was used. Average rates of correct classification of SDAR and SAR models in a hundred CV tests were 60% and 61% for CYP3A4, and 62% and 70% for CYP2D6, respectively. The rates of correct classification of SDAR and SAR models in the EV test were 73% and 86% for CYP3A4, and 76% and 90% for CYP2D6, respectively. Thus, both SDAR and SAR methods demonstrated a comparable performance in modeling a large set of structurally diverse data. Based on unique NMR structural descriptors, the new SDAR modeling method complements the existing SAR

  2. The structure-activity relationship in herbicidal monosubstituted sulfonylureas

    SciTech Connect

    Li, Zheng-Ming; Ma, Yi; Guddat, Luke; Cheng, Pei-Quan; Wang, Jian-Guo; Pang, Siew S; Dong, Yu-Hui; Lai, Cheng-Ming; Wang, Ling-Xiu; Jia, Guo-Feng; Li, Yong-Hong; Wang, Su-Hua; Liu, Jie; Zhao, Wei-Guang; Wang, Bao-Lei

    2012-05-24

    The herbicide sulfonylurea (SU) belongs to one of the most important class of herbicides worldwide. It is well known for its ecofriendly, extreme low toxicity towards mammals and ultralow dosage application. The original inventor, G Levitt, set out structure-activity relationship (SAR) guidelines for SU structural design to attain superhigh bioactivity. A new approach to SU molecular design has been developed. After the analysis of scores of SU products by X-ray diffraction methodology and after greenhouse herbicidal screening of 900 novel SU structures synthesized in the authors laboratory, it was found that several SU structures containing a monosubstituted pyrimidine moiety retain excellent herbicidal characteristics, which has led to partial revision of the Levitt guidelines. Among the novel SU molecules, monosulfuron and monosulfuron-ester have been developed into two new herbicides that have been officially approved for field application and applied in millet and wheat fields in China. A systematic structural study of the new substrate-target complex and the relative mode of action in comparison with conventional SU has been carried out. A new mode of action has been postulated.

  3. Multistep continuous-flow synthesis in medicinal chemistry: discovery and preliminary structure-activity relationships of CCR8 ligands.

    PubMed

    Petersen, Trine P; Mirsharghi, Sahar; Rummel, Pia C; Thiele, Stefanie; Rosenkilde, Mette M; Ritzén, Andreas; Ulven, Trond

    2013-07-01

    A three-step continuous-flow synthesis system and its application to the assembly of a new series of chemokine receptor ligands directly from commercial building blocks is reported. No scavenger columns or solvent switches are necessary to recover the desired test compounds, which were obtained in overall yields of 49-94%. The system is modular and flexible, and the individual steps of the sequence can be interchanged with similar outcome, extending the scope of the chemistry. Biological evaluation confirmed activity on the chemokine CCR8 receptor and provided initial structure-activity-relationship (SAR) information for this new ligand series, with the most potent member displaying full agonist activity with single-digit nanomolar potency. To the best of our knowledge, this represents the first published example of efficient use of multistep flow synthesis combined with biological testing and SAR studies in medicinal chemistry.

  4. SAR-Based Optimization of a 4-Quinoline Carboxylic Acid Analogue with Potent Antiviral Activity

    PubMed Central

    2013-01-01

    It is established that drugs targeting viral proteins are at risk of generating resistant strains. However, drugs targeting host factors can potentially avoid this problem. Herein, we report structure–activity relationship studies leading to the discovery of a very potent lead compound 6-fluoro-2-(5-isopropyl-2-methyl-4-phenoxyphenyl)quinoline-4-carboxylic acid (C44) that inhibits human dihydroorotate dehydrogenase (DHODH) with an IC50 of 1 nM and viral replication of VSV and WSN-Influenza with an EC50 of 2 nM and 41 nM. We also solved the X-ray structure of human DHODH bound to C44, providing structural insight into the potent inhibition of biaryl ether analogues of brequinar. PMID:23930152

  5. Identification of New Nonsteroidal RORα Ligands; Related Structure–Activity Relationships and Docking Studies

    PubMed Central

    2013-01-01

    A high throughput screen was developed to identify novel, nonsteroidal RORα agonists. Among the validated hit compounds, the 4-(4-(benzyloxy)phenyl)-5-carbonyl-2-oxo-1,2,3,4-tetrahydropyrimidine scaffold was the most prominent. Among the numerous analogues tested, compounds 8 and 9 showed the highest activity. Key structure–activity relationships (SAR) were established, where benzyl and urea moieties were both identified as very important elements to maintain the activity. Most notably, the SAR were consistent with the binding mode of the compound 8 (S-isomer) in the RORα docking model that was developed in this program. As predicted by the model, the urea moiety is engaged in the formation of key hydrogen bonds with the backbone of Tyr380 and Asp382. The benzyl group is located in a wide hydrophobic pocket. The structural relationships reported in this letter will help in further optimization of this compound series and will provide novel synthetic probes helpful for elucidation of complex RORα physiopathology. PMID:24900700

  6. Identification of New Nonsteroidal RORα Ligands; Related Structure-Activity Relationships and Docking Studies.

    PubMed

    Dubernet, Mathieu; Duguet, Nicolas; Colliandre, Lionel; Berini, Christophe; Helleboid, Stéphane; Bourotte, Marilyne; Daillet, Matthieu; Maingot, Lucie; Daix, Sébastien; Delhomel, Jean-François; Morin-Allory, Luc; Routier, Sylvain; Walczak, Robert

    2013-06-13

    A high throughput screen was developed to identify novel, nonsteroidal RORα agonists. Among the validated hit compounds, the 4-(4-(benzyloxy)phenyl)-5-carbonyl-2-oxo-1,2,3,4-tetrahydropyrimidine scaffold was the most prominent. Among the numerous analogues tested, compounds 8 and 9 showed the highest activity. Key structure-activity relationships (SAR) were established, where benzyl and urea moieties were both identified as very important elements to maintain the activity. Most notably, the SAR were consistent with the binding mode of the compound 8 (S-isomer) in the RORα docking model that was developed in this program. As predicted by the model, the urea moiety is engaged in the formation of key hydrogen bonds with the backbone of Tyr380 and Asp382. The benzyl group is located in a wide hydrophobic pocket. The structural relationships reported in this letter will help in further optimization of this compound series and will provide novel synthetic probes helpful for elucidation of complex RORα physiopathology.

  7. Applying PolSAR and PolInSAR to Forest Structure Information Extraction

    NASA Astrophysics Data System (ADS)

    Chen, E.; Li, Z.; Li, W.; Feng, Q.; Zhou, W.; Pottier, E.; Hong, W.

    2013-01-01

    The key research activities and achievements in the field of applying PolSAR and PolInSAR to forest structure information extraction in DRAGON 2 are summarized in this paper. The limitation of the ALOS PolInSAR dataset acquired in the Culai test site for forest height extraction because of its long temporal baseline (46 days), and how the PolInSAR coherence optimization methods can help improve the topography inversion accuracy under forest canopy were presented. We have analyzed and evaluated the capability of multiple polarization parameters extracted from different frequency PolSAR data for forest scar mapping in the Shibazhan test site, and developed the land cover classification method based on SVM (Support Vector Machine) using PolSAR data. With the L-band E-SAR PolInSAR data acquired in the test site in Germany, we developed forest above ground biomass (AGB) estimation approach based on polarization coherence tomography (PCT).

  8. Crystal Structures of the Reduced, Sulfenic Acid, and Mixed Disulfide Forms of SarZ, a Redox Active Global Regulator in Staphylococcus aureus

    SciTech Connect

    Poor, Catherine B.; Chen, Peng R.; Duguid, Erica; Rice, Phoebe A.; He, Chuan

    2010-01-20

    SarZ is a global transcriptional regulator that uses a single cysteine residue, Cys{sup 13}, to sense peroxide stress and control metabolic switching and virulence in Staphylococcus aureus. SarZ belongs to the single-cysteine class of OhrR-MgrA proteins that play key roles in oxidative resistance and virulence regulation in various bacteria. We present the crystal structures of the reduced form, sulfenic acid form, and mixed disulfide form of SarZ. Both the sulfenic acid and mixed disulfide forms are structurally characterized for the first time for this class of proteins. The Cys{sup 13} sulfenic acid modification is stabilized through two hydrogen bonds with surrounding residues, and the overall DNA-binding conformation is retained. A further reaction of the Cys{sup 13} sulfenic acid with an external thiol leads to formation of a mixed disulfide bond, which results in an allosteric change in the DNA-binding domains, disrupting DNA binding. Thus, the crystal structures of SarZ in three different states provide molecular level pictures delineating the mechanism by which this class of redox active regulators undergoes activation. These structures help to understand redox-mediated virulence regulation in S. aureus and activation of the MarR family proteins in general.

  9. Discovery and Structure-Activity Relationships of the Neoseptins: A New Class of Toll-like Receptor-4 (TLR4) Agonists.

    PubMed

    Morin, Matthew D; Wang, Ying; Jones, Brian T; Su, Lijing; Surakattula, Murali M R P; Berger, Michael; Huang, Hua; Beutler, Elliot K; Zhang, Hong; Beutler, Bruce; Boger, Dale L

    2016-05-26

    Herein, we report studies leading to the discovery of the neoseptins and a comprehensive examination of the structure-activity relationships (SARs) of this new class of small-molecule mouse Toll-like receptor 4 (mTLR4) agonists. The compounds in this class, which emerged from screening an α-helix mimetic library, stimulate the immune response, act by a well-defined mechanism (mouse TLR4 agonist), are easy to produce and structurally manipulate, exhibit exquisite SARs, are nontoxic, and elicit improved and qualitatively different responses compared to lipopolysaccharide, even though they share the same receptor.

  10. Qualitative and quantitative structure-activity relationship modelling for predicting blood-brain barrier permeability of structurally diverse chemicals.

    PubMed

    Gupta, S; Basant, N; Singh, K P

    2015-01-01

    In this study, structure-activity relationship (SAR) models have been established for qualitative and quantitative prediction of the blood-brain barrier (BBB) permeability of chemicals. The structural diversity of the chemicals and nonlinear structure in the data were tested. The predictive and generalization ability of the developed SAR models were tested through internal and external validation procedures. In complete data, the QSAR models rendered ternary classification accuracy of >98.15%, while the quantitative SAR models yielded correlation (r(2)) of >0.926 between the measured and the predicted BBB permeability values with the mean squared error (MSE) <0.045. The proposed models were also applied to an external new in vitro data and yielded classification accuracy of >82.7% and r(2) > 0.905 (MSE < 0.019). The sensitivity analysis revealed that topological polar surface area (TPSA) has the highest effect in qualitative and quantitative models for predicting the BBB permeability of chemicals. Moreover, these models showed predictive performance superior to those reported earlier in the literature. This demonstrates the appropriateness of the developed SAR models to reliably predict the BBB permeability of new chemicals, which can be used for initial screening of the molecules in the drug development process.

  11. High resolution SAR applications and instrument design

    NASA Technical Reports Server (NTRS)

    Dionisio, C.; Torre, A.

    1993-01-01

    The Synthetic Aperture Radar (SAR) has viewed, in the last two years, a huge increment of interest from many preset and potential users. The good spatial resolution associated to the all weather capability lead to considering SAR not only a scientific instrument but a tool for verifying and controlling the daily human relationships with the Earth Environment. New missions were identified for SAR as spatial resolution became lower than three meters: disasters, pollution, ships traffic, volcanic eruptions, earthquake effect are only a few of the possible objects which can be effectively detected, controlled and monitored by SAR mounted on satellites. High resolution radar design constraints and dimensioning are discussed.

  12. SARS-coronavirus spike S2 domain flanked by cysteine residues C822 and C833 is important for activation of membrane fusion.

    PubMed

    Madu, Ikenna G; Belouzard, Sandrine; Whittaker, Gary R

    2009-10-25

    The S2 domain of the coronavirus spike (S) protein is known to be responsible for mediating membrane fusion. In addition to a well-recognized cleavage site at the S1-S2 boundary, a second proteolytic cleavage site has been identified in the severe acute respiratory syndrome coronavirus (SARS-CoV) S2 domain (R797). C-terminal to this S2 cleavage site is a conserved region flanked by cysteine residues C822 and C833. Here, we investigated the importance of this well conserved region for SARS-CoV S-mediated fusion activation. We show that the residues between C822-C833 are well conserved across all coronaviruses. Mutagenic analysis of SARS-CoV S, combined with cell-cell fusion and pseudotyped virion infectivity assays, showed a critical role for the core-conserved residues C822, D830, L831, and C833. Based on available predictive models, we propose that the conserved domain flanked by cysteines 822 and 833 forms a loop structure that interacts with components of the SARS-CoV S trimer to control the activation of membrane fusion.

  13. SARS-coronavirus spike S2 domain flanked by cysteine residues C822 and C833 is important for activation of membrane fusion

    PubMed Central

    Madu, Ikenna G.; Belouzard, Sandrine; Whittaker, Gary R.

    2013-01-01

    The S2 domain of the coronavirus spike (S) protein is known to be responsible for mediating membrane fusion. In addition to a well-recognized cleavage site at the S1–S2 boundary, a second proteolytic cleavage site has been identified in the severe acute respiratory syndrome coronavirus (SARS-CoV) S2 domain (R797). C terminal to this S2 cleavage site is a conserved region flanked by cysteine residues C822 and C833. Here, we investigated the importance of this well conserved region for SARS-CoV S-mediated fusion activation. We show that the residues between C822-C833 are well conserved across all coronaviruses. Mutagenic analysis of SARS-CoV S, combined with cell–cell fusion and pseudotyped virion infectivity assays, showed a critical role for the core-conserved residues C822, D830, L831, and C833. Based on available predictive models, we propose that the conserved domain flanked by cysteines 822 and 833 forms a loop structure that interacts with components of the SARS-CoV S trimer to control the activation of membrane fusion. PMID:19717178

  14. SARS-coronavirus spike S2 domain flanked by cysteine residues C822 and C833 is important for activation of membrane fusion

    SciTech Connect

    Madu, Ikenna G.; Belouzard, Sandrine; Whittaker, Gary R.

    2009-10-25

    The S2 domain of the coronavirus spike (S) protein is known to be responsible for mediating membrane fusion. In addition to a well-recognized cleavage site at the S1-S2 boundary, a second proteolytic cleavage site has been identified in the severe acute respiratory syndrome coronavirus (SARS-CoV) S2 domain (R797). C-terminal to this S2 cleavage site is a conserved region flanked by cysteine residues C822 and C833. Here, we investigated the importance of this well conserved region for SARS-CoV S-mediated fusion activation. We show that the residues between C822-C833 are well conserved across all coronaviruses. Mutagenic analysis of SARS-CoV S, combined with cell-cell fusion and pseudotyped virion infectivity assays, showed a critical role for the core-conserved residues C822, D830, L831, and C833. Based on available predictive models, we propose that the conserved domain flanked by cysteines 822 and 833 forms a loop structure that interacts with components of the SARS-CoV S trimer to control the activation of membrane fusion.

  15. GPS and Satellite InSAR Observations of Landslide Activity at the Sinking Canyon in South Central Idaho

    NASA Astrophysics Data System (ADS)

    Aly, M. H.; Glenn, N. F.; Thackray, G. D.

    2014-12-01

    Multiple rotational, transitional, and lateral spread landslides have occurred in south central Idaho where basalt lava flows overly unconsolidated lake and fluvial sediments at the Sinking Canyon. The canyon is about 0.1 km deep and 0.25-1 km wide along a 4-km segment of the Salmon Falls Creek (SFC). Local topography and hydrological conditions are most likely the major triggering factors that have initiated landslides by increasing the gravitational stresses and weakening the canyon wall materials. Landslide activity has created natural dams of SFC, which in turn has resulted in forming large lakes with a potential flooding hazard to life and property downstream. In this study, we use campaign Global Positioning System (GPS) measurements of 2003-2004 and Synthetic Aperture Radar Interferometric (InSAR) data acquired during 1992-2007 by the European radar satellites (ERS-1 and ERS-2) to identify, monitor, and analyze recent landslide activity at SFC. Results show that three main landslides have been active during the period of observation: the Salmon Falls landslide (SFL) that has been first reported in 1999, the historical 1937 landslide, and a third unnamed landslide to the north of the 1937 slide. InSAR measurements indicate that the SFL has been active during the period of our earliest interferogram (1992-1993) whereas the slide head has detached and has moved away from the eastern canyon wall about 3 cm. Over the years, the SFL body and toe have been pushed westward repetitively at rates of about 3-7 cm/yr. The toe is confined by the western canyon wall and thus is pushed upward in some years causing slight uplift (2-3 cm). Our field observations reveal many transverse and radial cracks associated with the deformation pattern caused by recurring motions. The historic 1937 slide is the largest mass wasting and is the least active landslide in the study area. The unnamed slide shows episodic activity with varying rates (0-4 cm/yr) of line-of-sight motions. This

  16. Nonpeptidic Amphiphilic Xanthone Derivatives: Structure-Activity Relationship and Membrane-Targeting Properties.

    PubMed

    Koh, Jun-Jie; Zou, Hanxun; Lin, Shuimu; Lin, Huifen; Soh, Rui Ting; Lim, Fang Hui; Koh, Wee Luan; Li, Jianguo; Lakshminarayanan, Rajamani; Verma, Chandra; Tan, Donald T H; Cao, Derong; Beuerman, Roger W; Liu, Shouping

    2016-01-14

    We recently reported the bioinspired synthesis of a highly potent nonpeptidic xanthone, 2c (AM-0016), with potent antibacterial activity against MRSA. Herein, we report a thorough structure-activity relationship (SAR) analysis of a series of nonpeptidic amphiphilic xanthone derivatives in an attempt to identify more potent compounds with lower hemolytic activity and greater membrane selectivity. Forty-six amphiphilic xanthone derivatives were analyzed in this study and structurally classified into four groups based on spacer length, cationic moieties, lipophilic chains, and triarm functionalization. We evaluated and explored the effects of the structures on their membrane-targeting properties. The SAR analysis successfully identified 3a with potent MICs (1.56-3.125 μ/mL) and lower hemolytic activity (80.2 μg/mL for 3a versus 19.7 μg/mL for 2c). Compound 3a displayed a membrane selectivity of 25.7-50.4. Thus, 3a with improved HC50 value and promising selectivity could be used as a lead compound for further structural optimization for the treatment of MRSA infection. PMID:26681070

  17. Exploration of the structure-activity relationship of 1,2,4-oxadiazole antibiotics.

    PubMed

    Ding, Derong; Boudreau, Marc A; Leemans, Erika; Spink, Edward; Yamaguchi, Takao; Testero, Sebastian A; O'Daniel, Peter I; Lastochkin, Elena; Chang, Mayland; Mobashery, Shahriar

    2015-11-01

    We have recently disclosed the discovery of the class of 1,2,4-oxadiazole antibiotics, which emerged from in silico docking and scoring efforts. This class of antibacterials exhibits Gram-positive activity, particularly against Staphylococcus aureus. We define the structure-activity relationship (SAR) of this class of antibiotics with the synthesis and evaluation of a series of 59 derivatives with variations in the C ring or C and D rings. A total of 17 compounds showed activity against S. aureus. Four derivatives were evaluated against a panel of 16 Gram-positive strains, inclusive of several methicillin-resistant S. aureus strains. These compounds are broadly active against Gram-positive bacteria.

  18. Structure-activity relationships of 1'-acetoxychavicol acetate homologues as new nuclear export signal inhibitors.

    PubMed

    Liu, Y; Murakami, N; Zhang, S; Xu, T

    2007-09-01

    Bioassay-guided separation use of the fission yeast expressing NES of Rev, a HIV-1 viral regulatory protein, resulted in isolation of 1'-acetoxychavicol acetate (ACA) from Alpinia galanga as a new Rev-transport inhibitor from the nucleus to cytoplasm. Rational design and synthesis of eleven ACA derivatives containing systematic chemical variations were made, biological evaluation of inhibitory activities of these analogues provides the basis to formulate the structure-activity relationship (SAR). The key elements observed were: (1) The para substitution of the acetoxyl and 1'-acetoxypropenyl groups at the benzene ring was essential, (2) linear ethyl and propyl chain carbonates were more active than branching chain carbonates, (3) the substitution of acetoxyl groups with alkyl carbamate groups lost or reduced the activities. This study revealed a new salient pharmacophore features as potential drug leads against the HIV virus.

  19. Seamless integration of dose-response screening and flow chemistry: efficient generation of structure-activity relationship data of β-secretase (BACE1) inhibitors.

    PubMed

    Werner, Michael; Kuratli, Christoph; Martin, Rainer E; Hochstrasser, Remo; Wechsler, David; Enderle, Thilo; Alanine, Alexander I; Vogel, Horst

    2014-02-01

    Drug discovery is a multifaceted endeavor encompassing as its core element the generation of structure-activity relationship (SAR) data by repeated chemical synthesis and biological testing of tailored molecules. Herein, we report on the development of a flow-based biochemical assay and its seamless integration into a fully automated system comprising flow chemical synthesis, purification and in-line quantification of compound concentration. This novel synthesis-screening platform enables to obtain SAR data on b-secretase (BACE1) inhibitors at an unprecedented cycle time of only 1 h instead of several days. Full integration and automation of industrial processes have always led to productivity gains and cost reductions, and this work demonstrates how applying these concepts to SAR generation may lead to a more efficient drug discovery process.

  20. Relationships between solar activity and climate change

    NASA Technical Reports Server (NTRS)

    Roberts, W. O.

    1975-01-01

    The relationship between recurrent droughts in the High Plains of the United States and the double sunspot cycle is discussed in detail. It is suggested that high solar activity is generally related to an increase in meridional circulation and blocking patterns at high and intermediate latitudes, especially in winter, and the effect is related to the sudden formation of cirrus clouds during strong geomagnetic activity that originates in the solar corpuscular emission.

  1. INTER-SPECIES COMPARISONS AND SAR MODELLING OF ESTROGENICITY USING RAINBOW TROUT ER BINDING DATA

    EPA Science Inventory

    The U.S. EPA has been mandated to screen industrial chemicals and pesticides for potential endocrine activity. Structure-activity relationships (SARs) to predict receptor binding are being developed as a first step to rank and prioritize chemicals for testing in bioassays. First ...

  2. (Q)SAR assessments of potentially mutagenic impurities: a regulatory perspective on the utility of expert knowledge and data submission.

    PubMed

    Powley, Mark W

    2015-03-01

    (Quantitative) structure activity relationship [(Q)SAR] modeling is the primary tool used to evaluate the mutagenic potential associated with drug impurities. General recommendations regarding the use of (Q)SAR in regulatory decision making have recently been provided in the ICH M7 guideline. Although (Q)SAR alone is capable of achieving reasonable sensitivity and specificity, reliance on a simple positive or negative prediction can be problematic. The key to improving (Q)SAR performance is to integrate supporting information, also referred to as expert knowledge, into the final conclusion. In the regulatory context, expert knowledge is intended to (1) maximize confidence in a (Q)SAR prediction, (2) provide rationale to supersede a positive or negative (Q)SAR prediction, or (3) provide a basis for assessing mutagenicity in absence of a (Q)SAR prediction. Expert knowledge is subjective and is associated with great variability in regards to content and quality. However, it is still a critical component of impurity evaluations and its utility is acknowledged in the ICH M7 guideline. The current paper discusses the use of expert knowledge to support regulatory decision making, describes case studies, and provides recommendations for reporting data from (Q)SAR evaluations.

  3. Discovery and SAR of muscarinic receptor subtype 1 (M1) allosteric activators from a molecular libraries high throughput screen. Part I: 2,5-dibenzyl-2H-pyrazolo[4,3-c]quinolin-3(5H)-ones as positive allosteric modulators

    PubMed Central

    Han, Changho; Chatterjee, Arindam; Noetzel, Meredith J.; Panarese, Joseph D.; Niswender, Colleen; Conn, P. Jeffrey; Lindsley, Craig W.; Stauffer, Shaun R.

    2014-01-01

    Results from a 2012 high-throughput screen of the NIH Molecular Libraries Small Molecule Repository (MLSMR) against the human muscarinic receptor subtype 1 (M1) for positive allosteric modulators is reported. A content-rich screen utilizing an intracellular calcium mobilization triple-addition protocol allowed for assessment of all three modes of pharmacology at M1, including agonist, positive allosteric modulator, and antagonist activities in a single screening platform. We disclose a dibenzyl-2H-pyrazolo[4,3-c]quinolin-3(5H)-one hit (DBPQ, CID 915409) and examine N-benzyl pharmacophore/SAR relationships versus previously reported quinolin-3(5H)-ones and isatins, including ML137. SAR and consideration of recently reported crystal structures, homology modeling, and structure-function relationships using point mutations suggests a shared binding mode orientation at the putative common allosteric binding site directed by the pendant N-benzyl substructure. PMID:25435150

  4. TerraSAR-X mission

    NASA Astrophysics Data System (ADS)

    Werninghaus, Rolf

    2004-01-01

    The TerraSAR-X is a German national SAR- satellite system for scientific and commercial applications. It is the continuation of the scientifically and technologically successful radar missions X-SAR (1994) and SRTM (2000) and will bring the national technology developments DESA and TOPAS into operational use. The space segment of TerraSAR-X is an advanced high-resolution X-Band radar satellite. The system design is based on a sound market analysis performed by Infoterra. The TerraSAR-X features an advanced high-resolution X-Band Synthetic Aperture Radar based on the active phased array technology which allows the operation in Spotlight-, Stripmap- and ScanSAR Mode with various polarizations. It combines the ability to acquire high resolution images for detailed analysis as well as wide swath images for overview applications. In addition, experimental modes like the Dual Receive Antenna Mode allow for full-polarimetric imaging as well as along track interferometry, i.e. moving target identification. The Ground Segment is optimized for flexible response to (scientific and commercial) User requests and fast image product turn-around times. The TerraSAR-X mission will serve two main goals. The first goal is to provide the strongly supportive scientific community with multi-mode X-Band SAR data. The broad spectrum of scientific application areas include Hydrology, Geology, Climatology, Oceanography, Environmental Monitoring and Disaster Monitoring as well as Cartography (DEM Generation) and Interferometry. The second goal is the establishment of a commercial EO-market in Europe which is driven by Infoterra. The commercial goal is the development of a sustainable EO-business so that the e.g. follow-on systems can be completely financed by industry from the profit. Due to its commercial potential, the TerraSAR-X project will be implemented based on a public-private partnership with the Astrium GmbH. This paper will describe first the mission objectives as well as the

  5. (Q)SAR modeling and safety assessment in regulatory review.

    PubMed

    Kruhlak, N L; Benz, R D; Zhou, H; Colatsky, T J

    2012-03-01

    The ability to predict clinical safety based on chemical structures is becoming an increasingly important part of regulatory decision making. (Quantitative) structure-activity relationship ((Q)SAR) models are currently used to evaluate late-arising safety concerns and possible nonclinical effects of a drug and its related compounds when adequate safety data are absent or equivocal. Regulatory use will likely increase with the standardization of analytical approaches, more complete and reliable data collection methods, and a better understanding of toxicity mechanisms.

  6. Synthesis, antioxidant and cytoprotective evaluation of potential antiatherogenic phenolic hydrazones. A structure-activity relationship insight.

    PubMed

    Vanucci-Bacqué, Corinne; Carayon, Chantal; Bernis, Corinne; Camare, Caroline; Nègre-Salvayre, Anne; Bedos-Belval, Florence; Baltas, Michel

    2014-08-01

    A novel series of hydrazones derived from substituted benzaldehydes have been synthesized as potential antiatherogenic agents. Several methods were used for exploring their antioxidant and cytoprotective properties, such as their scavenging effect on 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical, the inhibition of superoxide anion (O₂(·-)) generation and the measurement of cell-induced low-density lipoprotein oxidation (monitored by the formation of TBARS). The cytoprotective efficacy was also evaluated by measuring the cell viability (monitored by the MTT assay) in the presence of cytotoxic oxidized LDL. In this report, we discuss the relationship between the chemical structure of phenolic hydrazones and their antioxidant and cytoprotective activities, for subsequent application as antiatherogenic agents. This SAR study confirms that the phenolic frame is not the only prerequisite for antioxidant activity and N-methylbenzothiazole hydrazone moiety magnifies the dual required properties in two most interesting derivatives. PMID:24924425

  7. InSAR analysis of surface deformation over permafrost to estimate active layer thickness based on one-dimensional heat transfer model of soils.

    PubMed

    Li, Zhiwei; Zhao, Rong; Hu, Jun; Wen, Lianxing; Feng, Guangcai; Zhang, Zeyu; Wang, Qijie

    2015-01-01

    This paper presents a novel method to estimate active layer thickness (ALT) over permafrost based on InSAR (Interferometric Synthetic Aperture Radar) observation and the heat transfer model of soils. The time lags between the periodic feature of InSAR-observed surface deformation over permafrost and the meteorologically recorded temperatures are assumed to be the time intervals that the temperature maximum to diffuse from the ground surface downward to the bottom of the active layer. By exploiting the time lags and the one-dimensional heat transfer model of soils, we estimate the ALTs. Using the frozen soil region in southern Qinghai-Tibet Plateau (QTP) as examples, we provided a conceptual demonstration of the estimation of the InSAR pixel-wise ALTs. In the case study, the ALTs are ranging from 1.02 to 3.14 m and with an average of 1.95 m. The results are compatible with those sparse ALT observations/estimations by traditional methods, while with extraordinary high spatial resolution at pixel level (~40 meter). The presented method is simple, and can potentially be used for deriving high-resolution ALTs in other remote areas similar to QTP, where only sparse observations are available now. PMID:26480892

  8. InSAR analysis of surface deformation over permafrost to estimate active layer thickness based on one-dimensional heat transfer model of soils

    PubMed Central

    Li, Zhiwei; Zhao, Rong; Hu, Jun; Wen, Lianxing; Feng, Guangcai; Zhang, Zeyu; Wang, Qijie

    2015-01-01

    This paper presents a novel method to estimate active layer thickness (ALT) over permafrost based on InSAR (Interferometric Synthetic Aperture Radar) observation and the heat transfer model of soils. The time lags between the periodic feature of InSAR-observed surface deformation over permafrost and the meteorologically recorded temperatures are assumed to be the time intervals that the temperature maximum to diffuse from the ground surface downward to the bottom of the active layer. By exploiting the time lags and the one-dimensional heat transfer model of soils, we estimate the ALTs. Using the frozen soil region in southern Qinghai-Tibet Plateau (QTP) as examples, we provided a conceptual demonstration of the estimation of the InSAR pixel-wise ALTs. In the case study, the ALTs are ranging from 1.02 to 3.14 m and with an average of 1.95 m. The results are compatible with those sparse ALT observations/estimations by traditional methods, while with extraordinary high spatial resolution at pixel level (~40 meter). The presented method is simple, and can potentially be used for deriving high-resolution ALTs in other remote areas similar to QTP, where only sparse observations are available now. PMID:26480892

  9. SAR/QSAR methods in public health practice

    SciTech Connect

    Demchuk, Eugene Ruiz, Patricia; Chou, Selene; Fowler, Bruce A.

    2011-07-15

    Methods of (Quantitative) Structure-Activity Relationship ((Q)SAR) modeling play an important and active role in ATSDR programs in support of the Agency mission to protect human populations from exposure to environmental contaminants. They are used for cross-chemical extrapolation to complement the traditional toxicological approach when chemical-specific information is unavailable. SAR and QSAR methods are used to investigate adverse health effects and exposure levels, bioavailability, and pharmacokinetic properties of hazardous chemical compounds. They are applied as a part of an integrated systematic approach in the development of Health Guidance Values (HGVs), such as ATSDR Minimal Risk Levels, which are used to protect populations exposed to toxic chemicals at hazardous waste sites. (Q)SAR analyses are incorporated into ATSDR documents (such as the toxicological profiles and chemical-specific health consultations) to support environmental health assessments, prioritization of environmental chemical hazards, and to improve study design, when filling the priority data needs (PDNs) as mandated by Congress, in instances when experimental information is insufficient. These cases are illustrated by several examples, which explain how ATSDR applies (Q)SAR methods in public health practice.

  10. Relationship between potential platelet activation and LCS

    NASA Astrophysics Data System (ADS)

    Shadden, Shawn

    2010-11-01

    In the study of blood flow, emphasis is often directed at understanding shear stress at the vessel wall due to its potentially disruptive influence on the endothelium. However, it is also known that shear stress has a potent effect on platelet activation. Platelet activation is a precursor for blood clotting, which in turn is the cause of most forms of death. Since most platelets are contained in the flow domain, it is important to consider stresses acting on the platelet as they are convected. Locations of high stress can correspond to boundaries between different dynamic regions and locations of hyperbolic points in the Eulerian sense. In the computation of LCS, strain in typically considered in the Lagrangian sense. In this talk we discuss the relationship between locations of potential platelet activation due to increased stress and locations of LCS marking increase Lagrangian deformation.

  11. Faults Activities And Crustal Deformation Along The Arc-Continent Collision Boundary, Eastern Taiwan - Observed From Persistent Scatterer SAR Interferometry

    NASA Astrophysics Data System (ADS)

    Yen, Jiun-Yee; Chang, Chung-Pai; Hooper, Andrew; Chang, Yo-Ho; Liang, Wen-Tzong; Chang, Tsui-Yu

    2010-05-01

    Located in the southeastern periphery of the Eurasian plate, eastern Taiwan marks the collional boundary between the Eurasian plate and the Philippine Sea plate. These two plates converge at about 8 cm/yr near Taiwan and nearly half of the shortening is consumed in eastern Taiwan. There have been many studies in this area about the dynamics of the plate convergence, however, most of the geodetic studies focused on small area (strainmeter), with very few data points (GPS), or only gather data along a specific profile (leveling). We applied the Persistent Scatterer SAR Interferometry in the Longitudinal Valley of eastern Taiwan to observe temporally-variable processes using both ERS and Envisat data. At the same time, leveling and GPS data were measured for the auxiliary tool to verify the deformation rate in this area. Our result indicated that although the area is under active collision, faults do not move in the same fashion along the boundary. In the very northern part of the collided arc, small subsidence has been detected, while in the north-central part very few activity is observed. In the central and southern part of the collisional boundary, patches of faults are moving as rapidly as 15 mm/yr along radar line-of-sight. In addition. between late 2004 and middle 2005 there had been an earthquake swarm consists of shallow earthquakes, which coincided with PSI observation of a large vertical displacement. The comparison between our leveling data and PS results indicated PSI is a reliable tool even in the highly vegetated area in eastern Taiwan.

  12. Application of Satellite SAR Imagery in Mapping the Active Layer of Arctic Permafrost

    NASA Technical Reports Server (NTRS)

    Zhang, Ting-Jun; Li, Shu-Sun

    2003-01-01

    The objective of this project is to map the spatial variation of the active layer over the arctic permafrost in terms of two parameters: (i) timing and duration of thaw period and (ii) differential frost heave and thaw settlement of the active layer. To achieve this goal, remote sensing, numerical modeling, and related field measurements are required. Tasks for the University of Colorado team are to: (i) determine the timing of snow disappearance in spring through changes in surface albedo (ii) simulate the freezing and thawing processes of the active layer and (iii) simulate the impact of snow cover on permafrost presence.

  13. SAR STUDY OF NASAL TOXICITY: LESSONS FOR MODELING SMALL TOXICITY DATASETS

    EPA Science Inventory

    Most toxicity data, particularly from whole animal bioassays, are generated without the needs or capabilities of structure-activity relationship (SAR) modeling in mind. Some toxicity endpoints have been of sufficient regulatory concern to warrant large scale testing efforts (e.g....

  14. Pyrazolo Derivatives as Potent Adenosine Receptor Antagonists: An Overview on the Structure-Activity Relationships

    PubMed Central

    Cheong, Siew Lee; Venkatesan, Gopalakrishnan; Paira, Priyankar; Jothibasu, Ramasamy; Mandel, Alexander Laurence; Federico, Stephanie; Spalluto, Giampiero; Pastorin, Giorgia

    2011-01-01

    In the past few decades, medicinal chemistry research towards potent and selective antagonists of human adenosine receptors (namely, A1, A2A, A2B, and A3) has been evolving rapidly. These antagonists are deemed therapeutically beneficial in several pathological conditions including neurological and renal disorders, cancer, inflammation, and glaucoma. Up to this point, many classes of compounds have been successfully synthesized and identified as potent human adenosine receptor antagonists. In this paper, an overview of the structure-activity relationship (SAR) profiles of promising nonxanthine pyrazolo derivatives is reported and discussed. We have emphasized the SAR for some representative structures such as pyrazolo-[4,3-e]-1,2,4-triazolo-[1,5-c]pyrimidines; pyrazolo-[3,4-c] or -[4,3-c]quinolines; pyrazolo-[4,3-d]pyrimidinones; pyrazolo-[3,4-d]pyrimidines and pyrazolo-[1,5-a]pyridines. This overview not only clarifies the structural requirements deemed essential for affinity towards individual adenosine receptor subtypes, but it also sheds light on the rational design and optimization of existing structural templates to allow us to conceive new, more potent adenosine receptor antagonists. PMID:25954519

  15. Representation of molecular structure using quantum topology with inductive logic programming in structure-activity relationships.

    PubMed

    Buttingsrud, Bård; Ryeng, Einar; King, Ross D; Alsberg, Bjørn K

    2006-06-01

    The requirement of aligning each individual molecule in a data set severely limits the type of molecules which can be analysed with traditional structure activity relationship (SAR) methods. A method which solves this problem by using relations between objects is inductive logic programming (ILP). Another advantage of this methodology is its ability to include background knowledge as 1st-order logic. However, previous molecular ILP representations have not been effective in describing the electronic structure of molecules. We present a more unified and comprehensive representation based on Richard Bader's quantum topological atoms in molecules (AIM) theory where critical points in the electron density are connected through a network. AIM theory provides a wealth of chemical information about individual atoms and their bond connections enabling a more flexible and chemically relevant representation. To obtain even more relevant rules with higher coverage, we apply manual postprocessing and interpretation of ILP rules. We have tested the usefulness of the new representation in SAR modelling on classifying compounds of low/high mutagenicity and on a set of factor Xa inhibitors of high and low affinity.

  16. Satellite SAR imagery for site discovery, change detection and monitoring activities in cultural heritage sites: experiments on the Nasca region, Peru

    NASA Astrophysics Data System (ADS)

    Tapete, D.; Cigna, F.; Masini, N.; Lasaponara, R.

    2012-04-01

    Besides their suitability for multi-temporal and spatial deformation analysis, the Synthetic Aperture Radar (SAR) image archives acquired by space-borne radar sensors can be exploited to support archaeological investigations over huge sites, even those partially or totally buried and still to be excavated. Amplitude information is one of the main properties of SAR data from which it is possible to retrieve evidences of buried structures, using feature extraction and texture analysis. Multi-temporality allows the reconstruction of past and recent evolution of both landscape and built-up environment, with the possibility to detect natural and/or anthropogenic changes, including human-induced damages to the conservation of cultural heritage. We present the methodology and first results of the experiments currently undertaken using SAR data in the Nasca region (Southern Peru), where two important civilizations such as Paracas and Nasca developed and flourished from 4th century BC to the 6th century AD. The study areas include a wide spectrum of archaeological and environmental elements to be preserved, among which: the archaeological site of Cahuachi and its surroundings, considered the largest adobe Ceremonial Centre in the World; the Nasca lines and geoglyphs in the areas of Palpa, Atarco and Nasca; the ancient networks of aqueducts and drainage galleries in the Puquios area, built by Nasca in the 1st-6th centuries AD. Archaeological prospection and multi-purpose remote sensing activities are currently carried out in the framework of the Italian mission of heritage Conservation and Archaeogeophysics (ITACA), with the direct involvement of researchers from the Institute for Archaeological and Monumental Heritage and the Institute of Methodologies for Environmental Analysis, Italian National Research Council. In this context, C- and L-band SAR images covering the Nasca region since 2001 were identified for the purposes of this research and, in particular, the following

  17. Active tectonic extension across the Alto Tiberina normal fault system from GPS data modeling and InSAR velocity maps: new perspectives within TABOO Near Fault Observatory

    NASA Astrophysics Data System (ADS)

    Vadacca, Luigi; Anderlini, Letizia; Casarotti, Emanuele; Serpelloni, Enrico; Chiaraluce, Lauro; Polcari, Marco; Albano, Matteo; Stramondo, Salvatore

    2014-05-01

    The Alto Tiberina fault (ATF) is a low-angle (east-dipping at 15°) normal fault (LANF) 70 km long placed in the Umbria-Marche Apennines (central Italy), characterized by SW-NE oriented extension occurring at rates of 2-3 mm/yr. These rates were measured by continuous GPS stations belonging to several networks, which are denser in the study area thanks to additional sites recently installed in the framework of the INGV national RING network and of the ATF observatory. In this area historical and instrumental earthquakes mainly occur on west-dipping high-angle normal faults. Within this context the ATF has accumulated 2 km of displacement over the past 2 Ma, but at the same time the deformation processes active along this misoriented fault, as well as its mechanical behavior, are still unknown. We tackle this issue by solving for interseismic deformation models obtained by two different methods. At first, through the 2D and 3D finite element modeling, we define the effects of locking depth, synthetic and antithetic fault activity and lithology on the velocity gradient measured along the ATF system. Subsequently through a block modeling approach, we model the GPS velocities by considering the major fault systems as bounds of rotating blocks, while estimating the corresponding geodetic fault slip-rates and maps of heterogeneous fault coupling. Thanks to the latest imaging of the ATF deep structure obtained from seismic profiles, we improve the proposed models by modeling the fault as a complex rough surface to understand where the stress accumulations are located and the interseismic coupling changes. The preliminary results obtained show firstly that the observed extension is mainly accommodated by interseismic deformation on both the ATF and antithetic faults, highlighting the important role of this LANF inside an active tectonic contest. Secondarily, using the ATF surface "topography", we find an interesting correlation between microseismicty and creeping portions

  18. Wetland InSAR

    NASA Astrophysics Data System (ADS)

    Wdowinski, S.; Kim, S.; Amelung, F.; Dixon, T.

    2006-12-01

    Wetlands are transition zones where the flow of water, the nutrient cycling, and the sun energy meet to produce a unique and very productive ecosystem. They provide critical habitat for a wide variety of plant and animal species, including the larval stages of many ocean fish. Wetlands also have a valuable economical importance, as they filter nutrients and pollutants from fresh water used by human and provide aquatic habitats for outdoor recreation, tourism, and fishing. Globally, many such regions are under severe environmental stress, mainly from urban development, pollution, and rising sea level. However, there is increasing recognition of the importance of these habitats, and mitigation and restoration activities have begun in a few regions. A key element in wetlands conservation, management, and restoration involves monitoring its hydrologic system, as the entire ecosystem depends on its water supply. Heretofore, hydrologic monitoring of wetlands are conducted by stage (water level) stations, which provide good temporal resolution, but suffer from poor spatial resolution, as stage station are typically distributed several, or even tens of kilometers, from one another. Wetland application of InSAR provides the needed high spatial resolution hydrological observations, complementing the high temporal resolution terrestrial observations. Although conventional wisdom suggests that interferometry does not work in vegetated areas, several studies have shown that both L- and C-band interferograms with short acquisition intervals (1-105 days) can maintain excellent coherence over wetlands. In this study we explore the usage of InSAR for detecting water level changes in various wetland environments around the world, including the Everglades (south Florida), Louisiana Coast (southern US), Chesapeake Bay (eastern US), Pantanal (Brazil), Okavango Delta (Botswana), and Lena Delta (Siberia). Our main study area is the Everglades wetland (south Florida), which is covered by

  19. Discretionary Time of Chinese College Students: Activities and Impact of SARS-Induced Constraints on Choices

    ERIC Educational Resources Information Center

    Yang, He; Hutchinson, Susan; Zinn, Harry; Watson, Alan

    2011-01-01

    How people make choices about activity engagement during discretionary time is a topic of increasing interest to those studying quality of life issues. Assuming choices are made to maximize individual welfare, several factors are believed to influence these choices. Constraints theory from the leisure research literature suggests these choices are…

  20. Design, Synthesis and Structure-Activity Relationship Studies of Novel 4 (1-adamantyl) Phenyl Analogues as HIF-1α Inhibitors.

    PubMed

    Xia, Yan; Duan, Qiong; Zhao, Bao-Hua; Li, Dong-Feng; Hou, Rui-Bin

    2016-01-01

    Hypoxia inducible factor-1 (HIF-1) is a key mediator during cancer cells to adapt tumor hypoxic condition. In this study, a series of adamantane-based compounds were synthesized and evaluated as potential inhibitors of HIF-1α. Examination of their structure-activity relationship (SAR) identified the adamantane-containing indole derivative 20a as a potent inhibitor of HIF-1α in Hep3B cell lines under tumor hypoxia (IC50 = 0.02 µM). The study herein may provide valuable information for the development of novel therapeutics against cancer and tumor angiogenesis. PMID:26548744

  1. Peptide Bacteriocins--Structure Activity Relationships.

    PubMed

    Etayash, Hashem; Azmi, Sarfuddin; Dangeti, Ramana; Kaur, Kamaljit

    2015-01-01

    With the growing concerns in the scientific and health communities over increasing levels of antibiotic resistance, antimicrobial peptide bacteriocins have emerged as promising alternatives to conventional small molecule antibiotics. A substantial attention has recently focused on the utilization of bacteriocins in food preservation and health safety. Despite the fact that a large number of bacteriocins have been reported, only a few have been fully characterized and structurally elucidated. Since knowledge of the molecular structure is a key for understanding the mechanism of action and therapeutic effects of peptide, we centered our focus in this review on the structure-activity relationships of bacteriocins with a particular focus in seven bacteriocins, namely, nisin, microcin J25, microcin B17, microcin C, leucocin A, sakacin P, and pediocin PA-1. Significant structural changes responsible for the altered activity of the recent bacteriocin analogues are discussed here. PMID:26265354

  2. In Vitro Antioxidant Activity of Selected 4-Hydroxy-chromene-2-one Derivatives—SAR, QSAR and DFT Studies

    PubMed Central

    Mladenović, Milan; Mihailović, Mirjana; Bogojević, Desanka; Matić, Sanja; Nićiforović, Neda; Mihailović, Vladimir; Vuković, Nenad; Sukdolak, Slobodan; Solujić, Slavica

    2011-01-01

    The series of fifteen synthesized 4-hydroxycoumarin derivatives was subjected to antioxidant activity evaluation in vitro, through total antioxidant capacity, 1,1-diphenyl-2-picryl-hydrazyl (DPPH), hydroxyl radical, lipid peroxide scavenging and chelating activity. The highest activity was detected during the radicals scavenging, with 2b, 6b, 2c, and 4c noticed as the most active. The antioxidant activity was further quantified by the quantitative structure-activity relationships (QSAR) studies. For this purpose, the structures were optimized using Paramethric Method 6 (PM6) semi-empirical and Density Functional Theory (DFT) B3LYP methods. Bond dissociation enthalpies of coumarin 4-OH, Natural Bond Orbital (NBO) gained hybridization of the oxygen, acidity of the hydrogen atom and various molecular descriptors obtained, were correlated with biological activity, after which we designed 20 new antioxidant structures, using the most favorable structural motifs, with much improved predicted activity in vitro. PMID:21686153

  3. In vitro inhibition effect and structure-activity relationships of some saccharin derivatives on erythrocyte carbonic anhydrase I and II.

    PubMed

    Sonmez, Fatih; Bilen, Cigdem; Sumersan, Sinem; Gencer, Nahit; Isik, Semra; Arslan, Oktay; Kucukislamoglu, Mustafa

    2014-02-01

    In this study, in vitro inhibitory effects of some saccharin derivatives on purified carbonic anhydrase I and II were investigated using CO2 as a substrate. The results showed that all compounds inhibited the hCA I and hCA II enzyme activities. Among the compounds, 6-(p-tolylthiourenyl) saccharin (6m) was found to be the most active one for hCA I activity (IC50=13.67 μM) and 6-(m-methoxyphenylurenyl) saccharin (6b) was found to be the most active one for hCA II activity (IC50=6.54 μM). Structure-activity relationships (SARs) study showed that, generally, thiourea derivatives (6l--v) inhibited more hCA I and hCA II than urea derivatives (6a-k). All compounds (excluding 6c and 6r) have higher inhibitory activity on hCA II than on hCA I.

  4. Obstacles to activity pacing: assessment, relationship to activity and functioning.

    PubMed

    Cane, Douglas; McCarthy, Mary; Mazmanian, Dwight

    2016-07-01

    Activity pacing is frequently included among the strategies provided to individuals with chronic pain to manage pain and improve functioning. Individuals with chronic pain may, however, limit their use of activity pacing because they perceive significant obstacles to its use. This study describes the development of a measure to assess obstacles to activity pacing and examines the relationship of this measure to activity patterns and functioning. A sample of 637 individuals with chronic pain completed items describing potential obstacles to activity pacing as part of their pretreatment assessment. Item analyses were used to construct a 14-item measure of obstacles to activity pacing. A subset of these individuals completed the measure again after completion of a group treatment program. The resulting measure demonstrated excellent internal consistency and was minimally affected by social desirability. Correlations with measures of activity and psychosocial functioning provided initial construct validity for the measure. Sex differences were found with women initially identifying more obstacles to activity pacing. Fewer obstacles were identified by both men and women after treatment, and these changes were related to modest changes in activity patterns and functioning. The present results identify a number of obstacles that may limit the use of activity pacing by individuals with chronic pain. Treatment may result in a decrease in the number of obstacles identified, and this change is related to changes in the individual's activity pattern and psychosocial functioning. PMID:26963845

  5. Summary of a workshop on regulatory acceptance of (Q)SARs for human health and environmental endpoints.

    PubMed Central

    Jaworska, Joanna S; Comber, M; Auer, C; Van Leeuwen, C J

    2003-01-01

    The "Workshop on Regulatory Use of (Q)SARs for Human Health and Environmental Endpoints," organized by the European Chemical Industry Council and the International Council of Chemical Associations, gathered more than 60 human health and environmental experts from industry, academia, and regulatory agencies from around the world. They agreed, especially industry and regulatory authorities, that the workshop initiated great potential for the further development and use of predictive models, that is, quantitative structure-activity relationships [(Q)SARs], for chemicals management in a much broader scope than is currently the case. To increase confidence in (Q)SAR predictions and minimization of their misuse, the workshop aimed to develop proposals for guidance and acceptability criteria. The workshop also described the broad outline of a system that would apply that guidance and acceptability criteria to a (Q)SAR when used for chemical management purposes, including priority setting, risk assessment, and classification and labeling. PMID:12896859

  6. Cationic phospholipids: structure transfection activity relationships

    SciTech Connect

    Koynova, Rumiana; Tenchov, Boris

    2010-01-18

    Synthetic cationic lipids are presently the most widely used non-viral gene carriers. Examined here is a particularly attractive cationic lipid class, triester phosphatidylcholines (PCs) exhibiting low toxicities and good transfection efficiency. Similarly to other cationic lipids, they form stable complexes (lipoplexes) with the polyanionic nucleic acids. A summary of studies on a set of {approx}30 cationic PCs reveals the existence of a strong, systematic dependence of their transfection efficiency on the lipid hydrocarbon chain structure: transfection activity increases with increase of chain unsaturation from 0 to 2 double bonds per lipid and decreases with increase of chain length in the range {approx}30-50 total number of chain carbon atoms. Maximum transfection was observed for ethyl phosphate PCs (EPCs) with monounsaturated 14:1 chains (total of 2 double bonds and 30 chain carbon atoms). Lipid phase behavior is known to depend strongly on the chain molecular structure and the above relationships thus substantiate a view that cationic PC phase propensities are an important determinant of their activity. Indeed, X-ray structural studies show that the rate of DNA release from lipoplexes as well as transfection activity well correlate with non-lamellar phase progressions observed in cationic PC mixtures with membrane lipids. These findings appear to be of considerable interest because, according to current views, key processes in lipid-mediated transfection such as lipoplex disassembly and DNA release within the cells are believed to take place upon cationic lipid mixing with cellular lipids.

  7. Pyridine-3-carboxamide-6-yl-ureas as novel inhibitors of bacterial DNA gyrase: structure based design, synthesis, SAR and antimicrobial activity.

    PubMed

    Yule, Ian A; Czaplewski, Lloyd G; Pommier, Stephanie; Davies, David T; Narramore, Sarah K; Fishwick, Colin W G

    2014-10-30

    The development of antibacterial drugs based on novel chemotypes is essential to the future management of serious drug resistant infections. We herein report the design, synthesis and SAR of a novel series of N-ethylurea inhibitors based on a pyridine-3-carboxamide scaffold targeting the ATPase sub-unit of DNA gyrase. Consideration of structural aspects of the GyrB ATPase site has aided the development of this series resulting in derivatives that demonstrate excellent enzyme inhibitory activity coupled to potent Gram positive antibacterial efficacy.

  8. SAR Product Control Software

    NASA Astrophysics Data System (ADS)

    Meadows, P. J.; Hounam, D.; Rye, A. J.; Rosich, B.; Börner, T.; Closa, J.; Schättler, B.; Smith, P. J.; Zink, M.

    2003-03-01

    As SAR instruments and their operating modes become more complex, as new applications place more and more demands on image quality and as our understanding of their imperfections becomes more sophisticated, there is increasing recognition that SAR data quality has to be controlled more completely to keep pace. The SAR product CONtrol software (SARCON) is a comprehensive SAR product control software suite tailored to the latest generation of SAR sensors. SARCON profits from the most up-to-date thinking on SAR image performance derived from other spaceborne and airborne SAR projects and is based on the newest applications. This paper gives an overview of the structure and the features of this new software tool, which is a product of a co-operation between teams at BAE SYSTEMS Advanced Technology Centre and DLR under contract to ESA (ESRIN). Work on SARCON began in 1999 and is continuing.

  9. SAR change detection MTI

    NASA Astrophysics Data System (ADS)

    Scarborough, Steven; Lemanski, Christopher; Nichols, Howard; Owirka, Gregory; Minardi, Michael; Hale, Todd

    2006-05-01

    This paper examines the theory, application, and results of using single-channel synthetic aperture radar (SAR) data with Moving Reference Processing (MRP) to focus and geolocate moving targets. Moving targets within a standard SAR imaging scene are defocused, displaced, or completely missing in the final image. Building on previous research at AFRL, the SAR-MRP method focuses and geolocates moving targets by reprocessing the SAR data to focus the movers rather than the stationary clutter. SAR change detection is used so that target detection and focusing is performed more robustly. In the cases where moving target returns possess the same range versus slow-time histories, a geolocation ambiguity results. This ambiguity can be resolved in a number of ways. This paper concludes by applying the SAR-MRP method to high-frequency radar measurements from persistent continuous-dwell SAR observations of a moving target.

  10. Recovering Seasat SAR Data

    NASA Astrophysics Data System (ADS)

    Logan, T. A.; Arko, S. A.; Rosen, P. A.

    2013-12-01

    To demonstrate the feasibility of orbital remote sensing for global ocean observations, NASA launched Seasat on June 27th, 1978. Being the first space borne SAR mission, Seasat produced the most detailed SAR images of Earth from space ever seen to that point in time. While much of the data collected in the USA was processed optically, a mere 150 scenes had been digitally processed by March 1980. In fact, only an estimated 3% of Seasat data was ever digitally processed. Thus, for over three decades, the majority of the SAR data from this historic mission has been dormant, virtually unavailable to scientists in the 21st century. Over the last year, researchers at the Alaska Satellite Facility (ASF) Distributed Active Archive Center (DAAC) have processed the Seasat SAR archives into imagery products. A telemetry decoding system was created and the data were filtered into readily processable signal files. Due to nearly 35 years of bit rot, the bit error rate (BER) for the ASF DAAC Seasat archives was on the order of 1 out of 100 to 1 out of 100,000. This extremely high BER initially seemed to make much of the data undecodable - because the minor frame numbers are just 7 bits and no range line numbers exist in the telemetry even the 'simple' tasks of tracking the minor frame number or locating the start of each range line proved difficult. Eventually, using 5 frame numbers in sequence and a handful of heuristics, the data were successfully decoded into full range lines. Concurrently, all metadata were stored into external files. Recovery of this metadata was also problematic, the BER making the information highly suspect and, initially at least, unusable in any sort of automated fashion. Because of the BER, all of the single bit metadata fields proved unreliable. Even fields that should be constant for a data take (e.g. receiving station, day of the year) showed high variability, each requiring a median filter to be usable. The most challenging, however, were the

  11. Accurate and interpretable nanoSAR models from genetic programming-based decision tree construction approaches.

    PubMed

    Oksel, Ceyda; Winkler, David A; Ma, Cai Y; Wilkins, Terry; Wang, Xue Z

    2016-09-01

    The number of engineered nanomaterials (ENMs) being exploited commercially is growing rapidly, due to the novel properties they exhibit. Clearly, it is important to understand and minimize any risks to health or the environment posed by the presence of ENMs. Data-driven models that decode the relationships between the biological activities of ENMs and their physicochemical characteristics provide an attractive means of maximizing the value of scarce and expensive experimental data. Although such structure-activity relationship (SAR) methods have become very useful tools for modelling nanotoxicity endpoints (nanoSAR), they have limited robustness and predictivity and, most importantly, interpretation of the models they generate is often very difficult. New computational modelling tools or new ways of using existing tools are required to model the relatively sparse and sometimes lower quality data on the biological effects of ENMs. The most commonly used SAR modelling methods work best with large datasets, are not particularly good at feature selection, can be relatively opaque to interpretation, and may not account for nonlinearity in the structure-property relationships. To overcome these limitations, we describe the application of a novel algorithm, a genetic programming-based decision tree construction tool (GPTree) to nanoSAR modelling. We demonstrate the use of GPTree in the construction of accurate and interpretable nanoSAR models by applying it to four diverse literature datasets. We describe the algorithm and compare model results across the four studies. We show that GPTree generates models with accuracies equivalent to or superior to those of prior modelling studies on the same datasets. GPTree is a robust, automatic method for generation of accurate nanoSAR models with important advantages that it works with small datasets, automatically selects descriptors, and provides significantly improved interpretability of models.

  12. Antileishmanial Activity and Structure-Activity Relationship of Triazolic Compounds Derived from the Neolignans Grandisin, Veraguensin, and Machilin G.

    PubMed

    Costa, Eduarda C; Cassamale, Tatiana B; Carvalho, Diego B; Bosquiroli, Lauriane S S; Ojeda, Mariáh; Ximenes, Thalita V; Matos, Maria F C; Kadri, Mônica C T; Baroni, Adriano C M; Arruda, Carla C P

    2016-01-01

    Sixteen 1,4-diaryl-1,2,3-triazole compounds 4-19 derived from the tetrahydrofuran neolignans veraguensin 1, grandisin 2, and machilin G 3 were tested against Leishmania (Leishmania) amazonensis intracellular amastigotes. Triazole compounds 4-19 were synthetized via Click Chemistry strategy by 1,3-dipolar cycloaddition between terminal acetylenes and aryl azides containing methoxy and methylenedioxy groups as substituents. Our results suggest that most derivatives were active against intracellular amastigotes, with IC50 values ranging from 4.4 to 32.7 µM. The index of molecular hydrophobicity (ClogP) ranged from 2.8 to 3.4, reflecting a lipophilicity/hydrosolubility rate suitable for transport across membranes, which may have resulted in the potent antileishmanial activity observed. Regarding structure-activity relationship (SAR), compounds 14 and 19, containing a trimethoxy group, were the most active (IC50 values of 5.6 and 4.4 µM, respectively), with low cytotoxicity on mammalian cells (SI = 14.1 and 10.6). These compounds induced nitric oxide production by the host macrophage cells, which could be suggested as the mechanism involved in the intracellular killing of parasites. These results would be useful for the planning of new derivatives with higher antileishmanial activities. PMID:27331807

  13. Antileishmanial Activity and Structure-Activity Relationship of Triazolic Compounds Derived from the Neolignans Grandisin, Veraguensin, and Machilin G.

    PubMed

    Costa, Eduarda C; Cassamale, Tatiana B; Carvalho, Diego B; Bosquiroli, Lauriane S S; Ojeda, Mariáh; Ximenes, Thalita V; Matos, Maria F C; Kadri, Mônica C T; Baroni, Adriano C M; Arruda, Carla C P

    2016-06-20

    Sixteen 1,4-diaryl-1,2,3-triazole compounds 4-19 derived from the tetrahydrofuran neolignans veraguensin 1, grandisin 2, and machilin G 3 were tested against Leishmania (Leishmania) amazonensis intracellular amastigotes. Triazole compounds 4-19 were synthetized via Click Chemistry strategy by 1,3-dipolar cycloaddition between terminal acetylenes and aryl azides containing methoxy and methylenedioxy groups as substituents. Our results suggest that most derivatives were active against intracellular amastigotes, with IC50 values ranging from 4.4 to 32.7 µM. The index of molecular hydrophobicity (ClogP) ranged from 2.8 to 3.4, reflecting a lipophilicity/hydrosolubility rate suitable for transport across membranes, which may have resulted in the potent antileishmanial activity observed. Regarding structure-activity relationship (SAR), compounds 14 and 19, containing a trimethoxy group, were the most active (IC50 values of 5.6 and 4.4 µM, respectively), with low cytotoxicity on mammalian cells (SI = 14.1 and 10.6). These compounds induced nitric oxide production by the host macrophage cells, which could be suggested as the mechanism involved in the intracellular killing of parasites. These results would be useful for the planning of new derivatives with higher antileishmanial activities.

  14. Friend Flips: A Story Activity about Relationships

    ERIC Educational Resources Information Center

    Szucs, Leigh; Reyes, Jovanni V.; Farmer, Jennifer; Wilson, Kelly L.; McNeill, Elisa Beth

    2015-01-01

    Adolescents are influenced by the type, length and quality of the connections shared with different people throughout their lifespan. Relationships with peers, friends, and adults help to shape knowledge, attitudes, and beliefs related to health. Recognizing healthy or unhealthy characteristics allow youth to strengthen relationships and…

  15. Brief Report: Activities in Heterosexual Romantic Relationships--Grade Differences and Associations with Relationship Satisfaction

    ERIC Educational Resources Information Center

    Carlson, Wendy; Rose, Amanda J.

    2012-01-01

    Whereas much research addresses relations of youths' heterosexual romantic relationships with sexual and/or delinquent activities, less attention has been paid to youths' more normative, day-to-day activities with romantic partners. This gap in the literature is problematic given that these activities define the substance of the relationships and…

  16. SAR studies on hydropentalene derivatives--Important core units of biologically active tetramic acid macrolactams and ptychanolides.

    PubMed

    Lutz, Vanessa; Mannchen, Fabian; Krebs, Michael; Park, Natja; Krüger, Claudia; Raja, Aruna; Sasse, Florenz; Baro, Angelika; Laschat, Sabine

    2014-07-01

    Structurally diverse bicyclo[3.3.0]octanes were prepared and tested for their biological activity. Both the antiproliferative activity and the results of phenotypic characterization varied with the substitution patterns. Two derivatives displayed high inhibitory (IC50 ≤3μM) activity against the L-929 cell line, but differed in their mode of action. A cluster analysis with impedance profiling data showed the two compounds in relationship to microtubule interfering compounds. In PtK2 cells treated with both derivatives a perturbing effect on the microtubular network was observed, whereas the actin cytoskeleton in incubated PtK2 cells was disturbed only by one compound. The effects on tubulin and actin polymerization could be confirmed by in vitro polymerization experiments.

  17. Synergistic measurements of ocean winds and waves from SAR

    NASA Astrophysics Data System (ADS)

    Zhang, Biao; Li, Xiaofeng; Perrie, William; He, Yijun

    2015-09-01

    In this study we present a synergistic method to retrieve both ocean surface wave and wind fields from spaceborne quad-polarization (QP) synthetic aperture radar (SAR) imaging mode data. This algorithm integrates QP-SAR wind vector retrieval model and the wave retrieval model, with consideration to the nonlinear mapping relationship between ocean wave spectra and SAR image spectra, in order to synergistically retrieve wind fields and wave directional spectra. The method does not require a priori information on the sea state. It combines the observed VV-polarized SAR image spectra with the retrieved wind vectors from the VH-polarized SAR image, to estimate the wind-generated wave directional spectra. The differences between the observed SAR spectra and optimal SAR image spectra associated with the wind waves are interpreted as the contributions from the swell waves. The retrieved ocean wave spectra are used to estimate the integrated spectral wave parameters such as significant wave heights, wavelengths, wave directions and wave periods. The wind and wave parameters retrieved by QP-SAR are validated against those measured by the National Data Buoy Center (NDBC) directional wave buoys under different sea states. The validation results show that the QP-SAR SAR has potential to simultaneously measure the ocean surface waves and wind fields from space.

  18. Real time SAR processing

    NASA Technical Reports Server (NTRS)

    Premkumar, A. B.; Purviance, J. E.

    1990-01-01

    A simplified model for the SAR imaging problem is presented. The model is based on the geometry of the SAR system. Using this model an expression for the entire phase history of the received SAR signal is formulated. From the phase history, it is shown that the range and the azimuth coordinates for a point target image can be obtained by processing the phase information during the intrapulse and interpulse periods respectively. An architecture for a VLSI implementation for the SAR signal processor is presented which generates images in real time. The architecture uses a small number of chips, a new correlation processor, and an efficient azimuth correlation process.

  19. Structure-activity relationships of 6-(2,6-dichlorophenyl)-8-methyl-2-(phenylamino)pyrido[2,3-d]pyrimidin-7-ones: toward selective Abl inhibitors

    PubMed Central

    Antczak, Christophe; Veach, Darren R.; Ramirez, Christina N.; Minchenko, Maria A.; Shum, David; Calder, Paul A.; Frattini, Mark G.; Clarkson, Bayard; Djaballah, Hakim

    2013-01-01

    We report the design, synthesis and structure-activity relationship (SAR) of a series of novel pyrido[2,3-d]pyrimidin-7-one compounds as potent Abl kinase inhibitors. We evaluate their specificity profile against a panel of human recombinant kinases, as well as their biological profile toward a panel of well characterized cancer cell lines. Our study reveals that substitutions in the -3 and -4 positions of the phenylamino moiety lead to improved potency and improved selectivity both in target-based and cell based assays. Altogether, our results provide an insight into the SAR of pyrido[2,3-d]pyrimidin-7-ones for the development of drug candidates with improved potency and selectivity for the targeted treatment of CML. PMID:19889540

  20. Synthesis and Structure-activity Relationship Studies of O-Biphenyl-3-yl Carbamates as Peripherally Restricted Fatty Acid Amide Hydrolase Inhibitors

    PubMed Central

    Moreno-Sanz, Guillermo; Duranti, Andrea; Melzig, Laurin; Fiorelli, Claudio; Ruda, Gian Filippo; Colombano, Giampiero; Mestichelli, Paola; Sanchini, Silvano; Tontini, Andrea; Mor, Marco; Bandiera, Tiziano; Scarpelli, Rita; Tarzia, Giorgio; Piomelli, Daniele

    2014-01-01

    The peripherally restricted fatty acid amide hydrolase (FAAH) inhibitor URB937 (3, cyclohexylcarbamic acid 3’-carbamoyl-6-hydroxybiphenyl-3-yl ester) is extruded from the brain and spinal cord by the Abcg2 efflux transporter. Despite its inability to enter the central nervous system (CNS), 3 exerts profound antinociceptive effects in mice and rats, which result from the inhibition of FAAH in peripheral tissues and the consequent enhancement of anandamide signaling at CB1 cannabinoid receptors localized on sensory nerve endings. In the present study, we examined the structure-activity relationships (SAR) for the biphenyl region of compound 3, focusing on the carbamoyl and hydroxyl groups in the distal and proximal phenyl rings. Our SAR studies generated a new series of peripherally restricted FAAH inhibitors and identified compound 35 (cyclohexylcarbamic acid 3’-carbamoyl-5-hydroxybiphenyl-3-yl ester) as the most potent brain-impermeant FAAH inhibitor disclosed to date. PMID:23822179

  1. Analysis of SARS-CoV E protein ion channel activity by tuning the protein and lipid charge.

    PubMed

    Verdiá-Báguena, Carmina; Nieto-Torres, Jose L; Alcaraz, Antonio; Dediego, Marta L; Enjuanes, Luis; Aguilella, Vicente M

    2013-09-01

    A partial characterization of the ion channels formed by the SARS coronavirus (CoV) envelope (E) protein was previously reported (C. Verdiá-Báguena et al., 2012 [12]). Here, we provide new significant insights on the involvement of lipids in the structure and function of the CoV E protein channel on the basis of three series of experiments. First, reversal potential measurements over a wide range of pH allow the dissection of the contributions to channel selectivity coming from ionizable residues of the protein transmembrane domain and also from the negatively charged groups of diphytanoyl phosphatidylserine (DPhPS) lipid. The corresponding effective pKas are consistent with the model pKas of the acidic residue candidates for titration. Second, the change of channel conductance with salt concentration reveals two distinct regimes (Donnan-controlled electrodiffusion and bulk-like electrodiffusion) fully compatible with the outcomes of selectivity experiments. Third, by measuring channel conductance in mixtures of neutral diphytanoyl phosphatidylcholine (DPhPC) lipids and negatively charged DPhPS lipids in low and high salt concentrations we conclude that the protein-lipid conformation in the channel is likely the same in charged and neutral lipids. Overall, the whole set of experiments supports the proteolipidic structure of SARS-CoV E channels and explains the large difference in channel conductance observed between neutral and charged membranes.

  2. Synthesis and structure-activity relationship of α-keto amides as enterovirus 71 3C protease inhibitors.

    PubMed

    Zeng, Debin; Ma, Yuying; Zhang, Rui; Nie, Quandeng; Cui, Zhengjie; Wang, Yaxin; Shang, Luqing; Yin, Zheng

    2016-04-01

    α-Keto amide derivatives as enterovirus 71 (EV71) 3C protease (3C(pro)) inhibitors have been synthesized and assayed for their biochemical and antiviral activities. structure-activity relationship (SAR) study indicated that small moieties were primarily tolerated at P1' and the introduction of para-fluoro benzyl at P2 notably improved the potency of inhibitor. Inhibitors 8v, 8w and 8x exhibited satisfactory activity (IC50=1.32±0.26μM, 1.88±0.35μM and 1.52±0.31μM, respectively) and favorable CC50 values (CC50>100μM). α-Keto amide may represent a good choice as a warhead for EV71 3C(pro) inhibitor.

  3. Synthesis, insecticidal activities, and SAR studies of novel pyridylpyrazole acid derivatives based on amide bridge modification of anthranilic diamide insecticides.

    PubMed

    Wang, Bao-Lei; Zhu, Hong-Wei; Ma, Yi; Xiong, Li-Xia; Li, Yong-Qiang; Zhao, Yu; Zhang, Ji-Feng; Chen, You-Wei; Zhou, Sha; Li, Zheng-Ming

    2013-06-12

    Anthranilic diamides are one of the most important classes of modern agricultural insecticides. To discover new structure-modified compounds with high activity, series of novel carbonyl thioureas, carbonyl ureas, oxadiazoles, carbonyl thiophosphorylureas, oxadiazole-containing amides, and thiazoline-containing amides were designed through the modification of the amide bridge based on the structure of chlorantraniliprole and were synthesized, and bioassays were carried out. The compounds were characterized and confirmed by melting point, IR, (1)H NMR, and elemental analyses or HRMS. Preliminary bioassays indicated that some compounds exhibited significant insecticidal activities against oriental armyworm, diamondback moth, beet armyworm, corn borer, and mosquito. Among them, trifluoroethoxyl-containing carbonyl thiourea 20a showed best larvicidal activity against oriental armyworm, with LC50 and LC95 values of 0.1812 and 0.7767 mg/L, respectively. Meanwhile, 20c and 20e showed 86 and 57% death rates against diamondback moth at 0.005 mg/L, and the LC50 values of the two compounds were 0.0017 and 0.0023 mg/L, respectively, which were lower than that of the control chlorantraniliprole. The relationship between structure and insecticidal activity was discussed, and the HF calculation results indicated that the carbonyl thiourea moiety plays an important role in the insecticidal activity. The present work demonstrated that the trifluoroethoxyl-containing carbonyl thioureas can be used as lead compounds for further development of novel insecticides.

  4. Characterizing hydrologic changes of Great Dismal Swamp using SAR/InSAR technology

    NASA Astrophysics Data System (ADS)

    Kim, J. W.; Lu, Z.; Zhu, Z.

    2015-12-01

    Great Dismal Swamp is one of the largest, northernmost peatlands on the Atlantic Coastal Plain, and the swamp is underlain by a thick water-logged organic soil layer (peat) made up of dead and decaying plant material. The peatlands play a role as the sink of large amount of soil organic carbon and methane. However, the disturbance of the peatland negatively impacted the ecosystem and contributed to the climate change caused by the released greenhouse gas. Our SAR/InSAR methods observed the hydrologic changes in the peatlands, which is a key factor to conserve the wetland, through several methods. First, we compared averaged SAR intensity from C- and L-band SAR sensors with groundwater level changes, and deduced a linear relationship between the SAR backscattering intensity and the groundwater level change. Second, we extracted the inundated area during wet season from InSAR coherence. Third, we measured the relative water level changes in the inundated area using the interferometric phases. Finally, we estimated the groundwater level changes corresponding to the soil moisture changes from time-series InSAR method. Our results can provide the unique opportunity to understand the occurring hydrologic and vegetation changes in the Great Dismal Swamp.

  5. Ongoing Active Deformation Processes at Fernandina Volcano (Galapagos) Detected via Multi-Orbit COSMO-SkyMed SAR Data Analysis

    NASA Astrophysics Data System (ADS)

    Pepe, Susi; Castaldo, Raffaele; De Luca, Claudio; Casu, Francesco; Tizzani, Pietro; Sansosti, Eugenio

    2014-05-01

    Fernandina Volcano, Galápagos (Ecuador), has experienced several uplift and eruption episodes over the last twenty-two years. The ground deformation between 2002 and 2006 was interpreted as the effect of an inflation phenomenon of two separate magma reservoirs beneath the caldera. Moreover, the uplift deformation occurred during the 2005 eruption was concentrated near the circumferential eruptive fissures, while being superimposed on a broad subsidence centred on the caldera. The geodetic studies emphasized the presence of two sub volcanic lateral intrusions from the central storage system in December 2006 and August 2007. The latest eruption in 2009 was characterized by lava flows emitted from the SW radial fissures. We analyze the spatial and temporal ground deformation between March 2012 and July 2013, by using data acquired by COSMO-SkyMed X-band constellation along both ascending and descending orbits and by applying advanced InSAR techniques. In particular, we use the SBAS InSAR approach and combine ascending and descending time series to produce vertical and East-West components of the mean deformation velocity and deformation time series. Our analysis revealed a new uplift phenomenon due to the stress concentration inside the shallow magmatic system of the volcano. In particular, the vertical mean velocity map shows that the deformation pattern is concentrated inside caldera region and is characterized by strongly radial symmetry with a maximum displacement of about 20 cm in uplift; an axial symmetry is also observed in the EW horizontal mean velocity map, showing a maximum displacement of about +12 cm towards East for the SE flank, and -12 cm towards West for the NW flank of the volcano. Moreover, the deformation time series show a rather linear uplift trend from March to September 2012, interrupted by a low deformation rate interval lasting until January 2013. After this stage, the deformation shows again a linear behaviour with an increased uplift rate

  6. Formation Flying for Distributed InSAR

    NASA Technical Reports Server (NTRS)

    Scharf, Daniel P.; Murray, Emmanuell A.; Ploen, Scott R.; Gromov, Konstantin G.; Chen, Curtis W.

    2006-01-01

    We consider two spacecraft flying in formation to create interferometric synthetic aperture radar (InSAR). Several candidate orbits for such in InSar formation have been previously determined based on radar performance and Keplerian orbital dynamics. However, with out active control, disturbance-induced drift can degrade radar performance and (in the worst case) cause a collision. This study evaluates the feasibility of operating the InSAR spacecraft as a formation, that is, with inner-spacecraft sensing and control. We describe the candidate InSAR orbits, design formation guidance and control architectures and algorithms, and report the (Delta)(nu) and control acceleration requirements for the candidate orbits for several tracking performance levels. As part of determining formation requirements, a formation guidance algorithm called Command Virtual Structure is introduced that can reduce the (Delta)(nu) requirements compared to standard Leader/Follower formation approaches.

  7. Crystal structure of the SarR protein from Staphylococcus aureus

    PubMed Central

    Liu, Yingfang; Manna, Adhar; Li, Ronggui; Martin, Wesley E.; Murphy, Robert C.; Cheung, Ambrose L.; Zhang, Gongyi

    2001-01-01

    The expression of virulence determinants in Staphylococcus aureus is controlled by global regulatory loci (e.g., sarA and agr). The sar (Staphylococcus accessory regulator) locus is composed of three overlapping transcripts (sarA P1, P3, and P2, transcripts initiated from the P1, P3, and P2 promoters, respectively), all encoding the 124-aa SarA protein. The level of SarA, the major regulatory protein, is partially controlled by the differential activation of the sarA promoters. We previously partially purified a 13.6-kDa protein, designated SarR, that binds to the sarA promoter region to down-modulate sarA transcription from the P1 promoter and subsequently SarA expression. SarR shares sequence similarity to SarA, and another SarA homolog, SarS. Here we report the 2.3 Å-resolution x-ray crystal structure of the dimeric SarR-MBP (maltose binding protein) fusion protein. The structure reveals that the SarR protein not only has a classic helix–turn–helix module for DNA binding at the major grooves, but also has an additional loop region involved in DNA recognition at the minor grooves. This interaction mode could represent a new functional class of the “winged helix” family. The dimeric SarR structure could accommodate an unusually long stretch of ≈27 nucleotides with two or four bending points along the course, which could lead to the bending of DNA by 90° or more, similar to that seen in the catabolite activator protein (CAP)–DNA complex. The structure also demonstrates the molecular basis for the stable dimerization of the SarR monomers and possible motifs for interaction with other proteins. PMID:11381122

  8. Volcano Deformation and Modeling on Active Volcanoes in the Philippines from ALOS InSAR Time Series

    NASA Astrophysics Data System (ADS)

    Morales Rivera, Anieri M.; Amelung, Falk; Eco, Rodrigo

    2015-05-01

    Bulusan, Kanlaon, and Mayon volcanoes have erupted over the last decade, and Taal caldera showed signs of volcanic unrest within the same time range. Eruptions at these volcanoes are a threat to human life and infrastructure, having over 1,000,000 people living within 10 km from just these 4 volcanic centers. For this reason, volcano monitoring in the Philippines is of extreme importance. We use the ALOS-1 satellite from the Japanese Aerospace Exploration Agency (JAXA) to make an InSAR time series analysis over Bulusan, Kanlaon, Mayon, and Taal volcanoes for the 2007-2011 period. Time-dependent deformation was detected at all of the volcanoes. Deformation related to changes in pressurization of the volcanic systems was found on Taal caldera and Bulusan volcanoes, with best fitting Mogi sources located at half-space depths of 3.07 km and 0.5 km respectively.

  9. Natural and Synthetic Flavonoids: Structure-Activity Relationship and Chemotherapeutic Potential for the Treatment of Leukemia.

    PubMed

    Menezes, José C J M D S; Orlikova, Barbora; Morceau, Franck; Diederich, Marc

    2016-07-29

    Flavonoids and their derivatives are polyphenolic secondary metabolites with an extensive spectrum of pharmacological activities, including antioxidants, antitumor, anti-inflammatory, and antiviral activities. These flavonoids can also act as chemopreventive agents by their interaction with different proteins and can play a vital role in chemotherapy, suggesting a positive correlation between a lower risk of cancer and a flavonoid-rich diet. These agents interfere with the main hallmarks of cancer by various individual mechanisms, such as inhibition of cell growth and proliferation by arresting the cell cycle, induction of apoptosis and differentiation, or a combination of these mechanisms. This review is an effort to highlight the therapeutic potential of natural and synthetic flavonoids as anticancer agents in leukemia treatment with respect to the structure-activity relationship (SAR) and their molecular mechanisms. Induction of cell death mechanisms, production of reactive oxygen species, and drug resistance mechanisms, including p-glycoprotein efflux, are among the best-described effects triggered by the flavonoid polyphenol family. PMID:26463658

  10. Crystal Structures and Structure–Activity Relationships of Imidazothiazole Derivatives as IDO1 Inhibitors

    PubMed Central

    2014-01-01

    Indoleamine 2,3-dioxygenase 1 (IDO1) is considered as a promising target for the treatment of several diseases, including neurological disorders and cancer. We report here the crystal structures of two IDO1/IDO1 inhibitor complexes, one of which shows that Amg-1 is directly bound to the heme iron of IDO1 with a clear induced fit. We also describe the identification and preliminary optimization of imidazothiazole derivatives as novel IDO1 inhibitors. Using our crystal structure information and structure–activity relationships (SAR) at the pocket-B of IDO1, we found a series of urea derivatives as potent IDO1 inhibitors and revealed that generation of an induced fit and the resulting interaction with Phe226 and Arg231 are essential for potent IDO1 inhibitory activity. The results of this study are very valuable for understanding the mechanism of IDO1 activation, which is very important for structure-based drug design (SBDD) to discover potent IDO1 inhibitors. PMID:25313323

  11. Building detection in SAR imagery

    SciTech Connect

    Steinbach, Ryan Matthew

    2015-04-01

    Current techniques for building detection in Synthetic Aperture Radar (SAR) imagery can be computationally expensive and/or enforce stringent requirements for data acquisition. I present two techniques that are effective and efficient at determining an approximate building location. This approximate location can be used to extract a portion of the SAR image to then perform a more robust detection. The proposed techniques assume that for the desired image, bright lines and shadows, SAR artifact effects, are approximately labeled. These labels are enhanced and utilized to locate buildings, only if the related bright lines and shadows can be grouped. In order to find which of the bright lines and shadows are related, all of the bright lines are connected to all of the shadows. This allows the problem to be solved from a connected graph viewpoint, where the nodes are the bright lines and shadows and the arcs are the connections between bright lines and shadows. For the first technique, constraints based on angle of depression and the relationship between connected bright lines and shadows are applied to remove unrelated arcs. The second technique calculates weights for the connections and then performs a series of increasingly relaxed hard and soft thresholds. This results in groups of various levels on their validity. Once the related bright lines and shadows are grouped, their locations are combined to provide an approximate building location. Experimental results demonstrate the outcome of the two techniques. The two techniques are compared and discussed.

  12. Synthesis and SAR requirements of adamantane-colchicine conjugates with both microtubule depolymerizing and tubulin clustering activities.

    PubMed

    Zefirova, Olga N; Nurieva, Evgeniya V; Shishov, Dmitrii V; Baskin, Igor I; Fuchs, Fabian; Lemcke, Heiko; Schröder, Fabian; Weiss, Dieter G; Zefirov, Nikolay S; Kuznetsov, Sergei A

    2011-09-15

    A series of analogues of conjugate 1, combining an adamantane-based paclitaxel (taxol) mimetic with colchicine was synthesized and tested for cytotoxicity in a cell-based assay with the human lung carcinoma cell line A549. The most active compounds (10 EC(50) 2 ± 1.0 nM, 23 EC(50) 6 ± 1.4 nM, 26 EC(50) 5 ± 1.8 nM, 28 EC(50) 11 ± 1.7 nM, 30 EC(50) 4.8 ± 0.5 nM) were found to interfere with the microtubule dynamics in an interesting manner. Treatment of the cells with these compounds promoted disassembly of microtubules followed by the formation of stable tubulin clusters. Structure-activity relationships for the analogues of 23 revealed the sensitivity of both cytotoxicity and tubulin clustering ability to the linker length. The presence of adamantane (or another bulky hydrophobic and non-aromatic moiety) in 23 was found to play an important role in the formation of tubulin clusters. Structural requirements for optimal activity have been partially explained by molecular modeling. PMID:21873068

  13. Antiviral drug discovery against SARS-CoV.

    PubMed

    Wu, Yu-Shan; Lin, Wen-Hsing; Hsu, John T-A; Hsieh, Hsing-Pang

    2006-01-01

    Severe Acute Respiratory Syndrome (SARS) is a life-threatening infectious disease caused by SARS-CoV. In the 2003 outbreak, it infected more than 8,000 people worldwide and claimed the lives of more than 900 victims. The high mortality rate resulted, at least in part, from the absence of definitive treatment protocols or therapeutic agents. Although the virus spreading has been contained, due preparedness and planning, including the successful development of antiviral drugs against SARS-CoV, is necessary for possible reappearance of SARS. In this review, we have discussed currently available strategies for antiviral drug discovery and how these technologies have been utilized to identify potential antiviral agents for the inhibition of SARS-CoV replication. Moreover, progress in the drug development based on different molecular targets is also summarized, including 1) Compounds that block the S protein-ACE2-mediated viral entry; 2) Compounds targeting SARS-CoV M(pro); 3) Compounds targeting papain-like protease 2 (PLP2); 4) Compounds targeting SARS-CoV RdRp; 5) Compounds targeting SARS-CoV helicase; 6) Active compounds with unspecified targets; and 7) Research on siRNA. This review aims to provide a comprehensive account of drug discovery on SARS. The experiences with the SARS outbreak and drug discovery would certainly be an important lesson for the drug development for any new viral outbreaks that may emerge in the future.

  14. Ethyl cinnamate derivatives as promising high-efficient acaricides against Psoroptes cuniculi: synthesis, bioactivity and structure-activity relationship.

    PubMed

    Zhang, Bingyu; Lv, Chao; Li, Weibo; Cui, Zhiming; Chen, Dongdong; Cao, Fangjun; Miao, Fang; Zhou, Le

    2015-01-01

    This paper reported the synthesis, structure-activity relationship (SAR) and acaricidal activity in vitro against Psoroptes cuniculi, a mange mite, of 25 ethyl cinnamate derivatives. All target compounds were synthesized and elucidated by means of MS, (1)H- and (13)C-NMR analysis. The results showed that 24 out of 25 tested compounds at 1.0 mg/mL demonstrated acaricidal activity in varying degrees. Among them, 6, 15, 26, 27 and 30 showed significant activity with median lethal concentration values (LC50) of 89.3, 119.0, 39.2, 29.8 and 41.2 µg/mL, respectively, which were 2.1- to 8.3-fold the activity of ivermectin (LC50=247.4 µg/mL), a standard drug in the treatment of Psoroptes cuniculi. Compared with ivermectin, with a median lethal time value (LT50) of 8.9 h, 27 and 30 showed smaller LT50 values of 7.9 and 1.3 h, respectively, whereas 6, 15 and 26 showed slightly larger LT50 values of 10.6, 11.0 and 10.4 h at 4.5 µmol/mL. SARs showed that the presence of o-NO2 or m-NO2 on the benzene ring significantly improved the activity, whereas the introduction of a hydroxy, methoxy, acetoxy, methylenedioxy, bromo or chloro group reduced the activity. (E)-Cinnamates were more effective than their (Z)-isomer. Nevertheless, the carbon-carbon double bond in the acrylic ester moiety was proven not to be essential to improve the activity of cinnamic acid esters. Thus, the results strongly indicate that cinnamate derivatives, especially their dihydro derivatives, should be promising candidates or lead compounds for the development of novel acaricides for the effective control of animal or human acariasis. PMID:25739666

  15. Synthesis, SAR, and series evolution of novel oxadiazole-containing 5-lipoxygenase activating protein inhibitors: discovery of 2-[4-(3-{(r)-1-[4-(2-amino-pyrimidin-5-yl)-phenyl]-1-cyclopropyl-ethyl}-[1,2,4]oxadiazol-5-yl)-pyrazol-1-yl]-N,N-dimethyl-acetamide (BI 665915).

    PubMed

    Takahashi, Hidenori; Riether, Doris; Bartolozzi, Alessandra; Bosanac, Todd; Berger, Valentina; Binetti, Ralph; Broadwater, John; Chen, Zhidong; Crux, Rebecca; De Lombaert, Stéphane; Dave, Rajvee; Dines, Jonathon A; Fadra-Khan, Tazmeen; Flegg, Adam; Garrigou, Michael; Hao, Ming-Hong; Huber, John; Hutzler, J Matthew; Kerr, Steven; Kotey, Adrian; Liu, Weimin; Lo, Ho Yin; Loke, Pui Leng; Mahaney, Paige E; Morwick, Tina M; Napier, Spencer; Olague, Alan; Pack, Edward; Padyana, Anil K; Thomson, David S; Tye, Heather; Wu, Lifen; Zindell, Renee M; Abeywardane, Asitha; Simpson, Thomas

    2015-02-26

    The synthesis, structure-activity relationship (SAR), and evolution of a novel series of oxadiazole-containing 5-lipoxygenase-activating protein (FLAP) inhibitors are described. The use of structure-guided drug design techniques provided compounds that demonstrated excellent FLAP binding potency (IC50 < 10 nM) and potent inhibition of LTB4 synthesis in human whole blood (IC50 < 100 nM). Optimization of binding and functional potencies, as well as physicochemical properties resulted in the identification of compound 69 (BI 665915) that demonstrated an excellent cross-species drug metabolism and pharmacokinetics (DMPK) profile and was predicted to have low human clearance. In addition, 69 was predicted to have a low risk for potential drug-drug interactions due to its cytochrome P450 3A4 profile. In a murine ex vivo whole blood study, 69 demonstrated a linear dose-exposure relationship and a dose-dependent inhibition of LTB4 production. PMID:25671290

  16. Structure-activity relationship study of spider polyamine toxins as inhibitors of ionotropic glutamate receptors.

    PubMed

    Xiong, Xiao-Feng; Poulsen, Mette H; Hussein, Rama A; Nørager, Niels G; Strømgaard, Kristian

    2014-12-01

    The spider polyamine toxins Joro spider toxin-3 (JSTX-3) and Nephila polyamine toxins-1 and -8 (NPTX-1 and NPTX-8) are isolated from the venom of the orb-weaver spider Nephila clavata (Joro spider). They share a high degree of structural resemblance, their aromatic head groups being the only difference, and were recently found to be very potent open-channel blockers of ionotropic glutamate (iGlu) receptors. In this study we designed and synthesized a collection of 24 analogues of these toxins using a recently developed solid-phase synthetic methodology. Systematic variation in two regions of the toxins and subsequent evaluation of biological activity at AMPA and NMDA subtypes of iGlu receptors provided succinct information on structure-activity relationships. In particular, one set of analogues were found to display exquisite selectivity and potency for AMPA receptors relative to the natural products. Thus, this systematic SAR study has provided new pharmacological tools for studies of iGlu receptors.

  17. Structure-activity relationship study of acridine analogs as haspin and DYRK2 kinase inhibitors

    PubMed Central

    Cuny, Gregory D.; Robin, Maxime; Ulyanova, Natalia P.; Patnaik, Debasis; Pique, Valerie; Casano, Gilles; Liu, Ji-Feng; Lin, Xiangjie; Xian, Jun; Glicksman, Marcie A.; Stein, Ross L.; Higgins, Jonathan M.G.

    2010-01-01

    Haspin is a serine/threonine kinase required for completion of normal mitosis that is highly expressed during cell proliferation, including in a number of neoplasms. Consequently, it has emerged as a potential therapeutic target in oncology. A high throughput screen of approximately 140,000 compounds identified an acridine analog as a potent haspin kinase inhibitor. Profiling against a panel of 270 kinases revealed that the compound also exhibited potent inhibitory activity for DYRK2, another serine/threonine kinase. An optimization study of the acridine series revealed that the structure-activity relationship (SAR) of the acridine series for haspin and DYRK2 inhibition had many similarities. However, several structural differences were noted that allowed generation of a potent haspin kinase inhibitor (33, IC50 < 60 nM) with 180-fold selectivity over DYRK2. In addition, a moderately potent DYRK2 inhibitor (41, IC50 < 400 nM) with a 5.4-fold selectivity over haspin was also identified. PMID:20529681

  18. Structure–activity relationship study of acridine analogs as haspin and DYRK2 kinase inhibitors

    PubMed Central

    Cuny, Gregory D.; Robin, Maxime; Ulyanova, Natalia P.; Patnaik, Debasis; Pique, Valerie; Casano, Gilles; Liu, Ji-Feng; Lin, Xiangjie; Xian, Jun; Glicksman, Marcie A.; Stein, Ross L.; Higgins, Jonathan M. G.

    2011-01-01

    Haspin is a serine/threonine kinase required for completion of normal mitosis that is highly expressed during cell proliferation, including in a number of neoplasms. Consequently, it has emerged as a potential therapeutic target in oncology. A high throughput screen of approximately 140,000 compounds identified an acridine analog as a potent haspin kinase inhibitor. Profiling against a panel of 270 kinases revealed that the compound also exhibited potent inhibitory activity for DYRK2, another serine/threonine kinase. An optimization study of the acridine series revealed that the structure–activity relationship (SAR) of the acridine series for haspin and DYRK2 inhibition had many similarities. However, several structural differences were noted that allowed generation of a potent haspin kinase inhibitor (33, IC50 <60 nM) with 180-fold selectivity over DYRK2. In addition, a moderately potent DYRK2 inhibitor (41, IC50 <400 nM) with a 5.4-fold selectivity over haspin was also identified. PMID:20836251

  19. SAR11 bacteria linked to ocean anoxia and nitrogen loss.

    PubMed

    Tsementzi, Despina; Wu, Jieying; Deutsch, Samuel; Nath, Sangeeta; Rodriguez-R, Luis M; Burns, Andrew S; Ranjan, Piyush; Sarode, Neha; Malmstrom, Rex R; Padilla, Cory C; Stone, Benjamin K; Bristow, Laura A; Larsen, Morten; Glass, Jennifer B; Thamdrup, Bo; Woyke, Tanja; Konstantinidis, Konstantinos T; Stewart, Frank J

    2016-08-11

    Bacteria of the SAR11 clade constitute up to one half of all microbial cells in the oxygen-rich surface ocean. SAR11 bacteria are also abundant in oxygen minimum zones (OMZs), where oxygen falls below detection and anaerobic microbes have vital roles in converting bioavailable nitrogen to N2 gas. Anaerobic metabolism has not yet been observed in SAR11, and it remains unknown how these bacteria contribute to OMZ biogeochemical cycling. Here, genomic analysis of single cells from the world's largest OMZ revealed previously uncharacterized SAR11 lineages with adaptations for life without oxygen, including genes for respiratory nitrate reductases (Nar). SAR11 nar genes were experimentally verified to encode proteins catalysing the nitrite-producing first step of denitrification and constituted ~40% of OMZ nar transcripts, with transcription peaking in the anoxic zone of maximum nitrate reduction activity. These results link SAR11 to pathways of ocean nitrogen loss, redefining the ecological niche of Earth's most abundant organismal group.

  20. The relationship between chitotriosidase activity and tuberculosis.

    PubMed

    Chen, M; Deng, J; Li, W; Su, C; Xia, Y; Wang, M; Li, X; Abuaku, B K; Tan, H; Wen, S W

    2015-11-01

    Chitotriosidase, secreted by activated macrophages, is a biomarker of activated macrophages. In this study, we explored whether chitotriosidase could be adopted as a biomarker to evaluate the curative effect on tuberculosis (TB). Five counties were randomly selected out of 122 counties/cities/districts in Hunan Province, China. Our cases were all TB patients who were newly diagnosed or had been receiving treatment at the Centers for Disease Control (CDCs) of these five counties between April and August in 2009. Healthy controls were selected from a community health facility in the Kaifu district of Changsha City after frequency-matching of gender and age with the cases. Chitotriosidase activity was evaluated by a fluorometric assay. Categorical variables were analysed with the χ 2 test. Measurement data in multiple groups were tested with analysis of variance and least significant difference (LSD). Correlation between chitotriosidase activity and the degree of radiological extent (DRE) was examined by Spearman's rank correlation test. The average chitotriosidase activity levels of new TB cases, TB cases with different periods of treatment (6 months) and the control group were 54·47, 34·77, 21·54, 12·73 and 10·53 nmol/h.ml, respectively. Chitotriosidase activity in TB patients declined along with the continuity of treatment. The chitotriosidase activity of both smear-positive and the smear-negative pulmonary TB patients decreased after 6 months' treatment to normal levels (P < 0·05). Moreover, chitotriosidase activity was positively correlated with DRE (r = 0·607, P < 0·001). Our results indicate that chitotriosidase might be a marker of TB treatment effects. However, further follow-up study of TB patients is needed in the future. PMID:26418349

  1. Web-GIS-based SARS epidemic situation visualization

    NASA Astrophysics Data System (ADS)

    Lu, Xiaolin

    2004-03-01

    In order to research, perform statistical analysis and broadcast the information of SARS epidemic situation according to the relevant spatial position, this paper proposed a unified global visualization information platform for SARS epidemic situation based on Web-GIS and scientific virtualization technology. To setup the unified global visual information platform, the architecture of Web-GIS based interoperable information system is adopted to enable public report SARS virus information to health cure center visually by using the web visualization technology. A GIS java applet is used to visualize the relationship between spatial graphical data and virus distribution, and other web based graphics figures such as curves, bars, maps and multi-dimensional figures are used to visualize the relationship between SARS virus tendency with time, patient number or locations. The platform is designed to display the SARS information in real time, simulate visually for real epidemic situation and offer an analyzing tools for health department and the policy-making government department to support the decision-making for preventing against the SARS epidemic virus. It could be used to analyze the virus condition through visualized graphics interface, isolate the areas of virus source, and control the virus condition within shortest time. It could be applied to the visualization field of SARS preventing systems for SARS information broadcasting, data management, statistical analysis, and decision supporting.

  2. Structure-activity relationships of phthalates in inhibition of human placental 3β-hydroxysteroid dehydrogenase 1 and aromatase.

    PubMed

    Xu, Ren-Ai; Mao, Baiping; Li, Senlin; Liu, Jianpeng; Li, Xiaojun; Li, Huitao; Su, Ying; Hu, Guoxin; Lian, Qing-Quan; Ge, Ren-Shan

    2016-06-01

    Phthalates are associated with preterm delivery. However, the mechanism is unclear. Progesterone formed by 3β-hydroxysteroid dehydrogenase 1 (HSD3B1) and estradiol by aromatase (CYP19A1) in placenta are critical for maintaining pregnancy. In this study, we compared structure-activity relationships (SAR) of 14 phthalates varied in carbon atoms in alcohol moiety to inhibit human HSD3B1 in COS1 and CYP19A1 in JEG-3 cells. There were responses in that only diphthalates with 4-7 carbon atoms were competitive HSD3B1 inhibitors and diphthalates with 6 carbon atoms were CYP19A1 inhibitors. IC50s of dipentyl (DPP), bis(2-butoxyethyl) (BBOP), dicyclohexyl (DCHP), dibutyl (DBP), and diheptyl phthalate (DHP) were 50.12, 32.41, 31.42, 9.69, and 4.87μM for HSD3B1, respectively. DCHP and BBOP inhibited CYP19A1, with IC50s of 64.70 and 56.47μM. DPP, BBOP, DCHP, DBP, and DHP inhibited progesterone production in JEG-3 cells. In conclusion, our results indicate that there is clear SAR for phthalates in inhibition of HSD3B1 and CYP19A1.

  3. Possible relationships between solar activity and meteorological phenomena

    NASA Technical Reports Server (NTRS)

    Bandeen, W. R. (Editor); Maran, S. P. (Editor)

    1975-01-01

    A symposium was conducted in which the following questions were discussed: (1) the evidence concerning possible relationships between solar activity and meteorological phenomena; (2) plausible physical mechanisms to explain these relationships; and (3) kinds of critical measurements needed to determine the nature of solar/meteorological relationships and/or the mechanisms to explain them, and which of these measurements can be accomplished best from space.

  4. Active Ageing: Intergenerational Relationships and Social Generativity.

    PubMed

    Rossi, Giovanna; Boccacin, Lucia; Bramanti, Donatella; Meda, Stefania G

    2014-01-01

    This contribution is a reflection on the concept of active ageing from the perspective of relational sociology. At the same time, it offers practical implications and outlines possible future courses of action, in the face of demographic and relational scenarios rapidly changing, and the challenges that each day people of all generations are called to cope with. Active ageing is quite a recent concept and indicates an attitude towards ageing that enhances the quality of life as people become older. The goal of active ageing is to enable people to realise their potential for physical, social and mental well-being and to participate in social life also in the last stage of the life cycle. In this phase, the presence of a network of support, security and care adequate to the possible onset of problems and criticalities is crucial. Relational sociology frames the phenomenon of an ageing population in a dense network of social relations, primarily at the level of family and community. For this reason, as supported by the most recent sociological literature and evidence from studies conducted in Italy and abroad (cf. SHARE), it is extremely important to investigate the link between active ageing, intergenerational orientation (solidarity and exchanges) and practices of prosociality (i.e. engagement in third-sector activities and volunteering in later life).

  5. Attachment relationships and physical activity motivation of college students.

    PubMed

    Ullrich-French, Sarah; Smith, Alan L; Cox, Anne E

    2011-08-01

    This study was designed to assess the link of attachment relationships with physical activity motivation. Potential mediators of this link were examined in a cross-sectional study targeting college student physical activity motivation and behaviour. Participants completed self-reports of attachment relationships (with mother, father and best friend), self-determined motivation for physical activity, physical activity behaviour and the hypothesised mediator variables of perceived competence, autonomy and relatedness. The results provide support for the mediating role of these variables in the association of father attachment with self-determined motivation. Meaningful variance in self-determined motivation for physical activity and physical activity behaviour was explained. Overall, attachment relationships appear to be relevant, albeit modestly, to physical activity motivation of college students. The findings support continued efforts to integrate attachment and motivational perspectives in the study of college student health behaviour.

  6. Structure activity relationships of selected naphthalene derivatives

    SciTech Connect

    Schultz, T.W.; Dumont, J.N.; Sankey, F.D.; Schmoyer, R.L. Jr.

    1983-01-01

    Twenty-two derivatives of naphthalene were assayed under an acute static regime with biological activity being monitored as population growth of Tetrahymena pyriformis. Activity varied over one log unit. Substituent constant structure-activity analyses revealed the model, log BR = 0.282Ha + 0.352..pi.. + 0.692F + 0.334/sup 1/X/sub sub//sup v/ - 0.326R + 0.027, to be best and to account for 85% of the variation in log BR (BR, biological response; Ha, hydrogen acceptance; ..pi.., hydrophobic substituent constant; F, polar electronic substituent constant, /sup 1/X/sub sub//sup v/, substituent molar connectivity index; R, resonance electronic substituent constant). The Ha and ..pi.. parameters are the most important, accounting for 71% of the log BR variability. 21 references, 1 figure, 7 tables.

  7. Orally Active Metabotropic Glutamate Subtype 2 Receptor Positive Allosteric Modulators: Structure-Activity Relationships and Assessment in a Rat Model of Nicotine Dependence

    PubMed Central

    Sidique, Shyama; Dhanya, Raveendra-Panickar; Sheffler, Douglas J.; Nickols, Hilary Highfield; Yang, Li; Dahl, Russell; Mangravita-Novo, Arianna; Smith, Layton H.; D’Souza, Manoranjan S.; Semenova, Svetlana; Conn, P. Jeffrey; Markou, Athina; Cosford, Nicholas D. P.

    2012-01-01

    Compounds that modulate metabotropic glutamate subtype 2 (mGlu2) receptors have the potential to treat several disorders of the central nervous system (CNS) including drug dependence. Herein we describe the synthesis and structure-activity relationship (SAR) studies around a series of mGlu2 receptor positive allosteric modulators (PAMs). The effects of N-substitution (R1) and substitutions on the aryl ring (R2) were identified as key areas for SAR exploration (Figure 3). Investigation of the effects of varying substituents in both the isoindolinone (2) and benzisothiazolone (3) series led to compounds with improved in vitro potency and/or efficacy. In addition, several analogues exhibited promising pharmacokinetic (PK) properties. Furthermore, compound 2 was shown to dose-dependently decrease nicotine self-administration in rats following oral administration. Our data, showing for the first time efficacy of an mGlu2 receptor PAM in this in vivo model, suggest potential utility for the treatment of nicotine dependence in humans. PMID:23009245

  8. Quantitative Structure-Activity Relationships (QSARs) - Applications and Methodology

    NASA Astrophysics Data System (ADS)

    Cronin, Mark T. D.

    The aim of this introduction is to describe briefly the applications and methodologies involved in (Q)SAR and relate these to the various chapters in this volume. This chapter gives the reader an overview of how, why and where in silico methods, including (Q)SAR, have been utilized to predict endpoints as diverse as those from pharmacology and toxicology. It provides an illustration of how all the various topics in this book interweave to form a single coherent area of science.

  9. Young Adolescents' Perceptions of Romantic Relationships and Sexual Activity

    ERIC Educational Resources Information Center

    Royer, Heather R.; Keller, Mary L.; Heidrich, Susan M.

    2009-01-01

    The purpose of this article is to describe young adolescents' perceptions of romantic relationships, ratings of important romantic partner characteristics, and acceptability of sexual activity with romantic relationships. Fifty-seven eighth-grade participants (average age = 13.8 years) from one urban US public middle school completed an anonymous…

  10. Relationships between Reading Activities and Language Use.

    ERIC Educational Resources Information Center

    Gordon, Sandra L.; Van Dongen, Richard

    1988-01-01

    Noting that the ways children encounter and use print in the classroom can be examined as surface and organizing content of curriculum, this article provides descriptions of innovative uses of print in the kindergarten and elementary school classroom. Curriculum "surface content" includes activities, use of classroom space, display, and materials…

  11. Social Relationships, Leisure Activity, and Health in Older Adults

    PubMed Central

    Chang, Po-Ju; Wray, Linda; Lin, Yeqiang

    2015-01-01

    Objective Although the link between enhanced social relationships and better health has generally been well established, few studies have examined the role of leisure activity in this link. This study examined how leisure influences the link between social relationships and health in older age. Methods Using data from the 2006 and 2010 waves of the nationally representative U.S. Health and Retirement Study and structural equation modelling analyses, we examined data on 2,965 older participants to determine if leisure activities mediated the link between social relationships and health in 2010, controlling for race, education level, and health in 2006. Results The results demonstrated that leisure activities mediate the link between social relationships and health in these age groups. Perceptions of positive social relationships were associated with greater involvement in leisure activities, and greater involvement in leisure activities was associated with better health in older age. Discussion & Conclusions The contribution of leisure to health in these age groups is receiving increasing attention, and the results of this study add to the literature on this topic, by identifying the mediating effect of leisure activity on the link between social relationships and health. Future studies aimed at increasing leisure activity may contribute to improved health outcomes in older adults. PMID:24884905

  12. Relationships between Interlibrary Loan and Research Activity in Canada

    ERIC Educational Resources Information Center

    Duy, Joanna; Larivière, Vincent

    2014-01-01

    Interlibrary Loan borrowing rates in academic libraries are influenced by an array of factors. This article explores the relationship between interlibrary loan borrowing activity and research activity at 42 Canadian academic institutions. A significant positive correlation was found between interlibrary loan borrowing activity and measures of…

  13. Antiproliferative and Structure Activity Relationships of Amaryllidaceae Alkaloids.

    PubMed

    Cedrón, Juan C; Ravelo, Ángel G; León, Leticia G; Padrón, José M; Estévez-Braun, Ana

    2015-07-30

    The antiproliferative activity of a set of seven natural Amaryllidaceae alkaloids and 32 derivatives against four cancer cell lines (A2780, SW1573, T47-D and WiDr) was determined. The best antiproliferative activities were achieved with alkaloids derived from pancracine (2), haemanthamine (6) and haemantidine (7). For each skeleton, some structure-activity relationships were outlined.

  14. Input of UAV, DTM photo-interpretation and SAR interferometry on active tectonics applied on the Southern Coastal Range (SE Taiwan)

    NASA Astrophysics Data System (ADS)

    Deffontaines, Benoit; Chang, Kuo-Jen; Champenois, Johann; Magalhaes, Samuel; Serries, Gregory

    2016-04-01

    Taiwan is an excellent geomorphic laboratory where both extreme climatic events and high active tectonics compete. Moreover many Earth Sciences and Environmental data bases exist nowadays that help to better constrain both structural geology and active deformations. The latter unfortunately is still poorly known in the Cosatal Range of E.Taiwan in terms of geology due to access difficulties, high relief, paucity of roads, tropical vegetation and high climatic events (typhoons and heavy rainfall) and so on. Indirect methods such as photogrammetric survey using UAV's helps a lot to get high resolution topographic DEM and DTM, better than 10cm in planimetry, that helps a lot to get through careful photo-interpretation, a bird's eye view of the geology. Therefore we were able to much update the famous pre-existing geological maps (Wang and Chen, 1993). Moreover, by combining our high resolution topographic results with those of SAR interferometry (database of Champenois et al, EPSL, 2012), we were able to identify, characterise and quantify the differential active features toward the LOS of the Coastal Range (eastern Taiwan). In order to synthetise and to model the deformation of that famous place, we herein constructed more than 500 parallel projected profiles in order to locate, characterize and quantify the active tectonic features and compare them to the topography and the updated photo-interpreted geology (this work). We then were able to reconstruct the structural geometry of the Coastal Range and the Longitudinal Valley in SE Taiwan. Among our results, we reveal and prove : 1. the whole 2cm differential surrection of the Coastal Range ; 2. the differential displacement between both Central and Coastal Ranges ; 3. we explain the location of the Pinantashi river situated within the Lichi melange that correspond to the maximum surrection of the Coastal Range ; 4. we reveal the different units and their relative displacement within the Coastal Range itself ; 5. we

  15. SAR calibration technology review

    NASA Technical Reports Server (NTRS)

    Walker, J. L.; Larson, R. W.

    1981-01-01

    Synthetic Aperture Radar (SAR) calibration technology including a general description of the primary calibration techniques and some of the factors which affect the performance of calibrated SAR systems are reviewed. The use of reference reflectors for measurement of the total system transfer function along with an on-board calibration signal generator for monitoring the temporal variations of the receiver to processor output is a practical approach for SAR calibration. However, preliminary error analysis and previous experimental measurements indicate that reflectivity measurement accuracies of better than 3 dB will be difficult to achieve. This is not adequate for many applications and, therefore, improved end-to-end SAR calibration techniques are required.

  16. Comparison of in vitro antiviral activity of tea polyphenols against influenza A and B viruses and structure-activity relationship analysis.

    PubMed

    Yang, Zi-Feng; Bai, Li-Ping; Huang, Wen-bo; Li, Xu-Zhao; Zhao, Sui-Shan; Zhong, Nan-Shan; Jiang, Zhi-Hong

    2014-03-01

    Influenza poses a particular risk of severe outcomes in the elderly, the very young and those with underlying diseases. Tea polyphenols are the natural phenolic compounds in teas, and principally consist of catechins, proanthocyanidins, flavonols, and theaflavins, which antiviral activities have been reported recently. This study is to gain a further insight into potential of various tea polyphenols for inhibiting influenza virus infection. Five tea polyphenols exhibited inhibitory activity against influenza A virus in the trend of theaflavin>procyanidin B-2>procyanidin B-2 digallate>(-)-epigallocatechin(EGC)>(-)-epigallocatechingallate(EGCG) with IC50 values in the range of 16.2-56.5 μg/ml. Six of the tested compounds showed anti-influenza B virus activity in the order of kaempferol>EGCG>procyanidin B-2>(-)-EGC~methylated EGC>theaflavin with IC50 values in the range of 9.0-49.7 μg/ml. Based on these results, the structure-activity relationship (SAR) was explained as follows. First, the dimeric molecules, such as theaflavin and procyanidin B-2, generally displayed more potent antiviral activity against both influenza A and B viruses than the catechin monomers. Second, the kaempferol for inhibition of influenza B virus indicated that the more planar flavonol structure with only one C-4' phenolic hydroxyl group in the B ring is necessary for the anti-influenza B virus activity. A similar SAR can be drawn from the assays of another enveloped RNA virus, such as respiratory syncytial virus. These results are expected to provide guides for rational design of antiviral drugs based on polyphenols.

  17. Structure-activity relationships by mass spectrometry: identification of novel MMP-3 inhibitors.

    PubMed

    Ockey, Denise A; Dotson, Jenna L; Struble, Martin E; Stults, John T; Bourell, James H; Clark, Kevin R; Gadek, Thomas R

    2004-01-01

    A novel class of nonpeptide inhibitors of stromelysin (MMP-3) has been discovered with the use of mass spectrometry. The method relies on the development of structure-activity relationships by mass spectrometry (SAR by MS) and utilizes information derived from the binding of known inhibitors to identify novel inhibitors of a target protein with a minimum of synthetic effort. Noncovalent complexes of known inhibitors with a target protein are analyzed; these inhibitors are deconstructed into sets of fragments which compete for common or overlapping binding sites on the target protein. The binding of each fragment set can be studied independently. With the use of competition studies, novel members of each fragment set are identified from compound libraries that bind to the same site on the target protein. A novel inhibitor of the target protein was then constructed by chemically linking a combination of members of each fragment set in a manner guided by the proximity and orientation of the fragments derived from the known inhibitors. In the case of stromelysin, a novel inhibitor composed of favorably linked fragments was observed to form a 1:1 complex with stromelysin. Compounds that were not linked appropriately formed higher order complexes with stoichiometries of 2:1 or greater. These linked molecules were subsequently assessed for their ability to block stromelysin function in a chromogenic substrate assay.

  18. InSAR Evidence for an active shallow thrust fault beneath the city of Spokane Washington, USA

    USGS Publications Warehouse

    Wicks, Charles W.; Weaver, Craig S.; Bodin, Paul; Sherrod, Brian

    2013-01-01

    In 2001, a nearly five month long sequence of shallow, mostly small magnitude earthquakes occurred beneath the city of Spokane, a city with a population of about 200,000, in the state of Washington. During most of the sequence, the earthquakes were not well located because seismic instrumentation was sparse. Despite poor-quality locations, the earthquake hypocenters were likely very shallow, because residents near the city center both heard and felt many of the earthquakes. The combination of poor earthquake locations and a lack of known surface faults with recent movement make assessing the seismic hazards related to the earthquake swarm difficult. However, the potential for destruction from a shallow moderate-sized earthquake is high, for example Christchurch New Zealand in 2011, so assessing the hazard potential of a seismic structure involved in the Spokane earthquake sequence is important. Using interferometric synthetic aperture radar (InSAR) data from the European Space Agency ERS2 and ENVISAT satellites and the Canadian Space Agency RADARSAT-1, satellite we are able to show that slip on a shallow previously unknown thrust fault, which we name the Spokane Fault, is the source of the earthquake sequence. The part of the Spokane Fault that slipped during the 2001 earthquake sequence underlies the north part of the city, and slip on the fault was concentrated between ~0.3 and 2 km depth. Projecting the buried fault plane to the surface gives a possible surface trace for the Spokane Fault that strikes northeast from the city center into north Spokane.

  19. InSAR Evidence for the Spokane Fault, an Active Shallow Thrust Fault Beneath the City of Spokane Washington, USA

    NASA Astrophysics Data System (ADS)

    Wicks, C.; Weaver, C. S.; Bodin, P.; Sherrod, B. L.

    2012-12-01

    In 2001 a nearly five month long sequence of shallow, mostly small magnitude earthquakes occurred beneath Spokane, a city with a population of about 200,000, in the state of Washington. The Spokane area, an area of low background seismicity, is on the northeastern edge of the Columbia Basin, a physiographic province largely covered with Miocene flood basalts of the Columbia River Basalt Group. The earthquake sequence appears to have begun with an isolated magnitude 2 earthquake on May 24, 2001, but began in earnest with a magnitude 3.9 earthquake on June 25, 2001 and ended on November 23, 2001, with a total of 105 earthquakes recorded up to a magnitude 4. During most of the sequence, the earthquakes were not well located because seismic instrumentation was sparse. Despite poor-quality locations, the earthquake hypocenters were likely very shallow, because residents in small areas of Spokane reported feeling many of the earthquakes in the sequence and hearing explosion-like noises associated with some of the earthquakes. Using interferometric synthetic aperture radar (InSAR) data from the European Space Agency ERS2 and ENVISAT satellites and the Canadian Space Agency RADARSAT-1 satellite we are able to show that slip on a shallow previously unknown thrust fault, that we name the Spokane Fault, is the source of the earthquake sequence. The fault strikes northeast, dips ~30 degrees to the northwest, and the maximum slip was ~45 mm. The part of the Spokane Fault that slipped during the 2001 earthquake sequence underlies the north part of the city, and slip on the fault was concentrated between ~0.3 and 2 km depth. Projecting the buried fault plane to the surface gives a possible surface trace for the Spokane Fault; it strikes northeast from the city center into north Spokane. An accurate assessment of the hazard potential of the Spokane Fault requires additional studies to delineate the fault and map the subsurface geology.

  20. Flavonoids and tyrosine nitration: structure-activity relationship correlation with enthalpy of formation.

    PubMed

    Sadeghipour, Mitra; Terreux, Raphael; Phipps, Jenny

    2005-03-01

    The ability of 11 flavonoids, naturally occurring polyphenols, and their related structure-activity relationships (SAR's) for inhibiting peroxynitrite-induced nitration of tyrosine was investigated. The flavonoids under study could be classified into four groups having very distinct in vitro inhibition effects. We also calculated the heat of formation (DeltaH(f)) of the corresponding flavonoids radicals which supported this finding. The most effective flavonoids included: catechin, taxifolin, luteolin, quercetin, and myricetin which have a common structural feature of ortho-dihydroxyl moiety (3',4'-OH substitution). Naringenin, kaempferol, and morin were 50% less effective inhibitors than the former group of flavonoid while their activities were in the range of trolox (an alpha-tocopherol analogue). The common structural aspect of this group of flavonoids is 4'-OH substitution. Therefore, these two groups of flavonoids may have similar mechanisms for their inhibition activity. No inhibition activity was observed by galangin. Apigenin behaved as a pro-oxidant in our in vitro study. Naringin was as effective as the second group at 4 mM tyrosine concentration while did not illustrate any inhibitory effect at 1 mM concentration of tyrosine. Our study provides further evidence for the importance of the catechol B ring and to a lesser effect the importance of 4'-OH substitution. Moreover, we observed very little or no influence on activity of flavonoids by 3-OH substitution and/or a C2-C3 double bond conjugated with 4-keto group within the subgroup containing the catechol moiety. Theoretical calculation of DeltaDeltaH(f) for tyrosyl radical repair by flavonoids (TyO*+FlOH-->TyOH+FlO*) correlated well with our in vitro results (inhibition% = -10 (DeltaDeltaH(f)), R2=0.906). Furthermore, this correlation was independent of tyrosine concentration. This model can be used to accurately predict the inhibitory effect of flavonoids on nitrotyrosine formation.

  1. Itraconazole Side Chain Analogues: Structure–Activity Relationship Studies for Inhibition of Endothelial Cell Proliferation, Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) Glycosylation, and Hedgehog Signaling

    PubMed Central

    Shi, Wei; Nacev, Benjamin A.; Aftab, Blake T.; Head, Sarah; Rudin, Charles M.; Liu, Jun O.

    2012-01-01

    Itraconazole is an antifungal drug that was recently found to possess potent antiangiogenic activity and anti-hedgehog (Hh) pathway activity. To search for analogues of itraconazole with greater potency and to understand the structure–activity relationship in both antiangiogenic and Hh targeting activity, 25 itraconazole side chain analogues were synthesized and assayed for inhibition of endothelial cell proliferation and Gli1 transcription in a medulloblastoma (MB) culture. Through this analysis, we have identified analogues with increased potency for inhibiting endothelial cell proliferation and the Hh pathway, as well as VEGFR2 glycosylation that was recently found to be inhibited by itraconazole. An SAR analysis of these activities revealed that potent activity of the analogues against VEGFR2 glycosylation was generally driven by side chains of at least four carbons in composition with branching at the α or β position. SAR trends for targeting the Hh pathway were divergent from those related to HUVEC proliferation or VEGFR2 glycosylation. These results also suggest that modification of the sec-butyl side chain can lead to enhancement of the biological activity of itraconazole. PMID:21936514

  2. Structure determination of glycogen synthase kinase-3 from Leishmania major and comparative inhibitor structure-activity relationships with Trypanosoma brucei GSK-3

    SciTech Connect

    Ojo, Kayode K; Arakaki, Tracy L; Napuli, Alberto J; Inampudi, Krishna K; Keyloun, Katelyn R; Zhang, Li; Hol, Wim G.J.; Verlind, Christophe L.M.J.; Merritt, Ethan A; Van Voorhis, Wesley C

    2012-04-24

    Glycogen synthase kinase-3 (GSK-3) is a drug target under intense investigation in pharmaceutical companies and constitutes an attractive piggyback target for eukaryotic pathogens. Two different GSKs are found in trypanosomatids, one about 150 residues shorter than the other. GSK-3 short (GeneDB: Tb927.10.13780) has previously been validated genetically as a drug target in Trypanosoma brucei by RNAi induced growth retardation; and chemically by correlation between enzyme and in vitro growth inhibition. Here, we report investigation of the equivalent GSK-3 short enzymes of L. major (LmjF18.0270) and L. infantum (LinJ18_V3.0270, identical in amino acid sequences to LdonGSK-3 short) and a crystal structure of LmajGSK-3 short at 2 Å resolution. The inhibitor structure-activity relationships (SARs) of L. major and L. infantum are virtually identical, suggesting that inhibitors could be useful for both cutaneous and visceral leishmaniasis. Leishmania spp. GSK-3 short has different inhibitor SARs than TbruGSK-3 short, which can be explained mostly by two variant residues in the ATP-binding pocket. Indeed, mutating these residues in the ATP-binding site of LmajGSK-3 short to the TbruGSK-3 short equivalents results in a mutant LmajGSK-3 short enzyme with SAR more similar to that of TbruGSK-3 short. The differences between human GSK-3β (HsGSK-3β) and LmajGSK-3 short SAR suggest that compounds which selectively inhibit LmajGSK-3 short may be found.

  3. Interplay Between Tectonics And Volcanic Processes Active In The Yellowstone Caldera Detected Via DInSAR And GPS Time-Series

    NASA Astrophysics Data System (ADS)

    Tizzani, Pietro; Battaglia, Maurizio; Castaldo, Raffaele; Pepe, Antonio; Zeni, Giovanni; Lanari, Riccardo

    2014-05-01

    We discriminate and quantify the effects of different stress sources that are active in the Yellowstone volcanic region. In particular, the use of long-term deformation time series allows us to separate the spatial and temporal contributions of the regional tectonic field due to North American (NA) plate motion from the dynamic of magmatic/hydrothermal sources beneath the caldera area. Yellowstone volcano was formed by three major caldera forming eruptions that occurred around 2.0, 1.3 and 0.64 Ma, the most recent one responsible for the 60 km-wide and 40 km-long Yellowstone caldera. Two structural resurgent domes emerged after the last caldera forming eruption: the Mallard Lake (ML) resurgent dome in the southwestern region of Yellowstone caldera, and the Sour Creek (SC) resurgent dome in the northeast part of the caldera. In this work, we extensively exploit DInSAR and GPS measurements to investigate surface deformation at Yellowstone caldera over the last 18 years. We start by analyzing the 1992-2010 deformation time series retrieved by applying the Small BAseline Subset (SBAS) DInSAR technique. This allows us identifying three macro-areas: i) Norris Geyser Basin (NGB), ii) ML and SC resurgent domes and iii) Snake River Plain (SRP), characterized by unique deformation behaviors. In particular, SRP shows a signal related to tectonic deformation, while the other two regions are influenced by the caldera unrest. To isolate the deformation signals related to different stress sources in the Yellowstone caldera, we also remove from the retrieved mean deformation velocity maps the mean displacement rate associated to the northern sector of the Snake River Plain. This latter is the result of tectonic processes controlled by complex interactions between the NA plate, moving in the ENE - WSW direction with a rate of about 2 cm/yr, and the flow of the asthenosphere plume beneath the Yellowstone volcanic region. These de-trended data allow recognizing four major deformation

  4. Design, Synthesis, and Structure--Activity Relationship of New 2-Aryl-3,4-dihydro-β-carbolin-2-ium Salts as Antifungal Agents.

    PubMed

    Hou, Zhe; Zhu, Li-Fei; Yu, Xin-chi; Sun, Ma-Qiang; Miao, Fang; Zhou, Le

    2016-04-13

    Twenty-two 2-aryl-9-methyl-3,4-dihydro-β-carbolin-2-ium bromides along with four 9-demethylated derivatives were synthesized and characterized by spectroscopic analysis. By using the mycelium growth rate method, the compounds were evaluated for antifungal activities in vitro against six plant pathogenic fungi, and structure-activity relationships (SAR) were derived. Almost all of the compounds showed obvious inhibition activity on each of the fungi at 150 μM. For all of the fungi, 10 of the compounds showed average inhibition rates of >80% at 150 μM, and most of their EC50 values were in the range of 2.0-30.0 μM. SAR analysis showed that the substitution pattern of the N-aryl ring significantly influences the activity; N9-alkylation improves the activity, whereas aromatization of ring-C reduces the activity. It was concluded that the present research provided a series of new 2-aryl-9-alkyl-3,4-dihydro-β-carbolin-2-iums with excellent antifungal potency and structure optimization design for the development of new carboline antifungal agents. PMID:27004437

  5. Expanding the synthesis of new trans-sulfonamide platinum complexes: cytotoxicity, SAR, fluorescent cell assays and stability studies.

    PubMed

    Del Solar, Virginia; Quiñones-Lombraña, Adolfo; Cabrera, Silvia; Padrón, José M; Ríos-Luci, Carla; Alvarez-Valdés, Amparo; Navarro-Ranninger, Carmen; Alemán, José

    2013-10-01

    In this manuscript, we describe the synthesis of new trans-N-sulfonamide platinum complexes and their antiproliferative activity (GI50, μM) in human solid tumors cells. The structure activity relationships (SAR), with different new synthesized complexes by variation in ligand, halogen and also in the stereochemistry of the ligand, has been studied. Solubility and stability studies have also been carried out as well as fluorescent cell assays in order to clarify the final target in the tumor cells. PMID:23474039

  6. The prospects for using (Q)SARs in a changing political environment--high expectations and a key role for the European Commission's joint research centre.

    PubMed

    Worth, A P; Van Leeuwen, C J; Hartung, T

    2004-01-01

    Recent policy developments in the European union (EU) and within the Organisation for Economic Cooperation and Development (OECD) have placed increased emphasis on the use of structure-activity relationships (SARs) and quantitative structure-activity relationships (QSARs), collectively referred to as (Q)SARs, within various regulatory programmes for the assessment of chemicals and products. The most significant example within the EU is the European commission's proposal (of 29 October 2003) to introduce a new system for managing chemicals (called REACH), which calls for an increased use of (Q)SARs and other non-animal methods, especially for the assessment of low production volume chemicals. Another development within the EU is the Seventh Amendment to the Cosmetics Directive, which foresees the phasing out of animal testing on cosmetics, combined with the imposition of marketing bans on cosmetics that have been tested on animals after certain deadlines. At the same time, the Existing Chemicals programme within the OECD is investigating ways of increasing the use of chemical category approaches, which depend heavily on the use of (Q)SARs, activity-activity relationships and read-across. Such developments are placing an enormous challenge on industry, regulatory bodies, and on the European commission's Joint Research Centre (JRC), which is responsible for providing independent scientific advice to policy makers in the European Commission and the Member States. This paper reviews the different scientific and regulatory purposes for which reliable (Q)SARs could be used, and describes the current work of the JRC in providing scientific support for the development, validation and implementation of (Q)SARs. PMID:15669693

  7. PHARUS airborne SAR concept

    NASA Astrophysics Data System (ADS)

    Snoeij, Paul; Pouwels, Henk; Koomen, Peter J.; Hoogeboom, Peter

    1995-11-01

    PHARUS (phased array universal SAR) is an airborne SAR concept which is being developed in the Netherlands. The PHARUS system differs from other airborne SARs by the use of a phased array antenna, which provides both for the flexibility in the design as well as for a compact, light-weight instrument that can be carried on small aircraft. The concept allows for the construction of airborne SAR systems on a common generic basis but tailored to specific user needs and can be seen as a preparation for future spaceborne SAR systems using solid state transmitters with electronically steerable phased array antenna. The whole approach is aimed at providing an economic and yet technically sophisticated solution to remote sensing or surveying needs of a specific user. The solid state phased array antenna consists of a collection of radiating patches; the design flexibility for a large part resides in the freedom to choose the number of patches, and thereby the essential radar performance parameters such as resolution and swath width. Another consequence of the use of the phased array antenna is the system's compactness and the possibility to rigidly mount it on a small aircraft. The use of small aircraft of course considerably improves the cost/benefit ratio of the use of airborne SAR. Flight altitude of the system is flexible between about 7,000 and 40,000 feet, giving much operational freedom within the meteo and airspace control limits. In the PHARUS concept the airborne segment is complemented by a ground segment, which consists of a SAR processor, possibly extended by a matching image processing package. (A quick look image is available in real-time on board the aircraft.) The SAR processor is UNIX based and runs on easily available hardware (SUN station). Although the additional image processing software is available, the SAR processing software is nevertheless designed to be able to interface with commercially available image processing software, as well as being able

  8. Gas-phase rate coefficients for the reactions of NO 3, OH and O 3 with α, β-unsaturated esters and ketones: Structure-activity relations (SARs)

    NASA Astrophysics Data System (ADS)

    Pfrang, Christian; King, Martin D.; Canosa-Mas, Carlos E.; Flugge, Mark; Wayne, Richard P.

    Gas-phase rate coefficients for the atmospherically important reactions of NO 3, OH and O 3 are predicted for 55 α, β-unsaturated esters and ketones. The rate coefficients were calculated using a correlation described previously [Pfrang, C., King, M.D., C. E. Canosa-Mas, C.E., Wayne, R.P., 2006. Atmospheric Environment 40, 1170-1179]. These rate coefficients were used to extend structure-activity relations for predicting the rate coefficients for the reactions of NO 3, OH or O 3 with alkenes to include α, β-unsaturated esters and ketones. Conjugation of an alkene with an α, β-keto or α, β-ester group will reduce the value of a rate coefficient by a factor of ˜110, ˜2.5 and ˜12 for reaction with NO 3, OH or O 3, respectively. The actual identity of the alkyl group, R, in -C(O)R or -C(O)OR has only a small influence. An assessment of the reliability of the SAR is given that demonstrates that it is useful for reactions involving NO 3 and OH, but less valuable for those of O 3 or peroxy nitrate esters.

  9. Hybrid polarity SAR architecture

    NASA Astrophysics Data System (ADS)

    Raney, R. Keith

    2009-05-01

    A space-based synthetic aperture radar (SAR) designed to provide quantitative information on a global scale implies severe requirements to maximize coverage and to sustain reliable operational calibration. These requirements are best served by the hybrid-polarity architecture, in which the radar transmits in circular polarization, and receives on two orthogonal linear polarizations, coherently, retaining their relative phase. This paper summarizes key attributes of hybrid-polarity dual- and quadrature-polarized SARs, reviews the associated advantages, formalizes conditions under which the signal-to-noise ratio is conserved, and describes the evolution of this architecture from first principles.

  10. Design, Synthesis, and Structure–Activity Relationship Studies of Fluorescent Inhibitors of Cycloxygenase-2 as Targeted Optical Imaging Agents

    PubMed Central

    2013-01-01

    Cycloxygenase-2 (COX-2) is an attractive target for molecular imaging because it is an inducible enzyme that is expressed in response to inflammatory and proliferative stimuli. Recently, we reported that conjugation of indomethacin with carboxy-X-rhodamine dyes results in the formation of effective, targeted, optical imaging agents able to detect COX-2 in inflammatory tissues and premalignant and malignant tumors (Uddin et al. Cancer Res. 2010, 70, 3618–3627). The present paper summarizes the details of the structure–activity relationship (SAR) studies performed for lead optimization of these dyes. A wide range of fluorescent conjugates were designed and synthesized, and each of them was tested for the ability to selectively inhibit COX-2 as the purified protein and in human cancer cells. The SAR study revealed that indomethacin conjugates are the best COX-2-targeted agents compared to the other carboxylic acid-containing nonsteroidal anti-inflammatory drugs (NSAIDs) or COX-2-selective inhibitors (COXIBs). An n-butyldiamide linker is optimal for tethering bulky fluorescent functionalities onto the NSAID or COXIB cores. The activity of conjugates also depends on the size, shape, and electronic properties of the organic fluorophores. These reagents are taken up by COX-2-expressing cells in culture, and the uptake is blocked by pretreatment with a COX inhibitor. In in vivo settings, these reagents become highly enriched in COX-2-expressing tumors compared to surrounding normal tissue, and they accumulate selectively in COX-2-expressing tumors as compared with COX-2-negative tumors grown in mice. Thus, COX-2-targeted fluorescent inhibitors are useful for preclinical and clinical detection of lesions containing elevated levels of COX-2. PMID:23488616

  11. BioSAR Airborne Biomass Sensing System

    SciTech Connect

    Graham, R.L.; Johnson, P.

    2007-05-24

    This CRADA was developed to enable ORNL to assist American Electronics, Inc. test a new technology--BioSAR. BioSAR is a an airborne, low frequency (80-120 MHz {approx} FM radio frequencies) synthetic aperture radar (SAR) technology which was designed and built for NASA by ZAI-Amelex under Patrick Johnson's direction. At these frequencies, leaves and small branches are nearly transparent and the majority of the energy reflected from the forest and returned to the radar is from the tree trunks. By measuring the magnitude of the back scatter, the volume of the tree trunk and therefore the biomass of the trunks can be inferred. The instrument was successfully tested on tropical rain forests in Panama. Patrick Johnson, with American Electronics, Inc received a Phase II SBIR grant from DOE Office of Climate Change to further test and refine the instrument. Mr Johnson sought ORNL expertise in measuring forest biomass in order for him to further validate his instrument. ORNL provided ground truth measurements of forest biomass at three locations--the Oak Ridge Reservation, Weyerhaeuser Co. commercial pine plantations in North Carolina, and American Energy and Power (AEP) Co. hardwood forests in southern Ohio, and facilitated flights over these forests. After Mr. Johnson processed the signal data from BioSAR instrument, the processed data were given to ORNL and we attempted to derive empirical relationships between the radar signals and the ground truth forest biomass measurements using standard statistical techniques. We were unsuccessful in deriving such relationships. Shortly before the CRADA ended, Mr Johnson discovered that FM signal from local radio station broadcasts had interfered with the back scatter measurements such that the bulk of the signal received by the BioSAR instrument was not backscatter from the radar but rather was local radio station signals.

  12. In vitro anticancer activity, toxicity and structure-activity relationships of phyllostictine A, a natural oxazatricycloalkenone produced by the fungus Phyllosticta cirsii

    SciTech Connect

    Le Calve, Benjamin; Lallemand, Benjamin; Perrone, Carmen; Lenglet, Gaelle; Depauw, Sabine; Van Goietsenoven, Gwendoline; Bury, Marina; Vurro, Maurizio; Herphelin, Francoise; Andolfi, Anna; Zonno, Maria Chiara; Mathieu, Veronique; Dufrasne, Francois; Van Antwerpen, Pierre; Poumay, Yves

    2011-07-01

    The in vitro anticancer activity and toxicity of phyllostictine A, a novel oxazatricycloalkenone recently isolated from a plant-pathogenic fungus (Phyllosticta cirsii) was characterized in six normal and five cancer cell lines. Phyllostictine A displays in vitro growth-inhibitory activity both in normal and cancer cells without actual bioselectivity, while proliferating cells appear significantly more sensitive to phyllostictine A than non-proliferating ones. The main mechanism of action by which phyllostictine displays cytotoxic effects in cancer cells does not seem to relate to a direct activation of apoptosis. In the same manner, phyllostictine A seems not to bind or bond with DNA as part of its mechanism of action. In contrast, phyllostictine A strongly reacts with GSH, which is a bionucleophile. The experimental data from the present study are in favor of a bonding process between GSH and phyllostictine A to form a complex though Michael attack at C=C bond at the acrylamide-like system. Considering the data obtained, two new hemisynthesized phyllostictine A derivatives together with three other natural phyllostictines (B, C and D) were also tested in vitro in five cancer cell lines. Compared to phyllostictine A, the two derivatives displayed a higher, phyllostictines B and D a lower, and phyllostictine C an almost equal, growth-inhibitory activity, respectively. These results led us to propose preliminary conclusions in terms of the structure-activity relationship (SAR) analyses for the anticancer activity of phyllostictine A and its related compounds, at least in vitro.

  13. The Structure-Activity Relationship of the 3-Oxy Site in the Anticonvulsant (R)-N-Benzyl 2-Acetamido-3-methoxypropionamide

    PubMed Central

    Morieux, Pierre; Salomé, Christophe; Park, Ki Duk; Stables, James P.; Kohn, Harold

    2010-01-01

    Lacosamide ((R)-N-benzyl 2-acetamido-3-methoxypropionamide, (R)-1) is a low molecular weight anticonvulsant recently introduced in the United States and Europe for adjuvant treatment of partial-onset seizures in adults. In this study, we define the structure-activity relationship (SAR) for the compound's 3-oxy site. Placement of small non-polar, non-bulky substituents at the 3-oxy site provided compounds with pronounced seizure protection in the maximal electroshock (MES) seizure test with activities similar to (R)-1. The anticonvulsant activity loss that accompanied introduction of larger moieties at the 3-oxy site in (R)-1 was offset, in part, by including unsaturated groups at this position. Our findings were similar to a recently reported SAR study of the 4′-benzylamide site in (R)-1 (J. Med. Chem.2010, 53, 1288–1305). Together, these results indicate that both the 3-oxy and 4′-benzylamide positions in (R)-1 can accommodate non-bulky, hydrophobic groups and still retain pronounced anticonvulsant activities in rodents in the MES seizure model. PMID:20614888

  14. A relational learning approach to Structure-Activity Relationships in drug design toxicity studies.

    PubMed

    Camacho, Rui; Pereira, Max; Costa, Vítor Santos; Fonseca, Nuno A; Adriano, Carlos; Simões, Carlos J V; Brito, Rui M M

    2011-09-16

    It has been recognized that the development of new therapeutic drugs is a complex and expensive process. A large number of factors affect the activity in vivo of putative candidate molecules and the propensity for causing adverse and toxic effects is recognized as one of the major hurdles behind the current "target-rich, lead-poor" scenario. Structure-Activity Relationship (SAR) studies, using relational Machine Learning (ML) algorithms, have already been shown to be very useful in the complex process of rational drug design. Despite the ML successes, human expertise is still of the utmost importance in the drug development process. An iterative process and tight integration between the models developed by ML algorithms and the know-how of medicinal chemistry experts would be a very useful symbiotic approach. In this paper we describe a software tool that achieves that goal--iLogCHEM. The tool allows the use of Relational Learners in the task of identifying molecules or molecular fragments with potential to produce toxic effects, and thus help in stream-lining drug design in silico. It also allows the expert to guide the search for useful molecules without the need to know the details of the algorithms used. The models produced by the algorithms may be visualized using a graphical interface, that is of common use amongst researchers in structural biology and medicinal chemistry. The graphical interface enables the expert to provide feedback to the learning system. The developed tool has also facilities to handle the similarity bias typical of large chemical databases. For that purpose the user can filter out similar compounds when assembling a data set. Additionally, we propose ways of providing background knowledge for Relational Learners using the results of Graph Mining algorithms.

  15. Biflavonoids from Torreya nucifera displaying SARS-CoV 3CL(pro) inhibition.

    PubMed

    Ryu, Young Bae; Jeong, Hyung Jae; Kim, Jang Hoon; Kim, Young Min; Park, Ji-Young; Kim, Doman; Nguyen, Thi Thanh Hanh; Park, Su-Jin; Chang, Jong Sun; Park, Ki Hun; Rho, Mun-Chual; Lee, Woo Song

    2010-11-15

    As part of our search for botanical sources of SARS-CoV 3CL(pro) inhibitors, we selected Torreya nucifera, which is traditionally used as a medicinal plant in Asia. The ethanol extract of T. nucifera leaves exhibited good SARS-CoV 3CL(pro) inhibitory activity (62% at 100μg/mL). Following bioactivity-guided fractionation, eight diterpenoids (1-8) and four biflavonoids (9-12) were isolated and evaluated for SARS-CoV 3CL(pro) inhibition using fluorescence resonance energy transfer analysis. Of these compounds, the biflavone amentoflavone (9) (IC(50)=8.3μM) showed most potent 3CL(pro) inhibitory effect. Three additional authentic flavones (apigenin, luteolin and quercetin) were tested to establish the basic structure-activity relationship of biflavones. Apigenin, luteolin, and quercetin inhibited 3CL(pro) activity with IC(50) values of 280.8, 20.2, and 23.8μM, respectively. Values of binding energy obtained in a molecular docking study supported the results of enzymatic assays. More potent activity appeared to be associated with the presence of an apigenin moiety at position C-3' of flavones, as biflavone had an effect on 3CL(pro) inhibitory activity.

  16. Quantitative structure-activity relationships for fluoroelastomer/chlorofluorocarbon systems

    SciTech Connect

    Paciorek, K.J.L.; Masuda, S.R.; Nakahara, J.H. ); Snyder, C.E. Jr.; Warner, W.M. )

    1991-12-01

    This paper reports on swell, tensile, and modulus data that were determined for a fluoroelastomer after exposure to a series of chlorofluorocarbon model fluids. Quantitative structure-activity relationships (QSAR) were developed for the swell as a function of the number of carbons and chlorines and for tensile strength as a function of carbon number and chlorine positions in the chlorofluorocarbons.

  17. Polarization effects and multipolarization SAR

    NASA Technical Reports Server (NTRS)

    Freeman, Anthony

    1992-01-01

    Imaging radar polarimeters are usually implemented using a Synthetic Aperture Radar (SAR) approach to give a high resolution image in two dimensions: range and azimuth. For each pixel in the image a polarimetric SAR gives sufficient information to characterize the polarimetric scattering properties of the imaged area (or target) as seen by the radar. Using a polarimetric SAR system as opposed to a single-polarization SAR system provides significantly more information about the target scattering mechanisms and allows better discrimination between different types of surfaces. In these notes a brief overview of SAR polarimetry is offered. The notes are intended as a text to accompany a lecture on SAR polarimetry as part of an AGARD-NATO course. Covered in the notes are the following: the polarization properties of electromagnetic waves; the concepts of radar scattering and measuring radar backscatter with a SAR; polarization synthesis; scattering matrix, Stokes matrix, and covariance matrix representations of polarimetric SAR data; polarization signature plots; design and calibration of polarimetric SAR systems; polarization filtering for target detection; fitting a simple model to polarimetric SAR measurements of naturally occurring features; and supervised classification of polarimetric SAR data.

  18. Bistatic SAR: Proof of Concept.

    SciTech Connect

    Yocky, David A.; Doren, Neall E.; Bacon, Terry A.; Wahl, Daniel E.; Eichel, Paul H.; Jakowatz, Charles V,; Delaplain, Gilbert G.; Dubbert, Dale F.; Tise, Bertice L.; White, Kyle R.

    2014-10-01

    Typical synthetic aperture RADAR (SAR) imaging employs a co-located RADAR transmitter and receiver. Bistatic SAR imaging separates the transmitter and receiver locations. A bistatic SAR configuration allows for the transmitter and receiver(s) to be in a variety of geometric alignments. Sandia National Laboratories (SNL) / New Mexico proposed the deployment of a ground-based RADAR receiver. This RADAR receiver was coupled with the capability of digitizing and recording the signal collected. SNL proposed the possibility of creating an image of targets the illuminating SAR observes. This document describes the developed hardware, software, bistatic SAR configuration, and its deployment to test the concept of a ground-based bistatic SAR. In the proof-of-concept experiments herein, the RADAR transmitter will be a commercial SAR satellite and the RADAR receiver will be deployed at ground level, observing and capturing RADAR ground/targets illuminated by the satellite system.

  19. Efficacy of various disinfectants against SARS coronavirus.

    PubMed

    Rabenau, H F; Kampf, G; Cinatl, J; Doerr, H W

    2005-10-01

    The recent severe acute respiratory syndrome (SARS) epidemic in Asia and Northern America led to broad use of various types of disinfectant in order to control the public spread of the highly contagious virus. However, only limited data were available to demonstrate their efficacy against SARS coronavirus (SARS-CoV). We therefore investigated eight disinfectants for their activity against SARS-CoV according to prEN 14476. Four hand rubs were tested at 30s (Sterillium, based on 45% iso-propanol, 30% n-propanol and 0.2% mecetronium etilsulphate; Sterillium Rub, based on 80% ethanol; Sterillium Gel, based on 85% ethanol; Sterillium Virugard, based on 95% ethanol). Three surface disinfectants were investigated at 0.5% for 30 min and 60 min (Mikrobac forte, based on benzalkonium chloride and laurylamine; Kohrsolin FF, based on benzalkonium chloride, glutaraldehyde and didecyldimonium chloride; Dismozon pur, based on magnesium monoperphthalate), and one instrument disinfectant was investigated at 4% for 15 min, 3% for 30 min and 2% for 60 min [Korsolex basic, based on glutaraldehyde and (ethylenedioxy)dimethanol]. Three types of organic load were used: 0.3% albumin, 10% fetal calf serum, and 0.3% albumin with 0.3% sheep erythrocytes. Virus titres were determined by a quantitative test (endpoint titration) in 96-well microtitre plates. With all tested preparations, SARS-CoV was inactivated to below the limit of detection (reduction factor mostly > or =4), regardless of the type of organic load. In summary, SARS-CoV can be inactivated quite easily with many commonly used disinfectants.

  20. Regional reconnaissance of seasonal landslide activity in the Eel River catchment, northern California, using InSAR and airborne LiDAR

    NASA Astrophysics Data System (ADS)

    Handwerger, A. L.; Schmidt, D. A.; Roering, J. J.

    2010-12-01

    Remote sensing techniques have greatly improved our ability to quantify deformation of the Earth’s surface and provide reconnaissance information with high temporal and spatial resolution. We use InSAR and airborne LiDAR to examine the spatial and temporal behavior of 15 landslides located in the Eel River catchment, northern California. The Eel River catchment is well known for its large, deep seated, slow-moving landslides. This region is ideal for landslide studies using InSAR because the landslides are continuously moving at a rate fast enough to observe deformation in a short time span, yet slow enough to avoid a loss in radar coherence (Roering et al., 2009). 10 of the 15 landslides presented here have not been previously identified using InSAR and were identified using statistical analysis to discriminate consistent small-scale deformation from artifacts. We produced 30 differential interferograms between February 2007 and May 2010 using ALOS PALSAR data from tracks 223 and 224 with the ROI_PAC processing package. The 15 identified landslides move at line-of sight rates ranging from 0.1 m yr -1 to 0.45 m yr -1, and have dimensions ranging from 0.5 to 5 km long and 0.27 to 3 km wide. To explore seasonal variations in landslide velocity, we construct InSAR time series from the inversion of small-baseline interferograms. Preliminary results show that slide acceleration lags the onset of rainfall events by weeks to months. Combining InSAR and a shaded relief LiDAR image, we identify distinct kinematic zones (e.g. source, transport, toe) within most landslides. This study demonstrates the capabilities of InSAR and airborne LiDAR to explore the spatial and temporal behavior of large, slow-moving landslides in a regional context. Although InSAR analyses of landslides is successful at this field site, there exists a bias toward optimally oriented landslides in our regional reconnaissance. InSAR is blind to surface displacement that is parallel to the satellite

  1. TRANSFORMATION OF DEVELOPMENTAL NEUROTOXICITY DATA INTO STRUCTURE-SEARCHABLE TOXML DATABASE IN SUPPORT OF STRUCTURE-ACTIVITY RELATIONSHIP (SAR) WORKFLOW.

    EPA Science Inventory

    Early hazard identification of new chemicals is often difficult due to lack of data on the novel material for toxicity endpoints, including neurotoxicity. At present, there are no structure searchable neurotoxicity databases. A working group was formed to construct a database to...

  2. InSAR monitoring of high risk geohazard sites

    NASA Astrophysics Data System (ADS)

    Singhroy, Vern

    InSAR techniques are increasingly being used in slope stability assessment, seismic and volcanic hazards. Our research has shown that differential InSAR and coherent target monitoring techniques using field corner reflectors are useful to monitor landslide activity along strategic transportation and energy corridors in Canada and China. We have also used InSAR techniques to monitor seismic activity on Vancouver Island. Our investigation has shown that differential InSAR and CTM techniques provide a useful monitoring technique for landslide activity under different slope, moisture and lithological conditions. On vegetated slopes, corner reflectors are being used to continuously monitor large active slopes. The series of InSAR images indicate the different level of activity of the slopes (large and small) during different periods of the year. The information produced by our InSAR activity maps are used to realign the pipeline route in sensitive permafrost areas, and to install slope stability measures along the Trans-Canada Highway. Recent RADARSAT-2 with its high resolution (3m) multi-incidence fully polarimetric capabilities are providing the high resolution rapid revisit capabilities needed to continuously monitor these active slopes along Canadian strategic energy and transportation corridors, as well as seismically active regions.

  3. Using theoretical descriptors in structure activity relationships: Validating toxicity predictions

    SciTech Connect

    Famini, G.R.; Wilson, L.Y.; Chester, N.A.; Sterling, P.A.

    1995-12-01

    Quantitative Structure Activity Relationships (QSAR) and Linear Free Energy Relationships (LFER) are very useful for correlating toxicological data, and in characterizating trends in terms of structural and electronic effects. Several years ago, we developed a series of equations correlating a number of toxicity tests with theoretically determined descriptors. One of these tests was the Microtox test, using the degradation in light from Photobacteriurn phosphoreum. Recently, several new compounds have been tested in our laboratory using the Microtox test, and compared against the predicted values. The agreement between experimental and theoretical results will be discussed, as will reasons for {open_quotes}good{close_quotes} or {open_quotes}poor{close_quotes} predictions.

  4. Rationalizing three-dimensional activity landscapes and the influence of molecular representations on landscape topology and the formation of activity cliffs.

    PubMed

    Peltason, Lisa; Iyer, Preeti; Bajorath, Jürgen

    2010-06-28

    Activity landscapes are defined by potency and similarity distributions of active compounds and reflect the nature of structure-activity relationships (SARs). Three-dimensional (3D) activity landscapes are reminiscent of topographical maps and particularly intuitive representations of compound similarity and potency distributions. From their topologies, SAR characteristics can be deduced. Accordingly, idealized theoretical landscape models have been utilized to rationalize SAR features, but "true" 3D activity landscapes have not yet been described in detail. Herein we present a computational approach to derive approximate 3D activity landscapes for actual compound data sets and to analyze exemplary landscape representations. These activity landscapes are generated within a consistent reference frame so that they can be compared across different activity classes. We show that SAR features of compound data sets can be derived from the topology of landscape models. A notable correlation is observed between global SAR phenotypes, assigned on the basis of SAR discontinuity scoring, and characteristic landscape topologies. We also show that different molecular representations can substantially alter the topology of activity landscapes for a given data set and modulate the formation of activity cliffs, which represent the most prominent landscape features. Depending on the choice of molecular representations, compounds forming a steep activity cliff in a given landscape might be separated in another and no longer form a cliff. However, comparison of alternative activity landscapes makes it possible to focus on compound subsets having high SAR information content.

  5. Structure-activity relationships of a novel pyranopyridine series of Gram-negative bacterial efflux pump inhibitors.

    PubMed

    Nguyen, Son T; Kwasny, Steven M; Ding, Xiaoyuan; Cardinale, Steven C; McCarthy, Courtney T; Kim, Hong-Suk; Nikaido, Hiroshi; Peet, Norton P; Williams, John D; Bowlin, Terry L; Opperman, Timothy J

    2015-05-01

    Recently we described a novel pyranopyridine inhibitor (MBX2319) of RND-type efflux pumps of the Enterobacteriaceae. MBX2319 (3,3-dimethyl-5-cyano-8-morpholino-6-(phenethylthio)-3,4-dihydro-1H-pyrano[3,4-c]pyridine) is structurally distinct from other known Gram-negative efflux pump inhibitors (EPIs), such as 1-(1-naphthylmethyl)-piperazine (NMP), phenylalanylarginine-β-naphthylamide (PAβN), D13-9001, and the pyridopyrimidine derivatives. Here, we report the synthesis and biological evaluation of 60 new analogs of MBX2319 that were designed to probe the structure activity relationships (SARs) of the pyranopyridine scaffold. The results of these studies produced a molecular activity map of the scaffold, which identifies regions that are critical to efflux inhibitory activities and those that can be modified to improve potency, metabolic stability and solubility. Several compounds, such as 22d-f, 22i and 22k, are significantly more effective than MBX2319 at potentiating the antibacterial activity of levofloxacin and piperacillin against Escherichia coli.

  6. Structure-Activity Relationships of a Novel Pyranopyridine Series of Gram-negative Bacterial Efflux Pump Inhibitors

    PubMed Central

    Nguyen, Son T.; Kwasny, Steven M.; Ding, Xiaoyuan; Cardinale, Steven C.; McCarthy, Courtney T.; Kim, Hong-Suk; Nikaido, Hiroshi; Peet, Norton P.; Williams, John D.; Bowlin, Terry L.; Opperman, Timothy J.

    2015-01-01

    Recently we described a novel pyranopyridine inhibitor (MBX2319) of RND-type efflux pumps of the Enterobacteriaceae. MBX2319 (3,3-dimethyl-5-cyano-8-morpholino-6-(phenethylthio)-3,4-dihydro-1H-pyrano[3,4-c]pyridine) is structurally distinct from other known Gram-negative efflux pump inhibitors (EPIs), such as 1-(1-naphthylmethyl)-piperazine (NMP), phenylalanylarginine-β-naphthylamide (PAβN), D13-9001, and the pyridopyrimidine derivatives. Here, we report the synthesis and biological evaluation of 60 new analogs of MBX2319 that were designed to probe the structure activity relationships (SARs) of the pyranopyridine scaffold. The results of these studies produced a molecular activity map of the scaffold, which identifies regions that are critical to efflux inhibitory activities and those that can be modified to improve potency, metabolic stability and solubility. Several compounds, such as 22d–f, 22i and 22k, are significantly more effective than MBX2319 at potentiating the antibacterial activity of levofloxacin and piperacillin against Escherichia coli. PMID:25818767

  7. The experience of SARS-related stigma at Amoy Gardens.

    PubMed

    Lee, Sing; Chan, Lydia Y Y; Chau, Annie M Y; Kwok, Kathleen P S; Kleinman, Arthur

    2005-11-01

    Severe Acute Respiratory Syndrome (SARS) possesses characteristics that render it particularly prone to stigmatization. SARS-related stigma, despite its salience for public health and stigma research, has had little examination. This study combines survey and case study methods to examine subjective stigma among residents of Amoy Gardens (AG), the first officially recognized site of community outbreak of SARS in Hong Kong. A total of 903 residents of AG completed a self-report questionnaire derived from two focus groups conducted toward the end of the 3-month outbreak. Case studies of two residents who lived in Block E, the heart of the SARS epidemic at AG, complement the survey data. Findings show that stigma affected most residents and took various forms of being shunned, insulted, marginalized, and rejected in the domains of work, interpersonal relationships, use of services and schooling. Stigma was also associated with psychosomatic distress. Residents' strategies for diminishing stigma varied with gender, age, education, occupation, and proximity to perceived risk factors for SARS such as residential location, previous SARS infection and the presence of ex-SARS household members. Residents attributed stigma to government mismanagement, contagiousness of the mysterious SARS virus, and alarmist media reporting. Stigma clearly decreased, but never completely disappeared, after the outbreak. The findings confirm and add to existing knowledge on the varied origins, correlates, and impacts of stigma. They also highlight the synergistic roles of inconsistent health policy responses and risk miscommunication by the media in rapidly amplifying stigma toward an unfamiliar illness. While recognizing the intrinsically stigmatizing nature of public health measures to control SARS, we recommend that a consistent inter-sectoral approach is needed to minimize stigma and to make an effective health response to future outbreaks.

  8. Modeling of SAR signatures of shallow water ocean topography

    NASA Technical Reports Server (NTRS)

    Shuchman, R. A.; Kozma, A.; Kasischke, E. S.; Lyzenga, D. R.

    1984-01-01

    A hydrodynamic/electromagnetic model was developed to explain and quantify the relationship between the SEASAT synthetic aperture radar (SAR) observed signatures and the bottom topography of the ocean in the English Channel region of the North Sea. The model uses environmental data and radar system parameters as inputs and predicts SAR-observed backscatter changes over topographic changes in the ocean floor. The model results compare favorably with the actual SEASAT SAR observed backscatter values. The developed model is valid for only relatively shallow water areas (i.e., less than 50 meters in depth) and suggests that for bottom features to be visible on SAR imagery, a moderate to high velocity current and a moderate wind must be present.

  9. 3D SAR approach to IF SAR processing

    NASA Astrophysics Data System (ADS)

    Doerry, Armin W.; Bickel, Doug

    2000-08-01

    Interferometric SAR (IFSAR) can be shown to be a special case of 3-D SAR image formation. In fact, traditional IFSAR processing results in the equivalent of merely a super- resolved, under-sampled, 3-D SAR image. However, when approached as a 3-D SAR problem, a number of IFSAR properties and anomalies are easily explained. For example, IFSAR decorrelation with height is merely ordinary migration in 3-D SAR. Consequently, treating IFSAR as a 3-D SAR problem allows insight and development of proper motion compensation techniques and image formation operations to facilitate optimal height estimation. Furthermore, multiple antenna phase centers and baselines are easily incorporated into this formulation, providing essentially a sparse array in the elevation dimension. This paper shows the Polar Format image formation algorithm extended to 3 dimensions, and then proceeds to apply it to the IFSAR collection geometry. This suggests a more optimal reordering of the traditional IFSAR processing steps.

  10. New cholinesterase inhibitors for Alzheimer's disease: Structure Activity Studies (SARs) and molecular docking of isoquinolone and azepanone derivatives.

    PubMed

    Bacalhau, Patrícia; San Juan, Amor A; Marques, Carolina S; Peixoto, Daniela; Goth, Albertino; Guarda, Cátia; Silva, Mara; Arantes, Sílvia; Caldeira, A Teresa; Martins, Rosário; Burke, Anthony J

    2016-08-01

    A library of isoquinolinone and azepanone derivatives were screened for both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activity. The strategy adopted included (a) in vitro biological assays, against eel AChE (EeAChE) and equine serum BuChE (EqBuChE) in order to determine the compounds IC50 and their dose-response activity, consolidated by (b) molecular docking studies to evaluate the docking poses and interatomic interactions in the case of the hit compounds, validated by STD-NMR studies. Compound (1f) was identified as one of these hits with an IC50 of 89.5μM for EeAChE and 153.8μM for EqBuChE, (2a) was identified as a second hit with an IC50 of 108.4μM (EeAChE) and 277.8μM (EqBuChE). In order to gain insights into the binding mode and principle active site interactions of these molecules, (R)-(1f) along with 3 other analogues (also as the R-enantiomer) were docked into both RhAChE and hBuChE models. Galantamine was used as the benchmark. The docking study was validated by performing an STD-NMR study of (1f) with EeAChE using galantamine as the benchmark. PMID:27231829

  11. Quantitative Structure-Antifungal Activity Relationships for cinnamate derivatives.

    PubMed

    Saavedra, Laura M; Ruiz, Diego; Romanelli, Gustavo P; Duchowicz, Pablo R

    2015-12-01

    Quantitative Structure-Activity Relationships (QSAR) are established with the aim of analyzing the fungicidal activities of a set of 27 active cinnamate derivatives. The exploration of more than a thousand of constitutional, topological, geometrical and electronic molecular descriptors, which are calculated with Dragon software, leads to predictions of the growth inhibition on Pythium sp and Corticium rolfsii fungi species, in close agreement to the experimental values extracted from the literature. A set containing 21 new structurally related cinnamate compounds is prepared. The developed QSAR models are applied to predict the unknown fungicidal activity of this set, showing that cinnamates like 38, 28 and 42 are expected to be highly active for Pythium sp, while this is also predicted for 28 and 34 in C. rolfsii. PMID:26410195

  12. INTEGRATION OF SHORT-TERM CO-SEISMIC DEFORMATION (InSAR) IN THE GEOMORPHIC DEVELOPMENT OF AN ACTIVELY UPLIFTING FOOTWALL, L’AQUILA EARTHQUAKE (06 APRIL, 2009), ITALY

    NASA Astrophysics Data System (ADS)

    Berti, C.; Pazzaglia, F. J.; Ramage, J. M.; Miccadei, E.; Piacentini, T.

    2009-12-01

    Central Italy is a well know region of frequent seismic activity focused along the topographic axis of the Apennines, with several, damaging > M. 5 events in the past decade. Conversely, the integrated effect of these earthquakes in shaping the long term development of the landscape is a poorly understood, but potentially powerful process in describing the region’s paleoseismicity and steadiness of hazardous earthquakes. The recent M. 6.3 L’Aquila earthquake of 06 April, 2009 ruptured a fault in a region of well-known geologic, geomorphic, and geodetic constraining data including hanging wall continental basin Quaternary deposits, footwall stream networks with distinct knickpoints, a dense GPS network, and InSAR interferometry. Collectively, the geodetic data describe the short-term, co- and immediately post-seismic behavior of the earthquake, whereas the geologic and geomorphic data record how discrete rupture events are encoded in the landscape and reflected in processes actively shaping the topography. Envisat and ALOS derived interferograms generated using ROI PAC show close spatial overlap of the InSAR-determined rupture and the Paganica fault, separating a deeply incised, uplifted carbonate footwall block and an actively subsiding Quaternary continental basin. Deposition in the continental basin has been unsteady and is commonly attributed to climate-modulated sediment flux from the uplifted footwall. We note however, that the longitudinal profiles of streams in the footwall are marked by distinct knickpoints that do not correspond to known or obvious lithologic or structural controls. Rather, the knickpoints are located a linear distance from the Paganica fault and at a topographic elevation consistent with detachment-limited stream-power erosional retreat processes instigated by instantaneous base level fall at the mountain front. Furthermore, the magnitude of river incision and elevation of the knickpoints scales with the co-seismic deformation pattern

  13. A single amino acid substitution (R441A) in the receptor-binding domain of SARS coronavirus spike protein disrupts the antigenic structure and binding activity

    SciTech Connect

    He Yuxian . E-mail: yhe@nybloodcenter.org; Li Jingjing; Jiang Shibo

    2006-05-26

    The spike (S) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) has two major functions: interacting with the receptor to mediate virus entry and inducing protective immunity. Coincidently, the receptor-binding domain (RBD, residues 318-510) of SAR-CoV S protein is a major antigenic site to induce neutralizing antibodies. Here, we used RBD-Fc, a fusion protein containing the RBD and human IgG1 Fc, as a model in the studies and found that a single amino acid substitution in the RBD (R441A) could abolish the immunogenicity of RBD to induce neutralizing antibodies in immunized mice and rabbits. With a panel of anti-RBD mAbs as probes, we observed that R441A substitution was able to disrupt the majority of neutralizing epitopes in the RBD, suggesting that this residue is critical for the antigenic structure responsible for inducing protective immune responses. We also demonstrated that the RBD-Fc bearing R441A mutation could not bind to soluble and cell-associated angiotensin-converting enzyme 2 (ACE2), the functional receptor for SARS-CoV and failed to block S protein-mediated pseudovirus entry, indicating that this point mutation also disrupted the receptor-binding motif (RBM) in the RBD. Taken together, these data provide direct evidence to show that a single amino acid residue at key position in the RBD can determine the major function of SARS-CoV S protein and imply for designing SARS vaccines and therapeutics.

  14. PS-InSAR measurements at the most active volcanoes in Iceland: role of the GEO supersite initiative in deformation monitoring at Bárðarbunga, Askja, Hekla, Katla and Eyjafjallajökull volcanoes

    NASA Astrophysics Data System (ADS)

    Parks, Michelle; Dumont, Stéphanie; Drouin, Vincent; Sigmundsson, Freysteinn; Spaans, Karsten; Hooper, Andrew; Ófeigsson, Benedikt; Árnadóttir, Þóra; Hreinsdóttir, Sigrún; Michalczewska, Karolina; Hjaltadóttir, Sigurlaug; María Friðriksdóttir, Hildur; Rut Hjartardóttir, Ásta; Magnússon, Eyjólfur; Vogfjörd, Kristín; Jónsdóttir, Kristín; Hensch, Martin; Guðmundsson, Gunnar; Geirsson, Halldór; Sturkell, Erik

    2015-04-01

    Analysis of a time series of ground deformation measurements at active volcanoes can provide an improved understanding of sub-volcanic and sub-aerial processes; including those related to magmatic, hydrothermal and structural development. Interpreting a long time series may also help determine background behavior, and identify any deviations from this, including the migration of new melt. We use Persistent Scatterer Interferometric Synthetic Aperture Radar (PS-InSAR) techniques to generate a time series of high-resolution deformation measurements, in the vicinity of the most active volcanoes in Iceland: Bárðarbunga, Askja, Hekla, Katla and Eyjafjallajökull and compare these to other geodetic measurements. A comprehensive network of continuous GPS stations is already deployed at these volcanoes and a series of campaign GPS measurements are routinely undertaken each summer. InSAR observations are complementary to these field based measurements and their high spatial resolution assists in resolving the geometry of the deformation field hence gaining improved constraints on the inferred source. The Committee on Earth Observation Satellites has recently declared Iceland a Permanent Geohazard Supersite, based on its propensity for relatively frequent eruptions and their potentially hazardous, long ranging effects. The recent Supersite award ensures a considerable amount of SAR data is made available for both past and future satellite acquisitions, including new X-band images (acquired by TerraSAR-X and Cosmo-SkyMed satellites), and historic C-band images from ERS and ENVISAT. We present a series of long-term deformation measurements for Hekla, Katla, Eyjafjallajökull and Askja volcanoes, derived using PS-InSAR techniques, and include recent interferograms spanning the 2014 unrest and eruption within the Bárðarbunga volcanic system. InSAR and tilt measurements at Hekla indicate renewed melt supply to a sub-volcanic reservoir after the last eruption in 2000. Recent

  15. A novel algorithm for QSAR (quantitative structure-activity relationships)

    SciTech Connect

    Carter, S. ); Nikolic, S.; Trinajstic, N. )

    1989-01-01

    A novel approach to quantitative structure-activity relationships (QSAR) is proposed. It is based on the molecular descriptor named the stereo-identification (SID) number. The applicability of this approach to QSAR studies is tested on aquatic toxicities of phenols against fathead minnows (Phimephales promelas). Our approach reproduced successfully the bioactivities of phenols and is superior to the Hall-Kier model based on Randic's connectivity index.

  16. (Quantitative structure-activity relationships in environmental toxicology)

    SciTech Connect

    Turner, J.E.

    1990-10-04

    The traveler attended the Fourth International Workshop on QSAR (Quantitative Structure-Activity Relationships) in Environmental Toxicology. He was an author or co-author on one platform and two poster presentations. The subject of the workshop offers a framework for analyzing and predicting the fate of chemical pollutants in organisms and the environment. QSAR is highly relevant to the ORNL program on the physicochemical characterization of chemical pollutants for health protection.

  17. Geologic process studies using Synthetic Aperture Radar (SAR) data

    NASA Technical Reports Server (NTRS)

    Evans, Diane L.

    1992-01-01

    The use of SAR data to study geologic processes for better understanding of recent tectonic activity and climate change as well as the mitigation of geologic hazards and exploration for nonrenewable resources is discussed. The geologic processes that are particularly amenable to SAR-based data include volcanism; soil erosion, degradation, and redistribution; coastal erosion and inundation; glacier fluctuations; permafrost; and crustal motions. When SAR data are combined with data from other planned spaceborne sensors including ESA ERS, the Japanese Earth Resources Satellite, and the Canadian Radarsat, it will be possible to build a time-series view of temporal changes over many regions of earth.

  18. Hospital Preparedness and SARS

    PubMed Central

    Wallington, Tamara; Rutledge, Tim; Mederski, Barbara; Rose, Keith; Kwolek, Sue; McRitchie, Donna; Ali, Azra; Wolff, Bryan; White, Diane; Glassman, Edward; Ofner, Marianna; Low, Don E.; Berger, Lisa; McGeer, Allison; Wong, Tom; Baron, David; Berall, Glenn

    2004-01-01

    On May 23, 2003, Toronto experienced the second phase of a severe acute respiratory syndrome (SARS) outbreak. Ninety cases were confirmed, and >620 potential cases were managed. More than 9,000 persons had contact with confirmed or potential case-patients; many required quarantine. The main hospital involved during the second outbreak was North York General Hospital. We review this hospital’s response to, and management of, this outbreak, including such factors as building preparation and engineering, personnel, departmental workload, policies and documentation, infection control, personal protective equipment, training and education, public health, management and administration, follow-up of SARS patients, and psychological and psychosocial management and research. We also make recommendations for other institutions to prepare for future outbreaks, regardless of their origin. PMID:15200807

  19. SAR peculiarities, ambiguities and constraints

    NASA Astrophysics Data System (ADS)

    Keydel, Wolfgang

    1992-08-01

    A synthetic aperture radar (SAR) is basically a coherent scatterometer that employs a coherent real aperture radar with highly sophisticated data evaluation and image processing capabilities. Therefore, the coherence of the system is very important; furthermore, the keypoints for SAR are data storage, evaluation, and processing. These facts entail peculiarities of SAR and special ambiguities which are different from those arising with real aperture radar (RAR). The objective of this paper is to point out the special peculiarities and ambiguities of SAR in comparison to the corresponding properties of RAR. Main topics in this connection are as follows: basic peculiarities like range dependency of signal to noise ratio; azimuth resolution; influence of platform velocity; range and azimuth ambiguities; pulse repetition frequency limitations; velocity effects; and phase error influence, on SAR-image, that can cause motion compensation problems. All these effects will be explained together with different contrast-equations between the target and clutter signals of SAR and RAR.

  20. What do sexually active adolescent females say about relationship issues?

    PubMed

    Bralock, Anita; Koniak-Griffin, Deborah

    2009-04-01

    Many sexually active teenagers face risk for contracting sexually transmitted infections (STIs) including HIV. The purpose of our study was to gain an understanding about influences on condom use among sexually active adolescents in relationships. Data were collected through semi-structured openended interviews. The findings of this study suggest that many adolescents desired the love of a male partner, and were willing to concede to his request of practicing unprotected sex. Findings support the urgent need for interventions that will promote skill-building techniques to negotiate safer sex behaviors among youth who are most likely to be exposed to STIs through risky behaviors.

  1. What do sexually active adolescent females say about relationship issues?

    PubMed

    Bralock, Anita; Koniak-Griffin, Deborah

    2009-04-01

    Many sexually active teenagers face risk for contracting sexually transmitted infections (STIs) including HIV. The purpose of our study was to gain an understanding about influences on condom use among sexually active adolescents in relationships. Data were collected through semi-structured openended interviews. The findings of this study suggest that many adolescents desired the love of a male partner, and were willing to concede to his request of practicing unprotected sex. Findings support the urgent need for interventions that will promote skill-building techniques to negotiate safer sex behaviors among youth who are most likely to be exposed to STIs through risky behaviors. PMID:19268234

  2. Dihydro-β-agarofuran sesquiterpenes from celastraceae species as anti-tumour-promoting agents: Structure-activity relationship.

    PubMed

    Núñez, Marvin J; Jiménez, Ignacio A; Mendoza, Cristina R; Chavez-Sifontes, Marvin; Martinez, Morena L; Ichiishi, Eiichiro; Tokuda, Ryo; Tokuda, Harukuni; Bazzocchi, Isabel L

    2016-03-23

    Inhibition of tumour promotion in multistage chemical carcinogenesis is considered a promising strategy for cancer chemoprevention. In an ongoing investigation of bioactive secondary metabolites from Celastraceae species, five new dihydro-β-agarofuran sesquiterpenes (1-5), named Chiapens A-E, and seventeen known ones, were isolated from Maytenus chiapensis. Their structures were elucidated by extensive NMR spectroscopic and mass spectrometric techniques, and their absolute configurations were determined by circular dichroism studies, chemical correlations and biogenic means. The isolated compounds, along with twenty known sesquiterpenes, previously isolated from Zinowiewia costaricensis, have been tested for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorpol-13-acetate (TPA). Thirty three compounds from this series showed stronger effects than that of β-carotene, the reference inhibitor. The structure-activity relationship (SAR) analysis revealed that the type of substituent, in particular at the C-1 position of the sesquiterpene scaffold, was able to modulate the anti-tumour promoting activity. Compounds 3, 6, and 33 showed significant effects in an in vivo two-stage mouse-skin carcinogenesis model. PMID:26854381

  3. Structure-Activity Relationships of Antimicrobial Gallic Acid Derivatives from Pomegranate and Acacia Fruit Extracts against Potato Bacterial Wilt Pathogen.

    PubMed

    Farag, Mohamed A; Al-Mahdy, Dalia A; Salah El Dine, Riham; Fahmy, Sherifa; Yassin, Aymen; Porzel, Andrea; Brandt, Wolfgang

    2015-06-01

    Bacterial wilts of potato, tomato, pepper, and or eggplant caused by Ralstonia solanacearum are among the most serious plant diseases worldwide. In this study, the issue of developing bactericidal agents from natural sources against R. solanacearum derived from plant extracts was addressed. Extracts prepared from 25 plant species with antiseptic relevance in Egyptian folk medicine were screened for their antimicrobial properties against the potato pathogen R. solancearum by using the disc-zone inhibition assay and microtitre plate dilution method. Plants exhibiting notable antimicrobial activities against the tested pathogen include extracts from Acacia arabica and Punica granatum. Bioactivity-guided fractionation of A. arabica and P. granatum resulted in the isolation of bioactive compounds 3,5-dihydroxy-4-methoxybenzoic acid and gallic acid, in addition to epicatechin. All isolates displayed significant antimicrobial activities against R. solanacearum (MIC values 0.5-9 mg/ml), with 3,5-dihydroxy-4-methoxybenzoic acid being the most effective one with a MIC value of 0.47 mg/ml. We further performed a structure-activity relationship (SAR) study for the inhibition of R. solanacearum growth by ten natural, structurally related benzoic acids.

  4. Structure-Activity Relationships of Antimicrobial Gallic Acid Derivatives from Pomegranate and Acacia Fruit Extracts against Potato Bacterial Wilt Pathogen.

    PubMed

    Farag, Mohamed A; Al-Mahdy, Dalia A; Salah El Dine, Riham; Fahmy, Sherifa; Yassin, Aymen; Porzel, Andrea; Brandt, Wolfgang

    2015-06-01

    Bacterial wilts of potato, tomato, pepper, and or eggplant caused by Ralstonia solanacearum are among the most serious plant diseases worldwide. In this study, the issue of developing bactericidal agents from natural sources against R. solanacearum derived from plant extracts was addressed. Extracts prepared from 25 plant species with antiseptic relevance in Egyptian folk medicine were screened for their antimicrobial properties against the potato pathogen R. solancearum by using the disc-zone inhibition assay and microtitre plate dilution method. Plants exhibiting notable antimicrobial activities against the tested pathogen include extracts from Acacia arabica and Punica granatum. Bioactivity-guided fractionation of A. arabica and P. granatum resulted in the isolation of bioactive compounds 3,5-dihydroxy-4-methoxybenzoic acid and gallic acid, in addition to epicatechin. All isolates displayed significant antimicrobial activities against R. solanacearum (MIC values 0.5-9 mg/ml), with 3,5-dihydroxy-4-methoxybenzoic acid being the most effective one with a MIC value of 0.47 mg/ml. We further performed a structure-activity relationship (SAR) study for the inhibition of R. solanacearum growth by ten natural, structurally related benzoic acids. PMID:26080741

  5. Circular SAR GMTI

    NASA Astrophysics Data System (ADS)

    Page, Douglas; Owirka, Gregory; Nichols, Howard; Scarborough, Steven

    2014-06-01

    We describe techniques for improving ground moving target indication (GMTI) performance in multi-channel synthetic aperture radar (SAR) systems. Our approach employs a combination of moving reference processing (MRP) to compensate for defocus of moving target SAR responses and space-time adaptive processing (STAP) to mitigate the effects of strong clutter interference. Using simulated moving target and clutter returns, we demonstrate focusing of the target return using MRP, and discuss the effect of MRP on the clutter response. We also describe formation of adaptive degrees of freedom (DOFs) for STAP filtering of MRP processed data. For the simulated moving target in clutter example, we demonstrate improvement in the signal to interference plus noise (SINR) loss compared to more standard algorithm configurations. In addition to MRP and STAP, the use of tracker feedback, false alarm mitigation, and parameter estimation techniques are also described. A change detection approach for reducing false alarms from clutter discretes is outlined, and processing of a measured data coherent processing interval (CPI) from a continuously orbiting platform is described. The results demonstrate detection and geolocation of a high-value target under track. The endoclutter target is not clearly visible in single-channel SAR chips centered on the GMTI track prediction. Detections are compared to truth data before and after geolocation using measured angle of arrival (AOA).

  6. Design, diversity-oriented synthesis and structure activity relationship studies of quinolinyl heterocycles as antimycobacterial agents.

    PubMed

    Rachakonda, Venkatesham; Alla, Manjula; Kotipalli, Sudha Sravanti; Ummani, Ramesh

    2013-01-01

    The current study reports design and diversity oriented synthesis of novel bis heterocycles with a common 2-methyl, C-4 unsubstituted quinoline moiety as the central key heterocycle. Employing reagent based skeletal diversity approach; a facile synthesis of bis heterocycles with different heterocyclic rings at C-3 position of the quinoline moiety has been accomplished. A broad range of heterocyclic frameworks thus obtained were evaluated for their antimycobacterial activity. The active scaffolds were further explored by a parallel library generation in order to establish SAR. Further, low cytotoxicity against A549 cell line enhances the potential of the synthesized molecules as promising antimycobacterial agents. PMID:24189497

  7. Antitumor agents 251: synthesis, cytotoxic evaluation, and structure-activity relationship studies of phenanthrene-based tylophorine derivatives (PBTs) as a new class of antitumor agents.

    PubMed

    Wei, Linyi; Brossi, Arnold; Kendall, Ross; Bastow, Kenneth F; Morris-Natschke, Susan L; Shi, Qian; Lee, Kuo-Hsiung

    2006-10-01

    Polar phenanthrene-based tylophorine derivatives (PBTs) were designed, synthesized and evaluated as potential antitumor agents. These compounds contain a core phenanthrene structure and can be synthesized efficiently in excellent yield. The newly synthesized PBTs were evaluated for cytotoxic activity against the A549 human cancer cell line. Among them, N-(2,3-methylenedioxy-6-methoxy-phenanthr-9-ylmethyl)-L-2-piperidinemethanol (34) and N-(2,3-methylenedioxy-6-methoxy-phenanthr-9-ylmethyl)-5-aminopentanol (28) showed the highest potency with IC50 values of 0.16 and 0.27 microM, respectively, which are comparable to those of currently used antitumor drugs. A structure-activity relationship (SAR) study was also explored to facilitate the further development of this new compound class.

  8. Novel phenolic inhibitors of the sarco/endoplasmic reticulum calcium ATPase: identification and characterization by quantitative structure-activity relationship modeling and virtual screening.

    PubMed

    Paula, Stefan; Hofmann, Emily; Burden, John; Stanton, David T

    2015-02-01

    Inhibitors of the sarco/endoplasmic reticulum calcium ATPase (SERCA) are valuable research tools and hold promise as a new generation of anti-prostate cancer agents. Based on previously determined potencies of phenolic SERCA inhibitors, we created quantitative structure-activity relationship (QSAR) models using three independent development strategies. The obtained QSAR models facilitated virtual screens of several commercial compound collections for novel inhibitors. Sixteen compounds were subsequently evaluated in SERCA activity inhibition assays and 11 showed detectable potencies in the micro- to millimolar range. The experimental results were then incorporated into a comprehensive master QSAR model, whose physical interpretation by partial least squares analysis revealed that properly positioned substituents at the central phenyl ring capable of forming hydrogen bonds and of undergoing hydrophobic interactions were prerequisites for effective SERCA inhibition. The established SAR was in good agreement with findings from previous structural studies, even though it was obtained independently using standard QSAR methodologies.

  9. InSAR Monitoring of Landslides using RADARSAT and Alos

    NASA Astrophysics Data System (ADS)

    Singhroy, V.; Pierre-Jean, A.; Pavlic, G.

    2009-05-01

    We present the results of InSAR monitoring of several landslides using RADARDAT, and ALOS satellites. InSAR techniques are increasingly being used in slope stability assessment. Our research has shown that differential InSAR and coherent target monitoring techniques using field corner reflectors are useful to monitor landslide activity along strategic transportation and energy corridors. The Mackenzie Valley in northern Canada is experiencing one of the highest rates on mean annual air temperature for any region in Canada, thereby triggering melting in the permafrost, which results in active layer detachment slides. There are approximately 2000 landslides along the proposed Mackenzie Valley pipeline route. In addition, the Trans Canada Highway in the Canadian Rockies are affected by several rock avalanches and slow retrogressive slides. The ALOS PALSAR InSAR results show that we can observe deformation on both vegetated and exposed rock areas on the Little Smokey slide and the Frank Slide. RADARSAT-1 InSAR images indicate the different level of activity of the slopes (large and small) during different periods of the year. RADARSAT-2 is providing the high resolution rapid revisit capabilities needed to continuously monitor these active slopes along Canadian strategic energy and transportation corridors. The information produced by our InSAR activity maps on various landslides are used to realign the pipeline route in sensitive permafrost areas, and to install slope stability measures along the Trans-Canada and Provincial Highways. Using these different satellites we are able to develop guidelines for more reliable uses of these SAR missions Keywords: InSAR, landslides, RADARSAT, ALOS .

  10. Sar1 localizes at the rims of COPII-coated membranes in vivo

    PubMed Central

    Suda, Yasuyuki; Nakano, Akihiko

    2016-01-01

    ABSTRACT The Sar1 GTPase controls coat assembly on coat protein complex II (COPII)-coated vesicles, which mediate protein transport from the endoplasmic reticulum (ER) to the Golgi. The GTP-bound form of Sar1, activated by the ER-localized guanine nucleotide exchange factor (GEF) Sec12, associates with the ER membrane. GTP hydrolysis by Sar1, stimulated by the COPII-vesicle-localized GTPase-activating protein (GAP) Sec23, in turn causes Sar1 to dissociate from the membrane. Thus, Sar1 is cycled between active and inactive states, and on and off vesicle membranes, but its precise spatiotemporal regulation remains unknown. Here, we examined Sar1 localization on COPII-coated membranes in living Saccharomyces cerevisiae cells. Two-dimensional (2D) observation demonstrated that Sar1 showed modest accumulation around the ER exit sites (ERES) in a manner that was dependent on Sec16 function. Detailed three-dimensional (3D) observation further demonstrated that Sar1 localized at the rims of the COPII-coated membranes, but was excluded from the rest of the COPII membranes. Additionally, a GTP-locked form of Sar1 induced abnormally enlarged COPII-coated structures and covered the entirety of these structures. These results suggested that the reversible membrane association of Sar1 GTPase leads to its localization being restricted to the rims of COPII-coated membranes in vivo. PMID:27432890

  11. Relationships between coordination, active drag and propelling efficiency in crawl.

    PubMed

    Seifert, Ludovic; Schnitzler, Christophe; Bideault, Gautier; Alberty, Morgan; Chollet, Didier; Toussaint, Huub Martin

    2015-02-01

    This study examines the relationships between the index of coordination (IdC) and active drag (D) assuming that at constant average speed, average drag equals average propulsion. The relationship between IdC and propulsive efficiency (ep) was also investigated at maximal speed. Twenty national swimmers completed two incremental speed tests swimming front crawl with arms only in free condition and using a measurement of active drag system. Each test was composed of eight 25-m bouts from 60% to 100% of maximal intensity whereby each lap was swum at constant speed. Different regression models were tested to analyse IdC-D relationship. Correlation between IdC and ep was calculated. IdC was linked to D by linear regression (IdC=0.246·D-27.06; R(2)=0.88, P<.05); swimmers switched from catch-up to superposition coordination mode at a speed of ∼1.55ms(-1) where average D is ∼110N. No correlation between IdC and ep at maximal speed was found. The intra-individual analysis revealed that coordination plays an important role in scaling propulsive forces with higher speed levels such that these are adapted to aquatic resistance. Inter-individual analysis showed that high IdC did not relate to a high ep suggesting an individual optimization of force and power generation is at play to reach high speeds.

  12. Relationships between sleep, physical activity and human health

    PubMed Central

    Atkinson, Greg; Davenne, Damien

    2009-01-01

    Although sleep and exercise may seem to be mediated by completely different physiological mechanisms, there is growing evidence for clinically important relationships between these two behaviors. It is known that passive body heating facilitates the nocturnal sleep of healthy elderly people with insomnia. This finding supports the hypothesis that changes in body temperature trigger somnogenic brain areas to initiate sleep. Nevertheless, little is known about how the core and distal thermoregulatory responses to exercise fit into this hypothesis. Such knowledge could also help in reducing sleep problems associated with nocturnal shiftwork. It is difficult to incorporate physical activity into a shiftworker's lifestyle, since it is already disrupted in terms of family commitments and eating habits. A multi-research strategy is needed to identify what the optimal amounts and timing of physical activity are for reducing shiftwork-related sleep problems. The relationships between sleep, exercise and diet are also important, given the recently reported associations between short sleep length and obesity. The cardiovascular safety of exercise timing should also be considered, since recent data suggest that the reactivity of blood pressure to a change in general physical activity is highest during the morning. This time is associated with an increased risk in general of a sudden cardiac event, but more research work is needed to separate the influences of light, posture and exercise per se on the haemodynamic responses to sleep and physical activity following sleep taken at night and during the day as a nap. PMID:17067643

  13. Relationships between sleep, physical activity and human health.

    PubMed

    Atkinson, Greg; Davenne, Damien

    2007-02-28

    Although sleep and exercise may seem to be mediated by completely different physiological mechanisms, there is growing evidence for clinically important relationships between these two behaviors. It is known that passive body heating facilitates the nocturnal sleep of healthy elderly people with insomnia. This finding supports the hypothesis that changes in body temperature trigger somnogenic brain areas to initiate sleep. Nevertheless, little is known about how the core and distal thermoregulatory responses to exercise fit into this hypothesis. Such knowledge could also help in reducing sleep problems associated with nocturnal shiftwork. It is difficult to incorporate physical activity into a shiftworker's lifestyle, since it is already disrupted in terms of family commitments and eating habits. A multi-research strategy is needed to identify what the optimal amounts and timing of physical activity are for reducing shiftwork-related sleep problems. The relationships between sleep, exercise and diet are also important, given the recently reported associations between short sleep length and obesity. The cardiovascular safety of exercise timing should also be considered, since recent data suggest that the reactivity of blood pressure to a change in general physical activity is highest during the morning. This time is associated with an increased risk in general of a sudden cardiac event, but more research work is needed to separate the influences of light, posture and exercise per se on the haemodynamic responses to sleep and physical activity following sleep taken at night and during the day as a nap.

  14. A class of promising acaricidal tetrahydroisoquinoline derivatives: synthesis, biological evaluation and structure-activity relationships.

    PubMed

    Yang, Rui; Ruan, Qiao; Zhang, Bing-Yu; Zheng, Zuo-Lue; Miao, Fang; Zhou, Le; Geng, Hui-Ling

    2014-01-01

    As part of our continuing research on isoquinoline acaricidal drugs, this paper reports the preparation of a series of the 2-aryl-1-cyano-1,2,3,4-tetrahydroisoquinolines with various substituents on the N-phenyl ring, their in vitro acaricidal activities against Psoroptes cuniculi, a mange mite, and discusses their SAR as well. The structures of all compounds, including 12 new ones, were elucidated by analysis of UV, IR, NMR, ESI-MS, HR-MS spectra and X-ray diffraction experiments. All target compounds showed varying degrees of activity at 0.4 mg/mL. Compound 1 showed the strongest activity, with a 50% lethal concentration value (LC50) of 0.2421 μg/mL and 50% lethal time value (LT50) of 7.79 h, comparable to the standard drug ivermectin (LC50 = 0.2474 μg/mL; LT50 = 20.9 h). The SAR showed that the substitution pattern on the N-aromatic ring exerted a significant effect on the activity. The substituents 2'-F, 3'-F, 2'-Cl, 2'-Br and 2'-CF3 remarkably enhanced the activity. Generally, for the isomers with the same substituents at different positions, the order of the activity was ortho > meta > para. It was concluded that the target compounds represent a class of novel promising candidates or lead compounds for the development of new tetrahydroisoquinoline acaricidal agents.

  15. The relationship between memory complaints, activity and perceived health status.

    PubMed

    Lee, P-L

    2014-04-01

    Subjective memory complaints (SMC) is a possible symptom of mild cognitive impairment which may progress to dementia. The present study examines the relationship of physical activity (PA), cognitive activity (CA), social activity (SA), and perceived health status (HS) with SMC for middle age and older adults. Participants were from the MIDUS II study (Midlife in the United States) recruited in 2004-2006 (Mean age = 55.99; N = 3030). Hierarchical multiple regression was performed with SMC as the dependent variable, along with PA, CA, SA, and HS as the independent variables. The study revealed that SMC was strongly related to PA, CA, and HS, while controlling covariates. Further, HS had the strongest link with SMC among these predictors while interaction effects (PA × HS, CA × HS, and SA × HS) were insignificant. In addition, different results were achieved in younger versus older groups. Participants with more CA, PA and perception of better health had lower frequency of memory complaints. PMID:24646046

  16. Structure-activity relationship studies of pyrrolone antimalarial agents.

    PubMed

    Murugesan, Dinakaran; Kaiser, Marcel; White, Karen L; Norval, Suzanne; Riley, Jennifer; Wyatt, Paul G; Charman, Susan A; Read, Kevin D; Yeates, Clive; Gilbert, Ian H

    2013-09-01

    Previously reported pyrrolones, such as TDR32570, exhibited potential as antimalarial agents; however, while these compounds have potent antimalarial activity, they suffer from poor aqueous solubility and metabolic instability. Here, further structure-activity relationship studies are described that aimed to solve the developability issues associated with this series of compounds. In particular, further modifications to the lead pyrrolone, involving replacement of a phenyl ring with a piperidine and removal of a potentially metabolically labile ester by a scaffold hop, gave rise to derivatives with improved in vitro antimalarial activities against Plasmodium falciparum K1, a chloroquine- and pyrimethamine-resistant parasite strain, with some derivatives exhibiting good selectivity for parasite over mammalian (L6) cells. Three representative compounds were selected for evaluation in a rodent model of malaria infection, and the best compound showed improved ability to decrease parasitaemia and a slight increase in survival.

  17. Analytical SAR-GMTI principles

    NASA Astrophysics Data System (ADS)

    Soumekh, Mehrdad; Majumder, Uttam K.; Barnes, Christopher; Sobota, David; Minardi, Michael

    2016-05-01

    This paper provides analytical principles to relate the signature of a moving target to parameters in a SAR system. Our objective is to establish analytical tools that could predict the shift and smearing of a moving target in a subaperture SAR image. Hence, a user could identify the system parameters such as the coherent processing interval for a subaperture that is suitable to localize the signature of a moving target for detection, tracking and geolocating the moving target. The paper begins by outlining two well-known SAR data collection methods to detect moving targets. One uses a scanning beam in the azimuth domain with a relatively high PRF to separate the moving targets and the stationary background (clutter); this is also known as Doppler Beam Sharpening. The other scheme uses two receivers along the track to null the clutter and, thus, provide GMTI. We also present results on implementing our SAR-GMTI analytical principles for the anticipated shift and smearing of a moving target in a simulated code. The code would provide a tool for the user to change the SAR system and moving target parameters, and predict the properties of a moving target signature in a subaperture SAR image for a scene that is composed of both stationary and moving targets. Hence, the SAR simulation and imaging code could be used to demonstrate the validity and accuracy of the above analytical principles to predict the properties of a moving target signature in a subaperture SAR image.

  18. Atypical SARS in Geriatric Patient

    PubMed Central

    Oh, Helen M.L.; Hui, K.P.; Lien, Christopher T.C.; Narendran, K.; Heng, B.H.; Ling, A.E.

    2004-01-01

    We describe an atypical presentation of severe acute respiratory syndrome (SARS) in a geriatric patient with multiple coexisting conditions. Interpretation of radiographic changes was confounded by cardiac failure, with resolution of fever causing delayed diagnosis and a cluster of cases. SARS should be considered even if a contact history is unavailable, during an ongoing outbreak. PMID:15030694

  19. Bistatic SAR: Imagery & Image Products.

    SciTech Connect

    Yocky, David A.; Wahl, Daniel E.; Jakowatz, Charles V,

    2014-10-01

    While typical SAR imaging employs a co-located (monostatic) RADAR transmitter and receiver, bistatic SAR imaging separates the transmitter and receiver locations. The transmitter and receiver geometry determines if the scattered signal is back scatter, forward scatter, or side scatter. The monostatic SAR image is backscatter. Therefore, depending on the transmitter/receiver collection geometry, the captured imagery may be quite different that that sensed at the monostatic SAR. This document presents imagery and image products formed from captured signals during the validation stage of the bistatic SAR research. Image quality and image characteristics are discussed first. Then image products such as two-color multi-view (2CMV) and coherent change detection (CCD) are presented.

  20. Relationship between ankle stiffness structure and muscle activation.

    PubMed

    Lee, Hyunglae; Wang, Shuo; Hogan, Neville

    2012-01-01

    This paper presents a characterization of the structure of ankle stiffness under multiple levels of muscle activation and the relationship between them. A multi-variable impedance estimation method using a wearable ankle robot enabled clear identification of ankle stiffness structure in the space consisting of the sagittal and frontal planes. With visual feedback showing current and target muscle activation levels, all subjects could successfully maintain multiple target levels (5%∼30% of the maximum voluntary contraction level). Stiffness increased with muscle activation, but the increase was more pronounced in the dorsiflexion-plantarflexion direction than in the inversion-eversion direction, which resulted in a characteristic "peanut" shape. The relation between measured muscle activation level and ankle stiffness was evaluated. All subjects showed a highly linear relation not only for the two principal axis directions of the ankle, i.e., dorsiflexion-plantarflexion and inversion-eversion, but also for the average stiffness value of all directions. These major findings were consistent both for the tibialis anterior and triceps surae activation.

  1. Conformation-Activity Relationships of Polyketide Natural Products

    PubMed Central

    Larsen, Erik M.; Wilson, Matthew R.; Taylor, Richard E.

    2015-01-01

    Polyketides represent an important class of secondary metabolites that interact with biological targets connected to a variety of disease-associated pathways. Remarkably, nature’s assembly lines, polyketide synthases, manufacture these privileged structures through a combinatorial mixture of just a few structural units. This review highlights the role of these structural elements in shaping a polyketide’s conformational preferences, the use of computer-based molecular modeling and solution NMR studies in the identification of low-energy conformers, and the importance of conformational analogues in probing the bound conformation. In particular, this review covers several examples wherein conformational analysis complements classic structure-activity relationships in the design of biologically active natural product analogues. PMID:25974024

  2. Thapsigargin, Origin, Chemistry, Structure-Activity Relationships and Prodrug Development.

    PubMed

    Quynh Doan, Nhu Thi; Christensen, Soren Brogger

    2015-01-01

    Thapsigargin was originally isolated from the roots of the Mediterranean umbelliferous plant Thapsia garganica in order to characterize the skin irritant principle. Characteristic chemical properties and semi-syntheses are reviewed. The biological activity was related to the subnanomolar affinity for the sarco/endoplasmic reticulum calcium ATPase. Prolonged inhibition of the pump afforded collapse of the calcium homeostasis and eventually apoptosis. Structure-activity relationships enabled design of an equipotent analogue containing a linker. Conjugation of the analogue containing the linker with peptides, which only are substrates for either prostate specific antigen (PSA) or prostate specific membrane antigen (PSMA) enabled design of prodrugs targeting a number of cancer diseases including prostate cancer (G115) and hepatocellular carcinoma (G202). Prodrug G202 has under the name of mipsagargin in phase II clinical trials shown promising properties against hepatocellular carcinoma.

  3. Possible Relationship of the Solar Activity and Earthquakes

    NASA Astrophysics Data System (ADS)

    Gonzalez-Trejo, J. I.; Cervantes, F.; Real-Ramírez, C. A.; Hoyos-Reyes, L. F.; Miranda-Tello, R.; Area de Sistemas Computacionales

    2013-05-01

    Several authors have recently argued that there is a relationship between solar activity and big earthquakes. This work compares Dst index fluctuations along 2012 and 2013, with the earthquake activity near La Paz, Baja California, Mexico. The earthquakes measurements at this place were divided according its deep focus. It was observed that the frequency of the deeper earthquakes increases shortly after considerable fluctuations in the Dst index are registered. We assume that the number of deep earthquakes increases because the interaction of the tectonic plate below that place and the tectonic plates in contact with it increases. This work also shows that the frequency of shallowest minor and light earthquakes increases shortly before a strongest earthquake takes place in the vicinity.

  4. Thapsigargin, Origin, Chemistry, Structure-Activity Relationships and Prodrug Development.

    PubMed

    Quynh Doan, Nhu Thi; Christensen, Soren Brogger

    2015-01-01

    Thapsigargin was originally isolated from the roots of the Mediterranean umbelliferous plant Thapsia garganica in order to characterize the skin irritant principle. Characteristic chemical properties and semi-syntheses are reviewed. The biological activity was related to the subnanomolar affinity for the sarco/endoplasmic reticulum calcium ATPase. Prolonged inhibition of the pump afforded collapse of the calcium homeostasis and eventually apoptosis. Structure-activity relationships enabled design of an equipotent analogue containing a linker. Conjugation of the analogue containing the linker with peptides, which only are substrates for either prostate specific antigen (PSA) or prostate specific membrane antigen (PSMA) enabled design of prodrugs targeting a number of cancer diseases including prostate cancer (G115) and hepatocellular carcinoma (G202). Prodrug G202 has under the name of mipsagargin in phase II clinical trials shown promising properties against hepatocellular carcinoma. PMID:26429715

  5. Research Data Management and Libraries: Relationships, Activities, Drivers and Influences

    PubMed Central

    Pinfield, Stephen; Cox, Andrew M.; Smith, Jen

    2014-01-01

    The management of research data is now a major challenge for research organisations. Vast quantities of born-digital data are being produced in a wide variety of forms at a rapid rate in universities. This paper analyses the contribution of academic libraries to research data management (RDM) in the wider institutional context. In particular it: examines the roles and relationships involved in RDM, identifies the main components of an RDM programme, evaluates the major drivers for RDM activities, and analyses the key factors influencing the shape of RDM developments. The study is written from the perspective of library professionals, analysing data from 26 semi-structured interviews of library staff from different UK institutions. This is an early qualitative contribution to the topic complementing existing quantitative and case study approaches. Results show that although libraries are playing a significant role in RDM, there is uncertainty and variation in the relationship with other stakeholders such as IT services and research support offices. Current emphases in RDM programmes are on developments of policies and guidelines, with some early work on technology infrastructures and support services. Drivers for developments include storage, security, quality, compliance, preservation, and sharing with libraries associated most closely with the last three. The paper also highlights a ‘jurisdictional’ driver in which libraries are claiming a role in this space. A wide range of factors, including governance, resourcing and skills, are identified as influencing ongoing developments. From the analysis, a model is constructed designed to capture the main aspects of an institutional RDM programme. This model helps to clarify the different issues involved in RDM, identifying layers of activity, multiple stakeholders and drivers, and a large number of factors influencing the implementation of any initiative. Institutions may usefully benchmark their activities against

  6. Research data management and libraries: relationships, activities, drivers and influences.

    PubMed

    Pinfield, Stephen; Cox, Andrew M; Smith, Jen

    2014-01-01

    The management of research data is now a major challenge for research organisations. Vast quantities of born-digital data are being produced in a wide variety of forms at a rapid rate in universities. This paper analyses the contribution of academic libraries to research data management (RDM) in the wider institutional context. In particular it: examines the roles and relationships involved in RDM, identifies the main components of an RDM programme, evaluates the major drivers for RDM activities, and analyses the key factors influencing the shape of RDM developments. The study is written from the perspective of library professionals, analysing data from 26 semi-structured interviews of library staff from different UK institutions. This is an early qualitative contribution to the topic complementing existing quantitative and case study approaches. Results show that although libraries are playing a significant role in RDM, there is uncertainty and variation in the relationship with other stakeholders such as IT services and research support offices. Current emphases in RDM programmes are on developments of policies and guidelines, with some early work on technology infrastructures and support services. Drivers for developments include storage, security, quality, compliance, preservation, and sharing with libraries associated most closely with the last three. The paper also highlights a 'jurisdictional' driver in which libraries are claiming a role in this space. A wide range of factors, including governance, resourcing and skills, are identified as influencing ongoing developments. From the analysis, a model is constructed designed to capture the main aspects of an institutional RDM programme. This model helps to clarify the different issues involved in RDM, identifying layers of activity, multiple stakeholders and drivers, and a large number of factors influencing the implementation of any initiative. Institutions may usefully benchmark their activities against the

  7. Research data management and libraries: relationships, activities, drivers and influences.

    PubMed

    Pinfield, Stephen; Cox, Andrew M; Smith, Jen

    2014-01-01

    The management of research data is now a major challenge for research organisations. Vast quantities of born-digital data are being produced in a wide variety of forms at a rapid rate in universities. This paper analyses the contribution of academic libraries to research data management (RDM) in the wider institutional context. In particular it: examines the roles and relationships involved in RDM, identifies the main components of an RDM programme, evaluates the major drivers for RDM activities, and analyses the key factors influencing the shape of RDM developments. The study is written from the perspective of library professionals, analysing data from 26 semi-structured interviews of library staff from different UK institutions. This is an early qualitative contribution to the topic complementing existing quantitative and case study approaches. Results show that although libraries are playing a significant role in RDM, there is uncertainty and variation in the relationship with other stakeholders such as IT services and research support offices. Current emphases in RDM programmes are on developments of policies and guidelines, with some early work on technology infrastructures and support services. Drivers for developments include storage, security, quality, compliance, preservation, and sharing with libraries associated most closely with the last three. The paper also highlights a 'jurisdictional' driver in which libraries are claiming a role in this space. A wide range of factors, including governance, resourcing and skills, are identified as influencing ongoing developments. From the analysis, a model is constructed designed to capture the main aspects of an institutional RDM programme. This model helps to clarify the different issues involved in RDM, identifying layers of activity, multiple stakeholders and drivers, and a large number of factors influencing the implementation of any initiative. Institutions may usefully benchmark their activities against the

  8. Optical and SAR data integration for automatic change pattern detection

    NASA Astrophysics Data System (ADS)

    Mishra, B.; Susaki, J.

    2014-09-01

    Automatic change pattern mapping in urban and sub-urban area is important but challenging due to the diversity of urban land use pattern. With multi-sensor imagery, it is possible to generate multidimensional unique information of Earth surface features that allow developing a relationship between a response of each feature to synthetic aperture radar (SAR) and optical sensors to track the change automatically. Thus, a SAR and optical data integration framework for change detection and a relationship for automatic change pattern detection were developed. It was carried out in three steps: (i) Computation of indicators from SAR and optical images, namely: normalized difference ratio (NDR) from multi-temporal SAR images and the normalized difference vegetation index difference (NDVI) from multi-temporal optical images, (ii) computing the change magnitude image from NDR and ΔNDVI and delineating the change area and (iii) the development of an empirical relationship, for automatic change pattern detection. The experiment was carried out in an outskirts part of Ho Chi Minh City, one of the fastest growing cities in the world. The empirical relationship between the response of surface feature to optical and SAR imagery has successfully delineated six changed classes in a very complex urban sprawl area that was otherwise impossible with multi-spectral imagery. The improvement of the change detection results by making use of the unique information on both sensors, optical and SAR, is also noticeable with a visual inspection and the kappa index was increased by 0.13 (0.75 to 0.88) in comparison to only optical images.

  9. Structure-activity relationship of cyanine tau aggregation inhibitors

    PubMed Central

    Chang, Edward; Congdon, Erin E.; Honson, Nicolette S.; Duff, Karen E.; Kuret, Jeff

    2009-01-01

    A structure-activity relationship for symmetrical cyanine inhibitors of human tau aggregation was elaborated using a filter trap assay. Antagonist activity depended on cyanine heterocycle, polymethine bridge length, and the nature of meso- and N-substituents. One potent member of the series, 3,3’-diethyl-9-methylthiacarbocyanine iodide (compound 11), retained submicromolar potency and had calculated physical properties consistent with blood-brain barrier and cell membrane penetration. Exposure of organotypic slices prepared from JNPL3 transgenic mice (which express human tau harboring the aggregation prone P301L tauopathy mutation) to compound 11 for one week revealed a biphasic dose response relationship. Low nanomolar concentrations decreased insoluble tau aggregates to half those observed in slices treated with vehicle alone. In contrast, high concentrations (≥300 nM) augmented tau aggregation and produced abnormalities in tissue tubulin levels. These data suggest that certain symmetrical carbocyanine dyes can modulate tau aggregation in the slice biological model at concentrations well below those associated with toxicity. PMID:19432420

  10. Phenolic acid derivatives with potential anticancer properties--a structure-activity relationship study. Part 1: methyl, propyl and octyl esters of caffeic and gallic acids.

    PubMed

    Fiuza, S M; Gomes, C; Teixeira, L J; Girão da Cruz, M T; Cordeiro, M N D S; Milhazes, N; Borges, F; Marques, M P M

    2004-07-01

    The antiproliferative and cytotoxic properties of polyphenolic acid derivatives, structurally related with the natural models caffeic and gallic acids, have been tested in human cervix adenocarcinoma cells (HeLa). Simultaneous structural information was obtained for these compounds through theoretical ab initio methods. This study was conducted for the following esters: methyl caffeate (MC, 1), propyl caffeate (PC, 2), octyl caffeate (OC, 3), methyl gallate (MG, 4), propyl gallate (PG, 5) and octyl gallate (OG, 6). A significant growth-inhibition effect was assessed for some of these compounds, clearly dependent on their structural characteristics. Marked structure-activity relationships (SARs)--namely the number of hydroxyl ring substituents--were found to rule the biological effect of such systems.

  11. Anatomy of a SAR impulse response.

    SciTech Connect

    Doerry, Armin Walter

    2007-08-01

    A principal measure of Synthetic Aperture Radar (SAR) image quality is the manifestation in the SAR image of a spatial impulse, that is, the SAR's Impulse Response (IPR). IPR requirements direct certain design decisions in a SAR. Anomalies in the IPR can point to specific anomalous behavior in the radar's hardware and/or software.

  12. Determination of boiling point of petrochemicals by gas chromatography-mass spectrometry and multivariate regression analysis of structural activity relationship.

    PubMed

    Fakayode, Sayo O; Mitchell, Breanna S; Pollard, David A

    2014-08-01

    Accurate understanding of analyte boiling points (BP) is of critical importance in gas chromatographic (GC) separation and crude oil refinery operation in petrochemical industries. This study reported the first combined use of GC separation and partial-least-square (PLS1) multivariate regression analysis of petrochemical structural activity relationship (SAR) for accurate BP determination of two commercially available (D3710 and MA VHP) calibration gas mix samples. The results of the BP determination using PLS1 multivariate regression were further compared with the results of traditional simulated distillation method of BP determination. The developed PLS1 regression was able to correctly predict analytes BP in D3710 and MA VHP calibration gas mix samples, with a root-mean-square-%-relative-error (RMS%RE) of 6.4%, and 10.8% respectively. In contrast, the overall RMS%RE of 32.9% and 40.4%, respectively obtained for BP determination in D3710 and MA VHP using a traditional simulated distillation method were approximately four times larger than the corresponding RMS%RE of BP prediction using MRA, demonstrating the better predictive ability of MRA. The reported method is rapid, robust, and promising, and can be potentially used routinely for fast analysis, pattern recognition, and analyte BP determination in petrochemical industries.

  13. Determination of boiling point of petrochemicals by gas chromatography-mass spectrometry and multivariate regression analysis of structural activity relationship.

    PubMed

    Fakayode, Sayo O; Mitchell, Breanna S; Pollard, David A

    2014-08-01

    Accurate understanding of analyte boiling points (BP) is of critical importance in gas chromatographic (GC) separation and crude oil refinery operation in petrochemical industries. This study reported the first combined use of GC separation and partial-least-square (PLS1) multivariate regression analysis of petrochemical structural activity relationship (SAR) for accurate BP determination of two commercially available (D3710 and MA VHP) calibration gas mix samples. The results of the BP determination using PLS1 multivariate regression were further compared with the results of traditional simulated distillation method of BP determination. The developed PLS1 regression was able to correctly predict analytes BP in D3710 and MA VHP calibration gas mix samples, with a root-mean-square-%-relative-error (RMS%RE) of 6.4%, and 10.8% respectively. In contrast, the overall RMS%RE of 32.9% and 40.4%, respectively obtained for BP determination in D3710 and MA VHP using a traditional simulated distillation method were approximately four times larger than the corresponding RMS%RE of BP prediction using MRA, demonstrating the better predictive ability of MRA. The reported method is rapid, robust, and promising, and can be potentially used routinely for fast analysis, pattern recognition, and analyte BP determination in petrochemical industries. PMID:24881546

  14. Synthesis and antiviral evaluation of 7-O-arylmethylquercetin derivatives against SARS-associated coronavirus (SCV) and hepatitis C virus (HCV).

    PubMed

    Park, Hye Ri; Yoon, Hyunjun; Kim, Mi Kyoung; Lee, Sung Dae; Chong, Youhoon

    2012-01-01

    Aryl diketoacid (ADK) is well known for antiviral activity which can be enhanced by introduction of an aromatic arylmethyl substituent. A natural flavonoid quercetin has a 3,5-dihydroxychromone pharmacophore which is in bioisosteric relationship with the 1,3-diketoacid moiety of the ADK. Thus, it was of our interest to test the antiviral activity of the quercetin derivatives with an arylmethyl group attached. In this study, we prepared a series of the 7-O-arylmethylquercetin derivatives with various aromatic substituents and evaluated their antiviral activity against the SARS-associated coronavirus (SARS-CoV, SCV) as well as hepatitis C virus (HCV). Single difference in the aromatic substituent fine-tuned the biological activity of the 7-O-arylmethylquercetin derivatives to result in two different classes of derivatives selectively active against SCV and HCV.

  15. Contribution of 2009-2014 COSMO-SkyMed SAR data to the interpretation of the Campi Flegrei caldera, Italy, activity.

    NASA Astrophysics Data System (ADS)

    Amoruso, Antonella; Crescentini, Luca; Luongo, Annamaria; Zinno, Ivana; Casu, Francesco

    2015-04-01

    ,b) used leveling data from 1980 to 1994, geodetic precise-traversing data for June 1980 and June 1983, ERS/ENVISAT SAR data from 1993 to 2010, and cGPS data from 2000 to 2013. Here we take advantage of the SAR images acquired by COSMO-SkyMed ASI constellation to analyze CF ground deformation via the SBAS-InSAR algorithm from 2009 to spring 2014, at high spatial (3x3 m2) and temporal resolution (8 days revisit time on average). Firstly, we have compared InSAR LOS and cGPS displacements, then we have generated the InSAR LOS residual time series after subtracting predictions for PTE and PS, using the best-fit source potency time histories. We show that residuals are always very small, apart from few sporadic (in time and place) local (<1 km2) short-duration (few weeks) displacement anomalies of about 1 cm, which are in any case on the order of the InSAR technique accuracy. The source potency time histories confirm the negligible role of PS during the 2011-2013 unrest. Amoruso et al. (2014a), J. Geophys. Res., 119 (2), 858-879 Amoruso et al. (2014b), Geophys. Res. Lett., 41 (9), 3081-3088

  16. Studies of ice sheet hydrology using SAR

    NASA Technical Reports Server (NTRS)

    Bindschadler, R. A.; Vornberger, P. L.

    1989-01-01

    Analysis of SAR data of the Greenland ice sheet in summer and winter suggest the use of SAR to monitor the temporal hydrology of ice sheets. Comparisons of each SAR data set with summer Landsat TM imagery show an areal-positive correlation with summer SAR data and a negative correlation with winter SAR data. It is proposed that the summer SAR data are most sensitive to the variable concentrations of free water in the surface snow and that the winter SAR data indicate variations in snow grain size.

  17. ERS-1 SAR data processing

    NASA Technical Reports Server (NTRS)

    Leung, K.; Bicknell, T.; Vines, K.

    1986-01-01

    To take full advantage of the synthetic aperature radar (SAR) to be flown on board the European Space Agency's Remote Sensing Satellite (ERS-1) (1989) and the Canadian Radarsat (1990), the implementation of a receiving station in Alaska is being studied to gather and process SAR data pertaining in particular to regions within the station's range of reception. The current SAR data processing requirement is estimated to be on the order of 5 minutes per day. The Interim Digital Sar Processor (IDP) which was under continual development through Seasat (1978) and SIR-B (1984) can process slightly more than 2 minutes of ERS-1 data per day. On the other hand, the Advanced Digital SAR Processore (ADSP), currently under development for the Shuttle Imaging Radar C (SIR-C, 1988) and the Venus Radar Mapper, (VMR, 1988), is capable of processing ERS-1 SAR data at a real time rate. To better suit the anticipated ERS-1 SAR data processing requirement, both a modified IDP and an ADSP derivative are being examined. For the modified IDP, a pipelined architecture is proposed for the mini-computer plus array processor arrangement to improve throughout. For the ADSP derivative, a simplified version is proposed to enhance ease of implementation and maintainability while maintaing real time throughput rates. These processing systems are discussed and evaluated.

  18. Design, synthesis, and structure-activity relationships of novel benzothiazole derivatives bearing the ortho-hydroxy N-carbamoylhydrazone moiety as potent antitumor agents.

    PubMed

    Ma, Junjie; Chen, Dong; Lu, Kuan; Wang, Lihui; Han, Xiaoqi; Zhao, Yanfang; Gong, Ping

    2014-10-30

    A series of novel benzothiazole derivatives bearing the ortho-hydroxy N-carbamoylhydrazone moiety were designed and synthesized and their cytotoxic activities against five cancer cell lines (NCI-H226, SK-N-SH, HT29, MKN45, and MDA-MB-231) were screened in vitro. Most of them showed moderate to excellent activity against all the tested cell lines. Among them, compounds 15g (procaspase-3 EC50 = 1.42 μM) and 16b (procaspase-3 EC50 = 0.25 μM) exhibited excellent antitumor activity with IC50 values ranging from 0.14 μM to 0.98 μM against all cancer cell lines, which were 1.8-8.7 times more active than the first procaspase activating compound (PAC-1) (procaspase-3 EC50 = 4.08 μM). The structure-activity relationship (SAR) analyses indicated that the introduction of a lipophilic group (a benzyloxy or heteroaryloxy group) at the 4-position of the 2-hydroxy phenyl ring was beneficial to antitumor activity, and the presence of substituents containing nitrogen that are positively charged at physiological pH could also improve antitumor activity. It was also confirmed that the steric effect of the 4-position substituent of the benzyloxy group had a significant influence on cytotoxic activity. PMID:25171780

  19. 49 CFR 173.434 - Activity-mass relationships for uranium and natural thorium.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 2 2013-10-01 2013-10-01 false Activity-mass relationships for uranium and....434 Activity-mass relationships for uranium and natural thorium. The table of activity-mass relationships for uranium and natural thorium are as follows: Thorium and uranium enrichment 1(Wt% 235 U...

  20. 49 CFR 173.434 - Activity-mass relationships for uranium and natural thorium.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 2 2012-10-01 2012-10-01 false Activity-mass relationships for uranium and....434 Activity-mass relationships for uranium and natural thorium. The table of activity-mass relationships for uranium and natural thorium are as follows: Thorium and uranium enrichment 1(Wt% 235 U...

  1. 49 CFR 173.434 - Activity-mass relationships for uranium and natural thorium.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 2 2011-10-01 2011-10-01 false Activity-mass relationships for uranium and....434 Activity-mass relationships for uranium and natural thorium. The table of activity-mass relationships for uranium and natural thorium are as follows: Thorium and uranium enrichment 1(Wt% 235 U...

  2. 49 CFR 173.434 - Activity-mass relationships for uranium and natural thorium.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false Activity-mass relationships for uranium and....434 Activity-mass relationships for uranium and natural thorium. The table of activity-mass relationships for uranium and natural thorium are as follows: Thorium and uranium enrichment 1(Wt% 235 U...

  3. 49 CFR 173.434 - Activity-mass relationships for uranium and natural thorium.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 2 2014-10-01 2014-10-01 false Activity-mass relationships for uranium and....434 Activity-mass relationships for uranium and natural thorium. The table of activity-mass relationships for uranium and natural thorium are as follows: Thorium and uranium enrichment 1(Wt% 235 U...

  4. SAR11 bacteria linked to ocean anoxia and nitrogen loss

    NASA Astrophysics Data System (ADS)

    Tsementzi, Despina; Wu, Jieying; Deutsch, Samuel; Nath, Sangeeta; Rodriguez-R, Luis M.; Burns, Andrew S.; Ranjan, Piyush; Sarode, Neha; Malmstrom, Rex R.; Padilla, Cory C.; Stone, Benjamin K.; Bristow, Laura A.; Larsen, Morten; Glass, Jennifer B.; Thamdrup, Bo; Woyke, Tanja; Konstantinidis, Konstantinos T.; Stewart, Frank J.

    2016-08-01

    Bacteria of the SAR11 clade constitute up to one half of all microbial cells in the oxygen-rich surface ocean. SAR11 bacteria are also abundant in oxygen minimum zones (OMZs), where oxygen falls below detection and anaerobic microbes have vital roles in converting bioavailable nitrogen to N2 gas. Anaerobic metabolism has not yet been observed in SAR11, and it remains unknown how these bacteria contribute to OMZ biogeochemical cycling. Here, genomic analysis of single cells from the world’s largest OMZ revealed previously uncharacterized SAR11 lineages with adaptations for life without oxygen, including genes for respiratory nitrate reductases (Nar). SAR11 nar genes were experimentally verified to encode proteins catalysing the nitrite-producing first step of denitrification and constituted ~40% of OMZ nar transcripts, with transcription peaking in the anoxic zone of maximum nitrate reduction activity. These results link SAR11 to pathways of ocean nitrogen loss, redefining the ecological niche of Earth’s most abundant organismal group.

  5. SAR11 bacteria linked to ocean anoxia and nitrogen loss.

    PubMed

    Tsementzi, Despina; Wu, Jieying; Deutsch, Samuel; Nath, Sangeeta; Rodriguez-R, Luis M; Burns, Andrew S; Ranjan, Piyush; Sarode, Neha; Malmstrom, Rex R; Padilla, Cory C; Stone, Benjamin K; Bristow, Laura A; Larsen, Morten; Glass, Jennifer B; Thamdrup, Bo; Woyke, Tanja; Konstantinidis, Konstantinos T; Stewart, Frank J

    2016-08-11

    Bacteria of the SAR11 clade constitute up to one half of all microbial cells in the oxygen-rich surface ocean. SAR11 bacteria are also abundant in oxygen minimum zones (OMZs), where oxygen falls below detection and anaerobic microbes have vital roles in converting bioavailable nitrogen to N2 gas. Anaerobic metabolism has not yet been observed in SAR11, and it remains unknown how these bacteria contribute to OMZ biogeochemical cycling. Here, genomic analysis of single cells from the world's largest OMZ revealed previously uncharacterized SAR11 lineages with adaptations for life without oxygen, including genes for respiratory nitrate reductases (Nar). SAR11 nar genes were experimentally verified to encode proteins catalysing the nitrite-producing first step of denitrification and constituted ~40% of OMZ nar transcripts, with transcription peaking in the anoxic zone of maximum nitrate reduction activity. These results link SAR11 to pathways of ocean nitrogen loss, redefining the ecological niche of Earth's most abundant organismal group. PMID:27487207

  6. Trypanocidal nitroimidazole derivatives: relationships among chemical structure and genotoxic activity.

    PubMed

    Buschini, Annamaria; Giordani, Federica; de Albuquerque, Cristina Northfleet; Pellacani, Claudia; Pelosi, Giorgio; Rossi, Carlo; Zucchi, Tânia Maria Araújo Domingues; Poli, Paola

    2007-05-15

    Human American trypanosomiasis is resurgent in Latin Americans, and new drugs are urgently required as current medications suffer from a number of drawbacks. Some nitroheterocycles have been demonstrated to exert a potent activity against trypanosomes. However, host toxicity issues halted their development as trypanocides. As part of the efforts to develop new compounds in order to treat parasitic infections, it is important to define their structure-activity relationship. In this study, 5-nitromegazol and two of its analogues, 4-nitromegazol, and 1-methyl-5-nitro-2-imidazolecarboxaldehyde 5-nitroimidazole-thiosemicarbazone, were tested and compared for in vitro induction of DNA damage in human leukocytes by the comet assay, performed at different pHs to better identify the types of damage. Specific oxidatively generated damage to DNA was also measured by using the comet assay with endonucleases. DNA damage was found in 5-nitromegazol-treated cells: oxidative stress appeared as the main source of DNA damage. 4-Nitromegazol did not produce any significant effect, thus confirming that 4-nitroimidazoles isomers have no important biological activity. The 5-nitroimidazole-thiosemicarbazone induced DNA damage with a higher efficiency than 5-nitromegazol. The central role in the reduction process played by the acidic hydrazine proton present in the thiosemicarbazone group but not in the cyclic (thiadiazole) form can contribute to rationalise our results. Given its versatility, thiosemicarbazone moiety could be involved in different reactions with nitrogenous bases (nucleophilic and/or electrophilic attacks).

  7. Structure activity relationships: their function in biological prediction

    SciTech Connect

    Schultz, T.W.

    1982-01-01

    Quantitative structure activity relationships provide a means of ranking or predicting biological effects based on chemical structure. For each compound used to formulate a structure activity model two kinds of quantitative information are required: (1) biological activity and (2) molecular properties. Molecular properties are of three types: (1) molecular shape, (2) physiochemical parameters, and (3) abstract quantitations of molecular structure. Currently the two best descriptors are the hydrophobic parameter, log 1-octanol/water partition coefficient (log P), and the /sup 1/X/sup v/(one-chi-v) molecular connectivity index. Biological responses can be divided into three main categories: (1) non-specific effects due to membrane perturbation, (2) non-specific effects due to interaction with functional groups of proteins, and (3) specific effects due to interaction with receptors. Twenty-six synthetic fossil fuel-related nitrogen-containing aromatic compounds were examined to determine the quantitative correlation between log P and /sup 1/X/sup v/ and population growth impairment of Tetrahymena pyriformis. Nitro-containing compounds are the most active, followed by amino-containing compounds and azaarenes. Within each analog series activity increases with alkyl substitution and ring addition. The planar model log BR = 0.5564 log P + 0.3000 /sup 1/X/sup v/ -2.0138 was determined using mono-nitrogen substituted compounds. Attempts to extrapolate this model to dinitrogen-containing molecules were, for the most part, unsuccessful because of a change in mode of action from membrane perturbation to uncoupling of oxidative phosphoralation.

  8. Synthesis and Structural Activity Relationship Study of Antitubercular Carboxamides

    PubMed Central

    Ugwu, D. I.; Ezema, B. E.; Eze, F. U.; Ugwuja, D. I.

    2014-01-01

    The unusual structure and chemical composition of the mycobacterial cell wall, the tedious duration of therapy, and resistance developed by the microorganism have made the recurrence of the disease multidrug resistance and extensive or extreme drug resistance. The prevalence of tuberculosis in synergy with HIV/AIDS epidemic augments the risk of developing the disease by 100-fold. The need to synthesize new drugs that will shorten the total duration of effective treatment and/or significantly reduce the dosage taken under DOTS supervision, improve on the treatment of multidrug-resistant tuberculosis which defies the treatment with isoniazid and rifampicin, and provide effective treatment for latent TB infections which is essential for eliminating tuberculosis prompted this review. In this review, we considered the synthesis and structure activity relationship study of carboxamide derivatives with antitubercular potential. PMID:25610646

  9. Capsaicin and its analogues: structure-activity relationship study.

    PubMed

    Huang, X-F; Xue, J-Y; Jiang, A-Q; Zhu, H-L

    2013-01-01

    Capsaicin, the main ingredient responsible for the hot pungent taste of chilli peppers, is an alkaloid found in the Capsicum family. Capsaicin was traditionally used for muscular pain, headaches, to improve circulation and for its gastrointestinal protective effects. It was also commonly added to herbal formulations because it acts as a catalyst for other herbs and aids in their absorption. In addition, capsaicin and other capsaicinoid compounds showed strong evidence of having promising potential in the fight against many types of cancer. The mechanism of action of capsaicin has been extensively studied over the past decade. It has been established that capsaicin binds to the transient receptor potential vanilloid 1 receptor which was expressed predominantly by sensory neurons. And many analogues of capsaicin have been synthesized and evaluated for diverse bioactivities. In this review, we will attempt to summarize the biology and structure-activity relationship of capsaicinoids.

  10. Synthetic Aperture Radar (SAR) data processing

    NASA Technical Reports Server (NTRS)

    Beckner, F. L.; Ahr, H. A.; Ausherman, D. A.; Cutrona, L. J.; Francisco, S.; Harrison, R. E.; Heuser, J. S.; Jordan, R. L.; Justus, J.; Manning, B.

    1978-01-01

    The available and optimal methods for generating SAR imagery for NASA applications were identified. The SAR image quality and data processing requirements associated with these applications were studied. Mathematical operations and algorithms required to process sensor data into SAR imagery were defined. The architecture of SAR image formation processors was discussed, and technology necessary to implement the SAR data processors used in both general purpose and dedicated imaging systems was addressed.

  11. The relationships between active extensibility, and passive and active stiffness of the knee flexors.

    PubMed

    Blackburn, J Troy; Padua, Darin A; Riemann, Bryan L; Guskiewicz, Kevin M

    2004-12-01

    Insufficient active knee flexor stiffness may predispose the anterior cruciate ligament to injury. Insufficient passive stiffness may result in insufficient active stiffness. Similarly, higher levels of musculotendinous extensibility may inhibit active and passive muscle stiffness, potentially contributing to an increased risk of injury. The literature is both limited and inconsistent concerning relationships between extensibility, passive stiffness, and active stiffness. Extensibility was measured as the maximal active knee extension angle from a supine position with the hip flexed to 90 degrees . Passive stiffness was calculated as the slope of the moment-angle curve resulting from passive knee extension. Active stiffness was assessed via acceleration associated with damped oscillatory motion about the knee. Stepwise multiple regression indicated that passive stiffness accounted for 25% of active muscle stiffness variance. The linear combination of extensibility and passive stiffness explained only 2% more variance compared to passive stiffness alone. Musculotendinous extensibility was moderately related to passive muscle stiffness, and weakly related to active muscle stiffness. The moderate relationship observed between active and passive stiffness emphasizes the dependence of active muscle stiffness on cross-bridge formation, and the relatively smaller contribution from parallel elastic tissues. Additionally, heightened extensibility does not appear to be a predisposing factor for reduced muscle stiffness. PMID:15491843

  12. Antioxidant, cytotoxic activities, and structure-activity relationship of gallic acid-based indole derivatives.

    PubMed

    Khaledi, Hamid; Alhadi, Abeer A; Yehye, Wagee A; Ali, Hapipah Mohd; Abdulla, Mahmood A; Hassandarvish, Pouya

    2011-11-01

    A new series of gallic hydrazones containing an indole moiety was synthesized through the reaction of gallic hydrazide and different indole carboxaldehydes. Their antioxidant activities were determined on DPPH radical scavenging and inhibition of lipid peroxidation. The in-vitro cytotoxic activities of the compounds were evaluated against HCT-116 (human colon cancer cell line) and MCF-7 (estrogen-dependent human breast cancer cell line) by the MTT method. An attempt to correlate the biological results with their structural characteristics has been done. A limited positive structure activity relationship was found between cytotoxic and antioxidant activities.

  13. InSAR Observations of Magmatic Processes in the East African Rift

    NASA Astrophysics Data System (ADS)

    Biggs, Juliet; Anthony, Elizabeth; Ebinger, Cynthia; Amelung, Falk; Gourmelen, Noel

    2010-05-01

    The role of magma in accommodating extension and it's relationship to fault-based extension in continental rifting is poorly understood. Here we present observations of the temporal and spatial evolution of surface displacements resulting from magmatic processes in the East African Rift. A systematic InSAR surveys have detected geodetic activity at six of the volcanoes in the East African Rift. In Kenya, subsidence of 2-5 cm occurred at Suswa and Menengai during 1997-2000, ~9cm of uplift at Longonot in 2004-2006 and ~21 cm of uplift at Paka during 2006-2007. The deformation is episodic, and no deformation was observed at these volcanoes during other time-periods. The best-fitting source models for each episode is inflation or deflation of a horizontal lensoid at a depth of 2-5 km. The episodic nature of the activity, its lack of correlation with seasons, and the preferred source geometry are all consistent with activity in the volatile-rich cap to a crystal-rich magma chamber beneath each of the 4 volcanoes. A seismic swarm occurred in Northern Tanzania from July 14 to August 4 2007. Using InSAR images from Envisat (IS2 and IS6) and ALOS, we show that the seismic swarm was accompanied by 1) subsidence that can be attributed to ~40 cm of normal motion on a NE striking fault, 2) the intrusion of ~2.4 m wide dyke, 3) deflation of a point source magma chamber and 4) collapse of a shallow graben. The large number of available SAR images allows us to examine the sequence and time-dependent behaviour of these processes and relationship between diking and faulting.

  14. Discovery and SAR of pyrrolo[2,1-f][1,2,4]triazin-4-amines as potent and selective PI3Kδ inhibitors.

    PubMed

    Bhide, Rajeev S; Neels, James; Qin, Lan-Ying; Ruan, Zheming; Stachura, Sylwia; Weigelt, Carolyn; Sack, John S; Stefanski, Kevin; Gu, Xiaomei; Xie, Jenny H; Goldstine, Christine B; Skala, Stacey; Pedicord, Donna L; Ruepp, Stefan; Dhar, T G Murali; Carter, Percy H; Salter-Cid, Luisa M; Poss, Michael A; Davies, Paul

    2016-09-01

    Aberrant Class I PI3K signaling is a key factor contributing to many immunological disorders and cancers. We have identified 4-amino pyrrolotriazine as a novel chemotype that selectively inhibits PI3Kδ signaling despite not binding to the specificity pocket of PI3Kδ isoform. Structure activity relationship (SAR) led to the identification of compound 30 that demonstrated efficacy in mouse Keyhole Limpet Hemocyanin (KLH) and collagen induced arthritis (CIA) models. PMID:27476421

  15. Interferometric processing of C-band SAR data for the improvement of stand age estimation in rubber plantation

    NASA Astrophysics Data System (ADS)

    Trisasongko, Bambang H.; Paull, David J.; Panuju, Dyah R.

    2015-01-01

    Rubber ranks the second largest plantation in Indonesia after oil palm. While oil palm plantations have been exploited mainly by large companies, many rubber plantations are still managed by peasant farmers who maintain its biodiversity. Due to its broad and scattered location, monitoring tropical rubber plantation is a crucial application of active remote sensing. In this paper, the backscatter coefficient of Envisat Advanced Synthetic Aperture Radar (ASAR) is compared to interferometric coherence to study the relationship between stand age and SAR parameters. It is shown that VV polarized C-band SAR achieves its saturation level in plantations aged about 5-10 years. Extension of saturation level can be achieved by processing an interferometric pair of ASAR data, which results in interferometric coherence. In this paper, coherence can take up to 20 years stand age to achieve prior to saturation. Since stand age is highly related to biomass, this finding argues that the biomass can be best estimated using coherence.

  16. Earth observing SAR data processing systems at the Jet Propulsion Laboratory - Seasat to EOS SAR

    NASA Technical Reports Server (NTRS)

    Nichols, David A.; Curlander, John C.

    1991-01-01

    The evolution of SAR digital data processing and management ground systems developed at the JPL for earth science missions is discussed. Attention is given to the SAR ground data system requirements, the early data processing systems, the Seasat SAR system, and the SIR-B data processing system. Special consideration is given to two currently operational SAR data systems: the JPL aircraft SAR processing system that flies on the NASA DC-8 and the Alaska SAR Facility at Fairbanks.

  17. The Tempo of Sexual Activity and Later Relationship Quality

    ERIC Educational Resources Information Center

    Sassler, Sharon; Addo, Fenaba R.; Lichter, Daniel T.

    2012-01-01

    Rapid sexual involvement may have adverse long-term implications for relationship quality. This study examined the tempo of sexual intimacy and subsequent relationship quality in a sample of married and cohabiting men and women. Data come from the Marital and Relationship Survey, which provides information on nearly 600 low- to moderate-income…

  18. Halogenated ligands and their interactions with amino acids: implications for structure-activity and structure-toxicity relationships.

    PubMed

    Kortagere, Sandhya; Ekins, Sean; Welsh, William J

    2008-09-01

    The properties of chemicals are rooted in their molecular structure. It follows that structural analysis of specific interactions between ligands and biomolecules at the molecular level is invaluable for defining structure-activity relationships (SARs) and structure-toxicity relationships (STRs). This study has elucidated the structural and molecular basis of interactions of biomolecules with alkyl and aryl halides that are extensively used as components in many commercial pesticides, disinfectants, and drugs. We analyzed the protein structures deposited in Protein Data Bank (PDB) for structural information associated with interactions between halogenated ligands and proteins. This analysis revealed distinct patterns with respect to the nature and structural characteristics of halogen interactions with specific types of atoms and groups in proteins. Fluorine had the highest propensity of interactions for glycine, while chlorine for leucine, bromine for arginine, and iodine for lysine. Chlorine, bromine and iodine had the lowest propensity of interactions for cysteine, while fluorine had a lowest propensity for proline. These trends for highest propensity shifted towards the hydrophobic residues for all the halogens when only interactions with the side chain were considered. Halogens had equal propensities of interaction for the halogen bonding partners (nitrogen and oxygen atoms), albeit with different geometries. The optimal angle for interactions with halogens was approximately 120 degrees for oxygen atoms, and approximately 96 degrees for nitrogen atoms. The distance distributions of halogens with various amino acids were mostly bimodal, and the angle distributions were unimodal. Insights gained from this study have implications for the rational design of safer drugs and commercially important chemicals.

  19. Quantitative structure-activity relationships for organophosphates binding to acetylcholinesterase.

    PubMed

    Ruark, Christopher D; Hack, C Eric; Robinson, Peter J; Anderson, Paul E; Gearhart, Jeffery M

    2013-02-01

    Organophosphates are a group of pesticides and chemical warfare nerve agents that inhibit acetylcholinesterase, the enzyme responsible for hydrolysis of the excitatory neurotransmitter acetylcholine. Numerous structural variants exist for this chemical class, and data regarding their toxicity can be difficult to obtain in a timely fashion. At the same time, their use as pesticides and military weapons is widespread, which presents a major concern and challenge in evaluating human toxicity. To address this concern, a quantitative structure-activity relationship (QSAR) was developed to predict pentavalent organophosphate oxon human acetylcholinesterase bimolecular rate constants. A database of 278 three-dimensional structures and their bimolecular rates was developed from 15 peer-reviewed publications. A database of simplified molecular input line entry notations and their respective acetylcholinesterase bimolecular rate constants are listed in Supplementary Material, Table I. The database was quite diverse, spanning 7 log units of activity. In order to describe their structure, 675 molecular descriptors were calculated using AMPAC 8.0 and CODESSA 2.7.10. Orthogonal projection to latent structures regression, bootstrap leave-random-many-out cross-validation and y-randomization were used to develop an externally validated consensus QSAR model. The domain of applicability was assessed by the William's plot. Six external compounds were outside the warning leverage indicating potential model extrapolation. A number of compounds had residuals >2 or <-2, indicating potential outliers or activity cliffs. The results show that the HOMO-LUMO energy gap contributed most significantly to the binding affinity. A mean training R (2) of 0.80, a mean test set R (2) of 0.76 and a consensus external test set R (2) of 0.66 were achieved using the QSAR. The training and external test set RMSE values were found to be 0.76 and 0.88. The results suggest that this QSAR model can be used in

  20. Landslide Mapping Using SqueeSAR Data

    NASA Astrophysics Data System (ADS)

    Ferretti, A.; Bellotti, F.; Alberti, S.; Allievi, J.; Del Conte, S.; Tamburini, A.; Broccolato, M.; Ratto, S.; Alberto, W.

    2011-12-01

    SqueeSAR represents the most recent advancement of PSInSAR algorithm. By exploiting signal radar returns both from Permanent and Distributed Scatterers (PS and DS), it is able to detect millimetre displacements over long periods and large areas and to obtain a significant increase in the spatial density of ground measurement points. SqueeSAR analysis is complementary to conventional geological and geomorphological studies in landslide mapping over wide areas, traditionally based on aerial-photo interpretation and field surveys. However, whenever surface displacement rates are low (mm to cm per year), assessing landslide activity is difficult or even impossible without a long-term monitoring tool, as in the case of Deep-seated Gravitational Slope Deformations (DGSD), typically characterized by large areal extent and subtle surface displacement. The availability of surface displacement time series per each measurement point allows one to have both a synoptic overview, at regional scale, as well as an in depth characterization of the instability phenomena analyzed, a meaningful support to the design of traditional monitoring networks and the efficiency testing of remedial works. When data archives are available, SqueeSAR can also provide valuable information before the installation of any terrestrial measurement system. The Italian authorities increasing interest in the application of SqueeSAR as a standard monitoring tool to help hydrogeological risk assessment, resulted in a national project, Piano Straordinario di Telerilevamento (PST), founded by the Ministry of the Environment. The aim of the project was to create the first interferometric database on a national scale for mapping unstable areas. More than 12,000 ERS and ENVISAT radar scenes acquired over Italy were processed spanning the period 1992-2010, proving that, in less than ten years, radar interferometry has become a standard monitoring tool. Recently, many regional governments in Italy have applied

  1. Ground subsidence and associated ground fracturing in urban areas: InSAR monitoring of active tectonic structures (Ciudad Guzman, Colima Graben - Mexico)

    NASA Astrophysics Data System (ADS)

    Bignami, C.; Brunori, C.; Zucca, F.; Groppelli, G.; Norini, G.; Hernandez, N. D.; Stramondo, S.

    2013-12-01

    This study focuses on the observation of a creeping phenomenon that produces subsidence of the Zapotlan basin and ground fracturing in correspondence of the Ciudad Guzmàn (Jalisco - Mexico). The September 21, 2012, the Ciudad Guzmàn has been struck by a phenomenon of ground fracturing of about 1.5 km of length. This event caused the deformation of the roads and the damage of 30 houses, of which eight have been declared uninhabitable. The alignment of fractures is coincident with the escarpments produced in September 19, 1985, in the Ciudad Guzman urban area, when a strong earthquake, magnitude 8.1, struck the Mexican area, causing the deaths of at least 10,000 people and serious damage in Mexico City. In Ciudad Guzmán, about 60% of the buildings were destroyed, with about 50 loss of life. The city is located in the Zapotlan basin (northern Colima graben), a wide tectonic depression where the depth of the infilling sediments is about 1 km. This subsidence cannot be measured outside the urbanized area, but it can be considered as a deformation mechanism of the central part of the basin. In order to detect and mapping the spatio-temporal features of the processes that led to this event, we applied InSAR multi-temporal techniques to analyze a dataset of ENVISAT satellite SAR images, acquired in a time span between 2003-2010. InSAR techniques detect a subsidence of the north-western part of Ciudad Guzmàn of about 15 mm/yr in the time interval 2003-2010. The displacement occurred in September 21, 2012, was detected using two RadarSAT2 acquisitions (2012-03-22 and 2013-03-17). The explanation of surface movements based on interferometric results, ground data and geological field observations, allowed confirming surface effect due to the overexploitation of the aquifers and highlights a subsidence due to anthropogenic causes coupled to buried tectonic structures.

  2. Statistical determination of whole-body average SARs in a 2 GHz whole-body exposure system for unrestrained pregnant and newborn rats

    NASA Astrophysics Data System (ADS)

    Wang, Jianqing; Wake, Kanako; Kawai, Hiroki; Watanabe, Soichi; Fujiwara, Osamu

    2012-01-01

    A 2 GHz whole-body exposure to rats over a multigeneration has been conducted as part of bio-effect research in Japan. In this study, the rats moved freely in the cage inside the exposure system. From observation of the activity of rats in the cage, we found that the rats do not stay in each position with uniform possibility. In order to determine the specific absorption rate (SAR) during the entire exposure period with high accuracy, we present a new approach to statistically determine the SAR level in an exposure system. First, we divided the rat cage in the exposure system into several small areas, and derived the fraction of time the rats spent in each small area based on the classification of the documentary photos of rat activity. Then, using the fraction of time spent in each small area as a weighting factor, we calculated the statistical characteristics of the whole-body average SAR for pregnant rats and young rats during the entire exposure period. As a result, this approach gave the statistical distribution as well as the corresponding mean value, median value and mode value for the whole-body SAR so that we can reasonably clarify the relationship between the exposure level and possible biological effect.

  3. Modeling chemical interaction profiles: II. Molecular docking, spectral data-activity relationship, and structure-activity relationship models for potent and weak inhibitors of cytochrome P450 CYP3A4 isozyme.

    PubMed

    Tie, Yunfeng; McPhail, Brooks; Hong, Huixiao; Pearce, Bruce A; Schnackenberg, Laura K; Ge, Weigong; Buzatu, Dan A; Wilkes, Jon G; Fuscoe, James C; Tong, Weida; Fowler, Bruce A; Beger, Richard D; Demchuk, Eugene

    2012-03-15

    Polypharmacy increasingly has become a topic of public health concern, particularly as the U.S. population ages. Drug labels often contain insufficient information to enable the clinician to safely use multiple drugs. Because many of the drugs are bio-transformed by cytochrome P450 (CYP) enzymes, inhibition of CYP activity has long been associated with potentially adverse health effects. In an attempt to reduce the uncertainty pertaining to CYP-mediated drug-drug/chemical interactions, an interagency collaborative group developed a consensus approach to prioritizing information concerning CYP inhibition. The consensus involved computational molecular docking, spectral data-activity relationship (SDAR), and structure-activity relationship (SAR) models that addressed the clinical potency of CYP inhibition. The models were built upon chemicals that were categorized as either potent or weak inhibitors of the CYP3A4 isozyme. The categorization was carried out using information from clinical trials because currently available in vitro high-throughput screening data were not fully representative of the in vivo potency of inhibition. During categorization it was found that compounds, which break the Lipinski rule of five by molecular weight, were about twice more likely to be inhibitors of CYP3A4 compared to those, which obey the rule. Similarly, among inhibitors that break the rule, potent inhibitors were 2-3 times more frequent. The molecular docking classification relied on logistic regression, by which the docking scores from different docking algorithms, CYP3A4 three-dimensional structures, and binding sites on them were combined in a unified probabilistic model. The SDAR models employed a multiple linear regression approach applied to binned 1D ¹³C-NMR and 1D ¹⁵N-NMR spectral descriptors. Structure-based and physical-chemical descriptors were used as the basis for developing SAR models by the decision forest method. Thirty-three potent inhibitors and 88 weak

  4. SarA positively controls bap-dependent biofilm formation in Staphylococcus aureus.

    PubMed

    Trotonda, María Pilar; Manna, Adhar C; Cheung, Ambrose L; Lasa, Iñigo; Penadés, José R

    2005-08-01

    The biofilm-associated protein Bap is a staphylococcal surface protein involved in biofilm formation. We investigated the influence of the global regulatory locus sarA on bap expression and Bap-dependent biofilm formation in three unrelated Staphylococcus aureus strains. The results showed that Bap-dependent biofilm formation was diminished in the sarA mutants by an agr-independent mechanism. Complementation studies using a sarA clone confirmed that the defect in biofilm formation was due to the sarA mutation. As expected, the diminished capacity to form biofilms in the sarA mutants correlated with the decreased presence of Bap in the bacterial surface. Using transcriptional fusion and Northern analysis data, we demonstrated that the sarA gene product acts as an activator of bap expression. Finally, the bap promoter was characterized and the transcriptional start point was mapped by the rapid amplification of cDNA ends technique. As expected, we showed that purified SarA protein binds specifically to the bap promoter, as determined by gel shift and DNase I footprinting assays. Based on the previous studies of others as well as our work demonstrating the role for SarA in icaADBC and bap expression, we propose that SarA is an essential regulator controlling biofilm formation in S. aureus.

  5. Reflection on SARS Precautions in a Severe Intellectual Disabilities Hospital in Hong Kong

    ERIC Educational Resources Information Center

    Wong, S. Y.; Lim, W. W. C.; Que, T. L.; Au, D. M. Y.

    2005-01-01

    Hong Kong went through a battle with a new respiratory disease, severe acute respiratory syndrome (SARS), from March to June 2003. All clinical settings, including rehabilitative and infirmary setting, have actively involved in fighting against the infection. The intent of this paper was to reflect on the SARS precautionary measures that had been…

  6. Antibacterial activity of xanthones from Garcinia mangostana (L.) and their structure-activity relationship studies.

    PubMed

    Dharmaratne, H R W; Sakagami, Yoshikazu; Piyasena, K G P; Thevanesam, Vasanthi

    2013-01-01

    Antibacterial activities of prenylated xanthones from Garcinia mangostana and their synthetic analogues were investigated, and their structure-activity relationships have been studied. γ-Mangostin has shown antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), methicillin sensitive Staphylococcus aureus (MSSA), vancomycin-resistant Enterococcus (VRE) and vancomycin-sensitive Enterococcus (VSE) strains at MICs 3.13, 6.25, 6.25 and 6.25 µg mL(-1), respectively. In these experiments, gentamicin was used as the positive control. Further, some analogues of γ-mangostin and α-mangostin were synthesised and their activity was tested against MRSA and VRE strains. The analysis of the bioassay results above indicated that, the combination of C-6 and C-3 hydroxyl groups along with the prenyl side chain at C-2 in the 1,3,6,7-tetraoxygenated xanthones from G. mangostana is essential to have a high antibacterial activity.

  7. Interferometric SAR to EO image registration problem

    NASA Astrophysics Data System (ADS)

    Rogers, George W.; Mansfield, Arthur W.; Rais, Houra

    2000-08-01

    Historically, SAR to EO registration accuracy has been at the multiple pixel level compared to sub-pixel EO to EO registration accuracies. This is due to a variety of factors including the different scattering characteristics of the ground for EO and SAR, SAR speckle, and terrain induced geometric distortion. One approach to improving the SAR to EO registration accuracy is to utilize the full information from multiple SAR surveys using interferometric techniques. In this paper we will examine this problem in detail with an example using ERS SAR imagery. Estimates of the resulting accuracy based on ERS are included.

  8. Structure-Activity Relationship Study of Hydroxycoumarins and Mushroom Tyrosinase.

    PubMed

    Asthana, Shailendra; Zucca, Paolo; Vargiu, Attilio V; Sanjust, Enrico; Ruggerone, Paolo; Rescigno, Antonio

    2015-08-19

    The structure-activity relationships of four hydroxycoumarins, two with the hydroxyl group on the aromatic ring of the molecule and two with the hydroxyl group replacing hydrogen of the pyrone ring, and their interactions with mushroom tyrosinase were studied. These compounds displayed different behaviors upon action of the enzyme. The two compounds, ar-hydroxylated 6-hydroxycoumarin and 7-hydroxycoumarin, were both weak substrates of the enzyme. Interestingly, in both cases, the product of the catalysis was the 6,7-hydroxycoumarin, although 5,6- and 7,8-isomers could also theoretically be formed. Additionally, both were able to reduce the formation of dopachrome when tyrosinase acted on its typical substrate, L-tyrosine. Although none of the compounds that contained a hydroxyl group on the pyrone ring were substrates of tyrosinase, the 3-hydroxycoumarin was a potent inhibitor of the enzyme, and the 4-hydroxycoumarin was not an inhibitor. These results were compared with those obtained by in silico molecular docking predictions to obtain potentially useful information for the synthesis of new coumarin-based inhibitors that resemble the structure of the 3-hydroxycoumarin.

  9. Determining cleanup levels in bioremediation: Quantitative structure activity relationship techniques

    SciTech Connect

    Arulgnanendran, V.R.J.; Nirmalakhandan, N.

    1995-12-31

    An important feature in the process of planning and initiating bioremediation is the quantification of the toxicity of either an individual chemical or a group of chemicals when multiple chemicals are involved. A laboratory protocol was developed to test the toxicity of single chemicals and mixtures of organic chemicals in a soil medium. Portions of these chemicals are used as a training set to develop Quantitative Structure Activity Relationship (QSAR) models. These predictive models are tested using the chemicals in the testing set, i.e., the remaining chemicals. Moreover mixtures with 10 contaminants in each mixture are tested experimentally to determine joint toxicity for mixtures of chemicals. Using the concepts of Toxic Units, Additivity Index, and Mixture Toxicity Index, the laboratory results are tested for additive, synergistic, or antagonistic effects of the contaminants. These concepts are further validated on mixtures containing eight chemicals that are tested in the laboratory. In addition to the use of the predictive models in evaluating cleanup levels for hazardous waste locations, they are useful to predict microbial toxicity in soils of new chemicals from a congeneric group acting by the same mode of toxicity. These models are applicable when the contaminants act singly or jointly in a mixture.

  10. Structure activity relationships to assess new chemicals under TSCA

    SciTech Connect

    Auletta, A.E.

    1990-12-31

    Under Section 5 of the Toxic Substances Control Act (TSCA), manufacturers must notify the US Environmental Protection Agency (EPA) 90 days before manufacturing, processing, or importing a new chemical substance. This is referred to as a premanufacture notice (PMN). The PMN must contain certain information including chemical identity, production volume, proposed uses, estimates of exposure and release, and any health or environmental test data that are available to the submitter. Because there is no explicit statutory authority that requires testing of new chemicals prior to their entry into the market, most PMNs are submitted with little or no data. As a result, EPA has developed special techniques for hazard assessment of PMN chemicals. These include (1) evaluation of available data on the chemical itself, (2) evaluation of data on analogues of the PMN, or evaluation of data on metabolites or analogues of metabolites of the PMN, (3) use of quantitative structure activity relationships (QSARs), and (4) knowledge and judgement of scientific assessors in the interpretation and integration of the information developed in the course of the assessment. This approach to evaluating potential hazards of new chemicals is used to identify those that are most in need of addition review of further testing. It should not be viewed as a replacement for testing. 4 tabs.

  11. Prediction of activated carbon adsorption capacities for organic vapors using quantitative structure-activity relationship methods

    SciTech Connect

    Nirmalakhandan, N.N. ); Speece, R.E. )

    1993-08-01

    Quantitative structure-activity relationship (QSAR) methods were used to develop models to estimate and predict activated carbon adsorption capacities for organic vapors. Literature isothermal data from two sources for 22 organic contaminants on six different carbons were merged to form a training set of 75 data points. Two different QSAR approaches were evaluated: the molecular connectivity approach and the linear solvation energy relationship approach. The QSAR model developed in this study using the molecular connectivity approach was able to fit the experimental data with r = 0.96 and standard error of 0.09. The utility of the model was demonstrated by using predicted k values to calculate adsorption capacities of 12 chemicals on two different carbons and comparing them with experimentally determined values. 9 refs., 1 fig., 3 tabs.

  12. Relationship between participation in leisure activities and constraints on Taiwanese breastfeeding mothers during leisure activities

    PubMed Central

    2013-01-01

    Background Participation in leisure activities strongly associates with health and well-being. Little research has explored the relationship between participation in leisure activities and constraints on breastfeeding mothers during leisure activities. The purposes of this study are: 1) to investigate constraints on breastfeeding mothers during leisure activities and participation in leisure activities; 2) to investigate the differences between preferences for leisure activities and actual participation by breastfeeding mothers; 3) to segment breastfeeding mothers with similar patterns, using a cluster analysis based on the delineated participation in leisure activities and leisure preferences; 4) to explore any differences between clusters of breastfeeding mothers with respect to socio-demographic characteristics, breastfeeding behaviours and leisure constraints. Methods This study has a cross-sectional design using an online survey conducted among mothers having breastfeeding experiences of more than four months. The questionnaire includes demographic variables, breastfeeding behaviours, preferences for leisure activities participation, and constraints on leisure activities. Collection of data occurred between March and July 2011, producing 415 valid responses for analysis. Results For breastfeeding mothers, this study identifies constraints on breastfeeding related to leisure activities in addition to the three traditional factors for constraints in the model. This study demonstrates that reports of constraints related to children, family, and nursing environments are the most frequent. Breastfeeding mothers in Taiwan participate regularly in family activities or activities related to their children. Cluster analysis classified breastfeeding mothers into Action and Contemplation groups, and found that mothers within the latter group participate less in leisure activities and experienced more constraints related to breastfeeding. Conclusions Implications provide

  13. Structure-Activity Relationship of Synthetic 2-Phenylnaphthalenes with Hydroxyl Groups that Inhibit Proliferation and Induce Apoptosis of MCF-7 Cancer Cells

    PubMed Central

    Chang, Chi-Fen; Ke, Ci-Yi; Wu, Yang-Chang; Chuang, Ta-Hsien

    2015-01-01

    In this study, six 2-phenylnaphthalenes with hydroxyl groups were synthesized in high yields by the demethylation of the corresponding methoxy-2-phenylnaphthalenes, and one 2-phenylnaphthalene with an amino group was obtained by hydrogenation. All of the 2-phenylnaphthalene derivatives were evaluated for cytotoxicity, and the structure-activity relationship (SAR) against human breast cancer (MCF-7) cells was also determined. The SAR results revealed that cytotoxicity was markedly promoted by the hydroxyl group at the C-7 position of the naphthalene ring. The introduction of hydroxyl groups at the C-6 position of the naphthalene ring and the C-4' position of the phenyl ring fairly enhanced cytotoxicity, but the introduction of a hydroxyl group at the C-3' position of the phenyl ring slightly decreased cytotoxicity. Overall, 6,7-dihydroxy-2-(4'-hydroxyphenyl)naphthalene (PNAP-6h) exhibited the best cytotoxicity, with an IC50 value of 4.8 μM against the MCF-7 cell line, and showed low toxicity toward normal human mammary epithelial cells (MCF-10A). PNAP-6h led to cell arrest at the S phase, most likely due to increasing levels of p21 and p27 and decreasing levels of cyclin D1, CDK4, cyclin E, and CDK2. In addition, PNAP-6h decreased CDK1 and cyclin B1 expression, most likely leading to G2/M arrest, and induced morphological changes, such as nuclear shrinkage, nuclear fragmentation, and nuclear hypercondensation, as observed by Hoechst 33342 staining. PNAP-6h induced apoptosis, most likely by the promotion of Fas expression, increased PARP activity, caspase-7, caspase-8, and caspase-9 expression, the Bax/Bcl-2 ratio, and the phosphorylation of p38, and decreased the phosphorylation of ERK. This study provides the first demonstration of the cytotoxicity of PNAPs against MCF-7 cells and elucidates the mechanism underlying PNAP-induced cytotoxicity. PMID:26492346

  14. Synthesis, biological activity, and quantitative structure-activity relationship study of azanaphthalimide and arylnaphthalimide derivatives.

    PubMed

    Braña, Miguel F; Gradillas, Ana; Gómez, Angel; Acero, Nuria; Llinares, Francisco; Muñoz-Mingarro, Dolores; Abradelo, Cristina; Rey-Stolle, Fernanda; Yuste, Mercedes; Campos, Joaquín; Gallo, Miguel A; Espinosa, Antonio

    2004-04-22

    A series of quinoline derivatives as aza analogues of the naphthalene chromophore and a series of "nonfused" tricyclic aromatic systems, in particular 5-arylquinolines and 5- or 6-aryl and heteroaryl naphthalene systems, were synthesized and evaluated for growth-inhibitory properties in several human cell lines. The analysis of quantitative structure-antitumor activity relationships for the growth-inhibitory properties is also reported. Findings suggest that these compounds may not express their cytotoxicity via interaction on DNA. PMID:15084122

  15. A TACSAT SAR concept

    NASA Astrophysics Data System (ADS)

    Hall, C. D.; Baker, C. J.; Keyte, G. E.; Murphy, L. M.

    1993-02-01

    The payload concept covered is that of a low cost, high performance radar sensor capable of detecting and recognizing static objects within an imaged scene of the Earth's surface using the Synthetic Aperture Radar (SAR) technique. The overall system is integrated with a TACSAT platform in Low Earth Orbit (LEO) and, although only passing reference is made to this feature, the radar could also have a capability for the detection of Ground Moving Targets (GMTI). A parametric review of such a sensor in the light of the target and background features to be observed is provided. A design concept is included showing the possible hardware realization of a candidate system, as well as budgets for the mass, size, power, and pointing requirements of the instrument. Additional design features considered are the influence that short duration missions may have on hardware redundancy and the effect of short, low duty-cycle observation periods on solar array and battery sizing. The way towards a low cost R and D demonstrator system allowing a practical investigation of the key techniques and technologies is addressed.

  16. Synthesis and SAR studies of novel 6,7,8-substituted 4-substituted benzyloxyquinolin-2(1H)-one derivatives for anticancer activity

    PubMed Central

    Chen, Yi-Fong; Lin, Yi-Chien; Morris-Natschke, Susan L; Wei, Chen-Fang; Shen, Ting-Chen; Lin, Hui-Yi; Hsu, Mei-Hua; Chou, Li-Chen; Zhao, Yu; Kuo, Sheng-Chu; Lee, Kuo-Hsiung; Huang, Li-Jiau

    2015-01-01

    Background and Purpose 4-Phenylquinolin-2(1H)-one (4-PQ) derivatives can induce cancer cell apoptosis. Additional new 4-PQ analogs were investigated as more effective, less toxic antitumour agents. Experimental Approach Forty-five 6,7,8-substituted 4-substituted benzyloxyquinolin-2(1H)-one derivatives were synthesized. Antiproliferative activities were evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliun bromide assay and structure–activity relationship correlations were established. Compounds 9b, 9c, 9e and 11e were also evaluated against the National Cancer Institute-60 human cancer cell line panel. Hoechst 33258 and Annexin V-FITC/PI staining assays were used to detect apoptosis, while inhibition of microtubule polymerization was assayed by fluorescence microscopy. Effects on the cell cycle were assessed by flow cytometry and on apoptosis-related proteins (active caspase-3, -8 and -9, procaspase-3, -8, -9, PARP, Bid, Bcl-xL and Bcl-2) by Western blotting. Key Results Nine 6,7,8-substituted 4-substituted benzyloxyquinolin-2(1H)-one derivatives (7e, 8e, 9b, 9c, 9e, 10c, 10e, 11c and 11e) displayed high potency against HL-60, Hep3B, H460, and COLO 205 cancer cells (IC50 < 1 μM) without affecting Detroit 551 normal human cells (IC50 > 50 μM). Particularly, compound 11e exhibited nanomolar potency against COLO 205 cancer cells. Mechanistic studies indicated that compound 11e disrupted microtubule assembly and induced G2/M arrest, polyploidy and apoptosis via the intrinsic and extrinsic signalling pathways. Activation of JNK could play a role in TRAIL-induced COLO 205 apoptosis. Conclusion and Implications New quinolone derivatives were identified as potential pro-apoptotic agents. Compound 11e could be a promising lead compound for future antitumour agent development. PMID:25363404

  17. Evaluation of DEM-assisted SAR coregistration

    NASA Astrophysics Data System (ADS)

    Nitti, D. O.; Hanssen, R. F.; Refice, A.; Bovenga, F.; Milillo, G.; Nutricato, R.

    2008-10-01

    Image alignment is without doubt the most crucial step in SAR Interferometry. Interferogram formation requires images to be coregistered with an accuracy of better than 1/8 pixel to avoid significant loss of phase coherence. Conventional interferometric precise coregistration methods for full-resolution SAR data (Single-Look Complex imagery, or SLC) are based on the cross-correlation of the SLC data, either in the original complex form or as squared amplitudes. Offset vectors in slant range and azimuth directions are computed on a large number of windows, according to the estimated correlation peaks. Then, a two-dimensional polynomial of a certain degree is usually chosen as warp function and the polynomial parameters are estimated through LMS fit from the shifts measured on the image windows. In case of rough topography and long baselines, the polynomial approximation for the warp function becomes inaccurate, leading to local misregistrations. Moreover, these effects increase with the spatial resolution and then with the sampling frequency of the sensor, as first results on TerraSAR-X interferometry confirm. An improved, DEM-assisted image coregistration procedure can be adopted for providing higher-order prediction of the offset vectors. Instead of estimating the shifts on a limited number of patches and using a polynomial approximation for the transformation, this approach computes pixel by pixel the correspondence between master and slave by using the orbital data and a reference DEM. This study assesses the performance of this approach with respect to the standard procedure. In particular, both analytical relationships and simulations will evaluate the impact of the finite vertical accuracy of the DEM on the final coregistration precision for different radar postings and relative positions of satellites. The two approaches are compared by processing real data at different carrier frequencies and using the interferometric coherence as quality figure.

  18. Surface deformation of Taipei basin detected by Differential SAR Interferometry

    NASA Astrophysics Data System (ADS)

    Chen, Y.; Chang, C.; Yen, J.; Lin, M.

    2006-12-01

    Taiwan island is located between the southeastern periphery of the Eurasian plate and the Philippine Sea plate. The two converging plates produced very active tectonics, and can be seen by the high seismicity and deformation rate. Taipei, the highest populated area, center of politics, and economics in Taiwan, is in Taipei basin at the northern part of the island. There are several faults in and surrounding the basin, and the city is threatened with a high geological hazard potential that we should keep monitoring the crustal deformation to prevent and mitigate the disaster effect. The aims of our study is to apply the DInSAR technique to determine the surface deformation of Taipei basin area, and discussing the relation between the manifestation of deformation and the tectonically active region, Shanjiao fault. In the past few years, Differential SAR Interferometry (DInSAR) has been proved to be a powerful technique for monitoring the neotectonic activities and natural hazards. High spatial sampling rate of DInSAR technique allows studies of surface deformations with centimeter accuracy. In this area, we used ERS-1/2 SAR images acquired from 1993 to 2005 to generate 10 differential interferograms and processed the data using DIAPASON developed by CNES and SRTM global DEM.From our results, the deformation rate in Taipei is generally high in the western end of the basin along the Shanjiao fault and decrease eastward, while the subsidence center often appeared in the center of the Taipei basin. The neotectonic activity of the Shanjiao fault appeared to be insignificant by itself but it seemed to separate the subsiding basin from the surrounding areas. Further comparison between our DInSAR results and isopach of the Taipei basin revealed that the subsidence centers appeared in the interferograms did not coincide with the location where the sediments are thickest. Our results from differential interferometry will be compared to other geodetic measurements such as the

  19. Relationship between balance and physical activity measured by an activity monitor in elderly COPD patients

    PubMed Central

    Iwakura, Masahiro; Okura, Kazuki; Shibata, Kazuyuki; Kawagoshi, Atsuyoshi; Sugawara, Keiyu; Takahashi, Hitomi; Shioya, Takanobu

    2016-01-01

    Background Little is known regarding the relationship between balance impairments and physical activity in COPD. There has been no study investigating the relationship between balance and objectively measured physical activity. Here we investigated the association between balance and physical activity measured by an activity monitor in elderly COPD patients. Materials and methods Twenty-two outpatients with COPD (mean age, 72±7 years; forced expiratory volume in 1 second, 53%±21% predicted) and 13 age-matched healthy control subjects (mean age, 72±6 years) participated in the study. We assessed all 35 subjects’ balance (one-leg standing test [OLST] times, Short Physical Performance Battery total scores, standing balance test scores, 4 m gait speed, and five-times sit-to-stand test [5STST]) and physical activity (daily steps and time spent in moderate-to-vigorous physical activity per day [MV-PA]). Possible confounders were assessed in the COPD group. The between-group differences in balance test scores and physical activity were analyzed. A correlation analysis and multivariate regression analysis were conducted in the COPD group. Results The COPD patients exhibited significant reductions in OLST times (P=0.033), Short Physical Performance Battery scores (P=0.013), 4 m gait speed (P<0.001), five-times sit-to-stand times (P=0.002), daily steps (P=0.003), and MV-PA (P=0.022) compared to the controls; the exception was the standing balance test scores. The correlation and multivariate regression analyses revealed significant independent associations between OLST times and daily steps (P<0.001) and between OLST times and MV-PA (P=0.014) in the COPD group after adjusting for possible confounding factors. Conclusion Impairments in balance and reductions in physical activity were observed in the COPD group. Deficits in balance are independently associated with physical inactivity. PMID:27445470

  20. Antileishmanial lead structures from nature: analysis of structure-activity relationships of a compound library derived from caffeic Acid bornyl ester.

    PubMed

    Glaser, Jan; Schultheis, Martina; Hazra, Sudipta; Hazra, Banasri; Moll, Heidrun; Schurigt, Uta; Holzgrabe, Ulrike

    2014-01-01

    Bioassay-guided fractionation of a chloroform extract of Valeriana wallichii (V. wallichii) rhizomes lead to the isolation and identification of caffeic acid bornyl ester (1) as the active component against Leishmania major (L. major) promastigotes (IC50 = 48.8 µM). To investigate the structure-activity relationship (SAR), a library of compounds based on 1 was synthesized and tested in vitro against L. major and L. donovani promastigotes, and L. major amastigotes. Cytotoxicity was determined using a murine J774.1 cell line and bone marrow derived macrophages (BMDM). Some compounds showed antileishmanial activity in the concentration range of pentamidine and miltefosine which are the standard drugs in use. In the L. major amastigote assay compounds 15, 19 and 20 showed good activity with relatively low cytotoxicity against BMDM, resulting in acceptable selectivity indices. Molecules with adjacent phenolic hydroxyl groups exhibited elevated cytotoxicity against murine cell lines J774.1 and BMDM. The Michael system seems not to be essential for antileishmanial activity. Based on the results compound 27 can be regarded as new lead structure for further structure optimization. PMID:24473204

  1. Design, Synthesis and Structure-Activity Relationship (SAR) Studies of 2,4-Disubstituted Pyrimidine Derivatives: Dual Activity as Cholinesterase and Aβ-Aggregation Inhibitors

    PubMed Central

    Mohamed, Tarek; Zhao, Xiaobei; Habib, Lila K.; Yang, Jerry; Rao, Praveen P. N.

    2011-01-01

    A novel class of 2,4-disubstituted pyrimidines (7a–u, 8a–f, 9a–e) that possess substituents with varying steric and electronic properties at the C-2 and C-4 positions, were designed, synthesized and evaluated as dual cholinesterase and amyloid-β (Aβ)-aggregation inhibitors. In vitro screening identified N-(naphth-1-ylmethyl)-2-(pyrrolidin-1-yl)pyrimidin-4-amine (9a) as the most potent AChE inhibitor (IC50 = 5.5 μM). Among this class of compounds, 2-(4-methylpiperidin-1-yl)-N-(naphth-1-ylmethyl)pyrimidin-4-amine (9e) was identified as the most potent and selective BuChE inhibitor (IC50 = 2.2 μM, Selectivity Index = 11.7) and was about 5.7-fold more potent compared to the commercial, approved reference drug galanthamine (BuChE IC50 = 12.6 μM). In addition, the selective AChE inhibitor N-benzyl-2-(4-methylpiperazin-1-yl)pyrimidin-4-amine (7d), exhibited good inhibition of hAChE-induced aggregation of Aβ1–40 fibrils (59% inhibition). Furthermore, molecular modeling studies indicate that a central pyrimidine ring serves as a suitable template to develop dual inhibitors of cholinesterase and AChE-induced Aβ aggregation thereby targeting multiple pathological routes in AD. PMID:21429752

  2. SARS Patients and Their Close Contacts

    MedlinePlus

    ... Fact Sheet for SARS Patients and Their Close Contacts Format: Select one PDF [256 KB] Recommend on ... that are not now known. What does "close contact" mean? In the context of SARS, close contact ...

  3. The Structure-Activity Relationship between Marine Algae Polysaccharides and Anti-Complement Activity

    PubMed Central

    Jin, Weihua; Zhang, Wenjing; Liang, Hongze; Zhang, Quanbin

    2015-01-01

    In this study, 33 different polysaccharides were prepared to investigate the structure-activity relationships between the polysaccharides, mainly from marine algae, and anti-complement activity in the classical pathway. Factors considered included extraction methods, fractionations, molecular weight, molar ratio of galactose to fucose, sulfate, uronic acid (UA) content, linkage, branching, and the type of monosaccharide. It was shown that the larger the molecular weights, the better the activities. The molar ratio of galactose (Gal) to fucose (Fuc) was a positive factor at a concentration lower than 10 µg/mL, while it had no effect at a concentration more than 10 µg/mL. In addition, sulfate was necessary; however, the sulfate content, the sulfate pattern, linkage and branching had no effect at a concentration of more than 10 µg/mL. Moreover, the type of monosaccharide had no effect. Laminaran and UA fractions had no activity; however, they could reduce the activity by decreasing the effective concentration of the active composition when they were mixed with the active compositions. The effect of the extraction methods could not be determined. Finally, it was observed that sulfated galactofucan showed good anti-complement activity after separation. PMID:26712768

  4. Identification of Lilial as a fragrance sensitizer in a perfume by bioassay-guided chemical fractionation and structure-activity relationships.

    PubMed

    Arnau, E G; Andersen, K E; Bruze, M; Frosch, P J; Johansen, J D; Menné, T; Rastogi, S C; White, I R; Lepoittevin, J P

    2000-12-01

    Fragrance materials are among the most common causes of allergic contact dermatitis. The aim of this study was to identify in a perfume fragrance allergens not included in the fragrance mix, by use of bioassay-guided chemical fractionation and chemical analysis/structure-activity relationships (SARs). The basis for the investigation was a 45-year-old woman allergic to her own perfume. She had a negative patch test to the fragrance mix and agreed to participate in the study. Chemical fractionation of the perfume concentrate was used for repeated patch testing and/or repeated open application test on the pre-sensitized patient. The chemical composition of the fractions giving a positive patch-test response and repeated open application test reactions was obtained by gas chromatography-mass spectrometry. From the compounds identified, those that contained a "structural alert" in their chemical structure, indicating an ability to modify skin proteins and thus behave as a skin sensitizer, were tested on the patient. The patient reacted positively to the synthetic fragrance p-t-butyl-alpha-methylhydrocinnamic aldehyde (Lilial), a widely used fragrance compound not present in the fragrance mix. The combination of bioassay-guided chemical fractionation and chemical analysis/structure-activity relationships seems to be a valuable tool for the investigation of contact allergy to fragrance materials.

  5. Targeted Radiosensitization by the Chk1 Inhibitor SAR-020106

    SciTech Connect

    Borst, Gerben R.; McLaughlin, Martin; Kyula, Joan N.; Neijenhuis, Sari; Khan, Aadil; Good, James; Zaidi, Shane; Powell, Ned G.; Meier, Pascal; Collins, Ian; Garrett, Michelle D.; Verheij, Marcel; Harrington, Kevin J.

    2013-03-15

    Purpose: To explore the activity of a potent Chk1 inhibitor (SAR-020106) in combination with radiation. Methods and Materials: Colony and mechanistic in vitro assays and a xenograft in vivo model. Results: SAR-020106 suppressed-radiation-induced G{sub 2}/M arrest and reduced clonogenic survival only in p53-deficient tumor cells. SAR-020106 promoted mitotic entry following irradiation in all cell lines, but p53-deficient cells were likely to undergo apoptosis or become aneuploid, while p53 wild-type cells underwent a postmitotic G{sub 1} arrest followed by subsequent normal cell cycle re-entry. Following combined treatment with SAR-020106 and radiation, homologous-recombination-mediated DNA damage repair was inhibited in all cell lines. A significant increase in the number of pan-γH2AX-staining apoptotic cells was observed only in p53-deficient cell lines. Efficacy was confirmed in vivo in a clinically relevant human head-and-neck cell carcinoma xenograft model. Conclusion: The Chk1 inhibitor SAR-020106 is a potent radiosensitizer in tumor cell lines defective in p53 signaling.

  6. Detecting and monitoring UCG subsidence with InSAR

    SciTech Connect

    Mellors, R J; Foxall, W; Yang, X

    2012-03-23

    The use of interferometric synthetic aperture radar (InSAR) to measure surface subsidence caused by Underground Coal Gasification (UCG) is tested. InSAR is a remote sensing technique that uses Synthetic Aperture Radar images to make spatial images of surface deformation and may be deployed from satellite or an airplane. With current commercial satellite data, the technique works best in areas with little vegetation or farming activity. UCG subsidence is generally caused by roof collapse, which adversely affects UCG operations due to gas loss and is therefore important to monitor. Previous studies have demonstrated the usefulness of InSAR in measuring surface subsidence related to coal mining and surface deformation caused by a coal mining roof collapse in Crandall Canyon, Utah is imaged as a proof-of-concept. InSAR data is collected and processed over three known UCG operations including two pilot plants (Majuba, South Africa and Wulanchabu, China) and an operational plant (Angren, Uzbekistan). A clear f eature showing approximately 7 cm of subsidence is observed in the UCG field in Angren. Subsidence is not observed in the other two areas, which produce from deeper coal seams and processed a smaller volume. The results show that in some cases, InSAR is a useful tool to image UCG related subsidence. Data from newer satellites and improved algorithms will improve effectiveness.

  7. P-3 SAR motion compensation techniques

    NASA Astrophysics Data System (ADS)

    Schwartz, Debra S.; Mansfield, Arthur W.; Roth, Duane; Rais, Houra

    2000-08-01

    The potential of airborne SAR to support the search and rescue mission needs to be investigated. Interferometric SAR (IFSAR) is to process P-3 airborne SAR data to evaluate products such as Coherent Change Detection (CCD) and Digital Elevation Models (DEM). The most crucial step in this process is the precise registration of the two SAR images obtained from separate passes. This paper presents a new technique for this registration step.

  8. Method for removing RFI from SAR images

    DOEpatents

    Doerry, Armin W.

    2003-08-19

    A method of removing RFI from a SAR by comparing two SAR images on a pixel by pixel basis and selecting the pixel with the lower magnitude to form a composite image. One SAR image is the conventional image produced by the SAR. The other image is created from phase-history data which has been filtered to have the frequency bands containing the RFI removed.

  9. Kronecker STAP and SAR GMTI

    NASA Astrophysics Data System (ADS)

    Greenewald, Kristjan H.; Zelnio, Edmund G.; Hero, Alfred O.

    2016-05-01

    As a high resolution radar imaging modality, SAR detects and localizes non-moving targets accurately, giving it an advantage over lower resolution GMTI radars. Moving target detection is more challenging due to target smearing and masking by clutter. Space-time adaptive processing (STAP) is often used on multiantenna SAR to remove the stationary clutter and enhance the moving targets. In (Greenewald et al., 2016),1 it was shown that the performance of STAP can be improved by modeling the clutter covariance as a space vs. time Kronecker product with low rank factors, providing robustness and reducing the number of training samples required. In this work, we present a massively parallel algorithm for implementing Kronecker product STAP, enabling application to very large SAR datasets (such as the 2006 Gotcha data collection) using GPUs. Finally, we develop an extension of Kronecker STAP that uses information from multiple passes to improve moving target detection.

  10. Monsoon '90 - Preliminary SAR results

    NASA Technical Reports Server (NTRS)

    Dubois, Pascale C.; Van Zyl, Jakob J.; Guerra, Abel G.

    1992-01-01

    Multifrequency polarimetric synthetic aperture radar (SAR) images of the Walnut Gulch watershed near Tombstone, Arizona were acquired on 28 Mar. 1990 and on 1 Aug. 1990. Trihedral corner reflectors were deployed prior to both overflights to allow calibration of the two SAR data sets. During both overflights, gravimetric soil moisture and dielectric constant measurements were made. Detailed vegetation height, density, and water content measurements were made as part of the Monsoon 1990 Experiment. Preliminary results based on analysis of the multitemporal polarimetric SAR data are presented. Only the C-band data (5.7-cm wavelength) radar images show significant difference between Mar. and Aug., with the strongest difference observed in the HV images. Based on the radar data analysis and the in situ measurements, we conclude that these differences are mainly due to changes in the vegetation and not due to the soil moisture changes.

  11. Monsoon 1990: Preliminary SAR results

    NASA Technical Reports Server (NTRS)

    Vanzyl, Jakob J.; Dubois, Pascale; Guerra, Abel

    1991-01-01

    Multifrequency polarimetric synthetic aperture radar (SAR) images of the Walnut Gulch watershed near Tombstone, Arizona were acquired on 28 Mar. 1990 and on 1 Aug. 1990. Trihedral corner reflectors were deployed prior to both overflights to allow calibration of the two SAR data sets. During both overflights, gravimetric soil moisture and dielectric constant measurements were made. Detailed vegetation height, density, and water content measurements were made as part of the Monsoon 1990 Experiment. Preliminary results based on analysis of the multitemporal polarimetric SAR data are presented. Only the C-band data (5.7-cm wavelength) radar images show significant difference between Mar. and Aug., with the strongest difference observed in the HV images. Based on the radar data analysis and the in situ measurements, we conclude that these differences are mainly due to changes in the vegetation and not due to the soil moisture changes.

  12. Registration of interferometric SAR images

    NASA Technical Reports Server (NTRS)

    Lin, Qian; Vesecky, John F.; Zebker, Howard A.

    1992-01-01

    Interferometric synthetic aperture radar (INSAR) is a new way of performing topography mapping. Among the factors critical to mapping accuracy is the registration of the complex SAR images from repeated orbits. A new algorithm for registering interferometric SAR images is presented. A new figure of merit, the average fluctuation function of the phase difference image, is proposed to evaluate the fringe pattern quality. The process of adjusting the registration parameters according to the fringe pattern quality is optimized through a downhill simplex minimization algorithm. The results of applying the proposed algorithm to register two pairs of Seasat SAR images with a short baseline (75 m) and a long baseline (500 m) are shown. It is found that the average fluctuation function is a very stable measure of fringe pattern quality allowing very accurate registration.

  13. SAR650984 directly induces multiple myeloma cell death via lysosomal-associated and apoptotic pathways, which is further enhanced by pomalidomide.

    PubMed

    Jiang, H; Acharya, C; An, G; Zhong, M; Feng, X; Wang, L; Dasilva, N; Song, Z; Yang, G; Adrian, F; Qiu, L; Richardson, P; Munshi, N C; Tai, Y-T; Anderson, K C

    2016-02-01

    The anti-CD38 monoclonal antibody SAR650984 (SAR) is showing promising clinical activity in treatment of relapsed and refractory multiple myeloma (MM). Besides effector-mediated antibody-dependent cellular cytotoxicity and complement-mediated cytotoxicity, we here define molecular mechanisms of SAR-directed MM cell death and enhanced anti-MM activity triggered by SAR with Pomalidomide (Pom). Without Fc-cross-linking agents or effector cells, SAR specifically induces homotypic aggregation (HA)-associated cell death in MM cells dependent on the level of cell surface CD38 expression, actin cytoskeleton and membrane lipid raft. SAR and its F(ab)'2 fragments trigger caspase 3/7-dependent apoptosis in MM cells highly expressing CD38, even with p53 mutation. Importantly, SAR specifically induces lysosome-dependent cell death (LCD) by enlarging lysosomes and increasing lysosomal membrane permeabilization associated with leakage of cathepsin B and LAMP-1, regardless of the presence of interleukin-6 or bone marrow stromal cells. Conversely, the lysosomal vacuolar H+-ATPase inhibitor blocks SAR-induced LCD. SAR further upregulates reactive oxygen species. Pom enhances SAR-induced direct and indirect killing even in MM cells resistant to Pom/Len. Taken together, SAR is the first therapeutic monoclonal antibody mediating direct cytotoxicity against MM cells via multiple mechanisms of action. Our data show that Pom augments both direct and effector cell-mediated MM cytotoxicity of SAR, providing the framework for combination clinical trials. PMID:26338273

  14. Structure-activity relationships for biodistribution, pharmacokinetics, and excretion of atomically precise nanoclusters in a murine model

    NASA Astrophysics Data System (ADS)

    Wong, O. Andrea; Hansen, Ryan J.; Ni, Thomas W.; Heinecke, Christine L.; Compel, W. Scott; Gustafson, Daniel L.; Ackerson, Christopher J.

    2013-10-01

    The absorption, distribution, metabolism and excretion (ADME) and pharmacokinetic (PK) properties of inorganic nanoparticles with hydrodynamic diameters between 2 and 20 nm are presently unpredictable. It is unclear whether unpredictable in vivo properties and effects arise from a subset of molecules in a nanomaterials preparation, or if the ADME/PK properties are ensemble properties of an entire preparation. Here we characterize the ADME/PK properties of atomically precise preparations of ligand protected gold nanoclusters in a murine model system. We constructed atomistic models and tested in vivo properties for five well defined compounds, based on crystallographically resolved Au25(SR)18 and Au102(SR)44 nanoclusters with different (SR) ligand shells. To rationalize unexpected distribution and excretion properties observed for several clusters in this study and others, we defined a set of atomistic structure-activity relationships (SAR) for nanoparticles, which includes previously investigated parameters such as particle hydrodynamic diameter and net charge, and new parameters such as hydrophobic surface area and surface charge density. Overall we find that small changes in particle formulation can provoke dramatic yet potentially predictable changes in ADME/PK.The absorption, distribution, metabolism and excretion (ADME) and pharmacokinetic (PK) properties of inorganic nanoparticles with hydrodynamic diameters between 2 and 20 nm are presently unpredictable. It is unclear whether unpredictable in vivo properties and effects arise from a subset of molecules in a nanomaterials preparation, or if the ADME/PK properties are ensemble properties of an entire preparation. Here we characterize the ADME/PK properties of atomically precise preparations of ligand protected gold nanoclusters in a murine model system. We constructed atomistic models and tested in vivo properties for five well defined compounds, based on crystallographically resolved Au25(SR)18 and Au102(SR

  15. SARS: hospital infection control and admission strategies.

    PubMed

    Ho, Pak-Leung; Tang, Xiao-Ping; Seto, Wing-Hong

    2003-11-01

    Nosocomial clustering with transmission to health care workers, patients and visitors is a prominent feature of severe acute respiratory syndrome (SARS). Hospital outbreaks of SARS typically occurred within the first week after admission of the very first SARS cases when the disease was not recognized and before isolation measures were implemented. In the majority of nosocomial infections, there was a history of close contact with a SARS patient, and transmission occurred via large droplets, direct contact with infectious material or by contact with fomites contaminated by infectious material. In a few instances, potential airborne transmission was reported in association with endotracheal intubation, nebulised medications and non-invasive positive pressure ventilation of SARS patients. In all SARS-affected countries, nosocomial transmission of the disease was effectively halted by enforcement of routine standard, contact and droplet precautions in all clinical areas and additional airborne precautions in the high-risk areas. In Hong Kong, where there are few private rooms for patient isolation, some hospitals have obtained good outcome by having designated SARS teams and separate wards for patient triage, confirmed SARS cases and step-down of patients in whom SARS had been ruled out. In conclusion, SARS represents one of the new challenges for those who are involved in hospital infection control. As SARS might re-emerge, all hospitals should take advantage of the current SARS-free interval to review their infection control programmes, alert mechanisms, response capability and to repair any identified inadequacies.

  16. Categorization of fragrance contact allergens for prioritization of preventive measures: clinical and experimental data and consideration of structure-activity relationships.

    PubMed

    Uter, Wolfgang; Johansen, Jeanne D; Börje, Anna; Karlberg, Ann-Therese; Lidén, Carola; Rastogi, Suresh; Roberts, David; White, Ian R

    2013-10-01

    Contact allergy to fragrances is still relatively common, affecting ∼ 16% of patients patch tested for suspected allergic contact dermatitis, considering all current screening allergens. The objective of the review is to systematically retrieve, evaluate and classify evidence on contact allergy to fragrances, in order to arrive at recommendations for targeting of primary and secondary prevention. Besides published evidence on contact allergy in humans, animal data (local lymph node assay), annual use volumes and structure-activity relationships (SARs) were considered for an algorithmic categorization of substances as contact allergens. A total of 54 individual chemicals and 28 natural extracts (essential oils) can be categorized as established contact allergens in humans, including all 26 substances previously identified as contact allergens (SCCNFP/0017/98). Twelve of the 54 individual chemicals are considered to be of special concern, owing to the high absolute number of reported cases of contact allergy (>100). Additionally, 18 single substances and one natural mixture are categorized as established contact allergens in animals. SARs, combined with limited human evidence, contributed to the categorization of a further 26 substances as likely contact allergens. In conclusion, the presence of 127 single fragrance substances and natural mixtures should, owing to their skin sensitizing properties, be disclosed, for example on the label. As an additional preventive measure, the maximum use concentration of 11 substances of special concern should be limited to 100 ppm. The substance hydroxyisohexyl 3-cyclohexene carboxaldehyde and the two ingredients chloroatranol and atranol in the natural extracts Evernia prunastri and Evernia furfuracea should not be present in cosmetic products.

  17. Synthesis and Structure–Activity Relationships of N-(2-Oxo-3-oxetanyl)amides as N-Acylethanolamine-hydrolyzing Acid Amidase Inhibitors

    PubMed Central

    Solorzano, Carlos; Antonietti, Francesca; Duranti, Andrea; Tontini, Andrea; Rivara, Silvia; Lodola, Alessio; Vacondio, Federica; Tarzia, Giorgio; Piomelli, Daniele; Mor, Marco

    2010-01-01

    The fatty acid ethanolamides (FAEs) are a family of bioactive lipid mediators that include the endogenous agonist of peroxisome proliferator-activated receptor-α, palmitoylethanolamide (PEA). FAEs are hydrolyzed intracellularly by either fatty acid amide hydrolase or N-acylethanolamine-hydrolyzing acid amidase (NAAA). Selective inhibition of NAAA by (S)-N-(2-oxo-3-oxetanyl)-3-phenylpropionamide [(S)-OOPP, 7a] prevents PEA degradation in mouse leukocytes and attenuates responses to proinflammatory stimuli. Starting from the structure of 7a a series of β-lactones was prepared and tested on recombinant rat NAAA to explore structure-activity relationships (SARs) for this class of inhibitors and improve their in vitro potency. Following the hypothesis that these compounds inhibit NAAA by acylation of the catalytic cysteine, we identified several requirements for recognition at the active site and obtained new potent inhibitors. In particular, (S)-N-(2-oxo-3-oxetanyl)biphenyl-4-carboxamide (7h) was more potent than 7a at inhibiting recombinant rat NAAA activity (7a, IC50 = 420 nM; 7h, IC50 = 115 nM) in vitro and at reducing carrageenan-induced leukocyte infiltration in vivo. PMID:20604568

  18. Hybrid-Polarity SAR Architecture

    NASA Astrophysics Data System (ADS)

    Raney, R. K.; Freeman, A.

    2009-04-01

    A space-based synthetic aperture radar (SAR) designed to provide quantitative information on a global scale implies severe requirements to maximize coverage and to sustain reliable operational calibration. These requirements are best served by the hybrid-polarity architecture, in which the radar transmits in circular polarization, and receives on two orthogonal linear polarizations, coherently, retaining their relative phase. This paper reviews those advantages,summarizes key attributes of hybrid-polarity dual- and quadrature-polarized SARs including conditions under which the signal-to-noise ratio is conserved, and describes the evolution of this architecture from first principles.

  19. Foliage problem in interferometric SAR

    NASA Astrophysics Data System (ADS)

    Rogers, George W.; Mansfield, Arthur W.; Roth, Duane; Poehler, Paul L.; Rais, Houra

    1999-08-01

    Interferometric SAR exploits the coherent nature of multiple synthetic aperture radar images to recover phase (range difference) information and thence terrain evaluation data as well as other phase derivative products such as Coherent Change Detection (CCD). Of the numerous factors that can degrade the coherency of multiple SAR collections, foliage constitutes one of the most challenging. The foliage problem in IFSAR is discussed and an airborne multiple pass collection is used to illustrate some facets of the problem. Resolution as a variable in the tradeoff between the bias and variance of the interferogram is discussed in the context of the example.

  20. Quantitative Structure Activity Relationship Models for the Antioxidant Activity of Polysaccharides

    PubMed Central

    Nie, Kaiying; Wang, Zhaojing

    2016-01-01

    In this study, quantitative structure activity relationship (QSAR) models for the antioxidant activity of polysaccharides were developed with 50% effective concentration (EC50) as the dependent variable. To establish optimum QSAR models, multiple linear regressions (MLR), support vector machines (SVM) and artificial neural networks (ANN) were used, and 11 molecular descriptors were selected. The optimum QSAR model for predicting EC50 of DPPH-scavenging activity consisted of four major descriptors. MLR model gave EC50 = 0.033Ara-0.041GalA-0.03GlcA-0.025PC+0.484, and MLR fitted the training set with R = 0.807. ANN model gave the improvement of training set (R = 0.96, RMSE = 0.018) and test set (R = 0.933, RMSE = 0.055) which indicated that it was more accurately than SVM and MLR models for predicting the DPPH-scavenging activity of polysaccharides. 67 compounds were used for predicting EC50 of the hydroxyl radicals scavenging activity of polysaccharides. MLR model gave EC50 = 0.12PC+0.083Fuc+0.013Rha-0.02UA+0.372. A comparison of results from models indicated that ANN model (R = 0.944, RMSE = 0.119) was also the best one for predicting the hydroxyl radicals scavenging activity of polysaccharides. MLR and ANN models showed that Ara and GalA appeared critical in determining EC50 of DPPH-scavenging activity, and Fuc, Rha, uronic acid and protein content had a great effect on the hydroxyl radicals scavenging activity of polysaccharides. The antioxidant activity of polysaccharide usually was high in MW range of 4000–100000, and the antioxidant activity could be affected simultaneously by other polysaccharide properties, such as uronic acid and Ara. PMID:27685320

  1. KNApSAcK Metabolite Activity Database for retrieving the relationships between metabolites and biological activities.

    PubMed

    Nakamura, Yukiko; Afendi, Farit Mochamad; Parvin, Aziza Kawsar; Ono, Naoaki; Tanaka, Ken; Hirai Morita, Aki; Sato, Tetsuo; Sugiura, Tadao; Altaf-Ul-Amin, Md; Kanaya, Shigehiko

    2014-01-01

    Databases (DBs) are required by various omics fields because the volume of molecular biology data is increasing rapidly. In this study, we provide instructions for users and describe the current status of our metabolite activity DB. To facilitate a comprehensive understanding of the interactions between the metabolites of organisms and the chemical-level contribution of metabolites to human health, we constructed a metabolite activity DB known as the KNApSAcK Metabolite Activity DB. It comprises 9,584 triplet relationships (metabolite-biological activity-target species), including 2,356 metabolites, 140 activity categories, 2,963 specific descriptions of biological activities and 778 target species. Approximately 46% of the activities described in the DB are related to chemical ecology, most of which are attributed to antimicrobial agents and plant growth regulators. The majority of the metabolites with antimicrobial activities are flavonoids and phenylpropanoids. The metabolites with plant growth regulatory effects include plant hormones. Over half of the DB contents are related to human health care and medicine. The five largest groups are toxins, anticancer agents, nervous system agents, cardiovascular agents and non-therapeutic agents, such as flavors and fragrances. The KNApSAcK Metabolite Activity DB is integrated within the KNApSAcK Family DBs to facilitate further systematized research in various omics fields, especially metabolomics, nutrigenomics and foodomics. The KNApSAcK Metabolite Activity DB could also be utilized for developing novel drugs and materials, as well as for identifying viable drug resources and other useful compounds.

  2. Molecular modeling and snake venom phospholipase A2 inhibition by phenolic compounds: Structure-activity relationship.

    PubMed

    Alam, Md Iqbal; Alam, Mohammed A; Alam, Ozair; Nargotra, Amit; Taneja, Subhash Chandra; Koul, Surrinder

    2016-05-23

    In our earlier study, we have reported that a phenolic compound 2-hydroxy-4-methoxybenzaldehyde from Janakia arayalpatra root extract was active against Viper and Cobra envenomations. Based on the structure of this natural product, libraries of synthetic structurally variant phenolic compounds were studied through molecular docking on the venom protein. To validate the activity of eight selected compounds, we have tested them in in vivo and in vitro models. The compound 21 (2-hydroxy-3-methoxy benzaldehyde), 22 (2-hydroxy-4-methoxybenzaldehyde) and 35 (2-hydroxy-3-methoxybenzylalcohol) were found to be active against venom-induced pathophysiological changes. The compounds 20, 15 and 35 displayed maximum anti-hemorrhagic, anti-lethal and PLA2 inhibitory activity respectively. In terms of SAR, the presence of a formyl group in conjunction with a phenolic group was seen as a significant contributor towards increasing the antivenom activity. The above observations confirmed the anti-venom activity of the phenolic compounds which needs to be further investigated for the development of new anti-snake venom leads. PMID:26986086

  3. A quantitative structure-activity relationship model for radical scavenging activity of flavonoids.

    PubMed

    Om, A; Kim, J H

    2008-03-01

    A quantitative structure-activity relationship (QSAR) study has been carried out for a training set of 29 flavonoids to correlate and predict the 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity (RSA) values obtained from published data. Genetic algorithm and multiple linear regression were employed to select the descriptors and to generate the best prediction model that relates the structural features to the RSA activities using (1) three-dimensional (3D) Dragon (TALETE srl, Milan, Italy) descriptors and (2) semi-empirical descriptor calculations. The predictivity of the models was estimated by cross-validation with the leave-one-out method. The result showed that a significant improvement of the statistical indices was obtained by deleting outliers. Based on the data for the compounds used in this study, our results suggest a QSAR model of RSA that is based on the following descriptors: 3D-Morse, WHIM, and GETAWAY. Therefore, satisfactory relationships between RSA and the semi-empirical descriptors were found, demonstrating that the energy of the highest occupied molecular orbital, total energy, and energy of heat of formation contributed more significantly than all other descriptors.

  4. Structure-activity relationships for antioxidant activities of a series of flavonoids in a liposomal system.

    PubMed

    Arora, A; Nair, M G; Strasburg, G M

    1998-06-01

    Structurally diverse plant phenolics were examined for their abilities to inhibit lipid peroxidation induced either by Fe(II) and Fe(III) metal ions or by azo-derived peroxyl radicals in a liposomal membrane system. The antioxidant abilities of flavonoids were compared with those of coumarin and tert-butylhydroquinone (TBHQ). The antioxidant efficacies of these compounds were evaluated on the basis of their abilities to inhibit the fluorescence intensity decay of an extrinsic probe, 3-(p-(6-phenyl)-I,3,5-hexatrienyl)phenylpropionic acid (DPH-PA), caused by the free radicals generated during lipid peroxidation. All the flavonoids tested exhibited higher antioxidant efficacies against metal-ion-induced peroxidations than peroxyl-radical-induced peroxidation, suggesting that metal chelation may play a larger role in determining the antioxidant activities of these compounds than has previously been believed. Distinct structure-activity relationships were also revealed for the antioxidant abilities of the flavonoids. Presence of hydroxyl substituents on the flavonoid nucleus enhanced activity, whereas substitution by methoxy groups diminished antioxidant activity. Substitution patterns on the B-ring especially affected antioxidant potencies of the flavonoids. In cases where the B-ring could not contribute to the antioxidant activities of flavonoids, hydroxyl substituents in an catechol structure on the A-ring were able to compensate and become a larger determinant of flavonoid antioxidant activity. PMID:9641252

  5. How change of public transportation usage reveals fear of the SARS virus in a city.

    PubMed

    Wang, Kuo-Ying

    2014-01-01

    The outbreaks of the severe acute respiratory syndrome (SARS) epidemic in 2003 resulted in unprecedented impacts on people's daily life. One of the most significant impacts to people is the fear of contacting the SARS virus while engaging daily routine activity. Here we use data from daily underground ridership in Taipei City and daily reported new SARS cases in Taiwan to model the dynamics of the public fear of the SARS virus during the wax and wane of the SARS period. We found that for each reported new SARS case there is an immediate loss of about 1200 underground ridership (the fresh fear). These daily loss rates dissipate to the following days with an e-folding time of about 28 days, reflecting the public perception on the risk of contacting SARS virus when traveling with the underground system (the residual fear). About 50% of daily ridership was lost during the peak of the 2003 SARS period, compared with the loss of 80% daily ridership during the closure of the underground system after Typhoon Nari, the loss of 50-70% ridership due to the closure of the governmental offices and schools during typhoon periods, and the loss of 60% daily ridership during Chinese New Year holidays.

  6. SarA based novel therapeutic candidate against Staphylococcus aureus associated with vascular graft infections.

    PubMed

    Arya, Rekha; Ravikumar, R; Santhosh, R S; Princy, S Adline

    2015-01-01

    Staphylococcus aureus is a common pathogen seen in prosthetic vascular graft, leading to high morbidity and mortality. The virulence genes for severity of infections are under the control of global regulators. Staphylococcal accessory regulator A (SarA) a known master controller of biofilm formation is an attractive target for the drug development. A structure based screening of lead compounds was employed for the identification of novel small molecule inhibitors targeted to interact to the DNA binding domain of the transcriptional activator, SarA and hinder its response over the control of genes that up-regulate the phenotype, biofilm. The top-hit SarA selective inhibitor, 4-[(2,4-diflurobenzyl)amino] cyclohexanol (SarABI) was further validated in-vitro for its efficacy. The SarABI was found to have MBIC50value of 200 μg/ml and also down-regulated the expression of the RNA effector, (RNAIII), Hemolysin (hld), and fibronectin-binding protein (fnbA). The anti-adherence property of SarABI on S. aureus invasion to the host epithelial cell lines (Hep-2) was examined where no significant attachment of S. aureus was observed. The SarABI inhibits the colonization of MDR S. aureus in animal model experiment significantly cohere to the molecular docking studies and in vitro experiments. So, we propose that the SarABI could be a novel substitute to overcome a higher degree of MDR S. aureus colonization on vascular graft. PMID:26074884

  7. SarA based novel therapeutic candidate against Staphylococcus aureus associated with vascular graft infections

    PubMed Central

    Arya, Rekha; Ravikumar, R.; Santhosh, R. S.; Princy, S. Adline

    2015-01-01

    Staphylococcus aureus is a common pathogen seen in prosthetic vascular graft, leading to high morbidity and mortality. The virulence genes for severity of infections are under the control of global regulators. Staphylococcal accessory regulator A (SarA) a known master controller of biofilm formation is an attractive target for the drug development. A structure based screening of lead compounds was employed for the identification of novel small molecule inhibitors targeted to interact to the DNA binding domain of the transcriptional activator, SarA and hinder its response over the control of genes that up-regulate the phenotype, biofilm. The top-hit SarA selective inhibitor, 4-[(2,4-diflurobenzyl)amino] cyclohexanol (SarABI) was further validated in-vitro for its efficacy. The SarABI was found to have MBIC50value of 200 μg/ml and also down-regulated the expression of the RNA effector, (RNAIII), Hemolysin (hld), and fibronectin-binding protein (fnbA). The anti-adherence property of SarABI on S. aureus invasion to the host epithelial cell lines (Hep-2) was examined where no significant attachment of S. aureus was observed. The SarABI inhibits the colonization of MDR S. aureus in animal model experiment significantly cohere to the molecular docking studies and in vitro experiments. So, we propose that the SarABI could be a novel substitute to overcome a higher degree of MDR S. aureus colonization on vascular graft. PMID:26074884

  8. How change of public transportation usage reveals fear of the SARS virus in a city.

    PubMed

    Wang, Kuo-Ying

    2014-01-01

    The outbreaks of the severe acute respiratory syndrome (SARS) epidemic in 2003 resulted in unprecedented impacts on people's daily life. One of the most significant impacts to people is the fear of contacting the SARS virus while engaging daily routine activity. Here we use data from daily underground ridership in Taipei City and daily reported new SARS cases in Taiwan to model the dynamics of the public fear of the SARS virus during the wax and wane of the SARS period. We found that for each reported new SARS case there is an immediate loss of about 1200 underground ridership (the fresh fear). These daily loss rates dissipate to the following days with an e-folding time of about 28 days, reflecting the public perception on the risk of contacting SARS virus when traveling with the underground system (the residual fear). About 50% of daily ridership was lost during the peak of the 2003 SARS period, compared with the loss of 80% daily ridership during the closure of the underground system after Typhoon Nari, the loss of 50-70% ridership due to the closure of the governmental offices and schools during typhoon periods, and the loss of 60% daily ridership during Chinese New Year holidays. PMID:24647278

  9. How Change of Public Transportation Usage Reveals Fear of the SARS Virus in a City

    PubMed Central

    Wang, Kuo-Ying

    2014-01-01

    The outbreaks of the severe acute respiratory syndrome (SARS) epidemic in 2003 resulted in unprecedented impacts on people's daily life. One of the most significant impacts to people is the fear of contacting the SARS virus while engaging daily routine activity. Here we use data from daily underground ridership in Taipei City and daily reported new SARS cases in Taiwan to model the dynamics of the public fear of the SARS virus during the wax and wane of the SARS period. We found that for each reported new SARS case there is an immediate loss of about 1200 underground ridership (the fresh fear). These daily loss rates dissipate to the following days with an e-folding time of about 28 days, reflecting the public perception on the risk of contacting SARS virus when traveling with the underground system (the residual fear). About 50% of daily ridership was lost during the peak of the 2003 SARS period, compared with the loss of 80% daily ridership during the closure of the underground system after Typhoon Nari, the loss of 50–70% ridership due to the closure of the governmental offices and schools during typhoon periods, and the loss of 60% daily ridership during Chinese New Year holidays. PMID:24647278

  10. Salt Kinematics and InSAR

    NASA Technical Reports Server (NTRS)

    Aftabi, Pedarm; Talbot, hristopher; Fielding, Eric

    2005-01-01

    As part of a long-term attempt to learn how the climatic and tectonic signal interact to shape a steady state mountain monitored displacement of a markers in SE termination and also near the summit of a small viscous salt fountain extruding onto the Central plateau of Iran. The marker displacements relate to the first InSAR interferograms of salt extrusion (980913 to 990620) calculated Earth tides, winds, air pressures and temperatures. In the first documented staking exercise, hammered wooden stakes vertically through the surgical marl (c. 1 Ocm deep) onto the top of crystalline salt. These stakes installed in an irregular array elongate E-W along the c.50 m high cliff marking the effective SE terminus of the glacier at Qum Kuh(Centra1 Iran) ,just to the E of a NE trending river cliff about 40 m high. We merely measured the distances between pairs of stakes with known azimuth about 2 m apart to calculate sub horizontal strain in a small part of Qum Kuh. Stakes moved and micro strains for up to 46 pairs of stakes (p strain= ((lengthl-length2)/1engthl) x 10-1) was calculated for each seven stake epochs and plotted against their azimuth on simplified array maps. The data fit well the sine curves cxpected of the maximum and minimum strain ellipses. The first documented stakes located on the SE where the InSAR image show -1 1 to 0 mm pink to purple, 0 to lOmm purple to blue, and show high activity of salt in low activity area of the InSAR image (980913 to 990620).Short term micro strains of stake tie lines record anisotropic expansions due to heating and contraction due to cooling. All epochs changed between 7 to 1 17 days (990928 to000 1 16), showed 200 to 400 micro strain lengthening and shortening. The contraction and extension existed in each epoch, but the final strain was extension in E-W in Epoch land 6, contraction in E-W direction during epochs 2-3-4-5 and 7. The second pair of stakes hammered about 20 cm deep into the deep soils(more than 1 m) , near summit

  11. Anthocyanidins inhibit activator protein 1 activity and cell transformation: structure-activity relationship and molecular mechanisms.

    PubMed

    Hou, De-Xing; Kai, Keiko; Li, Jian-Jian; Lin, Shigang; Terahara, Norihiko; Wakamatsu, Mika; Fujii, Makoto; Young, Mattew R; Colburn, Nancy

    2004-01-01

    Anthocyanins are the chemical components that give the intense color to many fruits and vegetables, such as blueberries, red cabbages and purple sweet potatoes. Extensive studies have indicated that anthocyanins have strong antioxidant activities. To investigate the mechanism of anthocyanidins as an anticancer food source, six kinds of anthocyanidins representing the aglycons of most anthocyanins, were used to examine their effects on tumor promotion in mouse JB6 cells, a validated model for screening cancer chemopreventive agents and elucidating the molecular mechanisms. Of the six anthocyanins tested, only those with an ortho-dihydroxyphenyl structure on the B-ring suppressed 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cell transformation and activator protein-1 transactivation, suggesting that the ortho-dihydroxyphenyl may contribute to the inhibitory action. Delphinidin, but not peonidin, blocked the phosphorylation of protein kinases in the extracellular signal-regulated protein kinase (ERK) pathway at early times and the c-Jun N-terminal kinase (JNK) signaling pathway at later times. p38 kinase was not inhibited by delphinidin. Furthermore, two mitogen-activated protein kinase (MAPK) specific inhibitors (SP600125 for JNK and UO126 for ERK) could specifically block the activation of JNK and ERK and cell transformation. Those results demonstrate that anthocyanidins contribute to the inhibition of tumorigenesis by blocking activation of the MAPK pathway. These findings provide the first molecular basis for the anticarcinogenic action of anthocyanidins. PMID:14514663

  12. Anthocyanidins inhibit activator protein 1 activity and cell transformation: structure-activity relationship and molecular mechanisms.

    PubMed

    Hou, De-Xing; Kai, Keiko; Li, Jian-Jian; Lin, Shigang; Terahara, Norihiko; Wakamatsu, Mika; Fujii, Makoto; Young, Mattew R; Colburn, Nancy

    2004-01-01

    Anthocyanins are the chemical components that give the intense color to many fruits and vegetables, such as blueberries, red cabbages and purple sweet potatoes. Extensive studies have indicated that anthocyanins have strong antioxidant activities. To investigate the mechanism of anthocyanidins as an anticancer food source, six kinds of anthocyanidins representing the aglycons of most anthocyanins, were used to examine their effects on tumor promotion in mouse JB6 cells, a validated model for screening cancer chemopreventive agents and elucidating the molecular mechanisms. Of the six anthocyanins tested, only those with an ortho-dihydroxyphenyl structure on the B-ring suppressed 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cell transformation and activator protein-1 transactivation, suggesting that the ortho-dihydroxyphenyl may contribute to the inhibitory action. Delphinidin, but not peonidin, blocked the phosphorylation of protein kinases in the extracellular signal-regulated protein kinase (ERK) pathway at early times and the c-Jun N-terminal kinase (JNK) signaling pathway at later times. p38 kinase was not inhibited by delphinidin. Furthermore, two mitogen-activated protein kinase (MAPK) specific inhibitors (SP600125 for JNK and UO126 for ERK) could specifically block the activation of JNK and ERK and cell transformation. Those results demonstrate that anthocyanidins contribute to the inhibition of tumorigenesis by blocking activation of the MAPK pathway. These findings provide the first molecular basis for the anticarcinogenic action of anthocyanidins.

  13. Structure-activity relationship of synthetic branched-chain distearoylglycerol (distearin) as protein kinase C activators

    SciTech Connect

    Zhou, Qingzhong; Raynor, R.L.; Wood, M.G. Jr.; Menger, F.M.; Kuo, J.F. )

    1988-09-20

    Several representative branched-chain analogues of distearin (DS) were synthesized and tested for their abilities to activate protein kinase C (PKC) and to compete for the binding of ({sup 3}H)phorbol 12,13-dibutyrate (PDBu) to the enzyme. Substitutions of stearoyl moieties at sn-1 and sn-2 with 8-methylstearate decreased activities on these parameters, relative to those of the parental diacylglycerol DS, a weak PKC activator. Substitutions with 8-butyl, 4-butyl, or 8-phenyl derivatives, on the other hand, increased activities of the resulting analogues to levels comparable to those seen for diolein (DO), a diacylglycerol prototype shown to be a potent PKC activator. Kinetic analysis indicated that 8-methyldistearin (8-MeDS) acted by decreasing, whereas 8-butyldistearin (8-BuDS) and 8-phenyldistearin (8-PhDS) acted by increasing, the affinities of PKC for phosphatidylserine (PS, a phospholipid cofactor) and Ca{sup 2+} compared to the values seen in the absence or presence of DS. The stimulatory effect of 8-BuDS and 8-PhDS on PKC, as DO, was additive to that of 1,2-(8-butyl)distearoylphosphatidylcholine (1,2(8-Bu)DSPC) and, moreover, they abolished the marked inhibition of the enzyme activity caused by high concentrations of 1,2(8-Bu)DSPC. The present findings demonstrated a structure-activity relationship of the branched-chain DS analogues in the regulation of PKC, perhaps related to their abilities to specifically modify interactions of PKC with PS and/or Ca{sup 2+} critically involved in enzyme activation/inactivation.

  14. Moderators of the Relationship between Physical Activity and Alcohol Consumption in College Students

    ERIC Educational Resources Information Center

    Buscemi, Joanna; Martens, Matthew P.; Murphy, James G.; Yurasek, Ali M.; Smith, Ashley E.

    2011-01-01

    Objective: Among college students, several studies have found a positive relationship between physical activity and alcohol use. The current study tested gender, Greek status, and ethnicity as potential moderators of the physical activity-alcohol use relationship. Participants: Participants were college freshmen (n = 310) endorsing alcohol/drug…

  15. Adolescents' Perception of the Relationship between Movement Skills, Physical Activity and Sport

    ERIC Educational Resources Information Center

    Barnett, Lisa; Cliff, Ken; Morgan, Philip; van Beurden, Eric

    2013-01-01

    Movement skill competence is important to organised youth physical activity participation, but it is unclear how adolescents view this relationship. The primary aim of this study was to explore adolescents' perception of the relationship between movement skills, physical activity and sport, and whether their perceptions differed according to…

  16. Relationship Status and Activated Kin Support: The Role of Need and Norms

    ERIC Educational Resources Information Center

    Mazelis, Joan Maya; Mykyta, Laryssa

    2011-01-01

    Using data from the Fragile Families and Child Wellbeing Study, we examined whether mothers' (N = 4,127) and fathers' (N = 3,405) relationship status influenced their activation of financial support from relatives over time. We found that relationship status influenced the activation of financial support from relatives but that the effects…

  17. An Examination of the Relationship between Enjoyment, Physical Education, Physical Activity and Health in Irish Adolescents

    ERIC Educational Resources Information Center

    Woods, Catherine B.; Tannehill, Deborah; Walsh, Julia

    2012-01-01

    Enjoyment of physical activity (EPA) is positively correlated with activity, yet little is known of its relationship with enjoyment of physical education (EPE). This study's purpose was to explore EPE and its relationship to EPA. Cross-sectional data (N = 4122, average age 14.5 plus or minus 1.7 years, 48% male) were collected as part of the CSPPA…

  18. The Relationship between Traits of Creativity and Physical Activity in the Elderly.

    ERIC Educational Resources Information Center

    Malone, Harry Nevin

    The purpose of this study was to determine if a relationship exists between traits of creativity in the elderly and their level of physical activity. Another purpose was to determine if there was a relationship between traits of creativity focusing on arousal, sensation-seeking, and playfulness and activity. The study used an ex post facto…

  19. Relationship between Frequency and Intensity of Physical Activity and Health Behaviors of Adolescents

    ERIC Educational Resources Information Center

    Delisle, Tony T.; Werch, Chudley E.; Wong, Alvin H.; Bian, Hui; Weiler, Robert

    2010-01-01

    Background: While studies have determined the importance of physical activity in advancing health outcomes, relatively few have explored the relationship between exercise and various health behaviors of adolescents. The purpose of this study is to examine the relationship between frequency and intensity of physical activity and both health risk…

  20. Study of the relationship between solar activity and terrestrial weather

    NASA Technical Reports Server (NTRS)

    Sturrock, P. A.; Brueckner, G. E.; Dickinson, R. E.; Fukuta, N.; Lanzerotti, L. J.; Lindzen, R. S.; Park, C. G.; Wilcox, J. M.

    1976-01-01

    Evidence for some connection between weather and solar related phenomena is presented. Historical data of world wide temperature variations with relationship to change in solar luminosity are examined. Several test methods for estimating the statistical significance of such phenomena are discussed in detail.

  1. Structure-activity relationship of caffeoylquinic acids on the accelerating activity on ATP production.

    PubMed

    Miyamae, Yusaku; Kurisu, Manami; Han, Junkyu; Isoda, Hiroko; Shigemori, Hideyuki

    2011-01-01

    Caffeoylquinic acid (CQA) is one of the phenylpropanoids which have various bioactivities such as antioxidant, antibacterial, anticancer, antihistamic, and other biological effects. We previously reported that 3,5-di-O-caffeoylquinic acid inhibited amyloid β(1-42)-induced cellular toxicity on human neuroblastoma SH-SY5Y cells and increased the mRNA expression level of glycolytic enzymes and the intracellular ATP level. To investigate structure-activity relationship on the accelerating activity on ATP production, we synthesized 1,4,5-tri-O-caffeoylquinic acid, 4,5-di-O-caffeoylquinic acid, 3,4,5-tri-O-caffeoylquinic acid, and other derivatives. Additionally, we evaluated intracellular ATP level in SH-SY5Y treated with each CQA derivative. As a result, 3,4,5-tri-O-caffeoylquinic acid showed the highest accelerating activity on ATP production among tested compounds. It was suggested that caffeoyl groups bound to quinic acid are important for activity and the more caffeoyl groups are bound to quinic acid, the higher accelerating activity on ATP production exhibits.

  2. Quantitative structure-activity relationship of antifungal activity of rosin derivatives.

    PubMed

    Wang, Hui; Nguyen, Thi Thanh Hien; Li, Shujun; Liang, Tao; Zhang, Yuanyuan; Li, Jian

    2015-01-15

    To develop new rosin-based wood preservatives with good antifungal activity, 24 rosin derivatives were synthesized, bioassay tested with Trametes versicolor and Gloeophyllum trabeum, and subjected to analysis of their quantitative structure-activity relationships (QSAR). A QSAR analysis using Ampac 9.2.1 and Codessa 2.7.16 software built two QSAR models of antifungal ratio for T. versicolor and G. trabeum with values of R(2)=0.9740 and 0.9692, respectively. Based on the models, tri-N-(3-hydroabietoxy-2-hydroxy) propyl-triethyl ammonium chloride was designed and the bioassay test result proved its better inhibitory effect against the two selected fungi as expected.

  3. Quantitative structure-activity relationship of antifungal activity of rosin derivatives.

    PubMed

    Wang, Hui; Nguyen, Thi Thanh Hien; Li, Shujun; Liang, Tao; Zhang, Yuanyuan; Li, Jian

    2015-01-15

    To develop new rosin-based wood preservatives with good antifungal activity, 24 rosin derivatives were synthesized, bioassay tested with Trametes versicolor and Gloeophyllum trabeum, and subjected to analysis of their quantitative structure-activity relationships (QSAR). A QSAR analysis using Ampac 9.2.1 and Codessa 2.7.16 software built two QSAR models of antifungal ratio for T. versicolor and G. trabeum with values of R(2)=0.9740 and 0.9692, respectively. Based on the models, tri-N-(3-hydroabietoxy-2-hydroxy) propyl-triethyl ammonium chloride was designed and the bioassay test result proved its better inhibitory effect against the two selected fungi as expected. PMID:25466709

  4. SARS: a health system's perspective.

    PubMed

    Beard, Leslie; Clark, Caroline

    2003-01-01

    Effective communications with different stakeholders was critical for health systems everywhere during the worldwide SARS outbreak earlier this year. For Capital Health in Edmonton, Alberta, the health system was able to build on its past experiences in dealing with meningococcal outbreaks and its planning for a pandemic flu. PMID:14628532

  5. Quantitative structure-activity relationship (QSAR) for insecticides: development of predictive in vivo insecticide activity models.

    PubMed

    Naik, P K; Singh, T; Singh, H

    2009-07-01

    Quantitative structure-activity relationship (QSAR) analyses were performed independently on data sets belonging to two groups of insecticides, namely the organophosphates and carbamates. Several types of descriptors including topological, spatial, thermodynamic, information content, lead likeness and E-state indices were used to derive quantitative relationships between insecticide activities and structural properties of chemicals. A systematic search approach based on missing value, zero value, simple correlation and multi-collinearity tests as well as the use of a genetic algorithm allowed the optimal selection of the descriptors used to generate the models. The QSAR models developed for both organophosphate and carbamate groups revealed good predictability with r(2) values of 0.949 and 0.838 as well as [image omitted] values of 0.890 and 0.765, respectively. In addition, a linear correlation was observed between the predicted and experimental LD(50) values for the test set data with r(2) of 0.871 and 0.788 for both the organophosphate and carbamate groups, indicating that the prediction accuracy of the QSAR models was acceptable. The models were also tested successfully from external validation criteria. QSAR models developed in this study should help further design of novel potent insecticides.

  6. Further SEASAT SAR coastal ocean wave analysis

    NASA Technical Reports Server (NTRS)

    Kasischke, E. S.; Shuchman, R. A.; Meadows, G. A.; Jackson, P. L.; Tseng, Y.

    1981-01-01

    Analysis techniques used to exploit SEASAT synthetic aperture radar (SAR) data of gravity waves are discussed and the SEASAT SAR's ability to monitor large scale variations in gravity wave fields in both deep and shallow water is evaluated. The SAR analysis techniques investigated included motion compensation adjustments and the semicausal model for spectral analysis of SAR wave data. It was determined that spectra generated from fast Fourier transform analysis (FFT) of SAR wave data were not significantly altered when either range telerotation adjustments or azimuth focus shifts were used during processing of the SAR signal histories, indicating that SEASAT imagery of gravity waves is not significantly improved or degraded by motion compensation adjustments. Evaluation of the semicausal (SC) model using SEASAT SAR data from Rev. 974 indicates that the SC spectral estimates were not significantly better than the FFT results.

  7. Shared social and emotional activities within adolescent romantic and non-romantic sexual relationships.

    PubMed

    Williams, Lela Rankin; Russell, Stephen T

    2013-05-01

    Typically, "non-romantic" sexual relationships are assumed to be casual; however, the emotional and social distinctions between romantic and non-romantic contexts are not well understood, particularly in adolescence. Data from the National Longitudinal Study of Adolescent Health (Add Health) was used to compare shared emotional (e.g., telling partner that they love her/him) and social (e.g., going out in a group) activities within romantic and non-romantic sexual relationships. Adolescents who reported exclusively romantic sexual relationships (n = 1,891) shared more emotional, but not social, activities with their partners than adolescents who were in non-romantic sexual relationships (n = 315; small effect size, r = .07-.13), akin to adolescents who experienced both relationship types (n = 519; small-to-medium effect size, r = .18-.38). Girls shared more emotional and social activities with their partners than boys when in romantic relationships (small effect size, r = .06-.10); there were no significant gender differences within non-romantic sexual relationships. Findings suggest that gendered scripts remain for sexual relationships that are romantic but not for those that are non-romantic. Notably, for the majority of adolescents, non-romantic relationships still held many emotional and social dimensions typical of romantic relationships and differences between relationship types were small. Although non-romantic relationships were less intimate than romantic sexual relationships, there was remarkable heterogeneity within this relationship type. Caution is advised when working with adolescents engaged in "casual" sexual relationships. Understanding the complexity of adolescent sexual relationships is critical for the advancement of effective sex education programming.

  8. Jatrophane Diterpenoids as Modulators of P-Glycoprotein-Dependent Multidrug Resistance (MDR): Advances of Structure-Activity Relationships and Discovery of Promising MDR Reversal Agents.

    PubMed

    Zhu, Jianyong; Wang, Ruimin; Lou, Lanlan; Li, Wei; Tang, Guihua; Bu, Xianzhang; Yin, Sheng

    2016-07-14

    The phytochemical study of Pedilanthus tithymaloides led to the isolation of 13 jatrophane diterpenoids (1-13), of which eight (1-8) are new. Subsequent structural modification of the major components by esterification, hydrolysis, hydrogenation, or epoxidation yielded 22 new derivatives (14-35). Thus, a jatrophane library containing two series of compounds was established to screen for P-glycoprotein (Pgp)-dependent MDR modulators. The activity was evaluated through a combination of Rho123 efflux and chemoreversal assays on adriamycin resistant human hepatocellular carcinoma cell line HepG2 (HepG2/ADR) and adriamycin resistant human breast adenocarcinoma cell line MCF-7 (MCF-7/ADR). Compounds 19, 25, and 26 were identified as potent MDR modulators with greater chemoreversal ability and less cytotoxicity than the third-generation drug tariquidar. The structure-activity relationship (SAR) was discussed, which showed that modifications beyond just increasing the lipophilicity of this class of Pgp inhibitors are beneficial to the activity. Compound 26, which exhibited a remarkable metabolic stability in vitro and a favorable antitumor effect in vivo, would serve as a promising lead for the development of new MDR reversal agents. PMID:27328029

  9. Relationship between anticoagulant activities and polyanionic properties of rabbit thrombomodulin.

    PubMed

    Bourin, M C; Ohlin, A K; Lane, D A; Stenflo, J; Lindahl, U

    1988-06-15

    Rabbit thrombomodulin displays three distinct blood anticoagulant activities: it promotes the activation of protein C by thrombin (protein C activation cofactor activity); it promotes the inactivation of thrombin by thrombin (direct anticoagulant activity). The effects on these activities of mouse anti-thrombomodulin monoclonal antibodies and of the heparin-neutralizing proteins, platelet factor 4, histidine-rich glycoprotein, and S-protein, were investigated. One of the antibodies, which did not influence the functional properties of thrombomodulin, was used as an immunoaffinity ligand for purification of the protein. Two other antibodies, which were found to abrogate the protein C activation cofactor activity of the purified thrombomodulin, also abolished the antithrombin-dependent and the direct anticoagulant activities. The heparin-neutralizing proteins all inhibited the two latter activities, albeit to a varying extent, but did not appreciably affect the activation of protein C. These results are interpreted in relation to our previous finding that rabbit thrombomodulin contains an acidic domain, tentatively identified as a sulfated glycosaminoglycan (Bourin, M.-C., Boffa, M.-C., Björk, I., and Lindahl, U. (1986) Proc. Natl. Acad. Sci. U.S.A. 83, 5924-5928). It is proposed that the acidic domain interacts with thrombin at the protein C activation site and that this interaction is a prerequisite to the expression of direct as well as antithrombin-dependent anticoagulant activity. The interaction is not essential to, but compatible with, the activation of protein C. Experiments involving treatment of thrombomodulin with various glycanases or with nitrous acid, followed by measurement of anticoagulant activities, indicated that the acidic domain is constituted by a sulfated galactosaminoglycan and not by a heparin-related polysaccharide as previously suggested.

  10. Inhibition of Angiotensin-Converting Enzyme Activity by Flavonoids: Structure-Activity Relationship Studies

    PubMed Central

    Guerrero, Ligia; Castillo, Julián; Quiñones, Mar; Garcia-Vallvé, Santiago; Arola, Lluis; Pujadas, Gerard; Muguerza, Begoña

    2012-01-01

    Previous studies have demonstrated that certain flavonoids can have an inhibitory effect on angiotensin-converting enzyme (ACE) activity, which plays a key role in the regulation of arterial blood pressure. In the present study, 17 flavonoids belonging to five structural subtypes were evaluated in vitro for their ability to inhibit ACE in order to establish the structural basis of their bioactivity. The ACE inhibitory (ACEI) activity of these 17 flavonoids was determined by fluorimetric method at two concentrations (500 µM and 100 µM). Their inhibitory potencies ranged from 17 to 95% at 500 µM and from 0 to 57% at 100 µM. In both cases, the highest ACEI activity was obtained for luteolin. Following the determination of ACEI activity, the flavonoids with higher ACEI activity (i.e., ACEI >60% at 500 µM) were selected for further IC50 determination. The IC50 values for luteolin, quercetin, rutin, kaempferol, rhoifolin and apigenin K were 23, 43, 64, 178, 183 and 196 µM, respectively. Our results suggest that flavonoids are an excellent source of functional antihypertensive products. Furthermore, our structure-activity relationship studies show that the combination of sub-structures on the flavonoid skeleton that increase ACEI activity is made up of the following elements: (a) the catechol group in the B-ring, (b) the double bond between C2 and C3 at the C-ring, and (c) the cetone group in C4 at the C-ring. Protein-ligand docking studies are used to understand the molecular basis for these results. PMID:23185345

  11. Airborne SAR/IFSAR for mapping in urban areas

    NASA Astrophysics Data System (ADS)

    Chayakula, Thongthit

    There are many problems in topographic mapping in an urban area. Traditional land survey is a very time consuming technique and can be very expensive. Photogrammetry is a popular choice but there are some problems such as clouds and limited operational time. Since Synthetic Aperture Radar, (SAR), is an active remote sensing system and its signal can penetrate through clouds, it can be operated at any time of day and is a independent of the weather. SAR could be a good solution for topographic mapping in an urban area. Combining SAR data and Interferometric radar technology can provide enough information for topographic mapping. Information can be extracted from SAR intensity Image. This thesis focuses on feature extraction and classification for topographic mapping in an urban area from airborne interferometric SAR data. A new algorithm is described which is simple and practical but yet very efficient for feature extraction and for object-based feature classification. An adapted Canny-Petrou-Kittler algorithm is applied for edge detection. Since the algorithm provides good detection, good localization and only one response to a single edge, it is an ideal edge detection for dense urban areas. Since the SAR image is noisy by its nature, small weak edges are expected. The modified non-maximal technique is also proposed to reduce unwanted edge. The technique of generation of bald earth DEM is proposed to obtain a normalised DEM for feature extraction. Region growing from edge detection is then applied to extract a more accurate shape of the feature and generate feature surface by using topographic parameters. The extracted feature is then classified by object-oriented classification technique, in which the classification is performed at object level not pixel level. And at the end of the process 3D city model can be produced.

  12. Developing an Error Model for Ionospheric Phase Distortions in L-Band SAR and InSAR Data

    NASA Astrophysics Data System (ADS)

    Meyer, F. J.; Agram, P. S.

    2014-12-01

    Many of the recent and upcoming spaceborne SAR systems are operating in the L-band frequency range. The choice of L-band has a number of advantages especially for InSAR applications. These include deeper penetration into vegetation, higher coherence, and higher sensitivity to soil moisture. While L-band SARs are undoubtedly beneficial for a number of earth science disciplines, their signals are susceptive to path delay effects in the ionosphere. Many recent publications indicate that the ionosphere can have detrimental effects on InSAR coherence and phase. It has also been shown that the magnitude of these effects strongly depends on the time of day and geographic location of the image acquisition as well as on the coincident solar activity. Hence, in order to provide realistic error estimates for geodetic measurements derived from L-band InSAR, an error model needs to be developed that is capable of describing ionospheric noise. With this paper, we present a global ionospheric error model that is currently being developed in support of NASA's future L-band SAR mission NISAR. The system is based on a combination of empirical data analysis and modeling input from the ionospheric model WBMOD, and is capable of predicting ionosphere-induced phase noise as a function of space and time. The error model parameterizes ionospheric noise using a power spectrum model and provides the parameters of this model in a global 1x1 degree raster. From the power law model, ionospheric errors in deformation estimates can be calculated. In Polar Regions, our error model relies on a statistical analysis of ionospheric-phase noise in a large number of SAR data from previous L-band SAR missions such as ALOS PALSAR and JERS-1. The focus on empirical analyses is due to limitations of WBMOD in high latitude areas. Outside of the Polar Regions, the ionospheric model WBMOD is used to derive ionospheric structure parameters for as a function of solar activity. The structure parameters are

  13. Classical Nuclear Hormone Receptor Activity as a Mediator of Complex Concentration Response Relationships for Endocrine Active Compounds

    PubMed Central

    Cookman, Clifford J.; Belcher, Scott M.

    2014-01-01

    Nonmonotonic concentration response relationships are frequently observed for endocrine active ligands that act via nuclear receptors. The curve of best fit for nonmonotonic concentration response relationships are often inverted U-shaped with effects at intermediate concentrations that are different from effects at higher or lower concentrations. Cytotoxicity is a major mode of action responsible for inverted U-shaped concentration response relationships. However, evidence suggests that ligand selectivity, activation of multiple molecular targets, concerted regulation of multiple opposing endpoints, and multiple ligand binding sites within nuclear receptors also contribute to nonmonotonic concentration response relationships of endocrine active ligands. This review reports the current understanding of mechanisms involved in classical nuclear receptor mediated nonmonotonic concentration response relationships with a focus on studies published between 2012 and 2014. PMID:25299165

  14. The impact of SARS on a tertiary care pediatric emergency department

    PubMed Central

    Boutis, Kathy; Stephens, Derek; Lam, Kelvin; Ungar, Wendy J.; Schuh, Suzanne

    2004-01-01

    Background The Greater Toronto Area (GTA) was considered a “hot zone” for severe acute respiratory syndrome (SARS) in 2003. In accordance with mandated city-wide infection control measures, the Hospital for Sick Children (HSC) drastically reduced all services while maintaining a fully operational emergency department. Because of the GTA health service suspensions and the overlap of SARS-like symptoms with many common childhood illnesses, this introduced the potential for a change in the volumes of patients visiting the emergency department of the only regional tertiary care children's hospital. Methods We compared HSC emergency department patient volumes, admission rates and length of stay in the emergency department in the baseline years of 2000–2002 (non-SARS years) with those in 2003 (SARS year). The data from the prior years were modeled as a time series. Using an interrupted time series analysis, we compared the 2003 data for the periods before, during and after the SARS periods with the modeled data for significant differences in the 3 aforementioned outcomes of interest. Results Compared with the 2000–2002 data, we found no differences in visits, admission rates or length of stay in the pre-SARS period in 2003. There were significant decreases in visits and length of stay (p < 0.001) and increases in admission rates (p < 0.001) during the periods in 2003 when there were new and active cases of SARS in the GTA. All 3 outcomes returned to expected estimates coincident with the absence of SARS cases from September to December 2003. Interpretation During the SARS outbreak in the GTA, the HSC emergency department experienced significantly reduced volumes of patients with low-acuity complaints. This gives insight into utilization rates of a pediatric emergency department during a time when there was additional perceived risk in using emergency department services and provides a foundation for emergency department preparedness policies for SARS-like public

  15. Developing Methods for Mapping Soil Moisture in Nash Draw, NM Using RADARSAT 1 SAR Fine Imagery

    NASA Astrophysics Data System (ADS)

    Hossain, A. A.; Easson, G.; Powers, D. W.; Holt, R. M.

    2006-12-01

    Nash Draw, in southeastern NM, is a karst valley that developed in response to subsurface dissolution of evaporites, including halite and sulfate rocks. The hydrologic system within Nash Draw is poorly understood. This study focuses on identifying the distribution and amount of recharge in Nash Draw to assist in understanding the existing processes modifying Nash Draw by solution. We hypothesize that 1) soil moisture contents will be higher in the areas where potential recharge occurs and 2) these areas can be identified using remote sensing. To test the second part of this hypothesis, this study has been designed to determine the spatial and temporal distribution of soil moisture in the study site using microwave data. An area of 225 sq. km in Nash Draw has been selected as the study site. Imagery was acquired from the Alaska SAR Facility (ASF) for 8 scenes of RADARDSAT 1 SAR Fine Beam imagery with different incidence angles (40° and 48°) and imaging modes (ascending and descending). We use RADARDSAT 1 SAR Fine Beam imagery acquired on August 1, 2006 and August 2, 2006 and near real-time ground truth data to develop suitable model to map the spatial distribution of soil moisture in the study site. During the image acquisitions on August 1 and 2, 80 soil samples were collected to determine the near real- time volumetric soil moisture in the study site. Soil samples were collected using a stratified sampling method, and locations of the samples were recorded using GPS. Soil water is compared, using linear regression, to radar backscatter to develop an empirical model of the relationship. The radar backscatter used in this model was acquired at different incidence angles. This study also provides an opportunity to investigate the impact of variable incidence angles on the potential of space-borne active microwave data for soil moisture mapping in semi-arid region like Nash Draw.

  16. Activity cliff networks for medicinal chemistry.

    PubMed

    Stumpfe, Dagmar; Bajorath, Jürgen

    2014-08-01

    Network representations are widely used in bioinformatics but have only been little explored in chemistry. Thus far, only a few attempts have been made to generate and analyze compound networks. Among these are the first activity cliff networks. In medicinal chemistry, activity cliffs are focal points of structure-activity relationships (SAR) analysis. Activity cliffs have generally been defined as pairs of structurally similar or analogous active compounds that have a large difference in potency against their target. However, most activity cliffs are not formed in isolation but in a coordinated manner involving multiple highly and weakly potent compounds. Recently, a comprehensive activity cliff network has been generated for current public domain bioactive compounds, hence providing a first global view of activity cliff formation. The design of activity cliff networks is discussed herein. From the global activity cliff network, local networks can be extracted for individual compound activity classes that provide graphical access to high-level SAR information for compound optimization efforts.

  17. SAR Image despeckling via sparse representation

    NASA Astrophysics Data System (ADS)

    Wang, Zhongmei; Yang, Xiaomei; Zheng, Liang

    2014-11-01

    SAR image despeckling is an active research area in image processing due to its importance in improving the quality of image for object detection and classification.In this paper, a new approach is proposed for multiplicative noise in SAR image removal based on nonlocal sparse representation by dictionary learning and collaborative filtering. First, a image is divided into many patches, and then a cluster is formed by clustering log-similar image patches using Fuzzy C-means (FCM). For each cluster, an over-complete dictionary is computed using the K-SVD method that iteratively updates the dictionary and the sparse coefficients. The patches belonging to the same cluster are then reconstructed by a sparse combination of the corresponding dictionary atoms. The reconstructed patches are finally collaboratively aggregated to build the denoised image. The experimental results show that the proposed method achieves much better results than many state-of-the-art algorithms in terms of both objective evaluation index (PSNR and ENL) and subjective visual perception.

  18. Characterizing forest stands with multi-incidence angle and multi-polarized SAR data

    NASA Technical Reports Server (NTRS)

    Hoffer, R. M.; Lozano-Garcia, D. F.; Gillespie, D. D.

    1987-01-01

    The potential for using HH-polarized L-band SAR data obtained at different incidence angles from satellite altitudes to identify and map different forest cover types and stand density classes is studied. Reasonably accurate results are obtained if the speckle characteristics of the data are suppressed by low-pass spatial filters and a contextual classification algorithm. Multipolarized L-band SAR data obtained from aircraft altitudes over the same test site are also analyzed to assess the relationships between polarization and forest stand characteristics. It is found that incidence angle controls, to a very large extent, the characteristics of the data and the type of information that can be obtained from L-band, HH-polarized satellite SAR data. Cross-polarization of L-band SAR data enhances and differentiates various forest stand characteristics which cannot be defined using only the like-polarized data, and vice-versa.

  19. Controlling Data Collection to Support SAR Image Rotation

    DOEpatents

    Doerry, Armin W.; Cordaro, J. Thomas; Burns, Bryan L.

    2008-10-14

    A desired rotation of a synthetic aperture radar (SAR) image can be facilitated by adjusting a SAR data collection operation based on the desired rotation. The SAR data collected by the adjusted SAR data collection operation can be efficiently exploited to form therefrom a SAR image having the desired rotational orientation.

  20. Neuroprotective and Antioxidant Activities of 4-Methylcoumarins: Development of Structure-Activity Relationships.

    PubMed

    Malhotra, Shashwat; Tavakkoli, Marjan; Edraki, Najmeh; Miri, Ramin; Sharma, Sunil Kumar; Prasad, Ashok Kumar; Saso, Luciano; Len, Christophe; Parmar, Virinder Singh; Firuzi, Omidreza

    2016-01-01

    Coumarins are a major class of polyphenols that are abundantly present in many dietary plants and possess different biological activities. Neuroprotective effect of 28 variously substituted 4-methylcoumarins was evaluated in a cell model of oxidative stress-induced neurodegeneration, which measures viability in PC12 cells challenged with hydrogen peroxide by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The inhibitory activity of these compounds against intracellular reactive oxygen species (ROS) formation was also determined by 2',7'-dichlorofluorescein diacetate method in the same cells. Chemical redox-based assays including 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) tests were employed to explore structure-antioxidant activity relationships in a cell-free environment. The results demonstrated that 4-methylcoumarins containing ortho-dihydroxy or ortho-diacetoxy substituents on the benzenoid ring possess considerable neuroprotective effects. ortho-Dihydroxy compounds inhibited cytotoxicity (44.7-62.9%) and ROS formation (41.6-71.1%) at 50 µM and showed considerable antioxidant effects. We conclude that 4-methylcoumarins are promising neuroprotective and antioxidant scaffolds potentially usefull for management of neurodegenerative diseases. PMID:27582333

  1. From SARS coronavirus to novel animal and human coronaviruses

    PubMed Central

    To, Kelvin K. W.; Hung, Ivan F. N.; Chan, Jasper F. W.

    2013-01-01

    In 2003, severe acute respiratory syndrome coronavirus (SARS-CoV) caused one of the most devastating epidemics known to the developed world. There were two important lessons from this epidemic. Firstly, coronaviruses, in addition to influenza viruses, can cause severe and rapidly spreading human infections. Secondly, bats can serve as the origin and natural animal reservoir of deadly human viruses. Since then, researchers around the world, especially those in Asia where SARS-CoV was first identified, have turned their focus to find novel coronaviruses infecting humans, bats, and other animals. Two human coronaviruses, HCoV-HKU1 and HCoV-NL63, were identified shortly after the SARS-CoV epidemic as common causes of human respiratory tract infections. In 2012, a novel human coronavirus, now called Middle East respiratory syndrome coronavirus (MERS-CoV), has emerged in the Middle East to cause fatal human infections in three continents. MERS-CoV human infection is similar to SARS-CoV in having a high fatality rate and the ability to spread from person to person which resulted in secondary cases among close contacts including healthcare workers without travel history to the Middle East. Both viruses also have close relationships with bat coronaviruses. New cases of MERS-CoV infection in humans continue to occur with the origins of the virus still unknown in many cases. A multifaceted approach is necessary to control this evolving MERS-CoV outbreak. Source identification requires detailed epidemiological studies of the infected patients and enhanced surveillance of MERS-CoV or similar coronaviruses in humans and animals. Early diagnosis of infected patients and appropriate infection control measures will limit the spread in hospitals, while social distancing strategies may be necessary to control the outbreak in communities if it remained uncontrolled as in the SARS epidemic. PMID:23977429

  2. Relationships

    ERIC Educational Resources Information Center

    Circle, David

    2006-01-01

    The author of this brief article asserts that one of the keys to being successful--whether one is a music teacher, a college professor, a business owner, a doctor, a lawyer, or in any other career--is his or her relationship with people. Music educators are in the people business. They do not make a tangible product. Instead, they provide a…

  3. A facile inhibitor screening of SARS coronavirus N protein using nanoparticle-based RNA oligonucleotide

    PubMed Central

    Roh, Changhyun

    2012-01-01

    Hundreds of million people worldwide have been infected with severe acute respiratory syndrome (SARS), and the rate of global death from SARS has remarkably increased. Hence, the development of efficient drug treatments for the biological effects of SARS is highly needed. We have previously shown that quantum dots (QDs)-conjugated RNA oligonucleotide is sensitive to the specific recognition of the SARS-associated coronavirus (SARS-CoV) nucleocapsid (N) protein. In this study, we found that a designed biochip could analyze inhibitors of the SARS-CoV N protein using nanoparticle-based RNA oligonucleotide. Among the polyphenolic compounds examined, (−)-catechin gallate and (−)-gallocatechin gallate demonstrated a remarkable inhibition activity on SARS-CoV N protein. (−)-catechin gallate and (−)-gallocatechin gallate attenuated the binding affinity in a concentrated manner as evidenced by QDs-conjugated RNA oligonucleotide on a designed biochip. At a concentration of 0.05 μg mL−1, (−)-catechin gallate and (−)-gallocatechin gallate showed more than 40% inhibition activity on a nanoparticle-based RNA oligonucleotide biochip system. PMID:22619553

  4. Small-molecule PSMA ligands. Current state, SAR and perspectives.

    PubMed

    Machulkin, Alexey E; Ivanenkov, Yan A; Aladinskaya, Anastasia V; Veselov, Mark S; Aladinskiy, Vladimir A; Beloglazkina, Elena K; Koteliansky, Victor E; Shakhbazyan, Artem G; Sandulenko, Yuri B; Majouga, Alexander G

    2016-09-01

    Prostate cancer (PC) is the prevalent malignancy widespread among men in the Western World. Prostate specific membrane antigen (PSMA) is an established PC marker and has been considered as a promising biological target for anti-PC drug delivery and diagnostics. The protein was found to be overexpressed in PC cells, including metastatic, and the neovasculature of solid tumors. These properties make PSMA-based approach quite appropriate for effective PC imaging and specific drug therapy. Through the past decade, a variety of PSMA-targeted agents has been systematically evaluated. Small-molecule compounds have several advantages over other classes, such as improved pharmacokinetics and rapid blood clearance. These low-weight ligands have similar structure and can be divided into three basic categories in accordance with the type of their zinc-binding core-head. Several PSMA binders are currently undergoing clinical trials generally for PC imaging. The main goal of the present review is to describe the recent progress achieved within the title field and structure activity relationships (SAR) disclosed for different PSMA ligands. Recent in vitro and in vivo studies for each type of the compounds described have also been briefly summarized. PMID:26887438

  5. Synthesis of a Sugar-Based Thiosemicarbazone Series and Structure-Activity Relationship versus the Parasite Cysteine Proteases Rhodesain, Cruzain, and Schistosoma mansoni Cathepsin B1

    PubMed Central

    Fonseca, Nayara Cristina; da Cruz, Luana Faria; da Silva Villela, Filipe; do Nascimento Pereira, Glaécia Aparecida; de Siqueira-Neto, Jair Lage; Kellar, Danielle; Suzuki, Brian M.; Ray, Debalina; de Souza, Thiago Belarmino; Alves, Ricardo José; Júnior, Policarpo Ademar Sales; Romanha, Alvaro José; Murta, Silvane Maria Fonseca; McKerrow, James H.; Caffrey, Conor R.; de Oliveira, Renata Barbosa

    2015-01-01

    The pressing need for better drugs against Chagas disease, African sleeping sickness, and schistosomiasis motivates the search for inhibitors of cruzain, rhodesain, and Schistosoma mansoni CB1 (SmCB1), the major cysteine proteases from Trypanosoma cruzi, Trypanosoma brucei, and S. mansoni, respectively. Thiosemicarbazones and heterocyclic analogues have been shown to be both antitrypanocidal and inhibitory against parasite cysteine proteases. A series of compounds was synthesized and evaluated against cruzain, rhodesain, and SmCB1 through biochemical assays to determine their potency and structure-activity relationships (SAR). This approach led to the discovery of 6 rhodesain, 4 cruzain, and 5 SmCB1 inhibitors with 50% inhibitory concentrations (IC50s) of ≤10 μM. Among the compounds tested, the thiosemicarbazone derivative of peracetylated galactoside (compound 4i) was discovered to be a potent rhodesain inhibitor (IC50 = 1.2 ± 1.0 μM). The impact of a range of modifications was determined; removal of thiosemicarbazone or its replacement by semicarbazone resulted in virtually inactive compounds, and modifications in the sugar also diminished potency. Compounds were also evaluated in vitro against the parasites T. cruzi, T. brucei, and S. mansoni, revealing active compounds among this series. PMID:25712353

  6. Synthesis and structure-activity relationship of trimebutine derivatives.

    PubMed

    Sai, H; Ozaki, Y; Hayashi, K; Onoda, Y; Yamada, K

    1996-06-01

    Trimebutine derivatives were synthesized by utilizing alkylation or acylation of isonitriles and nitrile as a key step. The colonic contractile effects of these compounds were examined, and T-1815 was found to have strong colonic propulsive activity. PMID:8814947

  7. Androgen receptor antagonists (antiandrogens): structure-activity relationships.

    PubMed

    Singh, S M; Gauthier, S; Labrie, F

    2000-02-01

    Prostate cancer, acne, seborrhea, hirsutism, and androgenic alopecia are well recognized to depend upon an excess or increased sensitivity to androgens or to be at least sensitive to androgens. It thus seems logical to use antiandrogens as therapeutic agents to prevent androgens from binding to the androgen receptor. The two predominant naturally occurring androgens are testosterone (T) and dihydrotestosterone (DHT). DHT is the more potent androgen in vivo and in vitro. All androgen-responsive genes are activated by androgen receptor (AR) bound to either T or DHT and it is believed that AR is more transcriptionally active when bound to DHT than T. The two classes of antiandrogens, presently available, are the steroidal derivatives, all of which possess mixed agonistic and antagonistic activities, and the pure non-steroidal antiandrogens of the class of flutamide and its derivatives. The intrinsic androgenic, estrogenic and glucocorticoid activities of steroidal derivatives have limited their use in the treatment of prostate cancer. The non-steroidal flutamide and its derivatives display pure antiandrogenic activity, without exerting agonistic or any other hormonal activity. Flutamide (89) and its derivatives, Casodex (108) and Anandron (114), are highly effective in the treatment of prostate cancer. The combination of flutamide and Anandron with castration has shown prolongation of life in prostate cancer. Furthermore, combined androgen blockade in association with radical prostatectomy or radiotherapy are very effective in the treatment of localized prostate cancer. Such an approach certainly raises the hope of a further improvement in prostate cancer therapy. However, all antiandrogens, developed so-far display moderate affinity for the androgen receptor, and thus moderate efficacy in vitro and in vivo. There is thus a need for next-generation antiandrogens, which could display an equal or even higher affinity for AR compared to the natural androgens, and at the

  8. 5. SWITCH TOWER AND JUNCTION OF S.A.R. #1 & S.A.R. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. SWITCH TOWER AND JUNCTION OF S.A.R. #1 & S.A.R. #2 TRANSMISSION LINES, MARCH 7, 1916. SCE drawing no. 4932. - Santa Ana River Hydroelectric System, Transmission Lines, Redlands, San Bernardino County, CA

  9. Predicting anti-androgenic activity of bisphenols using molecular docking and quantitative structure-activity relationships.

    PubMed

    Yang, Xianhai; Liu, Huihui; Yang, Qian; Liu, Jining; Chen, Jingwen; Shi, Lili

    2016-11-01

    Both in vivo and in vitro assay indicated that bisphenols can inhibit the androgen receptor. However, the underlying antagonistic mechanism is unclear. In this study, molecular docking was employed to probe the interaction mechanism between bisphenols and human androgen receptor (hAR). The binding pattern of ligands in hAR crystal structures was also analyzed. Results show that hydrogen bonding and hydrophobic interactions are the dominant interactions between the ligands and hAR. The critical amino acid residues involved in forming hydrogen bonding between bisphenols and hAR is Asn 705 and Gln 711. Furthermore, appropriate molecular structural descriptors were selected to characterize the non-bonded interactions. Stepwise multiple linear regressions (MLR) analysis was employed to develop quantitative structure-activity relationship (QSAR) models for predicting the anti-androgenic activity of bisphenols. Based on the QSAR development and validation guideline issued by OECD, the goodness-of-fit, robustness and predictive ability of constructed QSAR model were assessed. The model application domain was characterized by the Euclidean distance and Williams plot. The mechanisms of the constructed model were also interpreted based on the selected molecular descriptors i.e. the number of hydroxyl groups (nROH), the most positive values of the molecular surface potential (Vs,max) and the lowest unoccupied molecular orbital energy (ELUMO). Finally, based on the model developed, the data gap for other twenty-six bisphenols on their anti-androgenic activity was filled. The predicted results indicated that the anti-androgenic activity of seven bisphenols was higher than that of bisphenol A. PMID:27561732

  10. Design, synthesis, and in vivo SAR of a novel series of pyrazolines as potent selective androgen receptor modulators.

    PubMed

    Zhang, Xuqing; Li, Xiaojie; Allan, George F; Sbriscia, Tifanie; Linton, Olivia; Lundeen, Scott G; Sui, Zhihua

    2007-08-01

    A novel series of pyrazolines 2 have been designed, synthesized, and evaluated by in vivo screening as tissue-selective androgen receptor modulators (SARMs). Structure-activity relationships (SAR) were investigated at the R1 to R6 positions as well as the core pyrazoline ring and the anilide linker. Overall, strong electron-withdrawing groups at the R1 and R2 positions and a small group at the R5 and R6 position are optimal for AR agonist activity. The (S)-isomer of 7c exhibits more potent AR agonist activity than the corresponding (R)-isomer. (S)-7c exhibited an overall partial androgenic effect but full anabolic effect via oral administration in castrated rats. It demonstrated a noticeable antiandrogenic effect on prostate in intact rats with endogenous testosterone. Thus, (S)-7c is a tissue-selective nonsteroidal androgen receptor modulator with agonist activity on muscle and mixed agonist and antagonist activity on prostate.

  11. Advanced digital SAR processing study

    NASA Technical Reports Server (NTRS)

    Martinson, L. W.; Gaffney, B. P.; Liu, B.; Perry, R. P.; Ruvin, A.

    1982-01-01

    A highly programmable, land based, real time synthetic aperture radar (SAR) processor requiring a processed pixel rate of 2.75 MHz or more in a four look system was designed. Variations in range and azimuth compression, number of looks, range swath, range migration and SR mode were specified. Alternative range and azimuth processing algorithms were examined in conjunction with projected integrated circuit, digital architecture, and software technologies. The advaced digital SAR processor (ADSP) employs an FFT convolver algorithm for both range and azimuth processing in a parallel architecture configuration. Algorithm performace comparisons, design system design, implementation tradeoffs and the results of a supporting survey of integrated circuit and digital architecture technologies are reported. Cost tradeoffs and projections with alternate implementation plans are presented.

  12. Quantitative structure-antifungal activity relationships of some benzohydrazides against Botrytis cinerea.

    PubMed

    Reino, José L; Saiz-Urra, Liane; Hernandez-Galan, Rosario; Aran, Vicente J; Hitchcock, Peter B; Hanson, James R; Gonzalez, Maykel Perez; Collado, Isidro G

    2007-06-27

    Fourteen benzohydrazides have been synthesized and evaluated for their in vitro antifungal activity against the phytopathogenic fungus Botrytis cinerea. The best antifungal activity was observed for the N',N'-dibenzylbenzohydrazides 3b-d and for the N-aminoisoindoline-derived benzohydrazide 5. A quantitative structure-activity relationship (QSAR) study has been developed using a topological substructural molecular design (TOPS-MODE) approach to interpret the antifungal activity of these synthetic compounds. The model described 98.3% of the experimental variance, with a standard deviation of 4.02. The influence of an ortho substituent on the conformation of the benzohydrazides was investigated by X-ray crystallography and supported by QSAR study. Several aspects of the structure-activity relationships are discussed in terms of the contribution of different bonds to the antifungal activity, thereby making the relationships between structure and biological activity more transparent.

  13. Distinct Spatial Patterns of SAR11, SAR86, and Actinobacteria Diversity along a Transect in the Ultra-oligotrophic South Pacific Ocean

    PubMed Central

    West, Nyree J.; Lepère, Cécile; Manes, Carmem-Lara de O.; Catala, Philippe; Scanlan, David J.; Lebaron, Philippe

    2016-01-01

    Distinct distribution patterns of members of the major bacterial clades SAR11, SAR86, and Actinobacteria were observed across a transect from the Marquesas islands through the ultra-oligotrophic South Pacific Gyre into the Chilean upwelling using 16S rRNA gene sequencing and RNA–DNA fingerprinting. Three different Actinobacteria sequence clusters belonging to “Candidatus Actinomarinidae” were localized in the western half of the transect, one was limited to the gyre deep chlorophyll maximum (DCM) and sequences affiliated to the OCS155 clade were unique to the upwelling. The structure of the surface bacterial community was highly correlated with water mass and remained similar across the whole central gyre (1300 nautical miles). The surface hyperoligotrophic gyre was dominated (>70% of all sequences) by highly diverse SAR11 and SAR86 operational taxonomic units and these communities were significantly different from those in the DCM. Analysis of 16S rRNA fingerprints generated from RNA allowed insights into the potential activity of assigned bacterial groups. SAR11 and Prochlorococcus showed the highest potential activity in all water masses except for the upwelling, accounting together for 65% of the total bacterial 16S rRNA in the gyre surface waters in equal proportions whereas the contribution of SAR11 decreased significantly at the DCM. PMID:27014192

  14. Distinct Spatial Patterns of SAR11, SAR86, and Actinobacteria Diversity along a Transect in the Ultra-oligotrophic South Pacific Ocean.

    PubMed

    West, Nyree J; Lepère, Cécile; Manes, Carmem-Lara de O; Catala, Philippe; Scanlan, David J; Lebaron, Philippe

    2016-01-01

    Distinct distribution patterns of members of the major bacterial clades SAR11, SAR86, and Actinobacteria were observed across a transect from the Marquesas islands through the ultra-oligotrophic South Pacific Gyre into the Chilean upwelling using 16S rRNA gene sequencing and RNA-DNA fingerprinting. Three different Actinobacteria sequence clusters belonging to "Candidatus Actinomarinidae" were localized in the western half of the transect, one was limited to the gyre deep chlorophyll maximum (DCM) and sequences affiliated to the OCS155 clade were unique to the upwelling. The structure of the surface bacterial community was highly correlated with water mass and remained similar across the whole central gyre (1300 nautical miles). The surface hyperoligotrophic gyre was dominated (>70% of all sequences) by highly diverse SAR11 and SAR86 operational taxonomic units and these communities were significantly different from those in the DCM. Analysis of 16S rRNA fingerprints generated from RNA allowed insights into the potential activity of assigned bacterial groups. SAR11 and Prochlorococcus showed the highest potential activity in all water masses except for the upwelling, accounting together for 65% of the total bacterial 16S rRNA in the gyre surface waters in equal proportions whereas the contribution of SAR11 decreased significantly at the DCM. PMID:27014192

  15. Distinct Spatial Patterns of SAR11, SAR86, and Actinobacteria Diversity along a Transect in the Ultra-oligotrophic South Pacific Ocean.

    PubMed

    West, Nyree J; Lepère, Cécile; Manes, Carmem-Lara de O; Catala, Philippe; Scanlan, David J; Lebaron, Philippe

    2016-01-01

    Distinct distribution patterns of members of the major bacterial clades SAR11, SAR86, and Actinobacteria were observed across a transect from the Marquesas islands through the ultra-oligotrophic South Pacific Gyre into the Chilean upwelling using 16S rRNA gene sequencing and RNA-DNA fingerprinting. Three different Actinobacteria sequence clusters belonging to "Candidatus Actinomarinidae" were localized in the western half of the transect, one was limited to the gyre deep chlorophyll maximum (DCM) and sequences affiliated to the OCS155 clade were unique to the upwelling. The structure of the surface bacterial community was highly correlated with water mass and remained similar across the whole central gyre (1300 nautical miles). The surface hyperoligotrophic gyre was dominated (>70% of all sequences) by highly diverse SAR11 and SAR86 operational taxonomic units and these communities were significantly different from those in the DCM. Analysis of 16S rRNA fingerprints generated from RNA allowed insights into the potential activity of assigned bacterial groups. SAR11 and Prochlorococcus showed the highest potential activity in all water masses except for the upwelling, accounting together for 65% of the total bacterial 16S rRNA in the gyre surface waters in equal proportions whereas the contribution of SAR11 decreased significantly at the DCM.

  16. Initial insights into structure-activity relationships of avian defensins.

    PubMed

    Derache, Chrystelle; Meudal, Hervé; Aucagne, Vincent; Mark, Kevin J; Cadène, Martine; Delmas, Agnès F; Lalmanach, Anne-Christine; Landon, Céline

    2012-03-01

    Numerous β-defensins have been identified in birds, and the potential use of these peptides as alternatives to antibiotics has been proposed, in particular to fight antibiotic-resistant and zoonotic bacterial species. Little is known about the mechanism of antibacterial activity of avian β-defensins, and this study was carried out to obtain initial insights into the involvement of structural features or specific residues in the antimicrobial activity of chicken AvBD2. Chicken AvBD2 and its enantiomeric counterpart were chemically synthesized. Peptide elongation and oxidative folding were both optimized. The similar antimicrobial activity measured for both L- and D-proteins clearly indicates that there is no chiral partner. Therefore, the bacterial membrane is in all likelihood the primary target. Moreover, this work indicates that the three-dimensional fold is required for an optimal antimicrobial activity, in particular for gram-positive bacterial strains. The three-dimensional NMR structure of chicken AvBD2 defensin displays the structural three-stranded antiparallel β-sheet characteristic of β-defensins. The surface of the molecule does not display any amphipathic character. In light of this new structure and of the king penguin AvBD103b defensin structure, the consensus sequence of the avian β-defensin family was analyzed. Well conserved residues were highlighted, and the potential strategic role of the lysine 31 residue of AvBD2 was emphasized. The synthetic AvBD2-K31A variant displayed substantial N-terminal structural modifications and a dramatic decrease in activity. Taken together, these results demonstrate the structural as well as the functional role of the critical lysine 31 residue in antimicrobial activity. PMID:22205704

  17. Parallel strategies for SAR processing

    NASA Astrophysics Data System (ADS)

    Segoviano, Jesus A.

    2004-12-01

    This article proposes a series of strategies for improving the computer process of the Synthetic Aperture Radar (SAR) signal treatment, following the three usual lines of action to speed up the execution of any computer program. On the one hand, it is studied the optimization of both, the data structures and the application architecture used on it. On the other hand it is considered a hardware improvement. For the former, they are studied both, the usually employed SAR process data structures, proposing the use of parallel ones and the way the parallelization of the algorithms employed on the process is implemented. Besides, the parallel application architecture classifies processes between fine/coarse grain. These are assigned to individual processors or separated in a division among processors, all of them in their corresponding architectures. For the latter, it is studied the hardware employed on the computer parallel process used in the SAR handling. The improvement here refers to several kinds of platforms in which the SAR process is implemented, shared memory multicomputers, and distributed memory multiprocessors. A comparison between them gives us some guidelines to follow in order to get a maximum throughput with a minimum latency and a maximum effectiveness with a minimum cost, all together with a limited complexness. It is concluded and described, that the approach consisting of the processing of the algorithms in a GNU/Linux environment, together with a Beowulf cluster platform offers, under certain conditions, the best compromise between performance and cost, and promises the major development in the future for the Synthetic Aperture Radar computer power thirsty applications in the next years.

  18. Reflectors for SAR performance testing.

    SciTech Connect

    Doerry, Armin Walter

    2008-01-01

    Synthetic Aperture Radar (SAR) performance testing and estimation is facilitated by observing the system response to known target scene elements. Trihedral corner reflectors and other canonical targets play an important role because their Radar Cross Section (RCS) can be calculated analytically. However, reflector orientation and the proximity of the ground and mounting structures can significantly impact the accuracy and precision with which measurements can be made. These issues are examined in this report.

  19. Representing SAR complex image pixels

    NASA Astrophysics Data System (ADS)

    Doerry, A. W.

    2016-05-01

    Synthetic Aperture Radar (SAR) images are often complex-valued to facilitate specific exploitation modes. Furthermore, these pixel values are typically represented with either real/imaginary (also known as I/Q) values, or as Magnitude/Phase values, with constituent components comprised of integers with limited number of bits. For clutter energy well below full-scale, Magnitude/Phase offers lower quantization noise than I/Q representation. Further improvement can be had with companding of the Magnitude value.

  20. SAR Image Complex Pixel Representations

    SciTech Connect

    Doerry, Armin W.

    2015-03-01

    Complex pixel values for Synthetic Aperture Radar (SAR) images of uniform distributed clutter can be represented as either real/imaginary (also known as I/Q) values, or as Magnitude/Phase values. Generally, these component values are integers with limited number of bits. For clutter energy well below full-scale, Magnitude/Phase offers lower quantization noise than I/Q representation. Further improvement can be had with companding of the Magnitude value.

  1. Bats, civets and the emergence of SARS.

    PubMed

    Wang, L F; Eaton, B T

    2007-01-01

    Severe acute respiratory syndrome (SARS) was the first pandemic transmissible disease of previously unknown aetiology in the twenty-first century. Early epidemiologic investigations suggested an animal origin for SARS-CoV. Virological and serological studies indicated that masked palm civets ( Paguma larvata), together with two other wildlife animals, sampled from a live animal market were infected with SARS-CoV or a closely related virus. Recently, horseshoe bats in the genus Rhinolophus have been identified as natural reservoir of SARS-like coronaviruses. Here, we review studies by different groups demonstrating that SARS-CoV succeeded in spillover from a wildlife reservoir (probably bats) to human population via an intermediate host(s) and that rapid virus evolution played a key role in the adaptation of SARS-CoVs in at least two nonreservoir species within a short period.

  2. Spaceborne SAR Imaging Algorithm for Coherence Optimized.

    PubMed

    Qiu, Zhiwei; Yue, Jianping; Wang, Xueqin; Yue, Shun

    2016-01-01

    This paper proposes SAR imaging algorithm with largest coherence based on the existing SAR imaging algorithm. The basic idea of SAR imaging algorithm in imaging processing is that output signal can have maximum signal-to-noise ratio (SNR) by using the optimal imaging parameters. Traditional imaging algorithm can acquire the best focusing effect, but would bring the decoherence phenomenon in subsequent interference process. Algorithm proposed in this paper is that SAR echo adopts consistent imaging parameters in focusing processing. Although the SNR of the output signal is reduced slightly, their coherence is ensured greatly, and finally the interferogram with high quality is obtained. In this paper, two scenes of Envisat ASAR data in Zhangbei are employed to conduct experiment for this algorithm. Compared with the interferogram from the traditional algorithm, the results show that this algorithm is more suitable for SAR interferometry (InSAR) research and application. PMID:26871446

  3. Spaceborne SAR Imaging Algorithm for Coherence Optimized.

    PubMed

    Qiu, Zhiwei; Yue, Jianping; Wang, Xueqin; Yue, Shun

    2016-01-01

    This paper proposes SAR imaging algorithm with largest coherence based on the existing SAR imaging algorithm. The basic idea of SAR imaging algorithm in imaging processing is that output signal can have maximum signal-to-noise ratio (SNR) by using the optimal imaging parameters. Traditional imaging algorithm can acquire the best focusing effect, but would bring the decoherence phenomenon in subsequent interference process. Algorithm proposed in this paper is that SAR echo adopts consistent imaging parameters in focusing processing. Although the SNR of the output signal is reduced slightly, their coherence is ensured greatly, and finally the interferogram with high quality is obtained. In this paper, two scenes of Envisat ASAR data in Zhangbei are employed to conduct experiment for this algorithm. Compared with the interferogram from the traditional algorithm, the results show that this algorithm is more suitable for SAR interferometry (InSAR) research and application.

  4. Spaceborne SAR Imaging Algorithm for Coherence Optimized

    PubMed Central

    Qiu, Zhiwei; Yue, Jianping; Wang, Xueqin; Yue, Shun

    2016-01-01

    This paper proposes SAR imaging algorithm with largest coherence based on the existing SAR imaging algorithm. The basic idea of SAR imaging algorithm in imaging processing is that output signal can have maximum signal-to-noise ratio (SNR) by using the optimal imaging parameters. Traditional imaging algorithm can acquire the best focusing effect, but would bring the decoherence phenomenon in subsequent interference process. Algorithm proposed in this paper is that SAR echo adopts consistent imaging parameters in focusing processing. Although the SNR of the output signal is reduced slightly, their coherence is ensured greatly, and finally the interferogram with high quality is obtained. In this paper, two scenes of Envisat ASAR data in Zhangbei are employed to conduct experiment for this algorithm. Compared with the interferogram from the traditional algorithm, the results show that this algorithm is more suitable for SAR interferometry (InSAR) research and application. PMID:26871446

  5. Confined aquifer head measurements and storage properties in the San Luis Valley, Colorado, from spaceborne InSAR observations

    NASA Astrophysics Data System (ADS)

    Chen, Jingyi; Knight, Rosemary; Zebker, Howard A.; Schreüder, Willem A.

    2016-05-01

    Interferometric Synthetic Aperture Radar (InSAR), a remote sensing technique for measuring centimeter-level surface deformation, is used to estimate hydraulic head in the confined aquifer of the San Luis Valley (SLV), Colorado. Reconstructing head measurements from InSAR in agricultural regions can be difficult, as InSAR phase data are often decorrelated due to vegetation growth. Analysis of 17 L-band ALOS PALSAR scenes, acquired between January 2007 and March 2011, demonstrates that comprehensive InSAR deformation measurements can be recovered over the vegetated groundwater basin with an improved processing strategy. Local skeletal storage coefficients and time delays between the head change and deformation are estimated through a joint InSAR-well data analysis. InSAR subsidence estimates are transformed to head changes with finer temporal and spatial resolution than is possible using existing well records alone. Both InSAR and well data suggest that little long-term water-storage loss occurred in the SLV over the study period and that inelastic compaction was negligible. The seasonal head variations derived from InSAR are consistent with the existing well data at most locations where confined aquifer pumping activity dominates. Our results demonstrate the advantages of InSAR measurements for basin-wide characterization of aquifer storage properties and groundwater levels over agricultural regions.

  6. InSAR Forensics: Tracing InSAR Scatterers in High Resolution Optical Image

    NASA Astrophysics Data System (ADS)

    Wang, Yuanyuan; Zhu, XiaoXiang

    2015-05-01

    This paper presents a step towards a better interpretation of the scattering mechanism of different objects and their deformation histories in SAR interferometry (InSAR). The proposed technique traces individual SAR scatterer in high resolution optical images where their geometries, materials, and other properties can be better analyzed and classified. And hence scatterers of a same object can be analyzed in group, which brings us to a new level of InSAR deformation monitoring.

  7. Activities and Accomplishments in Various Domains: Relationships with Creative Personality and Creative Motivation in Adolescence

    ERIC Educational Resources Information Center

    Hong, Eunsook; Peng, Yun; O'Neil, Harold F., Jr.

    2014-01-01

    This study examined relationships between five personal traits and adolescents' creative activities and accomplishments in five domains--music, visual arts, creative writing, science, and technology. Participants were 439 tenth graders (220 males and 219 females) in China. The relationships were examined using confirmatory factor analysis.…

  8. Adolescents Online: The Importance of Internet Activity Choices to Salient Relationships

    ERIC Educational Resources Information Center

    Blais, Julie J.; Craig, Wendy M.; Pepler, Debra; Connolly, Jennifer

    2008-01-01

    The purpose of this study was to determine whether using the Internet for different activities affects the quality of close adolescent relationships (i.e., best friendships and romantic relationships). In a one-year longitudinal study of 884 adolescents (Mean age = 15, 46% male), we examined whether visiting chat rooms, using ICQ, using the…

  9. Microstrip antennas for SAR applications

    NASA Technical Reports Server (NTRS)

    Haddad, H. A.

    1983-01-01

    Current and future microstrip antenna technology development for Spaceborne Synthetic Aperture Radars (SAR) are summarized. Some of the electrical and mechanical characteristics of previously and presently developed microstrip SAR antennas are shown. The SEASAT, the SIR-A and presently the SIR-B antennas are all designed for operation at L-band with approximately 22 MHz of bandwidth. The antennas have linear polarization with minimum of 20 dB of polarization purity. Both the SEASAT and SIR-A antennas were designed for a fixed pointing angle of 20.5 deg and 47 deg, respectively. However, the SIR-B has the added feature of mechanical beam steering in elevation (range). With the exception of different mechanical characteristics, it is concluded that present spaceborne SAR antennas have only single frequency and single polarization performance. The lack of large spaceborne antennas operating at the higher degree of fabrication tolerance required for a given performance; and larger feed and radiating element losses.

  10. Does Physical Activity Intensity Moderate Social Cognition and Behavior Relationships?

    ERIC Educational Resources Information Center

    Scott, Felicity; Rhodes, Ryan E.; Downs, Danielle Symons

    2009-01-01

    Objective: Public health messaging about physical activity (PA) sometimes combines moderate and vigorous intensity, but the variance/invariance of the motives for PA by intensity has received scant attention. Thus, the purpose of this study was to examine the beliefs and motivations associated with regular moderate- and vigorous-intensity PA in a…

  11. The Relationship among Faculty Appointments and Scholarly Activities

    ERIC Educational Resources Information Center

    Gonzalez, Lynn Passmore

    2010-01-01

    The mission of higher education and the activities of faculty are often described in terms of teaching, research, and service. Additionally, tenure has been the standard model for employment in American college and universities since 1940. The traditional model of faculty earning tenure through high standards of teaching, research, and service is…

  12. Instructional Transaction Theory: Knowledge Relationships among Processes, Entities, and Activities.

    ERIC Educational Resources Information Center

    Merrill, M. David; And Others

    1993-01-01

    Discussion of instructional transaction theory focuses on knowledge representation in an automated instructional design expert system. A knowledge structure called PEA-Net (processes, entities, and activities) is explained; the refrigeration process is used as an example; text resources and graphic resources are described; and simulations are…

  13. Chirp Scaling Algorithms for SAR Processing

    NASA Technical Reports Server (NTRS)

    Jin, M.; Cheng, T.; Chen, M.

    1993-01-01

    The chirp scaling SAR processing algorithm is both accurate and efficient. Successful implementation requires proper selection of the interval of output samples, which is a function of the chirp interval, signal sampling rate, and signal bandwidth. Analysis indicates that for both airborne and spaceborne SAR applications in the slant range domain a linear chirp scaling is sufficient. To perform nonlinear interpolation process such as to output ground range SAR images, one can use a nonlinear chirp scaling interpolator presented in this paper.

  14. Deriving sea-state parameters using RISAT-1 SAR data

    NASA Astrophysics Data System (ADS)

    Ganguly, Debojyoti; Mishra, Manoj K.; Chauhan, Prakash

    2015-01-01

    A technique has been demonstrated for deriving various sea-wave parameters such as peak wavelength, peak direction, and significant wave height from two-dimensional synthetic aperture radar (SAR) data acquired by Indian active microwave remote-sensing satellite RISAT-1 (Radar Imaging Satellite 1). The significant wave height is obtained using the method of azimuth cutoff wavelength, which is the minimum wavelength that can be imaged in the azimuth direction and results due to the roll-off of the SAR image spectra at higher wave numbers. In the present paper, RISAT-1 SAR fine-resolution scan mode intensity image data are used for deriving various wave parameters at a high spatial resolution of 300 m. The changes in wavelength, wave height, and wave direction of sea waves are studied for a coastal wave system using high-resolution sea-wave spectral information. The SAR-derived coastal wave parameters are then compared with JASON-2 altimeter Geophysical Data Record (GDR) products and The European Center for Medium-Range Weather Forecasts (ECMWF)-modeled values, and are found to be in reasonable agreement.

  15. Remote sensing measurements of thermokarst subsidence using InSAR

    NASA Astrophysics Data System (ADS)

    Liu, L.; Schaefer, K. M.; Chen, A. C.; Gusmeroli, A.; Zebker, H. A.; Zhang, T.

    2015-09-01

    Thawing of ice-rich permafrost followed by surface subsidence results in irregular, depressed landforms known as thermokarst. Many remote sensing studies have identified thermokarst landforms and mapped their changes. However, the intrinsic dynamic thermokarst process of surface subsidence remains a challenge to quantify and is seldom examined using remote sensing methods. In this study we used spaceborne interferometric synthetic aperture radar (InSAR) data to map surface subsidence trends at a thermokarst landform located near Deadhorse on the North Slope of Alaska. A pipeline access road constructed in the 1970s triggered the thawing of the permafrost, causing subsequent expansion of the thermokarst landform. Using Phased Array type L band Synthetic Aperture Radar images acquired by the Advanced Land Observing Satellite-1, our InSAR analysis reveals localized thermokarst subsidence of 2-8 cm/yr between 2006 and 2010, equivalent to an ice volume loss of about 1.2 × 107 m3/yr. Comparisons between InSAR subsidence trends and lidar microtopography suggest a characteristic time of 8 years of thermokarst development. We also quantitatively explain the difficulty, uncertainties, and possible biases in separating thermokarst-induced, irreversible subsidence from cyclic seasonal deformation. Our study illustrates that InSAR is an effective tool for mapping and studying active thermokarst processes and quantifying ice loss.

  16. A fully automated TerraSAR-X based flood service

    NASA Astrophysics Data System (ADS)

    Martinis, Sandro; Kersten, Jens; Twele, André

    2015-06-01

    In this paper, a fully automated processing chain for near real-time flood detection using high resolution TerraSAR-X Synthetic Aperture Radar (SAR) data is presented. The processing chain including SAR data pre-processing, computation and adaption of global auxiliary data, unsupervised initialization of the classification as well as post-classification refinement by using a fuzzy logic-based approach is automatically triggered after satellite data delivery. The dissemination of flood maps resulting from this service is performed through an online service which can be activated on-demand for emergency response purposes (i.e., when a flood situation evolves). The classification methodology is based on previous work of the authors but was substantially refined and extended for robustness and transferability to guarantee high classification accuracy under different environmental conditions and sensor configurations. With respect to accuracy and computational effort, experiments performed on a data set of 175 different TerraSAR-X scenes acquired during flooding all over the world with different sensor configurations confirm the robustness and effectiveness of the proposed flood mapping service. These promising results have been further confirmed by means of an in-depth validation performed for three study sites in Germany, Thailand, and Albania/Montenegro.

  17. Prospective relationships of physical activity with quality of life among colorectal cancer survivors

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Physical activity can enhance quality of life for cancer survivors. However, few longitudinal studies have examined whether physical activity has a sustained effect on improvements in quality of life. The present study aims to examine the relationships between physical activity and quality of life o...

  18. Brief Report: Relationships between Physical Activity and Depressive Symptoms in Adolescent Girls

    ERIC Educational Resources Information Center

    Raudsepp, Lennart; Neissaar, Inga

    2012-01-01

    This study examined the relationships between changes in physical activity and depressive symptoms in adolescent girls. Participants were 277 urban adolescent girls. Physical activity was measured using the 3-Day Physical Activity Recall and depressive symptoms were assessed using questionnaire. Data were collected on three occasions over a 3-year…

  19. The Relationship between Aerobic Capacity and Physical Activity in Blind and Sighted Adolescents.

    ERIC Educational Resources Information Center

    Kobberling, G.; And Others

    1991-01-01

    This study investigated the relationship between habitual physical activity and aerobic capacity in 30 blind and 30 sighted adolescents. Both physical activity and maximal oxygen consumption were significantly higher among the sighted adolescents. A minimum of 30 minutes of daily activity at a minimal oxygen consumption of 8 METs (resting…

  20. Structure-activity relationships for selected fragrance allergens.

    PubMed

    Patlewicz, G Y; Wright, Z M; Basketter, D A; Pease, C K; Lepoittevin, J-P; Arnau, E Giménez

    2002-10-01

    Fragrance substances represent a very diverse group of chemicals, a proportion of them providing not only desirable aroma characteristics, but also being associated with adverse effects, notably the ability to cause allergic reactions in the skin. However, efforts to find substitute materials are hampered by the need to undertake animal testing to evaluate both the presence and the degree of skin sensitization hazard. One potential route to avoid such testing is to understand the relationships between chemical structure and skin sensitization. In the present work we have evaluated two groups of fragrance chemicals, saturated aldehydes (aryl substituted and aliphatic aldehydes) and alpha,beta-unsaturated aldehydes. Data on their skin sensitization potency defined using the local lymph node assay has been evaluated in relation to their physicochemical properties. The initial outcome has been consistent with the concept that alpha,beta-unsaturated aldehydes react largely via Michael addition, whilst the group of saturated aldehydes form Schiff bases with proteins. Simple models of chemical reactivity based on these mechanisms suggest that it may be possible to predict allergenic potency. Accordingly, the evaluation of an additional group of similar aldehydes is now underway to assess the robustness of these models, with some emphasis being based on ensuring a wider spread of chemical reactivity.

  1. A Modular and Configurable Instrument Electronics Architecture for "MiniSAR"- An Advanced Smallsat SAR Instrument

    NASA Astrophysics Data System (ADS)

    Gomez, Jaime; Pastena, Max; Bierens, Laurens

    2013-08-01

    MiniSAR is a Dutch program focused on the development of a commercial smallsat featuring a SAR instrument, led by SSBV as prime contractor. In this paper an Instrument Electronics (IEL) system concept to meet the MiniSAR demands is presented. This system has several specificities wrt similar initiatives in the European space industry, driven by our main requirement: keep it small.

  2. Multibaseline POLInSAR Module for SAR Data Processing and Analysis in RAT (Radar Tools)

    NASA Astrophysics Data System (ADS)

    Neumann, M.; Reiber, A.; Jäger, M.; Guillaso, S.; Hellwich, O.

    2007-03-01

    The combination of SAR Polarimetry (POL- SAR) and SAR Interferometry (InSAR) into Polarimetric SAR Interferometry (POLInSAR) has shown great potential for information extraction from SAR data. Applications have been developed and validated theoretically for POLInSAR data. But due to different reasons these methods are difficult to apply on real data. The SAR observables have to be increased, and the utilization of multiple baselines (MB) is one of the possibilities. There will be a need for data processing and analysis methods and tools to work effectively with multibaseline datasets. In this paper we present the newly developed module for the software package RAT (Radar Tools), which provides these abilities for multibaseline polarimetric interferometric SAR data. It is the first available package of tools for working with MBSAR data. RAT (RAdar Tools [1], [2]) is a collection of tools for advanced image processing of SAR remote sensing data, originally started as a student's project and currently under further development at the Department of Computer Vision and Remote Sensing of the Technical University of Berlin. It is programmed in IDL (Interactive Data Language) and uses IDL widgets as graphical user interface. The purpose of this paper is also to give an overview of the current development status of RAT through addressing the newest structural improvements in RAT as well as recently implemented methods for SAR polarimetry and interferometry.

  3. Relationships Between Vocal Activity and Perception of Communicators in Small Group Interaction

    ERIC Educational Resources Information Center

    Daley, John A.; And Others

    1977-01-01

    Discusses a study designed to investigate the relationships between vocal activity level and interpersonal attraction, perceived credibility, perceived homophily or interpersonal similarity and perceived power or ability to influence. (MH)

  4. MOLECULAR INTERACTION POTENTIALS FOR THE DEVELOPMENT OF STRUCTURE-ACTIVITY RELATIONSHIPS

    EPA Science Inventory

    Abstract
    One reasonable approach to the analysis of the relationships between molecular structure and toxic activity is through the investigation of the forces and intermolecular interactions responsible for chemical toxicity. The interaction between the xenobiotic and the bio...

  5. PREDICTING TOXICOLOGICAL ENDPOINTS OF CHEMICALS USING QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIPS (QSARS)

    EPA Science Inventory

    Quantitative structure-activity relationships (QSARs) are being developed to predict the toxicological endpoints for untested chemicals similar in structure to chemicals that have known experimental toxicological data. Based on a very large number of predetermined descriptors, a...

  6. Quantitative Structure--Activity Relationship Modeling of Rat Acute Toxicity by Oral Exposure

    EPA Science Inventory

    Background: Few Quantitative Structure-Activity Relationship (QSAR) studies have successfully modeled large, diverse rodent toxicity endpoints. Objective: In this study, a combinatorial QSAR approach has been employed for the creation of robust and predictive models of acute toxi...

  7. SAR investigations of glaciers in northwestern North America

    NASA Technical Reports Server (NTRS)

    Lingle, Craig S.; Harrison, William D.

    1995-01-01

    The objective of this project was to investigate the utility of satellite synthetic aperture radar (SAR) imagery for measurement of geophysical parameters on Alaskan glaciers relevant to their mass balance and dynamics, including: (1) the positions of firn lines (late-summer snow lines); (2) surface velocities on fast-flowing (surging) glaciers, and also on slower steady-flow glaciers; and (3) the positions and changes in the positions of glacier termini. Preliminary studies of topography and glacier surface velocity with SAR interferometry have also been carried out. This project was motivated by the relationships of multi-year to decadal changes in glacier geometry to changing climate, and the probable significant contribution of Alaskan glaciers to rising sea level.

  8. First Image Products from EcoSAR - Osa Peninsula, Costa Rica

    NASA Technical Reports Server (NTRS)

    Osmanoglu, Batuhan; Lee, SeungKuk; Rincon, Rafael; Fatuyinbo, Lola; Bollian, Tobias; Ranson, Jon

    2016-01-01

    Designed especially for forest ecosystem studies, EcoSAR employs state-of-the-art digital beamforming technology to generate wide-swath, high-resolution imagery. EcoSARs dual antenna single-pass imaging capability eliminates temporal decorrelation from polarimetric and interferometric analysis, increasing the signal strength and simplifying models used to invert forest structure parameters. Antennae are physically separated by 25 meters providing single pass interferometry. In this mode the radar is most sensitive to topography. With 32 active transmit and receive channels, EcoSARs digital beamforming is an order of magnitude more versatile than the digital beamforming employed on the upcoming NISAR mission. EcoSARs long wavelength (P-band, 435 MHz, 69 cm) measurements can be used to simulate data products for ESAs future BIOMASS mission, allowing scientists to develop algorithms before the launch of the satellite. EcoSAR can also be deployed to collect much needed data where BIOMASS satellite wont be allowed to collect data (North America, Europe and Arctic), filling in the gaps to keep a watchful eye on the global carbon cycle. EcoSAR can play a vital role in monitoring, reporting and verification schemes of internationals programs such as UN-REDD (United Nations Reducing Emissions from Deforestation and Degradation) benefiting global society. EcoSAR was developed and flown with support from NASA Earth Sciences Technology Offices Instrument Incubator Program.

  9. Relationship of gonadal activity and chemotherapy-induced gonadal damage

    SciTech Connect

    Rivkees, S.A.; Crawford, J.D.

    1988-04-08

    The authors tested the hypothesis that chemotherapy-induced gonadal damage is proportional to the degree of gonadal activity during treatment. Thirty studies that evaluated gonadal function after cyclophosphamide therapy for renal disease or combination chemotherapy for Hodgkin's disease or acute lymphocytic leukemia provided data for analysis. Data were stratified according to sex, illness, chemotherapeutic regimen and dose, and pubertal stage at the time of treatment. Chemotherapy-induced damage was more likely to occur in patients who were treated when sexually mature compared with those who were treated when prepubertal. Males were significantly more frequently affected than females when treated for renal disease of Hodgkin's disease. Chemotherapy-induced damage was also more likely to occur when patients were treated with large doses of alkylating agents. These data suggest that chemotherapy-induced damage is proportional to gonadal activity. Further efforts are needed to test whether induced gonadal quiescence during chemotherapy will reduce the strikingly high incidence of gonadal failure following chemotherapy.

  10. Bistatic SAR: Signal Processing and Image Formation.

    SciTech Connect

    Wahl, Daniel E.; Yocky, David A.

    2014-10-01

    This report describes the significant processing steps that were used to take the raw recorded digitized signals from the bistatic synthetic aperture RADAR (SAR) hardware built for the NCNS Bistatic SAR project to a final bistatic SAR image. In general, the process steps herein are applicable to bistatic SAR signals that include the direct-path signal and the reflected signal. The steps include preprocessing steps, data extraction to for a phase history, and finally, image format. Various plots and values will be shown at most steps to illustrate the processing for a bistatic COSMO SkyMed collection gathered on June 10, 2013 on Kirtland Air Force Base, New Mexico.

  11. [SARS-CoV infection and pregnancy].

    PubMed

    Ksiezakowska, Kinga; Laszczyk, Magdalena; Wilczyński, Jan; Nowakowska, Dorota

    2008-01-01

    SARS is a highly contagious infection, caused by new coronavirus SARS-CoV. Immunopathological mechanisms responsible for the reaction to SARS-CoV infection have not yet been fully elucidated. Cytokine profile of SARS patients showed marked elevation of Th1 cytokine, interferon gamma, inflammatory cytokines for at least 2 weeks after the onset of the disease. The clinical manifestation of SARS in patients has been of varied nature. Fever of more then 38 degrees C, lasting more then 24 hours, is the most frequently encountered symptom. Other symptoms are non specific and they may include: sore throat, myalgia and nausea. The results of the radiological investigation may appear normal. Infants born to pregnant women with SARS did not appear to have acquired the infection through vertical transmission. However, direct contact with the maternal body fluid which contained SARS-CoV, has put the infants in great danger of perinatal infection. Ribavirin and corticosteroids are usually suggested for the treatment of SARS. However, the ribavirin therapy increases the risk of teratogenic effects in newborns of pregnant women with SARS. Therefore, the usage of this drug is not recommended during pregnancy and lactation. PMID:18510050

  12. Time-activity relationships to VOC personal exposure factors

    NASA Astrophysics Data System (ADS)

    Edwards, Rufus D.; Schweizer, Christian; Llacqua, Vito; Lai, Hak Kan; Jantunen, Matti; Bayer-Oglesby, Lucy; Künzli, Nino

    Social and demographic factors have been found to play a significant role in differences between time-activity patterns of population subgroups. Since time-activity patterns largely influence personal exposure to compounds as individuals move across microenvironments, exposure subgroups within the population may be defined by factors that influence daily activity patterns. Socio-demographic and environmental factors that define time-activity subgroups also define quantifiable differences in VOC personal exposures to different sources and individual compounds in the Expolis study. Significant differences in exposures to traffic-related compounds ethylbenzene, m- and p-xylene and o-xylene were observed in relation to gender, number of children and living alone. Categorization of exposures further indicated time exposed to traffic at work and time in a car as important determinants. Increased exposures to decane, nonane and undecane were observed for males, housewives and self-employed. Categorization of exposures indicated exposure subgroups related to workshop use and living downtown. Higher exposures to 3-carene and α-pinene commonly found in household cleaning products and fragrances were associated with more children, while exposures to traffic compounds ethylbenzene, m- and p-xylene and o-xylene were reduced with more children. Considerable unexplained variation remained in categorization of exposures associated with home product use and fragrances, due to individual behavior and product choice. More targeted data collection methods in VOC exposure studies for these sources should be used. Living alone was associated with decreased exposures to 2-methyl-1-propanol and 1-butanol, and traffic-related compounds. Identification of these subgroups may help to reduce the large amount of unexplained variation in VOC exposure studies. Further they may help in assessing impacts of urban planning that result in changes in behavior of individuals, resulting in shifts in

  13. Structure-Activity Relationship of Chlorotoxin-Like Peptides

    PubMed Central

    Ali, Syed Abid; Alam, Mehtab; Abbasi, Atiya; Undheim, Eivind A. B.; Fry, Bryan Grieg; Kalbacher, Hubert; Voelter, Wolfgang

    2016-01-01

    Animal venom (e.g., scorpion) is a rich source of various protein and peptide toxins with diverse physio-/pharmaco-logical activities, which generally exert their action via target-specific modulation of different ion channel functions. Scorpion venoms are among the most widely-known source of peptidyl neurotoxins used for callipering different ion channels, such as; Na+, K+, Ca+, Cl−, etc. A new peptide of the chlorotoxin family (i.e., Bs-Tx7) has been isolated, sequenced and synthesized from scorpion Buthus sindicus (family Buthidae) venom. This peptide demonstrates 66% with chlorotoxin (ClTx) and 82% with CFTR channel inhibitor (GaTx1) sequence identities reported from Leiurus quinquestriatus hebraeus venom. The toxin has a molecular mass of 3821 Da and possesses four intra-chain disulphide bonds. Amino acid sequence analysis of Bs-Tx7 revealed the presence of a scissile peptide bond (i.e., Gly-Ile) for human MMP2, whose activity is increased in the case of tumour malignancy. The effect of hMMP2 on Bs-Tx7, or vice versa, observed using the FRET peptide substrate with methoxycoumarin (Mca)/dinitrophenyl (Dnp) as fluorophore/quencher, designed and synthesized to obtain the lowest Km value for this substrate, showed approximately a 60% increase in the activity of hMMP2 upon incubation of Bs-Tx7 with the enzyme at a micromolar concentration (4 µM), indicating the importance of this toxin in diseases associated with decreased MMP2 activity. PMID:26848686

  14. Structure-Activity Relationship of Chlorotoxin-Like Peptides.

    PubMed

    Ali, Syed Abid; Alam, Mehtab; Abbasi, Atiya; Undheim, Eivind A B; Fry, Bryan Grieg; Kalbacher, Hubert; Voelter, Wolfgang

    2016-02-02

    Animal venom (e.g., scorpion) is a rich source of various protein and peptide toxins with diverse physio-/pharmaco-logical activities, which generally exert their action via target-specific modulation of different ion channel functions. Scorpion venoms are among the most widely-known source of peptidyl neurotoxins used for callipering different ion channels, such as; Na⁺, K⁺, Ca⁺, Cl(-), etc. A new peptide of the chlorotoxin family (i.e., Bs-Tx7) has been isolated, sequenced and synthesized from scorpion Buthus sindicus (family Buthidae) venom. This peptide demonstrates 66% with chlorotoxin (ClTx) and 82% with CFTR channel inhibitor (GaTx1) sequence identities reported from Leiurus quinquestriatus hebraeus venom. The toxin has a molecular mass of 3821 Da and possesses four intra-chain disulphide bonds. Amino acid sequence analysis of Bs-Tx7 revealed the presence of a scissile peptide bond (i.e., Gly-Ile) for human MMP2, whose activity is increased in the case of tumour malignancy. The effect of hMMP2 on Bs-Tx7, or vice versa, observed using the FRET peptide substrate with methoxycoumarin (Mca)/dinitrophenyl (Dnp) as fluorophore/quencher, designed and synthesized to obtain the lowest Km value for this substrate, showed approximately a 60% increase in the activity of hMMP2 upon incubation of Bs-Tx7 with the enzyme at a micromolar concentration (4 µM), indicating the importance of this toxin in diseases associated with decreased MMP2 activity.

  15. Structure-activity relationship of buffalo antibacterial hepcidin analogs.

    PubMed

    Chanu, Khangembam Victoria; Kumar, Ashok; Kumar, Satish

    2011-10-01

    Hepcidin is an anti-microbial peptide expressed predominantly in the liver of many species. Based on the amino acid sequence deduced from buffalo (Bubalus bubalis) hepcidin cDNA (Accession no. EU399814), six peptides Hepc(1-25), Hepc(6-25), Hepc(7-25), Hepc(9-25), Hepc(11-25) and Hepc(15-25) were synthesized using solid-phase fluorenylmethoxycarbonyl (Fmoc) chemistry. CD spectroscopy revealed different spectra of the peptides in different solvents and in all the cases beta-structure was found to be dominant with less alpha-helix as predicted. Quantitation of secondary structure indicated the highest beta-structure for all the six peptides in SDS solution, when used as mimetic for membrane-like environment. The CD spectra of all the peptides taken in water showed that degree of randomness decreased with increase in chain length of the peptide. Out of the six peptides, only Hepc(1-25), Hepc(6-25) and Hepc(7-25) showed antibacterial activity against Staphylococcus aureus (Gram-positive bacteria). The peptides did not show any sensitivity toward E. coli (Gram-negative bacteria). Minimum inhibitory concentration (MIC) showed the lowest value for Hepc(7-25) as an antibacterial agent, followed by Hepc(6-25) and Hepc(1-25). The peptides Hepc(9-25), Hepc(11-25) and Hepc(15-25) with more random structure did not show any antimicrobial activity The study demonstrated that 5 amino acids at N-terminal in buffalo hepcidin can be truncated without loss of antimicrobial activity and further reduction of length of the analog from 20 to 19 amino acids resulted increase in the activity because of increase in beta-structure of the peptide shown by CD spectroscopy.

  16. Entrepreneurship education: relationship between education and entrepreneurial activity.

    PubMed

    Raposo, Mário; do Paço, Arminda

    2011-08-01

    The importance of entrepreneurial activity for the economic growth of countries is now well established. The relevant literature suggests important links between education, venture creation and entrepreneurial performance, as well as between entrepreneurial education and entrepreneurial activity. The primary purpose of this paper is to provide some insights about entrepreneurship education. The meaning of entrepreneurship education is explained, and the significant increase of these educational programmes is highlighted. Literature has been suggesting that the most suitable indicator to evaluate the results of entrepreneurship education is the rate of new business creation. However, some studies indicate that the results of such programmes are not immediate. Therefore, many researchers try to understand the precursors of venture creation, concluding that is necessary to carry out longitudinal studies. Based on an overview of the research published about the existing linkage of entrepreneurship education and entrepreneurial activity, the main topics studied by different academics are addressed. For the authors, the positive impact of entrepreneurship education puts a double challenge on governments in the future: the increased need of financial funds to support entrepreneurship education and the choice of the correct educational programme.

  17. Muscular activity and its relationship to biomechanics and human performance

    NASA Technical Reports Server (NTRS)

    Ariel, Gideon

    1994-01-01

    The purpose of this manuscript is to address the issue of muscular activity, human motion, fitness, and exercise. Human activity is reviewed from the historical perspective as well as from the basics of muscular contraction, nervous system controls, mechanics, and biomechanical considerations. In addition, attention has been given to some of the principles involved in developing muscular adaptations through strength development. Brief descriptions and findings from a few studies are included. These experiments were conducted in order to investigate muscular adaptation to various exercise regimens. Different theories of strength development were studied and correlated to daily human movements. All measurement tools used represent state of the art exercise equipment and movement analysis. The information presented here is only a small attempt to understand the effects of exercise and conditioning on Earth with the objective of leading to greater knowledge concerning human responses during spaceflight. What makes life from nonliving objects is movement which is generated and controlled by biochemical substances. In mammals. the controlled activators are skeletal muscles and this muscular action is an integral process composed of mechanical, chemical, and neurological processes resulting in voluntary and involuntary motions. The scope of this discussion is limited to voluntary motion.

  18. Definitive Metabolite Identification Coupled with Automated Ligand Identification System (ALIS) Technology: A Novel Approach to Uncover Structure-Activity Relationships and Guide Drug Design in a Factor IXa Inhibitor Program.

    PubMed

    Zhang, Ting; Liu, Yong; Yang, Xianshu; Martin, Gary E; Yao, Huifang; Shang, Jackie; Bugianesi, Randal M; Ellsworth, Kenneth P; Sonatore, Lisa M; Nizner, Peter; Sherer, Edward C; Hill, Susan E; Knemeyer, Ian W; Geissler, Wayne M; Dandliker, Peter J; Helmy, Roy; Wood, Harold B

    2016-03-10

    A potent and selective Factor IXa (FIXa) inhibitor was subjected to a series of liver microsomal incubations, which generated a number of metabolites. Using automated ligand identification system-affinity selection (ALIS-AS) methodology, metabolites in the incubation mixture were prioritized by their binding affinities to the FIXa protein. Microgram quantities of the metabolites of interest were then isolated through microisolation analytical capabilities, and structurally characterized using MicroCryoProbe heteronuclear 2D NMR techniques. The isolated metabolites recovered from the NMR experiments were then submitted directly to an in vitro FIXa enzymatic assay. The order of the metabolites' binding affinity to the Factor IXa protein from the ALIS assay was completely consistent with the enzymatic assay results. This work showcases an innovative and efficient approach to uncover structure-activity relationships (SARs) and guide drug design via microisolation-structural characterization and ALIS capabilities. PMID:26871940

  19. Forward Modeling of the Coumarin Antifungals; SPR/SAR Based Perspective

    PubMed Central

    Soltani, Saeed; Dianat, Shima; Sardari, Soroush

    2009-01-01

    Although, coumarins are a group of compounds which are naturally found in some plants, they can be synthetically produced as well. Because of their diverse derivatives, origin and properties most of them can be used for medicinal purposes. For example, they can be used against fungal diseases or in studying structure and biological properties of antifungal agents to discover new compounds with the similar activity. A Structure Property/Activity Relationship (SAR) can be utilized in prediction of biological activity of desired molecules. In order to represent a relationship between the physicochemical properties of coumarin compounds and their biological activities, 68 coumarins and coumarin derivatives with already reported antifungal activities were selected and eleven attributes were generated. The descriptors were used to perform artificial neural network (ANN) and to build a model for predicting effectiveness of the new ones. The correlation coefficient between the experimental and the predicted MIC values pertaining to all the coumarins was 0.984. This study paves the way for further researches about antifungal activity of coumarins, and offers a powerful tool in modeling and prediction of their bioactivities. PMID:23407575

  20. Pharmacological activities in thermal proteins: relationships in molecular evolution

    NASA Technical Reports Server (NTRS)

    Fox, S. W.; Hefti, F.; Hartikka, J.; Junard, E.; Przybylski, A. T.; Vaughan, G.

    1987-01-01

    The model of protobiological events that has been presented in these pages has increasing relevance to pharmacological research. The thermal proteins that function as key substances in the proteinoid theory have recently been found to prolong the survival of rat forebrain neurons in culture and to stimulate the growth of neurites. A search for such activity in thermal proteins added to cultures of modern neurons was suggested by the fact that some of the microspheres assembled from proteinoids rich in hydrophobic amino acids themselves generate fibrous outgrowths.

  1. Pharmacological activities in thermal proteins: relationships in molecular evolution.

    PubMed

    Fox, S W; Hefti, F; Hartikka, J; Junard, E; Przybylski, A T; Vaughan, G

    1987-01-01

    The model of protobiological events that has been presented in these pages has increasing relevance to pharmacological research. The thermal proteins that function as key substances in the proteinoid theory have recently been found to prolong the survival of rat forebrain neurons in culture and to stimulate the growth of neurites. A search for such activity in thermal proteins added to cultures of modern neurons was suggested by the fact that some of the microspheres assembled from proteinoids rich in hydrophobic amino acids themselves generate fibrous outgrowths.

  2. Creep Spatial and Temporal Evolution Revealed by InSAR Time Series Analysis

    NASA Astrophysics Data System (ADS)

    Jolivet, Romain; Lasserre, Cecile; Doin, Marie-Pierre; Peltzer, Gilles; Sun, Jianbao; Rong, Dailu; Shen, Zhengkang; Xu, Xiwei

    2013-01-01

    We characterize the present-day behaviour of the left-lateral Haiyuan fault system (Gansu, China), from InSAR data. The 260 km-long central segment of this fault is known as the "Tianzhu Seismic Gap" (Gaudemer et al. 1995), in between two segments that ruptured during the 1920 and 1927 earthquakes. Cavalié et al. (2008) has shown that shallow creep may occur near the junction between the "Tianzhu gap" and the 1920 rupture trace, from sparse ERS data stacking. We further investigate along-strike and temporal variations of strain accumulation across the Haiyuan fault. We first produce mean LOS velocity maps, revealing a variable creep-rate between 0 and 20 km and a constant slip-rate at depth (Jolivet et al. 2012). We then analyze temporal variations of the shallow creep distribution, and explore the relationships between the micro- and moderate seismic activity, the fault geometry and the surface creep rate.

  3. Immunomodulatory assays to study structure-activity relationships of thalidomide.

    PubMed

    Shannon, E J; Morales, M J; Sandoval, F

    1997-01-01

    Thalidomide, which has a long history of tragedy because of its ability to cause severe birth defects, is very effective in alleviating erythema nodosum leprosum in leprosy patients and aphthous ulcers in AIDS patients. The causes of these inflammatory diseases and the mechanism by which thalidomide diminishes them are unknown. It has been suggested that modulation of the immune response plays an important role. We found that thalidomide exerts immunomodulatory activity in three bioassays. It suppresses an IgM plaque forming cell response in mice injected with sheep erythrocytes: it inhibits TNF-alpha production by LPS stimulated human mononuclear cells: and it enhances IL-2 production by Con-A stimulated human mononuclear cells. We employed these bioassays to compare the activity of 15 analogs of thalidomide with thalidomide itself. Eight of the compounds were derivatives of the glutarimide moiety of thalidomide and the others were phthalimide or derivatives of the phthalimide moiety of thalidomide. N-hydroxyphthalimide, a simple derivative of phthalimide, was more effective than thalidomide and was also the most effective of the compounds assayed in suppressing the IgM plaque and TNF-alpha responses, but it did not enhance the IL-2 response, instead, it significantly suppressed it.

  4. Inhibition of 1-Deoxy-D-Xylulose-5-Phosphate Reductoisomerase by Lipophilic Phosphonates: SAR, QSAR and Crystallographic Studies

    PubMed Central

    Deng, Lisheng; Diao, Jiasheng; Chen, Pinhong; Pujari, Venugopal; Yao, Yuan; Cheng, Gang; Crick, Dean C.; Venkataram Prasad, B. V.; Song, Yongcheng

    2013-01-01

    1-Deoxy-D-xylulose-5-phosphate reductoisomerase (DXR) is a novel target for developing new antibacterial (including anti-tuberculosis) and antimalaria drugs. 41 lipophilic phosphonates, representing a new class of DXR inhibitors, were synthesized, among which 5-phenylpyridin-2-ylmethylphosphonic acid possesses the most activity against E. coli DXR (EcDXR) with a Ki of 420 nM. Structure activity relationships (SAR) are discussed, which can be rationalized using our EcDXR:inhibitor structures, and a predictive quantitative SAR (QSAR) model is also developed. Since inhibition studies of DXR from Mycobacterium tuberculosis (MtDXR) have not been well performed, 48 EcDXR inhibitors with a broad chemical diversity were found, however, to generally exhibit considerably reduced activity against MtDXR. The crystal structure of a MtDXR:inhibitor complex reveals the flexible loop containing the residues 198–208 has no strong interactions with the 3,4-dichlorophenyl group of the inhibitor, representing a structural basis for the reduced activity. Overall, these results provide implications in the future design and development of potent DXR inhibitors. PMID:21561155

  5. Beyond affinity: enthalpy-entropy factorization unravels complexity of a flat structure-activity relationship for inhibition of a tRNA-modifying enzyme.

    PubMed

    Neeb, Manuel; Betz, Michael; Heine, Andreas; Barandun, Luzi Jakob; Hohn, Christoph; Diederich, François; Klebe, Gerhard

    2014-07-10

    Lead optimization focuses on binding-affinity improvement. If a flat structure-activity relationship is detected, usually optimization strategies are abolished as unattractive. Nonetheless, as affinity is composed of an enthalpic and entropic contribution, factorization of both can unravel the complexity of a flat, on first sight tedious SAR. In such cases, the binding free energy of different ligands can be rather similar, but it can factorize into enthalpy and entropy distinctly. We investigated the thermodynamic signature of two classes of lin-benzopurines binding to tRNA-guanine transglycosylase. While the differences are hardly visible in the free energy, they involve striking enthalpic and entropic changes. Analyzing thermodynamics along with structural features revealed that one ligand set binds to the protein without inducing significant changes compared to the apo structure; however, the second series provokes complex adaptation, leading to a conformation similar to the substrate-bound state. In the latter state, a cross-talk between two pockets is suggested.

  6. Structure-activity relationships of 2-aminothiazoles effective against Mycobacterium tuberculosis

    PubMed Central

    Meissner, Anja; Boshoff, Helena I.; Vasan, Mahalakshmi; Duckworth, Benjamin P.; Barry, Clifton E.; Aldrich, Courtney C.

    2013-01-01

    A series of 2-aminothiazoles was synthesized based on a HTS scaffold from a whole-cell screen against Mycobacterium tuberculosis (Mtb). The SAR shows the central thiazole moiety and the 2-pyridyl moiety at C-4 of the thiazole are intolerant to modification. However, the N-2 position of the aminothiazole exhibits high flexibility and we successfully improved the antitubercular activity of the initial hit by more than 128-fold through introduction of substituted benzoyl groups at this position. N-(3-Chlorobenzoyl)-4-(2-pyridinyl)-1,3-thiazol-2-amine (55) emerged as one of the most promising analogues with a MIC of 0.024 μM or 0.008 μg/mL in 7H9 media and therapeutic index of nearly ~300. However, 55 is rapidly metabolized by human liver microsomes (t1/2 = 28 min) with metabolism occurring at the invariant aminothiazole moiety and Mtb develops spontaneous resistance with a high frequency of ~10−5. PMID:24075144

  7. Design and synthesis of chalcone derivatives as potent tyrosinase inhibitors and their structural activity relationship

    NASA Astrophysics Data System (ADS)

    Akhtar, Muhammad Nadeem; Sakeh, Nurshafika M.; Zareen, Seema; Gul, Sana; Lo, Kong Mun; Ul-Haq, Zaheer; Shah, Syed Adnan Ali; Ahmad, Syahida

    2015-04-01

    Browning of fruits and vegetables is a serious issue in the food industry, as it damages the organoleptic properties of the final products. Overproduction of melanin causes aesthetic problems such as melisma, freckles and lentigo. In this study, a series of chalcones (1-10) have been synthesized and examined for their tryrosinase inhibitory activity. The results showed that flavokawain B (1), flavokawain A (2) and compound 3 were found to be potential tyrosinase inhibitors, indicating IC50 14.20-14.38 μM values. This demonstrates that 4-substituted phenolic compound especially at ring A exhibited significant tyrosinase inhibition. Additionally, molecular docking results showed a strong binding affinity for compounds 1-3 through chelation between copper metal and ligands. The detailed molecular docking and SARs studies correlate well with the tyrosinase inhibition studies in vitro. The structures of these compounds were elucidated by the 1D and 2D NMR spectroscopy, mass spectrometry and single X-ray crystallographic techniques. These findings could lead to design and discover of new tyrosinase inhibitors to control the melanine overproduction and overcome the economic loss of food industry.

  8. Identification and Structure-Activity Relationships of Diarylhydrazides as Novel Potent and Selective Human Enterovirus Inhibitors.

    PubMed

    Han, Xin; Sun, Ningyuan; Wu, Haoming; Guo, Deyin; Tien, Po; Dong, Chune; Wu, Shuwen; Zhou, Hai-Bing

    2016-03-10

    Enterovirus 71 (EV71) plays an important role in hand-foot-and-mouth disease. In this study, a series of diarylhydrazide analogues was synthesized, and the systematic exploration of SAR led to potent enterovirus inhibitors, of which compound 15 exhibits significant improvements in inhibition potency with an EC50 value of 0.02 μM against EV71. It is very interesting that this class of diarylhydrazides exhibits activities against a series of human enteroviruses at the picomolar level, including EV71 and Coxsackieviruses B1 (CVB1), CVB2, CVB3, CVB4, CVB5, and CVB6 (EC50 as low as 0.5 nM). Compared with the reference antienterovirus drug 1 (enviroxime) and known inhibitor 5 (WIN 51711), the four highly selective compounds 15, 27, 41 and 47 inhibited EV71 replication with EC50 values of 0.17-0.02 μM and SI values in a range of 978.4-12338. A preliminary mechanistic study indicated that VP1 might be the target site for this type of compound.

  9. A snow wetness retrieval algorithm for SAR

    NASA Technical Reports Server (NTRS)

    Shi, Jian-Cheng; Dozier, Jeff

    1992-01-01

    The objectives of this study are: (1) to evaluate the backscattering signals response to snow wetness; and (2) to develop an algorithm for snow wetness measurement using C-band polarimetric synthetic aperture radar (SAR). In hydrological investigations, modeling and forecasting of snowmelt runoff requires information about snowpack properties and their spatial variability. In particular, timely measurement of snow parameters is needed for operational hydrology. The liquid water content of snowpack is one of the important parameters. Active microwave sensors are highly sensitive to liquid water in the snowpack because of the large dielectric contrast between ice and water in the microwave spectrum. They are not affected by weather and have a spatial resolution compatible with the topographic variation in alpine regions. However, a quantitative algorithm for retrieval snow wetness has not yet been developed.

  10. Mapping ground surface deformation using temporarily coherent point SAR interferometry: Application to Los Angeles Basin

    USGS Publications Warehouse

    Zhang, L.; Lu, Zhiming; Ding, X.; Jung, H.-S.; Feng, G.; Lee, C.-W.

    2012-01-01

    Multi-temporal interferometric synthetic aperture radar (InSAR) is an effective tool to detect long-term seismotectonic motions by reducing the atmospheric artifacts, thereby providing more precise deformation signal. The commonly used approaches such as persistent scatterer InSAR (PSInSAR) and small baseline subset (SBAS) algorithms need to resolve the phase ambiguities in interferogram stacks either by searching a predefined solution space or by sparse phase unwrapping methods; however the efficiency and the success of phase unwrapping cannot be guaranteed. We present here an alternative approach - temporarily coherent point (TCP) InSAR (TCPInSAR) - to estimate the long term deformation rate without the need of phase unwrapping. The proposed approach has a series of innovations including TCP identification, TCP network and TCP least squares estimator. We apply the proposed method to the Los Angeles Basin in southern California where structurally active faults are believed capable of generating damaging earthquakes. The analysis is based on 55 interferograms from 32 ERS-1/2 images acquired during Oct. 1995 and Dec. 2000. To evaluate the performance of TCPInSAR on a small set of observations, a test with half of interferometric pairs is also performed. The retrieved TCPInSAR measurements have been validated by a comparison with GPS observations from Southern California Integrated GPS Network. Our result presents a similar deformation pattern as shown in past InSAR studies but with a smaller average standard deviation (4.6. mm) compared with GPS observations, indicating that TCPInSAR is a promising alternative for efficiently mapping ground deformation even from a relatively smaller set of interferograms. ?? 2011.

  11. Molecular recognition of CYP26A1 binding pockets and structure-activity relationship studies for design of potent and selective retinoic acid metabolism blocking agents.

    PubMed

    Sun, Bin; Song, Shuai; Hao, Chen-Zhou; Huang, Wan-Xu; Liu, Chun-Chi; Xie, Hong-Lei; Lin, Bin; Cheng, Mao-Sheng; Zhao, Dong-Mei

    2015-03-01

    All-trans-retinoic acid (ATRA), the biologically most active metabolite of vitamin A, plays a major role in the regulation of cellular differentiation and proliferation, and it is also an important pharmacological agent particularly used in the treatment of cancer, skin, neurodegenerative and autoimmune diseases. However, ATRA is very easy to be metabolized into 4-hydroxyl-RA in vivo by CYP26A1, an inducible cytochrome P450 enzyme, eventually into more polar metabolites. Therefore, it is vital to develop specific retinoic acid metabolism blocking agents (RAMBAs) to inhibit the metabolic enzyme CYP26A1 in the treatment of relevant diseases aforementioned. In this study, CYP26A1 and its interactions with retinoic acid-competitive metabolism blocking agents were investigated by a combined ligand- and structure-based approach. First, since the crystal structure of CYP26A1 protein has not been determined, we constructed the 3D structure of CYP26A1 using homology modeling. In order to achieve a deeper insight into the mode of action of RAMBAs in the active site, the molecular superimposition model and the common feature pharmacophore model were constructed, and molecular docking was performed. The molecular superimposition model is composed of three features: the main chain groups, side chain groups, and azole groups. The common feature pharmacophore model consists of five chemical features: four hydrophobic groups and one hydrogen acceptor (HHHHA). The results of molecular docking show that the characteristic groups of RAMBAs were mapped into three different active pockets, respectively. A structure-activity relationship (SAR) was obtained by a combination of the molecular superimposition and docking results with the pharmacophore model. This study gives more insight into the interaction model inside the CYP26A1 active site and provides guidance for the design of more potent and possibly more selective RAMBAs. PMID:25541526

  12. Molecular recognition of CYP26A1 binding pockets and structure-activity relationship studies for design of potent and selective retinoic acid metabolism blocking agents.

    PubMed

    Sun, Bin; Song, Shuai; Hao, Chen-Zhou; Huang, Wan-Xu; Liu, Chun-Chi; Xie, Hong-Lei; Lin, Bin; Cheng, Mao-Sheng; Zhao, Dong-Mei

    2015-03-01

    All-trans-retinoic acid (ATRA), the biologically most active metabolite of vitamin A, plays a major role in the regulation of cellular differentiation and proliferation, and it is also an important pharmacological agent particularly used in the treatment of cancer, skin, neurodegenerative and autoimmune diseases. However, ATRA is very easy to be metabolized into 4-hydroxyl-RA in vivo by CYP26A1, an inducible cytochrome P450 enzyme, eventually into more polar metabolites. Therefore, it is vital to develop specific retinoic acid metabolism blocking agents (RAMBAs) to inhibit the metabolic enzyme CYP26A1 in the treatment of relevant diseases aforementioned. In this study, CYP26A1 and its interactions with retinoic acid-competitive metabolism blocking agents were investigated by a combined ligand- and structure-based approach. First, since the crystal structure of CYP26A1 protein has not been determined, we constructed the 3D structure of CYP26A1 using homology modeling. In order to achieve a deeper insight into the mode of action of RAMBAs in the active site, the molecular superimposition model and the common feature pharmacophore model were constructed, and molecular docking was performed. The molecular superimposition model is composed of three features: the main chain groups, side chain groups, and azole groups. The common feature pharmacophore model consists of five chemical features: four hydrophobic groups and one hydrogen acceptor (HHHHA). The results of molecular docking show that the characteristic groups of RAMBAs were mapped into three different active pockets, respectively. A structure-activity relationship (SAR) was obtained by a combination of the molecular superimposition and docking results with the pharmacophore model. This study gives more insight into the interaction model inside the CYP26A1 active site and provides guidance for the design of more potent and possibly more selective RAMBAs.

  13. New Insight into the Structure-Activity Relationships of the Selective Excitatory Amino Acid Transporter Subtype 1 (EAAT1) Inhibitors UCPH-101 and UCPH-102.

    PubMed

    Hansen, Stinne W; Erichsen, Mette N; Huynh, Tri H V; Ruiz, Josep A; Haym, Isabell; Bjørn-Yoshimoto, Walden E; Abrahamsen, Bjarke; Hansen, Jeanette; Storgaard, Morten; Eriksen, Anette L; Jensen, Anders A; Bunch, Lennart

    2016-02-17

    In the present study, we made further investigations on the structure-activity requirements of the selective excitatory amino acid transporter 1 (EAAT1) inhibitor, 2-amino-4-(4-methoxyphenyl)-7-(naphthalen-1-yl)-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (UCPH-101), by exploring 15 different substituents (R(1) ) at the 7-position in combination with eight different substituents (R(2) ) at the 4-position. Among the 63 new analogues synthesized, we identified a number of compounds that unexpectedly displayed inhibitory activities at EAAT1 in light of understanding the structure-activity relationship (SAR) of this inhibitor class extracted from previous studies. Moreover, the nature of the R(1) and R(2) substituents were observed to contribute to the functional properties of the various analogues in additive and non-additive ways. Finally, separation of the four stereoisomers of analogue 14 g (2-amino-4-([1,1'-biphenyl]-4-yl)-3-cyano-7-isopropyl-5-oxo-5,6,7,8-tetrahydro-4H-chromene) was carried out, and in agreement with a study of a related scaffold, the R configuration at C4 was found to be mandatory for inhibitory activity, while both the C7 diastereomers were found to be active as EAAT1 inhibitors. A study of the stereochemical stability of the four pure stereoisomers 14 g-A-D showed that epimerization takes places at C7 via a ring-opening, C-C bond rotation, ring-closing mechanism. PMID:26757239

  14. Deformation Survey of Volcanoes in Central America Using Japanese L-Band SAR Satellite ALOS-1

    NASA Astrophysics Data System (ADS)

    Amelug, F.; Lebowitz, J.

    2015-12-01

    The Japanese L-Band SAR satellite ALOS-1 has proven intself to be a useful tool for deformation monitoring of active volcanoes. Here we present a systematic deformation survey of volcanoes in Central America for the 2007-2011 time frame using the Small Baseline InSAR time-series approach. We present results for deforming volcanoes and non-deforming volcanoes, including simple elastic source models for the volcanoes that show surface deformation.

  15. Bradykinin actively modulates pulmonary vascular pressure-cardiac index relationships.

    PubMed

    Nyhan, D P; Clougherty, P W; Goll, H M; Murray, P A

    1987-07-01

    Our objectives were to investigate the pulmonary vascular effects of exogenously administered bradykinin at normal and reduced levels of cardiac index in intact conscious dogs and to assess the extent to which the pulmonary vascular response to bradykinin is the result of either cyclooxygenase pathway activation or reflex activation of sympathetic beta-adrenergic and -cholinergic receptors. Multipoint pulmonary vascular pressure-cardiac index (P/Q) plots were constructed during normoxia in conscious dogs by step-wise constriction of the thoracic inferior vena cava to reduce Q. In intact dogs, bradykinin (2 micrograms X kg-1 X min-1 iv) caused systemic vasodilation, i.e., systemic arterial pressure was slightly decreased (P less than 0.05), Q was markedly increased (P less than 0.01), and mixed venous PO2 and oxygen saturation (SO2) were increased (P less than 0.01). Bradykinin decreased (P less than 0.01) the pulmonary vascular pressure gradient (pulmonary arterial pressure-pulmonary capillary wedge pressure) over the entire range of Q studied (140-60 ml X min-1 X kg-1) in intact dogs. During cyclooxygenase pathway inhibition with indomethacin, bradykinin again decreased (P less than 0.05) pulmonary arterial pressure-pulmonary capillary wedge pressure at every level of Q, although the magnitude of the vasodilator response was diminished at lower levels of Q (60 ml X min-1 X kg-1). Following combined administration of sympathetic beta-adrenergic and -cholinergic receptor antagonists, bradykinin still decreased (P less than 0.01) pulmonary arterial pressure-pulmonary capillary wedge pressure over the range of Q from 160 to 60 ml X min-1 X kg-1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3114215

  16. Validation of Quantitative Structure-Activity Relationship (QSAR) Model for Photosensitizer Activity Prediction

    PubMed Central

    Frimayanti, Neni; Yam, Mun Li; Lee, Hong Boon; Othman, Rozana; Zain, Sharifuddin M.; Rahman, Noorsaadah Abd.

    2011-01-01

    Photodynamic therapy is a relatively new treatment method for cancer which utilizes a combination of oxygen, a photosensitizer and light to generate reactive singlet oxygen that eradicates tumors via direct cell-killing, vasculature damage and engagement of the immune system. Most of photosensitizers that are in clinical and pre-clinical assessments, or those that are already approved for clinical use, are mainly based on cyclic tetrapyrroles. In an attempt to discover new effective photosensitizers, we report the use of the quantitative structure-activity relationship (QSAR) method to develop a model that could correlate the structural features of cyclic tetrapyrrole-based compounds with their photodynamic therapy (PDT) activity. In this study, a set of 36 porphyrin derivatives was used in the model development where 24 of these compounds were in the training set and the remaining 12 compounds were in the test set. The development of the QSAR model involved the use of the multiple linear regression analysis (MLRA) method. Based on the method, r2 value, r2 (CV) value and r2 prediction value of 0.87, 0.71 and 0.70 were obtained. The QSAR model was also employed to predict the experimental compounds in an external test set. This external test set comprises 20 porphyrin-based compounds with experimental IC50 values ranging from 0.39 μM to 7.04 μM. Thus the model showed good correlative and predictive ability, with a predictive correlation coefficient (r2 prediction for external test set) of 0.52. The developed QSAR model was used to discover some compounds as new lead photosensitizers from this external test set. PMID:22272096

  17. Structure-activity relationship studies on cholecystokinin: Analogues with partial agonist activity

    SciTech Connect

    Galas, M.C.; Lignon, M.F.; Rodriguez, M.; Mendre, C.; Fulcrand, P.; Laur, J.; Martinez, J. )

    1988-02-01

    In the present study, hepta- and octapeptide analogues of the C-terminal part of cholecystokinin, modified on the C-terminal phenylalanine residue, were synthesized. CCK analogues were prepared in which the peptide bond between aspartic acid and phenylalanine had or had not been modified and were lacking the C-terminal primary amide function. These CCK derivatives were able to cause full stimulation of amylase release from rat pancreatic acini but without a decrease in amylase release at supramaximal concentrations. There was a close relationship between the abilities of these derivatives to stimulate amylase release and their abilities to inhibit binding of {sup 125}I-BH-CCK-9 to CCK receptors on rat and guinea pig pancreatic acini. These CCK analogues were also able to recognize the guinea pig brain CCK receptors, some of them being particularly potent. The findings indicate that the aromatic ring of phenylalanine is important for the binding to brain and pancreatic CCK receptors, whereas the C-terminal primary amide function is not essential for the binding to pancreatic CCK receptors but is crucial for biological activity of rat pancreatic acini.

  18. Antiproliferative Pt(IV) complexes: synthesis, biological activity, and quantitative structure-activity relationship modeling.

    PubMed

    Gramatica, Paola; Papa, Ester; Luini, Mara; Monti, Elena; Gariboldi, Marzia B; Ravera, Mauro; Gabano, Elisabetta; Gaviglio, Luca; Osella, Domenico

    2010-09-01

    Several Pt(IV) complexes of the general formula [Pt(L)2(L')2(L'')2] [axial ligands L are Cl-, RCOO-, or OH-; equatorial ligands L' are two am(m)ine or one diamine; and equatorial ligands L'' are Cl- or glycolato] were rationally designed and synthesized in the attempt to develop a predictive quantitative structure-activity relationship (QSAR) model. Numerous theoretical molecular descriptors were used alongside physicochemical data (i.e., reduction peak potential, Ep, and partition coefficient, log Po/w) to obtain a validated QSAR between in vitro cytotoxicity (half maximal inhibitory concentrations, IC50, on A2780 ovarian and HCT116 colon carcinoma cell lines) and some features of Pt(IV) complexes. In the resulting best models, a lipophilic descriptor (log Po/w or the number of secondary sp3 carbon atoms) plus an electronic descriptor (Ep, the number of oxygen atoms, or the topological polar surface area expressed as the N,O polar contribution) is necessary for modeling, supporting the general finding that the biological behavior of Pt(IV) complexes can be rationalized on the basis of their cellular uptake, the Pt(IV)-->Pt(II) reduction, and the structure of the corresponding Pt(II) metabolites. Novel compounds were synthesized on the basis of their predicted cytotoxicity in the preliminary QSAR model, and were experimentally tested. A final QSAR model, based solely on theoretical molecular descriptors to ensure its general applicability, is proposed.

  19. InfoTerra/TerraSAR initiative

    NASA Astrophysics Data System (ADS)

    Wahl, Manfred W.

    2004-01-01

    The overarching goal of the InfoTerra/TerraSAR Initiative is to establish a self-sustaining operational/commercial business built on Europe"s know-how and experience in space-borne Synthetic Aperture Radar (SAR) technology, in SAR data processing as well as in SAR applications. InfoTerra stands for a new business concept based on supplying innovative geo-information products and services. TerraSAR is a space and ground system conceived to consist of an initial deployment and operation of 2 Radar satellites (one in X- and one in L-band) flying in a tandem configuration in the same orbit. The design of TerraSAR is driven by the market and is user-oriented. TerraSAR is key to capturing a significant proportion of the existing market and to opening new market opportunities, when it becomes operational. The InfoTerra/TerraSAR Initiative has evolved gradually. It started in 1997 as a joint venture between German (DSS) and British (MMS-UK) space industry, strongly supported by both space agencies, DLR and BNSC. In early 2001, DLR and BNSC submitted to ESA the Formal Programme Proposal for InfoTerra/TerraSAR to become an essential element of ESA"s Earth Watch Programme. In summer 2001, when it became evident that there was not yet sufficient support from the ESA Member States to allow immediate start entering into TerraSAR Phase C/D, it has been decided to implement first a TerraSAR consolidation phase. In early 2002, in order to avoid further delays, a contract was signed between DLR and Astrium GmbH on the development of one component of TerraSAR, the TerraSAR-X, in the frame of a national programme, governed by a Public Private Partnership Agreement. Even if now the different launch dates for TerraSAR-X and TerraSAR-L are narrowing down the window of common data acquisition, it is a reasonable starting point, but it should always be kept in mind that the utmost goal for the longterm is to achieve self sustainability by supplying geo-information products and services

  20. The relationship between trunk muscle activation and trunk stiffness: examining a non-constant stiffness gain.

    PubMed

    Brown, Stephen H M; McGill, Stuart M

    2010-12-01

    The relationship between muscle activation, force and stiffness needs to be known to interpret the stability state of the spine. To test the relationship between these variables, a quick release approach was used to match quantified torso stiffness with an EMG activation-based estimate of individual muscle stiffnesses. The relationship between activation, force and stiffness was modelled as k = q x F/l, where k, F and l are muscle stiffness, force and length, respectively, and q is the dimensionless stiffness gain relating these variables. Under the tested experimental scenario, the 'stiffness gain', q, which linked activation with stiffness, demonstrated a decreasing trend with increasing levels of torso muscle activation. This highlights the likelihood that the choice of a single q value may be over simplistic to relate force to stiffness in muscles that control the spine. This has implications for understanding the potential for spine instability in situations requiring high muscular demand.

  1. Relationship between ionospheric electric fields and magnetic activity indices

    NASA Astrophysics Data System (ADS)

    Shirapov, D. Sh.

    2012-02-01

    The relations between electric fields in the daytime and nighttime sectors of the polar ionosphere and magnetic activity indices of auroral region (AL) and northern polar cap (PCN) are studied. It is found that the above relations do exist and are described by: a) equations U {pc/(1)} (kV) = 27.62 + 21.43PCN with a correlation coefficient R = 0.87 and U {pc/(1)} (kV) = 4.06 + 49.21PCN - 6.24 PCN2 between the difference in the electric potentials across the polar cap in the daytime sector U {pc/(1)} and PCN and b) regression equation U {pc/(2)} (kV) = 23.33 + 0.08|AL| with R = 0.86 between the difference in the electric potentials across the polar cap in the nighttime sector U {pc/(2)} and |AL|. It is shown that: a) it is possible to use the AL and PCN indices for real-time diagnostics of instantaneous values of the electric fields in the daytime and nighttime sectors of the polar ionosphere in the process of a substorm development; b) at the expansion phase of a substorm, due to calibration of PCN values by the values of the solar wind electric field E sw, the PCN index does not feel the contribution of the western electrojet and, accordingly, the contribution of the nighttime ionospheric electric field U {pc/(2)}, governed by the reconnection in the magnetospheric tail.

  2. Improving quantitative structure-activity relationships through multiobjective optimization.

    PubMed

    Nicolotti, Orazio; Giangreco, Ilenia; Miscioscia, Teresa Fabiola; Carotti, Angelo

    2009-10-01

    A multiobjective optimization algorithm was proposed for the automated integration of structure- and ligand-based molecular design. Driven by a genetic algorithm, the herein proposed approach enabled the detection of a number of trade-off QSAR models accounting simultaneously for two independent objectives. The first was biased toward best regressions among docking scores and biological affinities; the second minimized the atom displacements from a properly established crystal-based binding topology. Based on the concept of dominance, 3D QSAR equivalent models profiled the Pareto frontier and were, thus, designated as nondominated solutions of the search space. K-means clustering was, then, operated to select a representative subset of the available trade-off models. These were effectively subjected to GRID/GOLPE analyses for quantitatively featuring molecular determinants of ligand binding affinity. More specifically, it was demonstrated that a) diverse binding conformations occurred on the basis of the ligand ability to profitably contact different part of protein binding site; b) enzyme selectivity was better approached and interpreted by combining diverse equivalent models; and c) trade-off models were successful and even better than docking virtual screening, in retrieving at high sensitivity active hits from a large pool of chemically similar decoys. The approach was tested on a large series, very well-known to QSAR practitioners, of 3-amidinophenylalanine inhibitors of thrombin and trypsin, two serine proteases having rather different biological actions despite a high sequence similarity. PMID:19785453

  3. Oxazolidinone structure-activity relationships leading to linezolid.

    PubMed

    Barbachyn, Michael R; Ford, Charles W

    2003-05-01

    The development of bacterial resistance to currently available antibacterial agents is a growing global health problem. Of particular concern are infections caused by multidrug-resistant Gram-positive pathogens which are responsible for significant morbidity and mortality in both the hospital and community settings. A number of solutions to the problem of bacterial resistance are possible. The most common approach is to continue modifying existing classes of antibacterial agents to provide new analogues with improved attributes. Other successful strategies are to combine existing antibacterial agents with other drugs as well as the development of improved diagnostic procedures that may lead to rapid identification of the causative pathogen and permit the use of antibacterial agents with a narrow spectrum of activity. Finally, and most importantly, the discovery of novel classes of antibacterial agents employing new mechanisms of action has considerable promise. Such agents would exhibit a lack of cross-resistance with existing antimicrobial drugs. This review describes the work leading to the discovery of linezolid, the first clinically useful oxazolidinone antibacterial agent.

  4. Space Radar Image of West Texas - SAR scan

    NASA Technical Reports Server (NTRS)

    1999-01-01

    forthcoming Canadian RADARSAT satellite. Spaceborne Imaging Radar-C and X-band Synthetic Aperture Radar (SIR-C/X-SAR) is part of NASA's Mission to Planet Earth. The radars illuminate Earth with microwaves, allowing detailed observations at any time, regardless of weather or sunlight conditions. SIR-C/X-SAR uses three microwave wavelengths: L-band (24 cm), C-band (6 cm) and X-band (3 cm). The multi-frequency data will be used by the international scientific community to better understand the global environment and how it is changing. The SIR-C/X-SAR data, complemented by aircraft and ground studies, will give scientists clearer insights into those environmental changes which are caused by nature and those changes which are induced by human activity. SIR-C was developed by NASA's Jet Propulsion Laboratory. X-SAR was developed by the Dornier and Alenia Spazio companies for the German space agency, Deutsche Agentur fuer Raumfahrtangelegenheiten (DARA), and the Italian space agency, Agenzia Spaziale Italiana (ASI), with the Deutsche Forschungsanstalt fuer Luft und Raumfahrt e.v.(DLR), the major partner in science, operations, and data processing of X-SAR.

  5. Structure-activity relationships of ketolides vs. macrolides.

    PubMed

    Douthwaite, S

    2001-01-01

    's activity against MLS(B)-resistant respiratory pathogens.

  6. Relationship between Vitamin D Status and Autonomic Nervous System Activity.

    PubMed

    Burt, Morton G; Mangelsdorf, Brenda L; Stranks, Stephen N; Mangoni, Arduino A

    2016-01-01

    Vitamin D deficiency is associated with increased arterial stiffness. However, the mechanisms underlying this association have not been clarified. The aim was to investigate whether changes in autonomic nervous system activity could underlie an association between 25 hydroxy vitamin D and arterial stiffness. A total of 49 subjects (age = 60 ± 8 years, body mass index = 26.7 ± 4.6 kg/m², 25 hydroxy vitamin D = 69 ± 22 nmol/L) underwent measurements of pulse wave velocity (PWV) and augmentation index (AIx), spontaneous baroreflex sensitivity, plasma metanephrines and 25 hydroxy vitamin D. Subjects with 25 hydroxy vitamin D ≤ 50 nmol/L were restudied after 200,000 International Units 25 hydroxy vitamin D. Plasma metanephrine was positively associated with AIx (p = 0.02) independent of age, sex, smoking and cholesterol and negatively associated with 25 hydroxy vitamin D (p = 0.002) independent of age, sex and season. In contrast, there was no association between baroreflex sensitivity and 25 hydroxy vitamin D (p = 0.54). Treatment with vitamin D increased 25 hydroxy vitamin D from 43 ± 5 to 96 ± 24 nmol/L (p < 0.0001) but there was no significant change in plasma metanephrine (115 ± 25 vs. 99 ± 39 pmol/L, p = 0.12). We conclude that as plasma metanephrine was negatively associated with 25 hydroxy vitamin D and positively with AIx, it could mediate an association between these two variables. This hypothesis should be tested in larger interventional studies. PMID:27649235

  7. Relationship between Vitamin D Status and Autonomic Nervous System Activity

    PubMed Central

    Burt, Morton G.; Mangelsdorf, Brenda L.; Stranks, Stephen N.; Mangoni, Arduino A.

    2016-01-01

    Vitamin D deficiency is associated with increased arterial stiffness. However, the mechanisms underlying this association have not been clarified. The aim was to investigate whether changes in autonomic nervous system activity could underlie an association between 25 hydroxy vitamin D and arterial stiffness. A total of 49 subjects (age = 60 ± 8 years, body mass index = 26.7 ± 4.6 kg/m2, 25 hydroxy vitamin D = 69 ± 22 nmol/L) underwent measurements of pulse wave velocity (PWV) and augmentation index (AIx), spontaneous baroreflex sensitivity, plasma metanephrines and 25 hydroxy vitamin D. Subjects with 25 hydroxy vitamin D ≤ 50 nmol/L were restudied after 200,000 International Units 25 hydroxy vitamin D. Plasma metanephrine was positively associated with AIx (p = 0.02) independent of age, sex, smoking and cholesterol and negatively associated with 25 hydroxy vitamin D (p = 0.002) independent of age, sex and season. In contrast, there was no association between baroreflex sensitivity and 25 hydroxy vitamin D (p = 0.54). Treatment with vitamin D increased 25 hydroxy vitamin D from 43 ± 5 to 96 ± 24 nmol/L (p < 0.0001) but there was no significant change in plasma metanephrine (115 ± 25 vs. 99 ± 39 pmol/L, p = 0.12). We conclude that as plasma metanephrine was negatively associated with 25 hydroxy vitamin D and positively with AIx, it could mediate an association between these two variables. This hypothesis should be tested in larger interventional studies. PMID:27649235

  8. Sentinel-3 SAR Altimetry Toolbox

    NASA Astrophysics Data System (ADS)

    Benveniste, Jerome; Lucas, Bruno; DInardo, Salvatore

    2015-04-01

    The prime objective of the SEOM (Scientific Exploitation of Operational Missions) element is to federate, support and expand the large international research community that the ERS, ENVISAT and the Envelope programmes have build up over the last 20 years for the future European operational Earth Observation missions, the Sentinels. Sentinel-3 builds directly on a proven heritage of ERS-2 and Envisat, and CryoSat-2, with a dual-frequency (Ku and C band) advanced Synthetic Aperture Radar Altimeter (SRAL) that provides measurements at a resolution of ~300m in SAR mode along track. Sentinel-3 will provide exact measurements of sea-surface height along with accurate topography measurements over sea ice, ice sheets, rivers and lakes. The first of the two Sentinels is expected to be launched in early 2015. The current universal altimetry toolbox is BRAT (Basic Radar Altimetry Toolbox) which can read all previous and current altimetry mission's data, but it does not have the capabilities to read the upcoming Sentinel-3 L1 and L2 products. ESA will endeavour to develop and supply this capability to support the users of the future Sentinel-3 SAR Altimetry Mission. BRAT is a collection of tools and tutorial documents designed to facilitate the processing of radar altimetry data. This project started in 2005 from the joint efforts of ESA (European Space Agency) and CNES (Centre National d'Etudes Spatiales), and it is freely available at http://earth.esa.int/brat. The tools enable users to interact with the most common altimetry data formats, the BratGUI is the front-end for the powerful command line tools that are part of the BRAT suite. BRAT can also be used in conjunction with Matlab/IDL (via reading routines) or in C/C++/Fortran via a programming API, allowing the user to obtain desired data, bypassing the data-formatting hassle. BRAT can be used simply to visualise data quickly, or to translate the data into other formats such as netCDF, ASCII text files, KML (Google Earth

  9. CheS-Mapper 2.0 for visual validation of (Q)SAR models

    PubMed Central

    2014-01-01

    Background Sound statistical validation is important to evaluate and compare the overall performance of (Q)SAR models. However, classical validation does not support the user in better understanding the properties of the model or the underlying data. Even though, a number of visualization tools for analyzing (Q)SAR information in small molecule datasets exist, integrated visualization methods that allow the investigation of model validation results are still lacking. Results We propose visual validation, as an approach for the graphical inspection of (Q)SAR model validation results. The approach applies the 3D viewer CheS-Mapper, an open-source application for the exploration of small molecules in virtual 3D space. The present work describes the new functionalities in CheS-Mapper 2.0, that facilitate the analysis of (Q)SAR information and allows the visual validation of (Q)SAR models. The tool enables the comparison of model predictions to the actual activity in feature space. The approach is generic: It is model-independent and can handle physico-chemical and structural input features as well as quantitative and qualitative endpoints. Conclusions Visual validation with CheS-Mapper enables analyzing (Q)SAR information in the data and indicates how this information is employed by the (Q)SAR model. It reveals, if the endpoint is modeled too specific or too generic and highlights common properties of misclassified compounds. Moreover, the researcher can use CheS-Mapper to inspect how the (Q)SAR model predicts activity cliffs. The CheS-Mapper software is freely available at http://ches-mapper.org. Graphical abstract Comparing actual and predicted activity values with CheS-Mapper.

  10. Cross-calibration between airborne SAR sensors

    NASA Technical Reports Server (NTRS)

    Zink, Manfred; Olivier, Philippe; Freeman, Anthony

    1993-01-01

    As Synthetic Aperture Radar (SAR) system performance and experience in SAR signature evaluation increase, quantitative analysis becomes more and more important. Such analyses require an absolute radiometric calibration of the complete SAR system. To keep the expenditure on calibration of future multichannel and multisensor remote sensing systems (e.g., X-SAR/SIR-C) within a tolerable level, data from different tracks and different sensors (channels) must be cross calibrated. The 1989 joint E-SAR/DC-8 SAR calibration campaign gave a first opportunity for such an experiment, including cross sensor and cross track calibration. A basic requirement for successful cross calibration is the stability of the SAR systems. The calibration parameters derived from different tracks and the polarimetric properties of the uncalibrated data are used to describe this stability. Quality criteria for a successful cross calibration are the agreement of alpha degree values and the consistency of radar cross sections of equally sized corner reflectors. Channel imbalance and cross talk provide additional quality in case of the polarimetric DC-8 SAR.

  11. SAR Speckle Noise Reduction Using Wiener Filter

    NASA Technical Reports Server (NTRS)

    Joo, T. H.; Held, D. N.

    1983-01-01

    Synthetic aperture radar (SAR) images are degraded by speckle. A multiplicative speckle noise model for SAR images is presented. Using this model, a Wiener filter is derived by minimizing the mean-squared error using the known speckle statistics. Implementation of the Wiener filter is discussed and experimental results are presented. Finally, possible improvements to this method are explored.

  12. Coordinated Response to SARS, Vancouver, Canada

    PubMed Central

    Petric, Martin; Daly, Patricia; Parker, Robert A.; Bryce, Elizabeth; Doyle, Patrick W.; Noble, Michael A.; Roscoe, Diane L.; Tomblin, Joan; Yang, Tung C.; Krajden, Mel; Patrick, David M.; Pourbohloul, Babak; Goh, Swee Han; Bowie, William R.; Booth, Tim F.; Tweed, S. Aleina; Perry, Thomas L.; McGeer, Allison; Brunham, Robert C.

    2006-01-01

    Two Canadian urban areas received travelers with severe acute respiratory syndrome (SARS) before the World Health Organization issued its alert. By July 2003, Vancouver had identified 5 cases (4 imported); Toronto reported 247 cases (3 imported) and 43 deaths. Baseline preparedness for pandemic threats may account for the absence of sustained transmission and fewer cases of SARS in Vancouver. PMID:16494736

  13. The Relationship between Occupational Status and Physical Activity in Korea.

    PubMed

    So, Wi-Young; Yoo, Byoung-Wook; Sung, Dong Jun

    2016-10-01

    This study examined the association between occupational status and physical activity (PA) in Korea. A total of 9,000 Koreans age 10 to 89 years participated in the Korean Survey of Citizens' Sports Participation project in 2012. However, 3,851 participants were excluded from the analysis (housewives, students, and the jobless), providing a sample size of 5,149 participants (3,165 men and 1,984 women) for this study. The association between occupational status and PA was then evaluated using multivariate logistic regression analysis. The odds ratios (ORs; 95% confidence interval [CI]) for reporting at least weekly PA according to job intensity, after adjusting for sex and age, were as follows: moderate-intensity jobs, 1.164 [1.026, 1.320], p = .018; and vigorous-intensity jobs, 1.591 [1.318, 1.921], p < .001, compared with low-intensity jobs as a reference category. For PA intensity in low- and moderate-intensity jobs, after adjusting for sex and age, the ORs (95% CI) were as follows: low-intensity PA, 1.355 [1.033, 1.778], p = .028, moderate PA, 1.227 [1.096, 1.487], p = .002, and vigorous PA, 1.570 [1.213, 2.032], p < .001, compared with sedentary as a reference category. For the intensity of PA among participants with low- or vigorous-intensity jobs, after adjusting for sex and age, the ORs (95% CI) were as follows: low-intensity PA, 1.015 [0.649, 1.586], p = .948, moderate-intensity PA, 1.890 [1.416, 2.522], p < .001, and vigorous-intensity PA, 2.403 [1.395, 4.139], p = .002, compared with sedentary as a reference category. For the intensity of PA between moderate-intensity and vigorous-intensity jobs, after adjusting for sex and age, the ORs (95% CI) were as follows: low-intensity PA, 1.010 [0.759, 1.344], p = .945, moderate-intensity PA, 1.381 [1.136, 1.678], p = .001, and vigorous-intensity PA, 1.595 [1.023, 2.486], p = .039, compared to sedentary as a reference category. The presented findings show a strong association between

  14. Making SAR Data Accessible - ASF's ALOS PALSAR Radiometric Terrain Correction Project

    NASA Astrophysics Data System (ADS)

    Meyer, F. J.; Arko, S. A.; Gens, R.

    2015-12-01

    While SAR data have proven valuable for a wide range of geophysical research questions, so far, largely only the SAR-educated science communities have been able to fully exploit the information content of internationally available SAR archives. The main issues that have been preventing a more widespread utilization of SAR are related to (1) the diversity and complexity of SAR data formats, (2) the complexity of the processing flows needed to extract geophysical information from SAR, (3) the lack of standardization and automation of these processing flows, and (4) the often ignored geocoding procedures, leaving the data in image coordinate space. In order to improve upon this situation, ASF's radiometric terrain-correction (RTC) project is generating uniformly formatted and easily accessible value-added products from the ASF Distributed Active Archive Center's (DAAC) five-year archive of JAXA's ALOS PALSAR sensor. Specifically, the project applies geometric and radiometric corrections to SAR data to allow for an easy and direct combination of obliquely acquired SAR data with remote sensing imagery acquired in nadir observation geometries. Finally, the value-added data is provided to the user in the broadly accepted Geotiff format, in order to support the easy integration of SAR data into GIS environments. The goal of ASF's RTC project is to make SAR data more accessible and more attractive to the broader SAR applications community, especially to those users that currently have limited SAR expertise. Production of RTC products commenced October 2014 and will conclude late in 2015. As of July 2015, processing of 71% of ASF's ALOS PALSAR archive was completed. Adding to the utility of this dataset are recent changes to the data access policy that allow the full-resolution RTC products to be provided to the public, without restriction. In this paper we will introduce the processing flow that was developed for the RTC project and summarize the calibration and validation

  15. Monitoring and characterising slow-moving landslides using multiple SAR techniques

    NASA Astrophysics Data System (ADS)

    Singleton, Andrew; Li, Zhenhong; Hoey, Trevor; Wheeler, Simon

    2013-04-01

    The Three Gorges region, China, has long suffered from frequent, widespread and varied landslide hazards. Over the last decade, the Three Gorges dam has also created a 600 km long reservoir with a bi-annual fluctuating water-level which has connected new slopes to the Yangtze River and reactivated ancient landslides. InSAR has been frequently used to detect actively deforming slopes, although the well-known issues of temporal decorrelation, geometrical distortion and atmospheric water-vapour can often make time-series analysis difficult without ground data verification. Particularly in the Three Gorges area, the dense orange-tree vegetation and steep slopes pose a challenge for applying InSAR techniques beyond the most populated (i.e. more urban) areas. This study therefore attempts to extend remote slope monitoring and characterisation to non-urban areas within the Three Gorges (along the 60 km stretch between Badong and Zigui). A significant amount of SAR data from three different sensors (TerraSAR-X, Envisat and COSMO SkyMed, in various modes) have been analysed using multiple SAR techniques (InSAR, InSAR time-series and pixel-offset measurements). Despite the shorter wavelength, the faster repeat cycle and higher spatial resolution of the TerraSAR-X Spotlight images best highlight the landslide boundaries along with Line-of-Sight (LOS) measurements in the order of cm's over the 11-day period between acquisitions. Whilst significant difficulties have been found with InSAR time-series techniques, the use of high resolution SAR data with sub-pixel offset tracking techniques has proved successful, and can distinguish between horizontal and LOS displacements. The InSAR signals, combined with the time-series measurements from pixel-offset techniques can firstly help validate both datasets without ground data. Secondly, they have been used to provide a first-order characterisation of the landslide mechanism and can be compared with the results from simple limit

  16. Relationship between cefamandole and cefuroxime activity against oxacillin-resistant Staphylococcus epidermidis and oxacillin resistance phenotype.

    PubMed

    Woods, G L; Knapp, C C; Washington, J A

    1987-09-01

    The activity of cefamandole and cefuroxime against oxacillin-resistant staphylococcus epidermidis was studied in vitro to determine whether there was any relationship between oxacillin resistance phenotypes and cephalosporin activity. Oxacillin resistance phenotypes were determined by efficiency-of-plating studies on Mueller-Hinton agar containing oxacillin, with and without NaCl, and incubated at 30 and 35 degrees C. On the basis of MIC and MBC determinations, cefamandole was more active than cefuroxime against oxacillin-resistant S. epidermidis. Although temperature had minimal effect on the activity of either cefamandole or cefuroxime, NaCl significantly decreased the activity of cefuroxime but not of cefamandole. Neither cephalosporin consistently produced greater than or equal to 99.9% bactericidal activity within 24 h in timed killing-curve studies. No consistent relationship was observed between cefamandole or cefuroxime activity and oxacillin resistance phenotype.

  17. Relationship between cefamandole and cefuroxime activity against oxacillin-resistant Staphylococcus epidermidis and oxacillin resistance phenotype.

    PubMed

    Woods, G L; Knapp, C C; Washington, J A

    1987-09-01

    The activity of cefamandole and cefuroxime against oxacillin-resistant staphylococcus epidermidis was studied in vitro to determine whether there was any relationship between oxacillin resistance phenotypes and cephalosporin activity. Oxacillin resistance phenotypes were determined by efficiency-of-plating studies on Mueller-Hinton agar containing oxacillin, with and without NaCl, and incubated at 30 and 35 degrees C. On the basis of MIC and MBC determinations, cefamandole was more active than cefuroxime against oxacillin-resistant S. epidermidis. Although temperature had minimal effect on the activity of either cefamandole or cefuroxime, NaCl significantly decreased the activity of cefuroxime but not of cefamandole. Neither cephalosporin consistently produced greater than or equal to 99.9% bactericidal activity within 24 h in timed killing-curve studies. No consistent relationship was observed between cefamandole or cefuroxime activity and oxacillin resistance phenotype. PMID:3674845

  18. Relationships between fundamental movement skills and objectively measured physical activity in preschool children.

    PubMed

    Cliff, Dylan P; Okely, Anthony D; Smith, Leif M; McKeen, Kim

    2009-11-01

    Gender differences in cross-sectional relationships between fundamental movement skill (FMS) subdomains (locomotor skills, object-control skills) and physical activity were examined in preschool children. Forty-six 3- to 5-year-olds (25 boys) had their FMS video assessed (Test of Gross Motor Development II) and their physical activity objectively monitored (Actigraph 7164 accelerometers). Among boys, object-control skills were associated with physical activity and explained 16.9% (p = .024) and 13.7% (p = .049) of the variance in percent of time in moderate-to-vigorous physical activity (MVPA) and total physical activity, respectively, after controlling for age, SES and z-BMI. Locomotor skills were inversely associated with physical activity among girls, and explained 19.2% (p = .023) of the variance in percent of time in MVPA after controlling for confounders. Gender and FMS subdomain may influence the relationship between FMS and physical activity in preschool children. PMID:20128363

  19. Regularization Analysis of SAR Superresolution

    SciTech Connect

    DELAURENTIS,JOHN M.; DICKEY,FRED M.

    2002-04-01

    Superresolution concepts offer the potential of resolution beyond the classical limit. This great promise has not generally been realized. In this study we investigate the potential application of superresolution concepts to synthetic aperture radar. The analytical basis for superresolution theory is discussed. In a previous report the application of the concept to synthetic aperture radar was investigated as an operator inversion problem. Generally, the operator inversion problem is ill posed. This work treats the problem from the standpoint of regularization. Both the operator inversion approach and the regularization approach show that the ability to superresolve SAR imagery is severely limited by system noise.

  20. Advanced antennas for SAR spacecraft

    NASA Technical Reports Server (NTRS)

    Gail, William B.

    1993-01-01

    Single and multi-frequency antenna concepts were developed to evaluate the feasibility of building large aperture polarimetric synthetic aperture radar (SAR) systems to be launched in low cost vehicles such as the Delta 2. The antennas are 18.9 m long by 2.6 m wide (L-band) and achieve single polarization imaging to an incidence angle of 55 degrees and dual/quad imaging to 42 degrees. When combined with strawman spacecraft designs, both concepts meet the mass and volume constraints imposed by a Delta 2 launch.

  1. Relationships between Writing Motivation, Writing Activity, and Writing Performance: Effects of Grade, Sex, and Ability

    ERIC Educational Resources Information Center

    Troia, Gary A.; Harbaugh, Allen G.; Shankland, Rebecca K.; Wolbers, Kimberly A.; Lawrence, Ann M.

    2013-01-01

    A convenience sample of 618 children and adolescents in grades 4 through 10, excluding grade 8, were asked to complete a writing motivation and activity scale and to provide a timed narrative writing sample to permit an examination of the relationships between writing motivation, writing activity, writing performance, and the student…

  2. Relationships between Childhood and Adult Physical Activity Patterns in a Community Sample.

    ERIC Educational Resources Information Center

    Lamarine, Roland J.; Polkinghorne, Ori

    This study examined the relationship between adult physical activity levels and patterns of activity that were established during childhood. A random digit telephone survey was conducted of noninstitutionalized residents in a medium sized California city. Subjects ages 18 and over who volunteered to participate were questioned about their…

  3. Relationship of lactate dehydrogenase activity to body measurements of Angus x Charolais cows and calves

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objectives were to examine 1) relationships between lactate dehydrogenase (LDH) activity and body measurements of grazing beef cows, and 2) the association between maternal LDH activity in late gestation and subsequent calf birth weight (BRW), hip height (HH) at weaning, and adjusted weaning weight ...

  4. RELATIONSHIPS BETWEEN GIS ENVIRONMENTAL FEATURES AND ADOLESCENT MALE PHYSICAL ACTIVITY: GIS CODING DIFFERENCES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: It is not clear if relationships between GIS obtained environmental features and physical activity differ according to the method used to code GIS data. Methods: Physical activity levels of 210 Boy Scouts were measured by accelerometer. Numbers of parks, trails, gymnasia, bus stops, groc...

  5. Is Father-Child Rough-and-Tumble Play Associated with Attachment or Activation Relationships?

    ERIC Educational Resources Information Center

    Paquette, Daniel; Dumont, Caroline

    2013-01-01

    The activation relationship theory, primarily focused on parental stimulation of risk-taking along with parental control during exploration, predicts that boys will be activated more than girls by their fathers. This theory may explain why fathers engage in rough-and-tumble play (RTP) with children more frequently than mothers, especially with…

  6. The Relationship between Engagement in Cocurricular Activities and Academic Performance: Exploring Gender Differences

    ERIC Educational Resources Information Center

    Zacherman, Avi; Foubert, John

    2014-01-01

    The effects of time spent in cocurricular activities on academic performance was tested. A curvilinear relationship between hours per week spent involved in cocurricular activities and grade point average was discovered such that a low amount of cocurricular involvement was beneficial to grades, while a high amount can potentially hurt academic…

  7. High School Counselors' Perceived Self-Efficacy and Relationships with Actual and Preferred Job Activities

    ERIC Educational Resources Information Center

    Jellison, Vickie Dawn

    2013-01-01

    The purpose of this research was to explore the relationship between School Counselor self-efficacy, role definition and actual and preferred school counseling activities in a sample drawn from a population of school counselors. To measure these variables, the School Counselor Self-Efficacy Scale (SCSE) and the School Counselor Activity Rating…

  8. Relationship between skin temperature and muscle activation during incremental cycle exercise.

    PubMed

    Priego Quesada, Jose I; Carpes, Felipe P; Bini, Rodrigo R; Salvador Palmer, Rosario; Pérez-Soriano, Pedro; Cibrián Ortiz de Anda, Rosa M

    2015-02-01

    While different studies showed that better fitness level adds to the efficiency of the thermoregulatory system, the relationship between muscular effort and skin temperature is still unknown. Therefore, the present study assessed the relationship between neuromuscular activation and skin temperature during cycle exercise. Ten physically active participants performed an incremental workload cycling test to exhaustion while neuromuscular activations were recorded (via surface electromyography - EMG) from rectus femoris, vastus lateralis, biceps femoris and gastrocnemius medialis. Thermographic images were recorded before, immediately after and 10 min after finishing the cycling test, at four body regions of interest corresponding to the muscles where neuromuscular activations were monitored. Frequency band analysis was conducted to assess spectral properties of EMG signals in order to infer on priority in recruitment of motor units. Significant inverse relationship between changes in skin temperature and changes in overall neuromuscular activation for vastus lateralis was observed (r<-0.5 and p<0.04). Significant positive relationship was observed between skin temperature and low frequency components of neuromuscular activation from vastus lateralis (r>0.7 and p<0.01). Participants with larger overall activation and reduced low frequency component for vastus lateralis activation presented a better adaptive response of their thermoregulatory system by showing fewer changes in skin temperature after incremental cycling test.

  9. Developing sensor activity relationships for the JPL electronic nose sensors using molecular modeling and QSAR techniques

    NASA Technical Reports Server (NTRS)

    Shevade, A. V.; Ryan, M. A.; Homer, M. L.; Jewell, A. D.; Zhou, H.; Manatt, K.; Kisor, A. K.

    2005-01-01

    We report a Quantitative Structure-Activity Relationships (QSAR) study using Genetic Function Approximations (GFA) to describe the polymer-carbon composite sensor activities in the JPL Electronic Nose, when exposed to chemical vapors at parts-per-million concentration levels.

  10. A Qualitative Investigation of the Relationship between Consumption, Physical Activity, Eating Disorders, and Weight Consciousness

    ERIC Educational Resources Information Center

    Piazza-Gardner, Anna K.; Barry, Adam E.

    2014-01-01

    Background: Previous research has identified a positive relationship between alcohol consumption and disordered eating, alcohol consumption and physical activity, and physical activity and disordered eating. However, there is a paucity of published research examining the interrelatedness of all 3 behaviors together. Purpose: This study examines…

  11. The Relationship Between Passive and Active Vocabularies: Effects of Language Learning Context.

    ERIC Educational Resources Information Center

    Laufer, Batia; Paribakht, T. Sima

    1998-01-01

    Investigated the relationships among three types of vocabulary knowledge (passive, controlled active, and free active) within the same individuals, taking four variables into consideration: passive vocabulary size, language learning context, second (L2) for foreign (FL), length of residence in L2 context, and, among the Canadians, knowledge of…

  12. Structural Relationships between Social Activities and Longitudinal Trajectories of Depression among Older Adults

    ERIC Educational Resources Information Center

    Hong, Song-Iee; Hasche, Leslie; Bowland, Sharon

    2009-01-01

    Purpose: This study examines the structural relationships between social activities and trajectories of late-life depression. Design and Methods: Latent class analysis was used with a nationally representative sample of older adults (N = 5,294) from the Longitudinal Study on Aging II to classify patterns of social activities. A latent growth curve…

  13. The Risky Situation: A Procedure for Assessing the Father-Child Activation Relationship

    ERIC Educational Resources Information Center

    Paquette, Daniel; Bigras, Marc

    2010-01-01

    Initial validation data are presented for the Risky Situation (RS), a 20-minute observational procedure designed to assess the father-child activation relationship with children aged 12-18 months. The coding grid, which is simple and easy to use, allows parent-child dyads to be classified into three categories and provides an activation score. By…

  14. Australian Adolescents' Extracurricular Activity Participation and Positive Development: Is the Relationship Mediated by Peer Attributes?

    ERIC Educational Resources Information Center

    Blomfield, Corey; Barber, Bonnie

    2010-01-01

    Adolescent participation in extracurricular activities is associated with numerous positive outcomes, yet the mechanisms underlying this relationship are largely unknown. This study had two goals: to investigate the association between participation in extracurricular activities and indicators of positive and negative development for Australian…

  15. Technology progresses in microelectronics promote on-board imaging of spaceborne SAR

    NASA Astrophysics Data System (ADS)

    Xu, Xinfeng

    2007-11-01

    The realization of spaceborne SAR imaging on-board is a necessary trend for digital avionics in speedily advancing SAR remote sensors. Powerful and efficient application-specific instruction-set processors (ASIPs) play a leading role in this solution to keep data processing system functioning real-time. A few improving methodologies, technologies and advanced EDA tools in microelectronics make it possible to design such a SAR imaging processor easier and faster. Some evident and important delegates of them, including system-level modeling and simulation for SAR imaging algorithm, available IP library designed by experts, ideas of designing domain-specific SoC with multiple processors and the microelectronic ways to ruggedize avionics applied in space radiation-active environment, are presented heuristically in this paper.

  16. A New Open-Source Tool For Education of SAR Interferometry: ADORE-DORIS

    NASA Astrophysics Data System (ADS)

    Osmanoglu, B.

    2012-12-01

    Delft Object-oRiented Interferometry Software (DORIS) is an open source and actively developed package empowering students and scientists from all over the world with means to carry out high quality synthetic aperture radar (SAR) interferometry. Automated DORIS Environment (ADORE) attempts to automate the processing steps involved in generating interferograms using DORIS. Synthetic aperture radar interferometry (InSAR) is an imported tool for earth scientists in a wide spectrum of applications. The complexity involved with the generation of interferograms from synthetic aperture radar (SAR) data limits InSAR's wide-use by scientists, and it's education in undergraduate classes. ADORE attempts to soften the learning curve for generating interferograms using DORIS. In this presentation the founding idea and practical benefits of ADORE is outlined and main processing steps are highlighted using an example data set.

  17. Affordable miniaturized SAR for tactical UAV applications

    NASA Astrophysics Data System (ADS)

    Sloan, George R.; Dubbert, Dale F.

    2004-08-01

    Sandia"s fielded and experimental SAR systems are well known for their real time, high resolution imagery. Previous designs, such as the Lynx radar, have been successfully demonstrated on medium-payload UAVs, including Predator and Fire Scout. However, fielding a high performance SAR sensor on even smaller (sub-50 pound payload) UAVs will require at least a 5x reduction in size, weight, and cost. This paper gives an overview of Sandia"s system concept and roadmap for near-term SAR miniaturization. Specifically, the "miniSAR" program, which plans to demonstrate a 25 pound system with 4 inch resolution in early 2005, is detailed. Accordingly, the conceptual approach, current status, design tradeoffs, and key facilitating technologies are reviewed. Lastly, future enhancements and directions are described, such as the follow-on demonstration of a sub-20 pound version with multi-mode (SAR/GMTI) capability.

  18. A Spectral-SAR Model for the Anionic-Cationic Interaction in Ionic Liquids: Application to Vibrio fischeri Ecotoxicity

    PubMed Central

    Lacrămă, Ana-Maria; Putz, Mihai V.; Ostafe, Vasile

    2007-01-01

    Within the recently launched the spectral-structure activity relationship (S-SAR) analysis, the vectorial anionic-cationic model of a generic ionic liquid is proposed, along with the associated algebraic correlation factor in terms of the measured and predicted activity norms. The reliability of the present scheme is tested by assessing the Hansch factors, i.e. lipophylicity, polarizability and total energy, to predict the ecotoxicity endpoints of wide types of ionic liquids with ammonium, pyridinium, phosphonium, choline and imidazolium cations on the aquatic bacteria Vibrio fischeri. The results, while confirming the cationic dominant influence when only lipophylicity is considered, demonstrate that the anionic effect dominates all other more specific interactions. It was also proved that the S-SAR vectorial model predicts considerably higher activity for the ionic liquids than for its anionic and cationic subsystems separately, in all considered cases. Moreover, through applying the least norm-correlation path principle, the complete toxicological hierarchies are presented, unfolding the ecological rules of combined cationic and anionic influences in ionic liquid toxicity.

  19. Preliminary results of SAR soil moisture experiment, November 1975

    NASA Technical Reports Server (NTRS)

    Choudhury, B. J.; Chang, A. T. C.; Schmugge, T. J.; Salomonson, V. V.; Wang, J. R.

    1979-01-01

    The experiment was performed using the Environmental Research Institute of Michigan's (ERIM) dual-frequency and dual-polarization side-looking SAR system on board a C-46 aircraft. For each frequency, horizontally polarized pulses were transmitted and both horizontally and vertically polarized return signals were recorded on the signal film simultaneously. The test sites were located in St. Charles, Missouri; Centralia, Missouri; and Lafayette, Indiana. Each test site was a 4.83 km by 8.05 km (3 mile by 5 mile) rectangular strip of terrain. Concurrent with SAR overflight, ground soil samples of 0-to-2.5 cm and 0-to-15 cm layers were collected for soil moisture estimation. The surface features were also noted. Hard-copy image films and the digital data produced via optical processing of the signal films are analyzed in this report to study the relationship of radar backscatter to the moisture content and the surface roughness. Many difficulties associated with processing and analysis of the SAR imagery are noted. In particular, major uncertainty in the quantitative analysis appeared due to the difficulty of quality reproduction of digital data from the signal films.

  20. Low-level microwave irradiation and central cholinergic activity: a dose-response study

    SciTech Connect

    Lai, H.; Carino, M.A.; Horita, A.; Guy, A.W.

    1989-01-01

    Rats were irradiated with circularly polarized, 2,450-MHz pulsed microwaves (2-microseconds pulses, 500 pulses per second (pps)) for 45 min in the cylindrical waveguide system of Guy et al. Immediately after exposure, sodium-dependent high-affinity choline uptake, an indicator of cholinergic activity in neural tissue, was measured in the striatum, frontal cortex, hippocampus, and hypothalamus. The power density was set to give average whole-body specific absorption rates (SAR) of 0.3, 0.45, 0.6, 0.75, 0.9, or 1.2 W/kg to study the dose-response relationship between the rate of microwave energy absorption and cholinergic activity in the different areas of the brain. Decrease in choline uptake was observed in the striatum at a SAR of 0.75 W/kg and above, whereas for the frontal cortex and hippocampus, decreases in choline uptake were observed at a SAR of 0.45 W/kg and above. No significant effect was observed in the hypothalamus at the irradiation power densities studied. The probit analysis was used to determine the SAR50 in each brain area, i.e., the SAR at which 50% of maximum response was elicited. SAR50 values for the striatum, frontal cortex, and hippocampus were 0.65, 0.38, and 0.44 W/kg, respectively.