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Sample records for activity relationships sars

  1. Introducing Spectral Structure Activity Relationship (S-SAR) Analysis. Application to Ecotoxicology

    PubMed Central

    Putz, Mihai V.; Lacrămă, Ana-Maria

    2007-01-01

    A novel quantitative structure-activity (property) relationship model, namely Spectral-SAR, is presented in an exclusive algebraic way replacing the old-fashioned multi-regression one. The actual S-SAR method interprets structural descriptors as vectors in a generic data space that is further mapped into a full orthogonal space by means of the Gram-Schmidt algorithm. Then, by coordinated transformation between the data and orthogonal spaces, the S-SAR equation is given under simple determinant form for any chemical-biological interactions under study. While proving to give the same analytical equation and correlation results with standard multivariate statistics, the actual S-SAR frame allows the introduction of the spectral norm as a valid substitute for the correlation factor, while also having the advantage to design the various related SAR models through the introduced “minimal spectral path” rule. An application is given performing a complete S-SAR analysis upon the Tetrahymena pyriformis ciliate species employing its reported eco-toxicity activities among relevant classes of xenobiotics. By representing the spectral norm of the endpoint models against the concerned structural coordinates, the obtained S-SAR endpoints hierarchy scheme opens the perspective to further design the ecotoxicological test batteries with organisms from different species.

  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. Structure activity relationship (SAR) study of benzimidazole scaffold for different biological activities: A mini-review.

    PubMed

    Yadav, Geeta; Ganguly, Swastika

    2015-06-05

    Benzimidazoles are the fused heterocyclic ring systems which form an integral part of vitamin B12 and have been luring many researchers all over the world to assess their potential therapeutic significance. They are known for their crucial role in numerous diseases via various mechanisms. Substitution of benzimidazole nucleus is a crucial step in the drug discovery process. Therefore, it is necessary to gather the latest information along with the earlier information to understand the present status of benzimidazole nucleus in drug discovery. In the present review, benzimidazole derivatives with different pharmacological activities are described on the basis of SAR study using structural substitution pattern around the benzimidazole nucleus and aims to review the reported work related to the chemistry and pharmacological activities of benzimidazole derivatives during recent years. The present manuscript to the best of our knowledge is the first compilation on synthesis and medicinal aspects including structure-activity relationships of benzimidazole reported to date.

  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, crystal structure, structure-activity relationships, and antiviral activity of a potent SARS coronavirus 3CL protease inhibitor.

    PubMed

    Yang, Syaulan; Chen, Shu-Jen; Hsu, Min-Feng; Wu, Jen-Dar; Tseng, Chien-Te K; Liu, Yu-Fan; Chen, Hua-Chien; Kuo, Chun-Wei; Wu, Chi-Shen; Chang, Li-Wen; Chen, Wen-Chang; Liao, Shao-Ying; Chang, Teng-Yuan; Hung, Hsin-Hui; Shr, Hui-Lin; Liu, Cheng-Yuan; Huang, Yu-An; Chang, Ling-Yin; Hsu, Jen-Chi; Peters, Clarence J; Wang, Andrew H-J; Hsu, Ming-Chu

    2006-08-10

    A potent SARS coronavirus (CoV) 3CL protease inhibitor (TG-0205221, Ki = 53 nM) has been developed. TG-0205221 showed remarkable activity against SARS CoV and human coronavirus (HCoV) 229E replications by reducing the viral titer by 4.7 log (at 5 microM) for SARS CoV and 5.2 log (at 1.25 microM) for HCoV 229E. The crystal structure of TG-0205221 (resolution = 1.93 A) has revealed a unique binding mode comprising a covalent bond, hydrogen bonds, and numerous hydrophobic interactions. Structural comparisons between TG-0205221 and a natural peptide substrate were also discussed. This information may be applied toward the design of other 3CL protease inhibitors.

  8. Design, synthesis and structure--activity relationship (SAR) studies of imidazo[4,5-b]pyridine derived purine isosteres and their potential as cytotoxic agents.

    PubMed

    Sajith, Ayyiliath M; Abdul Khader, K K; Joshi, Nithin; Reddy, Manchala Nageswar; Syed Ali Padusha, M; Nagaswarupa, H P; Nibin Joy, M; Bodke, Yadav D; Karuvalam, Ranjith P; Banerjee, Rinti; Muralidharan, A; Rajendra, P

    2015-01-07

    Drug resistance to chemotherapeutic agents paved the way to develop novel synthetic molecules which are active on MDR cancer cell lines. Regio-isomeric imidazo[4,5-b]pyridine analogues were synthesized and evaluated for their cytotoxic activity against a range of cancer cell lines. The structure-activity relationship (SAR) studies of the imidazopyridine analogues are also described. Analogue 6b displayed strong cytotoxicity and good microsomal stability.

  9. Synthesis, antimicrobial activity and advances in structure-activity relationships (SARs) of novel tri-substituted thiazole derivatives.

    PubMed

    Reddy, Guda Mallikarjuna; Garcia, Jarem Raul; Reddy, Vemulapati Hanuman; de Andrade, Ageo Meier; Camilo, Alexandre; Pontes Ribeiro, Renan Augusto; de Lazaro, Sergio Ricardo

    2016-11-10

    Trisubstituted thiazoles were synthesized and studied for their antimicrobial activity and supported by theoretical calculations. In addition, MIC, MBC and MFC were also tested. Moreover, the present study was analyzed to scrutinize comprehensive structure-activity relationships. In fact, LUMO orbital energy and orbital orientation was reliable to explain their antibacterial and antifungal assay. Amongst the tested compounds, tri-methyl-substituted thiazole compound showed higher antimicrobial activity and low MIC value due to highest LUMO energy.

  10. 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

  11. Approach to using mechanism-based structure activity relationship (SAR) analysis to assess human health hazard potential of nanomaterials.

    PubMed

    Lai, David Y

    2015-11-01

    With the increasing use and development of engineered nanoparticles in electronics, consumer products, pesticides, food and pharmaceutical industries, there is a growing concern about potential human health hazards of these materials. A number of studies have demonstrated that nanoparticle toxicity is extremely complex, and that the biological activity of nanoparticles will depend on a variety of physicochemical properties such as particle size, shape, agglomeration state, crystal structure, chemical composition, surface area and surface properties. Nanoparticle toxicity can be attributed to nonspecific interaction with biological structures due to their physical properties (e.g., size and shape) and biopersistence, or to specific interaction with biomolecules through their surface properties (e.g., surface chemistry and reactivity) or release of toxic ions. The toxic effects of most nanomaterials have not been adequately characterized and currently, there are many issues and challenges in toxicity testing and risk assessment of nanoparticles. Based on the possible mechanisms of action and available in vitro and in vivo toxicity database, this paper proposes an approach to using mechanism-based SAR analysis to assess the relative human health hazard/risk potential of various types of nanomaterials.

  12. 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.

  13. A New Structure-Activity Relationship (SAR) Model for Predicting Drug-Induced Liver Injury, Based on Statistical and Expert-Based Structural Alerts

    PubMed Central

    Pizzo, Fabiola; Lombardo, Anna; Manganaro, Alberto; Benfenati, Emilio

    2016-01-01

    The prompt identification of chemical molecules with potential effects on liver may help in drug discovery and in raising the levels of protection for human health. Besides in vitro approaches, computational methods in toxicology are drawing attention. We built a structure-activity relationship (SAR) model for evaluating hepatotoxicity. After compiling a data set of 950 compounds using data from the literature, we randomly split it into training (80%) and test sets (20%). We also compiled an external validation set (101 compounds) for evaluating the performance of the model. To extract structural alerts (SAs) related to hepatotoxicity and non-hepatotoxicity we used SARpy, a statistical application that automatically identifies and extracts chemical fragments related to a specific activity. We also applied the chemical grouping approach for manually identifying other SAs. We calculated accuracy, specificity, sensitivity and Matthews correlation coefficient (MCC) on the training, test and external validation sets. Considering the complexity of the endpoint, the model performed well. In the training, test and external validation sets the accuracy was respectively 81, 63, and 68%, specificity 89, 33, and 33%, sensitivity 93, 88, and 80% and MCC 0.63, 0.27, and 0.13. Since it is preferable to overestimate hepatotoxicity rather than not to recognize unsafe compounds, the model's architecture followed a conservative approach. As it was built using human data, it might be applied without any need for extrapolation from other species. This model will be freely available in the VEGA platform. PMID:27920722

  14. Development of a new Structure-Activity Relationship (SAR) for gas-phase reactions of NO3 radicals with organic compounds

    NASA Astrophysics Data System (ADS)

    Kerdouci, J.; Picquet-Varrault, B.; Doussin, J.

    2010-12-01

    The nitrate radical (NO3) has long been recognized as the dominant night-time oxidant of organic species, in particular of unsaturated compounds. More recently, it has been shown that it can contribute significantly to the oxidation of very reactive VOC (e.g. terpenes) even during the day[1]. Volatile organic compounds are widely emitted into the atmosphere by both anthropogenic and biogenic sources. When released into the troposphere, they can undergo either photolysis or oxidation by OH and NO3 radicals and by ozone. These chemical processes are known to be responsible for the formation of photooxidants and SOA which are involved in photochemical smog events. Hence, to estimate their impact on the tropospheric chemistry, it is necessary to know their reactivity towards the atmospheric oxidants. But because of huge number of VOCs, it is impossible to perform kinetic experiments for all of them. For this reason, estimation methods have been developed to predict rate constants. A number of methods for the estimation of rate constants have been proposed. Many of them utilize the physical or chemical properties of the organic compounds such as the ionization energy[2] or the energy of molecular orbital[3]. However, these methods are restricted in their use because of the limited database concerning molecular properties and the discrepancies between the different molecular models used to calculate these parameters. For this reason, a structure-activity relationship has been developed by Atkinson[4] to predict rate constants of the OH-oxidation of VOCs. This kind of SAR is very easy to use and has been successfully integrated in chemical models[5, 6]. Concerning the reactivity of organic compounds with NO3 radicals, it has long been considered that the number of experimental data was not sufficient to use the approach proposed by Atkinson. But during the last decade, many experimental studies, in particular on the unsaturated oxygenated compounds, have enhanced the

  15. Synthesis and SAR studies of praziquantel derivatives with activity against Schistosoma japonicum.

    PubMed

    Wang, Wen-Long; Song, Li-Jun; Chen, Xia; Yin, Xu-Ren; Fan, Wen-Hua; Wang, Gu-Ping; Yu, Chuan-Xin; Feng, Bainian

    2013-07-31

    The synthesis and structure-activity relationship (SAR) studies of praziquantel derivatives with activity against adult Schistosoma japonicum are described. Several of them showed better worm killing activity than praziquantel and could serve as leads for further optimization.

  16. Design, synthesis, and biological evaluation of novel dipeptide-type SARS-CoV 3CL protease inhibitors: structure-activity relationship study.

    PubMed

    Thanigaimalai, Pillaiyar; Konno, Sho; Yamamoto, Takehito; Koiwai, Yuji; Taguchi, Akihiro; Takayama, Kentaro; Yakushiji, Fumika; Akaji, Kenichi; Kiso, Yoshiaki; Kawasaki, Yuko; Chen, Shen-En; Naser-Tavakolian, Aurash; Schön, Arne; Freire, Ernesto; Hayashi, Yoshio

    2013-07-01

    This work describes the design, synthesis, and evaluation of low-molecular weight peptidic SARS-CoV 3CL protease inhibitors. The inhibitors were designed based on the potent tripeptidic Z-Val-Leu-Ala(pyrrolidone-3-yl)-2-benzothiazole (8; Ki = 4.1 nM), in which the P3 valine unit was substituted with a variety of distinct moieties. The resulting series of dipeptide-type inhibitors displayed moderate to good inhibitory activities against 3CL(pro). In particular, compounds 26m and 26n exhibited good inhibitory activities with Ki values of 0.39 and 0.33 μM, respectively. These low-molecular weight compounds are attractive leads for the further development of potent peptidomimetic inhibitors with pharmaceutical profiles. Docking studies were performed to model the binding interaction of the compound 26m with the SARS-CoV 3CL protease. The preliminary SAR study of the peptidomimetic compounds with potent inhibitory activities revealed several structural features that boosted the inhibitory activity: (i) a benzothiazole warhead at the S1' position, (ii) a γ-lactam unit at the S1-position, (iii) an appropriately hydrophobic leucine moiety at the S2-position, and (iv) a hydrogen bond between the N-arylglycine unit and a backbone hydrogen bond donor at the S3-position.

  17. Design and realization of an active SAR calibrator for TerraSAR-X

    NASA Astrophysics Data System (ADS)

    Dummer, Georg; Lenz, Rainer; Lutz, Benjamin; Kühl, Markus; Müller-Glaser, Klaus D.; Wiesbeck, Werner

    2005-10-01

    TerraSAR-X is a new earth observing satellite which will be launched in spring 2006. It carries a high resolution X-band SAR sensor. For high image data quality, accurate ground calibration targets are necessary. This paper describes a novel system concept for an active and highly integrated, digitally controlled SAR system calibrator. A total of 16 active transponder and receiver systems and 17 receiver only systems will be fabricated for a calibration campaign. The calibration units serve for absolute radiometric calibration of the SAR image data. Additionally, they are equipped with an extra receiver path for two dimensional satellite antenna pattern recognition. The calibrator is controlled by a dedicated digital Electronic Control Unit (ECU). The different voltages needed by the calibrator and the ECU are provided by the third main unit called Power Management Unit (PMU).

  18. Design, synthesis, insecticidal activity, and structure-activity relationship (SAR): studies of novel triazone derivatives containing a urea bridge group based on transient receptor potential (TRP) channels.

    PubMed

    Yang, Yan; Liu, Yuxiu; Song, Hongjian; Li, Yongqiang; Wang, Qingmin

    2016-11-01

    Numerous compounds containing urea bridge and biurea moieties are used in a variety of fields, especially as drugs and pesticides. To search for novel, environmentally benign and ecologically safe pesticides with unique modes of action, four series of novel triazone analogues containing urea, thiourea, biurea, and thiobiurea bridge, respectively, were designed and synthesized, according to various calcium ion channel inhibitors which act on transient receptor potential protein. Their structures were characterized by [Formula: see text] NMR, [Formula: see text] NMR, and HRMS. The insecticidal activities of the new compounds were obtained. The bioassay results indicated that compounds containing a thiourea bridge and a thiobiurea bridge exhibited excellent insecticidal activities against bean aphid. Specifically, compounds [Formula: see text], [Formula: see text], and [Formula: see text] exhibited 85, 90, and 95 % activities, respectively, at 10 mg/kg. Compounds [Formula: see text] (30 %), [Formula: see text] (35 %), [Formula: see text] (30 %), and [Formula: see text] (40 %) exhibited the approximate aphicidal activity of pymetrozine (30 %) at 5 mg/kg. In addition, some target compounds exhibited insecticidal activities against lepidopteran pests. From a molecular design standpoint, the information obtained in this study could help in the further design of new derivatives with improved insecticidal activities.

  19. 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.

  20. 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...

  1. 76 FR 35949 - Agency Information Collection Activity (Servicer's Staff Appraisal Reviewer (SAR) Application...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-20

    ... Collection Activity (Servicer's Staff Appraisal Reviewer (SAR) Application) Under OMB Review AGENCY: Veterans...: Servicer's Staff Appraisal Reviewer (SAR) Application, VA Form 26-0829. OMB Control Number: 2900-0715. Type... servicers to nominate employees for approval as Staff Appraisal Reviewer (SAR). Servicers SAR's will...

  2. Structure-Activity Relationship (SAR) and Preliminary Mode of Action Studies of 3-Substituted Benzylthioquinolinium Iodide as Anti-opportunistic Infection Agents

    PubMed Central

    Bolden, Sidney; Zhu, Xue Y.; Etukala, Jagan R; Boateng, Comfort; Mazu, Tryphon; Flores-Rozas, Hernan; Jacob, Melissa R.; Khan, Shabana I; Walker, Larry A.; Ablordeppey, Seth Y.

    2013-01-01

    Opportunistic infections are devastating to immunocompromised patients. And in especially sub-Saharan Africa where the AIDS epidemic is still raging, the mortality rate was recently as high as 70%. The paucity of anti-opportunistic drugs, the decreasing efficacy and the development of resistance against the azoles and even amphotericin B have stimulated the search for new drugs with new mechanisms of action. In a previous work, we showed that a new chemotype derived from the natural product cryptolepine displayed selective toxicity against opportunistic pathogens with minimal cytotoxicity to normal cells. In this manuscript, we report the design and synthesis of substituted benzylthioquinolinium iodides, evaluated their anti-infective properties and formulated some initial structure-activity relationships around phenyl ring A from the original natural product. The sensitivity of the most potent analog 10l, to selected strains of C. cerevisiae was also evaluated leading to the observation that this scaffold may have a different mode of action from its predecessor, cryptolepine. PMID:24141203

  3. Structure-activity relationship (SAR) and preliminary mode of action studies of 3-substituted benzylthioquinolinium iodide as anti-opportunistic infection agents.

    PubMed

    Bolden, Sidney; Zhu, Xue Y; Etukala, Jagan R; Boateng, Comfort; Mazu, Tryphon; Flores-Rozas, Hernan; Jacob, Melissa R; Khan, Shabana I; Walker, Larry A; Ablordeppey, Seth Y

    2013-01-01

    Opportunistic infections are devastating to immunocompromised patients. And in especially sub-Saharan Africa where the AIDS epidemic is still raging, the mortality rate was recently as high as 70%. The paucity of anti-opportunistic drugs, the decreasing efficacy and the development of resistance against the azoles and even amphotericin B have stimulated the search for new drugs with new mechanisms of action. In a previous work, we showed that a new chemotype derived from the natural product cryptolepine displayed selective toxicity against opportunistic pathogens with minimal cytotoxicity to normal cells. In this manuscript, we report the design and synthesis of substituted benzylthioquinolinium iodides, evaluated their anti-infective properties and formulated some initial structure-activity relationships around phenyl ring A from the original natural product. The sensitivity of the most potent analog 10l, to selected strains of C. cerevisiae was also evaluated leading to the observation that this scaffold may have a different mode of action from its predecessor, cryptolepine.

  4. The SARS-like coronaviruses: the role of bats and evolutionary relationships with SARS coronavirus.

    PubMed

    Balboni, Andrea; Battilani, Mara; Prosperi, Santino

    2012-01-01

    Bats represent an order of great evolutionary success, with elevated geographical diffusion and species diversity. This order harbors viruses of high variability which have a great possibility of acquiring the capacity of infecting other animals,including humans. Bats are the natural reservoir for several viruses genetically closely related to the SARScoronavirus which is the etiological agent of severe acute respiratory syndrome (SARS), a human epidemic which emerged in China in 2002-2003. In the last few years, it has been discovered that the association between coronaviruses and bats is a worldwide phenomenon, and it has been hypothesised that all mammalian coronaviruses were derived from ancestral viruses residing in bats. This review analyzes the role of bats as a reservoir of zoonotic viruses focusing more extensively on SARS-related coronaviruses and taking into account the role of African and European strains in the evolutionary history of these viruses.

  5. DEVELOPMENT OF STRUCTURE ACTIVITY RELATIONSHIPS FOR ASSESSING ECOLOGICAL RISKS

    EPA Science Inventory

    In the field of environmental toxicology, structure activity relationships (SARs) have developed as scientifically-credible tools for predicting the effects of chemicals when little or no empirical data are available.

  6. Quantifying the fingerprint descriptor dependence of structure-activity relationship information on a large scale.

    PubMed

    Dimova, Dilyana; Stumpfe, Dagmar; Bajorath, Jürgen

    2013-09-23

    It is well-known that different molecular representations, e.g., graphs, numerical descriptors, fingerprints, or 3D models, change the numerical results of molecular similarity calculations. Because the assessment of structure-activity relationships (SARs) requires similarity and potency comparisons of active compounds, this representation dependence inevitably also affects SAR analysis. But to what extent? How exactly does SAR information change when alternative fingerprints are used as descriptors? What is the proportion of active compounds with substantial changes in SAR information induced by different fingerprints? To provide answers to these questions, we have quantified changes in SAR information across many different compound classes using six different fingerprints. SAR profiling was carried out on 128 target-based data sets comprising more than 60,000 compounds with high-confidence activity annotations. A numerical measure of SAR discontinuity was applied to assess SAR information on a per compound basis. For ~70% of all test compounds, changes in SAR characteristics were detected when different fingerprints were used as molecular representations. Moreover, the SAR phenotype of ~30% of the compounds changed, and distinct fingerprint-dependent local SAR environments were detected. The fingerprints we compared were found to generate SAR models that were essentially not comparable. Atom environment and pharmacophore fingerprints produced the largest differences in compound-associated SAR information. Taken together, the results of our systematic analysis reveal larger fingerprint-dependent changes in compound-associated SAR information than would have been anticipated.

  7. InSAR observations of active volcanoes in Latin America

    NASA Astrophysics Data System (ADS)

    Morales Rivera, A. M.; Chaussard, E.; Amelung, F.

    2012-12-01

    Over the last decade satellite-based interferometric synthetic aperture radar (InSAR) has developed into a well-known technique to gauge the status of active volcanoes. The InSAR technique can detect the ascent of magma to shallow levels of the volcanic plumbing system because new arriving magma pressurizes the system. This is likely associated with the inflation of the volcanic edifice and the surroundings. Although the potential of InSAR to detect magma migration is well known, the principal limitation was that only for few volcanoes frequent observations were acquired. The ALOS-1 satellite of the Japanese Aerospace Exploration Agency (JAXA) acquired a global L-band data set of 15-20 acquisitions during 2006-2011. Here we use ALOS InSAR and Small Baseline (SB) time-series methods for a ground deformation survey of Latin America with emphasis on the northern Andes. We present time-dependent ground deformation data for the volcanoes in Colombia, Ecuador and Peru and interpret the observations in terms of the dynamics of the volcanic systems.

  8. 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...

  9. 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.

  10. 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.

  11. Structure-activity relationship of crustacean peptide hormones.

    PubMed

    Katayama, Hidekazu

    2016-01-01

    In crustaceans, various physiological events, such as molting, vitellogenesis, and sex differentiation, are regulated by peptide hormones. To understanding the functional sites of these hormones, many structure-activity relationship (SAR) studies have been published. In this review, the author focuses the SAR of crustacean hyperglycemic hormone-family peptides and androgenic gland hormone and describes the detailed results of our and other research groups. The future perspectives will be also discussed.

  12. SARS-CoV nucleocapsid protein interacts with cellular pyruvate kinase protein and inhibits its activity.

    PubMed

    Wei, Wei-Yen; Li, Hui-Chun; Chen, Chiung-Yao; Yang, Chee-Hing; Lee, Shen-Kao; Wang, Chia-Wen; Ma, Hsin-Chieh; Juang, Yue-Li; Lo, Shih-Yen

    2012-04-01

    The pathogenesis of SARS-CoV remains largely unknown. To study the function of the SARS-CoV nucleocapsid protein, we have conducted a yeast two-hybrid screening experiment to identify cellular proteins that may interact with the SARS-CoV nucleocapsid protein. Pyruvate kinase (liver) was found to interact with SARS-CoV nucleocapsid protein in this experiment. The binding domains of these two proteins were also determined using the yeast two-hybrid system. The physical interaction between the SARS-CoV nucleocapsid and cellular pyruvate kinase (liver) proteins was further confirmed by GST pull-down assay, co-immunoprecipitation assay and confocal microscopy. Cellular pyruvate kinase activity in hepatoma cells was repressed by SARS-CoV nucleocapsid protein in either transiently transfected or stably transfected cells. PK deficiency in red blood cells is known to result in human hereditary non-spherocytic hemolytic anemia. It is reasonable to assume that an inhibition of PKL activity due to interaction with SARS-CoV N protein is likely to cause the death of the hepatocytes, which results in the elevation of serum alanine aminotransferase and liver dysfunction noted in most SARS patients. Thus, our results suggest that SARS-CoV could reduce pyruvate kinase activity via its nucleocapsid protein, and this may in turn cause disease.

  13. Considerations about the structure—activity relationships of 8-aminoquinoline antimalarial drugs

    PubMed Central

    McChesney, James D.

    1981-01-01

    A discussion of the structure-activity relationships (SAR) of 8-aminoquinoline antimalarial drugs is presented. Consideration is given to the potential role of metabolic transformations in the in vivo activation of 8-aminoquinolines. It is emphasized that the mechanism of action of 8-aminoquinoline agents has not yet been established and thus any analysis of SAR must be speculative. PMID:6976853

  14. Geosynchronous SAR Orbit Estimation Based on Active Radar Calibrators

    NASA Astrophysics Data System (ADS)

    Leanza, Antonio; Monti Guarnieri, Andrea; Boroquets Ibars, Antoni

    2016-08-01

    The Geosynchronous SAR (GEOSAR) is a system designed for continuous monitoring of a fixed region of the Earth. Differently from LEOSAR, the GEOSAR system requires very long times to form its Synthetic Aperture (SA). This entails the onset of several decorrelation sources, such as atmosphere propagation, orbit perturbations, clock drifts, that have to be compensated to avoid defocusing. In this paper, in particular, it is proposed a solution to cope with the phase error introduced by orbit perturbations within the SA by means of some Active Radar Calibrators (ARC) deployed at convenient positions in the illuminated area. Each ARC provides two-way pulse by pulse echo delay and carrier phase observations used to track the satellite position. The estimation follows an iterative approach whose steps are dividing the SA in sub-apertures, performing the estimation for each sub-aperture, applying the estimated orbit correction and repeating for longer sub-apertures.

  15. Relationship Between ELA and SAR Backscatter Parameters for Selected Transects of the Greenland Ice Sheet

    NASA Astrophysics Data System (ADS)

    Yurchak, B. S.; Abdalati, W.

    2008-12-01

    Changes in the position of the Equilibrium Line Altitude (ELA) provide important information on the state of mass balance of the Greenland Ice Sheet. Direct measurement of the ELA requires a significant amount of meteorological information, and is not practical on a large-scale basis, so it is desirable to develop reliable remote sensing methods for this purpose. The sensitivity of the backscatter of Synthetic Aperture Radar (SAR) to the snow characteristics suggests a possible relationship between the ELA and some backscatter features, and as a result, there have been several attempts to derive a SAR-based ELA retrieval technique. These attempts have focused on the detection of snow line, which is usually located close to the ELA; however no significant correlation was found between the ELA and the SAR-derived snow line. A new technique to monitor the ELA change by SAR is suggested and presented here. Based on an enhanced semi-empirical model of radar backscatter from snow pack, we developed a method to retrieve the snow depth normalized by the penetration depth (snow optical thickness). We exploit the fact that for areas where the snow optical thickness (SOT) is less than unit, the backscatter is sensitive to the snow depth changes. The SOT profiles for the end of the ablation season have been retrieved for period 1997-2003 from RADARSAT-1 C-band SAR data for several transects within an area around the Swiss Camp. These were compared to field data of the ELA (courtesy of Dr. K. Steffen). A high correlation (R2=0.845) has been found between the ELA and the position of the mathematical center of gravity (COG) of a section of the SOT profile that lies between 1000 m and 2000 m altitude. In accordance with the known field data, these altitudes are close to the borders of firn area impacted by melt-freeze cycles. Thus, we assume that the COG altitude change is governed by the firn warming zone extension and transformation and it can successfully be used to determine

  16. Synthesis and SAR studies of benzyl ether derivatives as potent orally active S1P₁ agonists.

    PubMed

    Tsuji, Takashi; Suzuki, Keisuke; Nakamura, Tsuyoshi; Goto, Taiji; Sekiguchi, Yukiko; Ikeda, Takuya; Fukuda, Takeshi; Takemoto, Toshiyasu; Mizuno, Yumiko; Kimura, Takako; Kawase, Yumi; Nara, Futoshi; Kagari, Takashi; Shimozato, Takaichi; Yahara, Chizuko; Inaba, Shinichi; Honda, Tomohiro; Izumi, Takashi; Tamura, Masakazu; Nishi, Takahide

    2014-08-01

    We report herein the synthesis and structure-activity relationships (SAR) of a series of benzyl ether compounds as an S1P₁ receptor modulator. From our SAR studies, the installation of substituents onto the central benzene ring of 2a was revealed to potently influence the S1P₁ and S1P₃ agonistic activities, in particular, an ethyl group on the 2-position afforded satisfactory S1P₁/S1P₃ selectivity. These changes of the S1P₁ and S1P₃ agonistic activities caused by the alteration of substituents on the 2-position were reasonably explained by a docking study using an S1P₁ X-ray crystal structure and S1P₃ homology modeling. We found that compounds 2b and 2e had a potent in vivo immunosuppressive efficacy along with acceptable S1P₁/S1P₃ selectivity, and confirmed that these compounds had less in vivo bradycardia risk through the evaluation of heart rate change after oral administration of the compounds (30 mg/kg, p.o.) in rats.

  17. 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

  18. 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.

  19. 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.

  20. Active-layer thickness estimation from X-band SAR backscatter intensity

    NASA Astrophysics Data System (ADS)

    Widhalm, Barbara; Bartsch, Annett; Leibman, Marina; Khomutov, Artem

    2017-02-01

    The active layer above the permafrost, which seasonally thaws during summer, is an important parameter for monitoring the state of permafrost. Its thickness is typically measured locally, but a range of methods which utilize information from satellite data exist. Mostly, the normalized difference vegetation index (NDVI) obtained from optical satellite data is used as a proxy. The applicability has been demonstrated mostly for shallow depths of active-layer thickness (ALT) below approximately 70 cm. Some permafrost areas including central Yamal are, however, characterized by larger ALT. Surface properties including vegetation structure are also represented by microwave backscatter intensity. So far, the potential of such data for estimating ALT has not been explored. We therefore investigated the relationship between ALT and X-band synthetic aperture radar (SAR) backscatter of TerraSAR-X (averages for 10 × 10 m window) in order to examine the possibility of delineating ALT with continuous and larger spatial coverage in this area and compare it to the already-established method of using NDVI from Landsat (30 m). Our results show that the mutual dependency of ALT and TerraSAR-X backscatter on land cover types suggests a connection of both parameters. A range of 5 dB can be observed for an ALT range of 100 cm (40-140 cm), and an R2 of 0.66 has been determined over the calibration sites. An increase of ALT with increasing backscatter can be determined. The root mean square error (RMSE) over a comparably heterogeneous validation site with maximum ALT of > 150 cm is 20 cm. Deviations are larger for measurement locations with mixed vegetation types (especially partial coverage by cryptogam crust) with respect to the spatial resolution of the satellite data.

  1. Prediction of compounds in different local structure-activity relationship environments using emerging chemical patterns.

    PubMed

    Namasivayam, Vigneshwaran; Gupta-Ostermann, Disha; Balfer, Jenny; Heikamp, Kathrin; Bajorath, Jürgen

    2014-05-27

    Active compounds can participate in different local structure-activity relationship (SAR) environments and introduce different degrees of local SAR discontinuity, depending on their structural and potency relationships in data sets. Such SAR features have thus far mostly been analyzed using descriptive approaches, in particular, on the basis of activity landscape modeling. However, compounds in different local SAR environments have not yet been predicted. Herein, we adapt the emerging chemical patterns (ECP) method, a machine learning approach for compound classification, to systematically predict compounds with different local SAR characteristics. ECP analysis is shown to accurately assign many compounds to different local SAR environments across a variety of activity classes covering the entire range of observed local SARs. Control calculations using random forests and multiclass support vector machines were carried out and a variety of statistical performance measures were applied. In all instances, ECP calculations yielded comparable or better performance than controls. The approach presented herein can be applied to predict compounds that complement local SARs or prioritize compounds with different SAR characteristics.

  2. Cardiac glycoside activities link Na(+)/K(+) ATPase ion-transport to breast cancer cell migration via correlative SAR.

    PubMed

    Magpusao, Anniefer N; Omolloh, George; Johnson, Joshua; Gascón, José; Peczuh, Mark W; Fenteany, Gabriel

    2015-02-20

    The cardiac glycosides ouabain and digitoxin, established Na(+)/K(+) ATPase inhibitors, were found to inhibit MDA-MB-231 breast cancer cell migration through an unbiased chemical genetics screen for cell motility. The Na(+)/K(+) ATPase acts both as an ion-transporter and as a receptor for cardiac glycosides. To delineate which function is related to breast cancer cell migration, structure-activity relationship (SAR) profiles of cardiac glycosides were established at the cellular (cell migration inhibition), molecular (Na(+)/K(+) ATPase inhibition), and atomic (computational docking) levels. The SAR of cardiac glycosides and their analogs revealed a similar profile, a decrease in potency when the parent cardiac glycoside structure was modified, for each activity investigated. Since assays were done at the cellular, molecular, and atomic levels, correlation of SAR profiles across these multiple assays established links between cellular activity and specific protein-small molecule interactions. The observed antimigratory effects in breast cancer cells are directly related to the inhibition of Na(+)/K(+) transport. Specifically, the orientation of cardiac glycosides at the putative cation permeation path formed by transmembrane helices αM1-M6 correlates with the Na(+) pump activity and cell migration. Other Na(+)/K(+) ATPase inhibitors that are structurally distinct from cardiac glycosides also exhibit antimigratory activity, corroborating the conclusion that the antiport function of Na(+)/K(+) ATPase and not the receptor function is important for supporting the motility of MDA-MB-231 breast cancer cells. Correlative SAR can establish new relationships between specific biochemical functions and higher-level cellular processes, particularly for proteins with multiple functions and small molecules with unknown or various modes of action.

  3. Occurrence rate of SAR arcs during the 23nd solar activity cycle

    NASA Astrophysics Data System (ADS)

    Ievenko, Igor

    By data of photometric observations at the Maimaga station (57° N, 200° E, geomagnetic coordinates) at the Yakutsk meridian the occurrence rate of subauroral red (SAR) arcs for the 1997 to 2006 period has been analysed. The observations were carried out during winterspring periods at moonless nights under favorable atmospheric conditions. For˜370 nights of observations (total duration is˜3170 hours) 114 cases of SAR arcs occurrence (˜500 hours) have been registered. The occurrence rate of SAR arcs have been determined as a ratio of the number of registration hour intervals of SAR arcs to the summary observation time in hours for particular months. Subauroral red arcs have been registered every year both in the maximum and in the minimum of the solar activity cycle. The most observation occurrence of red arcs is registered on the rise (˜27%) and decay of the maximum of the solar activity cycle (˜36%). The average occurrence rate of SAR arcs during these years was less than in the 22nd solar activity cycle and is equal to ˜16% of the total observation time. The occurrence rate of SAR arcs observations corresponds to the changes of geomagnetic activity during the 23nd solar activity cycle.

  4. 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.

  5. 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.

  6. Characterization of trans- and cis-cleavage activity of the SARS coronavirus 3CLpro protease: basis for the in vitro screening of anti-SARS drugs.

    PubMed

    Lin, Cheng-Wen; Tsai, Chang-Hai; Tsai, Fuu-Jen; Chen, Pei-Jer; Lai, Chien-Chen; Wan, Lei; Chiu, Hua-Hao; Lin, Kuan-Hsun

    2004-09-10

    Severe acute respiratory syndrome (SARS) has been globally reported. A novel coronavirus (CoV), SARS-CoV, was identified as the etiological agent of the disease. SARS-CoV 3C-like protease (3CLpro) mediates the proteolytic processing of replicase polypeptides 1a and 1ab into functional proteins, playing an important role in viral replication. In this study, we demonstrated the expression of the SARS-CoV 3CLpro in Escherichia coli and Vero cells, and then characterized the in vitro trans-cleavage and the cell-based cis-cleavage by the 3CLpro. Mutational analysis of the 3CLpro demonstrated the importance of His41, Cys145, and Glu166 in the substrate-binding subsite S1 for keeping the proteolytic activity. In addition, alanine substitution of the cleavage substrates indicated that Gln-(P1) in the substrates mainly determined the cleavage efficiency. Therefore, this study not only established the quantifiable and reliable assay for the in vitro and cell-based measurement of the 3CLpro activity, but also characterized the molecular interaction of the SARS-CoV 3CLpro with the substrates. The results will be useful for the rational development of the anti-SARS drugs.

  7. 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.

  8. SAR imagery of the Grand Banks (Newfoundland) pack ice pack and its relationship to surface features

    NASA Technical Reports Server (NTRS)

    Argus, S. D.; Carsey, F. D.

    1988-01-01

    Synthetic Aperture Radar (SAR) data and aerial photographs were obtained over pack ice off the East Coast of Canada in March 1987 as part of the Labrador Ice Margin Experiment (LIMEX) pilot project. Examination of this data shows that although the pack ice off the Canadian East Coast appears essentially homogeneous to visible light imagery, two clearly defined zones of ice are apparent on C-band SAR imagery. To identify factors that create the zones seen on the radar image, aerial photographs were compared to the SAR imagery. Floe size data from the aerial photographs was compared to digital number values taken from SAR imagery of the same ice. The SAR data of the inner zone acquired three days apart over the melt period was also examined. The studies indicate that the radar response is governed by floe size and meltwater distribution.

  9. The RNA polymerase activity of SARS-coronavirus nsp12 is primer dependent

    PubMed Central

    te Velthuis, Aartjan J. W.; Arnold, Jamie J.; Cameron, Craig E.; van den Worm, Sjoerd H. E.; Snijder, Eric J.

    2010-01-01

    An RNA-dependent RNA polymerase (RdRp) is the central catalytic subunit of the RNA-synthesizing machinery of all positive-strand RNA viruses. Usually, RdRp domains are readily identifiable by comparative sequence analysis, but biochemical confirmation and characterization can be hampered by intrinsic protein properties and technical complications. It is presumed that replication and transcription of the ∼30-kb severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) RNA genome are catalyzed by an RdRp domain in the C-terminal part of nonstructural protein 12 (nsp12), one of 16 replicase subunits. However, thus far full-length nsp12 has proven refractory to expression in bacterial systems, which has hindered both the biochemical characterization of coronavirus RNA synthesis and RdRp-targeted antiviral drug design. Here, we describe a combined strategy involving bacterial expression of an nsp12 fusion protein and its in vivo cleavage to generate and purify stable SARS-CoV nsp12 (106 kDa) with a natural N-terminus and C-terminal hexahistidine tag. This recombinant protein possesses robust in vitro RdRp activity, as well as a significant DNA-dependent activity that may facilitate future inhibitor studies. The SARS-CoV nsp12 is primer dependent on both homo- and heteropolymeric templates, supporting the likeliness of a close enzymatic collaboration with the intriguing RNA primase activity that was recently proposed for coronavirus nsp8. PMID:19875418

  10. Structure of the SARS coronavirus main proteinase as an active C{sub 2} crystallographic dimer

    SciTech Connect

    Xu, Ting; Ooi, Amy; Lee, Hooi Chen; Wilmouth, Rupert; Liu, Ding Xiang; Lescar, Julien

    2005-11-01

    An orthorhombic crystal form of the SARS CoV main proteinase diffracting to a resolution of 1.9 Å is reported. The conformation of residues in the catalytic site indicates an active enzyme. The 34 kDa main proteinase (M{sup pro}) from the severe acute respiratory syndrome coronavirus (SARS-CoV) plays an important role in the virus life cycle through the specific processing of viral polyproteins. As such, SARS-CoV M{sup pro} is a key target for the identification of specific inhibitors directed against the SARS virus. With a view to facilitating the development of such compounds, crystals were obtained of the enzyme at pH 6.5 in the orthorhombic space group P2{sub 1}2{sub 1}2 that diffract to a resolution of 1.9 Å. These crystals contain one monomer per asymmetric unit and the biologically active dimer is generated via the crystallographic twofold axis. The conformation of the catalytic site indicates that the enzyme is active in the crystalline form and thus suitable for structure-based inhibition studies.

  11. A G-quadruplex-binding macrodomain within the "SARS-unique domain" is essential for the activity of the SARS-coronavirus replication-transcription complex.

    PubMed

    Kusov, Yuri; Tan, Jinzhi; Alvarez, Enrique; Enjuanes, Luis; Hilgenfeld, Rolf

    2015-10-01

    The multi-domain non-structural protein 3 of SARS-coronavirus is a component of the viral replication/transcription complex (RTC). Among other domains, it contains three sequentially arranged macrodomains: the X domain and subdomains SUD-N as well as SUD-M within the "SARS-unique domain". The X domain was proposed to be an ADP-ribose-1"-phosphatase or a poly(ADP-ribose)-binding protein, whereas SUD-NM binds oligo(G)-nucleotides capable of forming G-quadruplexes. Here, we describe the application of a reverse genetic approach to assess the importance of these macrodomains for the activity of the SARS-CoV RTC. To this end, Renilla luciferase-encoding SARS-CoV replicons with selectively deleted macrodomains were constructed and their ability to modulate the RTC activity was examined. While the SUD-N and the X domains were found to be dispensable, the SUD-M domain was crucial for viral genome replication/transcription. Moreover, alanine replacement of charged amino-acid residues of the SUD-M domain, which are likely involved in G-quadruplex-binding, caused abrogation of RTC activity.

  12. The Soil Moisture Active/Passive (SMAP) Mission Radar: A Novel Conically Scanning SAR

    NASA Technical Reports Server (NTRS)

    Spencer, Michael; Chan, Samuel; Veilleux, Louise; Wheeler, Kevin

    2009-01-01

    The Soil Moisture Active/Passive (SMAP) mission is a NASA mission identified by the NRC "decadal survey" to measure both soil moisture and freeze/thaw state from space. The mission will use both active radar and passive radiometer instruments at L-Band. In order to achieve a wide swath at sufficiently high resolution for both active and passive chan-nels, an instrument architecture that uses a large rotating reflector is employed. The active radar will further utilize SAR processing in order to obtain the sub-footprint resolution necessary for the geophysical retrievals. The SMAP radar has a unique geometry where the antenna footprint is continuously rotated about nadir in a conical fashion, as opposed to the more common side-looking SAR design. In additional to the unconventional scan geometry, the SMAP radar must address the effects of Faraday rotation and radio frequency interference (RFI), both consequences of the L-Band frequency of operation.

  13. 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.

  14. The Structure of Sec12 Implicates Potassium Ion Coordination in Sar1 Activation*

    PubMed Central

    McMahon, Conor; Studer, Sean M.; Clendinen, Chaevia; Dann, Geoffrey P.; Jeffrey, Philip D.; Hughson, Frederick M.

    2012-01-01

    Coat protein II (COPII)-coated vesicles transport proteins and lipids from the endoplasmic reticulum to the Golgi. Crucial for the initiation of COPII coat assembly is Sec12, a guanine nucleotide exchange factor responsible for activating the small G protein Sar1. Once activated, Sar1/GTP binds to endoplasmic reticulum membranes and recruits COPII coat components (Sec23/24 and Sec13/31). Here, we report the 1.36 Å resolution crystal structure of the catalytically active, 38-kDa cytoplasmic portion of Saccharomyces cerevisiae Sec12. Sec12 adopts a β propeller fold. Conserved residues cluster around a loop we term the “K loop,” which extends from the N-terminal propeller blade. Structure-guided site-directed mutagenesis, in conjunction with in vitro and in vivo functional studies, reveals that this region of Sec12 is catalytically essential, presumably because it makes direct contact with Sar1. Strikingly, the crystal structure also reveals that a single potassium ion stabilizes the K loop; bound potassium is, moreover, essential for optimum guanine nucleotide exchange activity in vitro. Thus, our results reveal a novel role for a potassium-stabilized loop in catalyzing guanine nucleotide exchange. PMID:23109340

  15. 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.

  16. Structure and antioxidant activity relationships of isoflavonoids from Dalbergia parviflora.

    PubMed

    Promden, Worrawat; Monthakantirat, Orawan; Umehara, Kaoru; Noguchi, Hiroshi; De-Eknamkul, Wanchai

    2014-02-20

    The antioxidant activities of 24 isoflavonoids that were previously isolated as pure compounds from Dalbergia parviflora were evaluated using three different in vitro antioxidant-based assay systems: xanthine/xanthine oxidase (X/XO), ORAC, and DPPH. The isolates consisted of three subgroups, namely isoflavones, isoflavanones, and isoflavans, each of which appeared to have diversified substituents, and were thus ideal for the study of their structure-activity relationships (SARs). The SAR analysis was performed using the results obtained from both the inter-subgroup isoflavonoids with the same substitution pattern and the intra-subgroup compounds with different substitution patterns. The inter-subgroup comparison showed that the isoflavones exhibited the highest antioxidant activities based on all three assays. The intra-subgroup analysis showed that the additional presence of an OH group in Ring B at either R3' or R5' from the basic common structure of the R7-OH of Ring A and the R4'-OH (or -OMe) of Ring B greatly increased the antioxidant activities of all of the isoflavonoid subgroups and that other positions of OH and OMe substitutions exerted different effects on the activities depending on the subgroup and assay type. Therefore, based on the structural diversity of the isoflavonoids in D. parviflora, the present study provides the first clarification of the detailed antioxidant SARs of isoflavonoids.

  17. 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}.

  18. 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

  19. 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.

  20. Detection of Creep Displacement by DInSAR using TerraSAR-X data around Active Fault in the Metro Manila, the Philippine

    NASA Astrophysics Data System (ADS)

    Deguchi, T.

    2010-12-01

    Tomonori Deguchi (Nittetsu Mining Consultants Co., Ltd.) Yoshihiro Kinugasa (Association for the Development of Earthquake Prediction) Katsumi Kurita (Tokyo Metropolitan College of Industrial Technology) Makoto Omura (Kochi Womes's University) Tomoya Oku (Earth Remote Sensing Data Analysis Center) Many ground deformations have been occurred by earthquakes and volcanic activities in the Republic of the Philippines. The monitoring of deformation using InSAR, which is capable to observe a wide area at high spatial resolution, as well as GPS measurement and leveling survey, which are capable to measure the point-based but subtle land displacement less than a centimeter, is actively conducted in this country. The Valley fault exhibits fault creep displacement. It is a north-south trending active fault on the eastern edge of the Metro Manila district, central Luzon. Some buildings and road pavement are damaged by vertical displacement of the ground where the central segment of the fault passes through. Moreover, overpumping of groundwater in the Metro Manila district has occurred huge ground subsidences. The purpose of this study is to investigate the distribution of spatial and temporal change on the earth surface around Metro Manila. We measured long-term ground deformation from 2003 until 2010 by means of InSAR and time series analysis using ENVISAT/ASAR data. As a result, it shows that the uplift phenomena in the western part of Valley fault are uniform. On the other hand, the land movement in the eastern part of the Valley fault had reversed from subsidence to uplift in around 2007. It would be difficult to conceive that these tendencies resulted from groundwater pumping. We applied DInSAR using TerraSAR-X data in order to measure the detailed spatial distribution of creep displacement around the Valley fault. Additionally, we tried to detect a steep gradient of interferometric phase using the first differentiation. From this analysis, some segments in the direction

  1. SARS Basics

    MedlinePlus

    ... coronavirus (SARS-CoV). SARS was first reported in Asia in February 2003. Over the next few months, ... countries in North America, South America, Europe, and Asia before the SARS global outbreak of 2003 was ...

  2. The Role of mgrA and sarA in Autolysis and Resistance to Cell Wall-Active Antibiotics in Methicillin-Resistant Staphylococcus aureus

    PubMed Central

    Trotonda, María Pilar; Xiong, Yan Q.; Memmi, Guido; Bayer, Arnold S.; Cheung, Ambrose L.

    2009-01-01

    Background We have previously shown the importance of mgrA and sarA in controlling autolysis of Staphylococcus aureus, with MgrA and SarA both being negative regulators of murein hydrolases. Methods In this study, we analyzed the effects of mgrA and sarA on antibiotic-mediated lysis in vitro, and on the responses to cell wall-active antibiotic therapy in an experimental endocarditis model using two representative MRSA strains: laboratory strain COL and community-acquired clinical isolate, MW2. Results We found that mgrA and sarA independently down-regulated sarV (a marker for autolysis), although the alteration in sarV expression did not correlate directly with the autolysis profiles of single mgrA and sarA mutants. Importantly, the mgrA/sarA double mutants of both strains were more autolytic in vitro as compared with the single mutants. In vivo, we demonstrated that, despite equivalent intrinsic virulence between the parents and their isogenic mgrA/sarA double mutants in the endocarditis model, oxacillin and vancomycin treatment of the mgrA/sarA double mutants of MRSA strains COL and MW2 yielded significant reductions in vegetation bacterial densities vs. their respective parents. Conclusions These results suggest that down-regulation of mgrA/sarA in combination with cell wall-active antibiotics may represent a novel approach to treat MRSA infections. PMID:19072553

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

    PubMed

    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.

  4. 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

  5. Activity of Nyiragongo and Nyamulagira Volcanoes (Dem. Rep. of Congo) Revealed Using Geological, Geophysical and InSAR data

    NASA Astrophysics Data System (ADS)

    Wauthier, C.; Cayol, V.; Hooper, A.; Kervyn, F.; Marinkovic, P.; D'Oreye, N.; Poland, M. P.

    2010-12-01

    Ground-based monitoring of active volcanoes in Africa can be problematic due to political instabilities, safety issues and poor accessibility. Remote-sensing techniques such as Differential Interferometric Synthetic Aperture Radar (DInSAR, more commonly InSAR), are therefore very useful and provide robust observational tools for natural hazard assessment, regardless of local conditions. Nyiragongo and Nyamulagira volcanoes (which experienced nine eruptions from December 1996 to January 2010) are located in the western branch of the East African Rift (Virunga Volcanic Province, North Kivu, Dem. Rep. of Congo). InSAR has recorded ground displacements related to most of the tectonic and volcanic events that have occurred since 1996 using SAR images from the JERS, ERS-1/2, ENVISAT, RADARSAT-1, RADARSAT-2 and ALOS satellites. This database provides excellent spatial and temporal resolution of deformation, leading to insights into tectonic and volcanic processes. Loss of coherence within the SAR signal due to rapid-changing equatorial vegetation hampers the use of InSAR as a volcano-tectonic monitoring tool. We partially overcome this limitation using 1) a large number of SAR images, including about 150 ENVISAT and more than 100 RADARSAT-1 images, 2) short repeat times of 24 and 35 days for RADARSAT-1 and ENVISAT, respectively, and 3) satellites with longer wavelengths, such as JERS and ALOS. Using a large dataset combining short revisit time SAR images significantly increases the chances of producing interferograms with good coherence. A longer wavelength radar signal better penetrates vegetation cover, also increasing coherence. Furthermore, useful data were retrieved in low-coherence areas by applying the “StaMPS” (Stanford Method for Persistent Scatterers) method, which combines a small baseline and persistent scatterers approach, to our largest SAR datasets. Using several look angles from both ascending and descending orbital tracks, we were able to characterize

  6. DInSAR techniques for studying the October 23, 2011, Van earthquake (Turkey), and its relationship with neighboring structures

    NASA Astrophysics Data System (ADS)

    Bignami, C.; Brunori, C. A.; Chini, M.; Kyriakopoulos, C.; Melini, D.; Moro, M.; Picchiani, M.; Saroli, M.; Stramondo, S.

    2012-04-01

    We have investigated the possible causal relationship between three earthquakes occurred in Turkey. In particular the Mw 7.2 October 23, 2011 earthquakes occurred in the Van province, located in the Eastern Turkey near Lake Van, its aftershock occurred the November 9 few kilometers southward, and another major event (Ms = 7.3) occurred north of Van in East Anatolia on 24 November 1976 along the Caldiran fault. The Mw 7.2 Van event took place along a previously unrecognized east-west thrust fault. The largest aftershock has hit Van Province has a magnitude 5.5 at 4.3 km of depth very close to Van. For the Van earthquake and its aftershock we used DInSAR measures for retrieving the faults parameters. A couple of COSMO-SkyMed images has been used to measure the coseismic deformation of the first event, while two TerraSAR-X interferometric images have been used for the second one. For both the topography contribution has been removed using the SRTM digital elevation model. Based on DInSAR outcomes we have then inverted the coseismic displacement field using the a novel approach [1], based on the Okada model and Neural Networks (NNs), to investigate the fault geometry of the two latest earthquakes. One of the advantages of this method is that it rapidly achieves a determination of the rupture plane. Concerning the earthquake occurred on 1976 the fault plane has been deduced using surface ruptures from ground survey [2]. Once defined the geometries of the three seismogenic fault planes we have investigated the role of the Caldiran earthquake in promoting the Van rupture, and the latter in promoting its aftershock, by evaluating the Coulomb Failure Function. [1] Stramondo, S., Del Frate, F., Picchiani, M. & Schiavon, G. Seismic Source Quantitative Parameters Retrieval from InSAR Data and Neural Networks. IEEE Transactions on Geoscience and Remote Sensing 49, 96-104 (2011). [2] M. NAFI TOKSÖZ*, ESEN ARPAT† & FUAT ŞARO&GLU, "East Anatolian earthquake of 24 November 1976

  7. Proteolytic activation of the SARS-coronavirus spike protein: cutting enzymes at the cutting edge of antiviral research.

    PubMed

    Simmons, Graham; Zmora, Pawel; Gierer, Stefanie; Heurich, Adeline; Pöhlmann, Stefan

    2013-12-01

    The severe acute respiratory syndrome (SARS) pandemic revealed that zoonotic transmission of animal coronaviruses (CoV) to humans poses a significant threat to public health and warrants surveillance and the development of countermeasures. The activity of host cell proteases, which cleave and activate the SARS-CoV spike (S) protein, is essential for viral infectivity and constitutes a target for intervention. However, the identities of the proteases involved have been unclear. Pioneer studies identified cathepsins and type II transmembrane serine proteases as cellular activators of SARS-CoV and demonstrated that several emerging viruses might exploit these enzymes to promote their spread. Here, we will review the proteolytic systems hijacked by SARS-CoV for S protein activation, we will discuss their contribution to viral spread in the host and we will outline antiviral strategies targeting these enzymes. This paper forms part of a series of invited articles in Antiviral Research on "From SARS to MERS: 10years of research on highly pathogenic human coronaviruses.''

  8. A categorical structure-activity relationship analysis of GPR119 ligands.

    PubMed

    Kumar, Pritesh; Carrasquer, Carl A; Carter, Arren; Song, Zhao-Hui; Cunningham, Albert R

    2014-01-01

    The categorical structure-activity relationship (cat-SAR) expert system has been successfully used in the analysis of chemical compounds that cause toxicity. Herein we describe the use of this fragment-based approach to model ligands for the G protein-coupled receptor 119 (GPR119). Using compounds that are known GPR119 agonists and compounds that we have confirmed experimentally that are not GPR119 agonists, four distinct cat-SAR models were developed. Using a leave-one-out validation routine, the best GPR119 model had an overall concordance of 99%, a sensitivity of 99%, and a specificity of 100%. Our findings from the in-depth fragment analysis of several known GPR119 agonists were consistent with previously reported GPR119 structure-activity relationship (SAR) analyses. Overall, while our results indicate that we have developed a highly predictive cat-SAR model that can be potentially used to rapidly screen for prospective GPR119 ligands, the applicability domain must be taken into consideration. Moreover, our study demonstrates for the first time that the cat-SAR expert system can be used to model G protein-coupled receptor ligands, many of which are important therapeutic agents.

  9. 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.

  10. Out-of-Band 40 DB Bandwidth of EESS (Active) Spaceborne SARS

    NASA Technical Reports Server (NTRS)

    Huneycutt, Bryan L.

    2005-01-01

    This document presents a study of out of band (OOB) 40 dB bandwidth requirements of spaceborne SARs in the Earth Exploration-Satellite Service (active) and Space Research Service (active). The purpose of the document is to study the OOB 40 dB bandwidth requirements and compare the 40 dB bandwidth B-40 as measured in simulations with that calculated using the ITU-R Rec SM.1541 equations. The spectra roll-off and resulting OOB 40 dB bandwidth of the linear FM signal is affected by the time-bandwidth product and the rise/fall times. Typical values of these waveform characteristics are given for existing EESS (active) sensors.

  11. Activation of sarX by Rbf Is Required for Biofilm Formation and icaADBC Expression in Staphylococcus aureus

    PubMed Central

    Cue, David; Lei, Mei G.

    2013-01-01

    A major constituent of many Staphylococcus aureus biofilms is a polysaccharide known as the polysaccharide intercellular adhesin, or poly N-acetylglucosamine (PIA/PNAG). PIA/PNAG is synthesized by the 4 gene products of the icaADBC operon, which is negatively regulated by the divergently transcribed icaR gene. We previously reported the identification of a gene, rbf, involved in the positive transcriptional regulation of icaADBC transcription by repressing icaR in S. aureus strain 8325-4. However, we were unable to show binding of Rbf to DNA upstream of icaR or icaA, suggesting that Rbf may control expression of an unknown factor(s) that, in turn, regulates ica expression. Here we report that the unknown factor is SarX protein. Results from epistasis assays and genetic complementation analyses suggest that Rbf upregulates SarX, which then downregulates IcaR, thereby activating icaADBC. Electrophoretic mobility shift assays revealed that SarX protein bound to a sequence upstream of icaR within the icaA coding region. Cross-linking and immunoprecipitation experiments further suggested that Rbf binds to the sarX promoter in S. aureus. These results demonstrate that Rbf and SarX represent a regulatory cascade that promotes PIA-dependent biofilm formation in S. aureus. PMID:23354746

  12. SARANEA: a freely available program to mine structure-activity and structure-selectivity relationship information in compound data sets.

    PubMed

    Lounkine, Eugen; Wawer, Mathias; Wassermann, Anne Mai; Bajorath, Jürgen

    2010-01-01

    We introduce SARANEA, an open-source Java application for interactive exploration of structure-activity relationship (SAR) and structure-selectivity relationship (SSR) information in compound sets of any source. SARANEA integrates various SAR and SSR analysis functions and utilizes a network-like similarity graph data structure for visualization. The program enables the systematic detection of activity and selectivity cliffs and corresponding key compounds across multiple targets. Advanced SAR analysis functions implemented in SARANEA include, among others, layered chemical neighborhood graphs, cliff indices, selectivity trees, editing functions for molecular networks and pathways, bioactivity summaries of key compounds, and markers for bioactive compounds having potential side effects. We report the application of SARANEA to identify SAR and SSR determinants in different sets of serine protease inhibitors. It is found that key compounds can influence SARs and SSRs in rather different ways. Such compounds and their SAR/SSR characteristics can be systematically identified and explored using SARANEA. The program and source code are made freely available under the GNU General Public License.

  13. The relationship between aboveground biomass and radar backscatter as observed on airborne SAR imagery

    NASA Technical Reports Server (NTRS)

    Kasischke, Eric S.; Bourgeau-Chavez, Laura L.; Christensen, Norman L., Jr.; Dobson, M. Craig

    1991-01-01

    The initial results of an experiment to examine the dependence of radar image intensity on total above-ground biomass in a southern US pine forest ecosystem are presented. Two sets of data are discussed. First, we examine two L-band (VV-polarization) data sets which were collected 5 years apart. These data sets clearly illustrate the change in backscatter resulting from the growth of a young pine stand. Second, we examine the dependence between radar backscatter and biomass as a function of radar frequency using data from the JPL Airborne Synthetic Aperture Radar (AIRSAR) and ERIM/NADC P-3 SAR systems. These results show that there is a positive correlation between above-ground biomass and radar backscatter and at C-, L-, and P-bands, but very little correlation at C-band. The biomass level for which this positive correlation holds decreases as radar frequency increases. This positive correlation is stronger at HH and HV polarizations that VV polarization at L- and P-bands, but strongest at VV polarization for C-band.

  14. Applications of Systematic Molecular Scaffold Enumeration to Enrich Structure-Activity Relationship Information.

    PubMed

    Mok, N Yi; Brown, Nathan

    2017-01-23

    Establishing structure-activity relationships (SARs) in hit identification during early stage drug discovery is important in accelerating hit confirmation and expansion. We describe the development of EnCore, a systematic molecular scaffold enumeration protocol using single atom mutations, to enhance the application of objective scaffold definitions and to enrich SAR information from analysis of high-throughput screening output. A list of 43 literature medicinal chemistry compound series, each containing a minimum of 100 compounds, published in the Journal of Medicinal Chemistry was collated to validate the protocol. Analysis using the top representative Level 1 scaffolds this list of literature compound series demonstrated that EnCore could mimic the scaffold exploration conducted when establishing SAR. When EnCore was applied to analyze an HTS library containing over 200 000 compounds, we observed that over 70% of the molecular scaffolds matched extant scaffolds within the library after enumeration. In particular, over 60% of the singleton scaffolds with only one representative compound were found to have structurally related compounds after enumeration. These results illustrate the potential of EnCore to enrich SAR information. A case study using literature cyclooxygenase-2 inhibitors further demonstrates the advantage of EnCore application in establishing SAR from structurally related scaffolds. EnCore complements literature enumeration methods in enabling changes to the physicochemical properties of molecular scaffolds and structural modifications to aliphatic rings and linkers. The enumerated scaffold clusters generated would constitute a comprehensive collection of scaffolds for scaffold morphing and hopping.

  15. 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.

  16. Structure activity relationships of spiramycins.

    PubMed

    Omura, S; Sano, H; Sunazuka, T

    1985-07-01

    Sixty-six derivatives of spiramycin I and neospiramycin I were synthesized and evaluated by four parameters, MIC, affinity to ribosomes (ID50), therapeutic effect in mice and retention time in HPLC. Among the derivatives, 3,3'',4''-tri-O-propionyl- and 3,4''-di-O-acetyl-3''-O-butyrylspiramycin I showed the highest therapeutic effect which was superior to acetylspiramycin. Structure activity relationships of spiramycins are discussed.

  17. 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...

  18. Structure-activity relationship for the oxadiazole class of antibiotics.

    PubMed

    Spink, Edward; Ding, Derong; Peng, Zhihong; Boudreau, Marc A; Leemans, Erika; Lastochkin, Elena; Song, Wei; Lichtenwalter, Katerina; O'Daniel, Peter I; Testero, Sebastian A; Pi, Hualiang; Schroeder, Valerie A; Wolter, William R; Antunes, Nuno T; Suckow, Mark A; Vakulenko, Sergei; Chang, Mayland; Mobashery, Shahriar

    2015-02-12

    The structure-activity relationship (SAR) for the newly discovered oxadiazole class of antibiotics is described with evaluation of 120 derivatives of the lead structure. This class of antibiotics was discovered by in silico docking and scoring against the crystal structure of a penicillin-binding protein. They impair cell-wall biosynthesis and exhibit activities against the Gram-positive bacterium Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA) and vancomycin-resistant and linezolid-resistant S. aureus. 5-(1H-Indol-5-yl)-3-(4-(4-(trifluoromethyl)phenoxy)phenyl)-1,2,4-oxadiazole (antibiotic 75b) was efficacious in a mouse model of MRSA infection, exhibiting a long half-life, a high volume of distribution, and low clearance. This antibiotic is bactericidal and is orally bioavailable in mice. This class of antibiotics holds great promise in recourse against infections by MRSA.

  19. Semi-Automated Detection Of Terrain Activity In The Swiss Alpine Periglacial Environment From DInSAR Scenes

    NASA Astrophysics Data System (ADS)

    Barboux, Chloe; Dalaloye, Reynald; Lambiel, Christophe; Strozzi, Tazio; Raetzo, Hugo; Collet, Claude

    2013-12-01

    This paper proposes a semi-automated method to update inventory of moving slopes. First a Map of Terrain Activity (MTA) is created by partitioning an interferogram, using segmentation and classification processes, into 3 regions: stable areas, coherently moving parts and decorrelated areas (due to motion or not). Then, a Combined-Map of Terrain Activity (C- MTA) is computed describing the general behavior of the terrain at a specific time-lapse. Finally, C-MTA is used to determine the potential change in the activity rate of moving slopes. Tests are performed in a small area using large set of TSX DInSAR scenes from summers 2008 to 2012 in order to update past moving slope inventories produced from ERS DInSAR data.

  20. 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

  1. Synthesis, Fungicidal Activity, and Structure Activity Relationship of β-Acylaminocycloalkylsulfonamides against Botrytis cinerea

    PubMed Central

    Liu, Chun-Hui; Chen, Xiao-Yuan; Qin, Pei-Wen; Qi, Zhi-Qiu; Ji, Ming-Shan; Liu, Xing-Yu; Babu, P. Vijaya; Li, Xing-Hai; Cui, Zi-Ning

    2017-01-01

    In order to discover new antifungal agrochemicals that could have highly active and novel motifs, thirty-six new 2-acylaminocycloalkylsulfonamides (IV) were synthesized. Their structures were characterized and confirmed by 1H NMR, 13C NMR, IR, MS, elemental analysis and X-ray single crystal diffraction. In vitro and in vivo activities against various Botrytis cinerea strains were evaluated. Bioassay results revealed that most of the title compounds exhibited excellent in vitro fungicidal activity, in which compound IV-26 showed the highest activity against sensitive, low-resistant, moderate-resistant and high-resistant strains of B. cinerea compared with the positive fungicide procymidone. Meanwhile in vivo fungicidal activity of compound IV-31 was better than the commercial fungicides procymidone and chesulfamide in greenhouse trial. The structure activity relationship (SAR) was also discussed and the results were of importance to the structural optimization and development of more potent sulfonamides antifungal agents. PMID:28176837

  2. Structure-activity relationship in binding ligands to library of artificial receptors: the search for biocompatible sensor.

    PubMed

    Frączyk, Justyna; Mrozek, Agnieszka; Kamiński, Zbigniew J

    2010-11-01

    Structure-activity relationship (SAR) analysis was applied for studies of docking of colored ligands to library of artificial receptors formed by self-assembly of N-lipidated amino acids immobilised on the cellulose support. The studies show that the binding depends mainly on the structure of amino acid fragment but influence of N-lipidic fragment is less important.

  3. 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

  4. SAR transmitter

    NASA Astrophysics Data System (ADS)

    1983-06-01

    In the follow-on of the ESA contract 4122/79 it was intended to demonstrate on breadboard the feasibility of a modular EPC supplied by a multibus for a KLYSTRON power transmitter. The aim of this final report is to give details on the design and on test results of the electronics required to drive a KLYSTRON for a SAR system. The concept utilized for the DC/DC conversion is a Series Resonant type (SCHWARZ Converter). An elegant Breadboard of 2 Modules (over 4 required for the complete EPC) has been realized and the tests have demonstrated the envisaged feasibility of an active redundancy with modular EPC both for output voltage generation and for output power. Also the concept of the multibus has been implemented (2 bus over 4) and verified in the EPC breadboard.

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

    PubMed

    Sahu, Pramod K

    2016-10-04

    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.

  6. Short peptides derived from the interaction domain of SARS coronavirus nonstructural protein nsp10 can suppress the 2'-O-methyltransferase activity of nsp10/nsp16 complex.

    PubMed

    Ke, Min; Chen, Yu; Wu, Andong; Sun, Ying; Su, Ceyang; Wu, Hao; Jin, Xu; Tao, Jiali; Wang, Yi; Ma, Xiao; Pan, Ji-An; Guo, Deyin

    2012-08-01

    Coronaviruses are the etiological agents of respiratory and enteric diseases in humans and livestock, exemplified by the life-threatening severe acute respiratory syndrome (SARS) caused by SARS coronavirus (SARS-CoV). However, effective means for combating coronaviruses are still lacking. The interaction between nonstructural protein (nsp) 10 and nsp16 has been demonstrated and the crystal structure of SARS-CoV nsp16/10 complex has been revealed. As nsp10 acts as an essential trigger to activate the 2'-O-methyltransferase activity of nsp16, short peptides derived from nsp10 may have inhibitory effect on viral 2'-O-methyltransferase activity. In this study, we revealed that the domain of aa 65-107 of nsp10 was sufficient for its interaction with nsp16 and the region of aa 42-120 in nsp10, which is larger than the interaction domain, was needed for stimulating the nsp16 2'-O-methyltransferase activity. We further showed that two short peptides derived from the interaction domain of nsp10 could inhibit the 2'-O-methyltransferase activity of SARS-CoV nsp16/10 complex, thus providing a novel strategy and proof-of-principle study for developing peptide inhibitors against SARS-CoV.

  7. Active faults in Lebanon : kinematics and interseismic behavior measured from radar interferometry (InSAR)

    NASA Astrophysics Data System (ADS)

    Lasserre, C.; Pinel-Puysségur, B.; Vergnolle, M.; Klinger, Y.; Pathier, E.

    2012-12-01

    The Levant fault system, more than 1000 km-long, marks the limit between the Arabian and Sinaï tectonic plates, extending from the Aqaba gulf in the Red Sea to Turkey. Mostly left-lateral, it forms a transpression zone in Lebanon, associating strike-slip faults such as the Yammouneh fault and thrust faults such as the Mount Lebanon thrust. This fault system in Lebanon is at the origin of large historical earthquakes during the past two thousand years (551 AD on the thrust offshore and 1837 along the Roum fault inland, 1759 along the Rashaia and Sergaya faults). We aim at characterizing the present-day behavior of active faults in Lebanon, in particular the Yammouneh fault which did not break since 1202, to contribute to a better assessment of the seismic hazard in this region. Space geodesy techniques (GPS, InSAR) allow to quantify the present-day displacements across faults (a few mm/yr during the interseismic period), and to model stress loading and relaxation processes during the seismic cycle, at the fault scale and at the regional scale. GPS campaign measurements have been made along profiles perpendicular to the Yammouneh fault. In addition, an important archive of radar images covering Lebanon (acquired by the ERS and Envisat satellites, along descending and ascending orbits) is also available. We process ERS and Envisat radar data to obtain the average interseismic velocity field across faults over the past 15-20 years. Techniques of interferograms networks processing (MuLSAR), atmospheric phase delays correction from global atmospherical models, DEM correction and time series inversion (NSBAS) are used to overcome the main remaining limitations in the measurements accuracy (low coherence, strong atmospheric delays, long wavelength deformation signal). The final goal is to propose a modelling of the surface displacement field to quantify the present-day kinematics of active fauts in Lebanon, taking into account GPS data as well as tectonic and

  8. Monitoring the kinematic of active landslides with ALOS/PALSAR DInSAR processing.

    NASA Astrophysics Data System (ADS)

    Schlögel, Romy; Doubre, Cécile; Malet, Jean-Philippe

    2014-05-01

    This study targets the analysis of the kinematics of large active landslide through the interpretation of L-band ALOS/PALSAR interferograms. In mountainous areas, landslide monitoring with radar images is often difficult to interpret because of the complex topography, important changes in vapor content in the atmosphere, and the presence of highly variable surface states (vegetation, soil humidity, snow cover, superficial mass transfer). Sliding sub-units of two large and continuously active landslides (La Valette and Poche), exhibiting displacement rates ranging from 0.1 to 4.0 cm.day-1, are used as case studies to develop and explain the methodology. The results corresponding to positive or negative difference in phase value allow for the detection of landslide sub-units characterized by different kinematic patterns (e.g. single rotational slide, translational slide, multiple rotational slides). In the upper parts of the landslides, predominance of vertical displacements (subsidence) is observed in addition to a displacement in the downslope direction; this kinematic pattern is highlighted by either positive phase values corresponding to motion far away from the satellite. In the lower parts of the landslides, accumulation is observed in addition to a displacement in the downslope direction; this kinematic pattern is highlighted by negative phase values in the interferograms corresponding to motion toward the satellite. Extension of the landslides (downhill, uphill or laterally) is discussed according to geomorphological observations and a priori knowledge on the landslides. Quantitative measurements of the displacement are projected along the slope and the vertical components according to the observed landslide patterns. The InSAR displacements are in good agreement with on-site field measurements (permanent GNSS observations, GNSS campaigns on benchmarks, and terrestrial laser scanner surveys). Peaks in displacement rates are correlated to meteorological data.

  9. Mixed jamming method for SAR

    NASA Astrophysics Data System (ADS)

    Zhao, Hong-feng; Zhang, Peng; Wang, Yong-sheng

    2007-11-01

    The mixed jamming method of synthetic aperture radar is analyzed and discussed. The methods of active noise and deception jamming and the signal model of transmitting is described. The raw echo signal of SAR and the model of jammed echo signal are expatiated, the characteristic of SAR and the evaluating method of jamming effect are established. Finally, the mixed jamming imaging of SAR is simulated.

  10. Three data mining techniques to improve lazy structure-activity relationships for noncongeneric compounds.

    PubMed

    Sommer, Selina; Kramer, Stefan

    2007-01-01

    We present three simple, yet effective data mining techniques for lazy structure-activity relationships (SARs) of noncongeneric compounds. In lazy SARs, classifications are particularly tailored for each test compound. Therefore, it is possible to make the most of the structure of a test compound. In our case, we derive its substructures and use them to determine similar structures. To obtain a well-balanced and representative set of structural descriptors, we enrich this set by strongly activating or deactivating fragments from the training set and subsequently remove redundant fragments. Finally, we perform k-Nearest Neighbor classification for several values of k and take a vote among the resulting predictions. These techniques (enrichment, removing redundancy, and voting) are integrated into the system iSAR (instance-based structure-activity relationships) and tested individually to show the relative contribution to the system's performance. Experiments on three data sets indicate that this simple and lightweight approach performs at least on the same level as other, more complex approaches.

  11. 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.

  12. Comparison of quantitative structure-activity relationship model performances on carboquinone derivatives.

    PubMed

    Bolboacă, Sorana-Daniela; Jäntschi, Lorentz

    2009-10-14

    Quantitative structure-activity relationship (qSAR) models are used to understand how the structure and activity of chemical compounds relate. In the present study, 37 carboquinone derivatives were evaluated and two different qSAR models were developed using members of the Molecular Descriptors Family (MDF) and the Molecular Descriptors Family on Vertices (MDFV). The usual parameters of regression models and the following estimators were defined and calculated in order to analyze the validity and to compare the models: Akaike's information criteria (three parameters), Schwarz (or Bayesian) information criterion, Amemiya prediction criterion, Hannan-Quinn criterion, Kubinyi function, Steiger's Z test, and Akaike's weights. The MDF and MDFV models proved to have the same estimation ability of the goodness-of-fit according to Steiger's Z test. The MDFV model proved to be the best model for the considered carboquinone derivatives according to the defined information and prediction criteria, Kubinyi function, and Akaike's weights.

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

    PubMed Central

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

    2016-01-01

    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. PMID:26879383

  14. 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.

  15. Crustal deformation induced by volcanic activity measured by InSAR time series analysis (Volcan de Colima-Mexico)

    NASA Astrophysics Data System (ADS)

    Brunori, Carlo Alberto; Norini, Gianluca; Stramondo, Salvatore; Capra, Lucia; Zucca, Francesco; Groppelli, Gianluca; Bignami, Christian; Chini, Marco; Manea, Marina; Manea, Vlad

    2010-05-01

    The Volcán de Colima (CV) is currently the most active Mexican volcano. After the 1913 plinian activity the volcano presented several eruptive phases that lasted few years, but since 1991 its activity became more persistent with vulcanian eruptions, lava and dome extrusions. During the last 15 years the volcano suffered several eruptive episodes as in 1991, 1994, 1998-1999, 2001-2003, 2004 and 2005 with the emplacement of pyroclastic flows. During rain seasons lahars are frequent affecting several infrastructures such as bridges and electric towers. This work is focused on the detection of surface deformation with centimetre or sub-centimeter accuracy of the Volcán de Colima and surrounding areas. We try to assess the amount and the spatial extension of surface movements of the CV and to get insights into the causes of the surface deformation by using Interferometric Synthetic Aperture Radar (InSAR), a powerful tool ensuring measurements at high-accuracy over large areas. The image dataset acquired by ESA ENVISAT ASAR (C band) sensor, has been processed using Advanced interferometric techniques (A-InSAR) to overcome the really challenging sources of decorrelation related to the setting context, mainly vegetation and atmosphere, in order to give us the opportunity to detect also very low rates of deformations. The main objectives of the interferometric analysis is the measurement of deformations in the CV in relation with active tectonics and gravity induced spreading, the identification of magma migration below the surface in the last decade, the detection of the incipient movements of volcanic landslides and large scale volcano instability, and the kinematics of the Colima rift. We present preliminary results of the A-InSAR processing, in the framework of the interdisciplinary Colima Deformation project (ColDef).

  16. Safety assessment of widely used fermented virgin coconut oil (Cocos nucifera) in Malaysia: Chronic toxicity studies and SAR analysis of the active components.

    PubMed

    Ibrahim, Ahmad H; Khan, Md Shamsuddin Sultan; Al-Rawi, Sawsan S; Ahamed, Mohamed B Khadeer; Majid, Aman Shah Bin Abdul; Al-Suede, Fouad Saleih R; Ji, Dan; Majid, Amin Malik Shah Abdul

    2016-11-01

    Fermented Virgin Coconut Oil (FVCO) is widely used in the Southeast Asia as food and traditional medicine. The objective of the present study is the evaluation of chronic safety of the commercialized FVCO of Malaysia and other Southeast Asian countries. A single dose of 5000 mg/kg of FVCO was administered orally in rats (each group, n = 5) for the acute toxicity study and 175, 550 and 2000 mg/kg for sub-chronic and chronic studies (each group, n = 10), respectively. The behavior, mortality, and body weight of the rats were assessed to determine the toxic effects of FVCO. The haematology, biochemistry and histopathology of the treated rats were evaluated. The treated rats were safe with the dose of 5000 mg/kg in acute, sub-chronic and chronic indication. Abnormal clinical signs and morphology (gross necroscopy), changes of organ weight, anomalous haematology and biochemistry indexes were not found in comparison with the control (p > 0.05). In general, food and water intake were higher in the treated rats related to control. It was concluded that the presence of the antioxidant active compounds of FVCO might be the reason of safety. The structure activity relationship (SAR) provides a comprehensive mechanism to determine the safety that is the presence of the electron donating phenolic groups, carbonyl groups, and carboxylic acid in the ortho and meta position of the aromatic rings. The SAR showed the antioxidant properties of myristic acid and lauric acid determined by GC-MS analysis. This result suggests the safety of FVCO for chronic use, nutritional activity that FVCO formulation complies the requirements of regulatory agencies.

  17. 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

  18. A structure-activity relationship study of ABCC2 inhibitors.

    PubMed

    Wissel, Gloria; Deng, Feng; Kudryavtsev, Pavel; Ghemtio, Leo; Wipf, Peter; Xhaard, Henri; Kidron, Heidi

    2017-02-07

    Multidrug resistance associated protein 2 (MRP2/ABCC2) is a membrane transport protein that can potentially affect the disposition of many substrate drugs and their metabolites. Recently, we studied the interaction of a library of 432 compounds with ABCC2, and the structure-activity relationship (SAR) of a subset of 64 compounds divided into four scaffolds (Wissel, G. et al., 2015. Bioorg Med Chem., 23(13), pp.3513-25). We have now expanded this test set by investigating 114 new compounds, of which 71 are representative of the previous four scaffolds and 43 compounds belong to a new scaffold. Interaction with ABCC2 was assessed by measuring the compounds effect on 5(6)-carboxy-2',7'-dichlorofluorescein transport in the vesicular transport assay. In line with our previous study, we observed that anionic charge is not essential for inhibition of ABCC2 transport, even though it often increases the inhibitory activity within the analogue series. Additionally, we found that halogen substitutions often increase the inhibitory activity. The results confirm the importance of structural features such as aromaticity and lipophilicity for ABCC2 inhibitory activity.

  19. 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...

  20. Design, synthesis and insight into the structure-activity relationship of 1,3-disubstituted indazoles as novel HIF-1 inhibitors.

    PubMed

    An, Hongchan; Kim, Nam-Jung; Jung, Jong-Wha; Jang, Hannah; Park, Jong-Wan; Suh, Young-Ger

    2011-11-01

    Design, synthesis and insight into the structure-activity relationship (SAR) of 1,3-disubstituted indazoles as novel HIF-1 inhibitors are described. In particular, the substituted furan moiety on indazole skeleton as well as its substitution pattern turns out crucial for the high HIF-1 inhibition.

  1. Forest Information Extraction from Airborne P-Band PolSAR and X-Band InSAR Data

    NASA Astrophysics Data System (ADS)

    Chen, Erxue; Li, Zengyuan; Tian, Xin; Feng, Qi; Zhao, Lei; Li, Lan; Hong, Wen; Pottier, Eric

    2014-11-01

    The key research progress of forest information extraction from high resolution PolSAR/InSAR data acquired by one China airborne system were summarized. Firstly, the airborne campaign activities carried out in 2012, 2013, in China were introduced. Secondly, the key SAR/InSAR data processing steps, such as, InSAR processing, SAR image geocoding terrain correction (GTC),the methods used to derive forest height, forest above ground biomass (AGB)from LiDAR, CCD and ground plots data were described. Finally, we introduced the forest information extraction methods and preliminary validation results from P-band PolSAR data and single baseline X-band InSAR data: (1)Forest height inversion using high resolution X-band InSAR data;(2) Forest AGB estimation using P-band PolSAR data; (3) Forest land cover types classification using PolSAR data.

  2. Forest Information Extraction from Airborne P-Band PolSAR and X-Band InSAR Data

    NASA Astrophysics Data System (ADS)

    Chen, Erxue; Li, Zengyuan; Tian, Xin; Feng, Qi; Zhao, Lei; Li, Lan; Hong, Wen; Pottier, Eric

    2014-11-01

    The key research progress of forest information extraction from high resolution PolSAR/InSAR data acquired by one China airborne system were summarized. Firstly, the airborne campaign activities carried out in 2012, 2013, in China were introduced. Secondly, the key SAR/InSAR data processing steps, such as, InSAR processing, SAR image geocoding terrain correction (GTC), the methods used to derive forest height, forest above ground biomass (AGB) from LiDAR, CCD and ground plots data were described. Finally, we introduced the forest information extraction methods and preliminary validation results from P-band PolSAR data and single baseline X-band InSAR data: (1) Forest height inversion using high resolution X-band InSAR data; (2) Forest AGB estimation using P-band PolSAR data; (3) Forest land cover types classification using PolSAR data.

  3. Identification and structure-activity relationship study of carvacrol derivatives as Mycobacterium tuberculosis chorismate mutase inhibitors.

    PubMed

    Alokam, Reshma; Jeankumar, Variam Ullas; Sridevi, Jonnalagadda Padma; Matikonda, Siddharth Sai; Peddi, Santosh; Alvala, Mallika; Yogeeswari, Perumal; Sriram, Dharmarajan

    2014-08-01

    In the present study, we identified carvacrol, a major phenolic component of oregano oil as a novel small molecule inhibitor of Mycobacterium tuberculosis (MTB) chorismate mutase (CM) enzyme with IC50 of 1.06 ± 0.4 µM. Virtual screening of the BITS-Pilani in-house database using the crystal structure of the MTB CM bound transition state intermediate (PDB: 2FP2) as framework identified carvacrol as a potential lead. Further various carvacrol derivatives were evaluated in vitro for their ability to inhibit MTB CM enzyme, whole cell MTB and cytotoxicity as steps toward the derivation of structure-activity relationships (SAR) and lead optimization.

  4. 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

  5. Structure activity relationship and modeling studies of inhibitors of lysine specific demethylase 1

    PubMed Central

    Lu, Lianghao; Wei, Liping; Pai, Eric; Yao, Yuan; Song, Yongcheng

    2017-01-01

    Post-translational modifications of histone play important roles in gene transcription. Aberrant methylation of histone lysine sidechains have been often found in cancer. Lysine specific demethylase 1 (LSD1), which can demethylate histone H3 lysine 4 (H3K4) and other proteins, has recently been found to be a drug target for acute myeloid leukemia. To understand structure activity/selectivity relationships of LSD1 inhibitors, several series of cyclopropylamine and related compounds were synthesized and tested for their activities against LSD1 and related monoamine oxidase (MAO) A and B. Several cyclopropylamine containing compounds were found to be highly potent and selective inhibitors of LSD1. A novel series cyclopropylimine compounds also exhibited strong inhibitory activity against LSD1. Structure activity relationships (SAR) of these compounds are discussed. Docking studies were performed to provide possible binding models of a representative compound in LSD1 and MAO-A. Moreover, these modeling studies can rationalize the observed SARs and selectivity. PMID:28158205

  6. Synthesis and structure-activity relationships of novel amino/nitro substituted 3-arylcoumarins as antibacterial agents.

    PubMed

    Matos, Maria J; Vazquez-Rodriguez, Saleta; Santana, Lourdes; Uriarte, Eugenio; Fuentes-Edfuf, Cristina; Santos, Ysabel; Muñoz-Crego, Angeles

    2013-01-24

    A new series of amino/nitro-substituted 3-arylcoumarins were synthesized and their antibacterial activity against clinical isolates of Staphylococcus aureus (Gram-positive) and Escherichia coli (Gram-negative) was evaluated. Some of these molecules exhibited antibacterial activity against S. aureus comparable to the standards used (oxolinic acid and ampicillin). The preliminary structure-activity relationship (SAR) study showed that the antibacterial activity against S. aureus depends on the position of the 3-arylcoumarin substitution pattern. With the aim of finding the structural features for the antibacterial activity and selectivity, in the present manuscript different positions of nitro, methyl, methoxy, amino and bromo substituents on the 3-arylcoumarin scaffold were reported.

  7. 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.

  8. 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

    2013-07-08

    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.

  9. [Perspective of predictive toxicity assessment of in vivo repeated dose toxicity using structural activity relationship].

    PubMed

    Ono, Atsushi

    2010-01-01

    Tens of thousands of existing chemicals have been widely used for manufacture, agriculture, household and other purposes in worldwide. Only approximately 10% of chemicals have been assessed for human health hazard. The health hazard assessment of residual large number of chemicals for which little or no information of their toxicity is available is urgently needed for public health. However, the conduct of traditional toxicity tests which involves using animals for all of these chemicals would be economically impractical and ethically unacceptable. (Quantitative) Structure-Activity Relationships [(Q)SARs] are expected as method to have the potential to estimate hazards of chemicals from their structure, while reducing time, cost and animal testing currently needed. Therefore, our studies have been focused on evaluation of available (Q)SAR systems for estimating in vivo repeated toxicity on the liver. The results from our preliminary analysis showed the distribution for LogP of the chemicals which have potential to induce liver toxicity was bell-shape and indicating the possibility to estimate liver toxicity of chemicals from their physicochemical property. We have developed (Q)SAR models to in vivo liver toxicity using three commercially available systems (DEREK, ADMEWorks and MultiCASE) as well as combinatorial use of publically available chemoinformatic tools (CDK, MOSS and WEKA). Distinct data-sets of the 28-day repeated dose toxicity test of new and existing chemicals evaluated in Japan were used for model development and performance test. The results that concordances of commercial systems and public tools were almost same which below 70% may suggest currently attainable knowledge of in silico estimation of complex biological process, though it possible to obtain complementary and enhanced performance by combining predictions from different programs. In future, the combinatorial application of in silico and in vitro tests might provide more accurate

  10. 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.

  11. Structural Antitumoral Activity Relationships of Synthetic Chalcones

    PubMed Central

    Echeverria, Cesar; Santibañez, Juan Francisco; Donoso-Tauda, Oscar; Escobar, Carlos A.; Ramirez-Tagle, Rodrigo

    2009-01-01

    Relationships between the structural characteristic of synthetic chalcones and their antitumoral activity were studied. Treatment of HepG2 cells for 24 h with synthetic 2’-hydroxychalcones resulted in apoptosis induction and dose-dependent inhibition of cell proliferation. The calculated reactivity indexes and the adiabatic electron affinities using the DFT method including solvent effects, suggest a structure-activity relationship between the Chalcones structure and the apoptosis in HepG2 cells. The absence of methoxy substituents in the B ring of synthetic 2’-hydroxychalcones, showed the mayor structure-activity pattern along the series. PMID:19333443

  12. Design and synthesis of a series of serine derivatives as small molecule inhibitors of the SARS coronavirus 3CL protease.

    PubMed

    Konno, Hiroyuki; Wakabayashi, Masaki; Takanuma, Daiki; Saito, Yota; Akaji, Kenichi

    2016-03-15

    Synthesis of serine derivatives having the essential functional groups for the inhibitor of SARS 3CL protease and evaluation of their inhibitory activities using SARS 3CL R188I mutant protease are described. The lead compounds, functionalized serine derivatives, were designed based on the tetrapeptide aldehyde and Bai's cinnamoly inhibitor, and additionally performed with simulation on GOLD softwear. Structure activity relationship studies of the candidate compounds were given reasonable inhibitors ent-3 and ent-7k against SARS 3CL R188I mutant protease. These inhibitors showed protease selectivity and no cytotoxicity.

  13. 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.

  14. 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.

  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. 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.

  17. Calibration of dual-frequency SAR ocean imagery

    NASA Technical Reports Server (NTRS)

    Kasischke, E. S.; Larson, R. W.; Lyzenga, D. R.

    1986-01-01

    A calibration procedure for digital aircraft SAR imagery is presented. Techniques to utilize internal and external calibration references are discussed. Examples of calibrated intensity scans from an oceanographic test site are presented. The relationship of the aircraft SAR calibration procedure to future spaceborne SAR systems is discussed.

  18. 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.

  19. Structure-activity relationships for antibacterial to antifungal conversion of kanamycin to amphiphilic analogues.

    PubMed

    Fosso, Marina; AlFindee, Madher N; Zhang, Qian; Nziko, Vincent de Paul Nzuwah; Kawasaki, Yukie; Shrestha, Sanjib K; Bearss, Jeremiah; Gregory, Rylee; Takemoto, Jon Y; Chang, Cheng-Wei Tom

    2015-05-01

    Novel fungicides are urgently needed. It was recently reported that the attachment of an octyl group at the O-4″ position of kanamycin B converts this antibacterial aminoglycoside into a novel antifungal agent. To elucidate the structure-activity relationship (SAR) for this phenomenon, a lead compound FG03 with a hydroxyl group replacing the 3″-NH2 group of kanamycin B was synthesized. FG03's antifungal activity and synthetic scheme inspired the synthesis of a library of kanamycin B analogues alkylated at various hydroxyl groups. SAR studies of the library revealed that for antifungal activity the O-4″ position is the optimal site for attaching a linear alkyl chain and that the 3″-NH2 and 6″-OH groups of the kanamycin B parent molecule are not essential for antifungal activity. The discovery of lead compound, FG03, is an example of reviving clinically obsolete drugs like kanamycin by simple chemical modification and an alternative strategy for discovering novel antimicrobials.

  20. Terrain Measurement with SAR/InSAR

    NASA Astrophysics Data System (ADS)

    Li, Deren; Liao, Mingsheng; Balz, Timo; Zhang, Lu; Yang, Tianliang

    2016-08-01

    Terrain measurement and surface motion estimation are the most important applications for commercial and scientific SAR missions. In Dragon-3, we worked on these applications, especially regarding DEM generation, surface motion estimation with SAR time- series for urban subsidence monitoring and landslide motion estimation, as well as developing tomographic SAR processing methods in urban areas.

  1. 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.

  2. Studies on the Synthesis of Derivatives of Marine-Derived Bostrycin and Their Structure-Activity Relationship against Tumor Cells

    PubMed Central

    Chen, Hong; Zhong, Lili; Long, Yuhua; Li, Jia; Wu, Jueheng; Liu, Lan; Chen, Shengping; Lin, Yongcheng; Li, Mengfeng; Zhu, Xun; She, Zhigang

    2012-01-01

    A series of new derivatives (5–29) of marine-derived bostrycin (1) were synthesized. The in vitro cytotoxic activities of all compounds were evaluated against MCF-7, MDA-MB-435, A549, HepG2, HCT-116 and MCF-10A cells using the MTT method. The compounds 7, 8, 22, 23, 25, 28 and 29 of the total showed comparable activity to epirubicin, the positive control, against the tested cancer cell lines. However, these compounds also exhibited cytotoxicity towards MCF-10A cells. The structure-activity relationship (SAR) of bostrycin derivatives was also discussed based on the obtained experimental data. PMID:22690152

  3. Aminopyrazolo[1,5-a]pyrimidines as potential inhibitors of Mycobacterium tuberculosis: Structure activity relationships and ADME characterization.

    PubMed

    Soares de Melo, Candice; Candice, Soares de Melo; Feng, Tzu-Shean; van der Westhuyzen, Renier; Gessner, Richard K; Street, Leslie J; Morgans, Garreth L; Warner, Digby F; Moosa, Atica; Naran, Krupa; Lawrence, Nina; Boshoff, Helena I M; Barry, Clifton E; Harris, C John; Gordon, Richard; Chibale, Kelly

    2015-11-15

    Whole-cell high-throughput screening of a diverse SoftFocus library against Mycobacterium tuberculosis (Mtb) generated a novel aminopyrazolo[1,5-a]pyrimidine hit series. The synthesis and structure activity relationship studies identified compounds with potent antimycobacterial activity. The SAR of over 140 compounds shows that the 2-pyridylmethylamine moiety at the C-7 position of the pyrazolopyrimidine scaffold was important for Mtb activity, whereas the C-3 position offered a higher degree of flexibility. The series was also profiled for in vitro cytotoxicity and microsomal metabolic stability as well as physicochemical properties. Consequently liabilities to be addressed in a future lead optimization campaign have been identified.

  4. 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 ...

  5. Quantitative structure-activity relationship of phenoxyphenyl-methanamine compounds with 5HT2A, SERT, and hERG activities.

    PubMed

    Mente, Scot; Gallaschun, Randall; Schmidt, Anne; Lebel, Lorrie; Vanase-Frawley, Michelle; Fliri, Anton

    2008-12-01

    QSAR models have been used to evaluate activities for compounds in the phenoxyphenyl-methanamine (PPMA) class of compounds. These models utilize Hammett-type donating-withdrawing substituent values as well as simple parameters to describe substituent size and elucidate the SAR of the 'A' and 'B' rings. Using this methodology, intuitive QSAR relationships were found for the three biological activities with R(2) values of 0.73, 0.45, and 0.58 for 5HT(2A), SerT, and hERG activities.

  6. Novel structurally varied N-alkyl 1,4-dihydropyridines as ABCB1 inhibitors: structure-activity relationships, biological activity and first bioanalytical evaluation.

    PubMed

    Hilgeroth, Andreas; Baumert, Christiane; Coburger, Claudius; Seifert, Marianne; Krawczyk, Sören; Hempel, Cornelius; Neubauer, Felix; Krug, Martin; Molnár, Josef; Lage, Hermann

    2013-06-01

    Series of structurally varied N-alkyl 1,4-dihydropyridines and novel benzo-annelated derivatives as 1,4- dihydroquinolines have been characterized as ABCB1 inhibitors. Structure-activity relationships (SARs) are discussed. Cytotoxic activities of selected compounds have been determined. A first bioanalysis of ABCB1 substrate properties has been carried out in a cell-based model. Compounds with highest ABCB1 inhibiting activities were no substrates of ABCB1 and not transported by the efflux pump, thus profiling the new ABCB1 inhibitors.

  7. Role of the staphylococcal accessory gene regulator (sar) in septic arthritis.

    PubMed Central

    Nilsson, I M; Bremell, T; Rydén, C; Cheung, A L; Tarkowski, A

    1996-01-01

    Staphylococcus aureus arthritis is a highly erosive disease in which both host and bacterial factors are of importance for its induction and progression. At the transcriptional level, three known loci act in regulating production of exoproteins and expression of cell wall structures. The aim of our study was to assess the role of the sar locus as a virulence determinant in the pathogenesis of septic arthritis. A recently established murine model of hematogenously spread S. aureus arthritis was employed. S. aureus strains, isogenic for the sar locus, were inoculated intravenously into NMRI mice, and the clinical, bacteriological, serological, and histopathological progression of the disease was studied. Within 1 week after inoculation of bacteria, the frequency of arthritis was 79% in the group of mice inoculated with the sar+ strain, whereas the corresponding frequency in sar mutants was 21% (P < 0.01). Mice inoculated with the sar+ staphylococcal strain exhibited a more pronounced T- and B-lymphocyte activation than those inoculated with the sar mutant, evidenced by splenomegaly, polyclonal B-cell activation, and high serum levels of interleukin 6 and gamma interferon. Also, infection with sar+ staphylococci induced a pronounced weight loss. To assess the relationship between clinical signs and spread of bacteria, we analyzed the homing pattern and persistence of S. aureus in host tissues. Kidneys and joints from sar+-inoculated subjects displayed a higher degree of bacterial persistence than other organs. Our results suggest that molecules controlled by the sar locus are important virulence determinants in the induction and progression of septic arthritis. PMID:8890189

  8. D-InSAR to inspect the active fault of Kunlun Mountains on Qinghai-Tibet Plateau

    NASA Astrophysics Data System (ADS)

    Miao, Fang; Ye, Chengming; Bi, Xiaojia; Wu, Zhenhan; Kong, Xiangsheng; Liu, Rui; Yan, Mingxing

    2007-11-01

    Differential Interferometric Synthetic Aperture Radar (D-InSAR) is a new technology which is capable of detecting the tiny ground deformation and extracting Digital Elevation Model (DEM). This paper introduces the basic principle of D-InSAR. Using of two pass model and SRTM DEM, acquired Kunlun Mountains region surface deformation of Ms8.1 in 2001. The result provides an important reference for Qinghai-Tibet Railway Disaster Prevention.

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

    PubMed

    Han, Changho; Chatterjee, Arindam; Noetzel, Meredith J; Panarese, Joseph D; Smith, Emery; Chase, Peter; Hodder, Peter; Niswender, Colleen; Conn, P Jeffrey; Lindsley, Craig W; Stauffer, Shaun R

    2015-01-15

    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.

  10. 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

  11. SAR image registration based on Susan algorithm

    NASA Astrophysics Data System (ADS)

    Wang, Chun-bo; Fu, Shao-hua; Wei, Zhong-yi

    2011-10-01

    Synthetic Aperture Radar (SAR) is an active remote sensing system which can be installed on aircraft, satellite and other carriers with the advantages of all day and night and all-weather ability. It is the important problem that how to deal with SAR and extract information reasonably and efficiently. Particularly SAR image geometric correction is the bottleneck to impede the application of SAR. In this paper we introduces image registration and the Susan algorithm knowledge firstly, then introduces the process of SAR image registration based on Susan algorithm and finally presents experimental results of SAR image registration. The Experiment shows that this method is effective and applicable, no matter from calculating the time or from the calculation accuracy.

  12. Structure-activity relationship study of 2,4-diaminothiazoles as cdk5/p25 kinase inhibitors

    PubMed Central

    Laha, Joydev K.; Zhang, Xuemei; Qiao, Lixin; Liu, Min; Chatterjee, Snigdha; Robinson, Shaughnessy; Kosik, Kenneth S.; Cuny, Gregory D.

    2011-01-01

    Cdk5/p25 has emerged as a principle therapeutic target for numerous acute and chronic neurodegenerative diseases, including Alzheimer’s disease. A structure-activity relationship study of 2,4-diaminothiazole inhibitors revealed that increased Cdk5/p25 inhibitory activity could be accomplished by incorporating pyridines on the 2-amino group and addition of substituents to the 2- or 3-position of the phenyl ketone moiety. Interpretation of the SAR results for many of the analogs was aided through in silico docking with Cdk5/p25 and calculating protein hydrations sites using WaterMap. Finally, improved in vitro mouse microsomal stability was also achieved. PMID:21353545

  13. Structural features, kinetics and SAR study of radical scavenging and antioxidant activities of phenolic and anilinic compounds

    PubMed Central

    2013-01-01

    Background Phenolic compounds are widely distributed in plant kingdom and constitute one of the most important classes of natural and synthetic antioxidants. In the present study fifty one natural and synthetic structurally variant phenolic, enolic and anilinic compounds were examined as antioxidants and radical scavengers against DPPH, hydroxyl and peroxyl radicals. The structural diversity of the used phenolic compounds includes monophenols with substituents frequently present in natural phenols e.g. alkyl, alkoxy, ester and carboxyl groups, besides many other electron donating and withdrawing groups, in addition to polyphenols with 1–3 hydroxyl groups and aminophenols. Some common groups e.g. alkyl, carboxyl, amino and second OH groups were incorporated in ortho, meta and para positions. Results SAR study indicates that the most important structural feature of phenolic compounds required to possess good antiradical and antioxidant activities is the presence of a second hydroxyl or an amino group in o- or p-position because of their strong electron donating effect in these positions and the formation of a stable quinone-like products upon two hydrogen-atom transfer process; otherwise, the presence of a number of alkoxy (in o or p-position) and /or alkyl groups (in o, m or p-position) should be present to stabilize the resulted phenoxyl radical and reach good activity. Anilines showed also similar structural feature requirements as phenols to achieve good activities, except o-diamines which gave low activity because of the high energy of the resulted 1,2-dimine product upon the 2H-transfer process. Enols with ene-1,2-diol structure undergo the same process and give good activity. Good correlations were obtained between DPPH inhibition and inhibition of both OH and peroxyl radicals. In addition, good correlations were obtained between DPPH inhibition and antioxidant activities in sunflower oil and liver homogenate systems. Conclusions In conclusion, the

  14. The 'SAR Matrix' method and its extensions for applications in medicinal chemistry and chemogenomics.

    PubMed

    Gupta-Ostermann, Disha; Bajorath, Jürgen

    2014-01-01

    We describe the 'Structure-Activity Relationship (SAR) Matrix' (SARM) methodology that is based upon a special two-step application of the matched molecular pair (MMP) formalism. The SARM method has originally been designed for the extraction, organization, and visualization of compound series and associated SAR information from compound data sets. It has been further developed and adapted for other applications including compound design, activity prediction, library extension, and the navigation of multi-target activity spaces. The SARM approach and its extensions are presented here in context to introduce different types of applications and provide an example for the evolution of a computational methodology in pharmaceutical research.

  15. Potent multitarget FAAH-COX inhibitors: Design and structure-activity relationship studies.

    PubMed

    Migliore, Marco; Habrant, Damien; Sasso, Oscar; Albani, Clara; Bertozzi, Sine Mandrup; Armirotti, Andrea; Piomelli, Daniele; Scarpelli, Rita

    2016-02-15

    Non-steroidal anti-inflammatory drugs (NSAIDs) exert their pharmacological effects by inhibiting cyclooxygenase (COX)-1 and COX-2. Though widely prescribed for pain and inflammation, these agents have limited utility in chronic diseases due to serious mechanism-based adverse events such as gastrointestinal damage. Concomitant blockade of fatty acid amide hydrolase (FAAH) enhances the therapeutic effects of the NSAIDs while attenuating their propensity to cause gastrointestinal injury. This favorable interaction is attributed to the accumulation of protective FAAH substrates, such as the endocannabinoid anandamide, and suggests that agents simultaneously targeting COX and FAAH might provide an innovative strategy to combat pain and inflammation with reduced side effects. Here, we describe the rational design and structure-active relationship (SAR) properties of the first class of potent multitarget FAAH-COX inhibitors. A focused SAR exploration around the prototype 10r (ARN2508) led to the identification of achiral (18b) as well as racemic (29a-c and 29e) analogs. Absolute configurational assignment and pharmacological evaluation of single enantiomers of 10r are also presented. (S)-(+)-10r is the first highly potent and selective chiral inhibitor of FAAH-COX with marked in vivo activity, and represents a promising lead to discover novel analgesics and anti-inflammatory drugs.

  16. On Ambiguities in SAR Design

    NASA Technical Reports Server (NTRS)

    Freeman, Anthony

    2006-01-01

    Ambiguities are an aliasing effect caused by the periodic sampling of the scene backscatter inherent to pulsed radar systems such as Synthetic Aperture radar (SAR). In this paper we take a fresh look at the relationship between SAR range and azimuth ambiguity constraints on the allowable pulse repetition frequency (PRF) and the antenna length. We show that for high squint angles smaller antennas may be feasible in some cases. For some applications, the ability to form a synthetic aperture at high squint angles is desirable, but the size of the antenna causes problems in the design of systems capable of such operation. This is because the SAR system design is optimized for a side-looking geometry. In two examples design examples we take a suboptimum antenna size and examine the performance in terms of azimuth resolution and swath width as a function of squint angle. We show that for stripmap SARs, the swath width is usually worse for off-boresight squint angles, because it is severely limited by range walk, except in cases where we relax the spatial resolution. We consider the implications for the design of modest-resolution, narrow swath, scanning SAR scatterometers .

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. SAR/QSAR methods in public health practice.

    PubMed

    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.

  2. 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.

  3. Synthesis, Anticonvulsant Activity, and SAR Study of Novel 4-Quinazolinone Derivatives.

    PubMed

    Noureldin, Nada A; Kothayer, Hend; Lashine, El-Sayed M; Baraka, Mohamed M; El-Eraky, Wafaa; Awdan, Sally A El

    2017-02-01

    Series of N-(4-substitutedphenyl)-4-(1-methyl (or 1,2-dimethyl)-4-oxo-1,2-dihydroquinazolin-3(4H)-yl)-alkanamides (5a-j) and 4-chloro-N'-((1-methyl (or 1,2-dimethyl)-4-oxo-1,2-dihydroquinazolin-3(4H)-yl)-alkaloyl)benzohydrazides (6a-f) were designed based on the previously reported essential structural features for anticonvulsant activity. Several amino acids were incorporated within the synthesized quinazolin-4(3H)-ones to improve their bioavailability and the anticonvulsant activity. Synthesis of the target compounds was accomplished in four steps starting from the reaction between N-methyl isatoic anhydride and the appropriate amino acid. Then, the carboxylic acid group was utilized to synthesize the required final structures. The new quinazolinone derivatives were evaluated for their anticonvulsant activity according to the Anticonvulsant Drug Development (ADD) Program protocol. All the 16 new quinazolinones exhibited good anticonvulsant activity; especially 5f, 5b, and 5c showed superior anticonvulsant activities in comparison to the reference drug, with ED50 values of 28.90, 47.38, and 56.40 mg/kg, respectively.

  4. 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....

  5. 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…

  6. 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

  7. 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

  8. Structure-activity relationships of lipopolysaccharide sequestration in N-alkylpolyamines.

    PubMed

    Shrestha, Anurupa; Sil, Diptesh; Malladi, Subbalakshmi S; Warshakoon, Hemamali J; David, Sunil A

    2009-05-01

    We have previously shown that simple N-acyl or N-alkyl polyamines bind to and sequester Gram-negative bacterial lipopolysaccharide, affording protection against lethality in animal models of endotoxicosis. Several iterative design-and-test cycles of SAR studies, including high-throughput screens, had converged on compounds with polyamine scaffolds which have been investigated extensively with reference to the number, position, and length of acyl or alkyl appendages. However, the polyamine backbone itself had not been explored sufficiently, and it was not known if incremental variations on the polymethylene spacing would affect LPS-binding and neutralization properties. We have now systematically explored the relationship between variously elongated spermidine [NH(2)-(CH(2))(3)-NH-(CH(2))(4)-NH(2)] and norspermidine [NH(2)-(CH(2))(3)-NH-(CH(2))(3)-NH(2)] backbones, with the N-alkyl group being held constant at C(16) in order to examine if changing the spacing between the inner secondary amines may yield additional SAR information. We find that the norspermine-type compounds consistently showed higher activity compared to corresponding spermine homologues.

  9. 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

  10. 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.

  11. Antenna motion errors in bistatic SAR imagery

    NASA Astrophysics Data System (ADS)

    Wang, Ling; Yazıcı, Birsen; Cagri Yanik, H.

    2015-06-01

    Antenna trajectory or motion errors are pervasive in synthetic aperture radar (SAR) imaging. Motion errors typically result in smearing and positioning errors in SAR images. Understanding the relationship between the trajectory errors and position errors in reconstructed images is essential in forming focused SAR images. Existing studies on the effect of antenna motion errors are limited to certain geometries, trajectory error models or monostatic SAR configuration. In this paper, we present an analysis of position errors in bistatic SAR imagery due to antenna motion errors. Bistatic SAR imagery is becoming increasingly important in the context of passive imaging and multi-sensor imaging. Our analysis provides an explicit quantitative relationship between the trajectory errors and the positioning errors in bistatic SAR images. The analysis is applicable to arbitrary trajectory errors and arbitrary imaging geometries including wide apertures and large scenes. We present extensive numerical simulations to validate the analysis and to illustrate the results in commonly used bistatic configurations and certain trajectory error models.

  12. Graph mining for SAR transfer series.

    PubMed

    Gupta-Ostermann, Disha; Wawer, Mathias; Wassermann, Anne Mai; Bajorath, Jürgen

    2012-04-23

    The transfer of SAR information from one analog series to another is a difficult, yet highly attractive task in medicinal chemistry. At present, the evaluation of SAR transfer potential from a data mining perspective is still in its infancy. Only recently, a first computational approach has been introduced to evaluate SAR transfer events. Here, a substructure relationship-based molecular network representation has been used as a starting point to systematically identify SAR transfer series in large compound data sets. For this purpose, a methodology is introduced that consists of two stages. For graph mining, an algorithm has been designed that extracts all parallel series from compound data sets. A parallel series is formed by two series of analogs with different core structures but pairwise corresponding substitution patterns. The SAR transfer potential of identified parallel series is then evaluated using a scoring function that emphasizes corresponding potency progression over many analog pairs and large potency ranges. The substructure relationship-based molecular network in combination with the graph mining algorithm currently represents the only generally applicable approach to systematically detect SAR transfer events in large compound data sets. The combined approach has been evaluated on a large number of compound data sets and shown to systematically identify SAR transfer series.

  13. Processing pharus data with the generic SAR processor

    SciTech Connect

    Otten, M.P.G.

    1996-11-01

    The Generic SAR Processor (GSP) is a SAR processing environment created to process airborne and spaceborne SAR data with a maximum amount of flexibility, while at the same time providing a user friendly and powerful environment for handling and analyzing SAR, including polarimetric calibration. PHARUS is an airborne polarimetric C-band SAR, utilizing an active (solid state) phased array. The absence of mechanical antenna stabilization, the use of electronic beam steering, in combination with high PRF, polarimetric operation, under motion condition which can be severe, requires a very large flexibility of the SAR processor. The GSP is designed to handle this type of SAR data with a very flexible motion compensation-, azimuth compression-, and radiometric correction approach. First experiences with the processing of PHARUS data show that this is a valid approach to obtain high quality polarimetric imagery with a phased array SAR. 4 refs., 5 figs.

  14. Synthesis, nematocidal activity and SAR study of novel difluoromethylpyrazole carboxamide derivatives containing flexible alkyl chain moieties.

    PubMed

    Liu, Xing-Hai; Zhao, Wen; Shen, Zhong-Hua; Xing, Jia-Hua; Xu, Tian-Ming; Peng, Wei-Li

    2017-01-05

    A series of novel difluoromethylpyrazole carboxamides derivatives were synthesized by introduction of flexible alkyl chain. Nematicidal bioassay results showed that some of them exhibited good control efficacy against M. incognita, which indicated that these difluoromethylpyrazole carboxamides derivatives might be potential novel lead compounds for discovery new nematicides. The nematicidal activity was affected by the substituted position in the molecule, especially the substitution group on the alkyl chain. It was found that the compound 6-9 and 6-23 possess about 50% inhibition effect against M. incognita even at 5.0 and 1.0 mg L(-1). Meanwhile, greenhouse field trial showed the nematicidal activity of compound 6-9 is a litter weaker than that of Abamectin. The mammalian toxicology results indicated that compound 6-9 was a low-toxicity and low-sensitive compound. In conclusion compound 6-9 is a potential candidate for further development. In addition, the molecular docking simulations revealed that compounds 6 with a flexible NHCOO show its binding affinities for the acetylcholine receptor (AChR), which may provide useful information for further design novel nematicides.

  15. STAP for SAR

    DTIC Science & Technology

    2003-04-01

    UNCLASSIFIED Defense Technical Information Center Compilation Part Notice ADP014042 TITLE: STAP for SAR DISTRIBUTION: Approved for public release...compilation report: ADP014040 thru ADP014047 UNCLASSIFIED 3-1 STAP for SAR A. Farina Technical Directorate, Radar & Technology Division Alenia...Adaptive Processing) to Synthetic Aperture Radar ( SAR ) systems. SAR is a microwave sensor that allows us to have a high resolution mapping of

  16. Cholinesterase inhibitors: SAR and enzyme inhibitory activity of 3-[omega-(benzylmethylamino)alkoxy]xanthen-9-ones.

    PubMed

    Piazzi, Lorna; Belluti, Federica; Bisi, Alessandra; Gobbi, Silvia; Rizzo, Stefano; Bartolini, Manuela; Andrisano, Vincenza; Recanatini, Maurizio; Rampa, Angela

    2007-01-01

    In this work, we further investigated a previously introduced class of cholinesterase inhibitors. The removal of the carbamic function from the lead compound xanthostigmine led to a reversible cholinesterase inhibitors 3. Some new 3-[omega-(benzylmethylamino)alkoxy]xanthen-9-one analogs were designed, synthesized, and evaluated for their inhibitory activity against both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The length of the alkoxy chain of compound 3 was increased and different substituents were introduced. From the IC(50) values, it clearly appears that the carbamic residue is crucial to obtain highly potent AChE inhibitors. On the other hand, peculiarity of these compounds is the high selectivity toward BuChE with respect to AChE, being compound 12 the most selective one (6000-fold). The development of selective BuChE inhibitors may be of great interest to clarify the physiological role of this enzyme and to provide novel therapeutics for various diseases.

  17. The structure-activity relationships of L3MBTL3 inhibitors: flexibility of the dimer interface.

    PubMed

    Camerino, Michelle A; Zhong, Nan; Dong, Aiping; Dickson, Bradley M; James, Lindsey I; Baughman, Brandi M; Norris, Jacqueline L; Kireev, Dmitri B; Janzen, William P; Arrowsmith, Cheryl H; Frye, Stephen V

    2013-11-01

    We recently reported the discovery of UNC1215, a potent and selective chemical probe for the L3MBTL3 methyllysine reader domain. In this article, we describe the development of structure-activity relationships (SAR) of a second series of potent L3MBTL3 antagonists which evolved from the structure of the chemical probe UNC1215. These compounds are selective for L3MBTL3 against a panel of methyllysine reader proteins, particularly the related MBT family proteins, L3MBTL1 and MBTD1. A co-crystal structure of L3MBTL3 and one of the most potent compounds suggests that the L3MBTL3 dimer rotates about the dimer interface to accommodate ligand binding.

  18. The structure-activity relationships of L3MBTL3 inhibitors: flexibility of the dimer interface

    PubMed Central

    Camerino, Michelle A.; Zhong, Nan; Dong, Aiping; Dickson, Bradley M.; James, Lindsey I.; Baughman, Brandi M.; Norris, Jacqueline L.; Kireev, Dmitri B.; Janzen, William P.; Arrowsmith, Cheryl H.

    2013-01-01

    We recently reported the discovery of UNC1215, a potent and selective chemical probe for the L3MBTL3 methyllysine reader domain. In this article, we describe the development of structure-activity relationships (SAR) of a second series of potent L3MBTL3 antagonists which evolved from the structure of the chemical probe UNC1215. These compounds are selective for L3MBTL3 against a panel of methyllysine reader proteins, particularly the related MBT family proteins, L3MBTL1 and MBTD1. A co-crystal structure of L3MBTL3 and one of the most potent compounds suggests that the L3MBTL3 dimer rotates about the dimer interface to accommodate ligand binding. PMID:24466405

  19. Structure-activity relationship of pyrrole based S-nitrosoglutathione reductase inhibitors: carboxamide modification.

    PubMed

    Sun, Xicheng; Qiu, Jian; Strong, Sarah A; Green, Louis S; Wasley, Jan W F; Blonder, Joan P; Colagiovanni, Dorothy B; Stout, Adam M; Mutka, Sarah C; Richards, Jane P; Rosenthal, Gary J

    2012-03-15

    The enzyme S-nitrosoglutathione reductase (GSNOR) is a member of the alcohol dehydrogenase family (ADH) that regulates the levels of S-nitrosothiols (SNOs) through catabolism of S-nitrosoglutathione (GSNO). GSNO and SNOs are implicated in the pathogenesis of many diseases including those in respiratory, gastrointestinal, and cardiovascular systems. The pyrrole based N6022 was recently identified as a potent, selective, reversible, and efficacious GSNOR inhibitor which is currently in clinical development for acute asthma. We describe here the synthesis and structure-activity relationships (SAR) of novel pyrrole based analogs of N6022 focusing on carboxamide modifications on the pendant N-phenyl moiety. We have identified potent and novel GSNOR inhibitors that demonstrate efficacy in an ovalbumin (OVA) induced asthma model in mice.

  20. Structure–Activity Relationship Studies Using Natural and Synthetic Okadaic Acid/Dinophysistoxin Toxins

    PubMed Central

    Twiner, Michael J.; Doucette, Gregory J.; Pang, Yucheng; Fang, Chao; Forsyth, Craig J.; Miles, Christopher O.

    2016-01-01

    Okadaic acid (OA) and the closely related dinophysistoxins (DTXs) are algal toxins that accumulate in shellfish and are known serine/threonine protein phosphatase (ser/thr PP) inhibitors. Phosphatases are important modulators of enzyme activity and cell signaling pathways. However, the interactions between the OA/DTX toxins and phosphatases are not fully understood. This study sought to identify phosphatase targets and characterize their structure–activity relationships (SAR) with these algal toxins using a combination of phosphatase activity and cytotoxicity assays. Preliminary screening of 21 human and yeast phosphatases indicated that only three ser/thr PPs (PP2a, PP1, PP5) were inhibited by physiologically saturating concentrations of DTX2 (200 nM). SAR studies employed naturally-isolated OA, DTX1, and DTX2, which vary in degree and/or position of methylation, in addition to synthetic 2-epi-DTX2. OA/DTX analogs induced cytotoxicity and inhibited PP activity with a relatively conserved order of potency: OA = DTX1 ≥ DTX2 >> 2-epi-DTX. The PPs were also differentially inhibited with sensitivities of PP2a > PP5 > PP1. These findings demonstrate that small variations in OA/DTX toxin structures, particularly at the head region (i.e., C1/C2), result in significant changes in toxicological potency, whereas changes in methylation at C31 and C35 (tail region) only mildly affect potency. In addition to this being the first study to extensively test OA/DTX analogs’ activities towards PP5, these data will be helpful for accurately determining toxic equivalence factors (TEFs), facilitating molecular modeling efforts, and developing highly selective phosphatase inhibitors. PMID:27827901

  1. Land Subsidence Monitoring Using PS-InSAR Technique for L-Band SAR Data

    NASA Astrophysics Data System (ADS)

    Thapa, S.; Chatterjee, R. S.; Singh, K. B.; Kumar, D.

    2016-10-01

    Differential SAR-Interferometry (D-InSAR) is one of the potential source to measure land surface motion induced due to underground coal mining. However, this technique has many limitation such as atmospheric in homogeneities, spatial de-correlation, and temporal decorrelation. Persistent Scatterer Interferometry synthetic aperture radar (PS-InSAR) belongs to a family of time series InSAR technique, which utilizes the properties of some of the stable natural and anthropogenic targets which remain coherent over long time period. In this study PS-InSAR technique has been used to monitor land subsidence over selected location of Jharia Coal field which has been correlated with the ground levelling measurement. This time series deformation observed using PS InSAR helped us to understand the nature of the ground surface deformation due to underground mining activity.

  2. Subsidence activity maps derived from DInSAR data: Orihuela case study

    NASA Astrophysics Data System (ADS)

    Sanabria, M. P.; Guardiola-Albert, C.; Tomás, R.; Herrera, G.; Prieto, A.; Sánchez, H.; Tessitore, S.

    2013-10-01

    A new methodology is proposed to produce subsidence activity maps based on the geostatistical analysis of persistent scatterer interferometry (PSI) data. PSI displacement measurements are interpolated based on Conditional Gaussian Simulation (CGS) to calculate multiple equiprobable realizations of subsidence. The result from this process is a series of interpolated subsidence values, with an estimation of the spatial uncertainty and a confidence level on the interpolation. These maps complement the PSI displacement map, improving the identification of wide subsiding areas at regional scale. At local scale, they can be used to identify buildings susceptible to suffer subsidence related damages. In order to do so, it is necessary to calculate the maximum differential settlement and the maximum angular distortion for each building of the study area. Based on PSI derived parameters those buildings in which serviceability limit state has been exceeded, and where in situ forensic analysis should be made, can be automatically identified. This methodology has been tested in Orihuela City (SE Spain) for the study of historical buildings, damaged during the last two decades by subsidence due to aquifer overexploitation.

  3. Subsidence activity maps derived from DInSAR data: Orihuela case study

    NASA Astrophysics Data System (ADS)

    Sanabria, M. P.; Guardiola-Albert, C.; Tomás, R.; Herrera, G.; Prieto, A.; Sánchez, H.; Tessitore, S.

    2014-05-01

    A new methodology is proposed to produce subsidence activity maps based on the geostatistical analysis of persistent scatterer interferometry (PSI) data. PSI displacement measurements are interpolated based on conditional Sequential Gaussian Simulation (SGS) to calculate multiple equiprobable realizations of subsidence. The result from this process is a series of interpolated subsidence values, with an estimation of the spatial variability and a confidence level on the interpolation. These maps complement the PSI displacement map, improving the identification of wide subsiding areas at a regional scale. At a local scale, they can be used to identify buildings susceptible to suffer subsidence related damages. In order to do so, it is necessary to calculate the maximum differential settlement and the maximum angular distortion for each building of the study area. Based on PSI-derived parameters those buildings in which the serviceability limit state has been exceeded, and where in situ forensic analysis should be made, can be automatically identified. This methodology has been tested in the city of Orihuela (SE Spain) for the study of historical buildings damaged during the last two decades by subsidence due to aquifer overexploitation. The qualitative evaluation of the results from the methodology carried out in buildings where damages have been reported shows a success rate of 100%.

  4. Synthesis and SAR of 4-methyl-5-pentylbenzene-1,3-diol (MPBD), produced by Dictyostelium discoideum.

    PubMed

    Murata, Chihiro; Ogura, Tetsuhiro; Narita, Shuhei; Kondo, Anna P; Iwasaki, Natsumi; Saito, Tamao; Usuki, Toyonobu

    2016-03-01

    4-Methyl-5-pentylbenzene-1,3-diol (MPBD) is a secondary metabolite of SteelyA polyketide synthase, which controls cell aggregation and spore maturation of Dictyostelium discoideum. In this study, chemical synthesis of MPBD and its derivatives was achieved. Structure-activity relationship (SAR) studies for antimicrobial activities against Escherichia coli and Bacillus subtilis were also conducted.

  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. The structure-AChE inhibitory activity relationships study in a series of pyridazine analogues.

    PubMed

    Saracoglu, M; Kandemirli, F

    2009-07-01

    The structure-activity relationships (SAR) are investigated by means of the Electronic-Topological Method (ETM) followed by the Neural Networks application (ETM-NN) for a class of anti-cholinesterase inhibitors (AChE, 53 molecules) being pyridazine derivatives. AChE activities of the series were measured in IC(50) units, and relative to the activity levels, the series was partitioned into classes of active and inactive compounds. Based on pharmacophores and antipharmacophores calculated by the ETM-software as sub-matrices containing important spatial and electronic characteristics, a system for the activity prognostication is developed. Input data for the ETM were taken as the results of conformational and quantum-mechanics calculations. To predict the activity, we used one of the most well known neural networks, namely, the feed-forward neural networks (FFNNs) trained with the back propagation algorithm. The supervised learning was performed using a variant of FFNN known as the Associative Neural Networks (ASNN). The result of the testing revealed that the high ETM's ability of predicting both activity and inactivity of potential AChE inhibitors. Analysis of HOMOs for the compounds containing Ph1 and APh1 has shown that atoms with the highest values of the atomic orbital coefficients are mainly those atoms that enter into the pharmacophores. Thus, the set of pharmacophores and antipharmacophores found as the result of this study forms a basis for a system of the anti-cholinesterase activity prediction.

  7. Structure-activity relationship of the pro- and anticoagulant effects of Fucus vesiculosus fucoidan.

    PubMed

    Zhang, Z; Till, S; Jiang, C; Knappe, S; Reutterer, S; Scheiflinger, F; Szabo, C M; Dockal, M

    2014-03-03

    Fucoidan is a highly complex sulfated polysaccharide commonly extracted from brown seaweed. In addition to their many biological activities, fucoidans have recently been demonstrated to inhibit or increase coagulation at different concentration ranges. Their structural features, i.e. molecular weight (Mw), Mw distribution, degree of sulfation, monosaccharide composition, and different linkages, are known to affect these activities. Therefore, structure-activity relationship (SAR) analysis of fucoidan is crucial for its potential use as a procoagulant. In this study, Fucus vesiculosus (F.v.) fucoidan was fractionated by charge and size as well as over- and desulfated to different degrees to yield preparations with various structural properties. The fractions' pro- and anticoagulant activities were assessed by calibrated automated thrombography (CAT) and activated partial thromboplastin time(aPTT) assays. Binding to and inhibition of the anticoagulant protein tissue factor pathway inhibitor (TFPI) and the ability to activate coagulation via the contact pathway were also investigated. This paper discusses the impact of charge density, size, and sugar composition on fucoidan's pro- and anticoagulant activities. Fucoidan requires a minimal charge density of 0.5 sulfates per sugar unit and a size of 70 sugar units to demonstrate desired procoagulant activities for improvement of haemostasis in factor VIII/factor IX-deficient plasma.

  8. 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.

  9. 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

  10. The structure-activity relationship study on 2-, 5-, and 6-position of the water soluble 1,4-dihydropyridine derivatives blocking N-type calcium channels.

    PubMed

    Yamamoto, Takashi; Niwa, Seiji; Ohno, Seiji; Tokumasu, Munetaka; Masuzawa, Yoko; Nakanishi, Chika; Nakajo, Akira; Onishi, Tomoyuki; Koganei, Hajime; Fujita, Shin-Ichi; Takeda, Tomoko; Kito, Morikazu; Ono, Yukitsugu; Saitou, Yuki; Takahara, Akira; Iwata, Seinosuke; Shoji, Masataka

    2008-09-01

    In order to find an injectable and selective N-type calcium channel blocker, we have performed the structure-activity relationship (SAR) study on the 2-, 5-, and 6-position of 1,4-dihydropyridine-3-carboxylate derivative APJ2708 (2), which is a derivative of Cilnidipine and has L/N-type calcium channel dual inhibitory activities. As a consequence of the optimization, 6-dimethylacetal derivative 7 was found to have an effective inhibitory activity against N-type calcium channels with more than 170-fold lower activity for L-type channel compared to that of APJ2708.

  11. In silico exploratory study using structure-activity relationship models and metabolic information for prediction of mutagenicity based on the Ames test and rodent micronucleus assay.

    PubMed

    Kamath, P; Raitano, G; Fernández, A; Rallo, R; Benfenati, E

    2015-12-01

    The mutagenic potential of chemicals is a cause of growing concern, due to the possible impact on human health. In this paper we have developed a knowledge-based approach, combining information from structure-activity relationship (SAR) and metabolic triggers generated from the metabolic fate of chemicals in biological systems for prediction of mutagenicity in vitro based on the Ames test and in vivo based on the rodent micronucleus assay. In the first part of the work, a model was developed, which comprises newly generated SAR rules and a set of metabolic triggers. These SAR rules and metabolic triggers were further externally validated to predict mutagenicity in vitro, with metabolic triggers being used only to predict mutagenicity of chemicals, which were predicted unknown, by SARpy. Hence, this model has a higher accuracy than the SAR model, with an accuracy of 89% for the training set and 75% for the external validation set. Subsequently, the results of the second part of this work enlist a set of metabolic triggers for prediction of mutagenicity in vivo, based on the rodent micronucleus assay. Finally, the results of the third part enlist a list of metabolic triggers to find similarities and differences in the mutagenic response of chemicals in vitro and in vivo.

  12. The antibacterial properties of 6-tuliposide B. Synthesis of 6-tuliposide B analogues and structure-activity relationship.

    PubMed

    Shigetomi, Kengo; Shoji, Kazuaki; Mitsuhashi, Shinya; Ubukata, Makoto

    2010-02-01

    6-Tuliposide B is a secondary metabolite occurring specifically in tulip anthers. Recently, a potent antibacterial activity of 6-tuliposide B has been reported. However, its molecular target has not yet been established, nor its action mechanism. To shed light on such issues, 6-tuliposide B and tulipalin B analogues were synthesized and a structure-activity relationship (SAR) was examined using a broad panel of bacterial strains. As the results of SAR among a total of 25 compounds, only tulipalin B and the compounds having 3',4'-dihydroxy-2'-methylenebutanoate (DHMB) moieties showed any significant antibacterial activity. Moreover, the 3'R analogues of these compounds displayed essentially the same activities as 6-tuliposide B and the structure of the 3'R-DMBA moiety was the same as that of the proposed active moiety of cnicin. These results suggest that 6-tuliposide B has the same action mechanism as proposed for cnicin and bacterial MurA is one of the major molecular targets of 6-tuliposide B.

  13. Brief report: Activities in heterosexual romantic relationships: grade differences and associations with relationship satisfaction.

    PubMed

    Carlson, Wendy; Rose, Amanda J

    2012-02-01

    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 likely are connected to relationship satisfaction. In the current study, 223 youths in fifth (28 boys; 32 girls), eighth (31 boys; 40 girls), and eleventh (36 boys; 56 girls) grades reporting current romantic relationships indicated their engagement in activities with romantic partners and relationship satisfaction. Findings revealed important grade differences in activity involvement, with eighth- and eleventh-graders reporting higher engagement than fifth-graders, especially in out-of-school activities. Additionally, engagement in out-of-school activities was most strongly associated with relationship satisfaction for all grades.

  14. 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.

  15. Structure -activity relationships of PDE5 inhibitors.

    PubMed

    Eros, D; Szántai-Kis, Cs; Kiss, R; Kéri, Gy; Hegymegi-Barakonyi, B; Kövesdi, I; Orfi, L

    2008-01-01

    cGMP has a short-term effect on smooth muscle tone and a longer-term effect on responses to chronic drug treatment or proliferative signals. cGMP-Phosphodiesterase type 5 (PDE5) hydrolizes cGMP, and the result is smooth muscle contraction. PDE5 is a relatively novel therapeutic target of various diseases, such as erectile dysfunction and pulmonary hypertension. The most intensively examined and marketed PDE5 inhibitor was sildenafil (Viagra) but recently vardenafil (Levitra) and tadalafil (Cialis) were launched with beneficial ADME parameters and PDE5 selectivity. The increasing interest in PDE5 inhibition made it reasonable to collect the available inhibitory data from the scientific literature and set up a structure-activity relationship study. Chemical structures of 438 compounds and their cGMP-PDE5 inhibitory data (IC50) were collected from recently published articles. In this paper physiology, regulation and inhibition of PDE5 (and briefly other PDE-s) are discussed and inhibitors are tabulated by the core structures. Finally, a general QSAR model built from these data is presented. All data used in the QSAR study were summarized in a Supplement (for description please see the online version of the article).

  16. 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…

  17. 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…

  18. Synthesis and structure-activity relationship of oleanolic mono- or di-glycosides against Magnaporthe oryzae.

    PubMed

    Huo, G; Liu, C; Hui, Y; Chen, X; Xiao, D

    2016-09-23

    Saponins are naturally-occurring units with broad diversity and are usually recognized as phytoanticipins. In order to develop new saponin chemical entities with high activity against Magnaporthe oryzae, we selected oleanolic acid (OA), which has wide natural distribution and rich content in plants. We used the ability of OA to act as an aglycone for glycosylation to obtain information on the structure-activity relationship (SAR) for rational molecular pesticide design. Oleanolic mono- or di-glycosides were synthesized at either the C3-hydroxy and/or C28-carboxyl position, using trichloroacetimidate or glycosyl bromide donors, respectively. Structures were confirmed by [(1)H]-,[(13)C]-NMR. Furthermore, the activity of the synthesized glycosides against M. oryzae was assessed in vitro, based on the mycelium growth rate. The twenty five oleanolic mono- or di-glycosides comprised fourteen saponins with 3-monosaccharide residue 1a-1n, six saponins with 28-monosaccharide residue 2a-2f, and five saponins with 3, 28-monosaccharide residue 3a-3e; all showed different activities against M. oryzae according to their different structures. We concluded that the optimal oleanolic mono- and di-glycoside structure for activity against M. oryzae is a C3 connection of a hexose such as mannose, galactose, or glucose, in combination with a C28 connection to a small group such as allyl or a C3 connection to a pentose accompanied by a larger group such as another pentose or heptenyl at C28.

  19. The anti-erbB3 antibody MM-121/SAR256212 in combination with trastuzumab exerts potent antitumor activity against trastuzumab-resistant breast cancer cells

    PubMed Central

    2013-01-01

    Background Elevated expression of erbB3 receptor has been reported to induce resistance to therapeutic agents, including trastuzumab in erbB2-overexpressing breast cancer. Our recent studies indicate that erbB3 interacts with both erbB2 and IGF-1 receptor to form a heterotrimeric complex in trastuzumab-resistant breast cancer cells. Herein, we investigate the antitumor activity of MM-121/SAR256212, a fully human anti-erbB3 antibody (Ab), against two erbB2-overexpressing breast cancer cell lines resistant to trastuzumab. Methods MTS-based proliferation assays were used to determine cell viability upon treatment of trastuzumab and/or MM-121/SAR256212. Cell cycle progression was examined by flow cytometric analysis. Western blot analyses were performed to determine the expression and activation of proteins. Tumor xenografts were established by inoculation of the trastuzumab-resistant BT474-HR20 cells into nude mice. The tumor-bearing mice were treated with trastuzumab and/or MM-121/SAR256212 via i.p injection to determine the Abs’ antitumor activity. Immunohistochemical analyses were carried out to study the Abs’ inhibitory effects on tumor cell proliferation and induction of apoptosis in vivo. Results MM-121 significantly enhanced trastuzumab-induced growth inhibition in two sensitive and two resistant breast cancer cell lines. MM-121 in combination with trastuzumab resulted in a dramatic reduction of phosphorylated erbB3 (P-erbB3) and Akt (P-Akt) in the in vitro studies. MM-121 combined with trastuzumab did not induce apoptosis in the trastuzumab-resistant cell lines under our cell culture condition, rather induced cell cycle G1 arrest mainly associated with the upregulation of p27kip1. Interestingly, in the tumor xenograft model established from the trastuzumab-resistant cells, MM-121 in combination with trastuzumab as compared to either agent alone dramatically inhibited tumor growth correlated with a significant reduction of Ki67 staining and increase of

  20. Structure-activity relationship study of human liver microsomes-catalyzed hydrolysis rate of ester prodrugs of MENT by comparative molecular field analysis (CoMFA).

    PubMed

    Bursi, Roberta; Grootenhuis, Arijan; van der Louw, Jaap; Verhagen, Jos; de Gooyer, Marcel; Jacobs, Peter; Leysen, Dirk

    2003-03-01

    A series of MENT esters (3-71) was designed, prepared and tested to study the structure-activity relationship (SAR) of the hydrolysis rate with human liver microsomes of these prodrugs. Compounds were obtained covering a wide range of metabolic stability. The results are useful for the proper selection of prodrugs for different pharmaceutical formulations to deliver the potent and prostate-sparing androgen MENT. The MENT esters can especially be administered for male hormone replacement therapy and male contraception. Comparative molecular field analysis (CoMFA) was applied to a dataset of 28 esters, for which ED50 values could be obtained. The CoMFA model where the electrostatic and H-bond molecular fields were combined turned out to be most predictive. Despite the limited size of the dataset, CoMFA can help to rationalize the SAR of the ester hydrolysis rate of ester prodrugs of MENT.

  1. A derivation of the statistical characteristics of SAR imagery data. [Rayleigh speckle statistics

    NASA Technical Reports Server (NTRS)

    Wu, C.

    1981-01-01

    Basic statistical properties of the speckle effect and the associated spatial correlation of SAR image data are discussed. Statistics of SAR sensed measurement and their relationships to the surface mean power reflectivity are derived. The Rayleigh speckle model is reviewed. Applications of the derived statistics to SAR radiometric measures and image processing are considered.

  2. Synthesis and structure-active relationship of 1-aryl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline anticonvulsants.

    PubMed

    Gitto, Rosaria; De Luca, Laura; Ferro, Stefania; Agnello, Stefano; Russo, Emilio; De Sarro, Giovanbattista; Chimirri, Alba

    2010-12-01

    We have previously disclosed that some 6,7-dimethoxyisoquinoline derivatives are able to produce anticonvulsant effects in different animal models of epilepsy. Following these studies this paper describes the synthesis of a small series of new 1-aryl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolines strictly related to previously reported analogues. This novel series of isoquinolines was designed on the basis of well defined structure-active relationship (SAR) information already acquired for this class of anticonvulsant agents. The pharmacological effects of the new synthesized compounds were evaluated against audiogenic seizures in Dilute Brown non-Agouti (DBA/2) mice. The preliminary pharmacological screening led to the identification of a new active molecule the 2-acetyl-1-(4'-methylphenyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (6d) that displayed significant anticonvulsant activity. Computational studies helped to rationalize these obtained pharmacological results.

  3. SAR Interferometry with TerraSAR-X

    NASA Astrophysics Data System (ADS)

    Eineder, M.; Runge, H.; Boerner, E.; Bamler, R.; Adam, N.; Schättler, B.; Breit, H.; Suchandt, S.

    2004-06-01

    The TerraSAR-X project is a public private partnership between Astrium GmbH and the German Aerospace Center DLR. Astrium will launch the satellite in late 2005 and holds the rights of commercial data exploitation. DLR is currently developing the ground segment and is responsible for the scientific exploitation of the data. Even if the mission goal is not primarily SAR interferometry, TerraSAR-X offers a number of new perspectives to SAR interferometry when compared to ERS and also ENVISAT: a) High resolution of 3 meters and better in stripmap and spotlight mode. b) The option for a burst synchronized ScanSAR mode. c) The high range bandwidth will allow large baselines and the option for highly precise DEM generation. d) X- Band will show new scattering properties. e) High observation frequency due to the short repeat cycle and variable incidence angles. f) An along track interferometric mode. The available products relevant for interferometry are presented and other relevant topics like orbit control and delta-k interferometry are discussed.

  4. Using SAR and QSAR analysis to model the activity and structure of the quinolone-DNA complex.

    PubMed

    Llorente, B; Leclerc, F; Cedergren, R

    1996-01-01

    A set of 78 quinolone derivatives were used in a structure-activity study to identify structural features correlating with antibacterial activity. Distinct combinations of functional properties were identified for Gram-negative and Gram-positive bacteria. 3-D Quantitative structure-activity relationship (QSAR) studies identified specific hydrophobic, topologic and electronic properties of the molecules for both in vitro and in vivo activities. From these results, a three-dimensional model of a DNA-quinolone complex was built using molecular modeling techniques. It was based on the intercalation of quinolone into the double helix of DNA. We conclude that the intercalation model is consistent with most available data on the structure of the quinolone complex. This predicted structure is stabilized by the binding of magnesium ion with the sp2 oxygens present in quinolone, a phosphate and a purine base of the DNA. Substituents R1 and R7 are predicted to make hydrophobic interactions in the major and minor groove of DNA, respectively. R7 could also form hydrogen bonds with amino groups of guanines and the aspartic acid residue at position 87 in DNA gyrase subunit A.

  5. Laboratory diagnosis of SARS.

    PubMed Central

    Bermingham, A; Heinen, P; Iturriza-Gómara, M; Gray, J; Appleton, H; Zambon, M C

    2004-01-01

    The emergence of new viral infections of man requires the development of robust diagnostic tests that can be applied in the differential diagnosis of acute illness, or to determine past exposure, so as to establish the true burden of disease. Since the recognition in April 2003 of the severe acute respiratory syndrome coronavirus (SARS-CoV) as the causative agent of severe acute respiratory syndrome (SARS), enormous efforts have been applied to develop molecular and serological tests for SARS which can assist rapid detection of cases, accurate diagnosis of illness and the application of control measures. International progress in the laboratory diagnosis of SARS-CoV infection during acute illness has led to internationally agreed World Health Organization criteria for the confirmation of SARS. Developments in the dissection of the human immune response to SARS indicate that serological tests on convalescent sera are essential to confirm SARS infection, given the sub-optimal predictive value of molecular detection tests performed during acute SARS illness. PMID:15306394

  6. 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.

  7. 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.

  8. Building Detection in SAR Imagery

    SciTech Connect

    Steinbach, Ryan Matthew; Koch, Mark William; Moya, Mary M; Goold, Jeremy

    2014-08-01

    Current techniques for building detection in Synthetic Aperture Radar (SAR) imagery can be computationally expensive and/or enforce stringent requirements for data acquisition. The desire is to present a technique that is 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 technique assumes 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. Constraints based on angle of depression and the relationship between connected bright lines and shadows are applied to remove unrelated arcs. Once the related bright lines and shadows are grouped, their locations are combined to provide an approximate building location. Experimental results are provided showing the outcome of the technique.

  9. 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.

  10. 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.

  11. Synthesis and Structure–Activity Relationship Study of 1-Phenyl-1-(quinazolin-4-yl)ethanols as Anticancer Agents

    PubMed Central

    2015-01-01

    A quinazoline derivative PVHD121 (1a) was shown to have strong antiproliferative activity against various tumor-derived cell lines, including A549 (lung), NCI-H460 (lung), HCT116 (colon), MCF7 (breast), PC3 (prostate), and HeLa (cervical) cells with IC50 values from 0.1 to 0.3 μM. A structure–activity relationship (SAR) study at the 2- and 4-position of the quinazoline core lead to the discovery of more potent anticancer agents (14, 16, 17, 19, 24, and 31). The results of an in vitro tubulin polymerization assay and fluorescent-based colchicine site competition assay with purified tubulin indicated that 1a inhibits tubulin polymerization by binding to the colchicine site. PMID:25815147

  12. 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.

  13. The Relationship between Physical Activity and Productivity

    DTIC Science & Technology

    1984-04-01

    CONTINUED Aerobic exercises were the primary type of physical activity considered. The research focused on two specific objectives: (1) to review and... physical fitness and exercise activities . One of the priority objectives is to increase the proportion of adults (aged 18 to 65) participating in... physical activity will be used to encompass both aerobic fitness and exercise . This will allow consideration of the impact of varying levels of exercise

  14. A cancer/testis antigen, NY-SAR-35, induces EpCAM, CD44, and CD133, and activates ERK in HEK293 cells.

    PubMed

    Song, Myung-Ha; Kim, Ye-Rin; Bae, Jae-Ho; Shin, Dong-Hoon; Lee, Sang-Yull

    2017-03-04

    The cancer/testis (CT) antigen NY-SAR-35 gene is located on the X chromosome and is aberrantly expressed in various cancers but not in normal tissues, other than testes. Previously, we reported the expression of NY-SAR-35 enhanced cell growth, proliferation, and invasion in HEK293 and cancer cells. To extend understanding of the NY-SAR-35 gene, we used a next generation sequencing (NGS) approach. NY-SAR-35 expression induced growth, proliferation, metastasis, and stemness genes, as indicated by the up-regulations of CXCR4, EpCAM, CD133, and CD44, at the mRNA and protein levels. The expression of NY-SAR-35 in HEK293 cells significantly increased ERK phosphorylation, but not the phosphorylation of AKT. In HEK293/NY-SAR-35 cells, the expressions of pro-apoptotic proteins, including p53, Bax, and p21, were reduced and that of cyclin E was increased. Also, NY-SAR-35 increased the expressions of pluripotency genes (Nanog, Oct-4, and Sox2) and the ability of HEK293 cells to form colonies. Taken together, the present study indicates NY-SAR-35 functions as a CT antigen that triggers oncogenesis and self-renewal.

  15. SAR antenna calibration techniques

    NASA Technical Reports Server (NTRS)

    Carver, K. R.; Newell, A. C.

    1978-01-01

    Calibration of SAR antennas requires a measurement of gain, elevation and azimuth pattern shape, boresight error, cross-polarization levels, and phase vs. angle and frequency. For spaceborne SAR antennas of SEASAT size operating at C-band or higher, some of these measurements can become extremely difficult using conventional far-field antenna test ranges. Near-field scanning techniques offer an alternative approach and for C-band or X-band SARs, give much improved accuracy and precision as compared to that obtainable with a far-field approach.

  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. 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.

  18. 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).

  19. Processing of TerraSAR-X payload data: first results

    NASA Astrophysics Data System (ADS)

    Breit, H.; Balss, U.; Bamler, R.; Fritz, T.; Eineder, M.

    2007-10-01

    TerraSAR-X is Germany's new radar remote sensing flagship. It carries an advanced high-resolution X-band SAR instrument. The key element of the system is the active phased array antenna nominally operated with a bandwidth of 100 MHz or 150 MHz and an experimental 300 MHz capability. The instrument's flexibility with respect to electronic beam steering and pulse-to-pulse polarization switching allows the acquisition of SAR data in Stripmap, Spotlight and ScanSAR imaging configurations in different polarization modes for a wide range of incidence angles. The mission is implemented in the framework of a public-private partnership between the German Aerospace Center (DLR) and EADS Astrium GmbH Germany and will provide high resolution SAR data products for commercial use and scientific exploitation. Processing of the payload data will be performed at DLR's Payload Ground Segment (PGS) for TerraSAR-X. The central part of PGS is the TerraSAR Multi-Mode SAR Processor (TMSP) focusing the SAR data in a unified way for the different imaging configurations. A wide range of processing options spanning from phase preserving complex products in slant range geometry to orthorectified terrain corrected intensity images lead to a comprehensive collection of SAR product types and variants. During the 5 months lasting commissioning phase the complete processing chain will be properly tuned and adjusted. The TMSP algorithms have to be configured, e.g. thresholds for calibration pulse analysis, estimation window sizes for SAR data analysis, parameterization of estimation algorithms. Also the configuration of product variants with respect to resolution and radiometric quality will be checked and refined. This paper shortly reviews the different imaging configurations and product variants and gives a report on the SAR processor checkout activities and presents the first results.

  20. Structure-activity relationship for noncoplanar polychlorinated biphenyl congeners toward the ryanodine receptor-Ca2+ channel complex type 1 (RyR1).

    PubMed

    Pessah, Isaac N; Hansen, Larry G; Albertson, Timothy E; Garner, C Edwin; Ta, Tram Anh; Do, Zung; Kim, Kyung Ho; Wong, Patty W

    2006-01-01

    Ryanodine receptor isoforms are expressed in both excitable and nonexcitable tissues where they form microsomal Ca2+ release channels broadly involved in shaping cellular signaling. In this report, we provide a detailed structure-activity relationship (SAR) for polychlorinated biphenyl (PCB) congeners and metabolites necessary for enhancing ryanodine receptor type 1 (RyR1) activity using [3H]ryanodine ([3H]Ry) binding analysis. The 2,3,6-Cl PCB configuration is most important for optimal recognition by the RyR1 complex and/or critical for sensitizing its activation. Para substitution(s) diminishes the activity with para-chloro having a higher potency than the corresponding para-hydroxy derivative. The addition of a more bulky para-methyl-sulfonyl group eliminates the activity toward RyR1, supporting the importance of the para positions in binding RyR1. The requirement for an intact major T cell immunophilin FKBP12-RyR1 complex was observed with each of 12 active PCB congeners indicating a common mechanism requiring an immunophilin-regulated Ca2+ release channel. An excellent correlation between the relative potencies for doubling [3H]Ry binding and the corresponding initial rates of PCB-induced Ca2+ efflux indicates that [3H]Ry binding analysis provides a measure of dysregulation of microsomal Ca2+ transport. The SAR for activating RyR1 is consistent with those previously reported in several in vivo and in vitro studies, suggesting that a common mechanism may contribute to the toxicity of noncoplanar PCBs. A practical application of the receptor-based screen developed here with RyR1 is that it provides a quantitative SAR that may be useful in predicting biological activity and risk of mixtures containing noncoplanar PCB congeners that have low or a lack of aryl hydrocarbon receptor activity.

  1. 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

  2. Quantum-SAR extension of the spectral-SAR algorithm: application to polyphenolic anticancer bioactivity.

    PubMed

    Putz, Mihai V; Putz, Ana-Maria; Lazea, Marius; Ienciu, Luciana; Chiriac, Adrian

    2009-03-01

    Aiming to assess the role of individual molecular structures in the molecular mechanism of ligand-receptor interaction correlation analysis, the recent Spectral-SAR approach is employed to introduce the Quantum-SAR (QuaSAR) "wave" and "conversion factor" in terms of difference between inter-endpoint inter-molecular activities for a given set of compounds; this may account for inter-conversion (metabolization) of molecular (concentration) effects while indicating the structural (quantum) based influential/detrimental role on bio-/eco- effect in a causal manner rather than by simple inspection of measured values; the introduced QuaSAR method is then illustrated for a study of the activity of a series of flavonoids on breast cancer resistance protein.

  3. Quantum-SAR Extension of the Spectral-SAR Algorithm. Application to Polyphenolic Anticancer Bioactivity

    PubMed Central

    Putz, Mihai V.; Putz, Ana-Maria; Lazea, Marius; Ienciu, Luciana; Chiriac, Adrian

    2009-01-01

    Aiming to assess the role of individual molecular structures in the molecular mechanism of ligand-receptor interaction correlation analysis, the recent Spectral-SAR approach is employed to introduce the Quantum-SAR (QuaSAR) “wave” and “conversion factor” in terms of difference between inter-endpoint inter-molecular activities for a given set of compounds; this may account for inter-conversion (metabolization) of molecular (concentration) effects while indicating the structural (quantum) based influential/detrimental role on bio-/eco- effect in a causal manner rather than by simple inspection of measured values; the introduced QuaSAR method is then illustrated for a study of the activity of a series of flavonoids on breast cancer resistance protein. PMID:19399244

  4. 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…

  5. 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.

  6. 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…

  7. 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.

  8. 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…

  9. Verification of L-band SAR calibration

    NASA Technical Reports Server (NTRS)

    Larson, R. W.; Jackson, P. L.; Kasischke, E.

    1985-01-01

    Absolute calibration of a digital L-band SAR system to an accuracy of better than 3 dB has been verified. This was accomplished with a calibration signal generator that produces the phase history of a point target. This signal relates calibration values to various SAR data sets. Values of radar cross-section (RCS) of reference reflectors were obtained using a derived calibration relationship for the L-band channel on the ERIM/CCRS X-C-L SAR system. Calibrated RCS values were compared to known RCS values of each reference reflector for verification and to obtain an error estimate. The calibration was based on the radar response to 21 calibrated reference reflectors.

  10. Structure-activity relationships of pyrrole based S-nitrosoglutathione reductase inhibitors: pyrrole regioisomers and propionic acid replacement.

    PubMed

    Sun, Xicheng; Qiu, Jian; Strong, Sarah A; Green, Louis S; Wasley, Jan W F; Colagiovanni, Dorothy B; Mutka, Sarah C; Blonder, Joan P; Stout, Adam M; Richards, Jane P; Chun, Lawrence; Rosenthal, Gary J

    2011-06-15

    S-Nitrosoglutathione reductase (GSNOR) is a member of the alcohol dehydrogenase family (ADH) that regulates the levels of S-nitrosothiols (SNOs) through catabolism of S-nitrosoglutathione (GSNO). GSNO and SNOs are implicated in the pathogenesis of many diseases including those in respiratory, cardiovascular, and gastrointestinal systems. The pyrrole based N6022 was recently identified as a potent, selective, reversible, and efficacious GSNOR inhibitor which is currently undergoing clinical development. We describe here the synthesis and structure-activity relationships (SAR) of novel pyrrole based analogues of N6022 focusing on scaffold modification and propionic acid replacement. We identified equally potent and novel GSNOR inhibitors having pyrrole regioisomers as scaffolds using a structure based approach.

  11. Gas-phase rate coefficients for reactions of NO 3, OH, O 3 and O( 3P) with unsaturated alcohols and ethers: Correlations and structure-activity relations (SARs)

    NASA Astrophysics Data System (ADS)

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

    Experimental difficulties sometimes force modellers to use predicted rate coefficients for reactions of oxygenated volatile organic compounds (oVOCs). We examine here methods for making the predictions for reactions of atmospheric initiators of oxidation, NO 3, OH, O 3 and O( 3P), with unsaturated alcohols and ethers. Logarithmic correlations are found between measured rate coefficients and calculated orbital energies, and these correlations may be used directly to estimate rate coefficients for compounds where measurements have not been performed. To provide a shortcut that obviates the need to calculate orbital energies, structure-activity relations (SARs) are developed. Our SARs are tested for predictive power against compounds for which experimental rate coefficients exist, and their accuracy is discussed. Estimated atmospheric lifetimes for oVOCs are presented. The SARs for alkenols successfully predict key rate coefficients, and thus can be used to enhance the scope of atmospheric models incorporating detailed chemistry. SARs for the ethers have more limited applicability, but can still be useful in improving tropospheric models.

  12. 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.

  13. Synthesis, modification and docking studies of 5-sulfonyl isatin derivatives as SARS-CoV 3C-like protease inhibitors.

    PubMed

    Liu, Wei; Zhu, He-Min; Niu, Guo-Jun; Shi, En-Zhi; Chen, Jie; Sun, Bo; Chen, Wei-Qiang; Zhou, Hong-Gang; Yang, Cheng

    2014-01-01

    The Severe Acute Respiratory Syndrome (SARS) is a serious life-threatening and strikingly mortal respiratory illness caused by SARS-CoV. SARS-CoV which contains a chymotrypsin-like main protease analogous to that of the main picornavirus protease, 3CL(pro). 3CL(pro) plays a pivotal role in the viral replication cycle and is a potential target for SARS inhibitor development. A series of isatin derivatives as possible SARS-CoV 3CL(pro) inhibitors was designed, synthesized, and evaluated by in vitro protease assay using fluorogenic substrate peptide, in which several showed potent inhibition against the 3CL(pro). Structure-activity relationship was analyzed, and possible binding interaction modes were proposed by molecular docking studies. Among all compounds, 8k₁ showed most potent inhibitory activity against 3CL(pro) (IC₅₀=1.04 μM). These results indicated that these inhibitors could be potentially developed into anti-SARS drugs.

  14. ECCM performance analysis of chaotic coded orthogonal frequency division multiplexing (COFDM) SAR

    NASA Astrophysics Data System (ADS)

    Feng, Xiangzhi; Xu, Xiaojian

    2011-06-01

    Conventional linear frequency modulation (LFM) synthetic aperture radar (SAR) is incapable of countering deceptive repeat jamming. In this paper, a new SAR signal based on chaotic coded orthogonal frequency division multiplexing (COFDM) is studied. The fact that chaotic codes are sensitive to the initial values allows generating a large number of different chaotic sequences to form SAR transmitting waveforms, where all the signal sequences are orthogonal to each other, enabling COFDM-SAR countering not only active noise but also deceptive repeat jamming. The procedures for COFDM waveform generation and SAR anti-jamming processing are discussed. Comparative studies of the electronic counter-countermeasure performance (ECCM) between COFDM-SAR and conventional LFM-SAR are made. Simulation results are presented to demonstrate the superior performance of COFDM-SAR in countering repeat deception as well as active noise jamming.

  15. Conformation-activity relationships of opiate analgesics

    NASA Astrophysics Data System (ADS)

    Martin, Jennifer; Andrews, Peter

    1987-04-01

    Extensive conformational calculations were performed on the potent opiate analgesics etorphine, PET, R30490 and etonitazene to determine all of their many low-energy conformations. The results were used to characterize four possible models for binding of a simple pharmacophore, comprising two phenyl rings plus a protonated nitrogen, to opiate analgesic receptors. These four models may define the necessary three-dimensional features leading to particular opiate actions. The model favoured for μ receptor activity can accommodate a protonated nitrogen, an aromatic ring (which may be substituted with an electronegative group) and a second lipophilic group. These structural features must be presented in a precise three-dimensional arrangement. It appears likely that a hydrophilic substituent in a certain region of the analgesic pharmacophore may also interact with the receptor as a secondary binding group.

  16. 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

  17. 12 CFR 563.180 - Suspicious Activity Reports and other reports and statements.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ....C. 1813(u) and 1818(b)(9)). (iii) SAR means a Suspicious Activity Report. (3) SARs required. A... action. (11) Obtaining SARs. A savings association or service corporation may obtain SARs and the...) Confidentiality of SARs. A SAR, and any information that would reveal the existence of a SAR, are...

  18. 12 CFR 563.180 - Suspicious Activity Reports and other reports and statements.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ....C. 1813(u) and 1818(b)(9)). (iii) SAR means a Suspicious Activity Report. (3) SARs required. A... action. (11) Obtaining SARs. A savings association or service corporation may obtain SARs and the...) Confidentiality of SARs. A SAR, and any information that would reveal the existence of a SAR, are...

  19. 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.

  20. Structural Basis for the Ubiquitin-Linkage Specificity and deISGylating Activity of SARS-CoV Papain-Like Protease

    PubMed Central

    Ratia, Kiira; Kilianski, Andrew; Baez-Santos, Yahira M.; Baker, Susan C.; Mesecar, Andrew

    2014-01-01

    Severe acute respiratory syndrome coronavirus (SARS-CoV) encodes a papain-like protease (PLpro) with both deubiquitinating (DUB) and deISGylating activities that are proposed to counteract the post-translational modification of signaling molecules that activate the innate immune response. Here we examine the structural basis for PLpro's ubiquitin chain and interferon stimulated gene 15 (ISG15) specificity. We present the X-ray crystal structure of PLpro in complex with ubiquitin-aldehyde and model the interaction of PLpro with other ubiquitin-chain and ISG15 substrates. We show that PLpro greatly prefers K48- to K63-linked ubiquitin chains, and ISG15-based substrates to those that are mono-ubiquitinated. We propose that PLpro's higher affinity for K48-linked ubiquitin chains and ISG15 stems from a bivalent mechanism of binding, where two ubiquitin-like domains prefer to bind in the palm domain of PLpro with the most distal ubiquitin domain interacting with a “ridge” region of the thumb domain. Mutagenesis of residues within this ridge region revealed that these mutants retain viral protease activity and the ability to catalyze hydrolysis of mono-ubiquitin. However, a select number of these mutants have a significantly reduced ability to hydrolyze the substrate ISG15-AMC, or be inhibited by K48-linked diubuiquitin. For these latter residues, we found that PLpro antagonism of the nuclear factor kappa-light-chain-enhancer of activated B-cells (NFκB) signaling pathway is abrogated. This identification of key and unique sites in PLpro required for recognition and processing of diubiquitin and ISG15 versus mono-ubiquitin and protease activity provides new insight into ubiquitin-chain and ISG15 recognition and highlights a role for PLpro DUB and deISGylase activity in antagonism of the innate immune response. PMID:24854014

  1. 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

  2. Structure-activity relationships of benzothiazole GPR35 antagonists.

    PubMed

    Abdalhameed, Manahil M; Zhao, Pingwei; Hurst, Dow P; Reggio, Patricia H; Abood, Mary E; Croatt, Mitchell P

    2017-02-01

    The first structure-activity relationships for a benzothiazole scaffold acting as an antagonist at GPR35 is presented. Analogues were designed based on a lead compound that was previously determined to have selective activity as a GPR35 antagonist. The synthetic route was modular in nature to independently explore the role of the middle and both ends of the scaffold. The activities of the analogues illustrate the importance of all three segments of the compound.

  3. Structure-activity relationships of benzothiazole GPR35 antagonists

    PubMed Central

    Abdalhameed, Manahil M.; Zhao, Pingwei; Hurst, Dow P.; Reggio, Patricia H.; Abood, Mary E.; Croatt, Mitchell P.

    2017-01-01

    The first structure-activity relationships for a benzothiazole scaffold acting as an antagonist at GPR35 is presented. Analogues were designed based on a lead compound that was previously determined to have selective activity as a GPR35 antagonist. The synthetic route was modular in nature to independently explore the role of the middle and both ends of the scaffold. The activities of the analogues illustrate the importance of all three segments of the compound. PMID:27989666

  4. Antenna trajectory error analysis in backprojection-based SAR images

    NASA Astrophysics Data System (ADS)

    Wang, Ling; Yazıcı, Birsen; Yanik, H. Cagri

    2014-06-01

    We present an analysis of the positioning errors in Backprojection (BP)-based Synthetic Aperture Radar (SAR) images due to antenna trajectory errors for a monostatic SAR traversing a straight linear trajectory. Our analysis is developed using microlocal analysis, which can provide an explicit quantitative relationship between the trajectory error and the positioning error in BP-based SAR images. The analysis is applicable to arbitrary trajectory errors in the antenna and can be extended to arbitrary imaging geometries. We present numerical simulations to demonstrate our analysis.

  5. 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.

  6. SARS and Common Viral Infections

    PubMed Central

    Hacker, Jill K.; Mark, Jennifer; Gavali, Shilpa S.; Yagi, Shigeo; Espinosa, Alex; Schnurr, David P.; Cossen, Cynthia K.; Isaacson, Erin R.; Glaser, Carol A.; Fischer, Marc; Reingold, Arthur L.; Vugia, Duc J.

    2004-01-01

    In California, molecular testing was useful in decreasing suspicion for severe acute respiratory syndrome (SARS), by detecting common respiratory pathogens (influenza A/B, human metapneumovirus, picornavirus, Mycoplasma pneumoniae, Chlamydia spp., parainfluenza virus, respiratory syncytial virus, and adenovirus) in 23 (45%) of 51 patients with suspected SARS and 9 (47%) of 19 patients with probable SARS. PMID:15207072

  7. ProSAR: a new methodology for combinatorial library design.

    PubMed

    Chen, Hongming; Börjesson, Ulf; Engkvist, Ola; Kogej, Thierry; Svensson, Mats A; Blomberg, Niklas; Weigelt, Dirk; Burrows, Jeremy N; Lange, Tim

    2009-03-01

    A method is introduced for performing reagent selection for chemical library design based on topological (2D) pharmacophore fingerprints. Optimal reagent selection is achieved by optimizing the Shannon entropy of the 2D pharmacophore distribution for the reagent set. The method, termed ProSAR, is therefore expected to enumerate compounds that could serve as a good starting point for deriving a structure activity relationship (SAR) in combinatorial library design. This methodology is exemplified by library design examples where the active compounds were already known. The results show that most of the pharmacophores on the substituents for the active compounds are covered by the designed library. This strategy is further expanded to include product property profiles for aqueous solubility, hERG risk assessment, etc. in the optimization process so that the reagent pharmacophore diversity and the product property profile are optimized simultaneously via a genetic algorithm. This strategy is applied to a two-dimensional library design example and compared with libraries designed by a diversity based strategy which minimizes the average ensemble Tanimoto similarity. Our results show that by using the PSAR methodology, libraries can be designed with simultaneously good pharmacophore coverage and product property profile.

  8. Relationship Between Evoked and Spontaneous Activity in Cultured Neuronal Circuits

    NASA Astrophysics Data System (ADS)

    Kiyohara, Ai; Taguchi, Takahisa; Kudoh, Suguru N.

    Relationship between evoked activity and spontaneous activity in neuronal circuits is one of the important theme for the improvement of neuroprosthetic apparatus. The spontaneous activity and evoked action potentials are mutually related in the cultured neuronal network autonomously reconstructed on the culture dish, but there is a question whether spontaneous activity and the evoked action potentials constitute one state respectively or the spontaneous activity is only a random background noise. Comparing the frequencies and standard deviations of spontaneous activity with those of evoked activity, we found that the silent and reproducible period lasting for 1 sec immediately after the activity evoked primally. In addition, the repetitive stimuli suppress the spontaneously occurring bursting activity in frequency, even though the inter-stimulus-interval was more than 10 sec. These results suggests that distinct internal state of the neuronal circuit was triggered by an electrical stimulation, and there were state of spontaneous mode and evoked mode in a neuronal circuit.

  9. Therapeutic targeting of erbB3 with MM-121/SAR256212 enhances antitumor activity of paclitaxel against erbB2-overexpressing breast cancer

    PubMed Central

    2013-01-01

    Introduction Elevated expression of erbB3 rendered erbB2-overexpressing breast cancer cells resistant to paclitaxel via PI-3 K/Akt-dependent upregulation of Survivin. It is unclear whether an erbB3-targeted therapy may abrogate erbB2-mediated paclitaxel resistance in breast cancer. Here, we study the antitumor activity of an anti-erbB3 antibody MM-121/SAR256212 in combination with paclitaxel against erbB2-overexpressing breast cancer. Methods Cell growth assays were used to determine cell viability. Cells undergoing apoptosis were quantified by a specific apoptotic ELISA. Western blot analyses were performed to assess the protein expression and activation. Lentiviral vector containing shRNA was used to specifically knockdown Survivin. Tumor xenografts were established by inoculation of BT474-HR20 cells into nude mice. The tumor-bearing mice were treated with paclitaxel and/or MM-121/SAR256212 to determine whether the antibody (Ab) enhances paclitaxel’s antitumor activity. Immunohistochemistry was carried out to study the combinatorial effects on tumor cell proliferation and induction of apoptosis in vivo. Results MM-121 significantly facilitated paclitaxel-mediated anti-proliferative/anti-survival effects on SKBR3 cells transfected with a control vector or erbB3 cDNA. It specifically downregulated Survivin associated with inactivation of erbB2, erbB3, and Akt. MM-121 enhances paclitaxel-induced poly(ADP-ribose) polymerase (PARP) cleavage, activation of caspase-8 and -3, and apoptosis in both paclitaxel-sensitive and -resistant cells. Specific knockdown of Survivin in the trastuzumab-resistant BT474-HR20 cells dramatically enhanced paclitaxel-induced apoptosis, suggesting that increased Survivin caused a cross-resistance to paclitaxel. Furthermore, the studies using a tumor xenograft model-established from BT474-HR20 cells revealed that either MM-121 (10 mg/kg) or low-dose (7.5 mg/kg) paclitaxel had no effect on tumor growth, their combinations significantly

  10. Activity Landscape Plotter: A Web-Based Application for the Analysis of Structure-Activity Relationships.

    PubMed

    González-Medina, Mariana; Méndez-Lucio, Oscar; Medina-Franco, José L

    2017-03-27

    Activity landscape modeling is a powerful method for the quantitative analysis of structure-activity relationships. This cheminformatics area is in continuous growth, and several quantitative and visual approaches are constantly being developed. However, these approaches often fall into disuse due to their limited access. Herein, we present Activity Landscape Plotter as the first freely available web-based tool to automatically analyze structure-activity relationships of compound data sets. Based on the concept of activity landscape modeling, the online service performs pairwise structure and activity relationships from an input data set supplied by the user. For visual analysis, Activity Landscape Plotter generates Structure-Activity Similarity and Dual-Activity Difference maps. The user can interactively navigate through the maps and export all the pairwise structure-activity information as comma delimited files. Activity Landscape Plotter is freely accessible at https://unam-shiny-difacquim.shinyapps.io/ActLSmaps /.

  11. Partitioning and lipophilicity in quantitative structure-activity relationships.

    PubMed Central

    Dearden, J C

    1985-01-01

    The history of the relationship of biological activity to partition coefficient and related properties is briefly reviewed. The dominance of partition coefficient in quantitation of structure-activity relationships is emphasized, although the importance of other factors is also demonstrated. Various mathematical models of in vivo transport and binding are discussed; most of these involve partitioning as the primary mechanism of transport. The models describe observed quantitative structure-activity relationships (QSARs) well on the whole, confirming that partitioning is of key importance in in vivo behavior of a xenobiotic. The partition coefficient is shown to correlate with numerous other parameters representing bulk, such as molecular weight, volume and surface area, parachor and calculated indices such as molecular connectivity; this is especially so for apolar molecules, because for polar molecules lipophilicity factors into both bulk and polar or hydrogen bonding components. The relationship of partition coefficient to chromatographic parameters is discussed, and it is shown that such parameters, which are often readily obtainable experimentally, can successfully supplant partition coefficient in QSARs. The relationship of aqueous solubility with partition coefficient is examined in detail. Correlations are observed, even with solid compounds, and these can be used to predict solubility. The additive/constitutive nature of partition coefficient is discussed extensively, as are the available schemes for the calculation of partition coefficient. Finally the use of partition coefficient to provide structural information is considered. It is shown that partition coefficient can be a valuable structural tool, especially if the enthalpy and entropy of partitioning are available. PMID:3905374

  12. Endochin optimization: structure-activity and structure-property relationship studies of 3-substituted 2-methyl-4(1H)-quinolones with antimalarial activity.

    PubMed

    Cross, R Matthew; Monastyrskyi, Andrii; Mutka, Tina S; Burrows, Jeremy N; Kyle, Dennis E; Manetsch, Roman

    2010-10-14

    Since the 1940s endochin and analogues thereof were known to be causal prophylactic and potent erythrocytic stage agents in avian models. Preliminary screening in a current in vitro assay identified several 4(1H)-quinolones with nanomolar EC(50) against erythrocytic stages of multidrug resistant W2 and TM90-C2B isolates of Plasmodium falciparum. Follow-up structure-activity relationship (SAR) studies on 4(1H)-quinolone analogues identified several key features for biological activity. Nevertheless, structure-property relationship (SPR) studies conducted in parallel revealed that 4(1H)-quinolone analogues are limited by poor solubilities and rapid microsomal degradations. To improve the overall efficacy, multiple 4(1H)-quinolone series with varying substituents on the benzenoid quinolone ring and/or the 3-position were synthesized and tested for in vitro antimalarial activity. Several structurally diverse 6-chloro-2-methyl-7-methoxy-4(1H)-quinolones with EC(50) in the low nanomolar range against the clinically relevant isolates W2 and TM90-C2B were identified with improved physicochemical properties while maintaining little to no cross-resistance with atovaquone.

  13. SARS: just another viral acronym?

    PubMed

    Broxmeyer, L

    2003-08-01

    Recent observations and experimental evidence have purported that a virus causes SARS, but such viruses have been isolated in only less than half of SARS patients in some studies and virologist Vincent Plummer of Winnipeg's National Microbiology Laboratory found that indeed 1 in 5 perfectly healthy Canadians with a history of recent travel to Asia had the virus. Therefore SARS microbiologic origins remain unclear. Outbreaks of multi-drug resistant (MDR) tuberculosis and the atypical mycobacteria simulate SARS on clinical, radiologic, epidemiologic, and diagnostic laboratory grounds and it is only logical then to include them in the differential to find a definitive cause and cure for SARS.

  14. SAR11 bacteria linked to ocean anoxia and nitrogen loss

    PubMed Central

    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.

    2016-01-01

    Summary Bacteria of the SAR11 clade constitute up to one half of all microbial cells in the oxygen-rich surface ocean. DNA sequences from SAR11 are also abundant in oxygen minimum zones (OMZs) where oxygen falls below detection and anaerobic microbes play important roles in converting bioavailable nitrogen to N2 gas. Evidence for anaerobic metabolism in SAR11 has not yet been observed, and the question of how these bacteria contribute to OMZ biogeochemical cycling is unanswered. Here, we identify the metabolic basis for SAR11 activity in anoxic ocean waters. Genomic analysis of single cells from the world’s largest OMZ revealed diverse and previously uncharacterized SAR11 lineages that peak in abundance at anoxic depths, but are largely undetectable in oxygen-rich ocean regions. OMZ SAR11 contain adaptations to low oxygen, including genes for respiratory nitrate reductases (Nar). SAR11 nar genes were experimentally verified to encode proteins catalyzing the nitrite-producing first step of denitrification and constituted ~40% of all OMZ nar transcripts, with transcription peaking in the zone of maximum nitrate reduction rates. These results redefine the ecological niche of Earth’s most abundant organismal group and suggest an important contribution of SAR11 to nitrite production in OMZs, and thus to pathways of ocean nitrogen loss. PMID:27487207

  15. Design, synthesis, and structure-activity relationship studies of fluorescent inhibitors of cycloxygenase-2 as targeted optical imaging agents.

    PubMed

    Uddin, Md Jashim; Crews, Brenda C; Ghebreselasie, Kebreab; Marnett, Lawrence J

    2013-04-17

    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.

  16. 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

  17. 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.

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

    PubMed

    Le Calvé, Benjamin; Lallemand, Benjamin; Perrone, Carmen; Lenglet, Gaëlle; Depauw, Sabine; Van Goietsenoven, Gwendoline; Bury, Marina; Vurro, Maurizio; Herphelin, Françoise; Andolfi, Anna; Zonno, Maria Chiara; Mathieu, Véronique; Dufrasne, François; Van Antwerpen, Pierre; Poumay, Yves; David-Cordonnier, Marie-Hélène; Evidente, Antonio; Kiss, Robert

    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.

  19. Simple SAR demonstrator

    NASA Astrophysics Data System (ADS)

    Kulpa, Krzysztof; Misiurewicz, Jacek; Baranowski, Piotr; Wojdołowicz, Grzegorz

    2008-01-01

    In this paper we present a simple SAR radar demonstrator build using commercially available (COTS) components. For the microwave analog front end, a standard police radar microwave head has been used. The Motorola DSP processor board, equipped with ADC and DAC, has been used for generating of modulating signal and for signal acquisition. The raw radar signal (I and Q components) have been recorded on 2.5" HDD. The signal processing has been performed on standard PC computer after copying the recorded data. The aim of constructing simple and relatively cheap demonstrator was to provide the students the real-life unclassified radar signals and motivate them to test and develop various kinds of SAR and ISAR algorithms, including image formation, motion compensation and autofocusing. The simple microwave frontend hardware has a lot of non-idealities, so for obtaining nice SAR image it was necessary to develop the number of correction algorithms at the calibration stage. The SAR demonstrator have been tested using car as a moving platform. The flight tests with a small airborne platform are planned for the summer.

  20. Recursive SAR imaging

    NASA Astrophysics Data System (ADS)

    Moses, Randolph L.; Ash, Joshua N.

    2008-04-01

    We investigate a recursive procedure for synthetic aperture imaging. We consider a concept in which a SAR system persistently interrogates a scene, for example as it flies along or around that scene. In traditional SAR imaging, the radar measurements are processed in blocks, by partitioning the data into a set of non-overlapping or overlapping azimuth angles, then processing each block. We consider a recursive update approach, in which the SAR image is continually updated, as a linear combination of a small number of previous images and a term containing the current radar measurement. We investigate the crossrange sidelobes realized by such an imaging approach. We show that a first-order autoregression of the image gives crossrange sidelobes similar to a rectangular azimuth window, while a third-order autoregression gives sidelobes comparable to those obtained from widely-used windows in block-processing image formation. The computational and memory requirements of the recursive imaging approach are modest - on the order of M • N2 where M is the recursion order (typically <= 3) and N2 is the image size. We compare images obtained from the recursive and block processing techniques, both for a synthetic scene and for X-band SAR measurements from the Gotcha data set.

  1. Application of "hydrogen bonding interaction" in new drug development: design, synthesis, antiviral activity, and SARs of thiourea derivatives.

    PubMed

    Lu, Aidang; Wang, Ziwen; Zhou, Zhenghong; Chen, Jianxin; Wang, Qingmin

    2015-02-11

    A series of simple thiourea derivatives were designed based on the structure of natural product harmine and lead compound and synthesized from amines in one step. The antiviral activity of these thiourea derivatives was evaluated. Most of them exhibited significantly higher anti-TMV activity than commercial plant virucides ribavirin, harmine, and lead compound. The hydrogen bond was found to be important but not the more the better. The optimal compound (R,R)-20 showed the best anti-TMV activity in vitro and in vivo (in vitro activity, 75%/500 μg/mL and 39%/100 μg/mL; inactivation activity, 71%/500 μg/mL and 35%/100 μg/mL; curative activity, 73%/500 μg/mL and 37%/100 μg/mL; protection activity, 69%/500 μg/mL and 33%/100 μg/mL), which is significantly higher than that of Ningnanmycin. The systematic study provides strong evidence that these simple thiourea derivatives could become potential TMV inhibitors.

  2. 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.

  3. SARS in Hospital Emergency Room

    PubMed Central

    Chen, Yee-Chun; Huang, Li-Min; Chan, Chang-Chuan; Su, Chan-Ping; Chang, Ying-Ying; Chen, Mei-Ling; Hung, Chien-Ching; Chen, Wen-Jone; Lin, Fang-Yue; Lee, Yuan-Teh

    2004-01-01

    Thirty-one cases of severe acute respiratory syndrome (SARS) occurred after exposure in the emergency room at the National Taiwan University Hospital. The index patient was linked to an outbreak at a nearby municipal hospital. Three clusters were identified over a 3-week period. The first cluster (5 patients) and the second cluster (14 patients) occurred among patients, family members, and nursing aids. The third cluster (12 patients) occurred exclusively among healthcare workers. Six healthcare workers had close contact with SARS patients. Six others, with different working patterns, indicated that they did not have contact with a SARS patient. Environmental surveys found 9 of 119 samples of inanimate objects to be positive for SARS coronavirus RNA. These observations indicate that although transmission by direct contact with known SARS patients was responsible for most cases, environmental contamination with the SARS coronavirus may have lead to infection among healthcare workers without documented contact with known hospitalized SARS patients. PMID:15200809

  4. Fusion of Radarsat SAR interferograms with Other Image and Geological Data Sets to Establish Temporal, Spatial and Physical behaviors of the Active Layer at Sagwon, Alaska

    NASA Astrophysics Data System (ADS)

    Lovick, J.; Li, S.; Romanovski, V.

    2002-12-01

    Regional variations in ground surface parameters are seen, and inferred to be due to areas of differential frost heave, through the application differential interferometric techniques (DINSAR) to Interferometric Synthetic Aperture Radar (SAR) images centered around Sagwon in Alaska's north slope, from scenes covering a two year period from Jan 2000 to March 2002. Interpretation of the radar images is not straightforward so, several techniques are employed to assist in the interpretation. 1) Comparison with existing surficial geology maps, 2) Time series analysis of the radar dataset using Empirical Orthogonal Function analysis (a temporal equivalent of Principle Component analysis), and 3) Data Fusion between the Radar scenes and optical data sets, and principle component analysis of the Optical data sets. Comparison with existing surficial geological maps and analysis of radar backscatter images gives an indication of the amount of surface moisture, and its distribution. This correlates with areas of frost heave, wetter area's experiencing a greater degree of heaving. Analysis of the DINSAR images indicates frost heave distribution and shows its susceptibility to the ground lithology, areas such as abandoned riverbeds show less in the way of heave, and active riverbeds and bare rock do not frost heave. The analysis of coherence between radar scenes allows a delineation of area's of acidic tundra, and non acidic tundra. Optical datasets, from the MODIS and ASTER satellites are also examined to constrain the effects of weather and other shorter-term weather factors. Principle component analysis was performed on individual datasets, which gives an independent (from the radar data set) estimation of area's of acidic and non acidic tundra, and surficial geology. The combined data set improves characterization of the temporal, spatial and physical behaviors of the active layer in the region.

  5. 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.

  6. TerraSAR-X for CSCDA: Interface Evolution

    NASA Astrophysics Data System (ADS)

    Parlar, Selin; Mayhew, Ben; Doeberl, Michael; Langhans, Daniel; Arndt, Wolf-Christian; Bach, Katja

    2016-08-01

    The TerraSAR-X mission has been contributing to Copernicus Space Component Data Access (CSCDA) Data Warehouse (DWH) project since 2009. For this purpose, the mission has established specific interfaces to the ESA Coordinated Data Access System (CDS).This paper gives a background about the past activities performed by TerraSAR-X Copernicus Contributing Mission (TerraSAR-X CCM), provides a detailed overview of ongoing activities, and discusses lessons learnt as well as future opportunities in terms of Heterogeneous Missions Accessibility (HMA) interfaces.

  7. Structure-molluscicidal activity relationships of acylphloroglucinols from ferns.

    PubMed

    Socolsky, Cecilia; Borkosky, Susana; Bardón, Alicia

    2011-03-01

    The molluscicidal activity of 12 phloroglucinol derivatives previously isolated from Elaphoglossum piloselloides, E. gayanum, E. yungense, and E. lindbergii, as well as 3 known acylphloroglucinols, now reported from an Argentine collection of Dryopteris wallichiana, was evaluated against the schistosomiasis vector snail Biomphalaria peregrina. Molluscicidal effects were analyzed and compared with those previously observed for 4 acylphloroglucinols from E. piloselloides and their corresponding peracetylated derivatives, in order to draw structure-activity relationships. The most active compounds were the prenylated desaspidins elaphogayanin B and elaphopilosins A and B (LD50 = 1.90, 2.90, and 0.94 ppm, respectively), together with the only evaluated prenylated para-aspidin, elaphopilosin C (LD50 = 2.15 ppm). Quantitative structure-activity relationships (QSAR) were studied by means of a semiempirical method (PM3) for the 24 natural phloroglucinol derivatives included in this paper. The descriptor molecular volume was found to have good correlation with the observed molluscicidal activity (r2 = 0.77). The derived equation can be considered useful to predict the molluscicidal activity of bi and tricyclic acylphloroglucinols. The QSAR analysis showed that there is an optimum volume for high activity, probably related to the size of a receptor's active site. Bigger molecules display lower activity.

  8. 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.

  9. SarA, a global regulator of virulence determinants in Staphylococcus aureus, binds to a conserved motif essential for sar-dependent gene regulation.

    PubMed

    Chien, Y; Manna, A C; Projan, S J; Cheung, A L

    1999-12-24

    The expression of many virulence determinants in Staphylococcus aureus including alpha-hemolysin-, protein A-, and fibronectin-binding proteins is controlled by global regulatory loci such as sar and agr. In addition to controlling target gene expression via agr (e.g. alpha-hemolysin), the sar locus can also regulate target gene transcription via agr-independent mechanisms. In particular, we have found that SarA, the major regulatory protein encoded within sar, binds to a conserved sequence, homologous to the SarA-binding site on the agr promoter, upstream of the -35 promoter boxes of several target genes including hla (alpha-hemolysin gene), spa (protein A gene), fnb (fibronectin-binding protein genes), and sec (enterotoxin C gene). Deletion of the SarA recognition motif in the promoter regions of agr and hla in shuttle plasmids rendered the transcription of these genes undetectable in agr and hla mutants, respectively. Likewise, the transcription activity of spa (a gene normally repressed by sar), as measured by a XylE reporter fusion assay, became derepressed in a wild type strain containing a shuttle plasmid in which the SarA recognition site had been deleted from the spa promoter region. However, DNase I footprinting assays demonstrated that the SarA-binding region on the spa and hla promoter is more extensive than the predicted consensus sequence, thus raising the possibility that the consensus sequence is an activation site within a larger binding region. Because the sar and agr regulate an assortment of virulence factors in S. aureus, we propose, based on our data, a unifying hypothesis for virulence gene activation in S. aureus whereby SarA is a regulatory protein that binds to its consensus SarA recognition motif to activate (e.g. hla) or repress (e.g. spa) the transcription of sar target genes, thus accounting for both agr-dependent and agr-independent mode of regulation.

  10. Predicting allergic contact dermatitis: a hierarchical structure activity relationship (SAR) approach to chemical classification using topological and quantum chemical descriptors

    NASA Astrophysics Data System (ADS)

    Basak, Subhash C.; Mills, Denise; Hawkins, Douglas M.

    2008-06-01

    A hierarchical classification study was carried out based on a set of 70 chemicals—35 which produce allergic contact dermatitis (ACD) and 35 which do not. This approach was implemented using a regular ridge regression computer code, followed by conversion of regression output to binary data values. The hierarchical descriptor classes used in the modeling include topostructural (TS), topochemical (TC), and quantum chemical (QC), all of which are based solely on chemical structure. The concordance, sensitivity, and specificity are reported. The model based on the TC descriptors was found to be the best, while the TS model was extremely poor.

  11. 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...

  12. Research progress in structure-activity relationship of bioactive peptides.

    PubMed

    Li, Ying; Yu, Jianmei

    2015-02-01

    Bioactive peptides are specific protein fragments that have positive impact on health. They are important sources of new biomedicine, energy and high-performance materials. The beneficial effects of bioactive peptides are due to their antioxidant, antihypertensive, anticarcinogenic, antimicrobial, and immunomodulatory activities. The structure-activity relationship of bioactive peptides plays a significant role in the development of innovative and unconventional synthetic polymeric counterparts. It provides the basis of the stereospecific synthesis, transformation, and development of bioactive peptide products. This review covers the progress of studies in the structure-activity relationship of some bioactive peptides including antioxidant peptides, angiotensin-I-converting enzyme-inhibitory peptides, and anticarcinogenic peptides in the past decade.

  13. Structure-Activity Relationship of Fluoroquinolones Against K. pneumoniae

    NASA Astrophysics Data System (ADS)

    Li, Xiao-hong; Zhang, Rui-zhou; Cheng, Xin-lu; Yang, Xiang-dong

    2007-04-01

    The structure-activity relationship of fluoroquinolones, which show anti-K. pneumoniae activity, was studied by using principal component analysis (PCA) and hierarchical cluster analysis (HCA). The PCA results showed that the lowest unoccupied molecular orbital energy, energy difference between the highest occupied and the lowest unoccupied molecular orbital, dipole moment, net atomic charge on atom I, molecular polarizability, partition coefficient and molecular refractivity of these compounds are responsible for the separation between high-activity and low-activity groups. The HCA results were similar to those obtained with PCA. By using the chemometric results, four synthetic compounds were analyzed through PCA and HCA, and three of them are proposed as active molecules against K. pneumoniae which is consistent with the results of clinical experiments. The methodologies of PCA and HCA provide a reliable rule for classifying new fluoroquinolones with anti-K. pneumoniae activity.

  14. Synthetic and structure-activity relationship of insecticidal bufadienolides.

    PubMed

    Hidayat, Ace Tatang; Zainuddin, Achmad; Dono, Danar; Hermawan, Wawan; Hayashi, Hideo; Supratman, Unang

    2014-07-01

    A new synthetic analog of bufadienolide, methyl isobryophyllinate A (1), and a known synthetic analog, methyl isobersaldegenate-1,3,5-orthoacetate (2), were obtained by methanolysis of bryophyllin A (3) and bersaldegenin-1,3,5-orthoacetate (5) in basic solution. Structure-insecticidal activity relationship studies revealed both orthoacetate and alpha-pyrone moieties seemed to be essential structural elements for exhibiting insecticidal activity, whereas oxygenated substituents in the C ring enhanced the insecticidal activity against the third instar larvae of silkworm (Bombyx mori).

  15. Roads Centre-Axis Extraction in Airborne SAR Images: AN Approach Based on Active Contour Model with the Use of Semi-Automatic Seeding

    NASA Astrophysics Data System (ADS)

    Lotte, R. G.; Sant'Anna, S. J. S.; Almeida, C. M.

    2013-05-01

    Research works dealing with computational methods for roads extraction have considerably increased in the latest two decades. This procedure is usually performed on optical or microwave sensors (radar) imagery. Radar images offer advantages when compared to optical ones, for they allow the acquisition of scenes regardless of atmospheric and illumination conditions, besides the possibility of surveying regions where the terrain is hidden by the vegetation canopy, among others. The cartographic mapping based on these images is often manually accomplished, requiring considerable time and effort from the human interpreter. Maps for detecting new roads or updating the existing roads network are among the most important cartographic products to date. There are currently many studies involving the extraction of roads by means of automatic or semi-automatic approaches. Each of them presents different solutions for different problems, making this task a scientific issue still open. One of the preliminary steps for roads extraction can be the seeding of points belonging to roads, what can be done using different methods with diverse levels of automation. The identified seed points are interpolated to form the initial road network, and are hence used as an input for an extraction method properly speaking. The present work introduces an innovative hybrid method for the extraction of roads centre-axis in a synthetic aperture radar (SAR) airborne image. Initially, candidate points are fully automatically seeded using Self-Organizing Maps (SOM), followed by a pruning process based on specific metrics. The centre-axis are then detected by an open-curve active contour model (snakes). The obtained results were evaluated as to their quality with respect to completeness, correctness and redundancy.

  16. 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.

  17. 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

  18. 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.

  19. Very High Resolution SAR and Multichannel SAR/MTI

    DTIC Science & Technology

    2006-09-01

    single channel SAR system: • Detection outside the clutter bandwidth • Chirp slope analysis • Chirp filter bank • MTI via multilook images (change...53343 Wachtberg, Germany berens@fgan.de ABSTRACT SAR is widely used today in earth observation and is a potential means for military surveillance...However, systems only operating in the basic SAR mode will be superseded by new developments which fulfil much more user demands. Highest resolution

  20. 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.

  1. SAR based adaptive GMTI

    NASA Astrophysics Data System (ADS)

    Vu, Duc; Guo, Bin; Xu, Luzhou; Li, Jian

    2010-04-01

    We consider ground moving target indication (GMTI) and target velocity estimation based on multi-channel synthetic aperture radar (SAR) images. Via forming velocity versus cross-range images, we show that small moving targets can be detected even in the presence of strong stationary ground clutter. Moreover, the velocities of the moving targets can be estimated, and the misplaced moving targets can be placed back to their original locations based on the estimated velocities. Adaptive beamforming techniques, including Capon and generalizedlikelihood ratio test (GLRT), are used to form velocity versus cross-range images for each range bin of interest. The velocity estimation ambiguities caused by the multi-channel array geometry are analyzed. We also demonstrate the effectiveness of our approaches using the Air Force Research Laboratory (AFRL) publicly-released Gotcha SAR based GMTI data set.

  2. 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.

  3. On statistical relationship of solar, geomagnetic and human activities.

    PubMed

    Alania, M V; Gil, A; Modzelewska, R

    2004-01-01

    Data of galactic cosmic rays, solar and geomagnetic activities and solar wind parameters on the one side and car accident events (CAE) in Poland on the other have been analyzed in order to reveal the statistical relationships among them for the period of 1990-2001. Cross correlation and cross spectrum of the galactic cosmic ray intensity, the solar wind (SW) velocity, Kp index of geomagnetic activity and CAE in Poland have been carried out. It is shown that in some epochs of the above-mentioned period there is found a reliable relationship between CAE and solar and geomagnetic activities parameters in the range of the different periodicities, especially, 7 days. The periodicity of 7 days revealed in the data of the CAE has the maximum on Friday without any exception for the minimum and maximum epochs of solar activity. However, the periodicity of 7 days is reliably revealed in other parameters characterizing galactic cosmic rays, SW, solar and geomagnetic activities, especially for the minimum epoch of solar activity. The periodicity of 3.5 days found in the series of CAE data more or less can be completely ascribed to the social effects, while the periodicity of 7 days can be ascribed to the social effect or/to the processes on the Sun, in the interplanetary space and in the Earth's magnetosphere and atmosphere.

  4. 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

  5. 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

  6. Relationships between molecular structure and chromosomal aberrations in virto human lymphocytes induced by substituted nitrobenzenes

    SciTech Connect

    Huang, Q.G.; Kong, L.R.; Liu, Y.B.; Wang, L.S.

    1996-12-31

    Most nitrated aromatics are genotoxic, some structure-activity relationship (SAR) studies have been done about their mutagenicity, but most studies are concerned with the nitrated polycyclic aromatic hydrocarbons. This report studied the substituted nitrobenzenes and the relationship between molecular structure and genotoxicity of these compounds. 8 refs., 1 tab.

  7. 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.

  8. Synthesis and structure-activity relationships of 2-phenyl-1-[(pyridinyl- and piperidinylmethyl)amino]-3-(1H-1,2,4-triazol-1-yl)propan-2-ols as antifungal agents.

    PubMed

    Giraud, Francis; Guillon, Rémi; Logé, Cédric; Pagniez, Fabrice; Picot, Carine; Le Borgne, Marc; Le Pape, Patrice

    2009-01-15

    Continuous efforts on the synthesis and structure-activity relationships (SARs) studies of modified 1-benzylamino-2-phenyl-3-(1H-1,2,4-triazol-1-yl)propan-2-ols as antifungal agents, allowed identification of new 1-[(pyridinyl- and piperidinylmethyl)amino] derivatives with MIC(80) values ranging from 1410.0 to 23.0ngmL(-1) on Candidaalbicans. These results confirmed both the importance of pi-pi stacking and hydrogen bonding interactions in the active site of CYP51-C. albicans.

  9. 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).

  10. Preparation of Polyethylene Composites Containing Silver(I) Acylpyrazolonato Additives and SAR Investigation of their Antibacterial Activity.

    PubMed

    Marchetti, Fabio; Palmucci, Jessica; Pettinari, Claudio; Pettinari, Riccardo; Marangoni, Mirko; Ferraro, Stefano; Giovannetti, Rita; Scuri, Stefania; Grappasonni, Iolanda; Cocchioni, Mario; Maldonado Hodar, Francisco José; Gunnella, Roberto

    2016-11-02

    Novel composite materials PEn (n = 1-9) have been prepared by an easily up-scalable embedding procedure of three different families of Ag(I) acylpyrazolonato complexes in polyethylene (PE) matrix. In details, PE1-PE3 composites contain polynuclear [Ag(Q(R))]n complexes, PE4-PE6 contain mononuclear [Ag(Q(R))(L)m] complexes and PE7-PE9 are loaded with mononuclear [Ag(Q(R)) (PPh3)2] complexes, respectively (where L = 1-methylimidazole or 2-ethylimidazole, m = 1 or 2, and HQ(R) = 1-phenyl-3-methyl-4-RC(═O)-5-pyrazolone, where in detail HQ(fb), R = -CF2CF2CF3; HQ(cy), R = -cyclo-C6H11; HQ(be), R = -C(H)═C(CH3)2). The PEn composites, prepared by using a 1:1000 w/w silver additive/polyethylene ratio, have been characterized in bulk by IR spectroscopy and TGA analyses, which confirmed that the properties of polyethylene matrix are essentially unchanged. AFM, SEM, and EDX surface techniques show that silver additives form agglomerates with dimensions 10-100 μm on the polyethylene surface, with a slight increment of surface roughness of pristine plastic within 50 nm. However, the elastic properties of the composites are essentially the same of PE. The antibacterial activity of all composites has been tested against three bacterial strains (E. coli, P. aeruginosa and S. aureus) and results show that two classes of composites, PE1-PE3 and PE4-PE6, display high and persistent bactericidal and bacteriostatic activity, comparable to PE embedded with AgNO3. By contrast, composites PE7-PE9 exhibit a reduced antibacterial action. Contact and release tests in several conditions for specific migration of Ag(+) from plastics, indicate a very limited but time persistent release of silver ions from PE1-PE6 composites, thus suggesting that they are potential antibacterial materials for future applications. Instead, PE7-PE9 almost do not release silver, only trace levels of silver ions being detected, in accordance with their reduced antibacterial action. None of the composites is

  11. Relationship between antimold activity and molecular structure of cinnamaldehyde analogues.

    PubMed

    Zhang, Yuanyuan; Li, Shujun; Kong, Xianchao

    2013-03-01

    A quantitative structure-activity relationship (QSAR) modeling of the antimold activity of cinnamaldehyde analogues against of Aspergillus niger and Paecilomyces variotii was presented. The molecular descriptors of cinnamaldehyde analogues were calculated by the CODESSA program, and these descriptors were selected by best multi-linear regression method (BMLR). Satisfactory multilinear regression models of Aspergillus niger and Paecilomyces variotii were obtained with R(2)=0.9099 and 0.9444, respectively. The models were also satisfactorily validated using internal validation and leave one out validation. The QSAR models provide the guidance for further synthetic work.

  12. 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.

  13. Biologically relevant chemical space navigator: from patent and structure-activity relationship analysis to library acquisition and design.

    PubMed

    Rabal, Obdulia; Oyarzabal, Julen

    2012-12-21

    A new and versatile visualization tool, based on a descriptor accounting for ligand-receptor interactions (LiRIf), is introduced for guiding medicinal chemists in analyzing the R-groups from a congeneric series. Analysis is performed in a reference-independent scenario where the whole biologically relevant chemical space (BRCS) is represented. Using a real project-based data set, we show the impact of this tool on four key navigation strategies for the drug discovery process. First, this navigator analyzes competitors' patents, including a comparison of patents coverage and the identification of the most frequent fragments. Second, the tool analyzes the structure-activity relationship (SAR) leading to the representation of reference-independent activity landscapes that enable the identification not only of critical ligand-receptor interactions (LRI) and substructural features but also of activity cliffs. Third, this navigator enables comparison of libraries, thus selecting commercially available molecules that complement unexplored spaces or areas of interest. Finally, this tool also enables the design of new analogues, which is based on reaction types and the exploration purpose (focused or diverse), selecting the most appropriate reagents.

  14. Comprehensive Analysis of Structure Activity Relationships of α-Ketoheterocycles as sn-1-Diacylglycerol Lipase α Inhibitors

    PubMed Central

    Janssen, Freek J.; Baggelaar, Marc P.; Hummel, Jessica J. A.; Overkleeft, Herman S.; Cravatt, Benjamin F.; Boger, Dale L.; van der Stelt, Mario

    2015-01-01

    Diacylglycerol lipase α (DAGLα) is responsible for the formation of the endocannabinoid 2-arachidonoylglycerol (2-AG) in the central nervous system. DAGLα inhibitors are required to study the physiological role of 2-AG. Previously, we identified the α-ketoheterocycles as potent and highly selective DAGLα inhibitors. Here, we present the first comprehensive structure-activity relationship study of α-ketoheterocycles as DAGLα inhibitors. Our findings indicate that the active site of DAGLα is remarkably sensitive to the type of heterocyclic scaffold with oxazolo-4N-pyridines as the most active framework. We uncovered a fundamental substituent effect in which electron-withdrawing meta-oxazole substituents increased inhibitor potency. (C6-C9)-acyl chains with a distal phenyl group proved to be the most potent inhibitors. The integrated SAR data was consistent with the proposed binding pose in a DAGLα homology model. Altogether our results may guide the design of future DAGLα inhibitors as leads for molecular therapies to treat neuroinflammation, obesity and related metabolic disorders. PMID:26584396

  15. SAR Educational Resources From ASF

    NASA Astrophysics Data System (ADS)

    Gens, R.

    2006-12-01

    In parallel with developing software tools specifically for SAR data, the Alaska Satellite Facility (ASF) has a long history of supporting users in the use of the tools and the data. Over the years a number of educational resources have been developed as well. ASF distributes a number of educational CDs (Glacier Power, Dynamic Planet, and Ends of the Earth) that cover a wide range of imagery and applications. In addition, an extensive and frequently updated SAR bibliograpy is made available to users through the ASF website. Summer courses in SAR/InSAR and its applications are offered for credit and are being well received by the user community. The summer courses allow users to get a complete overview about SAR and InSAR as well as all the relevant techniques within an intense two week time frame. In order to explain the various processing steps in a Range-Doppler SAR Processor in detail the SAR Training Processor (STP) has been developed. This enhanced debugging mode of the fully functional, regular SAR processor allows the user to save all the intermediate products and have full control over all processing steps and parameters. This way, the user can evaluate the results of omitting a processing step or changing Doppler parameters. For the future, tailor made offsite training courses and workshops are planned. Updates on these can be found at http://www.asf.alaska.edu/educational/index.html.

  16. β-Glucans: Relationships between Modification, Conformation and Functional Activities.

    PubMed

    Wang, Qiang; Sheng, Xiaojing; Shi, Aimin; Hu, Hui; Yang, Ying; Liu, Li; Fei, Ling; Liu, Hongzhi

    2017-02-09

    β-glucan is a type of polysaccharide which widely exists in bacteria, fungi, algae, and plants, and has been well known for its biological activities such as enhancing immunity, antitumor, antibacterial, antiviral, and wound healing activities. The conformation of β-glucan plays a crucial role on its biological activities. Therefore, β-glucans obtained from different sources, while sharing the same basic structures, often show different bioactivities. The basic structure and inter-molecular forces of polysaccharides can be changed by modification, which leads to the conformational transformation in solution that can directly affect bioactivity. In this review, we will first determine different ways to modify β-glucan molecules including physical methods, chemical methods, and biological methods, and then reveal the relationship of the flexible helix form of the molecule chain and the helix conformation to their bioactivities. Last, we summarize the scientific challenges to modifying β-glucan's conformation and functional activity, and discuss its potential future development.

  17. Search for Hsp90 Inhibitors with Potential Anticancer Activity: Isolation and SAR Studies of Radicicol and Monocillin I from Two Plant-Associated Fungi of the Sonoran Desert1

    PubMed Central

    Turbyville, Thomas J.; Kithsiri Wijeratne, E. M.; Liu, Manping X.; Burns, Anna M.; Seliga, Christopher J.; Luevano, Libia A.; David, Cynthia L.; Faeth, Stanley H.; Whitesell, Luke; Leslie Gunatilaka, A. A.

    2006-01-01

    In an effort to discover small molecule inhibitors of Hsp90, we have screened over 500 EtOAc extracts of Sonoran desert plant-associated fungi using a two-stage strategy consisting of a primary cell-based heat shock induction assay (HSIA) followed by a secondary biochemical luciferase refolding assay (LRA). Bioassay-guided fractionation of extracts active in these assays derived from Chaetomium chiversii and Paraphaeosphaeria quadriseptata furnished the Hsp90 inhibitors radicicol (1) and monocillin I (2), respectively. In SAR studies, 1, 2, and their analogues, 3–16, were evaluated in these assays, and the antiproliferative activity of compounds active in both assays was determined using the breast cancer cell line MCF-7. Radicicol and monocillin I were also evaluated in a solid-phase competition assay for their ability to bind Hsp90 and to deplete cellular levels of two known Hsp90 client proteins with relevance to breast cancer, estrogen receptor (ER), and the type 1 insulin-like growth factor receptor (IGF-1R). Some inferences on SAR were made considering the crystal structure of the N-terminus of yeast Hsp90 bound to 1 and the observed biological activities of 1–16. Isolation of radicicol and monocillin I in this study provides evidence that we have developed an effective strategy for discovering natural product-based Hsp90 inhibitors with potential anticancer activity. PMID:16499313

  18. Using PS-InSAR data in landslide hazard management: the case of Veneto Region (NE Italy)

    NASA Astrophysics Data System (ADS)

    Floris, Mario; Viganò, Alessandro; Busnardo, Enrico; Arziliero, Luciano; Zanette, Doriano

    2013-04-01

    The Project Persistent Scatterers Interferometry, performed by the Italian Ministry of Environment and Territory of the Sea (METS) in the framework of the Extraordinary Plan of Environmental Remote Sensing, has made available a high quantity of data useful for local Authorities (Regions, Provinces, and Municipalities) in the management of the main geological hazards, such as landslides, subsidence, and sinkholes. The main output of the Project consists of ground displacements and velocities measured at target points over the entire Italian territory by using PS-InSAR processing technique applied to SAR data acquired by satellites ESA (European Space Agency) ERS-1 and ERS-2 (Earth Resources Satellite) and ENVISAT (Environmental Satellite) in the period 1992-2010. Description and results of the Project are available for public browsing at the geoportal of the METS (http://www.pcn.minambiente.it). On the basis of PS-InSAR data, several studies have been recently performed for the identification and characterization of landslides both at small and large scale. These studies led to a more precise delimitation of instable areas and to a better evaluation of the state of activity of mass movements. But, as now well known, interferometry techniques can't be applied to the whole territory due to geometric distortions in SAR data acquisition and to ground conditions. In this work we analyze the potentiality of PS-InSAR data from the Project Persistent Scatterers Interferometry in landslide hazard management of the Veneto Region, located in the north-eastern part of Italy. A synthetic description on the main features of landslides affecting the Region is reported, then the percentage of instabilities where PS-InSAR data can be used, is calculated. At the scale of the entire Region we suggest to follow the method proposed in the scientific literature to evaluate the state of activity of landslides on the basis of the measured velocities at the ground surface, while at local

  19. 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 .

  20. Predator-dependent species-area relationships.

    PubMed

    Ryberg, Wade A; Chase, Jonathan M

    2007-10-01

    In addition to having a positive effect on species richness (species-area relationships [SARs]), habitat area can influence the presence of predators, which can indirectly influence prey richness. While these direct and indirect effects of area on richness occur simultaneously, no research has examined how predation might contribute to SAR variation. We extend MacArthur and Wilson's equilibrium theory of island biogeography by including predation-induced shifts in prey extinction and predict that predators will reduce slopes of prey SARs. We provide support for this with data from two insular ecosystems: orthopteran richness in Ozark glades (rocky herbaceous communities within a forested matrix) with and without insectivorous lizards and zooplankton richness in freshwater ponds with and without zooplanktivorous fishes. Our results emphasize that anthropogenic activities yield simultaneous changes in processes altering diversity and that it is critical that we understand how these components of anthropogenic change interact to impact diversity.

  1. 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

  2. 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.

  3. Quantitative structure-activity relationships for the in vitro antimycobacterial activity of pyrazinoic acid esters.

    PubMed

    Bergmann, K E; Cynamon, M H; Welch, J T

    1996-08-16

    Substituted pyrazinoic acid esters have previously been reported to have in vitro activity against Mycobacterium avium and Mycobacterium kansasii as well as Mycobacterium tuberculosis. Modification of both the pyrazine nucleus and the ester functionality was successful in expanding the antimycobacterial activity associated with pyrazinamide to include M. avium and M. kansasii, organisms usually not susceptible to pyrazinamide. In an attempt to understand the relationship between the activity of the esters with the needed biostability, a quantitative structure-activity relationship has been developed. This derived relationship is consistent with the observation that tert-butyl 5-chloropyrazinoate (13) and 2'-(2'-methyldecyl) 5-chloropyrazinoate (25), compounds which are both 100-fold more active than pyrazinamide against M. tuberculosis and possess a serum stability 900-1000 times greater than the lead compounds in the series.

  4. (abstract) The SIR-C/X-SAR Mission

    NASA Technical Reports Server (NTRS)

    Way, JoBea; Evans, Diane; Elachi, Charles

    1993-01-01

    The Shuttle Imaging Radar-C and X-Band Synthetic Aperture Radar (SIR-C/X-SAR) is a cooperative experiment between the National Aeronautics and Space Administration (NASA), the German Space Agency (DARA), and the Italian Space Agency (ASI). The experiment is the next evolutionary step in NASA's Spaceborne Imaging Radar (SIR) program that began with the Seasat SAR in 1978, and continued with SAR -A in 1981 and SAR-B in 1984. The program will eventually lead to the Earth Observing System (EOS) SAR later in this decade. SIR-C will provide increased capability over Seasat, SIR-A, and SIR-B by acquiring polarimetric images simultaneously at two microwave frequencies: L-band (wavelength 24 cm) and C-band (wavelength 6 cm). X-SAR will operate at X-band (wavelength 3 cm) with VV polarization, resulting in a three-frequency capability. Because radar backscatter is most strongly influenced by objects comparable in size to the radar wavelength, this multifrequency capability will provide information about the Earth's surface over a wide range of scales not discernable with single-frequency experiments. The polarimetric data will yield quantitative information about the surface geometric structure, vegetation dielectric properties, and surface discontinuities. The first SIR-C/X-SAR flight is planned for early in 1994, with two subsequent flights in different seasons to enable data aquisition under different environmental conditions. SIR-C/X-SAR will collect data for a period of 6 to 9 days during each flight. The instrument will be flown in a 57(deg) inclination orbit with a nomimal orbit altitude of 215 km. This altitude will result in a slightly drifting orbit. The latest status of the SIR-C/X-SAR mission and instrument design, science activities, and expected results will be presented.

  5. 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

    2014-06-16

    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.

  6. Neuritogenic activity of gangliosides from echinoderms and their structure-activity relationship.

    PubMed

    Kaneko, Masafumi; Yamada, Koji; Miyamoto, Tomofumi; Inagaki, Masanori; Higuchi, Ryuichi

    2007-03-01

    The effects of the gangliosides isolated from echinoderms on the neuritogenesis of a rat pheochromocytoma cell line (PC-12 cells) in the presence of nerve growth factor were investigated. The results show that they displayed neuritogenic activity. Based on the observed results, a structure-activity relationship has been established.

  7. Lipid A structural modifications in extreme conditions and identification of unique modifying enzymes to define the Toll-like receptor 4 structure-activity relationship.

    PubMed

    Scott, Alison J; Oyler, Benjamin L; Goodlett, David R; Ernst, Robert K

    2017-01-17

    Strategies utilizing Toll-like receptor 4 (TLR4) agonists for treatment of cancer, infectious diseases, and other targets report promising results. Potent TLR4 antagonists are also gaining attention as therapeutic leads. Though some principles for TLR4 modulation by lipid A have been described, a thorough understanding of the structure-activity relationship (SAR) is lacking. Only through a complete definition of lipid A-TLR4 SAR is it possible to predict TLR4 signaling effects of discrete lipid A structures, rendering them more pharmacologically relevant. A limited 'toolbox' of lipid A-modifying enzymes has been defined and is largely composed of enzymes from mesophile human and zoonotic pathogens. Expansion of this 'toolbox' will result from extending the search into lipid A biosynthesis and modification by bacteria living at the extremes. Here, we review the fundamentals of lipid A structure, advances in lipid A uses in TLR4 modulation, and the search for novel lipid A-modifying systems in extremophile bacteria. This article is part of a Special Issue entitled: Bacterial Lipids edited by Russell E. Bishop.

  8. 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.

  9. Antitumor activity and structure-activity relationship of diterpenoids with a dehydroabietyl skeleton.

    PubMed

    Rao, Xiaoping; Huang, Xiuzhi; He, Ling; Song, Jie; Song, Zhanqian; Shang, Shibin

    2012-12-01

    A series of novel diterpenoids including imines, amides and ureas with a dehydroabietyl skeleton were screened to hepatocellular carcinoma (SMMC-7721), lung cancer (A-549), glioma (C-6) and breast carcinoma (MCF-7) tumor cells by MTT method. Their antitumor activity and structure activity relationship were analyzed. Several of the title compounds such as I-2, I-10, I-6 and I-5, possess noticeable antitumor activity against SMMC-7721, A-549, C-6 and MCF-7 tumor cells, with lowest IC(50) values of 6.65, 0.75, 0.81 and 10.65μM, respectively. Based on the structure-activity relationship investigation, the three kinds of diterpenoids with a dehydroabietyl skeleton show high activity to SMMC-7721 cells. Imines derivatives exhibit broad spectrum and highly efficient activities to the selected four kinds of tumor cells.

  10. Quantitative structure-activity relationship studies on nitrofuranyl antitubercular agents

    PubMed Central

    Hevener, Kirk E.; Ball, David M.; Buolamwini, John K.

    2008-01-01

    A series of nitrofuranylamide and related aromatic compounds displaying potent activity against M. tuberculosis has been investigated utilizing 3-Dimensional Quantitative Structure-Activity Relationship (3D-QSAR) techniques. Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) methods were used to produce 3D-QSAR models that correlated the Minimum Inhibitory Concentration (MIC) values against M. tuberculosis with the molecular structures of the active compounds. A training set of 95 active compounds was used to develop the models, which were then evaluated by a series of internal and external cross-validation techniques. A test set of 15 compounds was used for the external validation. Different alignment and ionization rules were investigated as well as the effect of global molecular descriptors including lipophilicity (cLogP, LogD), Polar Surface Area (PSA), and steric bulk (CMR), on model predictivity. Models with greater than 70% predictive ability, as determined by external validation, and high internal validity (cross validated r2 > .5) have been developed. Incorporation of lipophilicity descriptors into the models had negligible effects on model predictivity. The models developed will be used to predict the activity of proposed new structures and advance the development of next generation nitrofuranyl and related nitroaromatic anti-tuberculosis agents. PMID:18701298

  11. Nicotinamide phosphoribosyltransferase inhibitors, design, preparation, and structure-activity relationship.

    PubMed

    Christensen, Mette K; Erichsen, Kamille D; Olesen, Uffe H; Tjørnelund, Jette; Fristrup, Peter; Thougaard, Annemette; Nielsen, Søren Jensby; Sehested, Maxwell; Jensen, Peter B; Loza, Einars; Kalvinsh, Ivars; Garten, Antje; Kiess, Wieland; Björkling, Fredrik

    2013-11-27

    Existing pharmacological inhibitors for nicotinamide phosphoribosyltransferase (NAMPT) are promising therapeutics for treating cancer. By using medicinal and computational chemistry methods, the structure-activity relationship for novel classes of NAMPT inhibitors is described, and the compounds are optimized. Compounds are designed inspired by the NAMPT inhibitor APO866 and cyanoguanidine inhibitor scaffolds. In comparison with recently published derivatives, the new analogues exhibit an equally potent antiproliferative activity in vitro and comparable activity in vivo. The best performing compounds from these series showed subnanomolar antiproliferative activity toward a series of cancer cell lines (compound 15: IC50 0.025 and 0.33 nM, in A2780 (ovarian carcinoma) and MCF-7 (breast), respectively) and potent antitumor in vivo activity in well-tolerated doses in a xenograft model. In an A2780 xenograft mouse model with large tumors (500 mm(3)), compound 15 reduced the tumor volume to one-fifth of the starting volume at a dose of 3 mg/kg administered ip, bid, days 1-9. Thus, compounds found in this study compared favorably with compounds already in the clinic and warrant further investigation as promising lead molecules for the inhibition of NAMPT.

  12. 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.

  13. 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.

  14. Relationship between peptide membrane curvature generation and bactericidal activities

    NASA Astrophysics Data System (ADS)

    Schmidt, Nathan; Lee, Michelle; Kuo, David; Ouellette, Andre; Wong, Gerard

    2013-03-01

    Many amphipathic peptides and amphipathic domains in proteins can restructure biological membranes. Two examples are host defense antimicrobial peptides (AMPs) which disrupt and destabilize the cell membranes of microbes, and apolipoproteins which help stabilize nanoscale lipid aggregates. We use complementary x-ray and bacterial cell assays to elucidate the molecular length scale membrane deformations generated by amphipathic peptides with different structural motifs and relate these deformations to their activities on bacteria. Small angle x-ray scattering is used to study the interactions of model membranes with prototypical AMPs and consensus peptides from the amphipathic domains in apolipoproteins. By characterizing the nanoscale curvature deformations induced by these two distinct classes of membrane restructuring peptides we will discuss the role of amino acid composition on curvature generation. Bactericidal assays are used to access the in vivo activities of different amphipathic peptide motifs in order to understand the relationships between cell viability and membrane curvature generation.

  15. The Alaska SAR processor

    NASA Technical Reports Server (NTRS)

    Carande, R. E.; Charny, B.

    1988-01-01

    The Alaska SAR processor was designed to process over 200 100 km x 100 km (Seasat like) frames per day from the raw SAR data, at a ground resolution of 30 m x 30 m from ERS-1, J-ERS-1, and Radarsat. The near real time processor is a set of custom hardware modules operating in a pipelined architecture, controlled by a general purpose computer. Input to the processor is provided from a high density digital cassette recording of the raw data stream as received by the ground station. A two pass processing is performed. During the first pass clutter-lock and auto-focus measurements are made. The second pass uses the results to accomplish final image formation which is recorded on a high density digital cassette. The processing algorithm uses fast correlation techniques for range and azimuth compression. Radiometric compensation, interpolation and deskewing is also performed by the processor. The standard product of the ASP is a high resolution four-look image, with a low resolution (100 to 200 m) many look image provided simultaneously.

  16. 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

  17. 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

  18. Anticancer Activity of Estradiol Derivatives: A Quantitative Structure--Activity Relationship Approach

    NASA Astrophysics Data System (ADS)

    Muranaka, Ken

    2001-10-01

    Commercial packages to implement modern QSAR (quantitative structure-activity relationship) techniques are highly priced; however, the essence of QSAR can be taught without them. Microsoft Excel was used to analyze published data on anticancer activities of estradiol analogs by a QSAR approach. The resulting QSAR equations highly correlate the structural features and physicochemical properties of the analogs with the observed biological activities by multiple linear regression.

  19. admetSAR: a comprehensive source and free tool for assessment of chemical ADMET properties.

    PubMed

    Cheng, Feixiong; Li, Weihua; Zhou, Yadi; Shen, Jie; Wu, Zengrui; Liu, Guixia; Lee, Philip W; Tang, Yun

    2012-11-26

    Absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties play key roles in the discovery/development of drugs, pesticides, food additives, consumer products, and industrial chemicals. This information is especially useful when to conduct environmental and human hazard assessment. The most critical rate limiting step in the chemical safety assessment workflow is the availability of high quality data. This paper describes an ADMET structure-activity relationship database, abbreviated as admetSAR. It is an open source, text and structure searchable, and continually updated database that collects, curates, and manages available ADMET-associated properties data from the published literature. In admetSAR, over 210,000 ADMET annotated data points for more than 96,000 unique compounds with 45 kinds of ADMET-associated properties, proteins, species, or organisms have been carefully curated from a large number of diverse literatures. The database provides a user-friendly interface to query a specific chemical profile, using either CAS registry number, common name, or structure similarity. In addition, the database includes 22 qualitative classification and 5 quantitative regression models with highly predictive accuracy, allowing to estimate ecological/mammalian ADMET properties for novel chemicals. AdmetSAR is accessible free of charge at http://www.admetexp.org.

  20. Improving confidence in (Q)SAR predictions under Canada's Chemicals Management Plan - a chemical space approach.

    PubMed

    Kulkarni, S A; Benfenati, E; Barton-Maclaren, T S

    2016-10-20

    One of the key challenges of Canada's Chemicals Management Plan (CMP) is assessing chemicals with limited/no empirical hazard data for their risk to human health. In some instances, these chemicals have not been tested broadly for their toxicological potency; as such, limited information exists on their potential to induce human health effects following exposure. Although (quantitative) structure activity relationship ((Q)SAR) models are able to generate predictions to address data gaps for certain toxicological endpoints, the confidence in predictions also needs to be addressed. One way to address this issue is to apply a chemical space approach. This approach uses international toxicological databases, for example, those available in the Organisation for Economic Co-operation and Development (OECD) QSAR Toolbox. The approach,assesses a model's ability to predict the potential hazards of chemicals that have limited hazard data that require assessment under the CMP when compared to a larger, data-rich chemical space that is structurally similar to chemicals of interest. This evaluation of a model's predictive ability makes (Q)SAR analysis more transparent and increases confidence in the application of these predictions in a risk-assessment context. Using this approach, predictions for such chemicals obtained from four (Q)SAR models were successfully classified into high, medium and low confidence levels to better inform their use in decision-making.

  1. Discovery and structure-activity relationships of ent-Kaurene diterpenoids as potent and selective 11β-HSD1 inhibitors: potential impact in diabetes.

    PubMed

    Deng, Xu; Shen, Yu; Yang, Jing; He, Juan; Zhao, Yu; Peng, Li-Yan; Leng, Ying; Zhao, Qin-Shi

    2013-07-01

    The biological screening of a collection of nature occurring diterpenoids against 11β-HSD1 resulted in the discovery of the lead compound 1b, which pointed to the therapeutic potential for type 2 diabetes. Subsequently, an optimization project was initiated. Starting from compound 1b and its counterpart 2, the hemi-synthesis was performed on kaurenic acid scaffolds yielding 36 derivatives. Further evaluations on both human and mouse 11β-HSD revealed that seven urea derivatives exhibited significant improved potency and selectivity. Especially, the urea 19a has an IC50 (human 11β-HSD1) = 9.4 nM and selectivity index (human 11β-HSD) > 10,649. The 2D and 3D binding models of the complex 19a/11β-HSD1 were generated using docking simulations. Based on the results, the structural-activity relationships (SARs) of compounds 1b and 2 were also discussed.

  2. 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.

  3. Processor architecture for airborne SAR systems

    NASA Technical Reports Server (NTRS)

    Glass, C. M.

    1983-01-01

    Digital processors for spaceborne imaging radars and application of the technology developed for airborne SAR systems are considered. Transferring algorithms and implementation techniques from airborne to spaceborne SAR processors offers obvious advantages. The following topics are discussed: (1) a quantification of the differences in processing algorithms for airborne and spaceborne SARs; and (2) an overview of three processors for airborne SAR systems.

  4. Combination Chemistry: Structure-Activity Relationships of Novel Psychoactive Cannabinoids.

    PubMed

    Wiley, Jenny L; Marusich, Julie A; Thomas, Brian F

    2016-10-18

    Originally developed as research tools for use in structure-activity relationship studies, synthetic cannabinoids contributed to significant scientific advances in the cannabinoid field. Unfortunately, a subset of these compounds was diverted for recreational use beginning in the early 2000s. As these compounds were banned, they were replaced with additional synthetic cannabinoids with increasingly diverse chemical structures. This chapter focuses on integration of recent results with those covered in previous reviews. Whereas most of the early compounds were derived from the prototypic naphthoylindole JWH-018, currently popular synthetic cannabinoids include tetramethylcyclopropyl ketones and indazole-derived cannabinoids (e.g., AB-PINACA, AB-CHMINACA). Despite their structural differences, psychoactive synthetic cannabinoids bind with high affinity to CB1 receptors in the brain and, when tested, have been shown to activate these receptors and to produce a characteristic profile of effects, including suppression of locomotor activity, antinociception, hypothermia, and catalepsy, as well as Δ(9)-tetrahydrocannabinol (THC)-like discriminative stimulus effects in mice. When they have been tested, synthetic cannabinoids are often found to be more efficacious at activation of the CB1 receptor and more potent in vivo. Further, their chemical alteration by thermolysis during use and their uncertain stability and purity may result in exposure to degradants that differ from the parent compound contained in the original product. Consequently, while their intoxicant effects may be similar to those of THC, use of synthetic cannabinoids may be accompanied by unpredicted, and sometimes harmful, effects.

  5. Molecular Docking, Molecular Dynamics, and Structure-Activity Relationship Explorations of 14-Oxygenated N-Methylmorphinan-6-ones as Potent μ-Opioid Receptor Agonists.

    PubMed

    Noha, Stefan M; Schmidhammer, Helmut; Spetea, Mariana

    2017-02-09

    Among opioids, morphinans are of major importance as the most effective analgesic drugs acting primarily via μ-opioid receptor (μ-OR) activation. Our long-standing efforts in the field of opioid analgesics from the class of morphinans led to N-methylmorphinan-6-ones differently substituted at positions 5 and 14 as μ-OR agonists inducing potent analgesia and fewer undesirable effects. Herein we present the first thorough molecular modeling study and structure-activity relationship (SAR) explorations aided by docking and molecular dynamics (MD) simulations of 14-oxygenated N-methylmorphinan-6-ones to gain insights into their mode of binding to the μ-OR and interaction mechanisms. The structure of activated μ-OR provides an essential model for how ligand/μ-OR binding is encoded within small chemical differences in otherwise structurally similar morphinans. We reveal important molecular interactions that these μ-agonists share and distinguish them. The molecular docking outcomes indicate the crucial role of the relative orientation of the ligand in the μ-OR binding site, influencing the propensity of critical non-covalent interactions that are required to facilitate ligand/μ-OR interactions and receptor activation. The MD simulations point out minor differences in the tendency to form hydrogen bonds by the 4,5α-epoxy group, along with the tendency to affect the 3-7 lock switch. The emerged SARs reveal the subtle interplay between the substituents at positions 5 and 14 in the morphinan scaffold by enabling the identification of key structural elements that determine the distinct pharmacological profiles. This study provides a significant structural basis for understanding ligand binding and μ-OR activation by the 14-oxygenated N-methylmorphinan-6-ones, which should be useful for guiding drug design.

  6. Virulence factor activity relationships (VFARs): a bioinformatics perspective.

    PubMed

    Waseem, Hassan; Williams, Maggie R; Stedtfeld, Tiffany; Chai, Benli; Stedtfeld, Robert D; Cole, James R; Tiedje, James M; Hashsham, Syed A

    2017-03-06

    Virulence factor activity relationships (VFARs) - a concept loosely based on quantitative structure-activity relationships (QSARs) for chemicals was proposed as a predictive tool for ranking risks due to microorganisms relevant to water safety. A rapid increase in sequencing capabilities and bioinformatics tools has significantly increased the potential for VFAR-based analyses. This review summarizes more than 20 bioinformatics databases and tools, developed over the last decade, along with their virulence and antimicrobial resistance prediction capabilities. With the number of bacterial whole genome sequences exceeding 241 000 and metagenomic analysis projects exceeding 13 000 and the ability to add additional genome sequences for few hundred dollars, it is evident that further development of VFARs is not limited by the availability of information at least at the genomic level. However, additional information related to co-occurrence, treatment response, modulation of virulence due to environmental and other factors, and economic impact must be gathered and incorporated in a manner that also addresses the associated uncertainties. Of the bioinformatics tools, a majority are either designed exclusively for virulence/resistance determination or equipped with a dedicated module. The remaining have the potential to be employed for evaluating virulence. This review focusing broadly on omics technologies and tools supports the notion that these tools are now sufficiently developed to allow the application of VFAR approaches combined with additional engineering and economic analyses to rank and prioritize organisms important to a given niche. Knowledge gaps do exist but can be filled with focused experimental and theoretical analyses that were unimaginable a decade ago. Further developments should consider the integration of the measurement of activity, risk, and uncertainty to improve the current capabilities.

  7. 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.

  8. Structure-Activity Relationship and Signaling of New Chimeric CXCR4 Agonists.

    PubMed

    Mona, Christine E; Besserer-Offroy, Élie; Cabana, Jérôme; Lefrançois, Marilou; Boulais, Philip E; Lefebvre, Marie-Reine; Leduc, Richard; Lavigne, Pierre; Heveker, Nikolaus; Marsault, Éric; Escher, Emanuel

    2016-08-25

    The CXCR4 receptor binds with meaningful affinities only CXCL12 and synthetic antagonists/inverse agonists. We recently described high affinity synthetic agonists for this chemokine receptor, obtained by grafting the CXCL12 N-terminus onto the inverse agonist T140. While those chimeric molecules behave as agonists for CXCR4, their binding and activation mode are unknown. The present SAR of those CXCL12-oligopeptide grafts reveals the key determinants involved in CXCR4 activation. Position 3 (Val) controls affinity, whereas position 7 (Tyr) acts as an efficacy switch. Chimeric molecules bearing aromatic residues in position 3 possess high binding affinities for CXCR4 and are Gαi full agonists with robust chemotactic properties. Fine-tuning of electron-poor aromatic rings in position 7 enhances receptor activation. To rationalize these results, a homology model of a receptor-ligand complex was built using the published crystal structures of CXCR4. Molecular dynamics simulations reveal further details accounting for the observed SAR for this series.

  9. Neuromusculoskeletal disorders following SARS: a case series

    PubMed Central

    Stainsby, Brynne; Howitt, Scott; Porr, Jason

    2011-01-01

    Objective: To detail the presentation of three health care workers diagnosed with sudden acute respiratory syndrome (SARS) who later presented to a CMCC teaching clinic with neuromusculoskeletal sequelae and underwent conservative treatments. This case series aims to inform practitioners of the potential pathogenesis of these neuromuscular complaints and describes their treatment in a chiropractic practice. Clinical Features: Three patients presented with a variety of neurological, muscular and joint findings. Conservative treatment was aimed at decreasing hypertonic muscles, increasing joint mobility, and improving ability to perform activities of daily living. Intervention and Outcome: The conservative treatment approach utilized in these cases involved spinal manipulative therapy, soft tissue therapy, modalities, and rehabilitation. Outcome measures included subjective pain ratings, disability indices, and return to work. Conclusion: Three patients previously diagnosed with SARS presented with neuromusculoskeletal complaints and subjectively experienced intermittent relief of pain and improvement in disability status after conservative treatments. PMID:21403780

  10. 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.

  11. Inhibitors of the kinase IspE: structure-activity relationships and co-crystal structure analysis.

    PubMed

    Hirsch, Anna K H; Alphey, Magnus S; Lauw, Susan; Seet, Michael; Barandun, Luzi; Eisenreich, Wolfgang; Rohdich, Felix; Hunter, William N; Bacher, Adelbert; Diederich, François

    2008-08-07

    Enzymes of the non-mevalonate pathway for isoprenoid biosynthesis are therapeutic targets for the treatment of important infectious diseases. Whereas this pathway is absent in humans, it is used by plants, many eubacteria and apicomplexan protozoa, including major human pathogens such as Plasmodium falciparum and Mycobacterium tuberculosis. Herein, we report on the design, preparation and biological evaluation of a new series of ligands for IspE protein, a kinase from this pathway. These inhibitors were developed for the inhibition of IspE from Escherichia coli, using structure-based design approaches. Structure-activity relationships (SARs) and a co-crystal structure of Aquifex aeolicus IspE bound to a representative inhibitor validate the proposed binding mode. The crystal structure shows that the ligand binds in the substrate-rather than the adenosine 5'-triphosphate (ATP)-binding pocket. As predicted, a cyclopropyl substituent occupies a small cavity not used by the substrate. The optimal volume occupancy of this cavity is explored in detail. In the co-crystal structure, a diphosphate anion binds to the Gly-rich loop, which normally accepts the triphosphate moiety of ATP. This structure provides useful insights for future structure-based developments of inhibitors for the parasite enzymes.

  12. RISAT: first planned SAR mission of ISRO

    NASA Astrophysics Data System (ADS)

    Misra, Tapan; Rana, S. S.; Tyagi, R. N.; Thyagarajan, K.

    2006-12-01

    SAR Payload of RISAT (Radar Imaging Satellite), the first SAR satellite from ISRO, is currently under development. This payload is based on active antenna technology, and it supports variety of resolution and swath requirements in C-band. Both conventional stripmap and scanSAR modes are supported with dual polarization operation. Additionally a quad polarization stripmap mode is provided for availing additional resource classification. In all these modes resolutions from 3m-50 m can be achieved with swath ranging 30 km -240 km. On experimental basis, a sliding spotlight mode is also available. The payload hardware is organized in such a way that that co and cross polarization images are available for any operating modes. Additionally, a quad polarization mode is also supported. Active array configuration of this payload called for development of many new technologies ranging from MMICS, TR modules, miniaturised power supplies, high speed digitisers, dual polarized printed antenna and distributed control systems. A completely new bus is being designed for aiding the payload operation. The RISAT spacecraft is configured around the payload to minimize the spacecraft weight, suitable for launching by ISRO's PSLV launcher. RISAT will be placed on dawn to dusk sunsynchronous polar orbit to ensure maximum solar power availability. All the basic building blocks have already crossed design stage and have undergone rigorous space qualification program. Presently a complete SAR with one tile has been integrated as design verification model and is under rigorous testing. This development ensured demonstration of end to end hardware, on-board control software and beam control behavior.

  13. 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.

  14. Quantitative structure activity relationship studies of mushroom tyrosinase inhibitors

    NASA Astrophysics Data System (ADS)

    Xue, Chao-Bin; Luo, Wan-Chun; Ding, Qi; Liu, Shou-Zhu; Gao, Xing-Xiang

    2008-05-01

    Here, we report our results from quantitative structure-activity relationship studies on tyrosinase inhibitors. Interactions between benzoic acid derivatives and tyrosinase active sites were also studied using a molecular docking method. These studies indicated that one possible mechanism for the interaction between benzoic acid derivatives and the tyrosinase active site is the formation of a hydrogen-bond between the hydroxyl (aOH) and carbonyl oxygen atoms of Tyr98, which stabilized the position of Tyr98 and prevented Tyr98 from participating in the interaction between tyrosinase and ORF378. Tyrosinase, also known as phenoloxidase, is a key enzyme in animals, plants and insects that is responsible for catalyzing the hydroxylation of tyrosine into o-diphenols and the oxidation of o-diphenols into o-quinones. In the present study, the bioactivities of 48 derivatives of benzaldehyde, benzoic acid, and cinnamic acid compounds were used to construct three-dimensional quantitative structure-activity relationship (3D-QSAR) models using comparative molecular field (CoMFA) and comparative molecular similarity indices (CoMSIA) analyses. After superimposition using common substructure-based alignments, robust and predictive 3D-QSAR models were obtained from CoMFA ( q 2 = 0.855, r 2 = 0.978) and CoMSIA ( q 2 = 0.841, r 2 = 0.946), with 6 optimum components. Chemical descriptors, including electronic (Hammett σ), hydrophobic (π), and steric (MR) parameters, hydrogen bond acceptor (H-acc), and indicator variable ( I), were used to construct a 2D-QSAR model. The results of this QSAR indicated that π, MR, and H-acc account for 34.9, 31.6, and 26.7% of the calculated biological variance, respectively. The molecular interactions between ligand and target were studied using a flexible docking method (FlexX). The best scored candidates were docked flexibly, and the interaction between the benzoic acid derivatives and the tyrosinase active site was elucidated in detail. We believe

  15. 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.

  16. 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.

  17. Relationship between typhoon activity and upper ocean heat content

    NASA Astrophysics Data System (ADS)

    Wada, A.; Chan, J. C. L.

    2008-09-01

    A 44-year mean distribution of tropical cyclone heat potential (TCHP), a measure of the oceanic heat content from the surface to the 26°C-isotherm depth, shows that TCHP is locally high in the western North Pacific (WNP). TCHP varies on interannual time scales and has a relationship with tropical cyclone (TC) activity. The third mode of an empirical orthogonal function analysis of TCHP shows that an increase in the total number of TCs is accompanied with a warm central Pacific and cool WNP. Negative TCHP anomalies in the WNP suggest that an increase in total number of TCs results in cooling due to their passages. On the other hand, the first mode shows that the number of super typhoons increases in mature El Niño years. An increase in accumulated TCHP is related to the increase in the number of super typhoons due to long duration.

  18. Relationships between the stereochemistry and biological activity of fungal phytotoxins.

    PubMed

    Evidente, Antonio; Andolfi, Anna; Cimmino, Alessio

    2011-10-01

    Toxins produced by phytopathogenic fungi assume great importance because of their involvement in several plant diseases. Although such pathogens are known to have seriously damaged crops, forest, and environmental resources, they represent a very important tool to develop new environmentally friendly herbicides and fungicides. This review deals with the relationships between the biological activity of some phytotoxins produced by pathogenic fungi for major forest plants and for damaging weeds and their stereochemistry. In particular, the methods used to determine their relative and/or absolute configuration will be illustrated. These include the application of Mosher's and Murata's methods, X-ray diffractometric analysis, circular dichroism, and the use of computational methods to determine the theoretical optical rotatory power as well as the CD spectrum. The importance of determining the absolute configuration to achieve the total synthesis of some phytotoxins, interesting for their potential practical application, is also discussed.

  19. InSAR Analysis of Induced Seismicity: Examples From Southern Colorado

    NASA Astrophysics Data System (ADS)

    Barnhart, W. D.

    2015-12-01

    We present interferormetric synthetic aperture radar (InSAR) analysis of human-induced ground deformation in the Raton Basin of southern Colorado and northern New Mexico, including displacements from a wastewater injection-induced earthquake. Geodetic observations of both seismic and aseismic surface displacements provide an additional tool to further constrain spatially and temporally variable deformation within these basins. Using Envisat observations, we image co-seismic surface displacements of the 2011 Trinidad earthquake and find that the earthquake slipped within the crystalline basement underlying basin sedimentary rocks and in the vicinity of high-volume wastewater injection wells. The spatial and temporal separation between the earthquake and the wastewater wells suggests a pore pressure migration triggering mechanism is present. The finite slip distributions further highlight the location and orientation of previously unmapped, seismogenic faults. Lastly, the precise earthquake location afforded by InSAR observations provides a well-located earthquake source that can be used to calibrate other regional earthquakes locations. Additionally, we derive InSAR time series observations from ALOS imagery acquired from 2007-2011. These results highlight ongoing regions of surface subsidence within the basin, presumably caused by extraction of coal-bed methane and water that is later reinjected. While it is not clear if there is a causative relationship between regions of co-located surface subsidence and recorded earthquakes, the time series permits us to exclude several other hypotheses for the causes of increased seismicity in the Raton Basin, including volcanic activity related to the Rio Grande Rift. Furthermore, the InSAR time series analysis provides a calibration source for hydrological models that assess subsurface stress changes from the removal and injection of fluids. Forthcoming work will provide a detailed time series of surface deformation occurring

  20. Structure-activity relationship in cationic lipid mediated gene transfection.

    PubMed

    Niculescu-Duvaz, Dan; Heyes, James; Springer, Caroline J

    2003-07-01

    Non-viral synthetic vectors for gene delivery represent a safer alternative to viral vectors. Their main drawback is the low transfection efficiency, especially in vivo. Among the non-viral vectors currently in use, the cationic liposomes composed of cationic lipids are the most common. This review discusses the physicochemical properties of cationic lipids, the formation, macrostructure and specific parameters of the corresponding formulated liposomes, and the effect of all these parameters on transfection efficiency. The optimisation of liposomal vectors requires both the understanding of the biological variables involved in the transfection process, and the effect of the structural elements of the cationic lipids on these biological variables. The biological barriers relevant for in vitro and in vivo transfection are identified, and solutions to overcome them based on rational design of the cationic lipids are discussed. The review focuses on the relationship between the structure of the cationic lipid and the transfection activity. The structure is analysed in a modular manner. The hydrophobic domain, the cationic head group, the backbone that acts as a scaffold for the other domains, the linkers between backbone, hydrophobic domain and cationic head group, the polyethyleneglycol chains and the targeting moiety are identified as distinct elements of the cationic lipids used in gene therapy. The main chemical functionalities used to built these domains, as well as overall molecular features such as architecture and geometry, are presented. Studies of structure-activity relationships of each cationic lipid domain, including the authors', and the trends identified by these studies, help furthering the understanding of the mechanism governing the formation and behaviour of cationic liposomes in gene delivery, and therefore the rational design of new improved cationic lipids vectors capable of achieving clinical significance.

  1. Analysis of Benefits and Pitfalls of Satellite SAR for Coastal Area Monitoring

    NASA Astrophysics Data System (ADS)

    Nunziata, F.; Buono, A.; Mgliaccio, M.; Li, X.; Wei, Y.

    2016-08-01

    This study aims at describing the outcomes of the Dragon-3 project no. 10689. The undertaken activities deal with coastal area monitoring and they include sea pollution and coastline extraction. The key remote sensing tool is the Synthetic Aperture Radar (SAR) that provides fine resolution images of the microwave reflectivity of the observed scene. However, the interpretation of SAR images is not at all straightforward and all the above-mentioned coastal area applications cannot be easily addressed using single-polarization SAR. Hence, the main outcome of this project is investigating the capability of multi-polarization SAR measurements to generate added-vale product in the frame of coastal area management.

  2. Cyclooxygenase active bioflavonoids from Balaton tart cherry and their structure activity relationships.

    PubMed

    Wang, H; Nair, M G; Strasburg, G M; Booren, A M; Gray, I; Dewitt, D L

    2000-03-01

    Several flavonoids and isoflavonoids isolated from Balaton tart cherry were assayed for prostaglandin H endoperoxide synthase (PGHS-1) enzyme or cyclooxygenase isoform-1 (COX-1) activity. Genistein showed the highest COX-1 inhibitory activity among the isoflavonoids studied, with an IC50 value of 80 microM. Kaempferol gave the highest COX-1 inhibitory activity among the flavonoids tested, with an IC50 value of 180 microM. The structure-activity relationships of flavonoids and isoflavonoids revealed that hydroxyl groups at C4', C5 and C7 in isoflavonoids were essential for appreciable COX-1 inhibitory activity. Also, the C2-C3 double bond in flavonoids is important for COX-1 inhibitory activity. However, a hydroxyl group at the position decreased COX-1 inhibitory activity by flavonoids.

  3. 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.

  4. SAR imaging - Seeing the unseen

    NASA Technical Reports Server (NTRS)

    Kobrick, M.

    1982-01-01

    The functional abilities and operations of synthetic aperture radar (SAR) are described. SAR employs long wavelength radio waves in bursts, imaging a target by 'listening' to the small frequency changes that result from the Doppler shift due to the relative motion of the imaging craft and the motions of the target. The time delay of the signal return allows a determination of the location of the target, leading to the build up of a two-dimensional image. The uses of both Doppler shifts and time delay enable detailed imagery which is independent of distance. The synthetic aperture part of the name of SAR derives from the beaming of multiple pulses, which result in a picture that is effectively the same as using a large antenna. Mechanisms contributing to the fineness of SAR images are outlined.

  5. Novel thiol-based histone deacetylase inhibitors bearing 3-phenyl-1H-pyrazole-5-carboxamide scaffold as surface recognition motif: Design, synthesis and SAR study.

    PubMed

    Wen, Jiachen; Niu, Qun; Liu, Jiang; Bao, Yu; Yang, Jinyu; Luan, Shenglin; Fan, Yinbo; Liu, Dan; Zhao, Linxiang

    2016-01-15

    A series of novel thiol-based histone deacetylase (HDAC) inhibitors bearing 3-phenyl-1H-pyrazole-5-carboxamide scaffold as surface recognition motif was designed, synthesized, and evaluated for their HDAC inhibition activity. Among them, 15j (IC50=0.08μM) was identified as a better inhibitor than Vorinostat (IC50=0.25μM) against total HDACs. In addition, Structure-activity relationships (SAR) analyses indicated that (i) compounds with different substituents on pyrazole N-1 position exhibited superior activities than those on pyrazole N-2 position, (ii) variation of functional groups on N-1'-alkyl chain terminus followed the trends of carboxyl group>hydroxyl group≫alkyl group, and (iii) methylation on pyrazole C-4 position diminished the HDAC inhibition activity. The SAR will guide us to further refine compounds bearing 3-phenyl-1H-pyrazole-5-carboxamide scaffold to achieve better HDAC inhibitors.

  6. Focusing of bistatic SAR data

    NASA Astrophysics Data System (ADS)

    Bia, Pietro; Ricci, Nicola; Zonno, Mariantonietta; Nico, Giovanni; Catalao, Joao; Tesauro, Manlio

    2014-10-01

    The problems of simulation of bistatic SAR raw data and focusing are studied. A discrete target simulator is described. The simulator introduces the scene topography and compute the integration time of general bistatic configurations providing a means to derived maps of the range and azimuth spatial resolutions. The problem of focusing of bistatic SAR data acquired in a translational-invariant bistatic configuration is studied by deriving the bistatic Point Target Reference spectrum and presenting an analytical solution for its stationary points.

  7. Normal and Differential SAR Interferometry

    DTIC Science & Technology

    2007-02-01

    Geudtner, B. Schättler, P. Vachon, U. Steinbrecher, J. Holzner, J. Mittermayer , H. Breit, A. Moreira. RADARSAT ScanSAR interferometry. In: Proc.IGARSS’99...IV, Ottawa, Vol. XXXIV, part 4, pp. 470-475 Krieger, G., Wendler, M., Fiedler, H., Mittermayer , J., Moreira, A., 2002. Performance analysis for...bistatic interferometric SAR configurations. In: Proc.IGARSS 2002, Toronto, Canada, vol. 1, pp. 650-652. Krieger, G., Fiedler, H., Mittermayer , J

  8. Normal and Differential SAR Interferometry

    DTIC Science & Technology

    2005-02-01

    Geudtner, B. Schättler, P. Vachon, U. Steinbrecher, J. Holzner, J. Mittermayer , H. Breit, A. Moreira. RADARSAT ScanSAR interferometry. In: Proceedings of...part 4, pp. 470-475 Krieger, G., Wendler, M., Fiedler, H., Mittermayer , J., Moreira, A., 2002. Performance analysis for bistatic interferometric...SAR configurations. In: Proceedings of IGARSS 2002, Toronto, Canada, vol. 1, pp. 650-652. Krieger, G., Fiedler, H., Mittermayer , J., Papathanassiou, K

  9. 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…

  10. 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.

  11. 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

  12. 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.

  13. DEM-Based SAR Pixel Area Estimation For Enhanced Geocoding Refinement And Radiometric Normalization

    NASA Astrophysics Data System (ADS)

    Frey, Othmar; Santoro, Maurizio; Werner, Charles L.; Wegmuller, Urs

    2012-01-01

    Precise terrain-corrected georeferencing of SAR images and derived products in range-Doppler coordinates is important with respect to several aspects, such as data interpretation, combination with other geodata products, and transformation of, e.g., terrain heights into SAR geometry as used in DInSAR applications. For georeferencing a look-up table is calculated and refined based on a coregistration of the actual SAR image to a simulated SAR image. The impact of using two different implementations of such a simulator of topography-induced radar brightness, an approach based on angular relationships and a pixel-area based method are discussed in this paper. It is found that the pixel-area-based method leads to considerable improvements with regard to the robustness of georeferencing and also with regard to radiometric normalization in layover- affected areas.

  14. Mammary carcinogen-protein binding potentials: novel and biologically relevant structure-activity relationship model descriptors.

    PubMed

    Cunningham, A R; Qamar, S; Carrasquer, C A; Holt, P A; Maguire, J M; Cunningham, S L; Trent, J O

    2010-07-01

    Previously, SAR models for carcinogenesis used descriptors that are essentially chemical descriptors. Herein we report the development of models with the cat-SAR expert system using biological descriptors (i.e., ligand-receptor interactions) rat mammary carcinogens. These new descriptors are derived from the virtual screening for ligand-receptor interactions of carcinogens, non-carcinogens, and mammary carcinogens to a set of 5494 target proteins. Leave-one-out validations of the ligand mammary carcinogen-non-carcinogen model had a concordance between experimental and predicted results of 71%, and the mammary carcinogen-non-mammary carcinogen model was 72% concordant. The development of a hybrid fragment-ligand model improved the concordances to 85 and 83%, respectively. In a separate external validation exercise, hybrid fragment-ligand models had concordances of 81 and 76%. Analyses of example rat mammary carcinogens including the food mutagen and oestrogenic compound PhIP, the herbicide atrazine, and the drug indomethacin; the ligand model identified a number of proteins associated with each compound that had previously been referenced in Medline in conjunction with the test chemical and separately with association to breast cancer. This new modelling approach can enhance model predictivity and help bridge the gap between chemical structure and carcinogenic activity by descriptors that are related to biological targets.

  15. 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…

  16. Sar1 promotes vesicle budding from the endoplasmic reticulum but not Golgi compartments

    PubMed Central

    1994-01-01

    Two new members (Sar1a and Sar1b) of the SAR1 gene family have been identified in mammalian cells. Using immunoelectron microscopy, Sar1 was found to be restricted to the transitional region where the protein was enriched 20-40-fold in vesicular carriers mediating ER to Golgi traffic. Biochemical analysis revealed that Sar1 was essential for an early step in vesicle budding. A Sar1-specific antibody potently inhibited export of vesicular stomatitis virus glycoprotein (VSV-G) from the ER in vitro. Consistent with the role of guanine nucleotide exchange in Sar1 function, a trans-dominant mutant (Sar1a[T39N]) with a preferential affinity for GDP also strongly inhibited vesicle budding from the ER. In contrast, Sar1 was not found to be required for the transport of VSV-G between sequential Golgi compartments, suggesting that components active in formation of vesicular carriers mediating ER to Golgi traffic may differ, at least in part, from those involved in intra-Golgi transport. The requirement for novel components at different stages of the secretory pathway may reflect the recently recognized differences in protein transport between the Golgi stacks as opposed to the selective sorting and concentration of protein during export from the ER. PMID:8138575

  17. SarA Positively Controls Bap-Dependent Biofilm Formation in Staphylococcus aureus

    PubMed Central

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

    2005-01-01

    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 (J. Valle, A. Toledo-Arana, C. Berasain, J. M. Ghigo, B. Amorena, J. R. Penades, and I. Lasa, Mol. Microbiol. 48:1075-1087), we propose that SarA is an essential regulator controlling biofilm formation in S. aureus. PMID:16077127

  18. X-SAR as high-performance interferometric SAR

    NASA Astrophysics Data System (ADS)

    Werner, Marian U.; Schandl, Josef

    1995-11-01

    In April and October 1994 the X-SAR radar has been flown twice onboard the Space Shuttle, as part of the Space Radar Laboratory (SRL-1 and SRL-2). This radar payload is the first synthetic aperture radar (SAR) system of its kind in space, with three frequencies, multi- polarization, variable incidence angle and variable modes of operation. SIR-C/X-SAR, the new generation of imaging microwave remote sensing sensors from space, demonstrated successfully repeat pass interferometry in all three frequencies with a one day repeat as well as a six month repeat orbit. The major problems with the repeat orbit interferometry are the temporal target decorrelation, unsuitable baseline and different squint angles for the two passes to be processed. Therefore, for the third mission of the Space Radar Lab which shall be called SRTM (shuttle radar topographic mapper), single pass interferometry with a second receive antenna is proposed to generate a topographic map of all land surfaces between +60 degrees and -56 degrees latitude. X-SAR's 12 meter long and 40 cm wide main transmit and receive antenna is mounted directly to a tiltable part of the SIR-C antenna truss structure in the Shuttle cargo bay. The second receive antenna is 6 meters long and is mounted together with the second C-band antenna to a 31 meter long deployable boom structure perpendicular to the velocity direction to build the baseline. X-SAR is not capable of operating in a scan SAR model like SIR-C to allow continuous coverage, but will operate in a high resolution mode with a swath width of 30 - 35 km. The engineering design of the interferometric configuration for X-SAR, the requirement specifications, and the predicted performance as well as the mission operation aspects are described in this paper. SIR-C/X- SAR is a cooperative project. The SIR-C instrument was developed by NASA's Jet Propulsion Laboratory (JPL). The X-band radar (X-SAR) was developed by the Dornier and Alenia Spazio Companies for the German

  19. Structure-activity relationships of polybiguanides with activity against human immunodeficiency virus type 1

    PubMed Central

    Passic, Shendra R.; Ferguson, Mary Lee; Catalone, Bradley J.; Kish-Catalone, Tina; Kholodovych, Vladyslav; Zhu, Wei; Welsh, William; Rando, Robert; Howett, Mary K.; Wigdahl, Brian; Labib, Mohamed; Krebs, Fred C.

    2013-01-01

    Previous investigations showing that polydisperse biguanide (PDBG) molecules have activity against human immunodeficiency virus type 1 (HIV-1) also suggested a relationship between PDBG biologic activity and the lengths of hydrocarbon linkers surrounding the positively charged biguanide unit. To better define structure-activity relationships, PDBG molecules with select linker lengths were evaluated for cytotoxicity, anti-HIV-1 activity, and in vivo toxicity. Results of the in vitro experiments demonstrated that increases in linker length (and, therefore, increases in compound lipophilicity) were generally associated with increases in cytotoxicity and antiviral activity against HIV-1. However, a relationship between linker length asymmetry and in vitro therapeutic index (TI) suggested structural specificity in the mechanism of action against HIV-1. Polyethylene hexamethylene biguanide (PEHMB; biguanide units spaced between alternating ethylene and hexamethylene linkers) was found to have the highest in vitro TI (CC50/IC50) among the compounds examined. Recent improvements in PEHMB synthesis and purification have yielded preparations of PEHMB with in vitro TI values of 266 and 7000 against HIV-1 strains BaL and IIIB, respectively. The minimal toxicity of PEHMB relative to polyhexamethylene biguanide (PHMB; biguanide units alternating with hexamethylene linkers) in a murine model of cervicovaginal microbicide toxicity was consistent with considerable differences in cytotoxicity between PEHMB and PHMB observed during in vitro experiments. These structure-activity investigations increase our understanding of PDBG molecules as agents with activity against HIV-1 and provide the foundation for further preclinical studies of PEHMB and other biguanide-based compounds as antiviral and microbicidal agents. PMID:21106331

  20. TerraSAR-X for Oceanography- Mission Overview

    NASA Astrophysics Data System (ADS)

    Lehner, S.; Horstmann, J.; Schulz-Stellenfleth, J.; Roth, A.; Eineder, M.

    2004-06-01

    TerraSAR-X is a new generation, high resolution radar satellite to be launched at the end of 2005. The objective of the mission is the setup of an operational spaceborne X-Band synthetic aperture radar (SAR) system in order to produce remote sensing products for commercial and scientific use. TerraSAR-X is the scientific and technological continuation of the highly successful Space Shuttle missions Spaceborne Imaging Radar-C/X-band Synthetic Aperture Radar (SIR-C/X- SAR) in 1994 (Evans and Plaut, 1996) and Shuttle Radar Topography Mission (SRTM) in 2000 (Werner, 2000). After an in-orbit commissioning period of approximately 5 month, in which the instrument will be calibrated and the system performance will be verified, TerraSAR-X will be fully operational for an active lifetime of 5 years.The German Aerospace Center (DLR) and the ASTRIUM GmbH have agreed on an innovative co- operation scheme for the implementation of Earth observation satellites by realizing Germany's first Earth observation space project based on public-private partnership with considerable contributions from industry.The TerraSAR-X mission will serve two main objectives:• to provide the scientific community with high-quality, multi-mode X-band SAR-data forscientific research and applications• to support the establishment of a commercial EO-market; and• to develop a sustainable EO-service business inEurope, based on TerraSAR-X derivedinformation products.The broad spectrum of scientific applications, include: Hydrology, Geology, Climatology, Oceanography, Environmental- and Disaster Monitoring as well as Cartography. The scientific potential of TerraSAR-X is based on a combination of unprecedented features of the SAR instrument, which have never before been operational in space (Roth et al., 2002, Suess et al., 2002, Mittermayer et al., 2003). • High geometric and radiometric resolution with an experimental very high resolution ( 1 m) in 300 MHz mode• Single-, Dual- and Full

  1. Designing a Quantitative Structure-Activity Relationship for the ...

    EPA Pesticide Factsheets

    Toxicokinetic models serve a vital role in risk assessment by bridging the gap between chemical exposure and potentially toxic endpoints. While intrinsic metabolic clearance rates have a strong impact on toxicokinetics, limited data is available for environmentally relevant chemicals including nearly 8000 chemicals tested for in vitro bioactivity in the Tox21 program. To address this gap, a quantitative structure-activity relationship (QSAR) for intrinsic metabolic clearance rate was developed to offer reliable in silico predictions for a diverse array of chemicals. Models were constructed with curated in vitro assay data for both pharmaceutical-like chemicals (ChEMBL database) and environmentally relevant chemicals (ToxCast screening) from human liver microsomes (2176 from ChEMBL) and human hepatocytes (757 from ChEMBL and 332 from ToxCast). Due to variability in the experimental data, a binned approach was utilized to classify metabolic rates. Machine learning algorithms, such as random forest and k-nearest neighbor, were coupled with open source molecular descriptors and fingerprints to provide reasonable estimates of intrinsic metabolic clearance rates. Applicability domains defined the optimal chemical space for predictions, which covered environmental chemicals well. A reduced set of informative descriptors (including relative charge and lipophilicity) and a mixed training set of pharmaceuticals and environmentally relevant chemicals provided the best intr

  2. 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.

  3. Tropical stratospheric gravity wave activity and relationships to clouds

    NASA Astrophysics Data System (ADS)

    Alexander, M. Joan; Beres, Jadwiga H.; Pfister, Leonhard

    2000-09-01

    Wind measurements from NASA's ER-2 aircraft in the stratosphere are used to obtain information on the momentum flux carried by gravity waves with horizontal wavelengths between 5 and 150 km. Tropical data are compared with the cloud brightness temperature below the aircraft as an indicator of deep convective activity. A striking correlation between cold, high clouds and large gravity wave momentum flux is seen in data from the Stratosphere-Troposphere Exchange Project (STEP) tropical campaign during the monsoon season over northern Australia and Indonesia. There is an enhancement in the flux carried by waves propagating against the background wind in these observations. The same analysis was performed with data from more recent ER-2 flights over the tropical Pacific Ocean during the Airborne Southern Hemisphere Ozone Experiment/Measurements for Assessing the Effects of Stratospheric Aircraft (ASHOE/MAESA), Stratospheric Tracers of Atmospheric Transport (STRAT), and Photochemistry of Ozone Loss in the Arctic Region in Summer (POLARIS) campaigns which took place in 1994, 1995-1996, and 1997, respectively. These data also show a correlation between gravity wave momentum flux and deep convective clouds, but the relationship is much weaker, and the magnitudes of the momentum flux over the deepest clouds are about 7 times smaller than those seen in the STEP data. The reasons for these differences remain uncertain, but possibilities include both real geophysical differences and differences associated with the flight paths during the 1987 versus later campaigns.

  4. 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

  5. Epothilones as lead structures for new anticancer drugs--pharmacology, fermentation, and structure-activity-relationships.

    PubMed

    Altmann, Karl-Heinz; Memmert, Klaus

    2008-01-01

    Epothilones (Epo's) A and B are naturally occurring microtubule-stabilizers, which inhibit the growth of human cancer cells in vitro at low nM or sub-nM concentrations. In contrast to taxol (paclitaxel, Taxol) epothilones are also active against different types of multidrug-resistant cancer cell lines in vitro and against multidrug-resistant tumors in vivo. Their attractive preclinical profile has made epothilones important lead structures in the search for improved cytotoxic anticancer drugs and Epo B (EPO906, patupilone) is currently undergoing Phase III clinical trials. Numerous synthetic and semisynthetic analogs have been prepared since the absolute stereochemistry of epothilones was first disclosed in mid-1996 and their in vitro biological activity has been determined. Apart from generating a wealth of SAR information, these efforts have led to the identification of at least six compounds (in addition to Epo B), which are currently at various stages of clinical evaluation in humans. The most advanced of these compounds, Epo B lactam BMS-247550 (ixabepilone), has recently obtained FDA approval for the treatment of metastatic and advanced breast cancer. This chapter will first provide a summary of the basic features of the biological profile of Epo B in vitro and in vivo. This will be followed by a review of the processes that have been developed for the fermentative production of Epo B. The main part of the chapter will focus on the most relevant aspects of the epothilone SAR with regard to effects on tubulin polymerization, in vitro antiproliferative activity, and in vivo antitumor activity. Particular emphasis will be placed on work conducted in the authors' own laboratories, but data from other groups will also be included. In a final section, the current status of those epothilone analogs undergoing clinical development will be briefly discussed.

  6. 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

  7. The challenge of severe acute respiratory syndrome (SARS) in dentistry.

    PubMed

    Testarelli, L; D' Aversa, L; Dolci, G

    2004-01-01

    Severe Acute Respiratory Syndrome (SARS) is caused by a newly identified coronavirus, called SARS-associated coronavirus (SARS-CoV) that appears to be transmitted primarily through droplets of saliva. This is the reason why the most important international organizations recommend that the dentists adopt a unique preventive approach to the problem: SARS patients should not be treated in the dental office. This is possible only if a suspected case of SARS is correctly and promptly identified. But a correct identification is made difficult by several factors, such as the incubation period, a possibly asymptomatic onset of the illness, the still low specificity and sensitivity of laboratory and instrumental tests. A case or suspected case of SARS may thus unwillingly be treated at the dental office. It is therefore necessary to adopt protective measures for the dental personnel and to implement and enforce infection control measures in order to eliminate the risk of viral contamination. Nonetheless, these procedures do not ensure a complete elimination of SARS-CoV contamination risk since a major risk is represented by blood-borne infection, which is originated by the mouth of patients, and the contamination of dental units water lines (DUWLs) is most difficult to control. Blood-borne contamination may be achieved only by adopting a high level, between-patients disinfection protocol of the DUWLs based on the use of chemical agents with biocidal activity against spores, viruses, bacteria and fungi (Autosteril method). In conclusion a fully effective control of the cross-infection risk will be obtained only by adopting a correct, integrated use of different infection control procedures.

  8. Synthesis, Acaricidal Activity, and Structure-Activity Relationships of Pyrazolyl Acrylonitrile Derivatives.

    PubMed

    Yu, Haibo; Cheng, Yan; Xu, Man; Song, Yuquan; Luo, Yanmei; Li, Bin

    2016-12-28

    A series of novel pyrazolyl acrylonitrile derivatives was designed, targeting Tetranychus cinnabarinus, and synthesized. Their structures were identified by combination of (1)H NMR, (13)C NMR, and MS spectra. The structures of compounds 18 and 19 were further confirmed by X-ray diffraction. Extensive greenhouse bioassays indicated that compound 19 exhibits excellent acaricidal activity against all developmental stages of T. cinnabarinus, which is better than the commercialized compounds cyenopyrafen and spirodiclofen. It was shown that the acute toxicity of compounds 19 to mammals is quite low. The structure-activity relationships are also discussed.

  9. Synthesis and SAR optimization of diketo acid pharmacophore for HCV NS5B polymerase inhibition

    PubMed Central

    Bhatt, Aaditya; Gurukumar, K. R.; Basu, Amartya; Patel, Maulik R.; Kaushik-Basu, Neerja; Talele, Tanaji T.

    2011-01-01

    Hepatitis C virus (HCV) NS5B polymerase is a key target for anti-HCV therapeutics development. Here we report the synthesis and biological evaluation of a new series of α,γ-diketo acids (DKAs) as NS5B polymerase inhibitors. We initiated structure-activity relationship (SAR) optimization around the furan moiety of compound 1a [IC50 = 21.8 μM] to achieve more active NS5B inhibitors. This yielded compound 3a [IC50 = 8.2 μM] bearing the 5-bromobenzofuran-2-yl moiety, the first promising lead compound of the series. Varying the furan moiety with thiophene, thiazole and indazole moieties resulted in compound 11a [IC50 = 7.5 μM] bearing 3-methylthiophen-2-yl moiety. Finally replacement of the thiophene ring with a bioisosteric phenyl ring further improved the inhibitory activity as seen in compounds 21a [IC50 = 5.2 μM] and 24a [IC50 = 2.4 μM]. Binding mode of compound 24a using glide docking within the active site of NS5B polymerase will form the basis for future SAR optimization. PMID:21893371

  10. 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

  11. Basis for optronic ScanSAR processing

    NASA Astrophysics Data System (ADS)

    Marchese, Linda; Bourqui, Pascal; Turgeon, Sandra; Harnish, Bernd; Suess, Martin; Châteauneuf, François; Bergeron, Alain

    2011-11-01

    ScanSAR is an important imaging mode of operation for SAR systems. It allows extended range coverage albeit at the expense of azimuth resolution. Compared to stripmap, ScanSAR is used more for large swath coverage for mapping and monitoring over a wide area. Applications are numerous and include boreal forest mapping, wetland mapping and soil moisture monitoring. The goal of the present work was thus to explore the possibility of processing ScanSAR data optronicaly. Tests were performed with artificially bursted ASAR stripmap data demonstrating that reconstruction of ScanSAR data using the optronic SAR processor is feasible. This paper describes specifically how the data control and handling of ScanSAR data is performed to make it compatible with the optronic processor that was otherwise specifically designed for stripmap processing. As well, the ScanSAR images generated optronicaly are presented.

  12. 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 ...

  13. The Relationship between Social Activism and Feelings of Powerlessness among Low Socioeconomic College Students

    ERIC Educational Resources Information Center

    Garrahan, David P.

    1974-01-01

    The hypothesized curvilinear relationship between powerlessness and social activism was not supported; however, when social activism is defined as a nonviolent "within-the-system" intervention, there is a direct linear relationship between the variables--with the powerful students exhibiting a tendency to embrace this form of social activism.…

  14. Preliminary structure-activity relationships and biological evaluation of novel antitubercular indolecarboxamide derivatives against drug-susceptible and drug-resistant Mycobacterium tuberculosis strains.

    PubMed

    Onajole, Oluseye K; Pieroni, Marco; Tipparaju, Suresh K; Lun, Shichun; Stec, Jozef; Chen, Gang; Gunosewoyo, Hendra; Guo, Haidan; Ammerman, Nicole C; Bishai, William R; Kozikowski, Alan P

    2013-05-23

    Tuberculosis (TB) remains one of the leading causes of mortality and morbidity worldwide, with approximately one-third of the world's population infected with latent TB. This is further aggravated by HIV coinfection and the emergence of multidrug- and extensively drug-resistant (MDR and XDR, respectively) TB; hence the quest for highly effective antitubercular drugs with novel modes of action is imperative. We report herein the discovery of an indole-2-carboxamide analogue, 3, as a highly potent antitubercular agent, and the subsequent chemical modifications aimed at establishing a preliminary body of structure-activity relationships (SARs). These efforts led to the identification of three molecules (12-14) possessing an exceptional activity in the low nanomolar range against actively replicating Mycobacterium tuberculosis , with minimum inhibitory concentration (MIC) values lower than those of the most prominent antitubercular agents currently in use. These compounds were also devoid of apparent toxicity to Vero cells. Importantly, compound 12 was found to be active against the tested XDR-TB strains and orally active in the serum inhibition titration assay.

  15. Optimization of 1,2,3,4-tetrahydroacridin-9(10H)-ones as antimalarials utilizing structure-activity and structure-property relationships.

    PubMed

    Cross, R Matthew; Maignan, Jordany R; Mutka, Tina S; Luong, Lisa; Sargent, Justin; Kyle, Dennis E; Manetsch, Roman

    2011-07-14

    Antimalarial activity of 1,2,3,4-tetrahydroacridin-9(10H)-ones (THAs) has been known since the 1940s and has garnered more attention with the development of the acridinedione floxacrine (1) in the 1970s and analogues thereof such as WR 243251 (2a) in the 1990s. These compounds failed just prior to clinical development because of suboptimal activity, poor solubility, and rapid induction of parasite resistance. Moreover, detailed structure-activity relationship (SAR) studies of the THA core scaffold were lacking and SPR studies were nonexistent. To improve upon initial findings, several series of 1,2,3,4-tetrahydroacridin-9(10H)-ones were synthesized and tested in a systematic fashion, examining each compound for antimalarial activity, solubility, and permeability. Furthermore, a select set of compounds was chosen for microsomal stability testing to identify physicochemical liabilities of the THA scaffold. Several potent compounds (EC(50) < 100 nM) were identified to be active against the clinically relevant isolates W2 and TM90-C2B while possessing good physicochemical properties and little to no cross-resistance.

  16. Structure-Activity Relationship of Nerve-Highlighting Fluorophores

    PubMed Central

    Gibbs, Summer L.; Xie, Yang; Goodwill, Haley L.; Nasr, Khaled A.; Ashitate, Yoshitomo; Madigan, Victoria J.; Siclovan, Tiberiu M.; Zavodszky, Maria; Tan Hehir, Cristina A.; Frangioni, John V.

    2013-01-01

    Nerve damage is a major morbidity associated with numerous surgical interventions. Yet, nerve visualization continues to challenge even the most experienced surgeons. A nerve-specific fluorescent contrast agent, especially one with near-infrared (NIR) absorption and emission, would be of immediate benefit to patients and surgeons. Currently, there are only three classes of small molecule organic fluorophores that penetrate the blood nerve barrier and bind to nerve tissue when administered systemically. Of these three classes, the distyrylbenzenes (DSBs) are particularly attractive for further study. Although not presently in the NIR range, DSB fluorophores highlight all nerve tissue in mice, rats, and pigs after intravenous administration. The purpose of the current study was to define the pharmacophore responsible for nerve-specific uptake and retention, which would enable future molecules to be optimized for NIR optical properties. Structural analogs of the DSB class of small molecules were synthesized using combinatorial solid phase synthesis and commercially available building blocks, which yielded more than 200 unique DSB fluorophores. The nerve-specific properties of all DSB analogs were quantified using an ex vivo nerve-specific fluorescence assay on pig and human sciatic nerve. Results were used to perform quantitative structure-activity relationship (QSAR) modeling and to define the nerve-specific pharmacophore. All DSB analogs with positive ex vivo fluorescence were tested for in vivo nerve specificity in mice to assess the effect of biodistribution and clearance on nerve fluorescence signal. Two new DSB fluorophores with the highest nerve to muscle ratio were tested in pigs to confirm scalability. PMID:24039960

  17. Capability of geometric features to classify ships in SAR imagery

    NASA Astrophysics Data System (ADS)

    Lang, Haitao; Wu, Siwen; Lai, Quan; Ma, Li

    2016-10-01

    Ship classification in synthetic aperture radar (SAR) imagery has become a new hotspot in remote sensing community for its valuable potential in many maritime applications. Several kinds of ship features, such as geometric features, polarimetric features, and scattering features have been widely applied on ship classification tasks. Compared with polarimetric features and scattering features, which are subject to SAR parameters (e.g., sensor type, incidence angle, polarization, etc.) and environment factors (e.g., sea state, wind, wave, current, etc.), geometric features are relatively independent of SAR and environment factors, and easy to be extracted stably from SAR imagery. In this paper, the capability of geometric features to classify ships in SAR imagery with various resolution has been investigated. Firstly, the relationship between the geometric feature extraction accuracy and the SAR imagery resolution is analyzed. It shows that the minimum bounding rectangle (MBR) of ship can be extracted exactly in terms of absolute precision by the proposed automatic ship-sea segmentation method. Next, six simple but effective geometric features are extracted to build a ship representation for the subsequent classification task. These six geometric features are composed of length (f1), width (f2), area (f3), perimeter (f4), elongatedness (f5) and compactness (f6). Among them, two basic features, length (f1) and width (f2), are directly extracted based on the MBR of ship, the other four are derived from those two basic features. The capability of the utilized geometric features to classify ships are validated on two data set with different image resolutions. The results show that the performance of ship classification solely by geometric features is close to that obtained by the state-of-the-art methods, which obtained by a combination of multiple kinds of features, including scattering features and geometric features after a complex feature selection process.

  18. 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

  19. The Structure-Activity Relationship between Marine Algae Polysaccharides and Anti-Complement Activity.

    PubMed

    Jin, Weihua; Zhang, Wenjing; Liang, Hongze; Zhang, Quanbin

    2015-12-25

    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.

  20. 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.

  1. A human in vitro model system for investigating genome-wide host responses to SARS coronavirus infection

    PubMed Central

    Ng, Lisa FP; Hibberd, Martin L; Ooi, Eng-Eong; Tang, Kin-Fai; Neo, Soek-Ying; Tan, Jenny; Krishna Murthy, Karuturi R; Vega, Vinsensius B; Chia, Jer-Ming; Liu, Edison T; Ren, Ee-Chee

    2004-01-01

    Background The molecular basis of severe acute respiratory syndrome (SARS) coronavirus (CoV) induced pathology is still largely unclear. Many SARS patients suffer respiratory distress brought on by interstitial infiltration and frequently show peripheral blood lymphopenia and occasional leucopenia. One possible cause of this could be interstitial inflammation, following a localized host response. In this study, we therefore examine the immune response of SARS-CoV in human peripheral blood mononuclear cells (PBMCs) over the first 24 hours. Methods PBMCs from normal healthy donors were inoculated in vitro with SARS-CoV and the viral replication kinetics was studied by real-time quantitative assays. SARS-CoV specific gene expression changes were examined by high-density oligonucleotide array analysis. Results We observed that SARS-CoV was capable of infecting and replicating in PBMCs and the kinetics of viral replication was variable among the donors. SARS-CoV antibody binding assays indicated that SARS specific antibodies inhibited SARS-CoV viral replication. Array data showed monocyte-macrophage cell activation, coagulation pathway upregulation and cytokine production together with lung trafficking chemokines such as IL8 and IL17, possibly activated through the TLR9 signaling pathway; that mimicked clinical features of the disease. Conclusions The identification of human blood mononuclear cells as a direct target of SARS-CoV in the model system described here provides a new insight into disease pathology and a tool for investigating the host response and mechanisms of pathogenesis. PMID:15357874

  2. 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.

  3. Summary and analysis of the currently existing literature data on metal-based nanoparticles published for selected aquatic organisms: Applicability for toxicity prediction by (Q)SARs.

    PubMed

    Chen, Guangchao; Vijver, Martina G; Peijnenburg, Willie J G M

    2015-09-01

    This review establishes an inventory of existing toxicity data on nanoparticles (NPs) with the purpose of developing (Quantitative) Structure-Activity Relationships for NPs (nano-[Q]SARs), and also of maximising the use of scientific sources for NP risk assessment. From a data search carried out on 27 February 2014, a total of 910 publications were retrieved from the Web of Science™ Core Collection, and a database comprising 886 records of toxicity endpoints, based on these publications, was built. The test organisms mainly comprised bacteria, algae, yeast, protozoa, nematoda, crustacea and fish. The NPs consisted mostly of metals, metal oxides, nanocomposites and quantum dots. The data were analysed further, in order to: a) categorise each toxicity endpoint and the biological effects triggered by the NPs; b) survey the characterisation of the NPs used; and c) assess whether the data were suitable for nano-(Q)SAR development. Despite the efforts of numerous scientific programmes on nanomaterial safety and design, our study concluded that lack of data consistency prevents the use of experimental data in developing and validating nano-(Q)SARs. Finally, an outlook on the future of nano-(Q)SAR development is provided.

  4. 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.

  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. 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.

  7. 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.

  8. 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.

  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. Registration Of SAR Images With Multisensor Images

    NASA Technical Reports Server (NTRS)

    Evans, Diane L.; Burnette, Charles F.; Van Zyl, Jakob J.

    1993-01-01

    Semiautomated technique intended primarily to facilitate registration of polarimetric synthetic-aperture-radar (SAR) images with other images of same or partly overlapping terrain while preserving polarization information conveyed by SAR data. Technique generally applicable in sense one or both of images to be registered with each other generated by polarimetric or nonpolarimetric SAR, infrared radiometry, conventional photography, or any other applicable sensing method.

  11. System Turns SAR Images Into Maps

    NASA Technical Reports Server (NTRS)

    Curlander, J. C.; Kwok, Ronald; Pang, Shirley S. N.

    1988-01-01

    Postprocessing system for synthetic-aperture radar (SAR) transforms raw images from natural rotated and distorted SAR reference frame into geocoded images. Images automatically corrected to remove slant-range nonlinearities and Doppler skew. Produces multiple-frame mosaics for large-scale mapping. Does not require tedious manual registration of representative "tie" points in raw SAR imagery with known locations on Earth.

  12. Using Envisat InSAR time-series to investigate the surface kinematics of an active salt extrusion near Qum, Iran

    NASA Astrophysics Data System (ADS)

    Abdolmaleki, Nastaran; Motagh, Mahdi; Bahroudi, Abbas; Sharifi, Mohammad Ali; Haghshenas Haghighi, Mahmud

    2014-11-01

    Lower Oligocene-Miocene rock salt is exposed in several diapirs in the central plateau of Iran along the northern margin of the Great Kavir basin. These include a small but mature salt extrusion known as Qum Kuh located near the city of Qum. We use small-baseline interferograms to study the surface displacements of Qum Kuh. The interferometric dataset consisted of 149 interferometric displacement maps derived from 35 C-band ASAR images collected by Envisat satellite in both descending and ascending orbits from 2003 through 2009.The results of the displacement time series analyses show significant long-term trend of horizontal motion toward gentle slopes of Qum Kuh, punctuated by seasonal variations during dry and wet seasons. Interferometric Synthetic Aperture Radar (InSAR) time series results suggest that the salt near the spreading center, where the salt first surfaces from depth, is extruded to the more gentle flanks of Qum Kuh and that down-slope gravitational spreading of the extruded salt accelerates when it is wet.

  13. Antitumor agents 279. Structure-activity relationship and in vivo studies of novel 2-(furan-2-yl)naphthalen-1-ol (FNO) analogs as potent and selective anti-breast cancer agents

    PubMed Central

    Dong, Yizhou; Nakagawa-Goto, Kyoko; Lai, Chin-Yu; Kim, Yoon; Morris-Natschke, Susan L.; Lee, Eva Y.-H. P.; Bastow, Kenneth F.; Lee, Kuo-Hsiung

    2010-01-01

    In our ongoing modification study of neo-tanshinlactone (1), we discovered 2-(furan-2-yl)naphthalen-1-ol (FNO) derivatives 3 and 4 as a new class of anti-tumor agents. To explore structure-activity relationships (SAR) of this scaffold, 18 new analogs, 6–12 and 14–24, were designed and synthesized. The C11-esters 7 and 12 displayed broad anti-tumor activity (ED50 1.1–4.3 µg/mL against seven cancer cell lines), while C11-hydroxymethyl 14 showed unique selectivity against the SKBR-3 breast cancer cell line (ED50 0.73 µg/mL). Compounds 15 and 22 displayed potent and selective anti-breast tumor activity (ED50 1.7 and 0.85 µg/mL, respectively, against MDA-MB-231). The SAR results demonstrated that the substitutions from the ring-opened lactone ring C of 1 are critical to the anti-tumor potency as well as the apparent tumor-tissue type selectivity. Treatment with 3 in Brca1f11/f11p53f5&6/f5&6Crec mice models significantly inhibited the proliferation of mammary epithelial cells and branching of mammary glands. PMID:21147529

  14. Polarization Filtering of SAR Data

    NASA Technical Reports Server (NTRS)

    Dubois, Pascale C.; Van Zyl, Jakob J.

    1991-01-01

    Theoretical analysis of polarization filtering of synthetic-aperture-radar (SAR) returns provide hybrid method applied to either (1) maximize signal-to-noise ratio of return from given target or (2) enhance contrast between targets of two different types (that have different polarization properties). Method valid for both point and extended targets and for both monostatic and bistatic radars as well as SAR. Polarization information in return signals provides more complete description of radar-scattering properties of targets and used to obtain additional information about targets for use in classifying them, discriminating between them, or enhancing features of radar images.

  15. 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.

  16. Characterizing Freeze-Thaw Transitions Using L-Band Interferometric SAR over a Boreal Forest in Alaska

    NASA Astrophysics Data System (ADS)

    Ganem, D.; McDonald, K. C.; Podest, E.; Chapman, B. D.; Zimmermann, R.

    2008-12-01

    Land surface seasonal transitions between predominantly frozen and thawed conditions occur each year over roughly 50 million square kilometers of Earth´s Northern Hemisphere profoundly affecting surface meteorological conditions, ecological trace gas dynamics, and hydrologic activity. The study of freeze-thaw transitions is a key component in better understanding land-atmosphere carbon exchange and the cycling of water, carbon, and energy in the high latitudes. Microwave remote sensing techniques have been demonstrated to be effective tools for delineating seasonal freeze/thaw transitions in the terrestrial high latitudes as indicators of key growing season processes. Past efforts characterizing freeze/thaw processes in boreal forests have focused on application of time series radar backscatter amplitude to delineate landscape freeze/thaw state. In this study, we apply satellite radar time series observations to investigate the application of Interferometric Synthetic Aperture Radar (InSAR) to monitor seasonal freeze/thaw processes in a boreal forest. We employ time series data acquired over the Bonanza Creek Experimental Forest along the Tanana River floodplain to examine InSAR response. We compare the InSAR time series data to in situ observations of vegetation and soil temperature, and vegetation biophysical activity as inferred from xylem sap flux measurements. We investigate relationships between the remote sensing data products, soil freeze/thaw, vegetation freeze/thaw, and the initiation of seasonal growth processes in trees, and the potential of InSAR for distinguishing these processes. This work was carried out at the Jet Propulsion Laboratory, California Institute of Technology, under contract to the National Aeronautics and Space Administration.

  17. 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

  18. 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.

  19. 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.

  20. Interferometric synthetic aperture radar (InSAR) and its applications to study volcanoes, part 2: InSAR imaging of Alaskan Volcanoes

    USGS Publications Warehouse

    Lu, Zhong; Dzurisin, Daniel; Wicks, Charles W.; Power, John A.

    2006-01-01

    Interferometric synthetic aperture radar (InSAR) is a remote sensing technique which can measure ground surface deformation with sub-centimeter precision and spatial resolution in tens-of-meters over a large region. This paper summarizes our recent InSAR studies of Alaskan volcanoes, associated with both eruptive and non-eruptive activity. It shows that InSAR can improve our understanding of how the Alaskan volcanoes work and enhance our capability to predict future eruptions and the associated hazards. 

  1. Antitumor activity of 3,4-ethylenedioxythiophene derivatives and quantitative structure-activity relationship analysis

    NASA Astrophysics Data System (ADS)

    Jukić, Marijana; Rastija, Vesna; Opačak-Bernardi, Teuta; Stolić, Ivana; Krstulović, Luka; Bajić, Miroslav; Glavaš-Obrovac, Ljubica

    2017-04-01

    The aim of this study was to evaluate nine newly synthesized amidine derivatives of 3,4- ethylenedioxythiophene (3,4-EDOT) for their cytotoxic activity against a panel of human cancer cell lines and to perform a quantitative structure-activity relationship (QSAR) analysis for the antitumor activity of a total of 27 3,4-ethylenedioxythiophene derivatives. Induction of apoptosis was investigated on the selected compounds, along with delivery options for the optimization of activity. The best obtained QSAR models include the following group of descriptors: BCUT, WHIM, 2D autocorrelations, 3D-MoRSE, GETAWAY descriptors, 2D frequency fingerprint and information indices. Obtained QSAR models should be relieved in elucidation of important physicochemical and structural requirements for this biological activity. Highly potent molecules have a symmetrical arrangement of substituents along the x axis, high frequency of distance between N and O atoms at topological distance 9, as well as between C and N atoms at topological distance 10, and more C atoms located at topological distances 6 and 3. Based on the conclusion given in the QSAR analysis, a new compound with possible great activity was proposed.

  2. Species–fragmented area relationship

    PubMed Central

    Hanski, Ilkka; Zurita, Gustavo A.; Bellocq, M. Isabel; Rybicki, Joel

    2013-01-01

    The species–area relationship (SAR) gives a quantitative description of the increasing number of species in a community with increasing area of habitat. In conservation, SARs have been used to predict the number of extinctions when the area of habitat is reduced. Such predictions are most needed for landscapes rather than for individual habitat fragments, but SAR-based predictions of extinctions for landscapes with highly fragmented habitat are likely to be biased because SAR assumes contiguous habitat. In reality, habitat loss is typically accompanied by habitat fragmentation. To quantify the effect of fragmentation in addition to the effect of habitat loss on the number of species, we extend the power-law SAR to the species–fragmented area relationship. This model unites the single-species metapopulation theory with the multispecies SAR for communities. We demonstrate with a realistic simulation model and with empirical data for forest-inhabiting subtropical birds that the species–fragmented area relationship gives a far superior prediction than SAR of the number of species in fragmented landscapes. The results demonstrate that for communities of species that are not well adapted to live in fragmented landscapes, the conventional SAR underestimates the number of extinctions for landscapes in which little habitat remains and it is highly fragmented. PMID:23858440

  3. Ka-band Digitally Beamformed Airborne Radar Using SweepSAR Technique

    NASA Technical Reports Server (NTRS)

    Sadowy, Gregory A.; Chuang, Chung-Lun; Ghaemi, Hirad; Heavey, Brandon A.; Lin, Lung-Sheng S.; Quaddus, Momin

    2012-01-01

    A paper describes a frequency-scaled SweepSAR demonstration that operates at Ka-Band (35.6 GHz), and closely approximates the DESDynl mission antenna geometry, scaled by 28. The concept relies on the SweepSAR measurement technique. An array of digital receivers captures waveforms from a multiplicity of elements. These are combined using digital beamforming in elevation and SAR processing to produce imagery. Ka-band (35.6 GHz) airborne SweepSAR using array-fed reflector and digital beamforming features eight simultaneous receive beams generated by a 40-cm offset-fed reflector and eight-element active array feed, and eight digital receiver channels with all raw data recorded and later used for beamforming. Illumination of the swath is accomplished using a slotted-waveguide antenna radiating 250 W peak power. This experiment has been used to demonstrate digital beamforming SweepSAR systems.

  4. 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

  5. Phagocytic cells contribute to the antibody-mediated elimination of pulmonary-infected SARS coronavirus.

    PubMed

    Yasui, Fumihiko; Kohara, Michinori; Kitabatake, Masahiro; Nishiwaki, Tetsu; Fujii, Hideki; Tateno, Chise; Yoneda, Misako; Morita, Kouichi; Matsushima, Kouji; Koyasu, Shigeo; Kai, Chieko

    2014-04-01

    While the 2002-2003 outbreak of severe acute respiratory syndrome (SARS) resulted in 774 deaths, patients who were affected with mild pulmonary symptoms successfully recovered. The objective of the present work was to identify, using SARS coronavirus (SARS-CoV) mouse infection models, immune factors responsible for clearing of the virus. The elimination of pulmonary SARS-CoV infection required the activation of B cells by CD4(+) T cells. Furthermore, passive immunization (post-infection) with homologous (murine) anti-SARS-CoV antiserum showed greater elimination efficacy against SARS-CoV than that with heterologous (rabbit) antiserum, despite the use of equivalent titers of neutralizing antibodies. This distinction was mediated by mouse phagocytic cells (monocyte-derived infiltrating macrophages and partially alveolar macrophages, but not neutrophils), as demonstrated both by adoptive transfer from donors and by immunological depletion of selected cell types. These results indicate that the cooperation of anti-SARS-CoV antibodies and phagocytic cells plays an important role in the elimination of SARS-CoV.

  6. 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.

  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. Modulation of membrane mechanical properties by Sar1, a vesicle trafficking protein.

    NASA Astrophysics Data System (ADS)

    Parthasarathy, Raghuveer

    2009-03-01

    The trafficking of cargo in cells involves dramatic changes in membrane shape and topology. Though trafficking is widely studied and the identities and interactions of the responsible proteins are well mapped, remarkably little is known about the mechanics involved. We focus on Sar1, the key regulator of the coat protein complex II (COPII) family that ferries newly synthesized proteins from the ER to the Golgi. Sar1 is the only member of the COPII coat that interacts directly with the ER lipid bilayer membrane. It has an amphipathic N-terminal helix; when Sar1 is GTP-bound, the helix is exposed and the hydrophobic hemi-cylinder can insert into the bilayer. To investigate whether Sar1 has a role beyond merely localizing the other COPII proteins, we directly measure the force involved in membrane deformation as a function of its presence or absence, using optically trapped microspheres to pull tethers from lipid membranes whose composition and large surface area mimic the composition and geometry of the ER. Tether measurements allow extraction of the membrane bending modulus, the parameter that governs the energetics of deformation. We find that the bending modulus measured in the presence of Sar1 with a non-hydrolyzable GTP analogue is half that measured without Sar1 or with Sar1-GDP. These results reveal a paradigm-altering insight into COPII trafficking: Sar1 actively alters the material properties of the membranes it binds to, lowering the energetic cost of curvature generation.

  9. Small Molecule Reversible Inhibitors of Bruton’s Tyrosine Kinase (BTK): Structure–Activity Relationships Leading to the Identification of 7-(2-Hydroxypropan-2-yl)-4-[2-methyl-3-(4-oxo-3,4-dihydroquinazolin-3-yl)phenyl]-9 H -carbazole-1-carboxamide (BMS-935177)

    SciTech Connect

    De Lucca, George V.; Shi, Qing; Liu, Qingjie; Batt, Douglas G.; Beaudoin Bertrand, Myra; Rampulla, Rick; Mathur, Arvind; Discenza, Lorell; D’Arienzo, Celia; Dai, Jun; Obermeier, Mary; Vickery, Rodney; Zhang, Yingru; Yang, Zheng; Marathe, Punit; Tebben, Andrew J.; Muckelbauer, Jodi K.; Chang, ChiehYing J.; Zhang, Huiping; Gillooly, Kathleen; Taylor, Tracy; Pattoli, Mark A.; Skala, Stacey; Kukral, Daniel W.; McIntyre, Kim W.; Salter-Cid, Luisa; Fura, Aberra; Burke, James R.; Barrish, Joel C.; Carter, Percy H.; Tino, Joseph A.

    2016-09-08

    Bruton’s tyrosine kinase (BTK) belongs to the TEC family of nonreceptor tyrosine kinases and plays a critical role in multiple cell types responsible for numerous autoimmune diseases. This article will detail the structure–activity relationships (SARs) leading to a novel second generation series of potent and selective reversible carbazole inhibitors of BTK. With an excellent pharmacokinetic profile as well as demonstrated in vivo activity and an acceptable safety profile, 7-(2-hydroxypropan-2-yl)-4-[2-methyl-3-(4-oxo-3,4-dihydroquinazolin-3-yl)phenyl]-9H-carbazole-1-carboxamide 6 (BMS-935177) was selected to advance into clinical development.

  10. 12 CFR 390.355 - Suspicious Activity Reports and other reports and statements.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Activity Report on the form prescribed by the FDIC. (3) SARs required. A State savings association shall... to supervisory action. (11) Obtaining SARs. A State savings association may obtain SARs and the... SARs. SARs are confidential. Any institution or person subpoenaed or otherwise requested to disclose...

  11. 12 CFR 390.355 - Suspicious Activity Reports and other reports and statements.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Activity Report on the form prescribed by the FDIC. (3) SARs required. A State savings association shall... to supervisory action. (11) Obtaining SARs. A State savings association may obtain SARs and the... SARs. SARs are confidential. Any institution or person subpoenaed or otherwise requested to disclose...

  12. 12 CFR 390.355 - Suspicious Activity Reports and other reports and statements.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Activity Report on the form prescribed by the FDIC. (3) SARs required. A State savings association shall... to supervisory action. (11) Obtaining SARs. A State savings association may obtain SARs and the... SARs. SARs are confidential. Any institution or person subpoenaed or otherwise requested to disclose...

  13. Computerized ionospheric tomography based on geosynchronous SAR

    NASA Astrophysics Data System (ADS)

    Hu, Cheng; Tian, Ye; Dong, Xichao; Wang, Rui; Long, Teng

    2017-02-01

    Computerized ionospheric tomography (CIT) based on spaceborne synthetic aperture radar (SAR) is an emerging technique to construct the three-dimensional (3-D) image of ionosphere. The current studies are all based on the Low Earth Orbit synthetic aperture radar (LEO SAR) which is limited by long repeat period and small coverage. In this paper, a novel ionospheric 3-D CIT technique based on geosynchronous SAR (GEO SAR) is put forward. First, several influences of complex atmospheric environment on GEO SAR focusing are detailedly analyzed, including background ionosphere and multiple scattering effects (induced by turbulent ionosphere), tropospheric effects, and random noises. Then the corresponding GEO SAR signal model is constructed with consideration of the temporal-variant background ionosphere within the GEO SAR long integration time (typically 100 s to 1000 s level). Concurrently, an accurate total electron content (TEC) retrieval method based on GEO SAR data is put forward through subband division in range and subaperture division in azimuth, obtaining variant TEC value with respect to the azimuth time. The processing steps of GEO SAR CIT are given and discussed. Owing to the short repeat period and large coverage area, GEO SAR CIT has potentials of covering the specific space continuously and completely and resultantly has excellent real-time performance. Finally, the TEC retrieval and GEO SAR CIT construction are performed by employing a numerical study based on the meteorological data. The feasibility and correctness of the proposed methods are verified.

  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. 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…

  16. 49 CFR 173.434 - Activity-mass relationships for uranium and natural thorium.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... natural thorium. 173.434 Section 173.434 Transportation Other Regulations Relating to Transportation....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...

  17. 49 CFR 173.434 - Activity-mass relationships for uranium and natural thorium.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... natural thorium. 173.434 Section 173.434 Transportation Other Regulations Relating to Transportation....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...

  18. 49 CFR 173.434 - Activity-mass relationships for uranium and natural thorium.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... natural thorium. 173.434 Section 173.434 Transportation Other Regulations Relating to Transportation....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...

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

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... natural thorium. 173.434 Section 173.434 Transportation Other Regulations Relating to Transportation....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. 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…

  1. Relationship of lactate dehydrogenase activity with body measeurements of Angus x Charolais cows and calves

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Angus x Charolais cows (n = 87) and their Angus-sired, spring-born calves (n = 86) were utilized to examine relationships between lactate dehydrogenase (LDH) activity and body measurements of beef cows; and the relationship between maternal LDH activity in late gestation and subsequent calf birth we...

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

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... natural thorium. 173.434 Section 173.434 Transportation Other Regulations Relating to Transportation....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. Structure-Activity Relationship of Benzophenanthridine Alkaloids from Zanthoxylum rhoifolium Having Antimicrobial Activity

    PubMed Central

    Tavares, Luciana de C.; Zanon, Graciane; Weber, Andréia D.; Neto, Alexandre T.; Mostardeiro, Clarice P.; Da Cruz, Ivana B. M.; Oliveira, Raul M.; Ilha, Vinicius; Dalcol, Ionara I.; Morel, Ademir F.

    2014-01-01

    Zanthoxylum rhoifolium (Rutaceae) is a plant alkaloid that grows in South America and has been used in Brazilian traditional medicine for the treatment of different health problems. The present study was designed to evaluate the antimicrobial activity of the steam bark crude methanol extract, fractions, and pure alkaloids of Z. rhoifolium. Its stem bark extracts exhibited a broad spectrum of antimicrobial activity, ranging from 12.5 to 100 µg/mL using bioautography method, and from 125 to 500 µg/mL in the microdilution bioassay. From the dichloromethane basic fraction, three furoquinoline alkaloids (1–3), and nine benzophenanthridine alkaloids (4–12) were isolated and the antimicrobial activity of the benzophenanthridine alkaloids is discussed in terms of structure-activity relationships. The alkaloid with the widest spectrum of activity was chelerythrine (10), followed by avicine (12) and dihydrochelerythrine (4). The minimal inhibitory concentrations of chelerythrine, of 1.50 µg/mL for all bacteria tested, and between 3.12 and 6.25 µg/mL for the yeast tested, show this compound to be a more powerful antimicrobial agent when compared with the other active alkaloids isolated from Z. rhoifolium. To verify the potential importance of the methylenedioxy group (ring A) of these alkaloids, chelerythrine was selected to represent the remainder of the benzophenanthridine alkaloids isolated in this work and was subjected to a demethylation reaction giving derivative 14. Compared to chelerythrine, the derivative (14) was less active against the tested bacteria and fungi. Kinetic measurements of the bacteriolytic activities of chelerythrine against the bacteria Bacillus subtilis (Gram-positive) and Escherichia coli (Gram-negative) were determined by optical density based on real time assay, suggesting that its mechanism of action is not bacteriolytic. The present study did not detect hemolytic effects of chelerythrine on erythrocytes and found a protective effect

  4. 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.

  5. [Medical history from SARS to pneumonia].

    PubMed

    Zhen, Cheng

    2003-05-31

    SARS is a new kind of pneumonia. From the end of 2002 to the beginning of 2003, SARS broke in Guangdong province, Hong Kong and Beijing, and then gradually spread to the world. SARS is extremely contagious. The symptoms of SARS progress very quickly. SARS smashes the people's tranquil life and many people live in horror, worry and anxiety. But if we review the medical history of pneumonia, we would have a better understanding of SARS. This article focuses the history of people's understanding of pneumonia on the historical documents, diagnosis, etiology and treatment. Through the epidemic of SARS, the author hopes to express that contagion will live with us for a long time, but it is not a deadly disease. It is preventable and good care is essential for contagious patients. As Chinese people, we should have the best use of TCM in our combat with contagion.

  6. Spacecraft on-board SAR processing technology

    NASA Technical Reports Server (NTRS)

    Liu, K. Y.; Arens, W. E.

    1987-01-01

    This paper provides an assessment of the on-board SAR processing technology for Eos-type missions. The proposed Eos SAR sensor and flight data system are introduced, and the SAR processing requirements are described. The SAR on-board SAR processor architecture selection is discussed, and a baseline processor architecture using a frequency-domain processor for range correlation and a modular fault-tolerant VLSI time-domain parallel array for azimuth correlation are described. The mass storage and VLSI technologies needed for implementing the proposed SAR processing are assessed. It is shown that acceptable processor power and mass characteristics should be feasible for Eos-type applications. A proposed development strategy for the on-board SAR processor is presented.

  7. Bioelectromagnetic effects measurements - SAR and induced current.

    PubMed

    Dlugosz, Tomasz

    2015-01-01

    The paper discusses several theoretical and practical aspects of the application of currents flowing through the body of a radiotelephone operator and Specific Absorption Rate (SAR). SAR is known as the physical quantity which is a perfect solution for biological experiments. Unfortunately, SAR cannot be measured directly. Contrary to SAR, which is limited to the penetration depth, a current induced in a point of a body is measurable in any other point of the body. The main objective of this paper is to show that the current induced in a human body when using a radiotelephone or mobile phone is significant and should be analyzed as widely as SAR is. Computer simulations of a human's hand with a radiotelephone were made. Experiments were also conducted. The results of the experiments show that induced current is also as important as SAR and it cannot be omitted in bioelectromagnetic experiments. In biomedical studies both parameters: induced current and SAR play a major role.

  8. 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.

  9. Antimalarial activity of molecules interfering with Plasmodium falciparum phospholipid metabolism. Structure-activity relationship analysis.

    PubMed

    Calas, M; Cordina, G; Bompart, J; Ben Bari, M; Jei, T; Ancelin, M L; Vial, H

    1997-10-24

    A series of 80 compounds, primary, secondary, and tertiary amines and quaternary ammonium and bisammonium salts, most of them synthesized as potential choline or ethanolamine analogs, were tested against the in vitro growth of Plasmodium falciparum, the human malaria parasite. They were active over the 10(-3)-10(-8) M concentration range. A structure-activity relationship study was carried out using autocorrelation vectors as structural descriptors, and multidimensional analysis. Principal component analysis, ascending hierarchical classification, and stepwise discriminant analysis showed that both the size and shape of the molecule were essential for antimalarial potency, making the lipophilicity and electronegativity distribution in the molecular space essential. Using the autocorrelogram describing the molecular shape and the electronegativity distribution on the molecular graph, 98% of the molecules were correctly classified either as poorly active or active with only three explanatory variables. The most active compounds were quaternary ammoniums salts whose nitrogen atom had only one long lipophilic chain of 11 or 12 methylene groups (E5, E6, E10, E13, E20, E21, E22, E23, F4, F8), or the bisammoniums whose polar heads were linked by linear alkyl chains of 10 to 12 carbon atoms (G4, G23). The hydroxyethyl group of choline was not very beneficial, whereas the charge and substitutions of nitrogen (aimed at increasing lipophilicity) were essential for optimal interactions. A crude topographic model of the ligand (choline) binding site was thus drawn up.

  10. Synthesis, biological evaluation, and structure-activity relationships for 5-[(E)-2-arylethenyl]-3-isoxazolecarboxylic acid alkyl ester derivatives as valuable antitubercular chemotypes.

    PubMed

    Pieroni, Marco; Lilienkampf, Annamaria; Wan, Baojie; Wang, Yuehong; Franzblau, Scott G; Kozikowski, Alan P

    2009-10-22

    Tuberculosis (TB), mostly caused by Mycobacterium tuberculosis (Mtb), is one of the leading causes of death from infectious disease worldwide. Its coinfection with HIV and the emergence of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) strains have further worsened the TB pandemic. Despite its global impact, TB is considered a neglected disease and no new anti-TB therapeutics have been introduced over the last four decades. The nonreplicating persistent form of TB (NRP-TB) is responsible for the length of the treatment and is the putative cause of treatment failure. Therefore, new anti-TB agents, which are active against both the replicating form of Mtb (R-TB) and NRP-TB, are urgently needed. Herein, we report the synthesis and structure-activity relationships (SAR) of a series of 5-[(E)-2-arylethenyl]-3-isoxazolecarboxylic acid alkyl esters as potent anti-TB agents. Several compounds had submicromolar minimum inhibitory concentrations (MIC) against R-TB and were active against NRP-TB in the low micromolar range, thus representing attractive lead compounds for the possible development of new anti-TB agents.

  11. 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

  12. 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

  13. Possible relationships between solar activity and atmospheric constituents

    NASA Technical Reports Server (NTRS)

    Roosen, R. G.; Angione, R. J.

    1975-01-01

    The large body of data on solar variations and atmospheric constituents collected between 1902 and 1953 by the Astrophysical Observatory of the Smithsonian Institution (APO) was examined. Short-term variations in amounts of atmospheric aerosols and water vapor due to seasonal changes, volcanic activity, air pollution, and frontal activity are discussed. Preliminary evidence indicates that increased solar activity is at times associated with a decrease in attenuation due to airborne particulates.

  14. Public (Q)SAR Services, Integrated Modeling Environments, and Model Repositories on the Web: State of the Art and Perspectives for Future Development.

    PubMed

    Tetko, Igor V; Maran, Uko; Tropsha, Alexander

    2017-03-01

    Thousands of (Quantitative) Structure-Activity Relationships (Q)SAR models have been described in peer-reviewed publications; however, this way of sharing seldom makes models available for the use by the research community outside of the developer's laboratory. Conversely, on-line models allow broad dissemination and application representing the most effective way of sharing the scientific knowledge. Approaches for sharing and providing on-line access to models range from web services created by individual users and laboratories to integrated modeling environments and model repositories. This emerging transition from the descriptive and informative, but "static", and for the most part, non-executable print format to interactive, transparent and functional delivery of "living" models is expected to have a transformative effect on modern experimental research in areas of scientific and regulatory use of (Q)SAR models.

  15. 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.

  16. From SARS coronavirus to novel animal and human coronaviruses.

    PubMed

    To, Kelvin K W; Hung, Ivan F N; Chan, Jasper F W; Yuen, Kwok-Yung

    2013-08-01

    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.

  17. Active transport in complex media: Relationship between persistence and superdiffusion

    NASA Astrophysics Data System (ADS)

    Despósito, Marcelo A.; Pallavicini, Carla; Levi, Valeria; Bruno, Luciana

    2011-03-01

    We study the relationship between anomalous diffusion and persistent motion of micron-sized particles moving in a viscoelastic environment and subjected to an external noise. In the framework of a generalized Langevin equation, we compare the analytical expressions of the mean square displacement and the mean cosine of the turning angle. Both magnitudes can be easily computed from the particles trajectories, and allow us to investigate the different anomalous regimes typically obtained, for instance, in single particle tracking experiments within living cells. Finally, we analyze the directional changes occurring during the motion of pigment organelles driven by molecular motors in Xenopus laevis melanocytes, as an example of application of our model.

  18. Electrodermal activity during total sleep deprivation and its relationship with other activation and performance measures.

    PubMed

    Miró, E; Cano-Lozano, M C; Buela-Casal, G

    2002-06-01

    The present study analyses the variations of the skin resistance level (SRL) during 48 h of total sleep deprivation (TSD) and its relationship to body temperature, self-informed sleepiness in the Stanford Sleepiness Scale (SSS), and reaction time (RT). All of the variables were evaluated every 2 h except for the SSS, which was evaluated every hour. A total of 30 healthy subjects (15 men and 15 women) from 18 to 24 years old participated in the experiment. Analyses of variance (ANOVAs) with TSD days and time-of-day as factors showed a substantial increase of SRL, SSS, and RT, and a decrease in body temperature marked by strong circadian oscillations. The interaction between day by time-of-day was only significant for RT. Furthermore, Pearson's correlations showed that the increase of SRL is associated to the decrease in temperature (mean r=-0.511), the increase of SSS (mean r=0.509), and the deterioration of RT (mean r=0.425). The results support previous TSD reports and demonstrate the sensitivity of SRL to TSD. The non-invasive character of SRL, its simplicity, and its relationships with other activation parameters, widely validated by previous literature, convert SRL into an interesting and useful measure in this field.

  19. Anti-proliferative activities of terpenoids isolated from Alisma orientalis and their structure-activity relationships.

    PubMed

    Xu, Wen; Li, Ting; Qiu, Jian-Fang; Wu, Shui-Sheng; Huang, Ming-Qing; Lin, Li-Gen; Zhang, Qing-Wen; Chen, Xiu-Ping; Lu, Jin-Jian

    2015-01-01

    This study aimed to isolate terpenoids from Alisma orientalis (Sam.) Juzep. and elucidate their antiproliferative activities, as well as structure-activity relationships. Fourteen protostane-type triterpenoids were isolated from the rhizome of A. orientalis. Among these triterpenoids, alisol A (1), alisol A 24-acetate (2), alisol B (3), alisol B 23-acetate (4), and alisol G (8) presented inhibitory effects on cancer cell lines tested. Compounds 3 and 4 showed the highest potential; IC50 values for HepG2, MDA-MB-231, and MCF-7 cells were 16.28, 14.47, and 6.66 μM for 3 and 18.01, 15.97, and 13.56 μM for 4, respectively. Based on these results, we concluded that the degree of C-16 oxidation and the double bond between C-13 and C-17 may be significant in anti-proliferative activities. Further study showed that 3 and 4 effectively induced apoptosis, as confirmed by flow cytometry. Increased intracellular calcium concentration and endoplasmic reticulum stress were detected after treatment with 4 in HepG2 cells. Although compounds 1 and 2 induced minimal apoptosis, they evidently delayed the G2/M phase in HepG2 cells. Further study showed that 1-4 also enhanced LC3II expression, indicating autophagy is occured.

  20. Relationship between motor activity-related cortical potential and voluntary muscle activation.

    PubMed

    Siemionow, V; Yue, G H; Ranganathan, V K; Liu, J Z; Sahgal, V

    2000-08-01

    The purpose of this study was to investigate the relationship between EEG-derived motor activity-related cortical potential (MRCP) and voluntary muscle activation. Eight healthy volunteers participated in two experimental sessions. In one session, subjects performed isometric elbow-flexion contractions at four intensity levels [10%, 35%, 60%, and 85% maximal voluntary contraction (MVC)]. In another session, a given elbow-flexion force (35% MVC) was generated at three different rates (slow, intermediate, and fast). Thirty to 40 contractions were performed at each force level or rate. EEG signals were recorded from the scalp overlying the supplementary motor area (SMA) and contralateral sensorimotor cortex, and EMG signals were recorded from the skin surface overlying the belly of the biceps brachii and brachioradialis muscles during all contractions. In each trial, the force was used as the triggering signal for MRCP averaging. MRCP amplitude was measured from the beginning to the peak of the negative slope. The magnitude of MRCP from both EEG recording locations (sensorimotor cortex and SMA) was highly correlated with elbow-flexion force, rate of rising of force, and muscle EMG signals. These results suggest that MRCP represents cortical motor commands that scale the level of muscle activation.

  1. A facile inhibitor screening of SARS coronavirus N protein using nanoparticle-based RNA oligonucleotide.

    PubMed

    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.

  2. D-penicillamine-induced autoimmunity: relationship to macrophage activation.

    PubMed

    Li, Jinze; Uetrecht, Jack P

    2009-09-01

    Idiosyncratic drug reactions represent a serious health problem, and they remain unpredictable largely due to our limited understanding of the mechanisms involved. Penicillamine-induced autoimmunity in Brown Norway (BN) rats represents one model of an idiosyncratic reaction, and this drug can also cause autoimmune reactions in humans. We previously demonstrated that penicillamine binds to aldehydes on the surface of macrophages. There is evidence that an imine bond formed by aldehyde groups on macrophages and amine groups on T cells is one type of interaction between these two cells that is involved in the induction of an immune response. We proposed that the binding of penicillamine with aldehyde groups on macrophages could lead to their activation and in some patients could lead to autoimmunity. In this study, the transcriptome profile of spleen macrophages 6 h after penicillamine treatment was used to detect effects of penicillamine on macrophages with a focus on 20 genes known to be macrophage activation biomarkers. One biological consequence of macrophage activation was investigated by determining mRNA levels for IL-15 and IL-1 beta which are crucial for NK cell activation, as well as levels of mRNA for selected cytokines in spleen NK cells. Up-regulation of the macrophage activating cytokines, IFN-gamma and GM-CSF, and down-regulation of IL-13 indicated activation of NK cells, which suggests a positive feedback loop between macrophages and NK cells. Furthermore, treatment of a murine macrophage cell line, RAW264.7, with penicillamine increased the production of TNF-alpha, IL-6, and IL-23, providing additional evidence that penicillamine activates macrophages. Hydralazine and isoniazid cause a lupus-like syndrome in humans and also bind to aldehyde groups. These drugs were also found to activate RAW264.7 macrophages. Together, these data support the hypothesis that drugs that bind irreversibly with aldehydes lead to macrophage activation, which in some

  3. 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

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. SAR Object Change Detection Study.

    DTIC Science & Technology

    1980-03-01

    based techniques when applied to Synthetic Aperature Radar (SAR imagery. DOUGLA 3. PRASKA, 2LT, USAF Project Engineer viii Section 1 INTRODUCTION AND...to assess the applicability of three region-based change-detection methods to synthetic aperture radar imagery. I/ Ac .0ion For K:CTAB [ ft i . i...Section 2, the algorithms developed were applied to synthetic -aperture radar image data furnished by RADC. Some preprocessing of all images was required

  9. 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.

  10. Anti-HIV, anti-poxvirus, and anti-SARS activity of a nontoxic, acidic plant extract from the Trifollium species Secomet-V/anti-vac suggests that it contains a novel broad-spectrum antiviral.

    PubMed

    Kotwal, Girish J; Kaczmarek, Jennifer N; Leivers, Steven; Ghebremariam, Yohannes T; Kulkarni, Amod P; Bauer, Gabriele; De Beer, Corena; Preiser, Wolfgang; Mohamed, Abdu Rahman

    2005-11-01

    Enveloped animal viruses such as human immunodeficiency virus (HIV), hepatitis B virus, hepatitis C virus, human papillomavirus, Marburg, and influenza are major public health concerns around the world. The prohibitive cost of antiretroviral (ARV) drugs for most HIV-infected patients in sub-Saharan Africa and the serious side effects in those who have access to ARV drugs make a compelling case for the study of complementary and alternative therapies. Such therapies should have scientifically proved antiviral activity and minimal toxic effects. A plant extract, Secomet-V, with an anecdotal indication in humans for promise as an anti-HIV treatment, was investigated. Using a previously described attenuated vaccinia virus vGK5, we established the antiviral activity of Secomet-V. Chemical analysis showed that it has an acidic pH, nontoxic traces of iron (<10 ppm), and almost undetectable levels of arsenic (<1.0 ppm). The color varies from colorless to pale yellow to dark brown. The active agent is heat stable at least up to sterilizing temperature of 121 degrees C. The crude plant extract is a mixture of several small molecules separable by high-pressure liquid chromatography. The HIV viral loads were significantly reduced over several months in a few patients monitored after treatment with Secomet-V. Secomet-V was also found to have antiviral activity against the SARS virus but not against the West Nile virus. Secomet-V, therefore, is a broad-spectrum antiviral, which possibly works by neutralizing viral infectivity, resulting in the prevention of viral attachment.

  11. Synthesis of aromatase inhibitors and dual aromatase steroid sulfatase inhibitors by linking an arylsulfamate motif to 4-(4H-1,2,4-triazol-4-ylamino)benzonitrile: SAR, crystal structures, in vitro and in vivo activities.

    PubMed

    Bubert, Christian; Woo, L W Lawrence; Sutcliffe, Oliver B; Mahon, Mary F; Chander, Surinder K; Purohit, Atul; Reed, Michael J; Potter, Barry V L

    2008-11-01

    4-(((4-Cyanophenyl)(4H-1,2,4-triazol-4-yl)amino)methyl)phenyl sulfamate (6 a) was the first dual aromatase-sulfatase inhibitor (DASI) reported. Several series of its derivatives with various linker systems between the steroid sulfatase (STS) and the aromatase inhibitory pharmacophores were synthesised and evaluated in JEG-3 cells. The X-ray crystal structures of the aromatase inhibitors, DASI precursors 42 d and 60, and DASI 43 h were determined. Nearly all derivatives show improved in vitro aromatase inhibition over 6 a but decreased STS inhibition. The best aromatase inhibitor is 42 e (IC(50)=0.26 nM) and the best DASI is 43 e (IC(50 aromatase)=0.45 nM, IC(50 STS)=1200 nM). SAR for aromatase inhibition shows that compounds containing an alkylene- and thioether-based linker system are more potent than those that are ether-, sulfone-, or sulfonamide-based, and that the length of the linker has a limited effect on aromatase inhibition beyond two methylene units. Compounds 43 d-f were studied in vivo (10 mg kg(-1), single, p.o.). The most potent DASI is 43 e, which inhibited PMSG-induced plasma estradiol levels by 92 % and liver STS activity by 98 % 3 h after dosing. These results further strengthen the concept of designing and developing DASIs for potential treatment of hormone-related cancers.

  12. 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

  13. 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.

  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.

  15. 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

  16. Structure-activity relationship studies of phencyclidine derivatives in rats.

    PubMed

    Cone, E J; McQuinn, R L; Shannon, H E

    1984-01-01

    Phencyclidine (PCP), a semirigid molecule containing a cyclohexane ring with vicinally attached aromatic and piperidine rings, produces characteristic discriminative stimulus properties and pupillary miosis in rats. The effectiveness of a series of aromatic and nitrogen substituted analogs of PCP in producing PCP-like discriminative stimuli and changes in pupil diameter was determined in rats trained to discriminate between saline and 3.0 mg/kg of PCP. Dexoxadrol and its optical isomer levoxadrol were also evaluated for purposes of comparison. Analogs in which the electron-density of the aromatic ring was increased (3NH2-PCP) or only slightly reduced (3F-PCP) retained PCP-like activity. A loss of PCP-like activity occurred with analogs in which the electron-density of the aromatic ring was greatly reduced (3NO2-PCP) or extended to a larger system (1NCP and 2NCP). PCP-like activity also was abolished in analogs in which the distance between the aromatic ring and the remainder of the molecule was systematically increased by one, two or three methylene units. In contrast, substitutions on the nitrogen atom altered the potency, but not the efficacy, of such analogs. Dexoxadrol produced PCP-like activity whereas its optical enantiomer levoxadrol was devoid of such activity. These findings suggest a drug receptor surface with multiple domains or subsites which recognize regions of structural overlap among the phencyclidines, dioxolanes and psychotomimetic benzomorphan derivatives.

  17. 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.

  18. 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.

  19. Satellite SAR geocoding with refined RPC model

    NASA Astrophysics Data System (ADS)

    Zhang, Lu; Balz, Timo; Liao, Mingsheng

    2012-04-01

    Recent studies have proved that the Rational Polynomial Camera (RPC) model is able to act as a reliable replacement of the rigorous Range-Doppler (RD) model for the geometric processing of satellite SAR datasets. But its capability in absolute geolocation of SAR images has not been evaluated quantitatively. Therefore, in this article the problems of error analysis and refinement of SAR RPC model are primarily investigated to improve the absolute accuracy of SAR geolocation. Range propagation delay and azimuth timing error are identified as two major error sources for SAR geolocation. An approach based on SAR image simulation and real-to-simulated image matching is developed to estimate and correct these two errors. Afterwards a refined RPC model can be built from the error-corrected RD model and then used in satellite SAR geocoding. Three experiments with different settings are designed and conducted to comprehensively evaluate the accuracies of SAR geolocation with both ordinary and refined RPC models. All the experimental results demonstrate that with RPC model refinement the absolute location accuracies of geocoded SAR images can be improved significantly, particularly in Easting direction. In another experiment the computation efficiencies of SAR geocoding with both RD and RPC models are compared quantitatively. The results show that by using the RPC model such efficiency can be remarkably improved by at least 16 times. In addition the problem of DEM data selection for SAR image simulation in RPC model refinement is studied by a comparative experiment. The results reveal that the best choice should be using the proper DEM datasets of spatial resolution comparable to that of the SAR images.

  20. 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.

  1. 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…

  2. 29 CFR 784.137 - Relationship of exemption to exemption for “offshore” activities.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Relationship of exemption to exemption for âoffshoreâ...(a)(4) Exemption § 784.137 Relationship of exemption to exemption for “offshore” activities. The... or by the necessity for consumption or preservation of such products before spoilage occurs...

  3. 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.…

  4. Investigating the Relationship among Extracurricular Activities, Learning Approach and Academic Outcomes: A Case Study

    ERIC Educational Resources Information Center

    Chan, Yiu-Kong

    2016-01-01

    Learning effectiveness requires an understanding of the relationship among extracurricular activities, learning approach and academic performance and, it is argued, this helps educators develop techniques designed to enrich learning effectiveness. Biggs' Presage-Process-Product model on student learning has identified the relationship among…

  5. Design of Coltuximab Ravtansine, a CD19-Targeting Antibody-Drug Conjugate (ADC) for the Treatment of B-Cell Malignancies: Structure-Activity Relationships and Preclinical Evaluation.

    PubMed

    Hong, E Erica; Erickson, Hans; Lutz, Robert J; Whiteman, Kathleen R; Jones, Gregory; Kovtun, Yelena; Blanc, Veronique; Lambert, John M

    2015-06-01

    Coltuximab ravtansine (SAR3419) is an antibody-drug conjugate (ADC) targeting CD19 created by conjugating a derivative of the potent microtubule-acting cytotoxic agent, maytansine, to a version of the anti-CD19 antibody, anti-B4, that was humanized as an IgG1 by variable domain resurfacing. Four different linker-maytansinoid constructs were synthesized (average ∼3.5 maytansinoids/antibody for each) to evaluate the impact of linker-payload design on the activity of the maytansinoid-ADCs targeting CD19. The ADC composed of DM4 (N(2')-deacetyl-N(2')-[4-mercapto-4-methyl-1-oxopentyl]maytansine) conjugated to antibody via the N-succinimidyl-4-(2-pyridyldithio)butyrate (SPDB) linker was selected for development as SAR3419. A molar ratio for DM4/antibody of between 3 and 5 was selected for the final design of SAR3419. Evaluation of SAR3419 in Ramos tumor xenograft models showed that the minimal effective single dose was about 50 μg/kg conjugated DM4 (∼2.5 mg/kg conjugated antibody), while twice this dose gave complete regressions in 100% of the mice. SAR3419 arrests cells in the G2/M phase of the cell cycle, ultimately leading to apoptosis after about 24 h. The results of in vitro and in vivo studies with SAR3419 made with DM4 that was [(3)H]-labeled at the C20 methoxy group of the maytansinoid suggest a mechanism of internalization and intracellular trafficking of SAR3419, ultimately to lysosomes, in which the antibody is fully degraded, releasing lysine-N(ε)-SPDB-DM4 as the initial metabolite. Subsequent intracellular reduction of the disulfide bond between linker and DM4 generates the free thiol species, which is then converted to S-methyl DM4 by cellular methyl transferase activity. We provide evidence to suggest that generation of S-methyl DM4 in tumor cells may contribute to in vivo tumor eradication via bystander killing of neighboring tumor cells. Furthermore, we show that S-methyl DM4 is converted to the sulfoxide and sulfone derivatives in the liver

  6. 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.

  7. 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.

  8. 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.

  9. Motualevic Acids and Analogs: Synthesis and Antimicrobial Structure Activity Relationships

    PubMed Central

    Cheruku, Pradeep; Keffer, Jessica L.; Dogo-Isonagie, Cajetan; Bewley, Carole A.

    2010-01-01

    Synthesis of the marine natural products motualevic acids A, E, and analogs in which modifications have been made to the ω-brominated lipid (E)-14,14-dibromotetra-deca-2,13-dienoic acid or amino acid unit are reported, together with antimicrobial activities against Staphylococcus aureus, methicillin-resistant S. aureus, Enterococcus faecium, and vancomycin-resistant Enterococcus. PMID:20538459

  10. Analyzing Age-Rotation-Activity Relationships in Wide Binary Systems

    NASA Astrophysics Data System (ADS)

    Walton Clarke, Riley; Davenport, James R. A.

    2017-01-01

    We present an analysis of flare activity among equal mass wide binary pairs using a combination of value-added data sets from the NASA Kepler mission. Wide binary twins form from the same molecular cloud and are therefore coeval, making them ideal benchmarks for stellar evolution and formation studies. This implies that their magnetic activity should decay at the same rate, causing a similar decrease in flare activity over time. The first data set is the list of known wide binary candidates in the Kepler field, and contains pairs of stars that have similar proper motions. We then crossmatch these systems with data on relative flare luminosity for ~200,000 stars in the original Kepler field, provided by an automated flare-finding algorithm. This combined data set allows us to compare flare activity, mass, and pair separation between stars in binary pairs. We preliminarily find that the flare rates for these stars do not show strong correlation, indicating either a large intrinsic scatter in the flare rate as these stars age, or that the formation mechanism of wide binaries somehow affects their dynamo evolution. As a goal for future development of this work, we hope to compare flare rates with gyrochronology in these key systems.

  11. Relationship of The Tropical Cyclogenesis With Solar and Magnetospheric Activities

    NASA Astrophysics Data System (ADS)

    Vishnevsky, O.; Pankov, V.; Erokhine, N.

    Formation of tropical cyclones is a badly studied period in their life cycle even though there are many papers dedicated to analysis of influence of different parameters upon cyclones occurrence frequency (see e.g., Gray W.M.). Present paper is dedicated to study of correlation of solar and magnetospheric activity with the appearance of tropi- cal cyclones in north-west region of Pacific ocean. Study of correlation was performed by using both classical statistical methods (including maximum entropy method) and quite modern ones, for example multifractal analysis. Information about Wolf's num- bers and cyclogenesis intensity in period of 1944-2000 was received from different Internet databases. It was shown that power spectra maximums of Wolf's numbers and appeared tropical cyclones ones corresponds to 11-year period; solar activity and cyclogenesis processes intensity are in antiphase; maximum of mutual correlation co- efficient ( 0.8) between Wolf's numbers and cyclogenesis intensity is in South-China sea. There is a relation of multifractal characteristics calculated for both time series with the mutual correlation function that is another indicator of correlation between tropical cyclogenesis and solar-magnetospheric activity. So, there is the correlation between solar-magnetospheric activity and tropical cyclone intensity in this region. Possible physical mechanisms of such correlation including anomalous precipitations charged particles from the Earth radiation belts and wind intensity amplification in the troposphere are discussed.

  12. Relationship of The Tropical Cyclogenesis With Solar and Magnetospheric Activities

    NASA Astrophysics Data System (ADS)

    Vishnevsky, O. V.; Pankov, V. M.; Erokhine, N. S.

    Formation of tropical cyclones is a badly studied period in their life cycle even though there are many papers dedicated to analysis of influence of different parameters upon cyclones occurrence frequency (see e.g., Gray W.M.). Present paper is dedicated to study of correlation of solar and magnetospheric activity with the appearance of tropical cyclones in north-west region of Pacific ocean. Study of correlation was performed by using both classical statistical methods (including maximum entropy method) and quite modern ones, for example multifractal analysis. Information about Wolf's numbers and cyclogenesis intensity in period of 1944-2000 was received from different Internet databases. It was shown that power spectra maximums of Wolf's numbers and appeared tropical cyclones ones corresponds to 11-year period; solar activity and cyclogenesis processes intensity are in antiphase; maximum of mutual correlation coefficient (~ 0.8) between Wolf's numbers and cyclogenesis intensity is in South-China sea. There is a relation of multifractal characteristics calculated for both time series with the mutual correlation function that is another indicator of correlation between tropical cyclogenesis and solar-magnetospheric activity. So, there is the correlation between solar-magnetospheric activity and tropical cyclone intensity in this region. Possible physical mechanisms of such correlation including anomalous precipitations charged particles from the Earth radiation belts and wind intensity amplification in the troposphere are discussed.

  13. Relationship between diet/physical activity and health

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Obesity and four of the leading causes of death - heart disease, cancer, stroke, and type 2 diabetes mellitus - are related to lifestyle. The combination of a healthy weight, prudent diet, and daily physical activity clearly plays a role in primary, secondary, and tertiary prevention of these and o...

  14. 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…

  15. Relationship between disease activity and infection in patients with spondyloarthropathies

    PubMed Central

    Martinez, A; Pacheco-Tena, C; Vazquez-Mellado, J; Burgos-Vargas, R

    2004-01-01

    Methods: A cross sectional study of 95 non-selected patients with SpA (62 men; mean age 26.4 years), who were examined for signs and symptoms of infection and their association with disease activity. 52 had ankylosing spondylitis (AS), 32 undifferentiated SpA (uSpA), 6 chronic reactive arthritis (ReA), and 5 psoriatic arthritis (PsA). Categorical data were analysed by χ2 or Fisher's tests. Results: 53 (56%) patients had infections: 41 (43%) upper respiratory tract (URT), 34 (36%) enteric, and 20 (21%) genitourinary infections. More infections occurred in HLA-B27 positive patients as a whole (39 v 5; p = 0.003) and in uSpA (12 v 2; p = 0.005). In AS and uSpA, infections occurred in ∼50%. 30/39 (77%) patients with active disease (group A) and 23/56 (41%) (group B) (p = 0.001) had infection. There were more enteric infections in group A (47%; p<0.001) and more URT infections in group B (52%; p = NS). 22/30 (73%) patients attributed disease activity to infection. Conclusion: Enteric, and less commonly, URT infections in Mexican patients with SpA, particularly those who were HLA-B27 positive, seem to have a role in the active phase of AS and uSpA. PMID:15361397

  16. 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.

  17. 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…

  18. 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...

  19. SIR-C/X-SAR free flyer concept

    NASA Technical Reports Server (NTRS)

    Monson, R.

    1993-01-01

    Viewgraphs on Spaceborne Imaging Radar (SAR) - C/X- Synthetic Aperture Radar (SAR) Free Flyer concept are presented. An overview, science objectives, science rationale, geophysical parameters from SAR, programmatic goals, concept description, and a candidate mission description are included.

  20. Relationships Between Dog Ownership and Physical Activity in Postmenopausal Women

    PubMed Central

    Wertheim, Betsy C.; Manson, JoAnn E.; Chlebowski, Rowan T.; Volpe, Stella Lucia; Howard, Barbara V.; Stefanick, Marcia L.; Thomson, Cynthia A.

    2014-01-01

    Background Positive associations between dog ownership and physical activity in older adults have been previously reported. Purpose The objective of this study was to examine cross-sectional associations between dog ownership and physical activity measures in a well-characterized, diverse sample of postmenopausal women. Methods Analyses included 36,984 dog owners (mean age: 61.5 yrs), and 115,645 non-dog owners (mean age: 63.9 yrs) enrolled in a clinical trial or the observational study of the Women’s Health Initiative between 1993 and 1998. Logistic regression models were used to test for associations between dog ownership and physical activity, adjusted for potential confounders. Results Owning a dog was associated with a higher likelihood of walking ≥150 min/wk (OR, 1.14; 95% CI, 1.10–1.17) and a lower likelihood of being sedentary ≥8 hr/day (OR, 0.86; 95% CI, 0.83–0.89) as compared to not owning a dog. However, dog owners were less likely to meet ≥7.5 MET-hr/wk of total physical activity as compared to non-dog owners (OR, 1.03; 95% CI, 1.00–1.07). Conclusions Dog ownership is associated with increased physical activity in older women, particularly among women living alone. Health promotion efforts aimed at older adults should highlight the benefits of regular dog walking for both dog owners and non-dog owners. PMID:25449694

  1. Relationship between Jovian Hectometric Attenuation Lanes And Io Volcanic Activity

    NASA Technical Reports Server (NTRS)

    Menietti, J. D.; Gurnett, D. A.; Spencer, J. R.; Stansberry, J. A.

    2001-01-01

    Within the Galileo plasma wave instrument data a narrow (in frequency) attenuation band is seen in the hectometric (HOM) emission that varies in frequency with system III longitude. This attenuation lane is believed to be the result of near-grazing incidence or coherent scattering of radio emission near the outer edge of the Io torus, i.e., when the ray path is nearly tangent to an L shell containing the Io flux tube. Such a process should, therefore, be enhanced when the Io volcanic activity is increased and the Io flux tube has enhanced density. We have performed a systematic study of the existing Galileo radio emission data in an effort to determine the phenomenology and frequency of occurrence of the attenuation lanes and the association, if any, with published volcanic activity of Io. Our results indicate that the attenuation lanes are present almost all of the time but are enhanced on occasion. The best examples of attenuation lanes occur when Galileo is within approximately 65 R(sub J) of Jupiter and thus are probably more apparent because of the increased signal-to-noise ratio of the radio receivers. The lack of continuous monitoring of Io activity and the lack of known activity on the anti-Earthward side of Io are problematic and make detailed correlation with radio emission very difficult at this time. Nevertheless, if the data are displayed for periods when the spacecraft is within 65 R(sub J) (i.e., for each perijove pass), then the highest-contrast lanes occur on most passes when the Io volcanic activity is also high for that pass. These results support our current understanding of attenuation lane formation and suggest that future efforts can be made to better understand the interaction of HOM emission with the Io flux tube.

  2. 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.

  3. AI and SAR approaches for predicting chemical carcinogenicity: survey and status report.

    PubMed

    Richardt, A M; Benigni, R

    2002-03-01

    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 endpoint, the shared challenge of these approaches is to accurately delineate classes of active chemicals representing distinct biological and chemical mechanism domains, and within those classes determine the structural features and properties responsible for modulating activity. In the following discussion, we present a survey of AI and SAR approaches that have been applied to the prediction of rodent carcinogenicity, and discuss these in general terms and in the context of the results of two organized prediction exercises (PTE-1 and PTE-2) sponsored by the US National Cancer Institute/National Toxicology Program. Most models participating in these exercises were successful in identifying major structural-alerting classes of active carcinogens, but failed in modeling the more subtle modifiers to activity within those classes. In addition, methods that incorporated mechanism-based reasoning or biological data along with structural information outperformed models limited to structural information exclusively. Finally, a few recent carcinogenicity-modeling efforts are presented illustrating progress in tackling some aspects of the carcinogenicity prediction problem. The first example, a QSAR model for predicting carcinogenic potency of aromatic amines, illustrates that success is possible within well-represented classes of carcinogens. From the second example, a newly developed FDA/OTR MultiCASE model for predicting the carcinogenicity of pharmaceuticals, we conclude that the definitions of biological activity and nature of chemicals in the training set are important determinants of the predictive success and specificity/sensitivity characteristics of a derived model.

  4. 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.

  5. Isatin Derived Spirocyclic Analogues with α-Methylene-γ-butyrolactone as Anticancer Agents: A Structure-Activity Relationship Study.

    PubMed

    Rana, Sandeep; Blowers, Elizabeth C; Tebbe, Calvin; Contreras, Jacob I; Radhakrishnan, Prakash; Kizhake, Smitha; Zhou, Tian; Rajule, Rajkumar N; Arnst, Jamie L; Munkarah, Adnan R; Rattan, Ramandeep; Natarajan, Amarnath

    2016-05-26

    Design, synthesis, and evaluation of α-methylene-γ-butyrolactone analogues and their evaluation as anticancer agents is described. SAR identified a spirocyclic analogue 19 that inhibited TNFα-induced NF-κB activity, cancer cell growth and tumor growth in an ovarian cancer model. A second iteration of synthesis and screening identified 29 which inhibited cancer cell growth with low-μM potency. Our data suggest that an isatin-derived spirocyclic α-methylene-γ-butyrolactone is a suitable core for optimization to identify novel anticancer agents.

  6. 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...

  7. 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...

  8. 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...

  9. 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.

  10. Synthesis and structure-activity relationships of potent antitumor active quinoline and naphthyridine derivatives.

    PubMed

    Srivastava, Sanjay K; Jha, Amrita; Agarwal, Shiv K; Mukherjee, Rama; Burman, Anand C

    2007-11-01

    The disease of cancer has been ranked second after cardiovascular diseases and plant-derived molecules have played an important role for the treatment of cancer. Nine cytotoxic plant-derived molecules such as vinblastine, vincristine, navelbine, etoposide, teniposide, taxol, taxotere, topotecan and irinotecan have been approved as anticancer drugs. Recently, epothilones are being emerging as future potential anti-tumor agents. However, targeted cancer therapy has now been rapidly expanding and small organic molecules are being exploited for this purpose. Amongst target specific small organic molecules, quinazoline was found as one of the most successful chemical class in cancer chemotherapy as three drugs namely Gefitinib, Erlotinib and Canertinib belong to this series. Now, quinazoline related chemical classes such as quinolines and naphthyridines are being exploited in cancer chemotherapy and a number of molecules such as compounds EKB-569 (52), HKI-272 (78) and SNS-595 (127a) are in different phases of clinical trials. This review presents the synthesis of quinolines and naphthyridines derivatives, screened for anticancer activity since year 2000. The synthesis of most potent derivatives in each prototype has been delineated. A brief structure activity relationship for each prototype has also been discussed. It has been observed that aniline group at C-4, aminoacrylamide substituents at C-6, cyano group at C-3 and alkoxy groups at C-7 in the quinoline ring play an important role for optimal activity. While aminopyrrolidine functionality at C-7, 2'-thiazolyl at N-1 and carboxy group at C-3 in 1,8-naphthyridine ring are essential for eliciting the cytotoxicity. This review would help the medicinal chemist to design and synthesize molecules for targeted cancer chemotherapy.

  11. 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.

  12. Cytotoxicity and structure activity relationships of phytosterol from Phyllanthus emblica.

    PubMed

    Qi, Wei-Yan; Li, Ya; Hua, Lei; Wang, Ke; Gao, Kun

    2013-01-01

    Fourteen sterols (1-14), including two new sterols, trihydroxysitosterol (2) and 5α,6β,7α-7α-acetoxysitosterol (3), were isolated from the branches and leaves of Phyllanthus emblica L. The isolated compounds and a structurally related sterol 15 from Aphanamixis grandifolia were screened for cytotoxicity in two tumor cell lines (HL-60 and SMMC-7721) and a non-tumor cell line (HL-7702) using RSB assay. Within the series of phytosterol derivatives tested, compound 15 was the most active, displaying potent cytotoxicity against HL-60 with IC(50) of 5.10μmol/L, and most of the active compounds showed selective cytotoxicity against tumor and non-tumor cell lines, especially compound 10 with a safety index of 4.42.

  13. Morpheus: a conformation-activity relationships and receptor modeling package.

    PubMed

    Andrews, P R; Quint, G; Winkler, D A; Richardson, D; Sadek, M; Spurling, T H

    1989-09-01

    Our molecular modeling software package, MORPHEUS, allows the study of the interactions between biologically active molecules and their receptors. The package is capable of exploring the multidimensional conformational space accessible to each molecule of the data set under study. By specifying distance constraints or hypothetical receptor binding points, the package is able to filter the biologically accessible conformations of each active compound and deduce a three-dimensional model of the binding sites consistent with the properties of the agonists (or antagonists) under scrutiny. The electrostatic potentials in the environment of a putative binding site can also be investigated using the MORPHEUS package. The molecular modeling module CRYS-X, which is written in FORTRAN 77 for IBM PC machines, is capable of building, displaying and manipulating molecules.

  14. Activities, family relationships and feelings about aging in a multicultural elderly sample.

    PubMed

    Harris, M B; Begay, C; Page, P

    1989-01-01

    This study looked at ethnic and gender differences in activities, family relationships, and feelings about aging in 128 American Indian, Anglo, and Hispanic adults over sixty. Reading, visiting, and watching television were the most popular activities for all subjects, with a number of sex and ethnic differences appearing. Most subjects reported improved relationships with their families on various dimensions after turning sixty. A number of advantages and disadvantages of aging were mentioned. Few ethnic or gender differences were found on these latter variables.

  15. 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

  16. 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

  17. Sparse Neural Network Models of Antimicrobial Peptide-Activity Relationships.

    PubMed

    Müller, Alex T; Kaymaz, Aral C; Gabernet, Gisela; Posselt, Gernot; Wessler, Silja; Hiss, Jan A; Schneider, Gisbert

    2016-12-01

    We present an adaptive neural network model for chemical data classification. The method uses an evolutionary algorithm for optimizing the network structure by seeking sparsely connected architectures. The number of hidden layers, the number of neurons in each layer and their connectivity are free variables of the system. We used the method for predicting antimicrobial peptide activity from the amino acid sequence. Visualization of the evolved sparse network structures suggested a high charge density and a low aggregation potential in solution as beneficial for antimicrobial activity. However, different training data sets and peptide representations resulted in greatly varying network structures. Overall, the sparse network models turned out to be less accurate than fully-connected networks. In a prospective application, we synthesized and tested 10 de novo generated peptides that were predicted to either possess antimicrobial activity, or to be inactive. Two of the predicted antibacterial peptides showed cosiderable bacteriostatic effects against both Staphylococcus aureus and Escherichia coli. None of the predicted inactive peptides possessed antibacterial properties. Molecular dynamics simulations of selected peptide structures in water and TFE suggest a pronounced peptide helicity in a hydrophobic environment. The results of this study underscore the applicability of neural networks for guiding the computer-assisted design of new peptides with desired properties.

  18. 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.

  19. 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.

  20. Three-dimensional surface reconstruction from multistatic SAR images.

    PubMed

    Rigling, Brian D; Moses, Randolph L

    2005-08-01

    This paper discusses reconstruction of three-dimensional surfaces from multiple bistatic synthetic aperture radar (SAR) images. Techniques for surface reconstruction from multiple monostatic SAR images already exist, including interferometric processing and stereo SAR. We generalize these methods to obtain algorithms for bistatic interferometric SAR and bistatic stereo SAR. We also propose a framework for predicting the performance of our multistatic stereo SAR algorithm, and, from this framework, we suggest a metric for use in planning strategic deployment of multistatic assets.

  1. 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.

  2. DNA damage and repair in mutagenesis and carcinogenesis: implications of structure-activity relationships for cross-species extrapolation.

    PubMed

    Vogel, E W; Nivard, M J; Ballering, L A; Bartsch, H; Barbin, A; Nair, J; Comendador, M A; Sierra, L M; Aguirrezabalaga, I; Tosal, L; Ehrenberg, L; Fuchs, R P; Janel-Bintz, R; Maenhaut-Michel, G; Montesano, R; Hall, J; Kang, H; Miele, M; Thomale, J; Bender, K; Engelbergs, J; Rajewsky, M F

    1996-06-12

    Previous studies on structure-activity relationships (SARs) between types of DNA modifications and tumour incidence revealed linear positive relationships between the log TD50 estimates and s-values for a series of mostly monofunctional alkylating agents. The overall objective of this STEP project was to further elucidate the mechanistic principles underlying these correlations, because detailed knowledge on mechanisms underlying the formation of genotoxic damage is an absolute necessity for establishing guidance values for exposures to genotoxic agents. The analysis included: (1) the re-calculation and further extension of TD50 values in mmol/kg body weight for chemicals carcinogenic in rodents. This part further included the checking up data for Swain-Scott s-values and the use of the covalent binding index (CBI); (2) the elaboration of genetic toxicity including an analysis of induced mutation spectra in specific genes at the DNA level, i.e., the vermilion gene of Drosophila, a plasmid system (pX2 assay) and the HPRT gene in cultured mammalian cells (CHO-9); and (3) the measurement of specific DNA alkylation adducts in animal models (mouse, rat, hamster) and mammalian cells in culture. The analysis of mechanisms controlling the expression of mammalian DNA repair genes (alkyltransferases, glycosylases) as a function of the cell type, differentiation stage, and cellular microenvironment in mammalian cells. The 3 classes of genotoxic carcinogens selected for the project were: (1) chemicals forming monoalkyl adducts upon interaction with DNA; (2) genotoxins capable of forming DNA etheno-adducts; and (3) N-substituted aryl compounds forming covalent adducts at the C8 position of guanine in DNA. In general, clear SARs and AARs (activity-activity relationships) between physiochemical parameters (s-values, O6/N7-alkylguanine ratios, CBI), carcinogenic potency in rodents and several descriptors of genotoxic activity in germ cells (mouse, Drosophila) became apparent when

  3. Structure-photodynamic activity relationships of substituted zinc trisulfophthalocyanines.

    PubMed

    Cauchon, Nicole; Tian, Hongjian; Langlois, Réjean; La Madeleine, Carole; Martin, Stephane; Ali, Hasrat; Hunting, Darel; van Lier, Johan E

    2005-01-01

    To identify optimal features of metalated sulfophthalocyanine dyes for their use as photosensitizers in the photodynamic therapy of cancer, we synthesized a series of alkynyl-substituted trisulfonated phthalocyanines and compared their amphiphilic properties to a number of parameters related to their photodynamic potency. Varying the length of the substituted alkynyl side-chain modulates the hydrophobic/hydrophilic properties of the dyes providing a linear relationship between their n-octanol/water partition coefficients and retention times on reversed-phase HPLC. Aggregate formation of the dyes in aqueous solution increased with increasing hydrophobicity while monomer formation was favored by the addition of serum proteins or organic solvent. Trisulfonated zinc phthalocyanines bearing hexynyl and nonynyl substituents exhibited high cellular uptake with strong localization at the mitochondrial membranes, which coincided with effective photocytotoxicity toward EMT-6 murine mammary tumor cells. Further increase in the length of the alkynyl chains (dodecynyl, hexadecynyl) did not improve their phototoxicity, likely resulting from extensive aggregation of the dyes in aqueous medium and reduced cell uptake. Aggregation was evident from shifts in the electronic spectra and reduced capacity to generate singlet oxygen. When monomerized through the addition of Cremophor EL all sulfonated zinc phthalocyanines gave similar singlet oxygen yields. Accordingly, differences in the tendency of the dyes to aggregate do not appear to be a determining factor in their photodynamic potency. Our results confirm that the latter in particular relates to their amphiphilic properties, which facilitate cell uptake and intracellular localization at photosensitive sites such as the mitochondria. Combined, these factors play a significant role in the overall photodynamic potency of the dyes.

  4. 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.

  5. Hi-res SAR data processing report

    NASA Astrophysics Data System (ADS)

    Lyzenga, D. R.; Malinas, N. P.; Pantalone, P. A.; Wackerman, C. C.

    1995-01-01

    This report summarizes the digital processing activities which have been carried out on the SAR data sets collected during the two ONR/NRL High Resolution field experiments held in September 1991 and June 1993. Features associated with the Gulf Stream boundary are observed in these data sets, with signatures that are dependent on the wind speed, radar frequency and polarization. Estimation of currents using the displacement of features observed on multiple passes appears to be possible. A simplified procedure for large-scale INSAR data processing has been developed and applied to one of the data sets collected in June 1993. Preliminary comparisons with OSCR measurements indicate that similar features are observed in both data sets. A capability was also developed during this contract to plot image locations on a Transverse Mercator map using the navigation data and radar operating parameters recorded on the P3 engineering data disks.

  6. The quinobenzoxazines: relationship between DNA binding and biological activity.

    PubMed

    Kwok, Y; Sun, D; Clement, J J; Hurley, L H

    1999-10-01

    The quinobenzoxazine compounds, derived from antibacterial quinolones, is active in vitro and in vivo against murine and human tumors. In this contribution, we show that the relative DNA binding affinity of the quinobenzoxazine compounds correlates with their cytotoxicity, their ability to inhibit gyrase-DNA complex formation, and the decatenation of kinetoplast DNA by human topoisomerase II. DNA binding studies with the descarboxy-A-62176 analogue indicate that the beta-keto acid moiety of the quinobenzoxazine compounds plays an important role in their interaction with DNA.

  7. 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.

  8. Identification of general linear relationships between activation energies and enthalpy changes for dissociation reactions at surfaces.

    PubMed

    Michaelides, Angelos; Liu, Z-P; Zhang, C J; Alavi, Ali; King, David A; Hu, P

    2003-04-02

    The activation energy to reaction is a key quantity that controls catalytic activity. Having used ab inito calculations to determine an extensive and broad ranging set of activation energies and enthalpy changes for surface-catalyzed reactions, we show that linear relationships exist between dissociation activation energies and enthalpy changes. Known in the literature as empirical Brønsted-Evans-Polanyi (BEP) relationships, we identify and discuss the physical origin of their presence in heterogeneous catalysis. The key implication is that merely from knowledge of adsorption energies the barriers to catalytic elementary reaction steps can be estimated.

  9. [Physical education, health and physical activities: difficult relationships].

    PubMed

    Cogérino, Geneviève

    2016-06-08

    Physical education (PE) is an appropriate subject to investigate the links between physical activity (PA) and health. The current training of PE teachers tends to emphasize the link between PA and physical fitness, to the detriment of other health components. The occupational, environmental, cultural dimensions of PA are frequently overlooked. This article lists four topics related to PA-health links, which could be more extensively included in initial PE teacher training, on the basis of abundant scientific literature: 1. the diversity of exercise motives, according to the subject’s age, gender, ability, competence, living conditions, etc.; 2. the role of body image on the desire or reluctance of teenagers to perform PA or certain physical activities; 3. the evolution of motivations towards PA throughout life; 4. the impact of the PE teachers’ masculinist conceptions, consubstantial of PE, due to its link with sport. These topics could contribute to a better analysis of what individuals seek through PA and the PA-health links they value. They could help teachers to adjust their teaching to contribute to the pupils’ health and not solely their physical fitness..

  10. 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

  11. 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.

  12. 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.

  13. Quantitative structure-activity relationship and molecular docking revealed a potency of anti-hepatitis C virus drugs against human corona viruses.

    PubMed

    Elfiky, Abdo A; Mahdy, Samah M; Elshemey, Wael M

    2016-11-19

    A number of human coronaviruses (HCoVs) were reported in the last and present centuries. Some outbreaks of which (eg, SARS and MERS CoVs) caused the mortality of hundreds of people worldwide. The problem of finding a potent drug against HCoV strains lies in the inability of finding a drug that stops the viral replication through inhibiting its important proteins. In spite of its limited efficacy and potential side effects, Ribavirin is extensively used as a first choice against HCoVs. Therefore, scientists reverted towards the investigation of different drugs that can more specifically target proteins. In this study, four anti-HCV drugs (one approved by FDA and others under clinical trials) are tested against HCoV polymerases. Quantitative Structure-Activity Relationship (QSAR) and molecular docking are both used to compare the performance of the selected nucleotide inhibitors to their parent nucleotides and Ribavirin. Both QSAR and molecular docking showed that IDX-184 is superior compared to Ribavirin against MERS CoV, a result that was also reported for HCV. MK-0608 showed a performance that is comparable to Ribavirin. We strongly suggest an in vitro study on the potency of these two drugs against MERS CoV.

  14. 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

  15. 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.

  16. Structure-activity relationships of semisynthetic mumbaistatin analogs.

    PubMed

    Lee, Taek Soon; Das, Abhirup; Khosla, Chaitan

    2007-08-01

    Mumbaistatin (1), a new anthraquinone natural product, is one of the most potent known inhibitors of hepatic glucose-6-phosphate translocase, an important target for the treatment of type II diabetes. Its availability, however, has been limited due to its extremely low yield from the natural source. Starting from DMAC (5, 3,8-dihydroxyanthraquinone-2-carboxylic acid), a structurally related polyketide product of engineered biosynthesis, we developed a facile semisynthetic method that afforded a variety of mumbaistatin analogs within five steps. This work was facilitated by the initial development of a DMAC overproduction system. In addition to reinforcing the biological significance of the anthraquinone moiety of mumbaistatin, several semisynthetic analogs were found to have low micromolar potency against the translocase in vitro. Two of them were also active in glucose release assays from primary hepatocytes. The synergistic combination of biosynthesis and synthesis is a promising avenue for the discovery of new bioactive substances.

  17. 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

  18. Synthesis, photodynamic activity, and quantitative structure-activity relationship modelling of a series of BODIPYs.

    PubMed

    Caruso, Enrico; Gariboldi, Marzia; Sangion, Alessandro; Gramatica, Paola; Banfi, Stefano

    2017-02-01

    Here we report the synthesis of eleven new BODIPYs (14-24) characterized by the presence of an aromatic ring on the 8 (meso) position and of iodine atoms on the pyrrolic 2,6 positions. These molecules, together with twelve BODIPYs already reported by us (1-12), represent a large panel of BODIPYs showing different atoms or groups as substituent of the aromatic moiety. Two physico-chemical features ((1)O2 generation rate and lipophilicity), which can play a fundamental role in the outcome as photosensitizers, have been studied. The in vitro photo-induced cell-killing efficacy of 23 PSs was studied on the SKOV3 cell line treating the cells for 24h in the dark then irradiating for 2h with a green LED device (fluence 25.2J/cm(2)). The cell-killing efficacy was assessed with the MTT test and compared with that one of meso un-substituted compound (13). In order to understand the possible effect of the substituents, a predictive quantitative structure-activity relationship (QSAR) regression model, based on theoretical holistic molecular descriptors, was developed. The results clearly indicate that the presence of an aromatic ring is fundamental for an excellent photodynamic response, whereas the electronic effects and the position of the substituents on the aromatic ring do not influence the photodynamic efficacy.

  19. 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.

  20. Relationships between pupil diameter and neuronal activity in the locus coeruleus, colliculi, and cingulate cortex

    PubMed Central

    Joshi, Siddhartha; Li, Yin; Kalwani, Rishi; Gold, Joshua I.

    2015-01-01

    SUMMARY Changes in pupil diameter that reflect effort and other cognitive factors are often interpreted in terms of the activity of norepinephrine-containing neurons in the brainstem nucleus locus coeruleus (LC), but there is little direct evidence for such a relationship. Here we show that LC activation reliably anticipates changes in pupil diameter that either fluctuate naturally or are driven by external events during near fixation, as in many psychophysical tasks. This relationship occurs on as fine a temporal and spatial scale as single spikes from single units. However, this relationship is not specific to the LC. Similar relationships, albeit with delayed timing and different reliabilities across sites, are evident in the inferior and superior colliculus and anterior and posterior cingulate cortex. Because these regions are interconnected with the LC, the results suggest that non-luminance-mediated changes in pupil diameter might reflect LC-mediated coordination of neuronal activity throughout some parts of the brain. PMID:26711118