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Sample records for activity relationships sars

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

    EPA Science Inventory

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

  2. 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.

  3. STRUCTURE-ACTIVITY RELATIONSHIPS (SARS) AMONG MUTAGENS AND CARCINOGENS: A REVIEW

    EPA Science Inventory

    The review is an introduction to methods for evaluating structure-activity relationships (SARs), and, in particular, to those methods that have been applied to study mutagenicity and carcinogenicity. A brief history and some background material on the earliest attempts to correla...

  4. 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

  5. HomoSAR: bridging comparative protein modeling with quantitative structural activity relationship to design new peptides.

    PubMed

    Borkar, Mahesh R; Pissurlenkar, Raghuvir R S; Coutinho, Evans C

    2013-11-15

    Peptides play significant roles in the biological world. To optimize activity for a specific therapeutic target, peptide library synthesis is inevitable; which is a time consuming and expensive. Computational approaches provide a promising way to simply elucidate the structural basis in the design of new peptides. Earlier, we proposed a novel methodology termed HomoSAR to gain insight into the structure activity relationships underlying peptides. Based on an integrated approach, HomoSAR uses the principles of homology modeling in conjunction with the quantitative structural activity relationship formalism to predict and design new peptide sequences with the optimum activity. In the present study, we establish that the HomoSAR methodology can be universally applied to all classes of peptides irrespective of sequence length by studying HomoSAR on three peptide datasets viz., angiotensin-converting enzyme inhibitory peptides, CAMEL-s antibiotic peptides, and hAmphiphysin-1 SH3 domain binding peptides, using a set of descriptors related to the hydrophobic, steric, and electronic properties of the 20 natural amino acids. Models generated for all three datasets have statistically significant correlation coefficients (r(2)) and predictive r2 (r(pred)2) and cross validated coefficient ( q(LOO)2). The daintiness of this technique lies in its simplicity and ability to extract all the information contained in the peptides to elucidate the underlying structure activity relationships. The difficulties of correlating both sequence diversity and variation in length of the peptides with their biological activity can be addressed. The study has been able to identify the preferred or detrimental nature of amino acids at specific positions in the peptide sequences. PMID:24105965

  6. 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. PMID:17077558

  7. Structure-activity relationships (SAR) and structure-kinetic relationships (SKR) of bicyclic heteroaromatic acetic acids as potent CRTh2 antagonists II: lead optimization.

    PubMed

    Alonso, Juan Antonio; Andrés, Miriam; Bravo, Mónica; Calbet, Marta; Eastwood, Paul R; Eichhorn, Peter; Esteve, Cristina; Ferrer, Manel; Gómez, Elena; González, Jacob; Mir, Marta; Moreno, Imma; Petit, Silvia; Roberts, Richard S; Sevilla, Sara; Vidal, Bernat; Vidal, Laura; Vilaseca, Pere; Zanuy, Miriam

    2014-11-01

    Extensive structure-activity relationship (SAR) and structure-kinetic relationship (SKR) studies in the bicyclic heteroaromatic series of CRTh2 antagonists led to the identification of several molecules that possessed both excellent binding and cellular potencies along with long receptor residence times. A small substituent in the bicyclic core provided an order of magnitude jump in dissociation half-lives. Selected optimized compounds demonstrated suitable pharmacokinetic profiles. PMID:25437505

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

    PubMed

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

    2013-06-28

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

  9. Benzoxazolone Carboxamides as Potent Acid Ceramidase Inhibitors: Synthesis and Structure-Activity Relationship (SAR) Studies.

    PubMed

    Bach, Anders; Pizzirani, Daniela; Realini, Natalia; Vozella, Valentina; Russo, Debora; Penna, Ilaria; Melzig, Laurin; Scarpelli, Rita; Piomelli, Daniele

    2015-12-10

    Ceramides are lipid-derived intracellular messengers involved in the control of senescence, inflammation, and apoptosis. The cysteine amidase, acid ceramidase (AC), hydrolyzes these substances into sphingosine and fatty acid and, by doing so, regulates their signaling activity. AC inhibitors may be useful in the treatment of pathological conditions, such as cancer, in which ceramide levels are abnormally reduced. Here, we present a systematic SAR investigation of the benzoxazolone carboxamides, a recently described class of AC inhibitors that display high potency and systemic activity in mice. We examined a diverse series of substitutions on both benzoxazolone ring and carboxamide side chain. Several modifications enhanced potency and stability, and one key compound with a balanced activity-stability profile (14) was found to inhibit AC activity in mouse lungs and cerebral cortex after systemic administration. The results expand our arsenal of AC inhibitors, thereby facilitating the use of these compounds as pharmacological tools and their potential development as drug leads. PMID:26560855

  10. Potent α-amino-β-lactam carbamic acid ester as NAAA inhibitors. Synthesis and structure-activity relationship (SAR) studies.

    PubMed

    Nuzzi, Andrea; Fiasella, Annalisa; Ortega, Jose Antonio; Pagliuca, Chiara; Ponzano, Stefano; Pizzirani, Daniela; Bertozzi, Sine Mandrup; Ottonello, Giuliana; Tarozzo, Glauco; Reggiani, Angelo; Bandiera, Tiziano; Bertozzi, Fabio; Piomelli, Daniele

    2016-03-23

    4-Cyclohexylbutyl-N-[(S)-2-oxoazetidin-3-yl]carbamate (3b) is a potent, selective and systemically active inhibitor of intracellular NAAA activity, which produces profound anti-inflammatory effects in animal models. In the present work, we describe structure-activity relationship (SAR) studies on 3-aminoazetidin-2-one derivatives, which have led to the identification of 3b, and expand these studies to elucidate the principal structural and stereochemical features needed to achieve effective NAAA inhibition. Investigations on the influence of the substitution at the β-position of the 2-oxo-3-azetidinyl ring as well as on the effect of size and shape of the carbamic acid ester side chain led to the discovery of 3ak, a novel inhibitor of human NAAA that shows an improved physicochemical and drug-like profile relative to 3b. This favourable profile, along with the structural diversity of the carbamic acid chain of 3b, identify this compound as a promising new tool to investigate the potential of NAAA inhibitors as therapeutic agents for the treatment of pain and inflammation. PMID:26866968

  11. Oximes: Inhibitors of Human Recombinant Acetylcholinesterase. A Structure-Activity Relationship (SAR) Study

    PubMed Central

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

    2013-01-01

    Acetylcholinesterase (AChE) reactivators were developed for the treatment of organophosphate intoxication. Standard care involves the use of anticonvulsants (e.g., diazepam), parasympatolytics (e.g., atropine) and oximes that restore AChE activity. However, oximes also bind to the active site of AChE, simultaneously acting as reversible inhibitors. The goal of the present study is to determine how oxime structure influences the inhibition of human recombinant AChE (hrAChE). Therefore, 24 structurally different oximes were tested and the results compared to the previous eel AChE (EeAChE) experiments. Structural factors that were tested included the number of pyridinium rings, the length and structural features of the linker, and the number and position of the oxime group on the pyridinium ring. PMID:23959117

  12. Structure-activity relationships (SAR) and structure-kinetic relationships (SKR) of pyrrolopiperidinone acetic acids as CRTh2 antagonists.

    PubMed

    Andrés, Miriam; Buil, Maria Antonia; Calbet, Marta; Casado, Oscar; Castro, Jordi; Eastwood, Paul R; Eichhorn, Peter; Ferrer, Manel; Forns, Pilar; Moreno, Imma; Petit, Silvia; Roberts, Richard S

    2014-11-01

    Pyrrolopiperidinone acetic acids (PPAs) were identified as highly potent CRTh2 receptor antagonists. In addition, many of these compounds displayed slow-dissociation kinetics from the receptor. Structure-kinetic relationship (SKR) studies allowed optimisation of the kinetics to give potent analogues with long receptor residence half-lives of up to 23 h. Low permeability was a general feature of this series, however oral bioavailability could be achieved through the use of ester prodrugs. PMID:25437503

  13. 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

  14. 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. PMID:26111809

  15. Inhibition of monoamine oxidase-A activity in rat brain by synthetic hydrazines: structure-activity relationship (SAR).

    PubMed

    Dar, Ahsana; Khan, Khalid M; Ateeq, Humayun S; Khan, Shagufta; Rahat, Shagufta; Perveen, Shahnaz; Supuran, Claudiu T

    2005-06-01

    A series of hydrazine derivatives was synthesized in order to evaluate their monoamine oxidase A (MAO-A) inhibitory effects. MAO-A inhibitory activity of 4-tosyl benzoic acid carbohydrazide was quite potent, similarly to that of the corresponding 4-benzyloxy-benzoic acid carbohydrazide and its N-cyanoethylated derivative. Structural variations of these compounds, such as the replacement of the 4-substitutent, of the aromatic ring on which the carbohydrazide moiety is grafted, as well as cyclization of the hydrazide moiety in five- or six-membered rings caused either significant decline or complete loss of MAO inhibitory properties. The most active compound (4-tosyl benzoic acid carbohydrazide) was also subjected to the forced swim test, an animal model of depression, eliciting a marked reduction in immobility time in rats, without affecting the locomotor activity, implying that it possesses anti-depressant properties due to inhibition of MAO type-A. PMID:16119198

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

    PubMed

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

    2015-08-01

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

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

    PubMed Central

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

    1990-01-01

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

  18. 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

  19. Structure-activity relationships (SAR) and structure-kinetic relationships (SKR) of bicyclic heteroaromatic acetic acids as potent CRTh2 antagonists I.

    PubMed

    Alonso, Juan Antonio; Andrés, Miriam; Bravo, Mónica; Buil, Maria Antonia; Calbet, Marta; Castro, Jordi; Eastwood, Paul R; Eichhorn, Peter; Esteve, Cristina; Gómez, Elena; González, Jacob; Mir, Marta; Petit, Silvia; Roberts, Richard S; Vidal, Bernat; Vidal, Laura; Vilaseca, Pere; Zanuy, Miriam

    2014-11-01

    A knowledge-based design strategy led to the discovery of several new series of potent and orally bioavailable CRTh2 antagonists where a bicyclic heteroaromatic ring serves as the central core. Structure-kinetic relationships (SKR) opened up the possibility of long receptor residence times. PMID:25437504

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

    PubMed Central

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

    2015-01-01

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

  1. 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. PMID:14620481

  2. 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...

  3. TerraSAR InSAR Investigation of Active Crustal Deformation

    NASA Astrophysics Data System (ADS)

    Lei, L.; Burgmann, R.

    2009-12-01

    We aim to utilize advanced analysis of TerraSAR-X data to investigate the dynamics and interactions of solid Earth deformation processes, such as earthquakes and fault creep, and Earth surface processes, such as land subsidence and groundwater movements, in a densely populated, urban region, the San Francisco Bay Area. Ongoing deformation imaging reveals a number of natural hazards including elastic strain accumulation about seismologic faults, active landsliding, land subsidence and rebound, and settling of unconsolidated sediments that are highly susceptible to liquefaction. Up to now, we have ordered and received 20 more TerraSAR-X Spotlight Single Look Complex (SLC) images and a few Stripmap SLC images delivered by DLR and got a few preliminary results. The TerraSAR-X images were acquired over the San Francisco Bay Area particularly around an area of active landsliding, coastal subsidence and shallow Hayward fault creep near the city of Berkeley. Berkeley is situated between latitude 37.45 and 38.00, longitude 237.30 and 238.00. The data acquisition interval is from November, 2008 to now. Four types of Spotlight images and one type of Stripmap images in time sequence were ordered and acquired: spot_012, spot_038, spot_049, spot_075 and strip_003, having different look angles and pass directions. Access to the SAR data is via ftp about 10 days after acquisition date. The data is supplied in TerraSAR-X standard SLC COSAR (COmplex SAR) format with orbital information in an Extensible Markup Language (XML) header. The file contains integer real-complex components with double sampling and calibration constants for values. I am using ROI_PAC to do the interferograms. But ROI_PAC was designed to process the raw data rather SLC images. So there are some problems in azimuth processing with TerraSAR SLC data especially the Spotlight data. We now have some preliminary results of Stripmap interferograms and Spotlight interferograms but still work on those problems and

  4. 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

  5. 76 FR 20822 - Proposed Information Collection (Servicer's Staff Appraisal Reviewer (SAR) Application) Activity...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-13

    ... AFFAIRS Proposed Information Collection (Servicer's Staff Appraisal Reviewer (SAR) Application) Activity... (SAR) Application, VA Form 26-0829. OMB Control Number: 2900-0715. Type of Review: Extension of a... approval as Staff Appraisal Reviewer (SAR). Servicers SAR's will have the authority to review real...

  6. 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.

  7. 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...

  8. CONSIDERATION OF REACTION INTERMEDIATES IN STRUCTURE-ACTIVITY RELATIONSHIPS: A KEY TO UNDERSTANDING AND PREDICTION

    EPA Science Inventory

    Consideration of Reaction Intermediates in Structure- Activity Relationships: A Key to Understanding and Prediction

    A structure-activity relationship (SAR) represents an empirical means for generalizing chemical information relative to biological activity, and is frequent...

  9. 76 FR 8847 - Proposed Information Collection (Lenders Staff Appraisal Reviewer (SAR) Application) Activity...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-15

    ... AFFAIRS Proposed Information Collection (Lenders Staff Appraisal Reviewer (SAR) Application) Activity...: Lenders Staff Appraisal Reviewer (SAR) Application, VA Form 26-0785. OMB Control Number: 2900-0658. Type... lenders to nominate employees for approval as approved Staff Appraisal Reviewer (SAR). Once approved,...

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

    PubMed

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

    2009-10-01

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

  11. Structure-activity relationship of crustacean peptide hormones.

    PubMed

    Katayama, Hidekazu

    2016-04-01

    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. PMID:26624010

  12. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2014-12-01

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

  14. 76 FR 35949 - Agency Information Collection Activity (Servicer's Staff Appraisal Reviewer (SAR) Application...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-20

    ... AFFAIRS Agency Information Collection Activity (Servicer's Staff Appraisal Reviewer (SAR) Application....'' SUPPLEMENTARY INFORMATION: ] Title: Servicer's Staff Appraisal Reviewer (SAR) Application, VA Form 26-0829. OMB... 26-0829 is completed by servicers to nominate employees for approval as Staff Appraisal Reviewer...

  15. Ecological Structure Activity Relationships

    EPA Science Inventory

    Ecological Structure Activity Relationships, v1.00a, February 2009
    ECOSAR (Ecological Structure Activity Relationships) is a personal computer software program that is used to estimate the toxicity of chemicals used in industry and discharged into water. The program predicts...

  16. 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

  17. 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. PMID:24803014

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

    PubMed

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

    2016-02-01

    Sap-feeding insect pests constitute a major insect pest complex that includes a range of aphids, whiteflies, planthoppers and other insect species. Sulfoxaflor (Isoclast™ active), a new sulfoximine class insecticide, targets sap-feeding insect pests including those resistant to many other classes of insecticides. A structure activity relationship (SAR) investigation of the sulfoximine insecticides revealed the importance of a 3-pyridyl ring and a methyl substituent on the methylene bridge linking the pyridine and the sulfoximine moiety to achieving strong Myzus persicae activity. A more in depth QSAR investigation of pyridine ring substituents revealed a strong correlation with the calculated logoctanol/water partition coefficient (SlogP). Model development resulted in a highly predictive model for a set of 18 sulfoximines including sulfoxaflor. The model is consistent with and helps explain the highly optimized pyridine substitution pattern for sulfoxaflor. PMID:26706115

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

    PubMed

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

    2015-01-01

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

  20. 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.

  1. Sar1 GTPase Activity Is Regulated by Membrane Curvature*♦

    PubMed Central

    Hanna, Michael G.; Mela, Ioanna; Wang, Lei; Henderson, Robert M.; Chapman, Edwin R.; Edwardson, J. Michael; Audhya, Anjon

    2016-01-01

    The majority of biosynthetic secretory proteins initiate their journey through the endomembrane system from specific subdomains of the endoplasmic reticulum. At these locations, coated transport carriers are generated, with the Sar1 GTPase playing a critical role in membrane bending, recruitment of coat components, and nascent vesicle formation. How these events are appropriately coordinated remains poorly understood. Here, we demonstrate that Sar1 acts as the curvature-sensing component of the COPII coat complex and highlight the ability of Sar1 to bind more avidly to membranes of high curvature. Additionally, using an atomic force microscopy-based approach, we further show that the intrinsic GTPase activity of Sar1 is necessary for remodeling lipid bilayers. Consistent with this idea, Sar1-mediated membrane remodeling is dramatically accelerated in the presence of its guanine nucleotide-activating protein (GAP), Sec23-Sec24, and blocked upon addition of guanosine-5′-[(β,γ)-imido]triphosphate, a poorly hydrolysable analog of GTP. Our results also indicate that Sar1 GTPase activity is stimulated by membranes that exhibit elevated curvature, potentially enabling Sar1 membrane scission activity to be spatially restricted to highly bent membranes that are characteristic of a bud neck. Taken together, our data support a stepwise model in which the amino-terminal amphipathic helix of GTP-bound Sar1 stably penetrates the endoplasmic reticulum membrane, promoting local membrane deformation. As membrane bending increases, Sar1 membrane binding is elevated, ultimately culminating in GTP hydrolysis, which may destabilize the bilayer sufficiently to facilitate membrane fission. PMID:26546679

  2. 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.

  3. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2015-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2014-10-01

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

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

    PubMed

    Dimova, Dilyana; Stumpfe, Dagmar; Bajorath, Jürgen

    2014-08-14

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

  7. Structure-activity Relationship Analysis of N-Benzoylpyrazoles for Elastase Inhibitory Activity: A Simplified Approach Using Atom Pair Descriptors

    PubMed Central

    Khlebnikov, Andrei I.; Schepetkin, Igor A.; Quinn, Mark T.

    2008-01-01

    Previously, we utilized high throughput screening of a chemical diversity library to identify potent inhibitors of human neutrophil elastase and found that many of these compounds had N-benzoylpyrazole core structures. We also found individual ring substituents had significant impact on elastase inhibitory activity and compound stability. In the present study, we utilized computational structure–activity relationship (SAR) analysis of a series of 53 N-benzoylpyrazole derivatives to further optimize these lead molecules. We present an improved approach to SAR methodology based on atom pair descriptors in combination with 2-dimentional (2D) molecular descriptors. This approach utilizes the rich representation of chemical structure and leads to SAR analysis that is both accurate and intuitively easy to understand. A sequence of ANOVA, linear discriminant, and binary classification tree analyses of the molecular descriptors led to the derivation of SAR rule-based algorithms. These rules revealed that the main factors influencing elastase inhibitory activity of N-benzoylpyrazole molecules were the presence of methyl groups in the pyrazole moiety and ortho-substituents in the benzoyl radical. Furthermore, our data showed that physicochemical characteristics (energy of frontier molecular orbitals, molar refraction, lipophilicity) were not necessary for achieving good SAR, as comparable quality of SAR classification was obtained with atom pairs and 2D descriptors only. This simplified SAR approach may be useful to qualitative SAR recognition problems in a variety of data sets. PMID:18234502

  8. Structure-activity relationship analysis of N-benzoylpyrazoles for elastase inhibitory activity: a simplified approach using atom pair descriptors.

    PubMed

    Khlebnikov, Andrei I; Schepetkin, Igor A; Quinn, Mark T

    2008-03-15

    Previously, we utilized high throughput screening of a chemical diversity library to identify potent inhibitors of human neutrophil elastase and found that many of these compounds had N-benzoylpyrazole core structures. We also found individual ring substituents had significant impact on elastase inhibitory activity and compound stability. In the present study, we utilized computational structure-activity relationship (SAR) analysis of a series of 53 N-benzoylpyrazole derivatives to further optimize these lead molecules. We present an improved approach to SAR methodology based on atom pair descriptors in combination with 2-dimensional (2D) molecular descriptors. This approach utilizes the rich representation of chemical structure and leads to SAR analysis that is both accurate and intuitively easy to understand. A sequence of ANOVA, linear discriminant, and binary classification tree analyses of the molecular descriptors led to the derivation of SAR rule-based algorithms. These rules revealed that the main factors influencing elastase inhibitory activity of N-benzoylpyrazole molecules were the presence of methyl groups in the pyrazole moiety and ortho-substituents in the benzoyl radical. Furthermore, our data showed that physicochemical characteristics (energy of frontier molecular orbitals, molar refraction, lipophilicity) were not necessary for achieving good SAR, as comparable quality of SAR classification was obtained with atom pairs and 2D descriptors only. This simplified SAR approach may be useful to qualitative SAR recognition problems in a variety of data sets. PMID:18234502

  9. 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.

  10. SARS Coronavirus 3b Accessory Protein Modulates Transcriptional Activity of RUNX1b

    PubMed Central

    Varshney, Bhavna; Agnihotram, Sudhakar; Tan, Yee-Joo; Baric, Ralph; Lal, Sunil K.

    2012-01-01

    Background The causative agent of severe acute respiratory syndrome, SARS coronavirus (SARS-CoV) genome encodes several unique group specific accessory proteins with unknown functions. Among them, accessory protein 3b (also known as ORF4) was lately identified as one of the viral interferon antagonist. Recently our lab uncovered a new role for 3b in upregulation of AP-1 transcriptional activity and its downstream genes. Thus, we believe that 3b might play an important role in SARS-CoV pathogenesis and therefore is of considerable interest. The current study aims at identifying novel host cellular interactors of the 3b protein. Methodology/Principal Findings In this study, using yeast two-hybrid and co-immunoprecipitation techniques, we have identified a host transcription factor RUNX1b (Runt related transcription factor, isoform b) as a novel interacting partner for SARS-CoV 3b protein. Chromatin immunoprecipitaion (ChIP) and reporter gene assays in 3b expressing jurkat cells showed recruitment of 3b on the RUNX1 binding element that led to an increase in RUNX1b transactivation potential on the IL2 promoter. Kinase assay and pharmacological inhibitor treatment implied that 3b also affect RUNX1b transcriptional activity by regulating its ERK dependent phosphorylation levels. Additionally, mRNA levels of MIP-1α, a RUNX1b target gene upregulated in SARS-CoV infected monocyte-derived dendritic cells, were found to be elevated in 3b expressing U937 monocyte cells. Conclusions/Significance These results unveil a novel interaction of SARS-CoV 3b with the host factor, RUNX1b, and speculate its physiological relevance in upregulating cytokines and chemokine levels in state of SARS virus infection. PMID:22253733

  11. Identification and SAR Evaluation of Hemozoin-Inhibiting Benzamides Active against Plasmodium falciparum.

    PubMed

    Wicht, Kathryn J; Combrinck, Jill M; Smith, Peter J; Hunter, Roger; Egan, Timothy J

    2016-07-14

    Quinoline antimalarials target hemozoin formation causing a cytotoxic accumulation of ferriprotoporphyrin IX (Fe(III)PPIX). Well-developed SAR models exist for β-hematin inhibition, parasite activity, and cellular mechanisms for this compound class, but no comparably detailed investigations exist for other hemozoin inhibiting chemotypes. Here, benzamide analogues based on previous HTS hits have been purchased or synthesized. Only derivatives containing an electron deficient aromatic ring and capable of adopting flat conformations, optimal for π-π interactions with Fe(III)PPIX, inhibited β-hematin formation. The two most potent analogues showed nanomolar parasite activity, with little CQ cross-resistance, low cytotoxicity, and high in vitro microsomal stability. Selected analogues inhibited hemozoin formation in Plasmodium falciparum causing high levels of free heme. In contrast to quinolines, introduction of amine side chains did not lead to benzamide accumulation in the parasite. These data reveal complex relationships between heme binding, free heme levels, cellular accumulation, and in vitro activity of potential novel antimalarials. PMID:27299916

  12. 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.

  13. 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

  14. 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.

  15. Active extreme learning machines for quad-polarimetric SAR imagery classification

    NASA Astrophysics Data System (ADS)

    Samat, Alim; Gamba, Paolo; Du, Peijun; Luo, Jieqiong

    2015-03-01

    Supervised classification of quad-polarimetric SAR images is often constrained by the availability of reliable training samples. Active learning (AL) provides a unique capability at selecting samples with high representation quality and low redundancy. The most important part of AL is the criterion for selecting the most informative candidates (pixels) by ranking. In this paper, class supports based on the posterior probability function are approximated by ensemble learning and majority voting. This approximation is statistically meaningful when a large enough classifier ensemble is exploited. In this work, we propose to use extreme learning machines and apply AL to quad-polarimetric SAR image classification. Extreme learning machines are ideal because of their fast operation, straightforward solution and strong generalization. As inputs to the so-called active extreme learning machines, both polarimetric and spatial features (morphological profiles) are considered. In order to validate the proposed method, results and performance are compared with random sampling and state-of-the-art AL methods, such as margin sampling, normalized entropy query-by-bagging and multiclass level uncertainty. Experimental results for four quad-polarimetric SAR images collected by RADARSAT-2, AirSAR and EMISAR indicate that the proposed method achieves promising results in different scenarios. Moreover, the proposed method is faster than existing techniques in both the learning and the classification phases.

  16. 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.

  17. 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.

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

    PubMed Central

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

    2015-01-01

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

  19. Active landslides detection at regional scale: comparing multitemporal InSAR with "handmade" inventories

    NASA Astrophysics Data System (ADS)

    Derron, Marc-Henri; Michoud, Clément; Jaboyedoff, Michel; Runne Lauknes, Tom

    2013-04-01

    Advanced multitemporal differential SAR interferometry has proved to be able to detect unexpected active landslides in areas difficult to access. That makes this technique very useful to complete inventories. But that does not mean that applying A-DInSAR is a sufficient tool to build an inventory. Some A-DInSAR results have been compared in areas where independent landslides inventories exists, in Norway (J. Dehls at the Geological Survey of Norway) and Italy (A. Tamburini, TRE Milano). Roughly, depending on the surface cover, geomorphology and images availability, from 0 to 50% of the already known landslides can be detected with A-DInSAR results. We are testing a similar approach in Switzerland, in the county of Vaud where two landslides inventories are available (DUTI 1985, Jaboyedoff 2009). A set of 24 Envisat ASAR images (single frame/ single track) have been processed with PS-INSAR and SBAS techniques. Because of the large variety of surface cover (urban, forested, rocky) and morphology (plane and mountainous areas), both techniques provides very different results depending on local conditions.

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

    NASA Astrophysics Data System (ADS)

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

    2013-05-01

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

  1. The relationship between localised SAR in the arm and wrist current.

    PubMed

    Dimbylow, P J

    2001-01-01

    Calculations are presented of the specific energy absorption rate, SAR, in the lower arm of the NRPB anatomically realistic voxel model. NORMAN, for induced currents from 100 kHz to 80 MHz. The wrist region has a narrow cross section and contains little high conductivity muscle, comprising mainly low conductivity bone, tendon and fat. Consequently there is a channelling of the current through the high conductivity muscle, which produces high, localised values of the SAR. Values averaged over 10 g and 100 g of tissue are calculated as a function of the current flowing through the wrist. PMID:11572647

  2. 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

  3. 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.

  4. 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}.

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

    NASA Astrophysics Data System (ADS)

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

    2016-09-01

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

  6. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2014-09-01

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

  8. Synthesis and Structure Activity Relationship of 3-Hydroxypyridin-2-thione Based Histone Deacetylase Inhibitors

    PubMed Central

    Sodji, Quaovi H.; Patil, Vishal; Kornacki, James R.; Mrksich, Milan; Oyelere, Adegboyega K.

    2014-01-01

    We have previously identified 3-hydroxypyridin-2-thione (3HPT) as a novel zinc binding group for histone deacetylase (HDAC) inhibition. Early structure activity relationship (SAR) studies led to various small molecules possessing selective inhibitory activity against HDAC6 or HDAC8 but are devoid of HDAC1 inhibition. To further delineate the depth of the SAR of 3HPT-derived HDAC inhibitors (HDACi), we have extended the SAR studies to include the linker region and the surface recognition group to optimize the HDAC inhibition. The current efforts resulted in the identification of two lead compounds 10d and 14e with potent HDAC6 and HDAC8 activities, but that are inactive against HDAC1. These new HDACi possess anti-cancer activities against various cancer cell lines including Jurkat J-γ1 against which SAHA and the previously disclosed 3HPT-derived HDACi were inactive. PMID:24304348

  9. Synthesis, SAR and antibacterial activity of hybrid chloro, dichloro-phenylthiazolyl-s-triazines

    PubMed Central

    Gahtori, Prashant; Ghosh, Surajit Kumar; Singh, Brijesh; Singh, Udaya Pratap; Bhat, Hans Raj; Uppal, Archana

    2011-01-01

    A series of hybrid novel chloro (1a–9a) and dichloro (10b–18b) phenylthiazolyl-s-triazine were synthesized and subsequently subjected to their antibacterial activity against three gram positive viz. Lactobacillus casei (NCIM-2651); Bacillus cereus (NCIM-2458); Staphylococcus aureus (NCIM-2120) and three gram negative viz Salmonella typhimurium (NCIM-2501); Escherichia coli (NCIM-2065); Klebsiella aerogenes (NCIM-2098). The SAR studies around the lead compound revealed that introduction of electron withdrawing groups and amino (–NH–) and mercapto (–S–) linker bridge seemed more promising towards antibacterial activity. Moreover, the virtual Molinspiration screenings are in compliance with Ghose’s rule. PMID:23960775

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

    PubMed Central

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

    2016-01-01

    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. PMID:25401513

  11. Crustal-scale active deformation along the Ecuadorian Andes using Persistent Scatterers SAR Interferometry

    NASA Astrophysics Data System (ADS)

    Champenois, J.; Baize, S.; Audin, L.; Pinel, V.; Alvarado, A.; Jomard, H.; Yepes, H. A.

    2013-12-01

    Located in the Northern Andes along the active subduction zone of the Nazca plate beneath the South American continent, Ecuador is highly exposed to seismic hazard. For the last ten years, numerous multidisciplinary studies focused on major seismicity related to the subduction, whereas few investigations concentrated on M>7 crustal seismicity in the upper plate (like 1797 Riobamba earthquake, ML 8.3, 12.000 deaths). The active faults producing these earthquakes are poorly known in term of slip rate and for some cases are even not identified yet. Additionnally, Ecuador is one of the most active volcanic areas of the northern Andean volcanic zone. Three among the nine active volcanoes are actually erupting (Reventador, Tungurahua, and Sangay). For the last 5 years, geodetic networks have been deployed in Ecuador to enhance crustal deformation monitoring, but these point-wise techniques cannot provide spatially dense maps of ground deformation and are quite expensive methods. To address this issue, we applied the Persistent Scatterers SAR Interferometry technique (StaMPS/MTI freeware developed by A. Hooper) to ENVISAT SAR data between 2003 and 2009. Using these cost-effective techniques, we are able to investigate both tectonic and volcanic surface deformations with an unprecedented spatial density of measurements. This study presents new PS-InSAR results along the Ecuadorian Andes, close to the area of Riobamba. We generated average velocity maps and consistent time-series of displacements measured along the radar line of sight. These results evidence large scale deformation localized on the Pallatanga fault system (locked fault) compatible with a model of locked strike slip fault. Moreover, these results show an important growth of the Tungurahua volcanic complex (maximum rate about 9 mm/yr) with a rapid uplift prior and post 2006 explosive eruption. We investigate the time-series of displacement for 22 images. Our results permitted to propose two crustal source

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

    PubMed

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

    2015-01-01

    A continuing education (CE) course at the 2014 American College of Toxicology annual meeting covered the topic of (Quantitative) Structure-Activity Relationships [(Q)SAR]. The (Q)SAR methodologies use predictive computer modeling based on predefined rules to describe the relationship between chemical structure and a chemical's associated biological activity or statistical tools to find correlations between biologic activity and the molecular structure or properties of a compound. The (Q)SAR has applications in risk assessment, drug discovery, and regulatory decision making. Pressure within industry to reduce the cost of drug development and societal pressure for government regulatory agencies to produce more accurate and timely risk assessment of drugs and chemicals have necessitated the use of (Q)SAR. Producing a high-quality (Q)SAR model depends on many factors including the choice of statistical methods and descriptors, but first and foremost the quality of the data input into the model. Understanding how a (Q)SAR model is developed and applied is critical to the successful use of such a tool. The CE session covered the basic principles of (Q)SAR, practical applications of these computational models in toxicology, how regulatory agencies use and interpret (Q)SAR models, and potential pitfalls of using them. PMID:25979517

  13. 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. PMID:24710340

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

    PubMed Central

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

    2013-01-01

    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: 10 years of research on highly pathogenic human coronaviruses.” PMID:24121034

  15. In vivo structure-activity relationship studies support allosteric targeting of a dual specificity phosphatase.

    PubMed

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

    2014-07-01

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

  16. Syntheses, biological activities and SAR studies of novel carboxamide compounds containing piperazine and arylsulfonyl moieties.

    PubMed

    Wang, Bao-Lei; Shi, Yan-Xia; Zhang, Shu-Jun; Ma, Yi; Wang, Hong-Xue; Zhang, Li-Yuan; Wei, Wei; Liu, Xing-Hai; Li, Yong-Hong; Li, Zheng-Ming; Li, Bao-Ju

    2016-07-19

    A series of novel carboxamide compounds 19a-19j, 20a-20j and 22a-22d containing piperazine and arylsulfonyl moieties have been synthesized. The bioassay results showed that some compounds exhibited favorable herbicidal activities against dicotyledonous plants and many of them possessed excellent antifungal activities. Among 24 novel compounds, some showed superiority over the commercial fungicides Chlorothalonil, Dimethomorph, Thiophanate-methyl, Iprodione, and Zhongshengmycin at 500 mg/L concentration. Some compounds also exhibited high KARI inhibitory activity at 100 μg/mL concentration and could be used as new KARI lead inhibitors for further studies. Moreover, SAR of these new compounds were comprehensively investigated using different computational methods in which 3D-QSAR model obtained provided useful information for further structural optimization for the discovery of new fungicides. The results of this research will contribute to explore comprehensive biological activities of piperazine-containing compounds in different areas of chemistry. PMID:27092414

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

    PubMed

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

    2016-01-28

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

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

    NASA Astrophysics Data System (ADS)

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

    2014-12-01

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

  19. 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.

  20. Monitoring the Progression of Structure-Activity Relationship Information during Lead Optimization.

    PubMed

    Shanmugasundaram, Veerabahu; Zhang, Liying; Kayastha, Shilva; de la Vega de León, Antonio; Dimova, Dilyana; Bajorath, Jürgen

    2016-05-12

    Lead optimization (LO) in medicinal chemistry is largely driven by hypotheses and depends on the ingenuity, experience, and intuition of medicinal chemists, focusing on the key question of which compound should be made next. It is essentially impossible to predict whether an LO project might ultimately be successful, and it is also very difficult to estimate when a sufficient number of compounds has been evaluated to judge the odds of a project. Given the subjective nature of LO decisions and the inherent optimism of project teams, very few attempts have been made to systematically evaluate project progression. Herein, we introduce a computational framework to follow the evolution of structure-activity relationship (SAR) information over a time course. The approach is based on the use of SAR matrix data structures as a diagnostic tool and enables graphical analysis of SAR redundancy and project progression. This framework should help the process of making decisions in close-in analogue work. PMID:26569348

  1. Monitoring of Landslide Activity in Slovakia Territory Using Multi-Temporal InSAR Techniques

    NASA Astrophysics Data System (ADS)

    Bakon, M.; Papco, J.; Perissin, D.; Lazecky, M.; Sousa, J. J.; Hlavacova, I.; Batorova, K.; Ondrejka, P.; Liscak, P.; Paudits, P.; Real, N.

    2015-05-01

    Slope deformations are the most important geohazards in Slovakia which annually cause an extensive economic damage of significant influence. About 22000 slope deformations have been registered so far, covering an area of almost 2600 km2 . Since 2010, 639 new slope failures have been witnessed and their activation was driven mainly by the climatic anomalies such as extraordinary rainfalls. Many of these landslides currently represent a direct threat to the lives, health and property of the residents in the affected areas. The landslide Nizna Mysla is considered to be the second most catastrophic landslide in the history of Slovakia. Damages to buildings and engineering networks had not been identified in the ‘90s of the last century when the first problems with the slope stability appeared. Up-to-now monitoring techniques has currently been reassessed to account for the results from satellite Synthetic Aperture Radar (SAR) techniques.

  2. Understanding SARS with Wolfram approach.

    PubMed

    Li, Da-Wei; Pan, Yu-Xi; Duan, Yun; Hung, Zhen-De; Xu, Ming-Qing; He, Lin

    2004-01-01

    Stepping acquired immunodeficiency syndrome (AIDS), severe acute respiratory syndrome (SARS) as another type of disease has been threatening mankind since late last year. Many scientists worldwide are making great efforts to study the etiology of this disease with different approaches. 13 species of SARS virus have been sequenced. However, most people still largely rely on the traditional methods with some disadvantages. In this work, we used Wolfram approach to study the relationship among SARS viruses and between SARS viruses and other types of viruses, the effect of variations on the whole genome and the advantages in the analysis of SARS based on this novel approach. As a result, the similarities between SARS viruses and other coronaviruses are not really higher than those between SARS viruses and non-coronaviruses. PMID:14732867

  3. Structure-Activity Relationships in Nitro-Aromatic Compounds

    NASA Astrophysics Data System (ADS)

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

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

  4. 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.

  5. Structure-activity relationships of glutamate carboxypeptidase II (GCPII) inhibitors.

    PubMed

    Ferraris, D V; Shukla, K; Tsukamoto, T

    2012-01-01

    Glutamate carboxypeptidase II (GCPII, EC 3.4.17.21) is a zinc metallopeptidase that hydrolyzes N-acetylaspartylglutamate (NAAG) into N-acetylaspartate (NAA) and glutamate in the nervous system. Inhibition of GCPII has the potential to reduce extracellular glutamate and represents an opportune target for treating neurological disorders in which excess glutamate is considered pathogenic. Furthermore, GCPII was found to be identical to a tumor marker, prostate-specific membrane antigen (PSMA), and has drawn significant interest as a diagnostic and/or therapeutic target in oncology. Over the past 15 years, tremendous efforts have been made in the discovery of potent GCPII inhibitors, particularly those with phosphorus-, urea- and thiol-based zinc binding groups. In addition, significant progress has been made in understanding the three-dimensional structural characteristics of GCPII in complex with various ligands. The purpose of this review article is to analyze the structure-activity relationships (SAR) of GCPII inhibitors reported to date, which are classified on the basis of their zinc-binding group. SAR and crystallographic data are evaluated in detail for each of these series to highlight the future challenges and opportunities to identify clinically viable GCPII inhibitors. PMID:22304717

  6. Characterization of sarR, a Modulator of sar Expression in Staphylococcus aureus

    PubMed Central

    Manna, Adhar; Cheung, Ambrose L.

    2001-01-01

    The expression of virulence determinants in Staphylococcus aureus is controlled by global regulatory loci (e.g., sar and agr). The sar locus is composed of three overlapping transcripts (sar P1, P3, and P2 transcripts from P1, P3, and P2 promoters, respectively), all encoding the 372-bp sarA gene. The level of SarA, the major regulatory protein, is partially controlled by the differential activation of sar promoters. We previously partially purified a ∼12 kDa protein with a DNA-specific column containing a sar P2 promoter fragment. In this study, the putative gene, designated sarR, was identified and found to encode a 13.6-kDa protein with homology to SarA. Transcriptional and immunoblot studies revealed the sarR gene to be expressed in other staphylococcal strains. Recombinant SarR protein bound sar P1, P2, and P3 promoter fragments in gel shift and footprinting assays. A sarR mutant expressed a higher level of P1 transcript than the parent, as confirmed by promoter green fluorescent protein fusion assays. As the P1 transcript is the predominant sar transcript, we confirmed that the sarR mutant expressed more SarA than the parental strain. We thus proposed that SarR is a regulatory protein that binds to the sar promoters to down-regulate P1 transcription and the ensuing SarA protein expression. PMID:11159982

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

    EPA Science Inventory

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

  8. 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...

  9. Riccardin C derivatives as anti-MRSA agents: structure-activity relationship of a series of hydroxylated bis(bibenzyl)s.

    PubMed

    Sawada, Hiromi; Okazaki, Miki; Morita, Daichi; Kuroda, Teruo; Matsuno, Kenji; Hashimoto, Yuichi; Miyachi, Hiroyuki

    2012-12-15

    Members of a series of macrocyclic bis(bibenzyl) riccardin-class derivatives were found to exhibit antibacterial activity towards methicillin-resistant Staphylococcus aureus (anti-MRSA activity). Structure-activity relationship (SAR) studies were conducted, focusing on the number and position of the hydroxyl groups. The minimum essential structure for anti-MRSA activity was also investigated. PMID:23122868

  10. 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.

  11. 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

  12. Broadening of neutralization activity to directly block a dominant antibody-driven SARS-coronavirus evolution pathway.

    PubMed

    Sui, Jianhua; Aird, Daniel R; Tamin, Azaibi; Murakami, Akikazu; Yan, Meiying; Yammanuru, Anuradha; Jing, Huaiqi; Kan, Biao; Liu, Xin; Zhu, Quan; Yuan, Qing-An; Adams, Gregory P; Bellini, William J; Xu, Jianguo; Anderson, Larry J; Marasco, Wayne A

    2008-11-01

    Phylogenetic analyses have provided strong evidence that amino acid changes in spike (S) protein of animal and human SARS coronaviruses (SARS-CoVs) during and between two zoonotic transfers (2002/03 and 2003/04) are the result of positive selection. While several studies support that some amino acid changes between animal and human viruses are the result of inter-species adaptation, the role of neutralizing antibodies (nAbs) in driving SARS-CoV evolution, particularly during intra-species transmission, is unknown. A detailed examination of SARS-CoV infected animal and human convalescent sera could provide evidence of nAb pressure which, if found, may lead to strategies to effectively block virus evolution pathways by broadening the activity of nAbs. Here we show, by focusing on a dominant neutralization epitope, that contemporaneous- and cross-strain nAb responses against SARS-CoV spike protein exist during natural infection. In vitro immune pressure on this epitope using 2002/03 strain-specific nAb 80R recapitulated a dominant escape mutation that was present in all 2003/04 animal and human viruses. Strategies to block this nAb escape/naturally occurring evolution pathway by generating broad nAbs (BnAbs) with activity against 80R escape mutants and both 2002/03 and 2003/04 strains were explored. Structure-based amino acid changes in an activation-induced cytidine deaminase (AID) "hot spot" in a light chain CDR (complementarity determining region) alone, introduced through shuffling of naturally occurring non-immune human VL chain repertoire or by targeted mutagenesis, were successful in generating these BnAbs. These results demonstrate that nAb-mediated immune pressure is likely a driving force for positive selection during intra-species transmission of SARS-CoV. Somatic hypermutation (SHM) of a single VL CDR can markedly broaden the activity of a strain-specific nAb. The strategies investigated in this study, in particular the use of structural information in

  13. 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

  14. Development of structure-activity relationship rules for predicting carcinogenic potential of chemicals.

    PubMed

    Woo, Y T; Lai, D Y; Argus, M F; Arcos, J C

    1995-09-01

    Since the inception of Section 5 (Premanufacturing/Premarketing Notification, PMN) of the Toxic Substances Control Act (TSCA), structure-activity relationship (SAR) analysis has been effectively used by U.S. Environmental Protection Agency's (EPA) Structure Activity Team (SAT) in the assessment of potential carcinogenic hazard of new chemicals for which test data are not available. To capture, systematize and codify the Agency's predictive expertise in order to make it more widely available to assessors outside the TSCA program, a cooperative project was initiated to develop a knowledge rule-based expert system to mimic the thinking and reasoning of the SAT. In this communication, we describe the overall structure of this expert system, discuss the scientific bases and principles of SAR analysis of chemical carcinogens used in the development of SAR knowledge rules, and delineate the major factors/rules useful for assessing the carcinogenic potential of fibers, polymers, metals/metalloids and several major classes of organic chemicals. An integrative approach using available short-term predictive tests and non-cancer toxicological data to supplement SAR analysis has also been described. PMID:7570659

  15. Synthesis, evaluation and structure-activity relationship of new 3-carboxamide coumarins as FXIIa inhibitors.

    PubMed

    Bouckaert, Charlotte; Serra, Silvia; Rondelet, Grégoire; Dolušić, Eduard; Wouters, Johan; Dogné, Jean-Michel; Frédérick, Raphaël; Pochet, Lionel

    2016-03-01

    Inhibitors of the coagulation factor XIIa (FXIIa) are attractive to detail the roles of this protease in hemostasis and thrombosis, to suppress artifact due to contact pathway activation in blood coagulation assays, and they are promising as antithrombotic therapy. The 3-carboxamide coumarins have been previously described as small-molecular-weight FXIIa inhibitors. In this study, we report a structure-activity relationship (SAR) study around this scaffold with the aim to discover new selective FXIIa inhibitors with an improved physico-chemical profile. To better understand these SAR, docking experiments were undertaken. For this purpose, we built an original hybrid model of FXIIa. This model has the advantage to gather the best features from the recently published crystal structure of FXIIa in its zymogen form and a more classical homology model. Results with the hybrid model are encouraging as they help understanding the activity and selectivity of our best compounds. PMID:26827162

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

    PubMed

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

    2016-05-19

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

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

    PubMed

    Sahu, Pramod K

    2016-10-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-06-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2014-12-01

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

  20. A Categorical Structure-Activity Relationship Analysis of the Developmental Toxicity of Antithyroid Drugs

    PubMed Central

    Cunningham, Albert R.; Carrasquer, C. Alex; Mattison, Donald R.

    2009-01-01

    The choice of therapeutic strategies for hyperthyroidism during pregnancy is limited. Surgery and radioiodine are typically avoided, leaving propylthiouracil and methimazole in the US. Carbimazole, a metabolic precursor of methimazole, is available in some countries outside of the US. In the US propylthiouracil is recommended because of concern about developmental toxicity from methimazole and carbimazole. Despite this recommendation, the data on developmental toxicity of all three agents are extremely limited and insufficient to support a policy given the broad use of methimazole and carbimazole around the world. In the absence of new human or animal data we describe the development of a new structure-activity relationship (SAR) model for developmental toxicity using the cat-SAR expert system. The SAR model was developed from data for 323 compounds evaluated for human developmental toxicity with 130 categorized as developmental toxicants and 193 as nontoxicants. Model cross-validation yielded a concordance between observed and predicted results between 79% to 81%. Based on this model, propylthiouracil, methimazole, and carbimazole were observed to share some structural features relating to human developmental toxicity. Thus given the need to treat women with Graves's disease during pregnancy, new molecules with minimized risk for developmental toxicity are needed. To help meet this challenge, the cat-SAR method would be a useful in screening new drug candidates for developmental toxicity as well as for investigating their mechanism of action. PMID:20111734

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

    NASA Astrophysics Data System (ADS)

    Saepuloh, Asep; Trianaputri, Mila Olivia

    2015-04-01

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

  2. The Grand Banks ERS-1 SAR wave spectra validation experiment

    NASA Technical Reports Server (NTRS)

    Vachon, P. W.; Dobson, F. W.; Smith, S. D.; Anderson, R. J.; Buckley, J. R.; Allingham, M.; Vandemark, D.; Walsh, E. J.; Khandekar, M.; Lalbeharry, R.

    1993-01-01

    As part of the ERS-1 validation program, the ERS-1 Synthetic Aperture Radar (SAR) wave spectra validation experiment was carried out over the Grand Banks of Newfoundland (Canada) in Nov. 1991. The principal objective of the experiment was to obtain complete sets of wind and wave data from a variety of calibrated instruments to validate SAR measurements of ocean wave spectra. The field program activities are described and the rather complex wind and wave conditions which were observed are summarized. Spectral comparisons with ERS-1 SAR image spectra are provided. The ERS-1 SAR is shown to have measured swell and range traveling wind seas, but did not measure azimuth traveling wind seas at any time during the experiment. Results of velocity bunching forward mapping and new measurements of the relationship between wind stress and sea state are also shown.

  3. 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.

  4. Substituted indoles as selective protease activated receptor 4 (PAR-4) antagonists: Discovery and SAR of ML354.

    PubMed

    Wen, Wandong; Young, Summer E; Duvernay, Matthew T; Schulte, Michael L; Nance, Kellie D; Melancon, Bruce J; Engers, Julie; Locuson, Charles W; Wood, Michael R; Daniels, J Scott; Wu, Wenjun; Lindsley, Craig W; Hamm, Heidi E; Stauffer, Shaun R

    2014-10-01

    Herein we report the discovery and SAR of an indole-based protease activated receptor-4 (PAR-4) antagonist scaffold derived from a similarity search of the Vanderbilt HTS collection, leading to MLPCN probe ML354 (VU0099704). Using a novel PAC-1 fluorescent αIIbβ3 activation assay this probe molecule antagonist was found to have an IC50 of 140nM for PAR-4 with 71-fold selectivity versus PAR-1 (PAR-1IC50=10μM). PMID:25176330

  5. 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

  6. Design, Synthesis, and Structure–Activity Relationships of Highly Potent 5-HT3 Receptor Ligands

    PubMed Central

    2012-01-01

    The 5-HT3 receptor, a pentameric ligand-gated ion channel (pLGIC), is an important therapeutic target. During a recent fragment screen, 6-chloro-N-methyl-2-(4-methyl-1,4-diazepan-1-yl)quinazolin-4-amine (1) was identified as a 5-HT3R hit fragment. Here we describe the synthesis and structure–activity relationships (SAR) of a series of (iso)quinoline and quinazoline compounds that were synthesized and screened for 5-HT3R affinity using a [3H]granisetron displacement assay. These studies resulted in the discovery of several high affinity ligands of which compound 22 showed the highest affinity (pKi > 10) for the 5-HT3 receptor. The observed SAR is in agreement with established pharmacophore models for 5-HT3 ligands and is used for ligand–receptor binding mode prediction using homology modeling and in silico docking approaches. PMID:23006041

  7. 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...

  8. SARS/avian coronaviruses.

    PubMed

    Monceyron Jonassen, C

    2006-01-01

    In the hunt for the aetiology of the SARS outbreak in 2003, a newly developed virus DNA micro-array was successfully used to hybridise PCR products obtained by random amplification of nucleic acids extracted from a cell culture infected with material from a SARS patient. The SARS agent was found to hybridise with micro-array probes from both coronaviruses and astroviruses, but one of the coronavirus probes and the four astrovirus probes contained redundant sequences, spanning a highly conserved motif, named s2m, found at the 3' end of the genomes of almost all astroviruses, one picornavirus, and the poultry coronaviruses. The three other coronavirus probes, that hybridised with the SARS agent, were located in the replicase gene, and it could be concluded that the SARS agent was a novel coronavirus, harbouring s2m. The presence of this motif in different virus families is probably the result of recombinations between unrelated viruses, but its presence in both poultry and SARS coronaviruses could suggest a bird involvement in the history of the SARS coronavirus. A recent screening of wild birds for the presence of coronaviruses, using a pan-coronavirus RT-PCR, led to the identification of novel coronaviruses in the three species studied. Phylogenetic analyses performed on both replicase gene and nucleocapsid protein could not add support to a close relationship between avian and SARS coronaviruses, but all the novel avian coronaviruses were found to harbour s2m. The motif is inserted at a homologous place in avian and SARS coronavirus genomes, but in a somewhat different context for the SARS coronavirus. If the presence of s2m in these viruses is a result of two separate recombination events, this suggests that its particular position in these genomes is the only one that would not be deleterious for coronaviral replication, or that it is the result of a copy-choice recombination between coronaviruses, following an ancestral introduction in the coronavirus family by

  9. Synthesis and Structure-Activity Relationships of Substituted Urea Derivatives on Mouse Melanocortin Receptors.

    PubMed

    Singh, Anamika; Kast, Johannes; Dirain, Marvin L S; Huang, Huisuo; Haskell-Luevano, Carrie

    2016-02-17

    The melanocortin system is involved in the regulation of several complex physiological functions. In particular, the melanocortin-3 and -4 receptors (MC3R/MC4R) have been demonstrated to regulate body weight, energy homeostasis, and feeding behavior. Synthetic and endogenous melanocortin agonists have been shown to be anorexigenic in rodent models. Herein, we report synthesis and structure-activity relationship (SAR) studies of 27 nonpeptide small molecule ligands based on an unsymmetrical substituted urea core. Three templates containing key residues from the lead compounds, showing diversity at three positions (R(1), R(2), R(3)), were designed and synthesized. The syntheses were optimized for efficient microwave-assisted chemistry that significantly reduced total syntheses time compared to a previously reported room temperature method. The pharmacological characterization of the compounds on the mouse melanocortin receptors identified compounds 1 and 12 with full agonist activity at the mMC4R, but no activity was observed at the mMC3R when tested up to 100 μM concentrations. The SAR identified compounds possessing aliphatic or saturated cyclic amines at the R(1) position, bulky aromatic groups at the R(2) position, and benzyl group at the R(3) position resulted in mMC4R selectivity over the mMC3R. The small molecule template and SAR knowledge from this series may be helpful in further design of MC3R/MC4R selective small molecule ligands. PMID:26645732

  10. SARS Basics

    MedlinePlus

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

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

    PubMed

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

    2015-01-01

    In continuation of our program aimed at the development of natural product-based pesticidal agents, three series of novel camptothecin derivatives were designed, synthesized, and evaluated for their biological activities against T. Cinnabarinus, B. brassicae, and B. xylophilus. All of the derivatives showed good-to-excellent activity against three insect species tested, with LC50 values ranging from 0.00761 to 0.35496 mmol/L. Remarkably, all of the compounds were more potent than CPT against T. Cinnabarinus, and compounds 4d and 4c displayed superior activity (LC50 0.00761 mmol/L and 0.00942 mmol/L, respectively) compared with CPT (LC50 0.19719 mmol/L) against T. Cinnabarinus. Based on the observed bioactivities, preliminary structure-activity relationship (SAR) correlations were also discussed. Furthermore, a three-dimensional quantitative structure-activity relationship (3D-QSAR) model using comparative molecular field analysis (CoMFA) was built. The model gave statistically significant results with the cross-validated q2 values of 0.580 and correlation coefficient r2 of 0.991 and  of 0.993. The QSAR analysis indicated that the size of the substituents play an important in the activity of 7-modified camptothecin derivatives. These findings will pave the way for further design, structural optimization, and development of camptothecin-derived compounds as pesticidal agents. PMID:25985362

  12. Nano(Q)SAR: Challenges, pitfalls and perspectives.

    PubMed

    Tantra, Ratna; Oksel, Ceyda; Puzyn, Tomasz; Wang, Jian; Robinson, Kenneth N; Wang, Xue Z; Ma, Cai Y; Wilkins, Terry

    2015-01-01

    Regulation for nanomaterials is urgently needed, and the drive to adopt an intelligent testing strategy is evident. Such a strategy will not only provide economic benefits but will also reduce moral and ethical concerns arising from animal testing. For regulatory purposes, such an approach is promoted by REACH, particularly the use of quantitative structure-activity relationships [(Q)SAR] as a tool for the categorisation of compounds according to their physicochemical and toxicological properties. In addition to compounds, (Q)SAR has also been applied to nanomaterials in the form of nano(Q)SAR. Although (Q)SAR in chemicals is well established, nano(Q)SAR is still in early stages of development and its successful uptake is far from reality. This article aims to identify some of the pitfalls and challenges associated with nano-(Q)SARs in relation to the categorisation of nanomaterials. Our findings show clear gaps in the research framework that must be addressed if we are to have reliable predictions from such models. Three major barriers were identified: the need to improve quality of experimental data in which the models are developed from, the need to have practical guidelines for the development of the nano(Q)SAR models and the need to standardise and harmonise activities for the purpose of regulation. Of these three, the first, i.e. the need to improve data quality requires immediate attention, as it underpins activities associated with the latter two. It should be noted that the usefulness of data in the context of nano-(Q)SAR modelling is not only about the quantity of data but also about the quality, consistency and accessibility of those data. PMID:25211549

  13. Structure-activity relationship study between baicalein and wogonin by spectrometry, molecular docking and microcalorimetry.

    PubMed

    Tu, Bao; Li, Rong-Rong; Liu, Zhi-Juan; Chen, Zhi-Feng; Ouyang, Yu; Hu, Yan-Jun

    2016-10-01

    Flavones (e.g. baicalein and wogonin) extensively used worldwide in food preparation and traditional medicine. In this study, a systematically comparative study of their structure-activity relationships (SAR) on their interaction with BSA, antioxidant activity and antibacterial activity has been carried out by spectrometry, molecular docking and microcalorimetry. Our results show that the skeleton structure of flavones, the number of hydroxyl groups, the type of functional group, conjugated system and the steric hindrance may be responsible for their different biological activity. These findings not only would lay a scientific foundation for discovering and designing flavones-based food and drug, may also help us to understanding the structure-activity relationship between flavones at the molecular level. PMID:27132840

  14. Whole structure-activity relationships of the fat-accumulation inhibitor (-)-ternatin: recognition of the importance of each amino acid residue.

    PubMed

    Shimokawa, Kenichiro; Iwase, Yoshiaki; Miwa, Ryoka; Yamada, Kaoru; Uemura, Daisuke

    2008-10-01

    A series of Ala and Aoc analogues of (-)-ternatin were prepared, and their bioactivities were assessed by a fat-accumulation inhibition assay using 3T3-L1 adipocytes, which led to the discovery of key structure-activity relationships (SAR). PMID:18798610

  15. Insights into COPll Coat Nucleation from the Structure of Sec23 Sar1 Complexed with the Active Fragment of Sec31

    SciTech Connect

    Bi,X.; Mancias, J.; Goldberg, J.

    2007-01-01

    The COPII vesicular coat forms on the endoplasmic reticulum from Sar1-GTP, Sec23/24 and Sec13/31 protein subunits. Here, we define the interaction between Sec23/24{center_dot}Sar1 and Sec13/31, involving a 40 residue Sec31 fragment. In the crystal structure of the ternary complex, Sec31 binds as an extended polypeptide across a composite surface of the Sec23 and Sar1-GTP molecules, explaining the stepwise character of Sec23/24{center_dot}Sar1 and Sec13/31 recruitment to the membrane. The Sec31 fragment stimulates GAP activity of Sec23/24, and a convergence of Sec31 and Sec23 residues at the Sar1 GTPase active site explains how GTP hydrolysis is triggered leading to COPII coat disassembly. The Sec31 active fragment is accommodated in a binding groove supported in part by Sec23 residue Phe380. Substitution of the corresponding residue F382L in human Sec23A causes cranio-lenticulo-sutural dysplasia, and we suggest that this mutation disrupts the nucleation of COPII coat proteins at endoplasmic reticulum exit sites.

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

    PubMed Central

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

    2014-01-01

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

  17. 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.

  18. 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

    2012-01-01

    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

  19. COMPUTER-ASSISTED STUDIES OF MOLECULAR STRUCTURE AND GENOTOXIC ACTIVITY BY PATTERN RECOGNITION TECHNIQUES

    EPA Science Inventory

    Often a compound's biological activity is determined by complex relationships between its structural components. Such a relationship often can only be adequately described and exploited by multivariate structure-activity relationship (SAR) studies that can deal with many variable...

  20. Indolo[3,2-b]quinolines: Synthesis, Biological Evaluation and Structure Activity-Relationships

    PubMed Central

    Kumar, Eyunni V.K. Suresh; Etukala, Jagan R.; Ablordeppey, Seth Y.

    2013-01-01

    The tetracyclic indolo[3,2-b]quinoline ring system constitutes an important structural moiety in natural products exhibiting numerous biological activities. In particular, indolo [3, 2-b]quinoline, commonly known as linear quindo-line is of particular interest, because of its rigid structure and scope of derivatization. Although the core linear quindoline skeleton shows little or no activity in several biological systems, introduction of a methyl group on the N-5 atom leading to cryptolepine induces remarkable activity against a broad spectrum of biological targets. A number of analogs of quindoline and cryptolepine have been synthesized, incorporating various functional groups on the core quindoline skeleton leading to improved biological activities. In this review, we describe various synthetic methodologies leading to the quindoline scaffold, the biological activities and the structure activity relationships (SAR) of quindoline derivatives toward different disease states to give a better picture of the importance of this moiety in medicinal chemistry. PMID:18537709

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

    PubMed Central

    2013-01-01

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

  2. STUDIES OF RELATIONSHIPS BETWEEN MOLECULAR STRUCTURE AND BIOLOGICAL ACTIVITY BY PATTERN RECOGNITION METHODS

    EPA Science Inventory

    The attempt to rationalize the connections between the molecular structures of organic compounds and their biological activities comprises the field of structure-activity relations (SAR) studies. Correlations between structure and activity are important for the understanding and ...

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

    PubMed

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

    2016-05-26

    Herein, we report studies leading to the discovery of the neoseptins and a comprehensive examination of the structure-activity relationships (SARs) of this new class of small-molecule mouse Toll-like receptor 4 (mTLR4) agonists. The compounds in this class, which emerged from screening an α-helix mimetic library, stimulate the immune response, act by a well-defined mechanism (mouse TLR4 agonist), are easy to produce and structurally manipulate, exhibit exquisite SARs, are nontoxic, and elicit improved and qualitatively different responses compared to lipopolysaccharide, even though they share the same receptor. PMID:27050713

  4. 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.

  5. 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. PMID:26879854

  6. 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.

  7. Applying PolSAR and PolInSAR to Forest Structure Information Extraction

    NASA Astrophysics Data System (ADS)

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

    2013-01-01

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

  8. 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.

  9. 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

  10. 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.

  11. An active ring fault detected at Tendürek volcano by using InSAR

    NASA Astrophysics Data System (ADS)

    Bathke, H.; Sudhaus, H.; Holohan, E. P.; Walter, T. R.; Shirzaei, M.

    2013-08-01

    ring faults are present at many ancient, deeply eroded volcanoes, they have been detected at only very few modern volcanic centers. At the so far little studied Tendürek volcano in eastern Turkey, we generated an ascending and a descending InSAR time series of its surface displacement field for the period from 2003 to 2010. We detected a large (~105 km2) region that underwent subsidence at the rate of ~1 cm/yr during this period. Source modeling results show that the observed signal fits best to simulations of a near-horizontal contracting sill located at around 4.5 km below the volcano summit. Intriguingly, the residual displacement velocity field contains a steep gradient that systematically follows a system of arcuate fractures visible on the volcano's midflanks. RapidEye satellite optical images show that this fracture system has deflected Holocene lava flows, thus indicating its presence for at least several millennia. We interpret the arcuate fracture system as the surface expression of an inherited ring fault that has been slowly reactivated during the detected recent subsidence. These results show that volcano ring faults may not only slip rapidly during eruptive or intrusive phases, but also slowly during dormant phases.

  12. Structure—activity relationships for insecticidal carbamates*

    PubMed Central

    Metcalf, Robert L.

    1971-01-01

    Carbamate insecticides are biologically active because of their structural complementarity to the active site of acetylcholinesterase (AChE) and their consequent action as substrates with very low turnover numbers. Carbamates behave as synthetic neurohormones that produce their toxic action by interrupting the normal action of AChE so that acetylcholine accumulates at synaptic junctions. The necessary properties for a suitable insecticidal carbamate are lipid solubility, suitable structural complementarity to AChE, and sufficient stability to multifunction-oxidase detoxification. The relationships between the structure and the activity of a large number of synthetic carbamates are analysed in detail, with particular attention to the second of these properties. PMID:5315358

  13. Synthesis, anticancer activity, and SAR analyses of compounds containing the 5:7-fused 4,6,8-triaminoimidazo[4,5-e][1,3]diazepine ring system.

    PubMed

    Xie, Min; Lapidus, Rena G; Sadowska, Mariola; Edelman, Martin J; Hosmane, Ramachandra S

    2016-06-15

    Described herein are our limited structure-activity relationship (SAR) studies on a 5:7-fused heterocycle (1), containing the 4,6,8-triaminoimidazo[4,5-e][1,3]diazepine ring system, whose synthesis and potent broad-spectrum anticancer activity we reported a few years ago. Our SAR efforts in this study are mainly focused on judicial attachment of substituents at N-1 and N(6)-positions of the heterocyclic ring. Our results suggest that there is some subtle correlation between the substituents attached at the N-1 position and those attached at the N(6)-position of the heterocycle. It is likely that there is a common hydrophobic binding pocket on the target protein that is occupied by the substituents attached at the N-1 and N(6)-positions of the heterocyclic ligand. This pocket appears to be large enough to hold either a C-18 alkyl chain of N(6) and no attachment at N-1, or a combined C-10 at N(6) and a CH2Ph at N-1. Any alkyl chain shorter or longer than C-10 at N(6) with a CH2Ph attached at N-1, would result in decrease of biological activity. PMID:27134120

  14. Novel 2-aminopyrimidine carbamates as potent and orally active inhibitors of Lck: synthesis, SAR, and in vivo antiinflammatory activity.

    PubMed

    Martin, Matthew W; Newcomb, John; Nunes, Joseph J; McGowan, David C; Armistead, David M; Boucher, Christina; Buchanan, John L; Buckner, William; Chai, Lilly; Elbaum, Daniel; Epstein, Linda F; Faust, Theodore; Flynn, Shaun; Gallant, Paul; Gore, Anu; Gu, Yan; Hsieh, Faye; Huang, Xin; Lee, Josie H; Metz, Daniela; Middleton, Scot; Mohn, Deanna; Morgenstern, Kurt; Morrison, Michael J; Novak, Perry M; Oliveira-dos-Santos, Antonio; Powers, David; Rose, Paul; Schneider, Stephen; Sell, Stephanie; Tudor, Yanyan; Turci, Susan M; Welcher, Andrew A; White, Ryan D; Zack, Debra; Zhao, Huilin; Zhu, Li; Zhu, Xiaotian; Ghiron, Chiara; Amouzegh, Patricia; Ermann, Monika; Jenkins, James; Johnston, David; Napier, Spencer; Power, Eoin

    2006-08-10

    The lymphocyte-specific kinase (Lck) is a cytoplasmic tyrosine kinase of the Src family expressed in T cells and NK cells. Genetic evidence in both mice and humans demonstrates that Lck kinase activity is critical for signaling mediated by the T cell receptor (TCR), which leads to normal T cell development and activation. A small molecule inhibitor of Lck is expected to be useful in the treatment of T cell-mediated autoimmune and inflammatory disorders and/or organ transplant rejection. In this paper, we describe the synthesis, structure-activity relationships, and pharmacological characterization of 2-aminopyrimidine carbamates, a new class of compounds with potent and selective inhibition of Lck. The most promising compound of this series, 2,6-dimethylphenyl 2-((3,5-bis(methyloxy)-4-((3-(4-methyl-1-piperazinyl)propyl)oxy)phenyl)amino)-4-pyrimidinyl(2,4-bis(methyloxy)phenyl)carbamate (43) exhibits good activity when evaluated in in vitro assays and in an in vivo model of T cell activation. PMID:16884310

  15. Structure-activity relationship of anthelmintic cyclooctadepsipeptides.

    PubMed

    Ohyama, Makoto; Okada, Yumiko; Takahashi, Masaaki; Sakanaka, Osamu; Matsumoto, Maki; Atsumi, Kunio

    2011-01-01

    The relationship between cyclooctadepsipeptides and their anthelmintic efficacy was examined by converting the natural products, PF1022A, PF1022E and PF1022H. Some analogues substituted at the para position of the phenyllactate moiety showed higher or equivalent activity against the parasitic nematode, Ascaridia galli in chicken when compared with the parent compounds. It is suggested that lipophilicity and the polar surface area, in addition to structural requirements of the derivatives, influenced the anthelmintic efficacy in vivo. PMID:21737929

  16. 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 ...

  17. ROLE OF COMPUTATIONAL CHEMISTRY IN SUPPORT OF HAZARD IDENTIFICATION (ID) MECHANISM-BASED SARS

    EPA Science Inventory

    A mechanism-based structure-activity relationship (SAR) study attempts to determine a structural basis for activity by targeting a single or a few stages in a postulated mechanism of action.Computational chemistry approaches provide a valuable complement to experiment for probing...

  18. 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

  19. Structure activity relationship studies of 3-arylsulfonyl-pyrido[1,2-a]pyrimidin-4-imines as potent 5-HT₆ antagonists.

    PubMed

    Hu, Shuanghua; Huang, Yazhong; Wu, Yong-Jin; He, Huan; Grant-Young, Katherine A; Bertekap, Robert L; Whiterock, Valerie; Brassil, Patrick; Lentz, Kimberley; Sivaprakasam, Prasanna; Langley, David R; Westphal, Ryan S; Scola, Paul M

    2014-03-01

    Comprehensive structure activity relationship (SAR) studies were conducted on a focused screening hit, 2-(methylthio)-3-(phenylsulfonyl)-4H-pyrido[1,2-a]pyrimidin-4-imine (1, IC50: 4.0 nM), as 5-HT6 selective antagonists. Activity was improved some 2-4 fold when small, electron-donating groups were added to the central core as observed in 19, 20 and 26. Molecular docking of key compounds in a homology model of the human 5-HT6 receptor was used to rationalize our structure-activity relationship (SAR) findings. In pharmacokinetic experiments, compound 1 displayed good brain uptake in rats following intra-peritoneal administration, but limited oral bioavailability. PMID:24495863

  20. Structure-activity relationship of triazafluorenone derivatives as potent and selective mGluR1 antagonists.

    PubMed

    Zheng, Guo Zhu; Bhatia, Pramila; Daanen, Jerome; Kolasa, Teodozyj; Patel, Meena; Latshaw, Steven; El Kouhen, Odile F; Chang, Renjie; Uchic, Marie E; Miller, Loan; Nakane, Masaki; Lehto, Sonya G; Honore, Marie P; Moreland, Robert B; Brioni, Jorge D; Stewart, Andrew O

    2005-11-17

    SAR (structure-activity relationship) studies of triazafluorenone derivatives as potent mGluR1 antagonists are described. The triazafluorenone derivatives are non-amino acid derivatives and noncompetitive mGluR1 antagonists that bind at a putative allosteric recognition site located within the seven-transmembrane domain of the receptor. These triazafluorenone derivatives are potent, selective, and systemically active mGluR1 antagonists. Compound 1n, for example, was a very potent mGluR1 antagonist (IC50 = 3 nM) and demonstrated full efficacy in various in vivo animal pain models. PMID:16279797

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

    PubMed Central

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

    2014-01-01

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

  2. Synthesis, bioactivity and structure-activity relationships of new 2-aryl-8-OR-3,4-dihydroisoquinolin-2-iums salts as potential antifungal agents.

    PubMed

    Zhu, Li-Fei; Hou, Zhe; Zhou, Kun; Tong, Zong-Bo; Kuang, Qian; Geng, Hui-Ling; Zhou, Le

    2016-05-15

    As our continuing research on antifungal dihydroisoquinolin-2-ium salts, forty 2-aryl-8-OR-3,4-dihydroisoquinolin-2-ium bromides were synthesized and characterized by spectroscopic analysis. By using the mycelium growth rate method, the compounds were evaluated for antifungal activity against three plant pathogenic fungi and structure-activity relationships (SAR) were derived. The vast majority of the compounds displayed the medium to high activity with inhibition rates of 50-100% at 150μM. About half of the compounds were more active than their natural model compounds sanguinarine and chelerythrine for all the fungi, and part or most of them were more active than positive drugs thiabendazole and azoxystrobin. SAR analysis showed that both substitution patterns of the C-ring and the type of 8-OR group significantly influenced the activity. Thus, a series of new title compounds with excellent antifungal potency emerged. PMID:27072907

  3. Discovery of KDM5A inhibitors: Homology modeling, virtual screening and structure-activity relationship analysis.

    PubMed

    Wu, Xiaoai; Fang, Zhen; Yang, Bo; Zhong, Lei; Yang, Qiuyuan; Zhang, Chunhui; Huang, Shenzhen; Xiang, Rong; Suzuki, Takayoshi; Li, Lin-Li; Yang, Sheng-Yong

    2016-05-01

    Herein we report the discovery of a series of new KDM5A inhibitors. A three-dimensional (3D) structure model of KDM5A jumonji domain was firstly established based on homology modeling. Molecular docking-based virtual screening was then performed against commercial chemical databases. A number of hit compounds were retrieved. Further structural optimization and structure-activity relationship (SAR) analysis were carried out to the most active hit compound, 9 (IC50: 2.3μM), which led to the discovery of several new KDM5A inhibitors. Among them, compound 15e is the most potent one with an IC50 value of 0.22μM against KDM5A. This compound showed good selectivity for KDM5A and considerable ability to suppress the demethylation of H3K4me3 in intact cells. Compound 15e could be taken as a good lead compound for further studies. PMID:27020306

  4. 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.

  5. Molecular characterization of the receptor binding structure-activity relationships of influenza B virus hemagglutinin.

    PubMed

    Carbone, V; Kim, H; Huang, J X; Baker, M A; Ong, C; Cooper, M A; Li, J; Rockman, S; Velkov, T

    2013-01-01

    Selectivity of α2,6-linked human-like receptors by B hemagglutinin (HA) is yet to be fully understood. This study integrates binding data with structure-recognition models to examine the impact of regional-specific sequence variations within the receptor-binding pocket on selectivity and structure activity relationships (SAR). The receptor-binding selectivity of influenza B HAs corresponding to either B/Victoria/2/1987 or the B/Yamagata/16/88 lineages was examined using surface plasmon resonance, solid-phase ELISA and gel-capture assays. Our SAR data showed that the presence of asialyl sugar units is the main determinant of receptor preference of α2,6 versus α2,3 receptor binding. Changes to the type of sialyl-glycan linkage present on receptors exhibit only a minor effect upon binding affinity. Homology-based structural models revealed that structural properties within the HA pocket, such as a glyco-conjugate at Asn194 on the 190-helix, sterically interfere with binding to avian receptor analogs by blocking the exit path of the asialyl sugars. Similarly, naturally occurring substitutions in the C-terminal region of the 190-helix and near the N-terminal end of the 140-loop narrows the horizontal borders of the binding pocket, which restricts access of the avian receptor analog LSTa. This study helps bridge the gap between ligand structure and receptor recognition for influenza B HA; and provides a consensus SAR model for the binding of human and avian receptor analogs to influenza B HA. PMID:24020757

  6. 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

  7. 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. PMID:25383183

  8. Synthesis and structure–activity relationships of tyrosine-based inhibitors of autotaxin (ATX)

    PubMed Central

    East, James E.; Kennedy, Andrew J.; Tomsig, Jose L.; De Leon, Alexandra R.; Lynch, Kevin R.; Macdonald, Timothy L.

    2010-01-01

    Autotaxin (ATX) is a secreted soluble enzyme that generates lysophosphatidic acid (LPA) through its lysophospholipase D activity. Because of LPA’s role in neoplastic diseases, ATX is an attractive therapeutic target due to its involvement in LPA biosynthesis. Here we describe the SAR of ATX inhibitor, VPC8a202, and apply this SAR knowledge towards developing a high potency inhibitor. We found that electron density in the pyridine region greatly influences activity of our inhibitors at ATX. PMID:20951039

  9. STATISTICALLY-BASED STRUCTURE-ACTIVITY RELATIONSHIP (SAR) SYSTEMS FOR DEVELOPMENTAL TOXICITY

    EPA Science Inventory

    The first Drinking Water Contaminant Candidate List (CCL), created in response to the Safe Drinking Water Act (SDWA) Amendments of 1996, consists of a list of chemicals or groups of chemicals that are known drinking water contaminants. The SDWA amendments of 1996 stipulated that...

  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. PMID:26265354

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

    PubMed

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

    2006-06-01

    The requirement of aligning each individual molecule in a data set severely limits the type of molecules which can be analysed with traditional structure activity relationship (SAR) methods. A method which solves this problem by using relations between objects is inductive logic programming (ILP). Another advantage of this methodology is its ability to include background knowledge as 1st-order logic. However, previous molecular ILP representations have not been effective in describing the electronic structure of molecules. We present a more unified and comprehensive representation based on Richard Bader's quantum topological atoms in molecules (AIM) theory where critical points in the electron density are connected through a network. AIM theory provides a wealth of chemical information about individual atoms and their bond connections enabling a more flexible and chemically relevant representation. To obtain even more relevant rules with higher coverage, we apply manual postprocessing and interpretation of ILP rules. We have tested the usefulness of the new representation in SAR modelling on classifying compounds of low/high mutagenicity and on a set of factor Xa inhibitors of high and low affinity. PMID:17054018

  12. SiSAR: advanced SAR simulation

    NASA Astrophysics Data System (ADS)

    Klaus, Ferdinand

    1995-11-01

    SiSAR was planned as a realistic as possible, modular, user-friendly and fast SAR raw data simulator running on ordinary workstations. Interest in (interferometric) SAR products is growing on an international scale. There is a concentration of manpower and financial resources. Dead ends, respectively failures, have to be avoided during design and mission of every SAR project by simulating the system thoroughly before the experiment. Another reason to make use of extensive reproducible simulations during design and development is the reduction of time and manpower costs. As it comes down to verifying and comparing different processing algorithms we see that (interferometric) SAR simulation is an indispensable tool for testing individual processing steps. SiSAR is a modular SAR raw data simulator for realistic description of the functions of a SAR-system. It contains an implementation of diverse models to characterize radar targets, various approaches to describe the trajectory and the motion of the footprint on the target surface and different raw data formation algorithms. Beyond there is a wide supply of tools for manipulation, analysis and user-friendly simulation handling. Results obtained by SiSAR and some first simulated interferometric SAR raw data are shown in the paper.

  13. 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 .

  14. 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

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

    PubMed

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

    2015-01-01

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

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

    PubMed

    Cane, Douglas; McCarthy, Mary; Mazmanian, Dwight

    2016-07-01

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

  17. Structural relationships and vasorelaxant activity of monoterpenes

    PubMed Central

    2012-01-01

    Background and purpose of the study The hypotensive activity of the essential oil of Mentha x villosa and its main constituent, the monoterpene rotundifolone, have been reported. Therefore, our objective was to evaluate the vasorelaxant effect of monoterpenes found in medicinal plants and establish the structure-activity relationship of rotundifolone and its structural analogues on the rat superior mesenteric artery. Methods Contractions of the vessels were induced with 10 μM of phenylephine (Phe) in rings with endothelium. During the tonic phase of the contraction, the monoterpenes (10-8 - 10-3, cumulatively) were added to the organ bath. The extent of relaxation was expressed as the percentage of Phe-induced contraction. Results The results from the present study showed that both oxygenated terpenes (rotundifolone, (+)-limonene epoxide, pulegone epoxide, carvone epoxide, and (+)-pulegone) and non-oxygenated terpene ((+)-limonene) exhibit relaxation activity. The absence of an oxygenated molecular structure was not a critical requirement for the molecule to be bioactive. Also it was found that the position of ketone and epoxide groups in the monoterpene structures influence the vasorelaxant potency and efficacy. Major conclusion The results suggest that the presence of functional groups in the chemical structure of rotundifolone is not essential for its vasorelaxant activity. PMID:23351149

  18. 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.

  19. SAR/QSAR methods in public health practice

    SciTech Connect

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

    2011-07-15

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

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

    PubMed

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

    2016-01-01

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

  1. 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....

  2. STRATEGIES FOR THE USE OF COMPUTATIONAL SAR METHODS IN ASSESSING GENOTOXICITY

    EPA Science Inventory

    The relationship between computational SAR studies and relevant data gathering and generation activities is complex. irst, the chemical class to be studied is selected on the basis of information requirements for hazard identification and assessment. Membership in the class is de...

  3. 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

  4. Severe acute respiratory syndrome (SARS)

    MedlinePlus

    ... when the virus spread from small mammals in China. When someone with SARS coughs or sneezes, infected ... causes SARS include: Antibody tests for SARS Direct isolation of the SARS virus Rapid polymerase chain reaction ( ...

  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. 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

  7. Structure-Activity Relationship of Oligomeric Flavan-3-ols: Importance of the Upper-Unit B-ring Hydroxyl Groups in the Dimeric Structure for Strong Activities.

    PubMed

    Hamada, Yoshitomo; Takano, Syota; Ayano, Yoshihiro; Tokunaga, Masahiro; Koashi, Takahiro; Okamoto, Syuhei; Doi, Syoma; Ishida, Masahiko; Kawasaki, Takashi; Hamada, Masahiro; Nakajima, Noriyuki; Saito, Akiko

    2015-01-01

    Proanthocyanidins, which are composed of oligomeric flavan-3-ol units, are contained in various foodstuffs (e.g., fruits, vegetables, and drinks) and are strongly biologically active compounds. We investigated which element of the proanthocyanidin structure is primarily responsible for this functionality. In this study, we elucidate the importance of the upper-unit of 4-8 condensed dimeric flavan-3-ols for antimicrobial activity against Saccharomyces cerevisiae (S. cerevisiae) and cervical epithelioid carcinoma cell line HeLa S3 proliferation inhibitory activity. To clarify the important constituent unit of proanthocyanidin, we synthesized four dimeric compounds, (-)-epigallocatechin-[4,8]-(+)-catechin, (-)-epigallocatechin-[4,8]-(-)-epigallocatechin, (-)-epigallocatechin-[4,8]-(-)-epigallocatechin-3-O-gallate, and (+)-catechin-[4,8]-(-)-epigallocatechin and performed structure-activity relationship (SAR) studies. In addition to antimicrobial activity against S. cerevisiae and proliferation inhibitory activity on HeLa S3 cells, the correlation of 2,2-diphenyl-l-picrylhydrazyl radical scavenging activity with the number of phenolic hydroxyl groups was low. On the basis of the results of our SAR studies, we concluded that B-ring hydroxyl groups of the upper-unit of the dimer are crucially important for strong and effective activity. PMID:26501251

  8. Surface Deformation Analysis of the Active Faults revealed by InSAR Observations and Geodetic Data in Southern Part of the Taitung Longitudinal Valley, Eastern Taiwan

    NASA Astrophysics Data System (ADS)

    Tung, H.; Chen, H. Y.; Hu, J. C.

    2009-04-01

    The NNE-striking Longitudinal Valley Fault (LVF) in eastern Taiwan is an extremely active inverse fault, which is considered as a collision boundary between the Eurasian and the Philippine Sea plates. The fault segments of the LVF demonstrate different slip behaviors, especially in the southern segment of the LVF. The deformation is partitioned by the strike-slip (Lichi fault segment) and the reverse faulting (Luyeh segment). Thus we investigate crustal deformation pattern along the southern LVF by using SAR interferometry and precise leveling data. The SAR data of the Longitudinal Valley area were collected by ERS-1, ERS-2 and Envisat satellite of the European Space Agency in both descending (track: 232; frame: 3141) and ascending (track: 311; frame: 459) orbits. However, this area is so heavily vegetated that high coherence area is limited in the Taitung City and good interfergrams with better coherence are limited to short time span and small perpendicular baseline pairs. Therefore we made three stacking image from the higher coherence interferograms representing deformation interval from 1995-1996, 1996-1998 and 2006-2008 separately. These three results show a same relative subsidence between Luyeh fault and Lichi fault, which is consistent with leveling data measured that time. Besides, we also used the PSInSAR technique to trace the discrete points that were minimally affected by the decorrelation of radar signals through time. Finally we constrain the deformation map based on PSInSAR with leveling data for better understanding the deformation patterns in the southern Longitudinal Valley area.

  9. 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

  10. 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

  11. 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. PMID:19689389

  12. Structure-activity relationships (SAR) and structure-kinetic relationships (SKR) of sulphone-based CRTh2 antagonists.

    PubMed

    Buil, Maria Antonia; Calbet, Marta; Castillo, Marcos; Castro, Jordi; Esteve, Cristina; Ferrer, Manel; Forns, Pilar; González, Jacob; López, Sara; Roberts, Richard S; Sevilla, Sara; Vidal, Bernat; Vidal, Laura; Vilaseca, Pere

    2016-05-01

    Monocyclic and bicyclic ring systems were investigated as the "core" section of a series of diphenylsulphone-containing acetic acid CRTh2 receptor antagonists. A range of potencies were observed and single-digit nanomolar potencies were obtained in both the monocyclic and bicyclic cores. Residence times for the monocyclic compounds were very short. Some of the bicyclic cores displayed better residence times. A methyl group in the northern part of the core, between the head and tail was a necessary requirement for the beginnings of long residence times. Variations of the tail substitution maximised potencies and residence times. PMID:26922232

  13. Antipoliovirus structure-activity relationships of some aporphine alkaloids.

    PubMed

    Boustie, J; Stigliani, J L; Montanha, J; Amoros, M; Payard, M; Girre, L

    1998-04-01

    A series of 18 aporphinoids have been tested in vitro against human poliovirus. The aporphines (+)-glaucine fumarate (1), (+)-N-methyllaurotetanine (4), (+)-isoboldine (7), and (-)-nuciferine, HCl (10) were found to be active with selectivity indices > 14. The nature of the 1, 2-substituents of the isoquinoline moiety appeared to be critical for antipoliovirus activity. An SAR study demonstrated the importance of a methoxyl group at C-2 on the tetrahydroisoquinoline ring for the induction of antipoliovirus activity. Molecular modeling of some compounds in this series revealed the close similarities between the three-dimensional conformational features of the inactive 1,2-substituted derivatives (+)-boldine (6) and (+)-laurolitsine (5) with derivatives containing the 1,2-(methylenedioxy) moiety, which were generally found to be inactive as exemplified by (+)-cassythicine (9). PMID:9584402

  14. 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%.

  15. Ground deformation associated with post-mining activity at the French-German border revealed by novel InSAR time series method

    NASA Astrophysics Data System (ADS)

    Samsonov, Sergey; d'Oreye, Nicolas; Smets, Benoît

    2013-08-01

    We present a novel methodology for integration of multiple InSAR data sets for computation of two dimensional time series of ground deformation. The proposed approach allows combination of SAR data acquired with different acquisition parameters, temporal and spatial sampling and resolution, wavelength and polarization. Produced time series have combined coverage, improved temporal resolution and lower noise level. We apply this methodology for mapping coal mining related ground subsidence and uplift in the Greater Region of Luxembourg along the French-German border. For this we processed 167 Synthetic Aperture Radar ERS-1/2 and ENVISAT images acquired between 1995 and 2009 from one ascending (track 29) and one descending (track 337) tracks and created over five hundred interferograms that were used for time series analysis. Derived vertical and east-west linear deformation rates show with remarkable precision a region of localized ground deformation located above and caused by mining and post-mining activities. Time series of ground deformation display temporal variability: reversal from subsidence to uplift and acceleration of subsidence in the vertical component, and horizontal motion toward the center of the subsidence on the east-west component. InSAR results are validated by leveling measurements collected by the French Geological Survey (BRGM) during 2006-2008. We determined that deformation rate changes are mainly caused by water level variations in the mines. Due to higher temporal and spatial resolution the proposed space-borne method detected a larger number of subsidence and uplift areas in comparison to leveling measurements restricted to annual monitoring of benchmark points along roads. We also identified one deformation region that is not precisely located above the mining sites. Comparison of InSAR measurements with the water levels measured in the mining pits suggest that part of the water that filled the galleries after termination of the

  16. COMPUTER-ASSISTED STRUCTURE ACTIVITY RELATIONSHIPS OF NITROGENOUS CYCLIC COMPOUNDS TESTED IN SALMONELLA ASSAYS FOR MUTAGENICITY

    EPA Science Inventory

    Study of the relationship between mutagenicity and molecular structure for a data set of nitrogenous cyclic compounds is reported. A computerized SAR system (ADAPT) was utilized to classify a data set of 114 nitrogenous cyclic compounds with 19 molecular descriptors. All of the d...

  17. 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…

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

    PubMed

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

    2016-01-01

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

  19. 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…

  20. SAR Product Control Software

    NASA Astrophysics Data System (ADS)

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

    2003-03-01

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

  1. 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.

  2. Application of an Integrated GPCR SAR-Modeling Platform To Explain the Activation Selectivity of Human 5-HT2C over 5-HT2B.

    PubMed

    Heifetz, Alexander; Storer, R Ian; McMurray, Gordon; James, Tim; Morao, Inaki; Aldeghi, Matteo; Bodkin, Mike J; Biggin, Philip C

    2016-05-20

    Agonism of the 5-HT2C serotonin receptor has been associated with the treatment of a number of diseases including obesity, psychiatric disorders, sexual health, and urology. However, the development of effective 5-HT2C agonists has been hampered by the difficulty in obtaining selectivity over the closely related 5-HT2B receptor, agonism of which is associated with irreversible cardiac valvulopathy. Understanding how to design selective agonists requires exploration of the structural features governing the functional uniqueness of the target receptor relative to related off targets. X-ray crystallography, the major experimental source of structural information, is a slow and challenging process for integral membrane proteins, and so is currently not feasible for every GPCR or GPCR-ligand complex. Therefore, the integration of existing ligand SAR data with GPCR modeling can be a practical alternative to provide this essential structural insight. To demonstrate this, we integrated SAR data from 39 azepine series 5-HT2C agonists, comprising both selective and unselective examples, with our hierarchical GPCR modeling protocol (HGMP). Through this work we have been able to demonstrate how relatively small differences in the amino acid sequences of GPCRs can lead to significant differences in secondary structure and function, as supported by experimental data. In particular, this study suggests that conformational differences in the tilt of TM7 between 5-HT2B and 5-HT2C, which result from differences in interhelical interactions, may be the major source of selectivity in G-protein activation between these two receptors. Our approach also demonstrates how the use of GPCR models in conjunction with SAR data can be used to explain activity cliffs. PMID:26900768

  3. Space-Borne and Ground-Based Sar Interferometry for Landslide Activity Analysis and Monitoring in the Appennines of Emilia Romagna (Italy): Review of Methods and Preliminary Results

    NASA Astrophysics Data System (ADS)

    Barbieri, M.; Corsini, A.; Casagli, N.; Farina, P.; Coren, F.; Sterzai, P.; Leva, D.; Tarchi, D.

    2004-06-01

    This work concerns the application of SAR interferometry for the assessment of the long-term analysis of the state of activity of deep seated mass movements affecting some urban areas in the northern Appennines of Emilia Romagna region (from 1994-2001 space-borne ERS data) and for the real-time monitoring of active flow-like landslides in year 2002 (from ground-based system). These activities are part of an ongoing research project supported by civil protection authorities of the Emilia-Romagna region that involves several research institutes with diverse expertises. A set of test sites characterized by a high landslide risk have been selected mainly taking into account phenomena characteristics such as deformation rates and vegetation coverage, with respect to the employed techniques. After a preliminary detailed geomorphologic characterization of the sites, the interferometric analyses, still in progress, have been implemented. In particular space-borne DInSAR has been applied for 10 unstable areas using a set of ERS1/ERS2 data acquired in the last 7 years. From 9 interferograms, the line-of-sight displacement maps have been calculated and, later on, post processed in GIS environment in order to have on-slope-direction displacement maps that could fully be integrated with geomorphologic and ancillary data and that could semi-quantitatively be compared with other traditional monitoring data. The results obtained have been rather satisfactory, especially in some test sites where entire villages are settled on the mass movement, as in the case of Berceto (Parma) presented in the paper, and post-processed products have proved a significant amelioration of basic interferometric ones. Moreover, in order to measure terrain displacements induced by landslide characterized by high deformation rates and little urbanisation, ground-based SAR interferometry (GBInSAR) has been used for the monitoring of a test site located in the province of Bologna. This application proved

  4. 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

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

    PubMed

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

    2016-09-01

    The number of engineered nanomaterials (ENMs) being exploited commercially is growing rapidly, due to the novel properties they exhibit. Clearly, it is important to understand and minimize any risks to health or the environment posed by the presence of ENMs. Data-driven models that decode the relationships between the biological activities of ENMs and their physicochemical characteristics provide an attractive means of maximizing the value of scarce and expensive experimental data. Although such structure-activity relationship (SAR) methods have become very useful tools for modelling nanotoxicity endpoints (nanoSAR), they have limited robustness and predictivity and, most importantly, interpretation of the models they generate is often very difficult. New computational modelling tools or new ways of using existing tools are required to model the relatively sparse and sometimes lower quality data on the biological effects of ENMs. The most commonly used SAR modelling methods work best with large datasets, are not particularly good at feature selection, can be relatively opaque to interpretation, and may not account for nonlinearity in the structure-property relationships. To overcome these limitations, we describe the application of a novel algorithm, a genetic programming-based decision tree construction tool (GPTree) to nanoSAR modelling. We demonstrate the use of GPTree in the construction of accurate and interpretable nanoSAR models by applying it to four diverse literature datasets. We describe the algorithm and compare model results across the four studies. We show that GPTree generates models with accuracies equivalent to or superior to those of prior modelling studies on the same datasets. GPTree is a robust, automatic method for generation of accurate nanoSAR models with important advantages that it works with small datasets, automatically selects descriptors, and provides significantly improved interpretability of models. PMID:26956430

  6. Synthesis, antitumor activity, and structure-activity relationship of some benzo[a]pyrano[2,3-c]phenazine derivatives.

    PubMed

    Gao, Jing; Chen, Ming; Tong, Xue; Zhu, He; Yan, Hongbin; Liu, Daichun; Li, Wanjing; Qi, Shengyu; Xiao, Dake; Wang, Yongzhi; Lu, Yuanyuan; Jiang, Feng

    2015-01-01

    A series of benzo[a]pyrano[2,3-c]phenazine derivatives with a wide range of substitutions at ring C of the benzophenazine were designed and synthesized using the one-pot, four-component domino reactions. The targeted compounds were evaluated for their antitumor activities against HCT116, MCF7, HepG2 and A549 cancer cell lines in vitro. The most active compound 6{1,2,1,9} featured the CN and p-dimethylamino phenyl substituents on γ-pyran structure on ring C. Significantly, compound 6{1,2,1,9} was found to have the highest growth inhibitory activity against the HepG2 cell line with IC50 values of 6.71 µM, which was 1.6-fold more potent than positive control anticancer drug Hydroxycamptothecine (HCPT). Furthermore, structure-activity relationship (SAR) studies on the substitutions at ring C were discussed in details. PMID:26369405

  7. A Binding Site Model and Structure-Activity Relationships for the Rat A3 Adenosine Receptor

    PubMed Central

    VAN GALEN, PHILIP J. M.; VAN BERGEN, ANDREW H.; GALLO-RODRIGUEZ, CAROLA; MELMAN, NELI; OLAH, MARK E.; IJZERMAN, AD P.; STILES, GARY L.; JACOBSON, KENNETH A.

    2012-01-01

    SUMMARY A novel adenosine receptor, the A3 receptor, has recently been cloned. We have systematically investigated the hitherto largely unexplored structure-activity relationships (SARs) for binding at A3 receptors, using 125I-N6-2-(4-aminophenyl)ethyladenosine as a radioligand and membranes from Chinese hamster ovary cells stably transfected with the rat A3-cDNA. As is the case for A1 and A2a, receptors, substitutions at the N6 and 5′ positions of adenosine, the prototypic agonist ligand, may yield fairly potent compounds. However, the highest affinity and A3 selectivity is found for N6,5′-disubstituted compounds, in contrast to A1 and A2a receptors. Thus, N6-benzyladenosine-5′-N-ethylcarboxamide is highly potent (Ki, 6.8 nM) and moderately selective (13- and 14-fold versus A1 and A2a). The N6 region of the A3 receptor also appears to tolerate hydrophilic substitutions, in sharp contrast to the other subtypes. Potencies of N6,5′-disubstituted compounds in inhibition of adenylate cyclase via A3 receptors parallel their high affinity in the binding assay. None of the typical xanthine or nonxanthine (A1/A2) antagonists tested show any appreciable affinity for rat A3 receptors. 1,3-Dialkylxanthines did not antagonize the A3 agonist-induced inhibition of adenylate cyclase. A His residue in helix 6 that is absent in A3 receptors but present in A1/A2 receptors may be causal in this respect. In a molecular model for the rat A3 receptor, this mutation, together with an increased bulkiness of residues surrounding the ligand, make antagonist binding unfavorable when compared with a previously developed A1 receptor model. Second, this A3 receptor model predicted similarities with A1 and A2 receptors in the binding requirements for the ribose moiety and that xanthine-7-ribosides would bind to rat A3 receptors. This hypothesis was supported experimentally by the moderate affinity (Ki 6 μM) of 7-riboside of 1,3-dibutylxanthine, which appears to be a partial agonist at

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

    PubMed

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

    2016-04-01

    α-Keto amide derivatives as enterovirus 71 (EV71) 3C protease (3C(pro)) inhibitors have been synthesized and assayed for their biochemical and antiviral activities. structure-activity relationship (SAR) study indicated that small moieties were primarily tolerated at P1' and the introduction of para-fluoro benzyl at P2 notably improved the potency of inhibitor. Inhibitors 8v, 8w and 8x exhibited satisfactory activity (IC50=1.32±0.26μM, 1.88±0.35μM and 1.52±0.31μM, respectively) and favorable CC50 values (CC50>100μM). α-Keto amide may represent a good choice as a warhead for EV71 3C(pro) inhibitor. PMID:26916437

  9. Synthesis and structure-activity relationship studies of O-biphenyl-3-yl carbamates as peripherally restricted fatty acid amide hydrolase inhibitors.

    PubMed

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

    2013-07-25

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

  10. Use of Global Meteorological Model to Correct for Stratified Tropospheric Delays in SAR Data: Application to Active Mexican Stratovolcanoes.

    NASA Astrophysics Data System (ADS)

    Pinel, V. M.; Doin, M.; de La Cruz-Reyna, S.; Hooper, A.

    2008-12-01

    Artefacts induced by temporal changes of water content within the tropospheric layer have long been recognised as the main limitation for the use of InSAR data in order to detect magma movement at depth beneath stratovolcanoes (Delacourt, 1998). Difficulty in discriminating between tropospheric artefacts and deformation induced by magma accumulation or withdrawal at depth is mainly due to the similarity of the expected signal centred on the volcanic edifice. However it is of prime importance to be able to detect magma storage which is the most reliable precursor for volcanic eruptions. We processed time series of InSAR data acquired by ENVISAT from December 2002 to August 2006 at Popocatépetl and Colima Volcano (Mexico) using both the Stanford method for persistent scatterers and a derived small baseline approach (Hooper, 2008). Tropospheric delays are estimated for each interferogram using temperature, pressure and water content profiles from the North American Regional Reanalysis (NARR), a global atmospheric model provided by the National Centers for Environmental Prediction. A strong seasonal effect is observed leading to maximum value for delays of 10 rad/km corresponding to 4 fringes on the volcano slopes. These delays are validated using the correlation between the wrapped phase and the elevation as well as spectrometer data acquired by the Medium Resolution Imaging System (MERIS) onboard on the ENVISAT platform. The tropospheric effect is removed from the wrapped phase which improves the unwrapping process. On Popocatépetl no significant deformations were observed. We could not detect any deep magma storage zone beneath Colima volcano, but its summit area exhibits a constant and almost linear subsidence of more than 1.5 cm/year mainly related to recent volcanic deposits loading. References: Delacourt, P. Briole and J. Achache, Tropospheric corrections of SAR interferograms with strong topography. Application to Etna. Geophys. Res. Lett., 25, 2849- 2852

  11. Synergistic measurements of ocean winds and waves from SAR

    NASA Astrophysics Data System (ADS)

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

    2015-09-01

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

  12. Hybrid reduced graph for SAR studies.

    PubMed

    Carrasco-Velar, R; Prieto-Entenza, J O; Antelo-Collado, A; Padrón-García, J A; Cerruela-García, G; Maceo-Pixa, Á L; Alcolea-Núñez, R; Silva-Rojas, L G

    2013-01-01

    The purpose of this work is the definition and evaluation of both atomic and local new hybrid indices. Inspired by the Refractotopological State Index for Atoms, the new atomic indices are theoretically supported by graph theory principles. The local indices, named Descriptor Centres (DCs), are obtained from the sum of the atomic values of the atoms in the selected group. Different classifiers were used for structure-activity relationship (SAR) studies, including multilayer perceptron (MLP), support vector machines (SVM) and meta-classifiers. Prediction with SVM and MLP was around 60%, but the best result was obtained with the meta-classifiers, bagging, decorate and others, with more than 92% accurate prediction. These new hybrid descriptors derived from the Refractotopological State Index for Atoms show a low mutual correlation coefficient. The same behaviour is found in the analogously defined Descriptors Centres. The best results are obtained with the inclusion of the distance between DCs with the use of meta-classifiers. PMID:23439282

  13. Nano-SAR development for bioactivity of nanoparticles with considerations of decision boundaries.

    PubMed

    Liu, Rong; Rallo, Robert; Weissleder, Ralph; Tassa, Carlos; Shaw, Stanley; Cohen, Yoram

    2013-05-27

    The development of classification nano-structure-activity Relationships (nano-SARs) of nanoparticle (NP) bioactivity is presented with the aim of demonstrating the integration of multiparametric toxicity/bioactivity assays to arrive at statistically meaningful class definitions (i.e., bioactivity/inactivity endpoints), as well as the implications of nano-SAR applicability domains and decision boundaries. Nano-SARs are constructed based on a dataset of 44 iron oxide core nanoparticles (NPs), used in molecular imaging and nano-sensing, containing bioactivity profiles for four cell types and four different assays. Class definitions are developed on the basis of 'hit' (i.e., significant bioactivity) identification analysis and self-organizing map based consensus clustering; these class definitions enable construction of nano-SARs of a high classification accuracy (>78%) with different NP descriptor combinations that include primary size, spin-lattice and spin-spin relaxivities, and zeta potentials. Analysis of the nano-SAR performance for different class definitions suggests that H4 (i.e., class with at least four hits) is a reasonable endpoint (from a 'regulatory' viewpoint) for keeping the level of false negatives (i.e., incorrect labeling of bioactive NPs as inactive) low. The establishment of a quantitative nano-SAR applicability domain is demonstrated, making use of a probability density with the H4 class definition and naive Bayesian classifier (NBC) model (with spin-lattice relaxivity and zeta potential as descriptors). Decision boundaries are determined for the above H4/NBC nano-SAR for different acceptance levels of false negative to false positive predictions, illustrating a practical approach that may assist in regulatory decision making with a consideration of reducing the likelihood of identifying bioactive NPs as being inactive. PMID:23423856

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

    PubMed Central

    2014-01-01

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

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

    PubMed

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

    2016-07-29

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

  16. 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

  17. [Severe acute respiratory syndrome (SARS)].

    PubMed

    Gillissen, Adrian; Ruf, Bernhard R

    2003-06-15

    Severe acute respiratory syndrome (SARS) is a viral disease, observed primarily in Southern China in November 2002, with variable flu-like symptoms and pneumonia, in approx. 5% leading to death from respiratory distress syndrome (RDS). The disease was spread over more than 30 states all over the globe by SARS-virus-infected travelers. WHO and CDC received first information about a new syndrome by the end of February 2003, after the first cases outside the Republic of China had been observed. A case in Hanoi, Vietnam, led to the first precise information about the new disease entity to WHO, by Dr. Carlo Urbani, a co-worker of WHO/Doctors without Borders, who had been called by local colleagues to assist in the management of a patient with an unknown severe disease by the end of February 2003. Dr. Urbani died from SARS, as did many other health care workers. In the meantime, more than 7,000 cases have been observed worldwide, predominantly in China and Hong Kong, but also in Taiwan, Canada, Singapore, and the USA, and many other countries, and more than 600 of these patients died from RDS. Since the beginning of March 2003, when WHO and CDC started their activities, in close collaboration with a group of international experts, including the Bernhard-Nocht-Institute in Hamburg and the Department of Virology in Frankfurt/Main, a previously impossible success in the disclosure of the disease was achieved. Within only 8 weeks of research it was possible to describe the infectious agent, a genetically modified coronavirus, including the genetic sequence, to establish specific diagnostic PCR methods and to find possible mechanisms for promising therapeutic approaches. In addition, intensifying classical quarantine and hospital hygiene measures, it was possible to limit SARS in many countries to sporadic cases, and to reduce the disease in countries such as Canada and Vietnam. This review article summarizes important information about many issues of SARS (May 15th, 2003

  18. 1-[(3-Aryloxy-3-aryl)propyl]-1H-imidazoles, new imidazoles with potent activity against Candida albicans and dermatophytes. Synthesis, structure-activity relationship, and molecular modeling studies.

    PubMed

    La Regina, Giuseppe; D'Auria, Felicia Diodata; Tafi, Andrea; Piscitelli, Francesco; Olla, Stefania; Caporuscio, Fabiana; Nencioni, Lucia; Cirilli, Roberto; La Torre, Francesco; De Melo, Nadja Rodrigues; Kelly, Steven L; Lamb, David C; Artico, Marino; Botta, Maurizio; Palamara, Anna Teresa; Silvestri, Romano

    2008-07-10

    New 1-[(3-aryloxy-3-aryl)propyl]-1 H-imidazoles were synthesized and evaluated against Candida albicans and dermatophytes in order to develop structure-activity relationships (SARs). Against C. albicans the new imidazoles showed minimal inhibitory concentrations (MICs) comparable to those of ketoconazole, miconazole, and econazole, and were more potent than fluconazole. Several derivatives ( 10, 12, 14, 18- 20, 24, 28, 29, 30, and 34) turned out to be potent inhibitors of C. albicans strains resistant to fluconazole, with MIC values less than 10 microg/mL. Against dermatophytes strains, compounds 20, 25, and 33 (MIC SARs of imidazoles 10- 44 were rationalized with reasonable accuracy by a previously developed quantitative pharmacophore for antifungal agents. PMID:18529046

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

    NASA Astrophysics Data System (ADS)

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

    2014-05-01

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

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

    PubMed

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

    2015-01-01

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

  1. 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.

  2. The relationship between chitotriosidase activity and tuberculosis.

    PubMed

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

    2015-11-01

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

  3. Possible relationships between solar activity and meteorological phenomena

    NASA Technical Reports Server (NTRS)

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

    1975-01-01

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

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

    PubMed

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

    2011-09-15

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-05-01

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

  6. 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.

  7. On the number of EINECS compounds that can be covered by (Q)SAR models for acute toxicity.

    PubMed

    Zvinavashe, Elton; Murk, Albertinka J; Rietjens, Ivonne M C M

    2009-01-10

    The new EU legislation for managing chemicals called REACH aims to fill in gaps in toxicity information that exist for the chemicals listed on the European Inventory of Existing Chemical Substances (EINECS). REACH advocates the use of alternatives to animal experimentation including, amongst others, (quantitative) structure-activity relationship models [(Q)SARs] to help fill in the toxicity data gaps. The aim of the present study was to provide a science-based estimate of the number of EINECS compounds that can be covered by (Q)SAR models for acute toxicity. Using the ECOSAR software, 54% of the 100196 EINECS chemicals were classified into 49 classes that can be potentially covered by (Q)SAR models. The largest proportion of the classified compounds (40% of the EINECS list) falls into the classes of non-polar and polar narcotics. Compounds that were not classified include, for example, fish oils, botanical and animal extracts, and crude oil distillates. With rapid improvements in analytical tools, the number of EINECS compounds for which toxicity evaluations may be based on (Q)SAR approaches may be extended by further developing the method recently developed for the safety assessment of natural flavor complexes used as ingredients in food. This method is based on identification of the individual components in a mixture, and judgment of the safety of these identified individual compounds using toxicity information on structurally similar congeners in the respective classes. Such (Q)SAR approaches may be applied to an additional 2938 EINECS compounds, representing botanical and animal extracts, leading to a total estimate of 57% of the EINECS compounds for which (Q)SAR-based approaches may assist in their safety assessment. It is concluded that, despite the fact that individual (Q)SARs may often each cover only a limited number, i.e. less than 1%, of the EINECS compounds, the potential for applying (Q)SAR approaches for safety assessment of EINECS compounds may prove

  8. 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…

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

    PubMed

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

    2015-02-26

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

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

    PubMed Central

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

    2015-01-01

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

  11. 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…

  12. Relationships between Reading Activities and Language Use.

    ERIC Educational Resources Information Center

    Gordon, Sandra L.; Van Dongen, Richard

    1988-01-01

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

  13. Distributed Anelastic Strain and its Relationship to Compliant Zones Surrounding Active Faults of the Eastern California Shear Zone

    NASA Astrophysics Data System (ADS)

    Shelef, E.; Oskin, M.; Fialko, Y.

    2006-12-01

    Geologic measurements of distributed anelastic strain (DAS) adjacent to active strike slip faults of the Mojave Desert portion of the Eastern California shear zone quantify the magnitude, mechanism, temporal evolution, and relationship of DAS to fault compliant zones imaged via InSAR. Prefaulting markers (mylonitic lineation, dikes, and faults assumed linear prior to dextral faulting) in crystalline rocks next to the Harper Lake fault and Calico fault indicate that DAS accounts for 6 to 23 percent of total displacement and that this displacement scales with fault slip. We conclude that DAS is a significant, active process that is not restricted to the initial fault propagation stage. We find that the width of the zone of DAS is 400-700 m on each side of the faults studied, irrespective of total fault slip. 60 percent of the displacement due to DAS occurs within 100 m of the Calico fault. A similar zone of more intense deformation occurs adjacent to the Harper Lake fault. These 100m- wide-zones are of the same extent but much less intensely deformed compared to the damage zones surrounding the San Andreas fault. Based on these relationships, we hypothesize that damage feedback progressively focuses DAS into a stable, approximately 100-m-wide-zone where its intensity can increase proportionally to fault slip. Disruption of linear markers supports that DAS in crystalline rocks occurs via slip along secondary faults and small-scale block rotation with block sizes decreasing with proximity to faults. The widths of the geologically documented zones of DAS in the Eastern California shear zone are similar to the approximately 1 km width of compliant zones modeled from InSAR observations of surface deformation due to stress changes caused by nearby earthquakes. This correlation suggests a relationship between damage- reduction of shear modulus and displacement via DAS. Paleomagnetic measurements of prefaulting and syntectonically emplaced volcanic rocks in sedimentary

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

    NASA Astrophysics Data System (ADS)

    Cronin, Mark T. D.

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

  15. Synthetic retinoids: structure-activity relationships.

    PubMed

    Barnard, Jonathan H; Collings, Jonathan C; Whiting, Andrew; Przyborski, Stefan A; Marder, Todd B

    2009-11-01

    Retinoid signalling pathways are involved in numerous processes in cells, particularly those mediating differentiation and apoptosis. The endogenous ligands that bind to the retinoid receptors, namely all-trans-retinoic acid (ATRA) and 9-cis-retinoic acid, are prone to double-bond isomerisation and to oxidation by metabolic enzymes, which can have significant and deleterious effects on their activities and selectivities. Many of these problems can be overcome through the use of synthetic retinoids, which are often much more stable, as well as being more active. Modification of their molecular structures can result in retinoids that act as antagonists, rather than agonists, or exhibit a large degree of selectivity for particular retinoid-receptor isotypes. Several such selective retinoids are likely to be of value as pharmaceutical agents with reduced toxicities, particularly in cancer therapy, as reagents for controlling cell differentiation, and as tools for elucidating the precise roles that specific retinoid signalling pathways play within cells. PMID:19821467

  16. Ground Deformation Associated With Post-Mining Activity at the French-German Border Revealed by Multidimensional Time Series Analysis of SAR Data Acquired in Various Orbital Geometries

    NASA Astrophysics Data System (ADS)

    Smets, B.; Samsonov, S. V.; d'Oreye, N.

    2012-12-01

    We present the application of an innovative methodology for producing multidimensional time series of ground deformation from satellite radar data acquired by sensors with various acquisition geometry, ground resolution, and wave band (Samsonov and d'Oreye, Resubmitted). This technique is based on the Small Baseline Subset (SBAS) method that is modified to produce horizontal and vertical time series of ground deformation. Produced time series have combined coverage, improved temporal resolution and lower noise level. We apply this methodology for mapping coal mining related ground subsidence and heave in the Greater Region of Luxembourg along the French-German border. For this we processed 167 Synthetic Aperture Radar ERS-1/2 and ENVISAT images acquired between 1995 and 2009 from one ascending (track 29) and one descending (track 337) tracks and created over five hundred interferograms that were used for time series analysis. Produced vertical and east-west linear deformation rates show with remarkable precision region of localized ground deformation located above and caused by mining and post-mining activities. Time series of ground de- formation display temporal variability: reversal from subsidence to uplift and acceleration of subsidence on the vertical component and horizontal motion towards the center of the subsidence on the east-west component. InSAR results are successfully validated by leveling measurements performed by the French Geological Survey (BRGM) during 2006-2008. We determined that deformation rate changes are mainly caused by water level variations in the mines. Due to higher temporal and spatial resolution the proposed space-born method detected a larger number of subsidence and uplift areas in comparison to leveling measurements restricted to annual monitoring of benchmark points along roads. We also identified deformation regions that are not precisely located above the mining sites. Comparison of InSAR measurements with the water levels

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

    PubMed Central

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

    2012-01-01

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

  18. Knowledge based SAR images exploitations

    NASA Astrophysics Data System (ADS)

    Wang, David L.

    1987-01-01

    One of the basic functions of SAR images exploitation system is the detection of man-made objects. The performance of object detection is strongly limited by performance of segmentation modules. This paper presents a detection paradigm composed of an adaptive segmentation algorithm based on a priori knowledge of objects followed by a top-down hierarchical detection process that generates and evaluates object hypotheses. Shadow information and inter-object relationships can be added to the knowledge base to improve performance over that of a statistical detector based only on the attributes of individual objects.

  19. Derivation of terrain slope from SAR interferometric phase gradient

    NASA Technical Reports Server (NTRS)

    Wegmueller, Urs; Werner, Charles L.; Rosen, Paul A.

    1994-01-01

    The relationship between the gradient of the interferometric phase and the terrain slope, which, it is thought, would allow a derivation of the terrain slopes without phase unwrapping, is presented. A linear relationship between the interferometric phase gradient and the terrain slopes was found. A quantitative error analysis showed that only very small errors are introduced by these approximations for orbital Synthetic Aperture Radar (SAR) geometries. An example of a slope map for repeat pass interferometry from ERS-1 SAR data is given. A number of direct and indirect applications of the terrain slope are indicated: erosion and avalanche hazard studies, radiometric calibration of SAR data, and normalization of the interferometric correlation coefficient.

  20. Web-GIS-based SARS epidemic situation visualization

    NASA Astrophysics Data System (ADS)

    Lu, Xiaolin

    2004-03-01

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

  1. Interaction between photoperiod and an endogenous seasonal factor in influencing the diel locomotor activity of the benthic polychaete Nereis virens Sars.

    PubMed

    Last, Kim S; Olive, Peter J W

    2004-04-01

    The locomotor activity of Nereis virens Sars associated with food prospecting was investigated in response to photoperiod and season using an actograph. Experimental animals which had been reared under natural photoperiods were exposed to two constant photoperiodic treatments, LD 16:8 and LD 8:16, in both the autumn and winter and in the absence of tidal entrainment. Autocorrelation analysis of rhythmicity showed that during the autumn, animals under the LD 16:8 photoperiod displayed a strong nocturnal rhythm of activity, whereas animals under the LD 8:16 photoperiod showed only a weak nocturnal activity rhythm. This is believed to represent an autumn feeding cessation that is triggered when the animals pass through a critical photoperiod LD(crit) <12:>12. Later in the winter, however, animals exposed to both photoperiodic treatments showed strong rhythms of foraging activity irrespective of the imposed photoperiod. It is suggested that the autumn cessation may maximize the fitness of N. virens, a spring-breeding semelparous organism, by reducing risk during gamete maturation, while spontaneous resurgence of activity after the winter solstice permits animals that are not physiologically competent to spawn to accrue further metabolic reserves. This response is believed to be initiated by a seasonal (possibly circannual) endogenous oscillator or interval timer. PMID:15111365

  2. 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.

  3. Structure–Activity Relationships of α-Keto Oxazole Inhibitors of Fatty Acid Amide Hydrolase

    PubMed Central

    Hardouin, Christophe; Kelso, Michael J.; Romero, F. Anthony; Rayl, Thomas J.; Leung, Donmienne; Hwang, Inkyu; Cravatt, Benjamin F.; Boger, Dale L.

    2008-01-01

    A systematic study of the structure–activity relationships (SAR) of 2b (OL-135), a potent inhibitor of fatty acid amide hydrolase (FAAH), is detailed targeting the C2 acyl side chain. A series of aryl replacements or substituents for the terminal phenyl group provided effective inhibitors (e.g., 5c, aryl = 1-napthyl, Ki = 2.6 nM) with 5hh (aryl = 3-Cl-Ph, Ki = 900 pM) being 5-fold more potent than 2b. Conformationally-restricted C2 side chains were examined and many provided exceptionally potent inhibitors of which 11j (ethylbiphenyl side chain) was established to be a 750 pM inhibitor. A systematic series of heteroatoms (O, NMe, S), electron-withdrawing groups (SO, SO2), and amides positioned within and hydroxyl substitutions on the linking side chain were investigated which typically led to a loss in potency. The most tolerant positions provided effective inhibitors (12p, 6-position S, Ki = 3 nM or 13d, 2-position OH, Ki = 8 nM) comparable in potency to 2b. Proteomic-wide screening of selected inhibitors from the systematic series of >100 candidates prepared revealed that they are selective for FAAH over all other mammalian serine proteases. PMID:17559203

  4. 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

  5. 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. PMID:19399244

  6. 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.

  7. 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.

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

    PubMed

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

    2016-04-13

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

  9. Antioxidant activity of taxifolin: an activity-structure relationship.

    PubMed

    Topal, Fevzi; Nar, Meryem; Gocer, Hulya; Kalin, Pınar; Kocyigit, Umit M; Gülçin, İlhami; Alwasel, Saleh H

    2016-08-01

    Taxifolin is a kind of flavanonol, whose biological ability. The objectives of this study were to investigate the antioxidants and antiradical activities of taxifolin by using different in vitro bioanalytical antioxidant methods including DMPD√(+), ABTS√(+), [Formula: see text], and DPPH√-scavenging effects, the total antioxidant influence, reducing capabilities, and Fe(2+)-chelating activities. Taxifolin demonstrated 81.02% inhibition of linoleic acid emulsion peroxidation at 30 µg/mL concentration. At the same concentration, standard antioxidants including trolox, α-tocopherol, BHT, and BHA exhibited inhibitions of linoleic acid emulsion as 88.57, 73.88, 94.29, and 90.12%, respectively. Also, taxifolin exhibited effective DMPD√(+), ABTS√(+), [Formula: see text], and DPPH√-scavenging effects, reducing capabilities, and Fe(2+)-chelating effects. The results obtained from this study clearly showed that taxifolin had marked antioxidant, reducing ability, radical scavenging and metal-chelating activities. Also, this study exhibits a scientific shore for the significant antioxidant activity of taxifolin and its structure-activity insight. PMID:26147349

  10. Discovery and SAR of Novel and Selective Inhibitors of Urokinase Plasminogen Activator (uPA) with an Imidazo[1,2-a]pyridine Scaffold.

    PubMed

    Gladysz, Rafaela; Adriaenssens, Yves; De Winter, Hans; Joossens, Jurgen; Lambeir, Anne-Marie; Augustyns, Koen; Van der Veken, Pieter

    2015-12-10

    Urokinase plasminogen activator (uPA) is a biomarker and therapeutic target for several cancer types. Its inhibition is regarded as a promising, noncytotoxic approach in cancer therapy by blocking growth and/or metastasis of solid tumors. Earlier, we reported the modified substrate activity screening (MSAS) approach and applied it for the identification of fragments with affinity for uPA's S1 pocket. Here, these fragments are transformed into a novel class of uPA inhibitors with an imidazo[1,2-a]pyridine scaffold. The SAR for uPA inhibition around this scaffold is explored, and the best compounds in the series have nanomolar uPA affinity and selectivity with respect to the related trypsin-like serine proteases (thrombin, tPA, FXa, plasmin, plasma kallikrein, trypsin, FVIIa). Finally, the approach followed for translating fragments into small molecules with a decorated scaffold architecture is conceptually straightforward and can be expected to be broadly applicable in fragment-based drug design. PMID:26575094

  11. 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

  12. 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

  13. The Relationship Between Neck Pain and Physical Activity

    PubMed Central

    Cheung, Janice; Kajaks, Tara; MacDermid, Joy C.

    2013-01-01

    Neck pain is a significant societal burden due to its high prevalence and healthcare costs. While physical activity can help to manage other forms of chronic musculoskeletal pain, little data exists on the relationship between physical activity and neck pain. The purpose of this study was to compare physical activity levels between individuals with neck pain and healthy controls, and then to relate disability, fear of movement, and pain sensitivity measures to physical activity levels in each of the two participant groups. 21 participants were recruited for each of the two participant groups (n = 42). Data collection included the use of the Neck Disability Index, the Tampa Scale for Kinesiophobia, electrocutaneous (Neurometer® CPT) and pressure stimulation (JTech algometer) for quantitative sensory testing, and 5 days of subjective (Rapid Assessment of Physical Activity) and objective (BioTrainer II) measurements of physical activity. Analysis of Variance and Pearson’s Correlation were used to determine if differences and relationships exist between dependent variables both within and between groups. The results show that individuals with mild neck pain and healthy controls do not differ in subjectively and objectively measured physical activity. While participants with neck pain reported higher neck disability and fear of movement, these factors did not significantly relate to physical activity levels. Perceived activity level was related to pain threshold and tolerance at local neck muscles sites (C2 paraspinal muscle and upper trapezius muscle), whereas measured activity was related to generalized pain sensitivity, as measured at the tibialis anterior muscle site. PMID:24133553

  14. Structure-activity relationship of indoloquinoline analogs anti-MRSA.

    PubMed

    Zhao, Min; Kamada, Tomonori; Takeuchi, Aya; Nishioka, Hiromi; Kuroda, Teruo; Takeuchi, Yasuo

    2015-12-01

    Indolo[3,2-b]quinoline analogs (3a-3s), 4-(acridin-9-ylamino) phenol hydrochloride (4), benzofuro[3,2-b]quinoline (3t), indeno[1,2-b]quinolines (3u and 3v) have been synthesized. Those compounds were found to exhibit anti-bacterial activity towards Methicillin-resistant Staphylococcus aureus (anti-MRSA activity). Structure-activity relationship studies were conducted that indoloquinoline ring, benzofuroquinoline ring and 4-aminophenol group are essential structure for anti-MRSA activity. PMID:26522949

  15. Discovery and structure-activity relationships of modified salicylanilides as cell permeable inhibitors of poly(ADP-ribose) glycohydrolase (PARG)

    PubMed Central

    Steffen, Jamin D.; Coyle, Donna L.; Damodaran, Komath; Beroza, Paul; Jacobson, Myron K.

    2011-01-01

    The metabolism of poly(ADP-ribose) (PAR) in response to DNA strand breaks, which involves the concerted activities of poly(ADP-ribose) polymerases (PARPs) and poly(ADP-ribose) glycohydrolase (PARG), modulates cell recovery or cell death depending upon the level of DNA damage. While PARP inhibitors show high promise in clinical trials due to their low toxicity and selectivity for BRCA related cancers, evaluation of the therapeutic potential of PARG is limited by the lack of well-validated cell permeable inhibitors. In this study, Target-related Affinity Profiling (TRAP), an alternative to high-throughput screening, was used to identify a number of drug-like compounds from several chemical classes that demonstrated PARG inhibition in the low-micromolar range. A number of analogs of one of the most active chemotypes were synthesized to explore structure-activity relationship (SAR) for that series. This led to the discovery of a putative pharmacophore for PARG inhibition that contains a modified salicylanilide structure. Interestingly, these compounds also inhibit PARP-1, indicating strong homology in the active sites of PARG and PARP-1, and raising a new challenge for development of PARG specific inhibitors. The cellular activity of a lead inhibitor was demonstrated by the inhibition of both PARP and PARG activity in squamous cell carcinoma cells, although preferential inhibition of PARG relative to PARP was observed. The ability of inhibitors to modulate PAR metabolism via simultaneous effects on PARPs and PARG may represent a new approach for therapeutic development. PMID:21692479

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

    SciTech Connect

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

    1991-12-01

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

  17. SAR calibration: A technology review

    NASA Technical Reports Server (NTRS)

    Larson, R. W.; Politis, D. T.; Shuchman, R. A.

    1983-01-01

    Various potential applications of amplitude-calibrated SAR systems are briefly described, along with an estimate of calibration performance requirements. A review of the basic SAR calibration problem is given. For background purposes and to establish consistent definition of terms, various conventional SAR performance parameters are reviewed along with three additional parameters which are directly related to calibrated SAR systems. Techniques for calibrating a SAR are described. Included in the results presented are: calibration philosophy and procedures; review of the calibration signal generator technology development with results describing both the development of instrumentation and internal calibration measurements for two SAR systems; summary of analysis and measurements required to determine optimum retroreflector design and configuration for use as a reference for the absolute calibration of a SAR system; and summary of techniques for in-flight measurements of SAR antenna response.

  18. Segmentation Of Polarimetric SAR Data

    NASA Technical Reports Server (NTRS)

    Rignot, Eric J. M.; Chellappa, Rama

    1994-01-01

    Report presents one in continuing series of studies of segmentation of polarimetric synthetic-aperture-radar, SAR, image data into regions. Studies directed toward refinement of method of automated analysis of SAR data.

  19. 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

  20. The potential of SAR directional spectra in operational wave forecasting

    NASA Technical Reports Server (NTRS)

    Beal, R. C.; Gerling, T. W.; Irvine, D. E.

    1983-01-01

    Digitally processed Seasat SAR ocean wave imagery, when digitally transformed, smoothed, and corrected for known instrument biases, can accurately track multiple (at least three) wave systems in the open ocean, across major currents, and into shallow water. Furthermore, the relative backscatterer of the digitally processed SAR image, when sampled within a single pass and along a constant range, responds to the local wind through a simple power law relationship. The results indicate that SAR spectra, if obtained from a low altitude satellite, could be an important supplement to global winds and non-directional wave heights obtained through other methods.

  1. 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.

  2. 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. PMID:21504755

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

    PubMed Central

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

    2010-01-01

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

  4. PHARUS airborne SAR concept

    NASA Astrophysics Data System (ADS)

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

    1995-11-01

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

  5. Discovery and preliminary structure-activity relationship studies on tecomaquinone I and tectol as novel farnesyltransferase and plasmodial inhibitors.

    PubMed

    Cadelis, Melissa M; Bourguet-Kondracki, Marie-Lise; Dubois, Joëlle; Valentin, Alexis; Barker, David; Copp, Brent R

    2016-07-15

    Biological screening of a library of synthesized benzo[c]chromene-7,10-dione natural products against human farnesyltransferase (FTase) has identified tecomaquinone I (IC50 of 0.065±0.004μM) as being one of the more potent natural product inhibitors identified to date. Anti-plasmodial screening of the same library against a drug-resistant strain of Plasmodium falciparum identified the structurally-related dichromenol tectol as a moderately active growth inhibitor with an IC50 3.44±0.20μM. Two novel series of analogues, based on the benzo[c]chromene-7,10-dione scaffold, were subsequently synthesized, with one analogue exhibiting farnesyltransferase inhibitory activity in the low micromolar range. A preliminary structure-activity relationship (SAR) study has identified different structural requirements for anti-malarial activity in comparison to FTase activities for these classes of natural products. Our results identify tecomaquinone I as a novel scaffold from which more potent inhibitors of human and parasitic FTase could be developed. PMID:27240468

  6. Structure-cardiac activity relationship of C19-diterpenoid alkaloids.

    PubMed

    Jian, Xi-Xian; Tang, Pei; Liu, Xiu-Xiu; Chao, Ruo-Bing; Chen, Qiao-Hong; She, Xue-Ke; Chen, Dong-Lin; Wang, Feng-Peng

    2012-06-01

    Thirty three C19-diterpenoid alkaloids, twenty-two prepared from known C19-diterpenoid alkaloids and eleven isolated from Aconitum and Delphinium spp. were evaluated for their cardiac activity in the isolated bullfrog heart assay. Among them, eleven compounds exhibited cardiac activity, with average rate of amplitude increase in the range of 16-118%. Compound 7, mesaconine (17), hypaconine (25), and beiwutinine (26) exhibited strong cardiac activities relative to the reference drug. The structure-activity relationship data acquired indicated that an alpha-hydroxyl group at C-15, a hydroxyl group at C-8, an alpha-methoxyl or hydroxyl group at C-1, and a secondary amine or N-methyl group in ring A are important structure features necessary for the cardiac activities of the aconitine-type C19-diterpenoid alkaloids without any ester groups. In addition, an alpha-hydroxyl group at C-3 is also helpful for the cardiac activity of these alkaloids. PMID:22816290

  7. 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.

  8. 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

  9. BioSAR Airborne Biomass Sensing System

    SciTech Connect

    Graham, R.L.; Johnson, P.

    2007-05-24

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

  10. POLYCHLORINATED DIBENZO-P-DIOXINS AND DIBENZOFURANS: CORRELATION BETWEEN IN VITRO AND IN VIVO STRUCTURE ACTIVITY RELATIONSHIPS (SARS)

    EPA Science Inventory

    Polychlorinated dibenzofurans (PCDFs) and dibenzo-p-dioxins (PCDDs) elicit a number of common biologic and toxic responses which are triggered by their initial binding to a cytosolic receptor protein. hese effects include the induction of several cytochrome P-448 dependent monoox...

  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. Multivariate SAR and QSAR of cucurbitacin derivatives as cytotoxic compounds in a human lung adenocarcinoma cell line.

    PubMed

    Lang, Karen L; Silva, Izabella T; Machado, Vanessa R; Zimmermann, Lara A; Caro, Miguel S B; Simões, Cláudia M O; Schenkel, Eloir P; Durán, Fernando J; Bernardes, Lílian S C; de Melo, Eduardo B

    2014-03-01

    This article describes structure-activity relationship (SAR/QSAR) studies on the cytotoxic activity in a human lung adenocarcinoma cell line (A549) of 43 cucurbitacin derivatives. Modeling was performed using the methods partial least squares with discriminant analysis (PLS-DA) and PLS. For both studies, the variables were selected using the ordered predictor selection (OPS) algorithm. The SAR study demonstrated that the presence or absence of cytotoxic activity of the cucurbitacins could be described using information derived from their chemical structures. The QSAR study displayed suitable internal and external predictivity, and the selected descriptors indicated that the observed activity might be related to electrophilic attack on cellular structures or genetic material. This study provides improves the understanding of the cytotoxic activity of cucurbitacins and could be used to propose new cytotoxic agents. PMID:24378396

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

    PubMed

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

    2015-12-01

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

  14. Insights into the structure activity relationship of mPGES-1 inhibitors: Hints for better inhibitor design.

    PubMed

    Gupta, Ashish; Aparoy, Polamarasetty

    2016-07-01

    Microsomal prostaglandin E synthase-1 (mPGES-1) is a membrane protein which plays crucial role in arachidonic acid metabolism, in the catalysis of PGH2 to PGE2. It is a potential drug target involved in variety of human cancers and inflammatory disorders. In the present study we made an attempt to identify crucial amino acid residues involved in the effective binding of its inhibitors at the active site. Molecular docking and Structure Activity Relationship (SAR) studies were performed. In the present study 127 inhibitors having significant variability in parent scaffold were considered. The results clearly indicated that in the GSH and PGH2 binding site Arg70, Arg73, Asn74, Glu77, His113, Tyr117, Arg126, Ser127, Tyr130, Thr131 and Ala138 consistently form crucial interactions with inhibitors of different classes/scaffolds. These findings are consistent with that of existing reports on the active site residues pivotal at mPGES-1 active site. Further analysis suggested that out of all important amino acid residues identified; Arg73, Asn74, His113, Tyr117, Arg126, Ser127, Tyr130, Thr131 and Ala138 play a crucial role in hydrogen and π-π interactions. The identified amino acid residues can act as target sites for the design and development of drug candidates against mPGES-1. PMID:27012893

  15. 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

  16. Design, synthesis and structure-activity relationships of novel 4-phenoxyquinoline derivatives containing pyridazinone moiety as potential antitumor agents.

    PubMed

    Zhou, Shunguang; Liao, Huimin; He, Chao; Dou, Yanan; Jiang, Mingyan; Ren, Lixiang; Zhao, Yanfang; Gong, Ping

    2014-08-18

    A series of novel 4-phenoxyquinoline derivatives containing pyridazinone moiety were synthesized and evaluated for their in vitro cytotoxic activity against five cancer cell lines (HT-29, H460, A549, MKN-45, and U87MG). Most of the compounds exhibited moderate-to-significant cytotoxicity and high selectivity against one or more cell lines. Compounds 15a, 20a, 15b, 15c, 20d, and 16e were further examined for their inhibitory activity against c-Met kinase. The most promising compound 15a (c-Met half-maximal inhibitory concentration [IC50] = 2.15 nM) showed remarkable cytotoxicity against HT-29, H460, and A549 cell lines with IC50 values of 0.10 μM, 0.13 μM, and 0.05 μM, respectively, and thus it was 1.5- to 2.3-fold more potent than foretinib. Their preliminary structure-activity relationships (SARs) studies indicate that electron-withdrawing groups on the terminal phenyl rings are beneficial for improving the antitumor activity. PMID:24996144

  17. Structure-activity relationships of 3-O-β-chacotriosyl ursolic acid derivatives as novel H5N1 entry inhibitors.

    PubMed

    Song, Gaopeng; Shen, Xintian; Li, Sumei; Li, Yibin; Liu, Yunpeng; Zheng, Yushan; Lin, Ruheng; Fan, Jihong; Ye, Hanming; Liu, Shuwen

    2015-03-26

    A series of methyl ursolate 3-O-β-chacotrioside analogs have been designed, synthesized and evaluated as H5N1 entry inhibitors based on a small molecule inhibitor saponin 3 previously discovered by us. Detailed structure-activity relationships (SARs) studies on the aglycone of compound 3 indicated that both the type of pentacyclic triterpene and the subtle modification of ursolic acid as an aglycon had key influences on the antiviral activity. These results suggested that either the introduction of a disubstituted amide structure at the 17-COOH of ursolic acid or alteration of the C-3 configuration of ursolic acid from 3β-to 3α-forms was helpful to significantly improve the selective index while keeping their antiviral activities. PMID:25728024

  18. Relationships among Fitness, Body Composition, and Physical Activity

    PubMed Central

    LOHMAN, TIMOTHY G.; RING, KIMBERLY; PFEIFFER, KARIN; CAMHI, SARAH; ARREDONDO, ELVA; PRATT, CHARLOTTE; PATE, RUSS; WEBBER, LARRY S.

    2008-01-01

    Purpose This study was designed to examine the associations of physical activity and body composition with cardiorespiratory fitness in eighth grade girls. Methods A random sample of 1440 eighth grade girls at 36 schools participated in this cross-sectional investigation, which represented an ethnically and geographically diverse group. Cardiorespiratory fitness was assessed using a modified physical work capacity test on a cycle ergometer that predicted workload at a heart rate of 170 beats·min−1. Physical activity was assessed over 6 d in each girl using an accelerometer and body composition was estimated from body mass index and triceps skinfolds using a previously validated equation. Pearson correlations and multiple regression analyses were used to determine the relationships among fitness, physical activity, and body composition. Results Significant linear relationships among cardiorespiratory fitness, body composition, and physical activity were found. The combination of fat and fat-free mass along with racial group and a race by fat-free-mass interaction accounted for 18% (R2) of the variation in physical fitness. Adding moderate-to-vigorous physical activity to the regression model increased the R2 to 22%. Black girls had somewhat lower fitness levels (P < 0.05) especially at higher levels of fat and fat-free mass than other racial/ethnic groups. Conclusions Physical activity, fat-free mass, and the interaction between fat-free mass and racial group are significantly associated with cardiorespiratory fitness in adolescent girls. PMID:18460987

  19. 4H-Chromene-based anticancer agents towards multi-drug resistant HL60/MX2 human leukemia: SAR at the 4th and 6th positions.

    PubMed

    Puppala, Manohar; Zhao, Xinghua; Casemore, Denise; Zhou, Bo; Aridoss, Gopalakrishnan; Narayanapillai, Sreekanth; Xing, Chengguo

    2016-03-15

    4H-Chromene-based compounds, for example, CXL017, CXL035, and CXL055, have a unique anticancer potential that they selectively kill multi-drug resistant cancer cells. Reported herein is the extended structure-activity relationship (SAR) study, focusing on the ester functional group at the 4th position and the conformation at the 6th position. Sharp SARs were observed at both positions with respect to cellular cytotoxic potency and selectivity between the parental HL60 and the multi-drug resistant HL60/MX2 cells. These results provide critical guidance for future medicinal optimization. PMID:26867486

  20. Polarization effects and multipolarization SAR

    NASA Technical Reports Server (NTRS)

    Freeman, Anthony

    1992-01-01

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

  1. 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.

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

    PubMed

    Bralock, Anita; Koniak-Griffin, Deborah

    2009-04-01

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

  3. EARSEC SAR processing system

    NASA Astrophysics Data System (ADS)

    Protheroe, Mark; Sloggett, David R.; Sieber, Alois J.

    1994-12-01

    Traditionally, the production of high quality Synthetic Aperture Radar imagery has been an area where a potential user would have to expend large amounts of money in either the bespoke development of a processing chain dedicated to his requirements or in the purchase of a dedicated hardware platform adapted using accelerator boards and enhanced memory management. Whichever option the user adopted there were limitations based on the desire for a realistic throughput in data load and time. The user had a choice, made early in the purchase, for either a system that adopted innovative algorithmic manipulation, to limit the processing time of the purchase of expensive hardware. The former limits the quality of the product, while the latter excludes the user from any visibility into the processing chain. Clearly there was a need for a SAR processing architecture that gave the user a choice into the methodology to be adopted for a particular processing sequence, allowing him to decide on either a quick (lower quality) product or a detailed slower (high quality) product, without having to change the algorithmic base of his processor or the hardware platform. The European Commission, through the Advanced Techniques unit of the Joint Research Centre (JRC) Institute for Remote Sensing at Ispra in Italy, realizing the limitations on current processing abilities, initiated its own program to build airborne SAR and Electro-Optical (EO) sensor systems. This program is called the European Airborne Remote Sensing Capabilities (EARSEC) program. This paper describes the processing system developed for the airborne SAR sensor system. The paper considers the requirements for the system and the design of the EARSEC Airborne SAR Processing System. It highlights the development of an open SAR processing architecture where users have full access to intermediate products that arise from each of the major processing stages. It also describes the main processing stages in the overall

  4. Penoxsulam--structure-activity relationships of triazolopyrimidine sulfonamides.

    PubMed

    Johnson, Timothy C; Martin, Timothy P; Mann, Richard K; Pobanz, Mark A

    2009-06-15

    The discovery of the sulfonamide herbicides, which inhibit the enzyme acetolactate synthase (ALS), has resulted in many investigations to exploit their herbicidal activity. One area which proved particularly productive was the N-aryltriazolo[1,5-c]pyrimidine sulfonamides, providing three commercial herbicides, cloransulam-methyl, diclosulam and florasulam. Additional structure-activity investigations by reversing the sulfonamide linkage resulted in the discovery of triazolopyrimidine sulfonamides with cereal crop selectivity and high levels of grass and broadleaf weed control. Research efforts to exploit these high levels of weed activity ultimately led to the discovery of penoxsulam, a new herbicide developed for grass, sedge and broadleaf weed control in rice. Synthetic efforts and structure-activity relationships leading to the discovery of penoxsulam will be discussed. PMID:19464188

  5. Design of potent and selective hybrid inhibitors of the mitotic kinase Nek2: SAR, structural biology and cellular activity

    PubMed Central

    Innocenti, Paolo; Cheung, Kwai-Ming J.; Solanki, Savade; Mas-Droux, Corine; Rowan, Fiona; Yeoh, Sharon; Boxall, Kathy; Westlake, Maura; Pickard, Lisa; Hardy, Tara; Baxter, Joanne E.; Aherne, G. Wynne; Bayliss, Richard; Fry, Andrew M.; Hoelder, Swen

    2013-01-01

    We report herein a series of Nek2 inhibitors based on an aminopyridine scaffold. These compounds have been designed by combining key elements of two previously discovered chemical series. Structure based design led to aminopyridine (R )-21, a potent and selective inhibitor able to modulate Nek2 activity in cells. PMID:22404346

  6. 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.

  7. The Selective PI3K Inhibitor XL147 (SAR245408) Inhibits Tumor Growth and Survival and Potentiates the Activity of Chemotherapeutic Agents in Preclinical Tumor Models.

    PubMed

    Foster, Paul; Yamaguchi, Kyoko; Hsu, Pin P; Qian, Fawn; Du, Xiangnan; Wu, Jianming; Won, Kwang-Ai; Yu, Peiwen; Jaeger, Christopher T; Zhang, Wentao; Marlowe, Charles K; Keast, Paul; Abulafia, Wendy; Chen, Jason; Young, Jenny; Plonowski, Artur; Yakes, F Michael; Chu, Felix; Engell, Kelly; Bentzien, Frauke; Lam, Sanh T; Dale, Stephanie; Yturralde, Olivia; Matthews, David J; Lamb, Peter; Laird, A Douglas

    2015-04-01

    Dysregulation of PI3K/PTEN pathway components, resulting in hyperactivated PI3K signaling, is frequently observed in various cancers and correlates with tumor growth and survival. Resistance to a variety of anticancer therapies, including receptor tyrosine kinase (RTK) inhibitors and chemotherapeutic agents, has been attributed to the absence or attenuation of downregulating signals along the PI3K/PTEN pathway. Thus, PI3K inhibitors have therapeutic potential as single agents and in combination with other therapies for a variety of cancer indications. XL147 (SAR245408) is a potent and highly selective inhibitor of class I PI3Ks (α, β, γ, and δ). Moreover, broad kinase selectivity profiling of >130 protein kinases revealed that XL147 is highly selective for class I PI3Ks over other kinases. In cellular assays, XL147 inhibits the formation of PIP3 in the membrane, and inhibits phosphorylation of AKT, p70S6K, and S6 in multiple tumor cell lines with diverse genetic alterations affecting the PI3K pathway. In a panel of tumor cell lines, XL147 inhibits proliferation with a wide range of potencies, with evidence of an impact of genotype on sensitivity. In mouse xenograft models, oral administration of XL147 results in dose-dependent inhibition of phosphorylation of AKT, p70S6K, and S6 with a duration of action of at least 24 hours. Repeat-dose administration of XL147 results in significant tumor growth inhibition in multiple human xenograft models in nude mice. Administration of XL147 in combination with chemotherapeutic agents results in antitumor activity in xenograft models that is enhanced over that observed with the corresponding single agents. PMID:25637314

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

    PubMed

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

    2015-06-01

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

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

    PubMed

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

    2016-03-23

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

  10. Synthesis and structure-activity relationships of 2-amino-3-carboxy-4-phenylthiophenes as novel atypical protein kinase C inhibitors

    PubMed Central

    Titchenell, Paul M.; Hollis Showalter, H. D.; Pons, Jean-François; Barber, Alistair J.; Jin, Yafei

    2013-01-01

    Recent evidence suggests atypical protein kinase C (aPKC) isoforms are required for both TNF- and VEGF-induced breakdown of the blood-retinal barrier (BRB) and endothelial permeability to 70kDa dextran or albumin. A chemical library screen revealed a series of novel small molecule phenylthiophene based inhibitors of aPKC isoforms that effectively block permeability in cell culture and in vivo. In an effort to further elucidate the structural requirements of this series of inhibitors, we detail in this study a structure-activity relationship (SAR) built on screening hit 1, which expands on our initial pharmacophore model. The biological activity of our analogues was evaluated in models of bona fide aPKC-dependent signaling including NFκB driven-gene transcription as a marker for an inflammatory response and VEGF/TNF-induced vascular endothelial permeability. The EC50 for the most efficacious inhibitors (6, 32) was in the low nanomolar range in these two cellular assays. Our study demonstrates the key structural elements that confer inhibitory activity and highlights the requirement for electron-donating moieties off the C-4 aryl moiety of the 2-amino-3-carboxy-4-phenylthiophene backbone. These studies suggest that this class has potential for further development into small molecule aPKC inhibitors with therapeutic efficacy in a host of diseases involving increased vascular permeability and inflammation. PMID:23566515

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

    PubMed

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

    2016-08-01

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

  12. 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. PMID:25461433

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

    PubMed

    Atkinson, Greg; Davenne, Damien

    2007-02-28

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

  14. 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

  15. 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.

  16. An analysis of Seasat SAR for detecting geologic linears

    NASA Technical Reports Server (NTRS)

    Yan, S.-Y.; Philipson, W. R.; Teng, W. L.

    1982-01-01

    The value of Seasat synthetic aperture radar (SAR) imagery for detecting geologic linears was assessed in a study of an 89,000 sq km section of New York's Adirondack Mountains. A photographic print of optically processed, 1:500,000 scale SAR imagery (one look direction) was analyzed visually, and the detected linears were compared to those recorded on a 1:250,000 scale geologic map. Eighty percent of the 4,170 km of mapped, geologic linears were detected with the SAR imagery. Moreover, nearly 6,900 km of unmapped linears were also detected. Of these, an estimated 90 percent could be observed on high altitude aerial photographs. The relationship between SAR image detection of linears and the different types of indicators (e.g., straight valleys or shorelines) is reported.

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

    PubMed

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

    2013-01-01

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

  18. 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. PMID:17891741

  19. 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.

  20. 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

  1. 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

  2. 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.

  3. Physical activity as a mediator of the relationship between active commuting to school and adiposity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Active commuting to school (ACS) has been associated with more moderate-to vigorous physical activity (MVPA) and decreased adiposity among youth. However, no studies have examined if MVPA mediates the relationship between ACS and adiposity. We hypothesized that ACS would be inversely associated with...

  4. Bayesian SAR imaging

    NASA Astrophysics Data System (ADS)

    Chen, Zhaofu; Tan, Xing; Xue, Ming; Li, Jian

    2010-04-01

    We introduce a maximum a posteriori (MAP) algorithm and a sparse learning via iterative minimization (SLIM) algorithm to synthetic aperture radar (SAR) imaging. Both MAP and SLIM are sparse signal recovery algorithms with excellent sidelobe suppression and high resolution properties. The former cyclically maximizes the a posteriori probability density function for a given sparsity promoting prior, while the latter cyclically minimizes a regularized least squares cost function. We show how MAP and SLIM can be adapted to the SAR imaging application and used to enhance the image quality. We evaluate the performance of MAP and SLIM using the simulated complex-valued backscattered data from a backhoe vehicle. The numerical results show that both MAP and SLIM satisfactorily suppress the sidelobes and yield higher resolution than the conventional matched filter or delay-and-sum (DAS) approach. MAP and SLIM outperform the widely used compressive sampling matching pursuit (CoSaMP) algorithm, which requires the delicate choice of user parameters. Compared with the recently developed iterative adaptive approach (IAA), MAP and SLIM are computationally more efficient, especially with the help of fast Fourier transform (FFT). Also, the a posteriori distribution given by the algorithms provides us with a basis for the analysis of the statistical properties of the SAR image pixels.

  5. Circular SAR GMTI

    NASA Astrophysics Data System (ADS)

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

    2014-06-01

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

  6. Synthesis, Pharmacological Characterization, and Structure–Activity Relationship Studies of Small Molecular Agonists for the Orphan GPR88 Receptor

    PubMed Central

    2014-01-01

    GPR88 is an orphan G-protein-coupled receptor (GPCR) enriched in the striatum. Genetic deletion and gene expression studies have suggested that GPR88 plays an important role in the regulation of striatal functions and is implicated in psychiatric disorders. The signal transduction pathway and receptor functions of GPR88, however, are still largely unknown due to the lack of endogenous and synthetic ligands. In this paper, we report the synthesis of a GPR88 agonist 2-PCCA and its pure diastereomers, which were functionally characterized in both transiently and stably expressing GPR88 HEK293 cells. 2-PCCA inhibited isoproterenol-stimulated cAMP accumulation in a concentration-dependent manner in cells expressing GPR88 but not in the control cells, suggesting that the observed cAMP inhibition is mediated through GPR88 and that GPR88 is coupled to Gαi. 2-PCCA did not induce calcium mobilization in GPR88 cells, indicating no Gαq-mediated response. A structure–activity relationship (SAR) study of 2-PCCA was also conducted to explore the key structural features for GPR88 agonist activity. PMID:24793972

  7. Interferometric SAR Persistent Scatterer Analysis of Mayon volcano, Albay, Philippines

    NASA Astrophysics Data System (ADS)

    Bato, M. P.; Lagmay, A. A.; Paguican, E. R.

    2011-12-01

    Persistent Scatterer Interferometry (PSInSAR) is a new method of interferometric processing that overcomes the limitations of conventional Synthetic Aperture Radar differential interferometry (DInSAR) and is capable of detecting millimeter scale ground displacements. PSInSAR eliminate anomalies due to atmospheric delays and temporal and geometric decorrelation eminent in tropical regions by exploiting the temporal and spatial characteristics of radar interferometric signatures derived from time-coherent point-wise targets. In this study, PSInSAR conducted in Mayon Volcano, Albay Province, Bicol, Philippines, reveal tectonic deformation passing underneath the volcano. Using 47 combined ERS and ENVISAT ascending and descending imageries, differential movement between the northern horst and graben on which Mayon volcano lies, is as much as 2.5 cm/year in terms of the line-of-sight (LOS) change in the radar signal. The northern horst moves in the northwest direction whereas the graben moves mostly downward. PSInSAR results when coupled with morphological interpretation suggest left-lateral oblique-slip movement of the northern bounding fault of the Oas graben. The PSInSAR results are validated with dGPS measurements. This work presents the functionality of PSInSAR in a humid tropical environment and highlights the probable landslide hazards associated with an oversteepened volcano that may have been further deformed by tectonic activity.

  8. 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.

  9. 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

  10. 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

  11. Synthesis and structure-activity relationship studies of 2-(N-substituted)-aminobenzimidazoles as potent negative gating modulators ofsmall conductance Ca2+-activated K+ channels.

    PubMed

    Sørensen, Ulrik S; Strøbaek, Dorte; Christophersen, Palle; Hougaard, Charlotte; Jensen, Marianne L; Nielsen, Elsebet Ø; Peters, Dan; Teuber, Lene

    2008-12-11

    Small conductance Ca2+-activated K+ channels (SK channels) participate in the control of neuronal excitability, in the shaping of action potential firing patterns, and in the regulation of synaptic transmission.SK channel inhibitors have the potential of becoming new drugs for treatment of various psychiatric and neurological diseases such as depression, cognition impairment, and Parkinson's disease. In the present study we describe the structure-activity relationship (SAR) of a class of 2-(N-substituted)-2-aminobenzimidazoles that constitute a novel class of selective SK channel inhibitors that, in contrast to classical SK inhibitors, do not block the pore of the channel. The pore blocker apamin is not displaced by these compounds in binding studies, and they still inhibit SK channels in which the apamin binding site has been abolished by point mutations. These novel SK inhibitors shift the concentration-response curve for Ca2+ toward higher values and represent the first example of negative gating modulation as a mode-of-action for inhibition of SK channels. The first described compound in this class is NS8593 (14), and the most potent analogue identified in this study is the racemic compound 39 (NS11757), which reversibly inhibits SK3-mediated currents with a K(d) value of 9 nM. PMID:18998663

  12. Relationship between immunoglobulin levels and extremes of solar activity

    NASA Astrophysics Data System (ADS)

    Stoupel, Elijahu G.; Abramson, Eugene; Gabbay, Uri; Pick, Albert I.

    1995-06-01

    The possible relationship between epidemics and extremes of solar activity has been discussed previously. The purpose of the present study was to verify whether differences in the levels of immunoglobulins (IgA, IgG, IgM) could be noted at the highest (July 1989) and lowest (September 1986) points of the last (21st) and present (22nd) 11-year solar cycle. The work was divided into a 1-month study (covering the month of minimal or maximal solar activity), a 3-month study (1 month before and after the month of minimal or maximal solar activity) and a 5-month study (2 months before and after the month of minimal or maximal solar activity). A trend of a drop-off for all three immunoglobulins was seen on the far side of the maximal point of the solar cycle. Statistical significance was achieved in the 5-month study for IgM ( P=0.04), and a strong trend was shown for IgG ( P=0.07). Differences between the sexes were also noted.

  13. The TerraSAR-L Interferometric Mission Objectives

    NASA Astrophysics Data System (ADS)

    Zink, M.

    2004-06-01

    TerraSAR-L is the new imaging radar mission of the European Space Agency. The platform, based on the novel Snapdragon concept, is built around the active phase array antenna of the L-band Synthetic Aperture Radar (SAR). Specification of the L-SAR has been guided by careful analysis of the product requirements resulting in a robust baseline design with considerable margins. Besides having a commercial role for the provision of geo-information products, TerraSAR-L will contribute to the Global Monitoring for Environment and Security (GMES) initiative and serve the scientific user community. Interferometry (INSAR) is a key element behind a number of mission objectives. A L-band SAR in a 14-day repeat orbit is an ideal sensor for solid earth applications (earth quake and volcano monitoring, landslides and subsidence) relying on differential interferometry. L-band penetration of vegetation cover facilitates these applications also over vegetated surfaces. Because of the high coherence, L-band is also the preferred frequency for monitoring ice sheet and glacier dynamics. Highly accurate orbit control (orbital tube <100m) and special wideband INSAR modes are required to support these applications globally and systematically. Precise burst synchronisation enables repeat-pass ScanSAR interferometry and global coverage within the short repeat cycle. A feasibility study into cartwheel constellations flying in close formation with TerraSAR-L revealed the potential for generating Digital Elevation Models (DEMs) of unprecedented quality (2m relative height accuracy @ 12m posting). The TerraSAR-L operations strategy is based on a long-term systematic and repetitive acquisition scenario to ensure consistent data archives and to maximise the exploitation of this very powerful SAR system.

  14. Design, synthesis, and structure-activity relationship studies of novel thienopyrrolidone derivatives with strong antifungal activity against Aspergillus fumigates.

    PubMed

    Cao, Xufeng; Xu, Yuanyuan; Cao, Yongbing; Wang, Ruilian; Zhou, Ran; Chu, Wenjing; Yang, Yushe

    2015-09-18

    In order to further enhance the anti-Aspergillus efficacy of our previously discovered antifungal lead compounds (I), two series of novel azoles featuring thieno[2,3-c]pyrrolidone and thieno[3,2-c]pyrrolidone nuclei were designed and evaluated for their in vitro activity on the basis of the binding mode of albaconazole using molecular docking, along with SARs of antifungal triazoles. Most of target compounds exhibited excellent activity against Candida and Cryptococcus spp., with MIC values in the range of 0.0625 μg/ml to 0.0156 μg/ml. The thieno[3,2-c]pyrrolidone unit was more suited for improving activity against Aspergillus spp. The most potent compound, 18a, was selected for further development due to its significant in vitro activity against Aspergillus spp. (MIC = 0.25 μg/ml), as well as its high metabolic stability in human liver microsomes. PMID:26310892

  15. 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. PMID:27434274

  16. Structure–activity relationship studies of naphthol AS-E and its derivatives as anticancer agents by inhibiting CREB-mediated gene transcription

    PubMed Central

    Li, Bingbing X.; Yamanaka, Kinrin; Xiao, Xiangshu

    2012-01-01

    CREB (cyclic AMP-response element binding protein) is a downstream transcription factor of a multitude of signaling pathways emanating from receptor tyrosine kinases or G-protein coupled receptors. CREB is not activated until it is phosphorylated at Ser133 and its subsequent binding to CREB-binding protein (CBP) through kinase-inducible domain (KID) in CREB and KID-interacting (KIX) domain in CBP. Tumor tissues from various organs present higher level of expression and activation of CREB. Thus CREB has been proposed as a promising cancer drug target. We previously described naphthol AS-E (1a) as a small molecule inhibitor of CREB-mediated gene transcription in living cells. Here we report the structure–activity relationship (SAR) studies of 1a by modifying the appendant phenyl ring. All the compounds were evaluated for in vitro inhibition of KIX–KID interaction, cellular inhibition of CREB-mediated gene transcription and inhibition of proliferation of four cancer cell lines (A549, MCF-7, MDA-MB-231 and MDA-MB-468). SAR indicated that a small and electron-withdrawing group was preferred at the para-position for KIX–KID interaction inhibition. Compound 1a was selected for further biological characterization and it was found that 1a down-regulated the expression of endogenous CREB target genes. Expression of a constitutively active CREB mutant, VP16-CREB in MCF-7 cells rendered the cells resistant to 1a, suggesting that CREB was critical in mediating its anticancer activity. Furthermore, 1a was not toxic to normal human cells. Collectively, these data support that 1a represents a structural template for further development into potential cancer therapeutics with a novel mechanism of action. PMID:23102993

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

    PubMed

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

    2014-08-01

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

  18. Synthesis and Structural Activity Relationship Study of Antitubercular Carboxamides

    PubMed Central

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

    2014-01-01

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

  19. Bistatic SAR: Imagery & Image Products.

    SciTech Connect

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

    2014-10-01

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

  20. Synthesis and SAR of vinca alkaloid analogues.

    PubMed

    Voss, Matthew E; Ralph, Jeffery M; Xie, Dejian; Manning, David D; Chen, Xinchao; Frank, Anthony J; Leyhane, Andrew J; Liu, Lei; Stevens, Jason M; Budde, Cheryl; Surman, Matthew D; Friedrich, Thomas; Peace, Denise; Scott, Ian L; Wolf, Mark; Johnson, Randall

    2009-02-15

    Versatile intermediates 12'-iodovinblastine, 12'-iodovincristine and 11'-iodovinorelbine were utilized as substrates for transition metal based chemistry which led to the preparation of novel analogues of the vinca alkaloids. The synthesis of key iodo intermediates, their transformation into final products, and the SAR based upon HeLa and MCF-7 cell toxicity assays is presented. Selected analogues 27 and 36 show promising anticancer activity in the P388 murine leukemia model. PMID:19147348

  1. 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.

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

    PubMed

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

    2014-10-30

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

  3. Surface displacement studies using differential SAR interferometry: an overview

    NASA Astrophysics Data System (ADS)

    Gupta, Sonal; Sajith V., K.; Arora, Manoj K.; Sharma, Mukut L.

    2006-12-01

    The differential SAR interferometry (DInSAR) has been increasing used to monitor ground surface displacements, which may be caused by various natural disasters such as earthquakes, landslides, mining activities, avalanches etc. Conventionally, these displacements were being estimated through field measurements, which are time consuming, hazardous and with data collected over few point locations. Since all the development and rehabilitation works after a natural disaster strikes is carried out on regional basis, any information at spatial level is advantageous in planning, management and monitoring activities. In recent years, the application of Differential SAR interferometry is gaining momentum to estimate the surface displacements at millimeter level accuracy. The displacement maps produced via this technique provide information at spatial level in the region thereby assisting in judicious developmental and planning works in an efficient and cost-effective manner. The aim of this paper is provide an overview of the use of Differential SAR Interferometry (DinSAR) technology for the study of surface displacements. As a case study, land subsidence occurred due to coal mining in Jharia coal fields, Jharkhand, have been estimated through this technique. All the procedural steps in implementing the approach based on DinSAR have been explained in a simplified manner.

  4. 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. PMID:23092397

  5. Autotaxin Structure Activity Relationships Revealed through Lysophosphatidylcholine Analogs

    PubMed Central

    North, E. Jeffrey; Osborne, Daniel A.; Bridson, Peter K.; Baker, Daniel L.; Parrill, Abby L.

    2009-01-01

    Autotaxin (ATX) catalyzes the hydrolysis of lysophosphatidylcholine (LPC) to form the bioactive lipid lysophosphatidic acid (LPA). LPA stimulates cell proliferation, cell survival, and cell migration and is involved in obesity, rheumatoid arthritis, neuropathic pain, atherosclerosis and various cancers, suggesting that ATX inhibitors have broad therapeutic potential. Product feedback inhibition of ATX by LPA has stimulated structure activity studies focused on LPA analogs. However, LPA displays mixed mode inhibition, indicating it can bind to both the enzyme and the enzyme-substrate complex. This suggests that LPA may not interact solely with the catalytic site. In this report we have prepared LPC analogs to help map out substrate structure activity relationships. The structural variances include length and unsaturation of the fatty tail, choline and polar linker presence, acyl versus ether linkage of the hydrocarbon chain, and methylene and nitrogen replacement of the choline oxygen. All LPC analogs were assayed in competition with the synthetic substrate, FS-3, to show the preference ATX has for each alteration. Choline presence and methylene replacement of the choline oxygen were detrimental to ATX recognition. These findings provide insights into the structure of the enzyme in the vicinity of the catalytic site as well as suggesting that ATX produces rate enhancement, at least in part, by substrate destabilization. PMID:19345587

  6. 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…

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

    NASA Astrophysics Data System (ADS)

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

    2015-04-01

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

  8. VOLInSAR-PF, the InSAR Volcano Observatory Service at Piton de la Fournaise Volcano (La Reunion Island).

    NASA Astrophysics Data System (ADS)

    Froger, Jean-Luc; Cayol, Valérie; Augier, Aurélien; Souriot, Thierry

    2010-05-01

    Since 2003, we carry out a systematic InSAR survey of the Piton de la Fournaise volcano, Reunion Island, in the framework of an AO-ENVISAT project. Since 2005 this activity gets the status of Observatory Service of the Observatoire de Physique du Globe de Clermont-Ferrand (OPGC). From 375 ASAR images acquired between 2003 and 2010, we have produced more than 2100 interferograms that allowed us to map the deformations related to 21 eruptions and thus to better understand the internal processes acting during each eruption. In the same time, we have developed an automatic procedure to provide full resolution interferograms, trough a dedicated WEB site, to the Volcano Observatory of Piton de la Fournaise (OVPF), and our other partners, within a few hours after receiving the ASAR images. In this way, our work is a first step toward an operational system of InSAR monitoring of volcanic activity. Since the beginning of 2010, the VOLInSAR-PF database is also open to the entire community, trough an anonymous login that gives access to slightly reduced resolution interferograms. We will present the VOLInSAR-PF database, the main results it provides concerning the way Piton de la Fournaise is deforming, and the main perspectives for monitoring provided by the new InSAR data (PALSAR-ALOS, TerraSAR-X, RADARSAT-2, COSMO-Skymed) we are beginning to integrate in the database.

  9. 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.

  10. 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.

  11. Structure-activity relationship of an ozonide carboxylic acid (OZ78) against Fasciola hepatica.

    PubMed

    Zhao, Qingjie; Vargas, Mireille; Dong, Yuxiang; Zhou, Lin; Wang, Xiaofang; Sriraghavan, Kamaraj; Keiser, Jennifer; Vennerstrom, Jonathan L

    2010-05-27

    In this paper, we describe the SAR of ozonide carboxylic acid OZ78 (1) as the first part of our search for a trematocidal synthetic peroxide drug development candidate. We found that relatively small structural changes to 1 resulted most commonly in loss of activity against Fasciola hepatica in vivo. A spiroadamantane substructure and acidic functional group (or ester prodrug) were required for activity. Of 26 new compounds administered at single 100 mg/kg oral doses to F. hepatica infected rats, 8 had statistically significant worm burden reductions, 7 were partially curative, and 1 (acylsulfonamide 6) was completely curative and comparable to 1 in flukicidal efficacy. This study also showed that the activity of 1 is peroxide-bond-dependent, suggesting that its flukicidal efficacy depends upon hemoglobin digestion in F. hepatica. PMID:20423101

  12. Novel spiropyrazolone antitumor scaffold with potent activity: Design, synthesis and structure-activity relationship.

    PubMed

    Wu, Shanchao; Li, Yu; Xu, Guixia; Chen, Shuqiang; Zhang, Yongqiang; Liu, Na; Dong, Guoqiang; Miao, Chaoyu; Su, Hua; Zhang, Wannian; Sheng, Chunquan

    2016-06-10

    Phenotypic screening of high quality compound library is an effective strategy to discover novel bioactive molecules. Previously, we developed the divergent organocatalytic cascade approach to efficiently construct a focused library with scaffold diversity and successfully identified a novel spiropyrazolone antitumor scaffold. Herein, a series of spiropyrazolone derivatives were designed, synthesized and assayed. Most of them showed good in vitro antitumor activity with a broad spectrum. Preliminary structure-activity relationship for the substitutions and the stereo configuration were obtained. Compound 5k showed good antitumor activity and could effectively induce cancer cell apoptosis, which represents a good starting point for the development of novel antitumor agents. PMID:27016707

  13. Studies of ice sheet hydrology using SAR

    NASA Technical Reports Server (NTRS)

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

    1989-01-01

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

  14. 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.

  15. Neurosteroid Structure-Activity Relationships for Functional Activation of Extrasynaptic δGABA(A) Receptors.

    PubMed

    Carver, Chase Matthew; Reddy, Doodipala Samba

    2016-04-01

    Synaptic GABAA receptors are primary mediators of rapid inhibition in the brain and play a key role in the pathophysiology of epilepsy and other neurologic disorders. The δ-subunit GABAA receptors are expressed extrasynaptically in the dentate gyrus and contribute to tonic inhibition, promoting network shunting as well as reducing seizure susceptibility. However, the neurosteroid structure-function relationship at δGABA(A) receptors within the native hippocampus neurons remains unclear. Here we report a structure-activity relationship for neurosteroid modulation of extrasynaptic GABAA receptor-mediated tonic inhibition in the murine dentate gyrus granule cells. We recorded neurosteroid allosteric potentiation of GABA as well as direct activation of tonic currents using a wide array of natural and synthetic neurosteroids. Our results shows that, for all neurosteroids, the C3α-OH group remains obligatory for extrasynaptic receptor functional activity, as C3β-OH epimers were inactive in activating tonic currents. Allopregnanolone and related pregnane analogs exhibited the highest potency and maximal efficacy in promoting tonic currents. Alterations at the C17 or C20 region of the neurosteroid molecule drastically altered the transduction kinetics of tonic current activation. The androstane analogs had the weakest modulatory response among the analogs tested. Neurosteroid potentiation of tonic currents was completely (approximately 95%) diminished in granule cells from δ-knockout mice, suggesting that δ-subunit receptors are essential for neurosteroid activity. The neurosteroid sensitivity of δGABA(A) receptors was confirmed at the systems level using a 6-Hz seizure test. A consensus neurosteroid pharmacophore model at extrasynaptic δGABA(A) receptors is proposed based on a structure-activity relationship for activation of tonic current and seizure protection. PMID:26857959

  16. Initial viral load and the outcomes of SARS

    PubMed Central

    Chu, Chung-Ming; Poon, Leo L.M.; Cheng, Vincent C.C.; Chan, Kin-Sang; Hung, Ivan F.N.; Wong, Maureen M.L.; Chan, Kwok-Hung; Leung, Wah-Shing; Tang, Bone S.F.; Chan, Veronica L.; Ng, Woon-Leung; Sim, Tiong-Chee; Ng, Ping-Wing; Law, Kin-Ip; Tse, Doris M.W.; Peiris, Joseph S.M.; Yuen, Kwok-Yung

    2004-01-01

    Background Severe acute respiratory syndrome (SARS) is caused by a novel coronavirus. It may progress to respiratory failure, and a significant proportion of patients die. Preliminary data suggest that a high viral load of the SARS coronavirus is associated with adverse outcomes in the intensive care unit, but the relation of viral load to survival is unclear. Methods We prospectively studied an inception cohort of 133 patients with virologically confirmed SARS who were admitted to 2 general acute care hospitals in Hong Kong from Mar. 24 to May 4, 2003. The patients were followed until death or for a minimum of 90 days. We used Cox proportional hazard modelling to analyze potential predictors of survival recorded at the time of presentation, including viral load from nasopharyngeal specimens (measured by quantitative reverse transcriptase polymerase chain reaction [PCR] of the SARS-associated coronavirus). Results Thirty-two patients (24.1%) met the criteria for acute respiratory distress syndrome, and 24 patients (18.0%) died. The following baseline factors were independently associated with worse survival: older age (61–80 years) (adjusted hazard ratio [HR] 5.24, 95% confidence interval [CI] 2.03–13.53), presence of an active comorbid condition (adjusted HR 3.36, 95% CI 1.44–7.82) and higher initial viral load of SARS coronavirus, according to quantitative PCR of nasopharyngeal specimens (adjusted HR 1.21 per log10 increase in number of RNA copies per millilitre, 95% CI 1.06–1.39). Interpretation We found preliminary evidence that higher initial viral load is independently associated with worse prognosis in SARS. Mortality data for patients with SARS should be interpreted in light of age, comorbidity and viral load. These considerations will be important in future studies of SARS. PMID:15557587

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

    PubMed

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

    2016-08-11

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

  18. 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

  19. SAR/InSAR observation by an HF sounder

    NASA Astrophysics Data System (ADS)

    Kobayashi, T.; Ono, T.

    2007-03-01

    Application of SAR imaging algorithm to spaceborne HF sounder observation was studied. Two types of image ambiguity problems were addressed in the application. One is surface/subsurface image ambiguity arising from deep penetration of HF wave, and another is mirror image ambiguity that is inherent to dipole antenna SAR. A numerical model demonstrated that the surface/subsurface ambiguity can be mitigated by taking a synthetic aperture large enough to defocus subsurface objects. In order to resolve the mirror image ambiguity problem, an image superposition technique was proposed. The performance of the technique was demonstrated by using simulation data of the HF sounder observation to confirm the feasibility of HF SAR and HF InSAR observation.

  20. 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.

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

    PubMed

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

    2016-09-01

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

  2. Mammary Carcinogen-Protein Binding Potentials: Novel and Biologically Relevant Structure-Activity Relationship Model Descriptors

    PubMed Central

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

    2010-01-01

    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 estrogenic 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. PMID:20818582

  3. 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.

  4. Relationship between back muscle endurance and voluntary activation.

    PubMed

    Bottle, Emily; Strutton, Paul H

    2012-06-01

    There is some evidence that the Biering-Sorensen endurance test can discriminate low back pain sufferers from healthy individuals and can predict future back pain. This test relies on the subject's ability to voluntarily drive the back muscles. This neural drive, termed voluntary activation (VA) can be measured using the twitch interpolation technique. The aim of the current study was to investigate the relationship between back muscle endurance and VA. Twenty-one healthy volunteers (10 males) participated. Bilateral electromyographic recordings were obtained from erector spinae and rectus abdominis. Back extensor torque was recorded using a dynamometer. The protocol consisted of measurement of VA (using magnetic stimulation of the brain and assessment of the sizes of the evoked twitches) and measurement of endurance. There was a linear correlation (r(2)=1, P<0.01) between voluntary torque and VA. The mean (SEM) endurance time was 174.9 (12.8)s. There was no correlation between endurance and VA at either 100% MVC (r(2)=0.01, P=0.72) or at 50% MVC (r(2)=0.11, P=0.16). These findings indicate that the endurance of the back muscles, as assessed using this widely utilised test does not appear to be related to a subject's ability to drive their back muscles voluntarily either maximally or submaximally. PMID:22387330

  5. Synthesis and structure-activity relationships of neuromuscular blocking agents.

    PubMed

    Tuba, Zoltan; Maho, Sandor; Vizi, E Sylvester

    2002-08-01

    The first use of neuromuscular blocking agents (muscle relaxants) in clinical practice (1942) revolutionised the practice of anaesthesia and started the modern era of surgery. Since 1942 introduction of tubocurarine (18) neuromuscular blocking agents have been used routinely to provide skeletal muscle relaxation during surgical procedures allowing access to body cavities without hindrance from voluntary or reflex muscle movement. After the introduction of tubocurarine and the depolarizing suxamethonium chloride (4) (1949) several nondepolarizing steroidal and nonsteroidal neuromuscular blocking agents with different onset time and duration of effect were introduced e.g. gallamine triethiodide (1) (1949), methocurine (2) (1949), alcuronium chloride (3) (1963), pancuronium bromide (9) (1968), vecuronium bromide (11) (1982), pipecuronium bromide (10) (1982), atracurium besylate (5) (1982), doxacurium chloride (6) (1991), mivacurium chloride (8) (1992), rocuronium bromide (12) (1994) cisatracurium besylate (7) (1996), and rapacuronium bromide (13) (2000). SZ 1677 (14) a steroid type nondepolarizing neuromuscular blocking agent under development (preclinical phase). This review article deals with a comprehensive survey of the progress in chemical, pharmacological and, in some respects, of clinical studies of neuromuscular blocking agents used in the clinical practice and under development, including the synthesis, structure elucidation, pharmacological actions, structure activity relationships studies of steroidal and nonsteroidal derivatives. PMID:12171561

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

    PubMed

    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

    2010-12-01

    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

  7. Synthesis, Antifungal Activity, and Structure Activity Relationships of Coruscanone A Analogs

    PubMed Central

    Babu, K. Suresh; Li, Xing-Cong; Jacob, Melissa R.; Zhang, Qifeng; Khan, Shabana I.; Ferreira, Daneel; Clark, Alice M.

    2008-01-01

    Coruscanone A, a plant derived cyclopentenedione derivative, showed potent in vitro antifungal activity against Candida albicans and Cryptococcus neoformans, comparable to amphotericin B and fluconazole. A series of analogs have been synthesized by modification of the cyclopentenedione ring, the enolic methoxy functionality, and the side chain styryl moiety of this natural product lead. A structurally close 1,4-benzoquinone analog was also prepared. All the compounds were examined for their in vitro activity against major opportunistic fungal pathogens including C. albicans, C. neoformans and Aspergillus fumigatus, and fluconazole-resistant C. albicans strains, with several analogs demonstrating potent antifungal activity. Structure activity relationship studies indicate that the 2-methoxymethylene-cyclopent-4-ene-1,3-dione structural moiety is the pharmacophore responsible for the antifungal activity of this class of compounds, while the side chain styryl-like moiety plays an important complementary role, presumably contributing to target binding. PMID:17181171

  8. 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.

  9. 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. PMID:26706171

  10. 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

  11. The Ups and Downs of Structure-Activity Landscapes

    PubMed Central

    Guha, Rajarshi

    2011-01-01

    In this chapter we discuss the landscape view of structure-activity relationships (SARs). The motivation for such a view is that SARs come in a variety of forms, such as those where small changes in structure lead to small changes in activity or where small structural lead to significant changes in activity (also termed activity cliffs). Thus, an SAR dataset is viewed as landscape comprised of smooth plains, rolling hills and jagged gorges. We review the history of this view and early quantitative approaches that attempted to encode the landscape. We then discuss some recent developments that directly characterize structure-activity landscapes, in one case with the goal of higlighting activity cliffs while the other allows one to resolve different types of SAR that may be present in a dataset. We highlight some applications of these approaches, such as predictive model development and SAR elucidation, to SAR datasets obtained from the literatur. Finally, we conclude with a sumary of the landscape approach and why it provides an intuitive and rigorous alternative to standard views of structure-activity data. PMID:20838965

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

    NASA Technical Reports Server (NTRS)

    Nichols, David A.; Curlander, John C.

    1991-01-01

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

  13. 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

  14. 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.

  15. SARS Antibody Test for Serosurveillance

    PubMed Central

    Hsueh, Po-Ren; Kao, Chuan-Liang; Lee, Chun-Nan; Chen, Li-Kuan; Ho, Mei-Shang; Sia, Charles; De Fang, Xin; Lynn, Shugene; Chang, Tseng Yuan; Liu, Shi Kau; Walfield, Alan M.

    2004-01-01

    A peptide-based enzyme-linked immunosorbent assay (ELISA) can be used for retrospective serosurveillance of severe acute respiratory syndrome (SARS) by helping identify undetected chains of disease transmission. The assay was developed by epitope mapping, using synthetic peptides from the spike, membrane, and nucleocapsid protein sequences of SARS-associated coronavirus. The new peptide ELISA consistently detected seroconversion by week 2 of onset of fever, and seropositivity remained through day 100. Specificity was 100% on normal blood donor samples, on serum samples associated with infection by other pathogens, and on an interference panel. The peptide-based test has advantages of safety, standardization, and automation over previous immunoassays for SARS. The assay was used for a retrospective survey of healthy healthcare workers in Taiwan who treated SARS patients. Asymptomatic seroconversions were detected in two hospitals that had nosocomial disease. PMID:15498156

  16. Rapid Disaster Analysis based on SAR Techniques

    NASA Astrophysics Data System (ADS)

    Yang, C. H.; Soergel, U.

    2015-03-01

    Due to all-day and all-weather capability spaceborne SAR is a valuable means for rapid mapping during and after disaster. In this paper, three change detection techniques based on SAR data are discussed: (1) initial coarse change detection, (2) flooded area detection, and (3) linear-feature change detection. The 2011 Tohoku Earthquake and Tsunami is used as case study, where earthquake and tsunami events provide a complex case for this study. In (1), pre- and post-event TerraSAR-X images are coregistered accurately to produce a false-color image. Such image provides a quick and rough overview of potential changes, which is useful for initial decision making and identifies areas worthwhile to be analysed further in more depth. In (2), the post-event TerraSAR-X image is used to extract the flooded area by morphological approaches. In (3), we are interested in detecting changes of linear shape as indicator for modified man-made objects. Morphological approaches, e.g. thresholding, simply extract pixel-based changes in the difference image. However, in this manner many irrelevant changes are highlighted, too (e.g., farming activity, speckle). In this study, Curvelet filtering is applied in the difference image not only to suppress false alarms but also to enhance the change signals of linear-feature form (e.g. buildings) in settlements. Afterwards, thresholding is conducted to extract linear-shaped changed areas. These three techniques mentioned above are designed to be simple and applicable in timely disaster analysis. They are all validated by comparing with the change map produced by Center for Satellite Based Crisis Information, DLR.

  17. 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.

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

    PubMed Central

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

    2015-01-01

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

  19. The X-SAR System

    NASA Technical Reports Server (NTRS)

    Oettl, Herwig

    1986-01-01

    During the past few years, there has been significant progress made in the planning for an X-band SAR, designed to fly in the shuttle together with the SIR-C system of NASA/JPL. New work and studies have been initiated to enable the goal of two missions in 1990 to be met. The antennas of X-SAR and SIR-C will be placed side-by-side on a pivoted steerable foldable structure, which will allow antenna movement without changing the attitude of the shuttle. This figure also shows the pallet, underneath the antenna structure, which houses the electronic sub-systems of both radars. Although the two radar systems, X-band SAR and the L- and C-band SAR of SIR-C, have different technical designs, their overall system performance, in terms of image quality, is expected to be similar. The current predicted performance of the X-SAR system based on results of the continuing Phase B studies is detailed. Differences between the performance parameters of X-SAR and those of SIR-C are only detailed in as far as they affect planning decisions to be made by experimenters.

  20. 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

  1. Landslide Mapping Using SqueeSAR Data

    NASA Astrophysics Data System (ADS)

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

    2011-12-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2012-01-01

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

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

    PubMed

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

    2016-01-01

    In this study, 33 different polysaccharides were prepared to investigate the structure-activity relationships between the polysaccharides, mainly from marine algae, and anti-complement activity in the classical pathway. Factors considered included extraction methods, fractionations, molecular weight, molar ratio of galactose to fucose, sulfate, uronic acid (UA) content, linkage, branching, and the type of monosaccharide. It was shown that the larger the molecular weights, the better the activities. The molar ratio of galactose (Gal) to fucose (Fuc) was a positive factor at a concentration lower than 10 µg/mL, while it had no effect at a concentration more than 10 µg/mL. In addition, sulfate was necessary; however, the sulfate content, the sulfate pattern, linkage and branching had no effect at a concentration of more than 10 µg/mL. Moreover, the type of monosaccharide had no effect. Laminaran and UA fractions had no activity; however, they could reduce the activity by decreasing the effective concentration of the active composition when they were mixed with the active compositions. The effect of the extraction methods could not be determined. Finally, it was observed that sulfated galactofucan showed good anti-complement activity after separation. PMID:26712768

  4. 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

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

    ERIC Educational Resources Information Center

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

    2005-01-01

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

  6. Antileishmanial lead structures from nature: analysis of structure-activity relationships of a compound library derived from caffeic Acid bornyl ester.

    PubMed

    Glaser, Jan; Schultheis, Martina; Hazra, Sudipta; Hazra, Banasri; Moll, Heidrun; Schurigt, Uta; Holzgrabe, Ulrike

    2014-01-01

    Bioassay-guided fractionation of a chloroform extract of Valeriana wallichii (V. wallichii) rhizomes lead to the isolation and identification of caffeic acid bornyl ester (1) as the active component against Leishmania major (L. major) promastigotes (IC50 = 48.8 µM). To investigate the structure-activity relationship (SAR), a library of compounds based on 1 was synthesized and tested in vitro against L. major and L. donovani promastigotes, and L. major amastigotes. Cytotoxicity was determined using a murine J774.1 cell line and bone marrow derived macrophages (BMDM). Some compounds showed antileishmanial activity in the concentration range of pentamidine and miltefosine which are the standard drugs in use. In the L. major amastigote assay compounds 15, 19 and 20 showed good activity with relatively low cytotoxicity against BMDM, resulting in acceptable selectivity indices. Molecules with adjacent phenolic hydroxyl groups exhibited elevated cytotoxicity against murine cell lines J774.1 and BMDM. The Michael system seems not to be essential for antileishmanial activity. Based on the results compound 27 can be regarded as new lead structure for further structure optimization. PMID:24473204

  7. Lightweight SAR GMTI radar technology development

    NASA Astrophysics Data System (ADS)

    Kirk, John C.; Lin, Kai; Gray, Andrew; Hseih, Chung; Darden, Scott; Kwong, Winston; Majumder, Uttam; Scarborough, Steven

    2013-05-01

    A small and lightweight dual-channel radar has been developed for SAR data collections. Using standard Displaced Phase Center Antenna (DPCA) radar digital signal processing, SAR GMTI images have been obtained. The prototype radar weighs 5-lbs and has demonstrated the extraction of ground moving targets (GMTs) embedded in high-resolution SAR imagery data. Heretofore this type of capability has been reserved for much larger systems such as the JSTARS. Previously, small lightweight SARs featured only a single channel and only displayed SAR imagery. Now, with the advent of this new capability, SAR GMTI performance is now possible for small UAV class radars.

  8. Extracellular melanogenesis inhibitory activity and the structure-activity relationships of ugonins from Helminthostachys zeylanica roots.

    PubMed

    Yamauchi, Kosei; Mitsunaga, Tohru; Itakura, Yuki; Batubara, Irmanida

    2015-07-01

    Ugonin J, K, and L, which are luteolin derivatives, were isolated from Helminthostachys zeylanica roots by a series of chromatographic separations of a 50% ethanol/water extract. They were identified using nuclear magnetic resonance (NMR), ultraviolet (UV) spectra, and ultra-performance liquid chromatography coupled to time-of-flight mass spectrometry (UPLC-TOF-MS). In this study, the intra and extracellular melanogenic activity of the ugonins were determined using B16 melanoma cells. The results showed that ugonin J at 12.5, 25, and 50μM reduced extracellular melanin contents to 75, 16, and 14%, respectively, compared to the control. This indicates that ugonin J showed a stronger activity than arbutin, used as the positive control. Moreover, ugonin K showed a more potent inhibition with 19, 8, and 9% extracellular melanin reduction at the same concentrations, than that shown by ugonin J. In contrast, ugonin L did not inhibit intra- or extracellular melanogenic activity. Furthermore, in order to investigate the structure-activity relationships of the ugonins, the intra- and extracellular melanogenic activity of luteolin, methylluteolin, quercetin, eriodictyol, apigenin, and chrysin were determined. Consequently, it was suggested that the catechol and flavone skeleton of ugonin K is essential for the extracellular melanogenic inhibitory activity, and the low polarity substituent groups on the A ring of ugonin K may increase the activity. PMID:25979512

  9. 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

  10. Design, Synthesis and Structure-Activity Relationship (SAR) Studies of 2,4-Disubstituted Pyrimidine Derivatives: Dual Activity as Cholinesterase and Aβ-Aggregation Inhibitors

    PubMed Central

    Mohamed, Tarek; Zhao, Xiaobei; Habib, Lila K.; Yang, Jerry; Rao, Praveen P. N.

    2011-01-01

    A novel class of 2,4-disubstituted pyrimidines (7a–u, 8a–f, 9a–e) that possess substituents with varying steric and electronic properties at the C-2 and C-4 positions, were designed, synthesized and evaluated as dual cholinesterase and amyloid-β (Aβ)-aggregation inhibitors. In vitro screening identified N-(naphth-1-ylmethyl)-2-(pyrrolidin-1-yl)pyrimidin-4-amine (9a) as the most potent AChE inhibitor (IC50 = 5.5 μM). Among this class of compounds, 2-(4-methylpiperidin-1-yl)-N-(naphth-1-ylmethyl)pyrimidin-4-amine (9e) was identified as the most potent and selective BuChE inhibitor (IC50 = 2.2 μM, Selectivity Index = 11.7) and was about 5.7-fold more potent compared to the commercial, approved reference drug galanthamine (BuChE IC50 = 12.6 μM). In addition, the selective AChE inhibitor N-benzyl-2-(4-methylpiperazin-1-yl)pyrimidin-4-amine (7d), exhibited good inhibition of hAChE-induced aggregation of Aβ1–40 fibrils (59% inhibition). Furthermore, molecular modeling studies indicate that a central pyrimidine ring serves as a suitable template to develop dual inhibitors of cholinesterase and AChE-induced Aβ aggregation thereby targeting multiple pathological routes in AD. PMID:21429752

  11. Structure-activity relationships for biodistribution, pharmacokinetics, and excretion of atomically precise nanoclusters in a murine model

    NASA Astrophysics Data System (ADS)

    Wong, O. Andrea; Hansen, Ryan J.; Ni, Thomas W.; Heinecke, Christine L.; Compel, W. Scott; Gustafson, Daniel L.; Ackerson, Christopher J.

    2013-10-01

    The absorption, distribution, metabolism and excretion (ADME) and pharmacokinetic (PK) properties of inorganic nanoparticles with hydrodynamic diameters between 2 and 20 nm are presently unpredictable. It is unclear whether unpredictable in vivo properties and effects arise from a subset of molecules in a nanomaterials preparation, or if the ADME/PK properties are ensemble properties of an entire preparation. Here we characterize the ADME/PK properties of atomically precise preparations of ligand protected gold nanoclusters in a murine model system. We constructed atomistic models and tested in vivo properties for five well defined compounds, based on crystallographically resolved Au25(SR)18 and Au102(SR)44 nanoclusters with different (SR) ligand shells. To rationalize unexpected distribution and excretion properties observed for several clusters in this study and others, we defined a set of atomistic structure-activity relationships (SAR) for nanoparticles, which includes previously investigated parameters such as particle hydrodynamic diameter and net charge, and new parameters such as hydrophobic surface area and surface charge density. Overall we find that small changes in particle formulation can provoke dramatic yet potentially predictable changes in ADME/PK.The absorption, distribution, metabolism and excretion (ADME) and pharmacokinetic (PK) properties of inorganic nanoparticles with hydrodynamic diameters between 2 and 20 nm are presently unpredictable. It is unclear whether unpredictable in vivo properties and effects arise from a subset of molecules in a nanomaterials preparation, or if the ADME/PK properties are ensemble properties of an entire preparation. Here we characterize the ADME/PK properties of atomically precise preparations of ligand protected gold nanoclusters in a murine model system. We constructed atomistic models and tested in vivo properties for five well defined compounds, based on crystallographically resolved Au25(SR)18 and Au102(SR

  12. A quantitative structure-activity relationship model for radical scavenging activity of flavonoids.

    PubMed

    Om, A; Kim, J H

    2008-03-01

    A quantitative structure-activity relationship (QSAR) study has been carried out for a training set of 29 flavonoids to correlate and predict the 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity (RSA) values obtained from published data. Genetic algorithm and multiple linear regression were employed to select the descriptors and to generate the best prediction model that relates the structural features to the RSA activities using (1) three-dimensional (3D) Dragon (TALETE srl, Milan, Italy) descriptors and (2) semi-empirical descriptor calculations. The predictivity of the models was estimated by cross-validation with the leave-one-out method. The result showed that a significant improvement of the statistical indices was obtained by deleting outliers. Based on the data for the compounds used in this study, our results suggest a QSAR model of RSA that is based on the following descriptors: 3D-Morse, WHIM, and GETAWAY. Therefore, satisfactory relationships between RSA and the semi-empirical descriptors were found, demonstrating that the energy of the highest occupied molecular orbital, total energy, and energy of heat of formation contributed more significantly than all other descriptors. PMID:18361735

  13. A quantitative structure--activity relationship model for the intrinsic activity of uncouplers of oxidative phosphorylation.

    PubMed

    Spycher, Simon; Escher, Beate I; Gasteiger, Johann

    2005-12-01

    A quantitative structure-activity relationship (QSAR) has been derived for the prediction of the activity of phenols in uncoupling oxidative and photophosphorylation. Twenty-one compounds with experimental data for uncoupling activity as well as for the acid dissociation constant, pKa, and for partitioning constants of the neutral and the charged species into model membranes were analyzed. From these measured data, the effective concentration in the membrane was derived, which allowed the study of the intrinsic activity of uncouplers within the membrane. A linear regression model for the intrinsic activity could be established using the following three descriptors: solvation free energies of the anions, an estimate for heterodimer formation describing transport processes, and pKa values describing the speciation of the phenols. In a next step, the aqueous effect concentrations were modeled by combining the model for the intrinsic uncoupling activity with descriptors accounting for the uptake into membranes. Results obtained with experimental membrane-water partitioning data were compared with the results obtained with experimental octanol-water partition coefficients, log Kow, and with calculated log Kow values. The properties of these different measures of lipophilicity were critically discussed. PMID:16359176

  14. Structure-Activity Relationships for the Antifungal Activity of Selective Estrogen Receptor Antagonists Related to Tamoxifen

    PubMed Central

    Butts, Arielle; Martin, Jennifer A.; DiDone, Louis; Bradley, Erin K.; Mutz, Mitchell; Krysan, Damian J.

    2015-01-01

    Cryptococcosis is one of the most important invasive fungal infections and is a significant contributor to the mortality associated with HIV/AIDS. As part of our program to repurpose molecules related to the selective estrogen receptor modulator (SERM) tamoxifen as anti-cryptococcal agents, we have explored the structure-activity relationships of a set of structurally diverse SERMs and tamoxifen derivatives. Our data provide the first insights into the structural requirements for the antifungal activity of this scaffold. Three key molecular characteristics affecting anti-cryptococcal activity emerged from our studies: 1) the presence of an alkylamino group tethered to one of the aromatic rings of the triphenylethylene core; 2) an appropriately sized aliphatic substituent at the 2 position of the ethylene moiety; and 3) electronegative substituents on the aromatic rings modestly improved activity. Using a cell-based assay of calmodulin antagonism, we found that the anti-cryptococcal activity of the scaffold correlates with calmodulin inhibition. Finally, we developed a homology model of C. neoformans calmodulin and used it to rationalize the structural basis for the activity of these molecules. Taken together, these data and models provide a basis for the further optimization of this promising anti-cryptococcal scaffold. PMID:26016941

  15. Isothiocyanate synthetic analogs: biological activities, structure-activity relationships and synthetic strategies.

    PubMed

    Milelli, Andrea; Fimognari, Carmela; Ticchi, Nicole; Neviani, Paolo; Minarini, Anna; Tumiatti, Vincenzo

    2014-01-01

    Sulforaphane is a natural product that is constantly under biological investigation for its unique biological properties. This naturally occurring isothiocyanate (ITC) and its analogs are the main components of cruciferous vegetables, such as cauliflower, watercress, broccoli, cabbage, Brussels sprouts, widely used as chemopreventive agents. Due to their interesting biological profiles, natural ITCs have been exploited as starting point to develop new synthetic analogs. The present mini-review briefly highlights the most important biological actions of selected new synthetic ITCs focusing on their structure-activity relationships and related synthetic strategies. PMID:25373847

  16. COMPUTER-ASSISTED STUDIES OF MOLECULAR STRUCTURE-BIOLOGICAL ACTIVITY RELATIONSHIPS

    EPA Science Inventory

    Computer-assisted methods can be used to investigate the relationships between the molecular structures of compounds and their biological activity. A number of approaches have been reported in the literature, including correlations of activity with substituent constants, conforma...

  17. SAR data exploitation: computational technology enabling SAR ATR algorithm development

    NASA Astrophysics Data System (ADS)

    Majumder, Uttam K.; Casteel, Curtis H., Jr.; Buxa, Peter; Minardi, Michael J.; Zelnio, Edmund G.; Nehrbass, John W.

    2007-04-01

    A fundamental issue with synthetic aperture radar (SAR) application development is data processing and exploitation in real-time or near real-time. The power of high performance computing (HPC) clusters, FPGA, and the IBM Cell processor presents new algorithm development possibilities that have not been fully leveraged. In this paper, we will illustrate the capability of SAR data exploitation which was impractical over the last decade due to computing limitations. We can envision that SAR imagery encompassing city size coverage at extremely high levels of fidelity could be processed at near-real time using the above technologies to empower the warfighter with access to critical information for the war on terror, homeland defense, as well as urban warfare.

  18. Structure-activity relationships of 3-O-β-chacotriosyl oleanane-type triterpenoids as potential H5N1 entry inhibitors.

    PubMed

    Song, Gaopeng; Shen, Xintian; Li, Sumei; Li, Yibin; Si, Hongzong; Fan, Jihong; Li, Junhua; Gao, Erqiang; Liu, Shuwen

    2016-08-25

    A series of 3-O-β-chacotriosyl oleanolic acid analogs have been designed, synthesized and evaluated as H5N1 entry inhibitors based on a small molecule inhibitor saponin 1 previously discovered by us. Detailed structure-activity relationships (SARs) studies on the aglycone of compound 1 indicated that the subtle modification of oleanolic acid as an aglycon has key influences on the antiviral activity. These results suggested that either the introduction of a disubstituted amide structure at the 17-COOH of OA or alteration of the C-3 configuration of OA from 3β-to 3α-forms can significantly improve the selective index while maintaining their antiviral activities in vitro. Compound 8 was selected for further mechanistic study because of its distinguished inhibition activity and good selective index. Molecular simulation study and surface plasmon resonance analysis confirmed that compound 8 stabilized HA2 subunit of hemagglutinin (HA) by binding with amino acid residues LYS-26, ASN-53, ASN-27 and ASN-50, therefore may prevent HA from conformational rearranging, which is a critical step for viral entry. PMID:27153348

  19. Synthesis and Structure–Activity Relationships of N-(2-Oxo-3-oxetanyl)amides as N-Acylethanolamine-hydrolyzing Acid Amidase Inhibitors

    PubMed Central

    Solorzano, Carlos; Antonietti, Francesca; Duranti, Andrea; Tontini, Andrea; Rivara, Silvia; Lodola, Alessio; Vacondio, Federica; Tarzia, Giorgio; Piomelli, Daniele; Mor, Marco

    2010-01-01

    The fatty acid ethanolamides (FAEs) are a family of bioactive lipid mediators that include the endogenous agonist of peroxisome proliferator-activated receptor-α, palmitoylethanolamide (PEA). FAEs are hydrolyzed intracellularly by either fatty acid amide hydrolase or N-acylethanolamine-hydrolyzing acid amidase (NAAA). Selective inhibition of NAAA by (S)-N-(2-oxo-3-oxetanyl)-3-phenylpropionamide [(S)-OOPP, 7a] prevents PEA degradation in mouse leukocytes and attenuates responses to proinflammatory stimuli. Starting from the structure of 7a a series of β-lactones was prepared and tested on recombinant rat NAAA to explore structure-activity relationships (SARs) for this class of inhibitors and improve their in vitro potency. Following the hypothesis that these compounds inhibit NAAA by acylation of the catalytic cysteine, we identified several requirements for recognition at the active site and obtained new potent inhibitors. In particular, (S)-N-(2-oxo-3-oxetanyl)biphenyl-4-carboxamide (7h) was more potent than 7a at inhibiting recombinant rat NAAA activity (7a, IC50 = 420 nM; 7h, IC50 = 115 nM) in vitro and at reducing carrageenan-induced leukocyte infiltration in vivo. PMID:20604568

  20. Synthesis, structure-activity, and structure-stability relationships of 2-substituted-N-(4-oxo-3-oxetanyl) N-acylethanolamine acid amidase (NAAA) inhibitors.

    PubMed

    Vitale, Romina; Ottonello, Giuliana; Petracca, Rita; Bertozzi, Sine Mandrup; Ponzano, Stefano; Armirotti, Andrea; Berteotti, Anna; Dionisi, Mauro; Cavalli, Andrea; Piomelli, Daniele; Bandiera, Tiziano; Bertozzi, Fabio

    2014-02-01

    N-Acylethanolamine acid amidase (NAAA) is a cysteine amidase that preferentially hydrolyzes saturated or monounsaturated fatty acid ethanolamides (FAEs), such as palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), which are endogenous agonists of nuclear peroxisome proliferator-activated receptor-α (PPAR-α). Compounds that feature an α-amino-β-lactone ring have been identified as potent and selective NAAA inhibitors and have been shown to exert marked anti-inflammatory effects that are mediated through FAE-dependent activation of PPAR-α. We synthesized and tested a series of racemic, diastereomerically pure β-substituted α-amino-β-lactones, as either carbamate or amide derivatives, investigating the structure-activity and structure-stability relationships (SAR and SSR) following changes in β-substituent size, relative stereochemistry at the α- and β-positions, and α-amino functionality. Substituted carbamate derivatives emerged as more active and stable than amide analogues, with the cis configuration being generally preferred for stability. Increased steric bulk at the β-position negatively affected NAAA inhibitory potency, while improving both chemical and plasma stability. PMID:24403170

  1. Surface deformation of Taipei basin detected by Differential SAR Interferometry

    NASA Astrophysics Data System (ADS)

    Chen, Y.; Chang, C.; Yen, J.; Lin, M.

    2006-12-01

    Taiwan island is located between the southeastern periphery of the Eurasian plate and the Philippine Sea plate. The two converging plates produced very active tectonics, and can be seen by the high seismicity and deformation rate. Taipei, the highest populated area, center of politics, and economics in Taiwan, is in Taipei basin at the northern part of the island. There are several faults in and surrounding the basin, and the city is threatened with a high geological hazard potential that we should keep monitoring the crustal deformation to prevent and mitigate the disaster effect. The aims of our study is to apply the DInSAR technique to determine the surface deformation of Taipei basin area, and discussing the relation between the manifestation of deformation and the tectonically active region, Shanjiao fault. In the past few years, Differential SAR Interferometry (DInSAR) has been proved to be a powerful technique for monitoring the neotectonic activities and natural hazards. High spatial sampling rate of DInSAR technique allows studies of surface deformations with centimeter accuracy. In this area, we used ERS-1/2 SAR images acquired from 1993 to 2005 to generate 10 differential interferograms and processed the data using DIAPASON developed by CNES and SRTM global DEM.From our results, the deformation rate in Taipei is generally high in the western end of the basin along the Shanjiao fault and decrease eastward, while the subsidence center often appeared in the center of the Taipei basin. The neotectonic activity of the Shanjiao fault appeared to be insignificant by itself but it seemed to separate the subsiding basin from the surrounding areas. Further comparison between our DInSAR results and isopach of the Taipei basin revealed that the subsidence centers appeared in the interferograms did not coincide with the location where the sediments are thickest. Our results from differential interferometry will be compared to other geodetic measurements such as the

  2. Molecular modeling and snake venom phospholipase A2 inhibition by phenolic compounds: Structure-activity relationship.

    PubMed

    Alam, Md Iqbal; Alam, Mohammed A; Alam, Ozair; Nargotra, Amit; Taneja, Subhash Chandra; Koul, Surrinder

    2016-05-23

    In our earlier study, we have reported that a phenolic compound 2-hydroxy-4-methoxybenzaldehyde from Janakia arayalpatra root extract was active against Viper and Cobra envenomations. Based on the structure of this natural product, libraries of synthetic structurally variant phenolic compounds were studied through molecular docking on the venom protein. To validate the activity of eight selected compounds, we have tested them in in vivo and in vitro models. The compound 21 (2-hydroxy-3-methoxy benzaldehyde), 22 (2-hydroxy-4-methoxybenzaldehyde) and 35 (2-hydroxy-3-methoxybenzylalcohol) were found to be active against venom-induced pathophysiological changes. The compounds 20, 15 and 35 displayed maximum anti-hemorrhagic, anti-lethal and PLA2 inhibitory activity respectively. In terms of SAR, the presence of a formyl group in conjunction with a phenolic group was seen as a significant contributor towards increasing the antivenom activity. The above observations confirmed the anti-venom activity of the phenolic compounds which needs to be further investigated for the development of new anti-snake venom leads. PMID:26986086

  3. Adolescents' Perception of the Relationship between Movement Skills, Physical Activity and Sport

    ERIC Educational Resources Information Center

    Barnett, Lisa; Cliff, Ken; Morgan, Philip; van Beurden, Eric

    2013-01-01

    Movement skill competence is important to organised youth physical activity participation, but it is unclear how adolescents view this relationship. The primary aim of this study was to explore adolescents' perception of the relationship between movement skills, physical activity and sport, and whether their perceptions differed according to…

  4. 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...

  5. 49 CFR 173.434 - Activity-mass relationships for uranium and natural thorium.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 2 2011-10-01 2011-10-01 false Activity-mass relationships for uranium and 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...

  6. 49 CFR 173.434 - Activity-mass relationships for uranium and natural thorium.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 2 2014-10-01 2014-10-01 false Activity-mass relationships for uranium and 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...

  7. 49 CFR 173.434 - Activity-mass relationships for uranium and natural thorium.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 2 2012-10-01 2012-10-01 false Activity-mass relationships for uranium and 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...

  8. 49 CFR 173.434 - Activity-mass relationships for uranium and natural thorium.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 2 2013-10-01 2013-10-01 false Activity-mass relationships for uranium and 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...

  9. 49 CFR 173.434 - Activity-mass relationships for uranium and natural thorium.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false Activity-mass relationships for uranium and 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...

  10. 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…

  11. 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…

  12. 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…

  13. Study of the relationship between solar activity and terrestrial weather

    NASA Technical Reports Server (NTRS)

    Sturrock, P. A.; Brueckner, G. E.; Dickinson, R. E.; Fukuta, N.; Lanzerotti, L. J.; Lindzen, R. S.; Park, C. G.; Wilcox, J. M.

    1976-01-01

    Evidence for some connection between weather and solar related phenomena is presented. Historical data of world wide temperature variations with relationship to change in solar luminosity are examined. Several test methods for estimating the statistical significance of such phenomena are discussed in detail.

  14. 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 ...

  15. 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.

  16. 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

  17. Quantitative structure-activity relationship of antifungal activity of rosin derivatives.

    PubMed

    Wang, Hui; Nguyen, Thi Thanh Hien; Li, Shujun; Liang, Tao; Zhang, Yuanyuan; Li, Jian

    2015-01-15

    To develop new rosin-based wood preservatives with good antifungal activity, 24 rosin derivatives were synthesized, bioassay tested with Trametes versicolor and Gloeophyllum trabeum, and subjected to analysis of their quantitative structure-activity relationships (QSAR). A QSAR analysis using Ampac 9.2.1 and Codessa 2.7.16 software built two QSAR models of antifungal ratio for T. versicolor and G. trabeum with values of R(2)=0.9740 and 0.9692, respectively. Based on the models, tri-N-(3-hydroabietoxy-2-hydroxy) propyl-triethyl ammonium chloride was designed and the bioassay test result proved its better inhibitory effect against the two selected fungi as expected. PMID:25466709

  18. Structure-Activity Relationships in Human Toll-like Receptor 7-Active Imidazoquinoline Analogues

    PubMed Central

    Shukla, Nikunj M.; Malladi, Subbalakshmi S.; Mutz, Cole A.; Balakrishna, Rajalakshmi; David, Sunil A.

    2010-01-01

    Engagement of toll-like receptors serve to link innate immune responses with adaptive immunity and can be exploited as powerful vaccine adjuvants for eliciting both primary and anamnestic immune responses. TLR7 agonists are highly immunostimulatory without inducing dominant proinflammatory cytokine responses. A structure-activity study was conducted on the TLR7-agonistic imidazoquinolines, starting with 1-(4-amino-2-((ethylamino)methyl)-1H-imidazo[4,5-c]quinolin-1-yl)-2-methylpropan-2-ol as a lead. Modifications of the secondary amine of the C2 ethylaminomethylene sidechain are poorly tolerated. The 4-amino group must be retained for activity. Replacement of the imidazole ring of the scaffold with triazole or cyclic urea led to complete loss of activity. A systematic exploration of N1-benzyl-C2-alkyl substituents showed a very distinct relationship between alkyl length and TLR7-agonistic potency with the optimal compound bearing a C2-n-butyl group. Transposition of the N1 and C2 substituents led to the identification of an extremely active TLR7-agonistic compound with an EC50 value of 8.6 nM. The relative potencies in human TLR7-based primary reporter gene assays were paralleled by interferon-α induction activities in whole human blood models. PMID:20481492

  19. 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

  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. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. Interrenal activity in the female lizard Lacerta vivipara J.: in vitro response to ACTH 1-39 and to [Sar1, Val5] angiotensin II (ANG II).

    PubMed

    Dauphin-Villemant, C; Leboulenger, F; Xavier, F; Vaudry, H

    1988-01-01

    A perifusion system technique was developed in order to determine in vitro the respective roles of ACTH and ANG II in the regulation of adrenal steroidogenesis in the lizard Lacerta vivipara. Synthetic human ACTH 1-39, administered as 20-min pulses, stimulated corticosterone (B) and aldosterone (A) release in a dose-dependent manner. The increase in corticosterone output was higher than that in aldosterone output, leading to an enhancement of the B/A ratio. Iterative stimulations with 1 nM ACTH (20-min pulses every 120 min) led to reproducible increases in corticosterone and aldosterone release. Prolonged stimulation with 1 nM ACTH (up to 240 min) caused a sustained increase in corticosteroid release, suggesting that, in the lizard, ACTH does not induce any desensitization phenomenon. The angiotensin II analogue [Sar1, Val5] ANG II also stimulated corticosterone and aldosterone release in a dose-dependent manner; the stimulatory effects of ANG II on both steroids were very similar. These results indicate that, in lizards, ACTH plays a major role in the regulation of adrenal steroidogenesis. Since ANG II stimulates the production of gluco- and mineralocorticoids, our data raise the question of the existence of two cell types synthesizing corticosterone and aldosterone, respectively, in reptiles. PMID:2838698

  7. Inhibition of Angiotensin-Converting Enzyme Activity by Flavonoids: Structure-Activity Relationship Studies

    PubMed Central

    Guerrero, Ligia; Castillo, Julián; Quiñones, Mar; Garcia-Vallvé, Santiago; Arola, Lluis; Pujadas, Gerard; Muguerza, Begoña

    2012-01-01

    Previous studies have demonstrated that certain flavonoids can have an inhibitory effect on angiotensin-converting enzyme (ACE) activity, which plays a key role in the regulation of arterial blood pressure. In the present study, 17 flavonoids belonging to five structural subtypes were evaluated in vitro for their ability to inhibit ACE in order to establish the structural basis of their bioactivity. The ACE inhibitory (ACEI) activity of these 17 flavonoids was determined by fluorimetric method at two concentrations (500 µM and 100 µM). Their inhibitory potencies ranged from 17 to 95% at 500 µM and from 0 to 57% at 100 µM. In both cases, the highest ACEI activity was obtained for luteolin. Following the determination of ACEI activity, the flavonoids with higher ACEI activity (i.e., ACEI >60% at 500 µM) were selected for further IC50 determination. The IC50 values for luteolin, quercetin, rutin, kaempferol, rhoifolin and apigenin K were 23, 43, 64, 178, 183 and 196 µM, respectively. Our results suggest that flavonoids are an excellent source of functional antihypertensive products. Furthermore, our structure-activity relationship studies show that the combination of sub-structures on the flavonoid skeleton that increase ACEI activity is made up of the following elements: (a) the catechol group in the B-ring, (b) the double bond between C2 and C3 at the C-ring, and (c) the cetone group in C4 at the C-ring. Protein-ligand docking studies are used to understand the molecular basis for these results. PMID:23185345

  8. 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.

  9. Progress towards SAR based ecosystem analysis

    NASA Technical Reports Server (NTRS)

    Ranson, K. Jon; Sun, Guoqing

    1991-01-01

    Recent progress towards a synthetic aperture radar (SAR) based system for determining forest ecosystem attributes is discussed. Our SAR data processing and analysis sequence, from calibration through classification, is described. In addition, the usefulness of SAR image data for identifying ecosystem classes is discussed.

  10. MapReady: An Open Source Tool for the Utilization of SAR in Geospatial Applications

    NASA Astrophysics Data System (ADS)

    Atwood, D.; Denny, P.; Hogenson, K.; Dixon, B.; Gens, R.

    2008-12-01

    Users of remote sensing data can now benefit from the wide availability of Synthetic Aperture Radar (SAR) satellites, including ERS-2, RADARSAT-2, ALOS PALSAR, Envisat, and TerraSAR-X. As an active sensor, SAR can acquire data independently of weather and at any time of day or night. Unfortunately, SAR data has not seen wide-spread usage by those engaged in mapping or Earth studies. The reason for this is two-fold: 1) the data comes in a format that most geospatial tools cannot ingest, and 2) SAR imagery is subject to geometric distortions that keep it from being co-registered with more conventional imagery. The Alaska Satellite Facility (ASF) has developed the free, open source MapReady Remote Sensing Tool Kit to facilitate the use of SAR data for even novice users of geospatial data. Through MapReady's intuitive GUI interface, the user is able to ingest a SAR image in its native format and process it to an orthorectified image in GeoTIFF format; ready to be used as a layer in a geographic information system (GIS). This presentation will outline the challenges facing the user of SAR and show how they are overcome through the use of MapReady. The principal innovation in the newest generation of SAR satellites is the implementation of polarimetric SAR, for which data exists in two or more polarizations. Like the bands in optical data, polarimetric bands reveal a great deal about targets in the imagery. In its most recent version, MapReady includes the ability to perform polarimetric decompositions and classifications. Specific examples will be shown using polarimetric data from the ALOS PALSAR sensor. Derived products will be analyzed and interpreted to show how SAR polarimetry can be used to perform land classification and identify land change.

  11. SAR and InSAR georeferencing algorithms for inertial navigation systems

    NASA Astrophysics Data System (ADS)

    Greco, M.; Kulpa, K.; Pinelli, G.; Samczynski, P.

    2011-10-01

    This paper presents the concept of Synthetic Aperture Radar (SAR) and Interferemetric SAR (InSAR) georeferencing algorithms dedicated for SAR based augmented Inertial Navigation Architecture (SARINA). The SARINA is a novel concept of the Inertial Navigation System (INS), which utilized the SAR radar as an additional sensor to provide information about the platform trajectory position and compensate an aircraft drift due to Inertial Measurement Unit (IMU) errors, Global Positioning System (GPS) lack of integrity, etc.

  12. SAR650984 directly induces multiple myeloma cell death via lysosomal-associated and apoptotic pathways, which is further enhanced by pomalidomide.

    PubMed

    Jiang, H; Acharya, C; An, G; Zhong, M; Feng, X; Wang, L; Dasilva, N; Song, Z; Yang, G; Adrian, F; Qiu, L; Richardson, P; Munshi, N C; Tai, Y-T; Anderson, K C

    2016-02-01

    The anti-CD38 monoclonal antibody SAR650984 (SAR) is showing promising clinical activity in treatment of relapsed and refractory multiple myeloma (MM). Besides effector-mediated antibody-dependent cellular cytotoxicity and complement-mediated cytotoxicity, we here define molecular mechanisms of SAR-directed MM cell death and enhanced anti-MM activity triggered by SAR with Pomalidomide (Pom). Without Fc-cross-linking agents or effector cells, SAR specifically induces homotypic aggregation (HA)-associated cell death in MM cells dependent on the level of cell surface CD38 expression, actin cytoskeleton and membrane lipid raft. SAR and its F(ab)'2 fragments trigger caspase 3/7-dependent apoptosis in MM cells highly expressing CD38, even with p53 mutation. Importantly, SAR specifically induces lysosome-dependent cell death (LCD) by enlarging lysosomes and increasing lysosomal membrane permeabilization associated with leakage of cathepsin B and LAMP-1, regardless of the presence of interleukin-6 or bone marrow stromal cells. Conversely, the lysosomal vacuolar H+-ATPase inhibitor blocks SAR-induced LCD. SAR further upregulates reactive oxygen species. Pom enhances SAR-induced direct and indirect killing even in MM cells resistant to Pom/Len. Taken together, SAR is the first therapeutic monoclonal antibody mediating direct cytotoxicity against MM cells via multiple mechanisms of action. Our data show that Pom augments both direct and effector cell-mediated MM cytotoxicity of SAR, providing the framework for combination clinical trials. PMID:26338273

  13. Realtime processor of SAR systems

    NASA Astrophysics Data System (ADS)

    Schotter, R.

    Attention is given to potential applications of a synthetic aperture radar (SAR) real time processor which was developed for Space Shuttle-based earth sensing, and which may prove useful in military surveillance, ocean wave studies, ship movements in territorial waters, land conservation, geology, and mineralogical prospecting. The SAR processor's signal processing task is characterized by complex algorithms and large quantities of raw data/time unit. A 'pipeline' configuration has been judged optimal for this type of processing, and it will consist of digital hardware modules for Fourier transform, digital filtering, two-dimensional image memory, and complex multiplication.

  14. Squint mode SAR processing algorithms

    NASA Technical Reports Server (NTRS)

    Chang, C. Y.; Jin, M.; Curlander, J. C.

    1989-01-01

    The unique characteristics of a spaceborne SAR (synthetic aperture radar) operating in a squint mode include large range walk and large variation in the Doppler centroid as a function of range. A pointing control technique to reduce the Doppler drift and a new processing algorithm to accommodate large range walk are presented. Simulations of the new algorithm for squint angles up to 20 deg and look angles up to 44 deg for the Earth Observing System (Eos) L-band SAR configuration demonstrate that it is capable of maintaining the resolution broadening within 20 percent and the ISLR within a fraction of a decibel of the theoretical value.

  15. 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.

  16. Jatrophane Diterpenoids as Modulators of P-Glycoprotein-Dependent Multidrug Resistance (MDR): Advances of Structure-Activity Relationships and Discovery of Promising MDR Reversal Agents.

    PubMed

    Zhu, Jianyong; Wang, Ruimin; Lou, Lanlan; Li, Wei; Tang, Guihua; Bu, Xianzhang; Yin, Sheng

    2016-07-14

    The phytochemical study of Pedilanthus tithymaloides led to the isolation of 13 jatrophane diterpenoids (1-13), of which eight (1-8) are new. Subsequent structural modification of the major components by esterification, hydrolysis, hydrogenation, or epoxidation yielded 22 new derivatives (14-35). Thus, a jatrophane library containing two series of compounds was established to screen for P-glycoprotein (Pgp)-dependent MDR modulators. The activity was evaluated through a combination of Rho123 efflux and chemoreversal assays on adriamycin resistant human hepatocellular carcinoma cell line HepG2 (HepG2/ADR) and adriamycin resistant human breast adenocarcinoma cell line MCF-7 (MCF-7/ADR). Compounds 19, 25, and 26 were identified as potent MDR modulators with greater chemoreversal ability and less cytotoxicity than the third-generation drug tariquidar. The structure-activity relationship (SAR) was discussed, which showed that modifications beyond just increasing the lipophilicity of this class of Pgp inhibitors are beneficial to the activity. Compound 26, which exhibited a remarkable metabolic stability in vitro and a favorable antitumor effect in vivo, would serve as a promising lead for the development of new MDR reversal agents. PMID:27328029

  17. Cardiac Contractility Structure-Activity Relationship and Ligand-Receptor Interactions; the Discovery Of Unique and Novel Molecular Switches in Myosuppressin Signaling

    PubMed Central

    Leander, Megan; Bass, Chloe; Marchetti, Kathryn; Maynard, Benjamin F.; Wulff, Juan Pedro; Ons, Sheila; Nichols, Ruthann

    2015-01-01

    Peptidergic signaling regulates cardiac contractility; thus, identifying molecular switches, ligand-receptor contacts, and antagonists aids in exploring the underlying mechanisms to influence health. Myosuppressin (MS), a decapeptide, diminishes cardiac contractility and gut motility. Myosuppressin binds to G protein-coupled receptor (GPCR) proteins. Two Drosophila melanogaster myosuppressin receptors (DrmMS-Rs) exist; however, no mechanism underlying MS-R activation is reported. We predicted DrmMS-Rs contained molecular switches that resembled those of Rhodopsin. Additionally, we believed DrmMS-DrmMS-R1 and DrmMS-DrmMS-R2 interactions would reflect our structure-activity relationship (SAR) data. We hypothesized agonist- and antagonist-receptor contacts would differ from one another depending on activity. Lastly, we expected our study to apply to other species; we tested this hypothesis in Rhodnius prolixus, the Chagas disease vector. Searching DrmMS-Rs for molecular switches led to the discovery of a unique ionic lock and a novel 3–6 lock, as well as transmission and tyrosine toggle switches. The DrmMS-DrmMS-R1 and DrmMS-DrmMS-R2 contacts suggested tissue-specific signaling existed, which was in line with our SAR data. We identified R. prolixus (Rhp)MS-R and discovered it, too, contained the unique myosuppressin ionic lock and novel 3–6 lock found in DrmMS-Rs as well as transmission and tyrosine toggle switches. Further, these motifs were present in red flour beetle, common water flea, honey bee, domestic silkworm, and termite MS-Rs. RhpMS and DrmMS decreased R. prolixus cardiac contractility dose dependently with EC50 values of 140 nM and 50 nM. Based on ligand-receptor contacts, we designed RhpMS analogs believed to be an active core and antagonist; testing on heart confirmed these predictions. The active core docking mimicked RhpMS, however, the antagonist did not. Together, these data were consistent with the unique ionic lock, novel 3–6 lock

  18. Cardiac contractility structure-activity relationship and ligand-receptor interactions; the discovery of unique and novel molecular switches in myosuppressin signaling.

    PubMed

    Leander, Megan; Bass, Chloe; Marchetti, Kathryn; Maynard, Benjamin F; Wulff, Juan Pedro; Ons, Sheila; Nichols, Ruthann

    2015-01-01

    Peptidergic signaling regulates cardiac contractility; thus, identifying molecular switches, ligand-receptor contacts, and antagonists aids in exploring the underlying mechanisms to influence health. Myosuppressin (MS), a decapeptide, diminishes cardiac contractility and gut motility. Myosuppressin binds to G protein-coupled receptor (GPCR) proteins. Two Drosophila melanogaster myosuppressin receptors (DrmMS-Rs) exist; however, no mechanism underlying MS-R activation is reported. We predicted DrmMS-Rs contained molecular switches that resembled those of Rhodopsin. Additionally, we believed DrmMS-DrmMS-R1 and DrmMS-DrmMS-R2 interactions would reflect our structure-activity relationship (SAR) data. We hypothesized agonist- and antagonist-receptor contacts would differ from one another depending on activity. Lastly, we expected our study to apply to other species; we tested this hypothesis in Rhodnius prolixus, the Chagas disease vector. Searching DrmMS-Rs for molecular switches led to the discovery of a unique ionic lock and a novel 3-6 lock, as well as transmission and tyrosine toggle switches. The DrmMS-DrmMS-R1 and DrmMS-DrmMS-R2 contacts suggested tissue-specific signaling existed, which was in line with our SAR data. We identified R. prolixus (Rhp)MS-R and discovered it, too, contained the unique myosuppressin ionic lock and novel 3-6 lock found in DrmMS-Rs as well as transmission and tyrosine toggle switches. Further, these motifs were present in red flour beetle, common water flea, honey bee, domestic silkworm, and termite MS-Rs. RhpMS and DrmMS decreased R. prolixus cardiac contractility dose dependently with EC50 values of 140 nM and 50 nM. Based on ligand-receptor contacts, we designed RhpMS analogs believed to be an active core and antagonist; testing on heart confirmed these predictions. The active core docking mimicked RhpMS, however, the antagonist did not. Together, these data were consistent with the unique ionic lock, novel 3-6 lock, transmission

  19. 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

  20. 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.

  1. Possible relationships between solar activity and atmospheric constituents

    NASA Technical Reports Server (NTRS)

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

    1974-01-01

    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) is 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.

  2. Structure Activity Relationship of Dendrimer Microbicides with Dual Action Antiviral Activity

    PubMed Central

    Tyssen, David; Henderson, Scott A.; Johnson, Adam; Sterjovski, Jasminka; Moore, Katie; La, Jennifer; Zanin, Mark; Sonza, Secondo; Karellas, Peter; Giannis, Michael P.; Krippner, Guy; Wesselingh, Steve; McCarthy, Tom; Gorry, Paul R.; Ramsland, Paul A.; Cone, Richard; Paull, Jeremy R. A.; Lewis, Gareth R.; Tachedjian, Gilda

    2010-01-01

    Background Topical microbicides, used by women to prevent the transmission of HIV and other sexually transmitted infections are urgently required. Dendrimers are highly branched nanoparticles being developed as microbicides. However, the anti-HIV and HSV structure-activity relationship of dendrimers comprising benzyhydryl amide cores and lysine branches, and a comprehensive analysis of their broad-spectrum anti-HIV activity and mechanism of action have not been published. Methods and Findings Dendrimers with optimized activity against HIV-1 and HSV-2 were identified with respect to the number of lysine branches (generations) and surface groups. Antiviral activity was determined in cell culture assays. Time-of-addition assays were performed to determine dendrimer mechanism of action. In vivo toxicity and HSV-2 inhibitory activity were evaluated in the mouse HSV-2 susceptibility model. Surface groups imparting the most potent inhibitory activity against HIV-1 and HSV-2 were naphthalene disulfonic acid (DNAA) and 3,5-disulfobenzoic acid exhibiting the greatest anionic charge and hydrophobicity of the seven surface groups tested. Their anti-HIV-1 activity did not appreciably increase beyond a second-generation dendrimer while dendrimers larger than two generations were required for potent anti-HSV-2 activity. Second (SPL7115) and fourth generation (SPL7013) DNAA dendrimers demonstrated broad-spectrum anti-HIV activity. However, SPL7013 was more active against HSV and blocking HIV-1 envelope mediated cell-to-cell fusion. SPL7013 and SPL7115 inhibited viral entry with similar potency against CXCR4-(X4) and CCR5-using (R5) HIV-1 strains. SPL7013 was not toxic and provided at least 12 h protection against HSV-2 in the mouse vagina. Conclusions Dendrimers can be engineered with optimized potency against HIV and HSV representing a unique platform for the controlled synthesis of chemically defined multivalent agents as viral entry inhibitors. SPL7013 is formulated as Viva

  3. 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

  4. How Change of Public Transportation Usage Reveals Fear of the SARS Virus in a City

    PubMed Central

    Wang, Kuo-Ying

    2014-01-01

    The outbreaks of the severe acute respiratory syndrome (SARS) epidemic in 2003 resulted in unprecedented impacts on people's daily life. One of the most significant impacts to people is the fear of contacting the SARS virus while engaging daily routine activity. Here we use data from daily underground ridership in Taipei City and daily reported new SARS cases in Taiwan to model the dynamics of the public fear of the SARS virus during the wax and wane of the SARS period. We found that for each reported new SARS case there is an immediate loss of about 1200 underground ridership (the fresh fear). These daily loss rates dissipate to the following days with an e-folding time of about 28 days, reflecting the public perception on the risk of contacting SARS virus when traveling with the underground system (the residual fear). About 50% of daily ridership was lost during the peak of the 2003 SARS period, compared with the loss of 80% daily ridership during the closure of the underground system after Typhoon Nari, the loss of 50–70% ridership due to the closure of the governmental offices and schools during typhoon periods, and the loss of 60% daily ridership during Chinese New Year holidays. PMID:24647278

  5. SarA based novel therapeutic candidate against Staphylococcus aureus associated with vascular graft infections.

    PubMed

    Arya, Rekha; Ravikumar, R; Santhosh, R S; Princy, S Adline

    2015-01-01

    Staphylococcus aureus is a common pathogen seen in prosthetic vascular graft, leading to high morbidity and mortality. The virulence genes for severity of infections are under the control of global regulators. Staphylococcal accessory regulator A (SarA) a known master controller of biofilm formation is an attractive target for the drug development. A structure based screening of lead compounds was employed for the identification of novel small molecule inhibitors targeted to interact to the DNA binding domain of the transcriptional activator, SarA and hinder its response over the control of genes that up-regulate the phenotype, biofilm. The top-hit SarA selective inhibitor, 4-[(2,4-diflurobenzyl)amino] cyclohexanol (SarABI) was further validated in-vitro for its efficacy. The SarABI was found to have MBIC50value of 200 μg/ml and also down-regulated the expression of the RNA effector, (RNAIII), Hemolysin (hld), and fibronectin-binding protein (fnbA). The anti-adherence property of SarABI on S. aureus invasion to the host epithelial cell lines (Hep-2) was examined where no significant attachment of S. aureus was observed. The SarABI inhibits the colonization of MDR S. aureus in animal model experiment significantly cohere to the molecular docking studies and in vitro experiments. So, we propose that the SarABI could be a novel substitute to overcome a higher degree of MDR S. aureus colonization on vascular graft. PMID:26074884

  6. Detection of Creep displacement along the North Anatolian Fault by ScanSAR-ScanSAR Interferometry

    NASA Astrophysics Data System (ADS)

    Deguchi, Tomonori

    North Anatolian Fault (NAF) has several records of a huge earthquake occurrence in the last one century, which is well-known as a risky active fault. Some signs indicating a creep displacement could be observed on the Ismetpasa segment. The fault with creep deformation is aseismic and never generates the large scale earthquakes. But the scale and rate of fault creep are important factors to watch the fault behavior and to understand the cycle of earthquake. The author had investigated the distribution of spatial and temporal change on the ground motion due to fault creep in the surrounding of the Ismetpasa by InSAR time series analysis using PALSAR datasets from 2007 until 2011. As a result, the land deformation that the northern and southern parts of the fault have slipped to east and west at a rate of 7.5 and 6.5 mm/year in line of sight respectively were obviously detected. These results had good agreement with GPS data. In addition, it became clear that the fault creep along the NAF extended 61 km in east to west direction. In this study, the author applied ScanSAR-ScanSAR Interferometry using PALSAR data to the Ismetpasa segment of NAF.

  7. 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...

  8. 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...

  9. 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...

  10. hPEPT1 affinity and translocation of selected Gln-Sar and Glu-Sar dipeptide derivatives.

    PubMed

    Eriksson, André Huss; Elm, Peter L; Begtrup, Mikael; Nielsen, Robert; Steffansen, Bente; Brodin, Birger

    2005-01-01

    The intestinal di- and tripeptide transporter hPEPT1 is considered responsible for the absorption of di- and tripeptides arising from digestion, along with several drugs and prodrugs. In order to gather information on the binding site of the protein, several structure-affinity relationships have been suggested. However, these are not necessarily predictive of compounds that are actually translocated by hPEPT1. More information on affinity to and translocation via hPEPT1 of side-chain-modified dipeptides may be gained by conducting a study of selected dipeptide derivatives with variety in size, hydrophobicity, and bond type. The aim of the present study was to synthesize new esters and amides based on L-Glu-Sar and investigate the effects that bond type and size of modification of the N-terminal side chain of sarcosine-containing dipeptides have on the affinity to and translocation via hPEPT1. The esters L-Glu(O-i-Bu)-Sar and L-Glu(OCH(2)Ada)-Sar and the amides L-Gln(N,N-dimethyl)-Sar and L-Gln(N-piperidinyl)-Sar were synthesized, and affinity to and translocation via hPEPT1 were investigated in mature Caco-2 cell monolayers, grown on permeable supports. Affinity was estimated in a competition assay using (14)C-labeled Gly-Sar. Translocation was measured as fluorescence ratios induced by the substrates using the fluorescent probe BCECF and an epifluorescence microscope setup. All compounds showed high affinity to hPEPT1, but only the amides L-Gln(N,N-dimethyl)-Sar and L-Gln(N-piperidinyl)-Sar were translocated by hPEPT1. hPEPT1 is very susceptible to modifications of the N-terminal amino acid side chain of dipeptidomimetic substrates, in terms of achieving compounds with high affinity for the transporter. However, as affinity is not predictive of translocation, derivatization in this position must be performed with great caution since some of the compounds investigated turn out not to be translocated by the transporter. PMID:15934785

  11. Neuroprotective and Antioxidant Activities of 4-Methylcoumarins: Development of Structure-Activity Relationships.

    PubMed

    Malhotra, Shashwat; Tavakkoli, Marjan; Edraki, Najmeh; Miri, Ramin; Sharma, Sunil Kumar; Prasad, Ashok Kumar; Saso, Luciano; Len, Christophe; Parmar, Virinder Singh; Firuzi, Omidreza

    2016-01-01

    Coumarins are a major class of polyphenols that are abundantly present in many dietary plants and possess different biological activities. Neuroprotective effect of 28 variously substituted 4-methylcoumarins was evaluated in a cell model of oxidative stress-induced neurodegeneration, which measures viability in PC12 cells challenged with hydrogen peroxide by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The inhibitory activity of these compounds against intracellular reactive oxygen species (ROS) formation was also determined by 2',7'-dichlorofluorescein diacetate method in the same cells. Chemical redox-based assays including 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) tests were employed to explore structure-antioxidant activity relationships in a cell-free environment. The results demonstrated that 4-methylcoumarins containing ortho-dihydroxy or ortho-diacetoxy substituents on the benzenoid ring possess considerable neuroprotective effects. ortho-Dihydroxy compounds inhibited cytotoxicity (44.7-62.9%) and ROS formation (41.6-71.1%) at 50 µM and showed considerable antioxidant effects. We conclude that 4-methylcoumarins are promising neuroprotective and antioxidant scaffolds potentially usefull for management of neurodegenerative diseases. PMID:27582333

  12. L band SAR ocean wave observations during Marsen

    NASA Astrophysics Data System (ADS)

    Jain, A.; Shemdin, O. H.

    1983-11-01

    The L Band Synthetic Aperture Radar (SAR) operated by the Jet Propulsion Laboratory (JPL) was flown over the Nordsee tower during the Marine Remote Sensing Experiment (MARSEN). The five-sided flight pattern allowed viewing of the same ocean surface patch from five different directions. The results form a unique and useful base which is needed for evaluating existing wave imaging theories and developing more realistic models. The results derived from analysis of radar and in situ measurements suggest that (1) the focus dependence for optimum imaging is that for a surface moving with a speed that is approximately equal to the wave phase velocity, (2) azimuthally traveling waves can be as visible as range traveling waves when the necessary focus adjustments are made in the SAR processor, (3) visibility of azimuthally traveling waves does not improve with decreasing integration time, (4) spectra and images of azimuthally traveling waves do not show observable distortions compared to those for range traveling waves, and (5) comparisons of SAR image spectra for September 28, 1979, with in situ wave height spectra suggest that for a multi-peaked wave system the SAR image spectrum and surface wave height spectrum are not connected by a simple relationship.

  13. Synthesis and structure-activity relationship of trimebutine derivatives.

    PubMed

    Sai, H; Ozaki, Y; Hayashi, K; Onoda, Y; Yamada, K

    1996-06-01

    Trimebutine derivatives were synthesized by utilizing alkylation or acylation of isonitriles and nitrile as a key step. The colonic contractile effects of these compounds were examined, and T-1815 was found to have strong colonic propulsive activity. PMID:8814947

  14. 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. PMID:25585976

  15. 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.

  16. Synthesis of a sugar-based thiosemicarbazone series and structure-activity relationship versus the parasite cysteine proteases rhodesain, cruzain, and Schistosoma mansoni cathepsin B1.

    PubMed

    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; Sales Júnior, Policarpo Ademar; Romanha, Alvaro José; Murta, Silvane Maria Fonseca; McKerrow, James H; Caffrey, Conor R; de Oliveira, Renata Barbosa; Ferreira, Rafaela Salgado

    2015-05-01

    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

  17. 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

  18. 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... Fleming v. Hawkeye Pearl Button Co., 113 F. 2d 52; cf. McComb v. Consolidated Fisheries, 174 F. 2d 74)....

  19. 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.…

  20. 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…

  1. Isoquinoline derivatives as potent CRTH2 antagonists: design, synthesis and SAR.

    PubMed

    Nishikawa-Shimono, Rie; Sekiguchi, Yoshinori; Koami, Takeshi; Kawamura, Madoka; Wakasugi, Daisuke; Watanabe, Kazuhito; Wakahara, Shunichi; Kimura, Kayo; Yamanobe, Susumu; Takayama, Tetsuo

    2013-12-15

    In this study, we describe the synthesis and structure-activity relationship (SAR) of a series of isoquinoline chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) antagonists. TASP0376377 (15-20), one of the most potent compounds, showed a potent binding affinity (IC50=19 nM) in addition to the excellent functional antagonist activity (IC50=13 nM). Moreover, the efficacy of this compound in a chemotaxis assay (IC50=23 nM) was in good agreement with its potency as a CRTH2 antagonist. In addition, 15-20 exhibited greater selectivity in binding to CRTH2 than to the DP1 prostanoid receptor (IC50 >1 μM) or the enzymes COX-1 and COX-2 (IC50 >10 μM). PMID:24216094

  2. Antitubercular Nucleosides that Inhibit Siderophore Biosynthesis: SAR of the Glycosyl Domain

    PubMed Central

    Somu, Ravindranadh V.; Wilson, Daniel; Bennett, Eric M.; Boshoff, Helena; Celia, Laura; Beck, Brian; Barry, Clifton E.; Aldrich, Courtney C.

    2008-01-01

    Tuberculosis (TB) is the leading cause of infectious disease mortality in the world by a bacterial pathogen. We previously demonstrated that a bisubstrate inhibitor of the adenylation enzyme MbtA, which is responsible for the second step of mycobactin biosynthesis, exhibited potent antitubercular activity. Here we systematically investigate the structure activity relationships of the bisubstrate inhibitor glycosyl domain resulting in the identification of a carbocyclic analogue that possesses a KIapp value of 2.3 nM and MIC99 values of 1.56 μM against M. tuberculosis H37Rv. The SAR data suggest the intriguing possibility that the bisubstrate inhibitors utilize a transporter for entry across the mycobacterial cell-envelope. Additionally, we report improved conditions for the expression of MbtA and biochemical analysis demonstrating that MbtA follows a random sequential enzyme mechanism for the adenylation half-reaction. PMID:17181146

  3. 4-Aminoquinolines Active against Chloroquine-Resistant Plasmodium falciparum: Basis of Antiparasite Activity and Quantitative Structure-Activity Relationship Analyses▿

    PubMed Central

    Hocart, Simon J.; Liu, Huayin; Deng, Haiyan; De, Dibyendu; Krogstad, Frances M.; Krogstad, Donald J.

    2011-01-01

    Chloroquine (CQ) is a safe and economical 4-aminoquinoline (AQ) antimalarial. However, its value has been severely compromised by the increasing prevalence of CQ resistance. This study examined 108 AQs, including 68 newly synthesized compounds. Of these 108 AQs, 32 (30%) were active only against CQ-susceptible Plasmodium falciparum strains and 59 (55%) were active against both CQ-susceptible and CQ-resistant P. falciparum strains (50% inhibitory concentrations [IC50s], ≤25 nM). All AQs active against both CQ-susceptible and CQ-resistant P. falciparum strains shared four structural features: (i) an AQ ring without alkyl substitution, (ii) a halogen at position 7 (Cl, Br, or I but not F), (iii) a protonatable nitrogen at position 1, and (iv) a second protonatable nitrogen at the end of the side chain distal from the point of attachment to the AQ ring via the nitrogen at position 4. For activity against CQ-resistant parasites, side chain lengths of ≤3 or ≥10 carbons were necessary but not sufficient; they were identified as essential factors by visual comparison of 2-dimensional (2-D) structures in relation to the antiparasite activities of the AQs and were confirmed by computer-based 3-D comparisons and differential contour plots of activity against P. falciparum. The advantage of the method reported here (refinement of quantitative structure-activity relationship [QSAR] descriptors by random assignment of compounds to multiple training and test sets) is that it retains QSAR descriptors according to their abilities to predict the activities of unknown test compounds rather than according to how well they fit the activities of the compounds in the training sets. PMID:21383099

  4. 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…

  5. 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...

  6. 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…

  7. 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...

  8. Does Physical Activity Intensity Moderate Social Cognition and Behavior Relationships?

    ERIC Educational Resources Information Center

    Scott, Felicity; Rhodes, Ryan E.; Downs, Danielle Symons

    2009-01-01

    Objective: Public health messaging about physical activity (PA) sometimes combines moderate and vigorous intensity, but the variance/invariance of the motives for PA by intensity has received scant attention. Thus, the purpose of this study was to examine the beliefs and motivations associated with regular moderate- and vigorous-intensity PA in a…

  9. The Relationship among Faculty Appointments and Scholarly Activities

    ERIC Educational Resources Information Center

    Gonzalez, Lynn Passmore

    2010-01-01

    The mission of higher education and the activities of faculty are often described in terms of teaching, research, and service. Additionally, tenure has been the standard model for employment in American college and universities since 1940. The traditional model of faculty earning tenure through high standards of teaching, research, and service is…

  10. Structure-antimicrobial activity relationship between pleurocidin and its enantiomer

    PubMed Central

    Lee, Juneyoung

    2008-01-01

    To develop novel antibiotic peptides useful as therapeutic drugs, the enantiomeric analogue of pleurocidin (Ple), which is a well known 25-mer antimicrobial peptide, was designed for proteolytic resistance by D-amino acids substitution. The proteolytic resistance was confirmed by using HPLC after the digestion with various proteases. To investigate the antibiotic effect of L- and D-Ple, the antibacterial activity and hemolytic effect were tested against human erythrocytes. The D-Ple showed a decreased antibacterial activity and a dramatically decreased hemolytic activity compared with L-Ple. The hemolytic effect of analogue was further confirmed by using calcein leakage measurement with liposome. To elucidate these results, the secondary structure of the peptides was investigated by using circular dichroism spectroscopy. The results revealed that D-Ple, as well as L-Ple, had typical α-helical structures which were mirror images, with a different helicity. These results suggested that the discrepancy of the structure between the two peptides made their antibacterial activity distinct. PMID:18779649

  11. Teaching as a Cultural and Relationship-Based Activity

    ERIC Educational Resources Information Center

    McConville, Alistair G.

    2013-01-01

    The process of teaching is not selfless, as some suggest. Rather, in its best manifestations it is an ideologically and culturally loaded activity in which teachers and institutions seek to perpetuate a certain integrated view of the world for their own benefit, for that of their learners, and for society more generally. This takes place most…

  12. Relationship between calpastatin activity and lamb carcass characteristics.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The purpose of this study was to determine if calpastatin activity (CALP) was related to the amount of intramuscular fat (IMF) and Warner-Bratzler shear force (WBS) in lamb carcasses. Market wethers representing three sire lines (n = 40, average live weight of 68.9 kg) were harvested at the OSU Mea...

  13. Synthesis, SAR and antibacterial studies on novel chalcone oxazolidinone hybrids.

    PubMed

    Selvakumar, N; Kumar, G Sunil; Azhagan, A Malar; Rajulu, G Govinda; Sharma, Shikha; Kumar, M Sitaram; Das, Jagattaran; Iqbal, Javed; Trehan, Sanjay

    2007-04-01

    With an intention to synergise the antibacterial activity of chalcones and oxazolidinones, several hybrid compounds possessing both chalcone and oxazolidinone moieties were synthesized and tested for antibacterial activity. The hybrid molecules containing heterocycles instead of aromatic ring were found to be active. A SAR study with various heterocycles resulted in a lead molecule 20, which was converted to one of the potent antibacterial compounds 27. PMID:17150281

  14. 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.

  15. Relationships between physical activity and musculoskeletal disorders in former athletes.

    PubMed

    Haljaste, Kaja; Unt, Eve

    2010-12-01

    The purpose of the study was to determine the prevalence and risks for musculoskeletal disorders (MSD) in relation to previous athletic status and current physical activity level in former athletes. Main anthropometric data, sports history, current physical activity and MSD were estimated using a questionnaire in 219 (148 males, 71 females) former athletes (35-75 years old) and 79 controls (33 males, 46 females). According to the previous participation in top-level sports, former athletes were divided into three groups: (a) endurance, n=120 (76 males, 44 females); (b) speed-power, n=57 (43 males, 14 females); (c) team sports, n=42 (29 males, 13 females). The most prevalent MSD among the male and female ex-athletes were back and knee pain. The endurance ex-athletes group (both males and females) had significantly higher risk for the knee problems than the control group (Odds ratio--OR 5.9, 95% CI 1.7-20.00, p < 0.05). Team sports athletes (males and females) showed significantly higher risk for Achilles' tendon injuries (OR 3.19 95% CI 1.19-8.5, p < 0.05) as compared to controls. Back pain did not show any significant associations with previous physical activity and current physical activity level. Current physical activity was significantly associated with a lower risk for the knee and hip pain. Body mass index was positively associated with knee problems. In conclusion, our study results revealed that previous participation in enduranve sports events is associated with a significantly higher risk for knee problems. At the same time current regular physical exercise 6-11 times per month is associated with a lower prevalence of knee and hip problems as compared to those who exercised less than 6 times per month. PMID:21874718

  16. 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

  17. 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...

  18. 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...

  19. 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...

  20. Relationships Between Vocal Activity and Perception of Communicators in Small Group Interaction

    ERIC Educational Resources Information Center

    Daley, John A.; And Others

    1977-01-01

    Discusses a study designed to investigate the relationships between vocal activity level and interpersonal attraction, perceived credibility, perceived homophily or interpersonal similarity and perceived power or ability to influence. (MH)

  1. 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

  2. Developing Methods for Mapping Soil Moisture in Nash Draw, NM Using RADARSAT 1 SAR Fine Imagery

    NASA Astrophysics Data System (ADS)

    Hossain, A. A.; Easson, G.; Powers, D. W.; Holt, R. M.

    2006-12-01

    Nash Draw, in southeastern NM, is a karst valley that developed in response to subsurface dissolution of evaporites, including halite and sulfate rocks. The hydrologic system within Nash Draw is poorly understood. This study focuses on identifying the distribution and amount of recharge in Nash Draw to assist in understanding the existing processes modifying Nash Draw by solution. We hypothesize that 1) soil moisture contents will be higher in the areas where potential recharge occurs and 2) these areas can be identified using remote sensing. To test the second part of this hypothesis, this study has been designed to determine the spatial and temporal distribution of soil moisture in the study site using microwave data. An area of 225 sq. km in Nash Draw has been selected as the study site. Imagery was acquired from the Alaska SAR Facility (ASF) for 8 scenes of RADARDSAT 1 SAR Fine Beam imagery with different incidence angles (40° and 48°) and imaging modes (ascending and descending). We use RADARDSAT 1 SAR Fine Beam imagery acquired on August 1, 2006 and August 2, 2006 and near real-time ground truth data to develop suitable model to map the spatial distribution of soil moisture in the study site. During the image acquisitions on August 1 and 2, 80 soil samples were collected to determine the near real- time volumetric soil moisture in the study site. Soil samples were collected using a stratified sampling method, and locations of the samples were recorded using GPS. Soil water is compared, using linear regression, to radar backscatter to develop an empirical model of the relationship. The radar backscatter used in this model was acquired at different incidence angles. This study also provides an opportunity to investigate the impact of variable incidence angles on the potential of space-borne active microwave data for soil moisture mapping in semi-arid region like Nash Draw.

  3. 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.

  4. 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

  5. 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

  6. Structure-Activity Relationship of Chlorotoxin-Like Peptides.

    PubMed

    Ali, Syed Abid; Alam, Mehtab; Abbasi, Atiya; Undheim, Eivind A B; Fry, Bryan Grieg; Kalbacher, Hubert; Voelter, Wolfgang

    2016-02-01

    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

  7. 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. PMID:18045063

  8. Neighborhood Design and Perceptions: Relationship with Active Commuting

    PubMed Central

    Voorhees, Carolyn C.; Ashwood, J. Scott; Evenson, Kelly R.; Sirard, John R.; Rung, Ariane L.; Dowda, Marsha; McKenzie, Thomas L.

    2010-01-01

    Purpose Walking to and from school contributes to total physical activity levels. This study investigated whether perceived and actual neighborhood features were associated with walking to or from school among adolescent girls. Methods A sample of geographically diverse 8th grade girls (N=890) from the Trial for Activity in Adolescent Girls (TAAG) study living within 1.5 miles of their middle school were recruited. Participants completed a self-administered survey on their neighborhood and walking behavior. Geographic information system (GIS) data were used to assess objective neighborhood features. Nested multivariable logistic regression analyses were conducted to determine the contribution of perceived and objective measures of walking to or from school. Results Fifty-six percent (N=500) of the girls walked to or from school at least one day of the week. White (42%) girls walked more frequently than Hispanic (25%) and African American (21%) girls. Girls were nearly twice as likely to walk to or from school if they perceived their neighborhoods as safe and perceived they had places they liked to walk, controlling for other potential confounders. Additionally, girls who lived closer to school, had more active destinations in their neighborhood, and smaller sized blocks were more likely to walk to or from school than those who did not. Conclusion Safety, land use, and school location issues need to be considered together when designing interventions to increase walking to and from school. PMID:20019628

  9. 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. PMID:21774900

  10. 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.

  11. Evidence for a curvilinear relationship between sympathetic nervous system activation and women's physiological sexual arousal.

    PubMed

    Lorenz, Tierney Ahrold; Harte, Christopher B; Hamilton, Lisa Dawn; Meston, Cindy M

    2012-01-01

    There is increasing evidence that women's physiological sexual arousal is facilitated by moderate sympathetic nervous system (SNS) activation. Literature also suggests that the level of SNS activation may play a role in the degree to which SNS activity affects sexual arousal. We provide the first empirical examination of a possible curvilinear relationship between SNS activity and women's genital arousal using a direct measure of SNS activation in 52 sexually functional women. The relationship between heart rate variability (HRV), a specific and sensitive marker of SNS activation, and vaginal pulse amplitude (VPA), a measure of genital arousal, was analyzed. Moderate increases in SNS activity were associated with higher genital arousal, while very low or very high SNS activation was associated with lower genital arousal. These findings imply that there is an optimal level of SNS activation for women's physiological sexual arousal. PMID:22092348

  12. Small-molecule PSMA ligands. Current state, SAR and perspectives.

    PubMed

    Machulkin, Alexey E; Ivanenkov, Yan A; Aladinskaya, Anastasia V; Veselov, Mark S; Aladinskiy, Vladimir A; Beloglazkina, Elena K; Koteliansky, Victor E; Shakhbazyan, Artem G; Sandulenko, Yuri B; Majouga, Alexander G

    2016-09-01

    Prostate cancer (PC) is the prevalent malignancy widespread among men in the Western World. Prostate specific membrane antigen (PSMA) is an established PC marker and has been considered as a promising biological target for anti-PC drug delivery and diagnostics. The protein was found to be overexpressed in PC cells, including metastatic, and the neovasculature of solid tumors. These properties make PSMA-based approach quite appropriate for effective PC imaging and specific drug therapy. Through the past decade, a variety of PSMA-targeted agents has been systematically evaluated. Small-molecule compounds have several advantages over other classes, such as improved pharmacokinetics and rapid blood clearance. These low-weight ligands have similar structure and can be divided into three basic categories in accordance with the type of their zinc-binding core-head. Several PSMA binders are currently undergoing clinical trials generally for PC imaging. The main goal of the present review is to describe the recent progress achieved within the title field and structure activity relationships (SAR) disclosed for different PSMA ligands. Recent in vitro and in vivo studies for each type of the compounds described have also been briefly summarized. PMID:26887438

  13. SAR Image despeckling via sparse representation

    NASA Astrophysics Data System (ADS)

    Wang, Zhongmei; Yang, Xiaomei; Zheng, Liang

    2014-11-01

    SAR image despeckling is an active research area in image processing due to its importance in improving the quality of image for object detection and classification.In this paper, a new approach is proposed for multiplicative noise in SAR image removal based on nonlocal sparse representation by dictionary learning and collaborative filtering. First, a image is divided into many patches, and then a cluster is formed by clustering log-similar image patches using Fuzzy C-means (FCM). For each cluster, an over-complete dictionary is computed using the K-SVD method that iteratively updates the dictionary and the sparse coefficients. The patches belonging to the same cluster are then reconstructed by a sparse combination of the corresponding dictionary atoms. The reconstructed patches are finally collaboratively aggregated to build the denoised image. The experimental results show that the proposed method achieves much better results than many state-of-the-art algorithms in terms of both objective evaluation index (PSNR and ENL) and subjective visual perception.

  14. From SARS coronavirus to novel animal and human coronaviruses

    PubMed Central

    To, Kelvin K. W.; Hung, Ivan F. N.; Chan, Jasper F. W.

    2013-01-01

    In 2003, severe acute respiratory syndrome coronavirus (SARS-CoV) caused one of the most devastating epidemics known to the developed world. There were two important lessons from this epidemic. Firstly, coronaviruses, in addition to influenza viruses, can cause severe and rapidly spreading human infections. Secondly, bats can serve as the origin and natural animal reservoir of deadly human viruses. Since then, researchers around the world, especially those in Asia where SARS-CoV was first identified, have turned their focus to find novel coronaviruses infecting humans, bats, and other animals. Two human coronaviruses, HCoV-HKU1 and HCoV-NL63, were identified shortly after the SARS-CoV epidemic as common causes of human respiratory tract infections. In 2012, a novel human coronavirus, now called Middle East respiratory syndrome coronavirus (MERS-CoV), has emerged in the Middle East to cause fatal human infections in three continents. MERS-CoV human infection is similar to SARS-CoV in having a high fatality rate and the ability to spread from person to person which resulted in secondary cases among close contacts including healthcare workers without travel history to the Middle East. Both viruses also have close relationships with bat coronaviruses. New cases of MERS-CoV infection in humans continue to occur with the origins of the virus still unknown in many cases. A multifaceted approach is necessary to control this evolving MERS-CoV outbreak. Source identification requires detailed epidemiological studies of the infected patients and enhanced surveillance of MERS-CoV or similar coronaviruses in humans and animals. Early diagnosis of infected patients and appropriate infection control measures will limit the spread in hospitals, while social distancing strategies may be necessary to control the outbreak in communities if it remained uncontrolled as in the SARS epidemic. PMID:23977429

  15. 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. PMID:27077228

  16. Controlling Data Collection to Support SAR Image Rotation

    SciTech Connect

    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.

  17. Asymptomatic SARS coronavirus infection among healthcare workers, Singapore.

    PubMed

    Wilder-Smith, Annelies; Teleman, Monica D; Heng, Bee H; Earnest, Arul; Ling, Ai E; Leo, Yee S

    2005-07-01

    We conducted a study among healthcare workers (HCWs) exposed to patients with severe acute respiratory syndrome (SARS) before infection control measures were instituted. Of all exposed HCWs, 7.5% had asymptomatic SARS-positive cases. Asymptomatic SARS was associated with lower SARS antibody titers and higher use of masks when compared to pneumonic SARS. PMID:16022801

  18. 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.

  19. The SARS-associated stigma of SARS victims in the post-SARS era of Hong Kong.

    PubMed

    Siu, Judy Yuen-man

    2008-06-01

    This article explores the disease-associated stigma attached to the SARS victims in the post-SARS era of Hong Kong. I argue that the SARS-associated stigma did not decrease over time. Based on the ethnographic data obtained from 16 months of participant observation in a SARS victims' self-help group and semistructured interviews, I argue that the SARS-associated stigma was maintained, revived, and reconstructed by the biomedical encounters, government institutions, and public perception. I also provide new insight on how the SARS-associated stigma could create problems for public health development in Hong Kong. As communicable diseases will be a continuing threat for the human society, understanding how the disease-associated stigma affects the outcomes of epidemic control measures will be crucial in developing a more responsive public health policy as well as medical follow-up and social support service to the diseased social groups of future epidemic outbreaks. PMID:18503014

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

    PubMed Central

    Roh, Changhyun

    2012-01-01

    Hundreds of million people worldwide have been infected with severe acute respiratory syndrome (SARS), and the rate of global death from SARS has remarkably increased. Hence, the development of efficient drug treatments for the biological effects of SARS is highly needed. We have previously shown that quantum dots (QDs)-conjugated RNA oligonucleotide is sensitive to the specific recognition of the SARS-associated coronavirus (SARS-CoV) nucleocapsid (N) protein. In this study, we found that a designed biochip could analyze inhibitors of the SARS-CoV N protein using nanoparticle-based RNA oligonucleotide. Among the polyphenolic compounds examined, (−)-catechin gallate and (−)-gallocatechin gallate demonstrated a remarkable inhibition activity on SARS-CoV N protein. (−)-catechin gallate and (−)-gallocatechin gallate attenuated the binding affinity in a concentrated manner as evidenced by QDs-conjugated RNA oligonucleotide on a designed biochip. At a concentration of 0.05 μg mL−1, (−)-catechin gallate and (−)-gallocatechin gallate showed more than 40% inhibition activity on a nanoparticle-based RNA oligonucleotide biochip system. PMID:22619553

  1. Thermal implications of high SAR's in the body extremities at the ANSI-recommended MF-VHF safety levels

    SciTech Connect

    Chen, J.Y.; Gandhi, O.P.

    1988-06-01

    Surface temperature elevation of the wrist and the ankle sections were measured for a healthy human subject at room temperature (22-25/sup 0/C) for a variety of RF currents and SAR's in the frequency band 1-50 MHz. The observed highest rates of temperature increase in /sup 0/C/min are given by the best-fit relationships: 0.0045 x SAR in W/kg for the ankle section and 0.0048 x SAR for the wrist section, the latter being involved for conditions of contact with undergrounded bodies like cars, trucks, fences, etc. Since ankle-section SAR's on the order of 182-243 W/kg and wrist-section SAR's as high as 1045 W/kg have previously been projected for the E fields recommended in the ANSI C95.1-1982 safety guide, fairly high rates of temperature increase are therefore anticipated.

  2. Bradykinin actively modulates pulmonary vascular pressure-cardiac index relationships.

    PubMed

    Nyhan, D P; Clougherty, P W; Goll, H M; Murray, P A

    1987-07-01

    Our objectives were to investigate the pulmonary vascular effects of exogenously administered bradykinin at normal and reduced levels of cardiac index in intact conscious dogs and to assess the extent to which the pulmonary vascular response to bradykinin is the result of either cyclooxygenase pathway activation or reflex activation of sympathetic beta-adrenergic and -cholinergic receptors. Multipoint pulmonary vascular pressure-cardiac index (P/Q) plots were constructed during normoxia in conscious dogs by step-wise constriction of the thoracic inferior vena cava to reduce Q. In intact dogs, bradykinin (2 micrograms X kg-1 X min-1 iv) caused systemic vasodilation, i.e., systemic arterial pressure was slightly decreased (P less than 0.05), Q was markedly increased (P less than 0.01), and mixed venous PO2 and oxygen saturation (SO2) were increased (P less than 0.01). Bradykinin decreased (P less than 0.01) the pulmonary vascular pressure gradient (pulmonary arterial pressure-pulmonary capillary wedge pressure) over the entire range of Q studied (140-60 ml X min-1 X kg-1) in intact dogs. During cyclooxygenase pathway inhibition with indomethacin, bradykinin again decreased (P less than 0.05) pulmonary arterial pressure-pulmonary capillary wedge pressure at every level of Q, although the magnitude of the vasodilator response was diminished at lower levels of Q (60 ml X min-1 X kg-1). Following combined administration of sympathetic beta-adrenergic and -cholinergic receptor antagonists, bradykinin still decreased (P less than 0.01) pulmonary arterial pressure-pulmonary capillary wedge pressure over the range of Q from 160 to 60 ml X min-1 X kg-1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3114215

  3. 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.

  4. 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

  5. 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.

  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. Representing SAR complex image pixels

    NASA Astrophysics Data System (ADS)

    Doerry, A. W.

    2016-05-01

    Synthetic Aperture Radar (SAR) images are often complex-valued to facilitate specific exploitation modes. Furthermore, these pixel values are typically represented with either real/imaginary (also known as I/Q) values, or as Magnitude/Phase values, with constituent components comprised of integers with limited number of bits. For clutter energy well below full-scale, Magnitude/Phase offers lower quantization noise than I/Q representation. Further improvement can be had with companding of the Magnitude value.

  8. Identification and Structure-Activity Relationships of Diarylhydrazides as Novel Potent and Selective Human Enterovirus Inhibitors.

    PubMed

    Han, Xin; Sun, Ningyuan; Wu, Haoming; Guo, Deyin; Tien, Po; Dong, Chune; Wu, Shuwen; Zhou, Hai-Bing

    2016-03-10

    Enterovirus 71 (EV71) plays an important role in hand-foot-and-mouth disease. In this study, a series of diarylhydrazide analogues was synthesized, and the systematic exploration of SAR led to potent enterovirus inhibitors, of which compound 15 exhibits significant improvements in inhibition potency with an EC50 value of 0.02 μM against EV71. It is very interesting that this class of diarylhydrazides exhibits activities against a series of human enteroviruses at the picomolar level, including EV71 and Coxsackieviruses B1 (CVB1), CVB2, CVB3, CVB4, CVB5, and CVB6 (EC50 as low as 0.5 nM). Compared with the reference antienterovirus drug 1 (enviroxime) and known inhibitor 5 (WIN 51711), the four highly selective compounds 15, 27, 41 and 47 inhibited EV71 replication with EC50 values of 0.17-0.02 μM and SI values in a range of 978.4-12338. A preliminary mechanistic study indicated that VP1 might be the target site for this type of compound. PMID:26885567

  9. 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.

  10. 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

  11. 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

  12. Distinct Spatial Patterns of SAR11, SAR86, and Actinobacteria Diversity along a Transect in the Ultra-oligotrophic South Pacific Ocean.

    PubMed

    West, Nyree J; Lepère, Cécile; Manes, Carmem-Lara de O; Catala, Philippe; Scanlan, David J; Lebaron, Philippe

    2016-01-01

    Distinct distribution patterns of members of the major bacterial clades SAR11, SAR86, and Actinobacteria were observed across a transect from the Marquesas islands through the ultra-oligotrophic South Pacific Gyre into the Chilean upwelling using 16S rRNA gene sequencing and RNA-DNA fingerprinting. Three different Actinobacteria sequence clusters belonging to "Candidatus Actinomarinidae" were localized in the western half of the transect, one was limited to the gyre deep chlorophyll maximum (DCM) and sequences affiliated to the OCS155 clade were unique to the upwelling. The structure of the surface bacterial community was highly correlated with water mass and remained similar across the whole central gyre (1300 nautical miles). The surface hyperoligotrophic gyre was dominated (>70% of all sequences) by highly diverse SAR11 and SAR86 operational taxonomic units and these communities were significantly different from those in the DCM. Analysis of 16S rRNA fingerprints generated from RNA allowed insights into the potential activity of assigned bacterial groups. SAR11 and Prochlorococcus showed the highest potential activity in all water masses except for the upwelling, accounting together for 65% of the total bacterial 16S rRNA in the gyre surface waters in equal proportions whereas the contribution of SAR11 decreased significantly at the DCM. PMID:27014192

  13. 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

  14. New Insight into the Structure-Activity Relationships of the Selective Excitatory Amino Acid Transporter Subtype 1 (EAAT1) Inhibitors UCPH-101 and UCPH-102.

    PubMed

    Hansen, Stinne W; Erichsen, Mette N; Huynh, Tri H V; Ruiz, Josep A; Haym, Isabell; Bjørn-Yoshimoto, Walden E; Abrahamsen, Bjarke; Hansen, Jeanette; Storgaard, Morten; Eriksen, Anette L; Jensen, Anders A; Bunch, Lennart

    2016-02-17

    In the present study, we made further investigations on the structure-activity requirements of the selective excitatory amino acid transporter 1 (EAAT1) inhibitor, 2-amino-4-(4-methoxyphenyl)-7-(naphthalen-1-yl)-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (UCPH-101), by exploring 15 different substituents (R(1) ) at the 7-position in combination with eight different substituents (R(2) ) at the 4-position. Among the 63 new analogues synthesized, we identified a number of compounds that unexpectedly displayed inhibitory activities at EAAT1 in light of understanding the structure-activity relationship (SAR) of this inhibitor class extracted from previous studies. Moreover, the nature of the R(1) and R(2) substituents were observed to contribute to the functional properties of the various analogues in additive and non-additive ways. Finally, separation of the four stereoisomers of analogue 14 g (2-amino-4-([1,1'-biphenyl]-4-yl)-3-cyano-7-isopropyl-5-oxo-5,6,7,8-tetrahydro-4H-chromene) was carried out, and in agreement with a study of a related scaffold, the R configuration at C4 was found to be mandatory for inhibitory activity, while both the C7 diastereomers were found to be active as EAAT1 inhibitors. A study of the stereochemical stability of the four pure stereoisomers 14 g-A-D showed that epimerization takes places at C7 via a ring-opening, C-C bond rotation, ring-closing mechanism. PMID:26757239

  15. Molecular recognition of CYP26A1 binding pockets and structure-activity relationship studies for design of potent and selective retinoic acid metabolism blocking agents.

    PubMed

    Sun, Bin; Song, Shuai; Hao, Chen-Zhou; Huang, Wan-Xu; Liu, Chun-Chi; Xie, Hong-Lei; Lin, Bin; Cheng, Mao-Sheng; Zhao, Dong-Mei

    2015-03-01

    All-trans-retinoic acid (ATRA), the biologically most active metabolite of vitamin A, plays a major role in the regulation of cellular differentiation and proliferation, and it is also an important pharmacological agent particularly used in the treatment of cancer, skin, neurodegenerative and autoimmune diseases. However, ATRA is very easy to be metabolized into 4-hydroxyl-RA in vivo by CYP26A1, an inducible cytochrome P450 enzyme, eventually into more polar metabolites. Therefore, it is vital to develop specific retinoic acid metabolism blocking agents (RAMBAs) to inhibit the metabolic enzyme CYP26A1 in the treatment of relevant diseases aforementioned. In this study, CYP26A1 and its interactions with retinoic acid-competitive metabolism blocking agents were investigated by a combined ligand- and structure-based approach. First, since the crystal structure of CYP26A1 protein has not been determined, we constructed the 3D structure of CYP26A1 using homology modeling. In order to achieve a deeper insight into the mode of action of RAMBAs in the active site, the molecular superimposition model and the common feature pharmacophore model were constructed, and molecular docking was performed. The molecular superimposition model is composed of three features: the main chain groups, side chain groups, and azole groups. The common feature pharmacophore model consists of five chemical features: four hydrophobic groups and one hydrogen acceptor (HHHHA). The results of molecular docking show that the characteristic groups of RAMBAs were mapped into three different active pockets, respectively. A structure-activity relationship (SAR) was obtained by a combination of the molecular superimposition and docking results with the pharmacophore model. This study gives more insight into the interaction model inside the CYP26A1 active site and provides guidance for the design of more potent and possibly more selective RAMBAs. PMID:25541526

  16. Current trends in the structure-activity relationships of sialyltransferases.

    PubMed

    Audry, Magali; Jeanneau, Charlotte; Imberty, Anne; Harduin-Lepers, Anne; Delannoy, Philippe; Breton, Christelle

    2011-06-01

    Sialyltransferases (STs) represent an important group of enzymes that transfer N-acetylneuraminic acid (Neu5Ac) from cytidine monophosphate-Neu5Ac to various acceptor substrates. In higher animals, sialylated oligosaccharide structures play crucial roles in many biological processes but also in diseases, notably in microbial infection and cancer. Cell surface sialic acids have also been found in a few microorganisms, mainly pathogenic bacteria, and their presence is often associated with virulence. STs are distributed into five different families in the CAZy database (http://www.cazy.org/). On the basis of crystallographic data available for three ST families and fold recognition analysis for the two other families, STs can be grouped into two structural superfamilies that represent variations of the canonical glycosyltransferase (GT-A and GT-B) folds. These two superfamilies differ in the nature of their active site residues, notably the catalytic base (a histidine or an aspartate residue). The observed structural and functional differences strongly suggest that these two structural superfamilies have evolved independently. PMID:21098518

  17. Improving quantitative structure-activity relationships through multiobjective optimization.

    PubMed

    Nicolotti, Orazio; Giangreco, Ilenia; Miscioscia, Teresa Fabiola; Carotti, Angelo

    2009-10-01

    A multiobjective optimization algorithm was proposed for the automated integration of structure- and ligand-based molecular design. Driven by a genetic algorithm, the herein proposed approach enabled the detection of a number of trade-off QSAR models accounting simultaneously for two independent objectives. The first was biased toward best regressions among docking scores and biological affinities; the second minimized the atom displacements from a properly established crystal-based binding topology. Based on the concept of dominance, 3D QSAR equivalent models profiled the Pareto frontier and were, thus, designated as nondominated solutions of the search space. K-means clustering was, then, operated to select a representative subset of the available trade-off models. These were effectively subjected to GRID/GOLPE analyses for quantitatively featuring molecular determinants of ligand binding affinity. More specifically, it was demonstrated that a) diverse binding conformations occurred on the basis of the ligand ability to profitably contact different part of protein binding site; b) enzyme selectivity was better approached and interpreted by combining diverse equivalent models; and c) trade-off models were successful and even better than docking virtual screening, in retrieving at high sensitivity active hits from a large pool of chemically similar decoys. The approach was tested on a large series, very well-known to QSAR practitioners, of 3-amidinophenylalanine inhibitors of thrombin and trypsin, two serine proteases having rather different biological actions despite a high sequence similarity. PMID:19785453

  18. Multiresolution FOPEN SAR image formation

    NASA Astrophysics Data System (ADS)

    DiPietro, Robert C.; Fante, Ronald L.; Perry, Richard P.; Soumekh, Mehrdad; Tromp, Laurens D.

    1999-08-01

    This paper presents a new technique for FOPEN SAR (foliage penetration synthetic aperture radar) image formation of Ultra Wideband UHF radar data. Planar Subarray Processing (PSAP) has successfully demonstrated the capability of forming multi- resolution images for X and Ka band radar systems under MITRE IR&D and the DARPA IBC program. We have extended the PSAP algorithm to provide the capability to form strip map, multi- resolution images for Ultra Wideband UHF radar systems. The PSAP processing can accommodate very large SAR integration angles and the resulting very large range migration. It can also accommodate long coherent integration times and wide swath coverage. Major PSAP algorithm features include: multiple SAR sub-arrays providing different look angles at the same image area that can enable man-made target responses to be distinguished from other targets and clutter by their angle dependent specular characteristics, the capability to provide a full resolution image in these and other selected areas without the processing penalty of full resolution in non required areas, and the capability to include angle-dependent motion compensation within the image formation process.

  19. 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.

  20. Structure-activity relationships at monoamine transporters for a series of N-substituted 3alpha-(bis[4-fluorophenyl]methoxy)tropanes: comparative molecular field analysis, synthesis, and pharmacological evaluation.

    PubMed

    Kulkarni, Santosh S; Grundt, Peter; Kopajtic, Theresa; Katz, Jonathan L; Newman, Amy Hauck

    2004-06-17

    The development of structure-activity relationships (SAR) with divergent classes of monoamine transporter ligands and comparison of their effects in animal models of cocaine abuse have provided insight into the complex relationship among structure, binding profiles, and behavioral activity. Many 3alpha-(diphenylmethoxy)tropane (benztropine) analogues are potent dopamine uptake inhibitors but exhibit behavioral profiles that differ from those of cocaine and other compounds in this class. One of the most potent and dopamine transporter (DAT) selective N-substituted benztropine analogues (N-(4-phenyl-n-butyl)-3alpha-(bis[4-fluorophenyl]methoxy)tropane, 1c) is devoid of cocaine-like behaviors in rodent models but is also highly lipophilic (cLogD = 5.01), which compromises its water solubility and may adversely affect its pharmacokinetic properties. To further explore the SAR in this series and ultimately to design dopamine uptake inhibitors with favorable lipophilicities for drug development, a comparative molecular field analysis (CoMFA) was performed on a set of benztropine analogues previously synthesized in our laboratory. The CoMFA field analysis on the statistically significant (r2(cv) = 0.632; r2(ncv) = 0.917) models provided valuable insight into the structural features required for optimal binding to the DAT, which was used to design a series of novel benztropine analogues with heteroatom substitutions at the tropane N-8. These compounds were evaluated for binding at DAT, serotonin (SERT) and norepinephrine (NET) transporters, and muscarinic M1 receptors in rat brain. Inhibition of [3H]DA uptake in synaptosomes was also evaluated. Most of the analogues showed high DAT affinity (12-50 nM), selectivity (10- to 120-fold), potent inhibition of dopamine uptake, and lower lipophilicities as predicted by cLogD values. PMID:15189035

  1. Discovery of small-molecule nonpeptide antagonists of nociceptin/orphanin FQ receptor: The studies of design, synthesis, and structure-activity relationships for (4-arylpiperidine substituted-methyl)-[bicyclic (hetero)cycloalkanobenzene] derivatives.

    PubMed

    Hayashi, Shigeo; Ohashi, Katsuyo; Mihara, Sachiko; Nakata, Eriko; Emoto, Chie; Ohta, Atsuko

    2016-05-23

    Nociceptin/orphanin FQ (N/OFQ) and N/OFQ peptide (NOP) receptor are expressed and distributed in various regions such as central nervous system (CNS), peripheral nervous system, immune system, and peripheral tissues. N/OFQ and NOP receptor have important roles on a variety of physiological, pathophysiological, regulatory, and dysregulatory mechanisms in the living body. Both activation and blockade of NOP receptor function have displayed clinical potential of NOP receptor agonists and antagonists for the treatment of various diseases or pathophysiological conditions, respectively. Potent and selective NOP receptor agonists/antagonists are also useful tools to investigate the various mechanisms mediated by NOP receptor-N/OFQ system. As the present study, a series of (4-arylpiperidine substituted-methyl)-[bicyclic (hetero)cycloalkanobenzene] analogs was designed, synthesized, and biologically evaluated in vitro to seek and identify potent and selective, small-molecules of nonpeptide NOP receptor antagonists, which resulted in the discovery of novel potent small-molecule 15 with high human NOP receptor selectivity over human μ receptor. The structure-activity relationship (SAR) of the potency and selectivity, structure-metabolic stability relationship (SMR), and SAR of hERG (human ether-a-go-go related gene) potassium ion channel binding affinity for the analogs in the present studies in vitro provided or suggested significant and/or useful structural determinants and insights for the respective purposes. The superior profiles of compound 15 are discussed with a viewpoint of multisite interactions between ligand and NOP receptor, together with the results of previous NOP receptor agonist/antagonist studies. PMID:27043173

  2. 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.

  3. Probing structure-antifouling activity relationships of polyacrylamides and polyacrylates.

    PubMed

    Zhao, Chao; Zhao, Jun; Li, Xiaosi; Wu, Jiang; Chen, Shenfu; Chen, Qiang; Wang, Qiuming; Gong, Xiong; Li, Lingyan; Zheng, Jie

    2013-07-01

    We have synthesized two different polyacrylamide polymers with amide groups (polySBAA and polyHEAA) and two corresponding polyacrylate polymers without amide groups (polySBMA and polyHEA), with particular attention to the evaluation of the effect of amide group on the hydration and antifouling ability of these systems using both computational and experimental approaches. The influence of polymer architectures of brushes, hydrogels, and nanogels, prepared by different polymerization methods, on antifouling performance is also studied. SPR and ELISA data reveal that all polymers exhibit excellent antifouling ability to repel proteins from undiluted human blood serum/plasma, and such antifouling ability can be further enhanced by presenting amide groups in polySBAA and polyHEAA as compared to polySBMA and polyHEA. The antifouling performance is positively correlated with the hydration properties. Simulations confirm that four polymers indeed have different hydration characteristics, while all presenting a strong hydration overall. Integration of amide group with pendant hydroxyl or sulfobetaine group in polymer backbones is found to increase their surface hydration of polymer chains and thus to improve their antifouling ability. Importantly, we present a proof-of-concept experiment to synthesize polySBAA nanogels, which show a switchable property between antifouling and pH-responsive functions driven by acid-base conditions, while still maintaining high stability in undiluted fetal bovine serum and minimal toxicity to cultured cells. This work provides important structural insights into how very subtle structural changes in polymers can yield great improvement in biological activity, specifically the inclusion of amide group in polymer backbone/sidechain enables to obtain antifouling materials with better performance for biomedical applications. PMID:23562049

  4. 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.

  5. 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.

  6. Relationships between fundamental movement skills and objectively measured physical activity in preschool children.

    PubMed

    Cliff, Dylan P; Okely, Anthony D; Smith, Leif M; McKeen, Kim

    2009-11-01

    Gender differences in cross-sectional relationships between fundamental movement skill (FMS) subdomains (locomotor skills, object-control skills) and physical activity were examined in preschool children. Forty-six 3- to 5-year-olds (25 boys) had their FMS video assessed (Test of Gross Motor Development II) and their physical activity objectively monitored (Actigraph 7164 accelerometers). Among boys, object-control skills were associated with physical activity and explained 16.9% (p = .024) and 13.7% (p = .049) of the variance in percent of time in moderate-to-vigorous physical activity (MVPA) and total physical activity, respectively, after controlling for age, SES and z-BMI. Locomotor skills were inversely associated with physical activity among girls, and explained 19.2% (p = .023) of the variance in percent of time in MVPA after controlling for confounders. Gender and FMS subdomain may influence the relationship between FMS and physical activity in preschool children. PMID:20128363

  7. 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.

  8. 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.

  9. 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.

  10. Forward Modeling of the Coumarin Antifungals; SPR/SAR Based Perspective

    PubMed Central

    Soltani, Saeed; Dianat, Shima; Sardari, Soroush

    2009-01-01

    Although, coumarins are a group of compounds which are naturally found in some plants, they can be synthetically produced as well. Because of their diverse derivatives, origin and properties most of them can be used for medicinal purposes. For example, they can be used against fungal diseases or in studying structure and biological properties of antifungal agents to discover new compounds with the similar activity. A Structure Property/Activity Relationship (SAR) can be utilized in prediction of biological activity of desired molecules. In order to represent a relationship between the physicochemical properties of coumarin compounds and their biological activities, 68 coumarins and coumarin derivatives with already reported antifungal activities were selected and eleven attributes were generated. The descriptors were used to perform artificial neural network (ANN) and to build a model for predicting effectiveness of the new ones. The correlation coefficient between the experimental and the predicted MIC values pertaining to all the coumarins was 0.984. This study paves the way for further researches about antifungal activity of coumarins, and offers a powerful tool in modeling and prediction of their bioactivities. PMID:23407575

  11. The Relationship between Occupational Status and Physical Activity in Korea.

    PubMed

    So, Wi-Young; Yoo, Byoung-Wook; Sung, Dong Jun

    2016-10-01

    This study examined the association between occupational status and physical activity (PA) in Korea. A total of 9,000 Koreans age 10 to 89 years participated in the Korean Survey of Citizens' Sports Participation project in 2012. However, 3,851 participants were excluded from the analysis (housewives, students, and the jobless), providing a sample size of 5,149 participants (3,165 men and 1,984 women) for this study. The association between occupational status and PA was then evaluated using multivariate logistic regression analysis. The odds ratios (ORs; 95% confidence interval [CI]) for reporting at least weekly PA according to job intensity, after adjusting for sex and age, were as follows: moderate-intensity jobs, 1.164 [1.026, 1.320], p = .018; and vigorous-intensity jobs, 1.591 [1.318, 1.921], p < .001, compared with low-intensity jobs as a reference category. For PA intensity in low- and moderate-intensity jobs, after adjusting for sex and age, the ORs (95% CI) were as follows: low-intensity PA, 1.355 [1.033, 1.778], p = .028, moderate PA, 1.227 [1.096, 1.487], p = .002, and vigorous PA, 1.570 [1.213, 2.032], p < .001, compared with sedentary as a reference category. For the intensity of PA among participants with low- or vigorous-intensity jobs, after adjusting for sex and age, the ORs (95% CI) were as follows: low-intensity PA, 1.015 [0.649, 1.586], p = .948, moderate-intensity PA, 1.890 [1.416, 2.522], p < .001, and vigorous-intensity PA, 2.403 [1.395, 4.139], p = .002, compared with sedentary as a reference category. For the intensity of PA between moderate-intensity and vigorous-intensity jobs, after adjusting for sex and age, the ORs (95% CI) were as follows: low-intensity PA, 1.010 [0.759, 1.344], p = .945, moderate-intensity PA, 1.381 [1.136, 1.678], p = .001, and vigorous-intensity PA, 1.595 [1.023, 2.486], p = .039, compared to sedentary as a reference category. The presented findings show a strong association between

  12. Relationship of lactate dehydrogenase activity to body measurements of Angus x Charolais cows and calves

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objectives were to examine 1) relationships between lactate dehydrogenase (LDH) activity and body measurements of grazing beef cows, and 2) the association between maternal LDH activity in late gestation and subsequent calf birth weight (BRW), hip height (HH) at weaning, and adjusted weaning weight ...

  13. Is Father-Child Rough-and-Tumble Play Associated with Attachment or Activation Relationships?

    ERIC Educational Resources Information Center

    Paquette, Daniel; Dumont, Caroline

    2013-01-01

    The activation relationship theory, primarily focused on parental stimulation of risk-taking along with parental control during exploration, predicts that boys will be activated more than girls by their fathers. This theory may explain why fathers engage in rough-and-tumble play (RTP) with children more frequently than mothers, especially with…

  14. Relationship between skin temperature and muscle activation during incremental cycle exercise.

    PubMed

    Priego Quesada, Jose I; Carpes, Felipe P; Bini, Rodrigo R; Salvador Palmer, Rosario; Pérez-Soriano, Pedro; Cibrián Ortiz de Anda, Rosa M

    2015-02-01

    While different studies showed that better fitness level adds to the efficiency of the thermoregulatory system, the relationship between muscular effort and skin temperature is still unknown. Therefore, the present study assessed the relationship between neuromuscular activation and skin temperature during cycle exercise. Ten physically active participants performed an incremental workload cycling test to exhaustion while neuromuscular activations were recorded (via surface electromyography - EMG) from rectus femoris, vastus lateralis, biceps femoris and gastrocnemius medialis. Thermographic images were recorded before, immediately after and 10 min after finishing the cycling test, at four body regions of interest corresponding to the muscles where neuromuscular activations were monitored. Frequency band analysis was conducted to assess spectral properties of EMG signals in order to infer on priority in recruitment of motor units. Significant inverse relationship between changes in skin temperature and changes in overall neuromuscular activation for vastus lateralis was observed (r<-0.5 and p<0.04). Significant positive relationship was observed between skin temperature and low frequency components of neuromuscular activation from vastus lateralis (r>0.7 and p<0.01). Participants with larger overall activation and reduced low frequency component for vastus lateralis activation presented a better adaptive response of their thermoregulatory system by showing fewer changes in skin temperature after incremental cycling test. PMID:25660627

  15. Developing sensor activity relationships for the JPL electronic nose sensors using molecular modeling and QSAR techniques

    NASA Technical Reports Server (NTRS)

    Shevade, A. V.; Ryan, M. A.; Homer, M. L.; Jewell, A. D.; Zhou, H.; Manatt, K.; Kisor, A. K.

    2005-01-01

    We report a Quantitative Structure-Activity Relationships (QSAR) study using Genetic Function Approximations (GFA) to describe the polymer-carbon composite sensor activities in the JPL Electronic Nose, when exposed to chemical vapors at parts-per-million concentration levels.

  16. Structure-activity relationships of aromatic diamines in the Ames Salmonella typhimurium assay. Part II.

    PubMed

    Kalopissis, G

    1992-09-01

    Structure-activity relationships in the case of aromatic monoamines, diversely substituted on the ring, using the mutagenic activity in the Ames test were studied in part I. This part II is based on the same general principles but applied to phenylene diamines (ortho, para and meta) diversely substituted on the ring. PMID:1381475

  17. The Relationship between Engagement in Cocurricular Activities and Academic Performance: Exploring Gender Differences

    ERIC Educational Resources Information Center

    Zacherman, Avi; Foubert, John

    2014-01-01

    The effects of time spent in cocurricular activities on academic performance was tested. A curvilinear relationship between hours per week spent involved in cocurricular activities and grade point average was discovered such that a low amount of cocurricular involvement was beneficial to grades, while a high amount can potentially hurt academic…

  18. Structural Relationships between Social Activities and Longitudinal Trajectories of Depression among Older Adults

    ERIC Educational Resources Information Center

    Hong, Song-Iee; Hasche, Leslie; Bowland, Sharon

    2009-01-01

    Purpose: This study examines the structural relationships between social activities and trajectories of late-life depression. Design and Methods: Latent class analysis was used with a nationally representative sample of older adults (N = 5,294) from the Longitudinal Study on Aging II to classify patterns of social activities. A latent growth curve…

  19. High School Counselors' Perceived Self-Efficacy and Relationships with Actual and Preferred Job Activities

    ERIC Educational Resources Information Center

    Jellison, Vickie Dawn

    2013-01-01

    The purpose of this research was to explore the relationship between School Counselor self-efficacy, role definition and actual and preferred school counseling activities in a sample drawn from a population of school counselors. To measure these variables, the School Counselor Self-Efficacy Scale (SCSE) and the School Counselor Activity Rating…

  20. A Qualitative Investigation of the Relationship between Consumption, Physical Activity, Eating Disorders, and Weight Consciousness

    ERIC Educational Resources Information Center

    Piazza-Gardner, Anna K.; Barry, Adam E.

    2014-01-01

    Background: Previous research has identified a positive relationship between alcohol consumption and disordered eating, alcohol consumption and physical activity, and physical activity and disordered eating. However, there is a paucity of published research examining the interrelatedness of all 3 behaviors together. Purpose: This study examines…