Science.gov

Sample records for structures selected topics

  1. Selected topics from the structural acoustics program for the B-1 aircraft

    NASA Technical Reports Server (NTRS)

    Belcher, P. M.

    1979-01-01

    The major elements of the structural acoustics program for the B-1 aircraft are considered. Acoustic pressures measured at 280 sites on the surface of the vehicle were used to develop pressure models for a resizing of airframe components for aircraft No. 4 (A/C4). Acoustical fatigue design data for two dynamically complex structural configurations were acquired in laboratory programs, the conceptions for and executions of which detailed significant departures from the conventional. Design requirements for mechanical fasteners for configurations other than these two made use of analytical extensions of regrettably limited available information.

  2. Selected topics of fluid mechanics

    USGS Publications Warehouse

    Kindsvater, Carl E.

    1958-01-01

    the Euler, Froude, Reynolds, Weber, and Cauchy numbers are defined as essential tools for interpreting and using experimental data. The derivations of the energy and momentum equations are treated in detail. One-dimensional equations for steady nonuniform flow are developed, and the restrictions applicable to the equations are emphasized. Conditions of uniform and gradually varied flow are discussed, and the origin of the Chezy equation is examined in relation to both the energy and the momentum equations. The inadequacy of all uniform-flow equations as a means of describing gradually varied flow is explained. Thus, one of the definitive problems of river hydraulics is analyzed in the light of present knowledge. This report is the outgrowth of a series of short schools conducted during the spring and summer of 1953 for engineers of the Surface Water Branch, Water Resources Division, U. S. Geological Survey. The topics considered are essentially the same as the topics selected for inclusion in the schools. However, in order that they might serve better as a guide and outline for informal study, the arrangement of the writer's original lecture notes has been considerably altered. The purpose of the report, like the purpose of the schools which inspired it, is to build a simple but strong framework of the fundamentals of fluid mechanics. It is believed that this framework is capable of supporting a detailed analysis of most of the practical problems met by the engineers of the Geological Survey. It is hoped that the least accomplishment of this work will be to inspire the reader with the confidence and desire to read more of the recent and current technical literature of modern fluid mechanics.

  3. Selected topics in robotics for space exploration

    NASA Technical Reports Server (NTRS)

    Montgomery, Raymond C. (Editor); Kaufman, Howard (Editor)

    1993-01-01

    Papers and abstracts included represent both formal presentations and experimental demonstrations at the Workshop on Selected Topics in Robotics for Space Exploration which took place at NASA Langley Research Center, 17-18 March 1993. The workshop was cosponsored by the Guidance, Navigation, and Control Technical Committee of the NASA Langley Research Center and the Center for Intelligent Robotic Systems for Space Exploration (CIRSSE) at RPI, Troy, NY. Participation was from industry, government, and other universities with close ties to either Langley Research Center or to CIRSSE. The presentations were very broad in scope with attention given to space assembly, space exploration, flexible structure control, and telerobotics.

  4. Selected topics on parton distribution functions

    SciTech Connect

    Hirai, M.; Saito, K.; Kawamura, H.; Kumano, S.

    2011-12-14

    We report recent studies on structure functions of the nucleon and nuclei. First, clustering effects are investigated in the structure function F{sub 2} of {sup 9}Be for explaining an unusual nuclear correction found in a JLab experiment. We propose that high densities created by formation of clustering structure like 2{alpha}+neutron in {sup 9}Be is the origin of the unexpected JLab result by using the antisymmetrized molecular dynamics (AMD). There is an approved proposal at JLab to investigate the structure functions of light nuclei including the cluster structure, so that much details will become clear in a few years. Second, tensor-polarized quark and antiquark distributions are obtained by analyzing HERMES measurements on the structure function b{sub 1} for the deuteron. The result suggests a finite tensor polarization for antiquark distributions, which is an interesting topic for further theoretical and experimental investigations. An experimental proposal exists at JLab for measuring b{sub 1} of the deuteron as a new tensor-structure study in 2010's. Furthermore, the antiquark tensor polarization could be measured by polarized deuteron Drell-Yan processes at hadron facilities such as J-PARC and GSI-FAIR. Third, the recent CDF dijet anomaly is investigated within the standard model by considering possible modifications of the strange-quark distribution. We find that the shape of a dijet-mass spectrum changes depending on the strange-quark distribution. It indicates that the CDF excess could be partially explained as a PDF effect, particularly by the strangeness in the nucleon, within the standard model if the excess at m{sub jj}{approx_equal}140 GeV is not a sharp peak.

  5. Symmetries and fundamental interactions—selected topics

    NASA Astrophysics Data System (ADS)

    Jungmann, Klaus P.

    2014-06-01

    High precision experiments at low energies on discrete and continuous symmetries offer the possibility to search for New Physics beyond the Standard Model. Examples are dedicated searches for violations of the C, P, CP and CPT as well as of Lorentz Invariance using matter and anti-matter. Atomic parity violation was not only essential in the past to verify the Standard Model, still today it has a potential to find Z' bosons, leptoquarks or dark matter. Electric Dipole Moments (EDMs) may provide clues to explain the matter-antimatter asymmetry in the universe. There is at present a some 4 standard deviations discrepancy between theory and experiment for the muon magnetic anomaly. At the same time while providing important information on physics beyond the Standard Model, new technology such as precise clocks is developed along with the experiments motivated by fundamental physics questions. This article summarizes an overview talk that was concerned primarily with a selection of topics from a very rich field, in particular such that were not covered otherwise at this conference.

  6. Quark-gluon plasma (Selected Topics)

    SciTech Connect

    Zakharov, V. I.

    2012-09-15

    Introductory lectures to the theory of (strongly interacting) quark-gluon plasma given at the Winter School of Physics of ITEP (Moscow, February 2010). We emphasize theoretical issues highlighted by the discovery of the low viscosity of the plasma. The topics include relativistic hydrodynamics, manifestations of chiral anomaly in hydrodynamics, superfluidity, relativistic superfluid hydrodynamics, effective stringy scalars, holographic models of Yang-Mills theories.

  7. Selected Topics in International Special Education.

    ERIC Educational Resources Information Center

    Kelly, Nancy

    2002-01-01

    This article provides information on special education topics on the international front. Information is presented on projects that evaluated early intervention programs, a life-centered career education program in the Philippines, a Peruvian vocational program for individuals with severe disabilities, and special classes for children with…

  8. Selected Antimicrobial Activity of Topical Ophthalmic Anesthetics

    PubMed Central

    Reynolds, Margaret M.; Greenwood-Quaintance, Kerryl E.; Patel, Robin; Pulido, Jose S.

    2016-01-01

    Purpose Endophthalmitis is a rare complication of intravitreal injection (IVI). It is recommended that povidone-iodine be the last agent applied before IVI. Patients have reported povidone-iodine application to be the most bothersome part of IVIs. Topical anesthetics have been demonstrated to have antibacterial effects. This study compared the minimum inhibitory concentration (MIC) of topical anesthetic eye drops (proparacaine 0.5%, tetracaine 0.5%, lidocaine 2.0%) and the antiseptic, 5.0% povidone-iodine, against two organisms causing endophthalmitis after IVI. Methods Minimum inhibitory concentration values of topical anesthetics, povidone-iodine, preservative benzalkonium chloride (0.01%), and saline control were determined using five isolates of each Staphylococcus epidermidis and viridans group Streptococcus species (VGS). A broth microdilution technique was used with serial dilutions. Results Lidocaine (8.53 × 10−5mol/mL) had MICs of 4.27 to 8.53 × 10−5 mol/mL, and tetracaine (1.89 × 10−5 mol/mL) had MICs of 9.45 × 10−6 mol/mL for all isolates. Proparacaine (1.7 × 10−5 mol/mL) had MICs of 1.32 to 5.3 × 10−7 and 4.25 × 10−6 mol/mL for S. epidermidis and VGS, respectively). Benzalkonium chloride (3.52 × 10−7 mol/mL) had MICs of 1.86 × 10−9 to 1.1 × 10−8 and 4.40 × 10−8 mol/mL for S. epidermidis and VGS, respectively. Povidone-iodine (1.37 × 10−4 mol/mL) had MICs of 2.14 to 4.28 × 10−6 and 8.56 × 10−6 mol/mL for S. epidermidis and VGS, respectively. Conclusion Proparacaine was the anesthetic with the lowest MICs, lower than that of povidone-iodine. Benzalkonium chloride had lower MICs than proparacaine. All tested anesthetics and povidone-iodine inhibited growth of S. epidermidis and VGS at commercially available concentrations. Translational Relevance For certain patients, it could be possible to use topical anesthetic after povidone-iodine for comfort without inhibiting and perhaps contributing additional antimicrobial

  9. Rheology of the lithosphere: selected topics.

    USGS Publications Warehouse

    Kirby, S.H.; Kronenberg, A.K.

    1987-01-01

    Reviews recent results concerning the rheology of the lithosphere with special attention to the following topics: 1) the flexure of the oceanic lithosphere, 2) deformation of the continental lithosphere resulting from vertical surface loads and forces applied at plate margins, 3) the rheological stratification of the continents, 4) strain localization and shear zone development, and 5) strain-induced crystallographic preferred orientations and anisotropies in body-wave velocities. We conclude with a section citing the 1983-1986 rock mechanics literature by category.-Authors

  10. Topical Structure in Arabic-English Interlanguage.

    ERIC Educational Resources Information Center

    Fakhri, Ahmed

    A study compared the topical structure (TS) of Arabic and English in order to determine whether Arab learners of English as a Second Language (ESL) transfer potential differences between Arabic and English in their English writing, or whether they use an altogether different TS indicative of developmental factors. Four sets of data were compared…

  11. Fundamental symmetries and interactions—selected topics

    NASA Astrophysics Data System (ADS)

    Jungmann, Klaus P.

    2015-11-01

    In the field of fundamental interactions and symmetries numerous experiments are underway or planned in order to verify the standard model in particle physics, to search for possible extensions to it or to exploit the standard model for extracting most precise values for fundamental constants. We cover selected recent developments, in particular such which exploit stored and confined particles. Emphasis is on experiments with transformative character, i.e. such which may be able to guide and steer theoretical model building into new but defined directions. Among those are projects with antiprotons, muons and certain selected atoms and atomic nuclei.

  12. COMPUTATIONAL SCIENCE AT BROOKHAVEN NATIONAL LABORATORY: THREE SELECTED TOPICS.

    SciTech Connect

    DAVENPORT,J.W.DENG,Y.GLIMM,J.SAMULYAK,R.

    2003-09-15

    We present an overview of computational science at Brookhaven National Laboratory (BNL), with selections from three areas: fluids, nanoscience, and biology. The work at BNL in each of these areas is itself very broad, and we select a few topics for presentation within each of them.

  13. Selection of Retapamulin, a Novel Pleuromutilin for Topical Use

    PubMed Central

    Rittenhouse, Stephen ; Biswas, Sanjoy; Broskey, John; McCloskey, Lynn; Moore, Terrance; Vasey, Sandra; West, Joshua; Zalacain, Magdalena; Zonis, Rimma; Payne, David

    2006-01-01

    The in vitro activity of retapamulin was determined and compared to that of topical and community antibiotics. The MIC90s of retapamulin against Staphylococcus aureus and Streptococcus pyogenes were 0.12 μg/ml and 0.016 μg/ml, respectively. Retapamulin has a low propensity to select resistance and produces an in vitro postantibiotic effect. PMID:17065625

  14. Pharmacists' Perceived Knowledge and Expertise in Selected Pediatric Topics

    PubMed Central

    Munzenberger, Paul J; Thomas, Ron L; Edwin, Stephanie B; Tutag-Lehr, Victoria

    2011-01-01

    OBJECTIVES The purpose of this study is to determine pharmacists' perceived knowledge and expertise required to make recommendations regarding selected pediatric topics. METHODS A questionnaire was distributed to 400 pharmacists practicing in community, hospital, and home care settings. This instrument explored their perceived knowledge, expertise, and comfort in providing recommendations related to 38 pediatric topics. The impact of responder demographics on differences in perceived knowledge and expertise for each topic were evaluated. RESULTS Ninety-five of 400 (24%) questionnaires were returned completed or partially completed. Forty-seven and 36 of responders practiced in the community or inpatient hospital setting, respectively. Seventy percent of responders reported that ≤ 40% of their patients were children. In general, responders believed they had the knowledge and expertise to make recommendations for the frequently occurring conditions or topics but not for the less familiar. Formal pediatric training was the most influential responder characteristic with a larger proportion having training that they believed enables them to have knowledge and expertise to make recommendations. Although less impressive, experience of more than 5 years and a community-based practice were also important factors. CONCLUSION Additional training is beneficial in increasing the perceived knowledge and comfort of pharmacists making recommendations regarding pediatric patients. PMID:22477824

  15. Selected Topics on Hadronic B Decays From BaBar

    SciTech Connect

    Suzuki, K.; /SLAC

    2011-11-23

    Recent measurements of branching fractions and decay-rate asymmetries in charmless hadronic B decays at the BaBar experiment are presented. The selected topics include Dalitz plot analyses of B {yields} K{sup +} {pi}{sup -}{pi} and signal searches in B {yields} PP and PV, where isoscalar mesons are involved, and in B {yields} b{sub 1}P, P and V denote a pseudoscalar and vector meson, respectively. Several measurements in charmless hadronic B decays have indicated possible deviations from the theoretical predictions within the Standard Model. The measurements presented would contribute to searching for and resolving such puzzles.

  16. A Review of Carbon Dioxide Selective Membranes: A Topical Report

    SciTech Connect

    Dushyant Shekhawat; David R. Luebke; Henry W. Pennline

    2003-12-01

    Carbon dioxide selective membranes provide a viable energy-saving alternative for CO2 separation, since membranes do not require any phase transformation. This review examines various CO2 selective membranes for the separation of CO2 and N2, CO2 and CH4, and CO2 and H2 from flue or fuel gas. This review attempts to summarize recent significant advances reported in the literature about various CO2 selective membranes, their stability, the effect of different parameters on the performance of the membrane, the structure and permeation properties relationships, and the transport mechanism applied in different CO2 selective membranes.

  17. Selecting Topics for Journals: Some Advice for Beginners

    ERIC Educational Resources Information Center

    Maddux, Cleborne D.

    2004-01-01

    This article provides suggestions for prospective authors searching for topics for manuscripts. The article first provides examples of topics for non-data-based articles, then for research topics. Authors are invited to submit manuscripts on these, and on any other topics to this journal.

  18. Advanced Gas Cooled Nuclear Reactor Materials Evaluation and Development Program: Topical report I, selection of candidate alloys. Volume 3. Selection of surface coating/substrate systems for screening creep and structural stability studies

    SciTech Connect

    Not Available

    1980-06-20

    Considering the high temperature, low O/sub 2/, high C environment of operation in the Very High Temperature Reactor (VHTR) Systems, the utilization of coatings is envisaged to hold potential for extending component lifetimes through the formation of stable and continuous oxide films with enhanced resistance to C diffusion. A survey of the current state of technology for high temperature coatings has been performed. The usefulness of these coatings on the Mo, Ni, and Fe base alloys is discussed. Specifically, no coating substitute was identified for TZM other than the well known W-3 (pack silicide) and Al/sub 2/O/sub 3/ forming coatings were recommended for the Fe and Ni base structural materials. Recommendations as to coating types and processng have been made based on the predicted VHTR component size, shape, base metal and operational environment. Four tests designed to evaluate the effects of selected combinations of coatings and substrate matrices are recommended for consideration.

  19. Topics

    ERIC Educational Resources Information Center

    Mathematics Teaching, 1972

    1972-01-01

    Topics discussed in this column include patterns of inverse multipliers in modular arithmetic; diagrams for product sets, set intersection, and set union; function notation; patterns in the number of partitions of positive integers; and tessellations. (DT)

  20. Topics in the structure of hadronic systems

    NASA Astrophysics Data System (ADS)

    Lebed, R. F.

    1994-04-01

    In this dissertation the author examines a variety of different problems in the physics of strongly-bound systems. Each is elucidated by a different standard method of analysis developed to probe the properties of such systems. It begins with an examination of the properties and consequences of the current algebra of weak currents in the limit of heavy quark spin-flavor symmetry. In particular, the assumptions in the proof of the Ademollo-Gatto theorem in general and for spin-flavor symmetry are examined, and the constraints imposed upon matrix elements by this theorem are exhibited. Then he utilizes the renormalization-group method to create composite fermions in a three-generation electroweak model. Such a model is found to reproduce the same low energy behavior as the top-condensate electroweak model, although in general it may have strong constraints upon its Higgs sector. Next the subtleties in the nonrelativistic quark model that drastically alter the picture of the physical origins of meson electromagnetic and hyperfine mass splittings are uncovered; in particular, the explicit contributions due to (m(sub d)(minus)m(sub u)) and electrostatic potentials may be overwhelmed by other effects. Such novel effects are used to explain the anomalous pattern of mass splittings recently measured in bottom mesons. Finally, the topic of baryon masses in heavy fermion chiral perturbation theory, including both tree-level and loop effects are considered.

  1. Topics in the structure of hadronic systems

    SciTech Connect

    Lebed, R. F.

    1994-04-01

    In this dissertation the author examines a variety of different problems in the physics of strongly-bound systems. Each is elucidated by a different standard method of analysis developed to probe the properties of such systems. He begins with an examination of the properties and consequences of the current algebra of weak currents in the limit of heavy quark spin-flavor symmetry. In particular, he examines the assumptions in the proof of the Ademollo-Gatto theorem in general and for spin-flavor symmetry, and exhibit the constraints imposed upon matrix elements by this theorem. Then he utilizes the renormalization-group method to create composite fermions in a three-generation electroweak model. Such a model is found to reproduce the same low energy behavior as the top-condensate electroweak model, although in general it may have strong constraints upon its Higgs sector. Next he uncovers subtleties in the nonrelativistic quark model that drastically alter the picture of the physical origins of meson electromagnetic and hyperfine mass splittings; in particular, the explicit contributions due to (m{sub d}{minus}m{sub u}) and electrostatic potentials may be overwhelmed by other effects. Such novel effects are used to explain the anomalous pattern of mass splittings recently measured in bottom mesons. Finally, he considers the topic of baryon masses in heavy fermion chiral perturbation theory, including both tree-level and loop effects.

  2. Topics in the Structure of Hadronic Systems

    NASA Astrophysics Data System (ADS)

    Lebed, Richard Felix

    In this dissertation we examine a variety of different problems in the physics of strongly-bound systems. Each is elucidated by a different standard method of analysis developed to probe the properties of such systems. We begin with an examination of the properties and consequences of the current algebra of weak currents in the limit of heavy quark spin-flavor symmetry. In particular, we examine the assumptions in the proof of the Ademollo -Gatto theorem in general and for spin-flavor symmetry, and exhibit the constraints imposed upon matrix elements by this theorem. Then we utilize the renormalization-group method to create composite fermions in a three-generation electroweak model. Such a model is found to reproduce the same low energy behavior as the top-condensate electroweak model, although in general it may have strong constraints upon its Higgs sector. Next we uncover subtleties in the nonrelativistic quark model that drastically alter our picture of the physical origins of meson electromagnetic and hyperfine mass splittings; in particular, the explicit contributions due to (m _{d}-m_{u} ) and electrostatic potentials may be overwhelmed by other effects. Such novel effects are used to explain the anomalous pattern of mass splittings recently measured in bottom mesons. Finally, we consider the topic of baryon masses in heavy fermion chiral perturbation theory, including both tree-level and loop effects. We find that certain mass relations holding at second-order in symmetry breaking (O(m_sp{rm q}{2} ) and O(Q_sp{rm q} {2})) have finite, computable, and numerically small loop corrections within the theory. The numerical values of these corrections are found to be in excellent agreement with experiment. We also find that, within chiral perturbation theory, the experimentally measured baryon masses alone are not enough to place stringent constraints upon the light quark masses.

  3. TOPICAL REVIEW: Mesoscale structures in microemulsions

    NASA Astrophysics Data System (ADS)

    Komura, S.

    2007-11-01

    Due to the existence of intermediate mesoscopic internal structures, soft matter exhibits various fascinating non-linear and non-equilibrium phenomena. In this review article, we focus on microemulsions consisting of water, oil, and surfactant from the viewpoint of soft matter physics. Microemulsions exhibit a rich phase behavior as the composition and/or the temperature is varied. In the middle phase, oil and water mix in the presence of surfactant molecules to form a mesoscopic bicontinuous structure. To explain the complex behavior of microemulsions, it is useful to employ phenomenological approaches such as the Ginzburg-Landau theory or the membrane theory. We discuss the Ginzburg-Landau theory and also review the Teubner-Strey model, the Gompper-Schick model, and the two-order-parameter model. Based on these models, we discuss the structure of the middle phase and its wetting transition. The membrane theory proposed by Helfrich is also useful for describing the physical properties of microemulsions. Various structures in microemulsions, such as droplets, bicontinuous and network structures, are properly accounted for by the curvature elasticity model. We focus on the Exxon model which clarifies the physical origin of the middle phase. Within the phenomenological level of description, we review the dynamical aspects of droplet and bicontinuous microemulsions. We also give an overview of microemulsions found in multicomponent polymeric systems (polymeric microemulsions). A discussion on recent applications of microemulsions completes the review.

  4. Topic Sequence and Emphasis Variability of Selected Organic Chemistry Textbooks

    ERIC Educational Resources Information Center

    Houseknecht, Justin B.

    2010-01-01

    Textbook choice has a significant effect upon course success. Among the factors that influence this decision, two of the most important are material organization and emphasis. This paper examines the sequencing of 19 organic chemistry topics, 21 concepts and skills, and 7 biological topics within nine of the currently available organic textbooks.…

  5. Culture, Diet, and Nutrition: Selected Themes and Topics

    ERIC Educational Resources Information Center

    Grivetti, Louis Evan

    1978-01-01

    The following topics are discussed: How do nutritious diets develop? What is the antiquity of nutritional disease? Why do humans consume nonfood items? What impact do religious prohibitions and practices have on nutritional status? And why are some toxic plants and animals consumed and desired by man? (Author/BB)

  6. Single photon emission computed tomography and other selected computer topics

    SciTech Connect

    Price, R.R.; Gilday, D.L.; Croft, B.Y.

    1980-01-01

    This volume includes an overview of single photon emission computed tomography and numerous papers that describe and evaluate specific systems and techniques. Papers cover such topics as Auger cameras; seven-pinhole and slant-hole collimators; brain; cardiac; and gated blood-pool studies; and the BICLET and SPECT systems.

  7. Topics in Finance. Part V--Capital Structure

    ERIC Educational Resources Information Center

    Laux, Judy

    2011-01-01

    Continuing this series on the theory of financial management, the current article investigates capital structure, offering insight into the roles of stockholder wealth maximization, the risk-return tradeoff, and agency conflicts. Much literature addresses this topic, and some of the most recent literature challenges certain theoretical…

  8. Summary of SMIRT20 Preconference Topical Workshop – Identifying Structural Issues in Advanced Reactors

    SciTech Connect

    William Richins; Stephen Novascone; Cheryl O'Brien

    2009-08-01

    Summary of SMIRT20 Preconference Topical Workshop – Identifying Structural Issues in Advanced Reactors William Richins1, Stephen Novascone1, and Cheryl O’Brien1 1Idaho National Laboratory, US Dept. of Energy, Idaho Falls, Idaho, USA, e-mail: William.Richins@inl.gov The Idaho National Laboratory (INL, USA) and IASMiRT sponsored an international forum Nov 5-6, 2008 in Porvoo, Finland for nuclear industry, academic, and regulatory representatives to identify structural issues in current and future advanced reactor design, especially for extreme conditions and external threats. The purpose of this Topical Workshop was to articulate research, engineering, and regulatory Code development needs. The topics addressed by the Workshop were selected to address critical industry needs specific to advanced reactor structures that have long lead times and can be the subject of future SMiRT technical sessions. The topics were; 1) structural/materials needs for extreme conditions and external threats in contemporary (Gen. III) and future (Gen. IV and NGNP) advanced reactors and 2) calibrating simulation software and methods that address topic 1 The workshop discussions and research needs identified are presented. The Workshop successfully produced interactive discussion on the two topics resulting in a list of research and technology needs. It is recommended that IASMiRT communicate the results of the discussion to industry and researchers to encourage new ideas and projects. In addition, opportunities exist to retrieve research reports and information that currently exists, and encourage more international cooperation and collaboration. It is recommended that IASMiRT continue with an off-year workshop series on select topics.

  9. Strategies for Finding and Selecting an Ideal Thesis or Dissertation Topic: A Review of Literature

    ERIC Educational Resources Information Center

    Lei, Simon A.

    2009-01-01

    Choosing an ideal master's thesis or doctoral dissertation topic is probably one of the most important decisions students will make while in graduate school. Some graduate students may spend a year or even longer looking for potential topics before finally selecting one for their thesis or dissertation. There are a number of successful strategies…

  10. Selected Topics in Tau Physics from BaBar

    SciTech Connect

    Paramesvaran, S.; /Royal Holloway, U. of London

    2012-04-06

    Selected results from {tau} analyses performed using the BABAR detector at the SLAC National Accelerator Laboratory are presented. A precise measurement of the {tau} mass and the {tau}{sup +}{tau}{sup -} mass difference is undertaken using the hadronic decay mode {tau}{sup {+-}} {yields} {pi}{sup +}{pi}{sup -}{pi}{sup {+-}}{nu}{sub {tau}}. In addition an investigation into the strange decay modes {tau}{sup -} {yields} K{sub S}{sup 0}{pi}{sup -}{pi}{sup 0}{nu}{sub {tau}} and {tau}{sup -} {yields} K{sub S}{sup 0}{pi}{sup -}{nu}{sub {tau}} is also presented, including a fit to the {tau}{sup -} {yields} K{sub S}{sup 0}{pi}{sup -}{nu}{sub {tau}} invariant mass spectrum. Precise values for M(K*(892)) and {Lambda}(K*(892)) are obtained.

  11. Selected topics on interactions between cirrus clouds and embedded contrails

    NASA Astrophysics Data System (ADS)

    Gierens, K.

    2012-09-01

    Persistent contrails and natural cirrus clouds often coexist in the upper troposphere and contrails can be embedded within cirrus clouds. The present paper deals with some questions regarding the interaction of cirrus clouds and embedded contrails. I have selected only questions that can be answered by analytical means. I find that (1) the emission index for water vapour is only slightly changed when an aircraft crosses a cirrus cloud, (2) that contrail formation is not affected by an ambient cirrus, (3) that cirrus ice crystals entrained into the trailing wing tip vortex do not efficiently retard the sublimation of contrail ice crystals, and (4) that cirrus can start to dissolve an embedded contrail after a couple of hours by aggregation.

  12. Beyond Topical Relevance: Document Selection Behavior of Real Users of IR Systems.

    ERIC Educational Resources Information Center

    Wang, Peiling; Soergel, Dagobert

    1993-01-01

    Describes a study of users' document selection behavior that was conducted to build a tentative cognitive model of document selection behavior to be used in designing intelligent information retrieval systems. Topics addressed include studies of relevance and of decision making; value judgments; and document information elements considered during…

  13. Structural features of ultradeformable archaeosomes for topical delivery of ovalbumin.

    PubMed

    Carrer, Dolores C; Higa, Leticia H; Tesoriero, Maria Victoria Defain; Morilla, Maria Jose; Roncaglia, Diana I; Romero, Eder Lilia

    2014-09-01

    The ultradeformable archaeosomes (UDA, made of total polar archaeolipids (TPA) extracted from the extreme halophile archaea Halorubrum tebenquichense:soybean phosphatidylcholine (SPC):sodium cholate (NaChol), 3:3:1 w:w), are promising topical adjuvants showing high deformability, an essential property for intact skin penetration up to the viable epidermis/dermis. To gain insights on UDA structure, the interactions between TPA, SPC and the edge activator NaChol, were assessed by electrospray ionization mass spectroscopy (ESI-MS) and confocal fluorescence microscopy of giant unilamellar vesicles (GUV). The non covalent heterodimers NaChol-SPC, NaChol-phosphatidylglycerophosphate methyl ether (PGPMe), NaChol-sulfated diglycosyl diphytanyl-glycerol diether (SDGD5) and SPC-PGPMe detected in the gas phase by ESI-MS after direct infusion of UDA, together with the homogeneous partition of FASTDiO and DiIC18 in GUV suggested that in these proportions, lipids and NaChol were miscible. We propose therefore, a model where in UDA the SPC diluted sufficient enough in the rich PGPMe TPA, so as to the low lateral mobility of molecules (typical of rich in PGPMe bilayers) was no longer experienced. We also found that 50μm deep within in vitro human skin canyons, the fluorescence of Alexa fluor 647-ovalbumin in UDL was ∼1.5 folds higher than in UDA, indicating a potential steric hindrance of the voluminous structure of PGPMe UDA bilayer, to the penetration of a particulate cargo such as the 7nm diameter ovalbumin. According to these observations, a further reduction in PGPMe - a lipid playing no immune role - content could help to improve the performance of UDA as topical adjuvants. PMID:24974012

  14. Cross sections for inelastic scattering of electrons by atoms: selected topics related to electron microscopy

    SciTech Connect

    Inokuti, M.; Manson, S.T.

    1982-01-01

    We begin with a resume of the Bethe theory, which provides a general framework for discussing the inelastic scattering of fast electrons and leads to powerful criteria for judging the reliability of cross-section data. The central notion of the theory is the generalized oscillator strength as a function of both the energy transfer and the momentum transfer, and is the only non-trivial factor in the inelastic-scattering cross section. Although the Bethe theory was initially conceived for free atoms, its basic ideas apply to solids, with suitable generalizations; in this respect, the notion of the dielectric response function is the most fundamental. Topics selected for discussion include the generalized oscillator strengths for the K-shell and L-shell ionization for all atoms with Z less than or equal to 30, evaluated by use of the Hartree-Slater potential. As a function of the energy transfer, the generalized oscillator strength most often shows a non-monotonic structure near the K-shell and L-shell thresholds, which has been interpreted as manifestations of electron-wave propagation through atomic fields. For molecules and solids, there are additional structures due to the scattering of ejected electrons by the fields of other atoms.

  15. Teachers and Teaching: Annotated Bibliographies on Selected Topics. Volume 3: Characteristics, Attitudes, and Values of Teachers.

    ERIC Educational Resources Information Center

    Sacay, Valerie Hakam, Ed.

    This bibliobraphy is comprised of annotations of 142 selected research articles and reports, on topics relating to factors which influence teachers' perception and fulfillment of their professional role, which have appeared in the literature from 1968 to 1972. Items relating to factors such as organizational climate, curriculum, job satisfaction,…

  16. Exploring and Contrasting EFL Learners' Perceptions of Textbook-Assigned and Self-Selected Discussion Topics

    ERIC Educational Resources Information Center

    Wolf, James P.

    2013-01-01

    In an attempt to explore the significance of a "willingness to communicate" (WTC) variable in second language (L2) acquisition, this article reports on a survey study that investigated 101 Japanese university English as a Foreign Language (EFL) learners' perceptions of textbook-assigned and self-selected discussion topics. Additionally, the study…

  17. Aging Management of Nuclear Power Plant Concrete Structures - Overview and Suggested Research Topics

    SciTech Connect

    Naus, Dan J

    2008-10-01

    Nuclear power plant concrete structures are described and their operating experience noted. Primary considerations related to management of their aging are noted and an indication of their status provided: degradation mechanisms, damage models, and material performance; assessment and remediation (i.e., component selection, in-service inspection, nondestructive examinations, and remedial actions); and estimation of performance at present or some future point in time (i.e., application of structural reliability theory to the design and optimization of in-service inspection/maintenance strategies, and determination of the effects of degradation on plant risk). Several activities are identified that provide background information and data on areas of concern with respect to nondestructive examination of nuclear power plant concrete structures: inspection of thick-walled, heavily-reinforced sections, basemats, and inaccessible areas of the containment metallic pressure boundary. Topics are noted where additional research would be of benefit to aging management of nuclear power plant concrete structures.

  18. Selected topics on the active control of helicopter aeromechanical and vibration problems

    NASA Technical Reports Server (NTRS)

    Friedmann, Peretz P.

    1994-01-01

    This paper describes in a concise manner three selected topics on the active control of helicopter aeromechanical and vibration problems. The three topics are as follows: (1) the active control of helicopter air-resonance using an LQG/LTR approach; (2) simulation of higher harmonic control (HHC) applied to a four bladed hingeless helicopter rotor in forward flight; and (3) vibration suppression in forward flight on a hingeless helicopter rotor using an actively controlled, partial span, trailing edge flap, which is mounted on the blade. Only a few selected illustrative results are presented. The results obtained clearly indicate that the partial span, actively controlled flap has considerable potential for vibration reduction in helicopter rotors.

  19. VDAC Structure, Selectivity, and Dynamics

    PubMed Central

    Colombini, Marco

    2012-01-01

    VDAC channels exist in the mitochondrial outer membrane of all eukaryotic organisms. Of the different isoforms present in one organism, it seems that one of these is the canonical VDAC whose properties and 3D structure is highly conserved. The fundamental role of these channels is to control the flux of metabolites between the cytosol and mitochondrial spaces. Based on many functional studies, the fundamental structure of the pore wall consists of one α helix and 13 β strands tilted at a 46° angle. This results in a pore with an estimated internal diameter of 2.5 nm. This structure has not yet been resolved. The published 3D structure consists of 19 β strands and is different from the functional structure that forms voltage-gated channels. The selectivity of the channel is exquisite, being able to select for ATP over molecules of the same size and charge. Voltage gating involves two separate gating processes. The mechanism involves the translocation of a positively charged portion of the wall of the channel to the membrane surface resulting in a reduction in pore diameter and volume and an inversion in ion selectivity. This mechanism is consistent with experiments probing changes in selectivity, voltage gating, kinetics and energetics. Other published mechanisms are in conflict with experimental results. PMID:22240010

  20. An Empirical Study of Knowledge Structures of Research Topics.

    ERIC Educational Resources Information Center

    Wang, Peiling

    1999-01-01

    Examines cognitive maps on research topics generated by experts and non-experts. Both experts and non-experts modified the given vocabulary by either adding or dropping terms. The dominant configuration for the maps was top-down. Experts tended to use a problem-oriented approach to organize vocabulary while non-experts often applied a…

  1. Strategy selection in structured populations

    PubMed Central

    Tarnita, Corina E.; Ohtsuki, Hisashi; Antal, Tibor; Fu, Feng; Nowak, Martin A.

    2009-01-01

    Evolutionary game theory studies frequency dependent selection. The fitness of a strategy is not constant, but depends on the relative frequencies of strategies in the population. This type of evolutionary dynamics occurs in many settings of ecology, infectious disease dynamics, animal behavior and social interactions of humans. Traditionally evolutionary game dynamics are studied in well-mixed populations, where the interaction between any two individuals is equally likely. There have also been several approaches to study evolutionary games in structured populations. In this paper we present a simple result that holds for a large variety of population structures. We consider the game between two strategies, A and B, described by the payoff matrix (abcd). We study a mutation and selection process. If the payoffs are linear in a, b, c, d, then for weak selection strategy A is favored over B if and only if σa + b > c + σd. This means the effect of population structure on strategy selection can be described by a single parameter, σ. We present the values of σ for various examples including the well-mixed population, games on graphs and games in phenotype space. We give a proof for the existence of such a σ, which holds for all population structures and update rules that have certain (natural) properties. We assume weak selection, but allow any mutation rate. We discuss the relationship between σ and the critical benefit to cost ratio for the evolution of cooperation. The single parameter, σ, allows us to quantify the ability of a population structure to promote the evolution of cooperation or to choose efficient equilibria in coordination games. PMID:19358858

  2. Strategy selection in structured populations.

    PubMed

    Tarnita, Corina E; Ohtsuki, Hisashi; Antal, Tibor; Fu, Feng; Nowak, Martin A

    2009-08-01

    Evolutionary game theory studies frequency dependent selection. The fitness of a strategy is not constant, but depends on the relative frequencies of strategies in the population. This type of evolutionary dynamics occurs in many settings of ecology, infectious disease dynamics, animal behavior and social interactions of humans. Traditionally evolutionary game dynamics are studied in well-mixed populations, where the interaction between any two individuals is equally likely. There have also been several approaches to study evolutionary games in structured populations. In this paper we present a simple result that holds for a large variety of population structures. We consider the game between two strategies, A and B, described by the payoff matrix(abcd). We study a mutation and selection process. For weak selection strategy A is favored over B if and only if sigma a+b>c+sigma d. This means the effect of population structure on strategy selection can be described by a single parameter, sigma. We present the values of sigma for various examples including the well-mixed population, games on graphs, games in phenotype space and games on sets. We give a proof for the existence of such a sigma, which holds for all population structures and update rules that have certain (natural) properties. We assume weak selection, but allow any mutation rate. We discuss the relationship between sigma and the critical benefit to cost ratio for the evolution of cooperation. The single parameter, sigma, allows us to quantify the ability of a population structure to promote the evolution of cooperation or to choose efficient equilibria in coordination games. PMID:19358858

  3. Structural, Linguistic and Topic Variables in Verbal and Computational Problems in Elementary Mathematics.

    ERIC Educational Resources Information Center

    Beardslee, Edward C.; Jerman, Max E.

    Five structural, four linguistic and twelve topic variables are used in regression analyses on results of a 50-item achievement test. The test items are related to 12 topics from the third-grade mathematics curriculum. The items reflect one of two cases of the structural variable, cognitive level; the two levels are characterized, inductive…

  4. Structural tailoring of select fiber composite structures

    NASA Technical Reports Server (NTRS)

    Chamis, Christos C.; Rubinstein, Robert I.

    1990-01-01

    A multidisciplinary design process for aerospace propulsion composite structures was formalized and embedded into computer codes. These computer codes are streamlined to obtain tailored designs for select composite structures. The codes available are briefly described with sample cases to illustrate their applications. The sample cases include aircraft engine blades, propfans (turboprops), flat, and cylindrical panels. Typical results illustrate that the use of these codes enable the designer to obtain designs which meet all the design requirements with maximum benefits in efficiency, noise, weight or thermal distortions.

  5. Selected Topical Agents Used in Traditional Chinese Medicine in the Treatment of Minor Injuries- A Review

    PubMed Central

    Leung, Ping-chung; Ko, Erik Chun-hay; Siu, Wing-sum; Pang, Ellie Suet-yee; Lau, Clara Bik-san

    2016-01-01

    Topical medicinal patches have been popular for the treatment of minor injuries like sprains and avulsions. Other inflammatory conditions like chronic musculo-tendinous pain and or fasciitis are also taken care of by local ointments or rubs. In the oriental communities, medicinal herbs frequently form the major components of the patches. In spite of the lack of scientific evidence of efficacy, the popularity of such traditional application persists for centuries. In this era of evidence-based clinical treatment, there is an urgent need to look into this traditional practice. The purpose should include a scientific verification of the efficacy of the practice, and once proven, further explorations would be indicated to bring the practice to a higher level. A system of comprehensive exploration was proposed and practiced in the past years to fulfill the aspiration. The research consisted of four areas: (1) Identification of the suitable medicinal herbs for the topical study; (2) Study of the biological activities of the selected herbs, concentrating on the areas of anti-inflammation, anti-oxidation, angiogenesis and cellular proliferation; (3) Study on the transcutaneous transport of the chemicals of the selected herbs to deeper tissues; and (4) Pilot clinical studies on common superficial inflammatory musculo-skeletal conditions to give objective clinical evidences to the topical applications. Five herbs were identified as suitable candidates of study. They were put into relevant laboratory platforms and were proven to be anti-oxidant, anti-inflammatory and pro-angiogenic. Three of the herbs were prepared as topical patches with an enhancer and used to treat three common ailments in pilot clinical trials, viz., plantar fasciitis, undisplaced metatarsal fracture and tendonitis of the wrist (de-Quervain’s disease) and the elbow (Tennis elbow). The clinical results of the pilot studies were very positive. It is therefore concluded that further explorations are

  6. Selected Topical Agents Used in Traditional Chinese Medicine in the Treatment of Minor Injuries- A Review.

    PubMed

    Leung, Ping-Chung; Ko, Erik Chun-Hay; Siu, Wing-Sum; Pang, Ellie Suet-Yee; Lau, Clara Bik-San

    2016-01-01

    Topical medicinal patches have been popular for the treatment of minor injuries like sprains and avulsions. Other inflammatory conditions like chronic musculo-tendinous pain and or fasciitis are also taken care of by local ointments or rubs. In the oriental communities, medicinal herbs frequently form the major components of the patches. In spite of the lack of scientific evidence of efficacy, the popularity of such traditional application persists for centuries. In this era of evidence-based clinical treatment, there is an urgent need to look into this traditional practice. The purpose should include a scientific verification of the efficacy of the practice, and once proven, further explorations would be indicated to bring the practice to a higher level. A system of comprehensive exploration was proposed and practiced in the past years to fulfill the aspiration. The research consisted of four areas: (1) Identification of the suitable medicinal herbs for the topical study; (2) Study of the biological activities of the selected herbs, concentrating on the areas of anti-inflammation, anti-oxidation, angiogenesis and cellular proliferation; (3) Study on the transcutaneous transport of the chemicals of the selected herbs to deeper tissues; and (4) Pilot clinical studies on common superficial inflammatory musculo-skeletal conditions to give objective clinical evidences to the topical applications. Five herbs were identified as suitable candidates of study. They were put into relevant laboratory platforms and were proven to be anti-oxidant, anti-inflammatory and pro-angiogenic. Three of the herbs were prepared as topical patches with an enhancer and used to treat three common ailments in pilot clinical trials, viz., plantar fasciitis, undisplaced metatarsal fracture and tendonitis of the wrist (de-Quervain's disease) and the elbow (Tennis elbow). The clinical results of the pilot studies were very positive. It is therefore concluded that further explorations are

  7. The Effects of Topic Familiarity, Author Expertise, and Content Relevance on Norwegian Students' Document Selection: A Mixed Methods Study

    ERIC Educational Resources Information Center

    McCrudden, Matthew T.; Stenseth, Tonje; Bråten, Ivar; Strømsø, Helge I.

    2016-01-01

    This mixed methods study investigated the extent to which author expertise and content relevance were salient to secondary Norwegian students (N = 153) when they selected documents that pertained to more familiar and less familiar topics. Quantitative results indicated that author expertise was more salient for the less familiar topic (nuclear…

  8. Chemistry {ampersand} Materials Science progress report summary of selected research and development topics, FY97

    SciTech Connect

    Newkirk, L.

    1997-12-01

    This report contains summaries of research performed in the Chemistry and Materials Science division. Topics include Metals and Ceramics, High Explosives, Organic Synthesis, Instrument Development, and other topics.

  9. Implications of Teachers' Recollections of Topics Selected by Boys and Girls for Science Fair Projects.

    ERIC Educational Resources Information Center

    Bunderson, Eileen D.; Bunderson, C. Victor

    1996-01-01

    Analyzes science fair choices of 2149 students for diversity of topics and scientific merit and matches them with teachers' recollections of topics thought most likely to be chosen. Reports that teachers recollections of topics seldom matched students' choices and teachers assumed more gender-based diversity in students' choice of topics than…

  10. TOPICAL REVIEW: Multimodality imaging of structure and function

    NASA Astrophysics Data System (ADS)

    Townsend, D. W.

    2008-02-01

    Historically, medical devices to image either anatomical structure or functional processes have developed along somewhat independent paths. The recognition that combining images from different modalities can nevertheless offer significant diagnostic advantages gave rise to sophisticated software techniques to coregister structure and function. Recently, alternatives to retrospective software-based fusion have become available through instrumentation that combines two imaging modalities within a single device, an approach that has since been termed hardware fusion. As a result, following their recent introduction into the clinic, combined PET/CT and SPECT/CT devices are now playing an increasingly important role in the diagnosis and staging of human disease. Recently, although limited to the brain, the first clinical MR scanner with a PET insert, a technically-challenging design, has been undergoing evaluation. This review will follow the development of multimodality instrumentation for clinical use from conception to present-day technology and assess the status and future potential for such devices.

  11. Selected topics in experimental aeroelasticity at the NASA Langley Research Center

    NASA Technical Reports Server (NTRS)

    Ricketts, R. H.

    1985-01-01

    The results of selected studies that have been conducted by the NASA Langley Research Center in the last three years are presented. The topics presented focus primarily on the ever-important transonic flight regime and include the following: body-freedom flutter of a forward-swept-wing configuration with and without relaxed static stability; instabilities associated with a new tilt-rotor vehicle; effects of winglets, supercritical airfoils, and spanwise curvature on wing flutter; wind-tunnel investigation of a flutter-like oscillation on a high-aspect-ratio flight research wing; results of wind-tunnel demonstration of the NASA decoupler pylon concept for passive suppression of wing/store flutter; and, new flutter testing methods which include testing at cryogenic temperatures for full scale Reynolds number simulation, subcritical response techniques for predicting onset of flutter, and a two-degree-of-freedom mount system for testing side-wall-mounted models.

  12. Selected topics in experimental aeroelasticity at the NASA Langley Research Center

    NASA Technical Reports Server (NTRS)

    Ricketts, R. H.

    1985-01-01

    The results of selected studies that have been conducted by the NASA Langley Research Center in the last three years are presented. The topics presented focus primarily on the ever-important transonic flight regime and include the following: body-freedom flutter of a forward-swept-wing configuration with and without relaxed static stability; instabilities associated with a new tilt-rotor vehicle; effects of winglets, supercritical airfoils, and spanwise curvature on wing flutter; wind-tunnel investigation of a flutter-like oscillation on a high-aspect-ratio flight research wing; results of wing-tunnel demonstration of the NASA decoupler pylon concept for passive suppression of wing/store flutter; and, new flutter testing methods which include testing at cryogenic temperatures for full scale Reynolds number simulation, subcritical response techniques for predicting onset of flutter, and a two-degree-of-freedom mount system for testing side-wall-mounted models.

  13. Combining Chemistry and Music to Engage Student Interest: Using Songs to Accompany Selected Chemical Topics

    ERIC Educational Resources Information Center

    Last, Arthur M.

    2009-01-01

    The use of recorded music to add interest to a variety of lecture topics is described. Topics include the periodic table, the formation of ionic compounds, thermodynamics, carbohydrates, nuclear chemistry, and qualitative analysis. (Contains 1 note.)

  14. A Comparison of Two Methods of Teaching Selected Topics in Plane Analytic Geometry.

    ERIC Educational Resources Information Center

    Bundrick, Charles Michael

    Reported are the results of a study to determine if there is a difference in learning as measured by an achievement test between high school students who study plane analytic geometric topics via a vector approach and those who study the same topics via a traditional approach. Secondary objectives concerned the transfer to further topics in solid…

  15. Topics in cosmology: Structure formation, dark energy and recombination

    NASA Astrophysics Data System (ADS)

    Alizadeh, Esfandiar

    The field of theoretical cosmology consists of numerous, inter-related branches, whose ambitious goal is to uncover the history of the universe from its beginning to its future. Achieving this, no doubt, requires a deep understanding of many areas of physics. In this thesis I touch upon a few of these areas in which I worked during my PhD studies. Chapter (2) describes our work in finding the accretion and merger history of dark matter halos. Dark matter halos are the collapsed dark matter structures in the late time evolution of the universe, whose existence is vital for the formation of galaxies in the Universe as they act as the potential wells where normal matter (collectively called Baryons) can accumulate, cool, and form stars. It is then no surprise that the properties of galaxies depends on the properties of the dark matter halo in which it resides, including its merger history, i.e. the number of times it merged with other halos. Even though these merger rates can be calculated theoretically for infinitesimal time steps, in order to find the merger history over an extended period of time one had to use either Monte-Carlo simulations to build up the total rates of merging and accreting from the infinitesimal rates or use N-body simulations. In chapter (2) we show how we used random walk formalism to write down an analytical (integral) equation for the merger history of halos. We have solved this equation numerically and find very good agreement with Monte-Carlo simulations. This work can be used in theories of galaxy formation and evolution. We then switch from the overdense regions of the Universe, halos, to the underdense ones, voids. These structures have not attracted as much attention from cosmologists as their overdense counterparts in probing the cosmological models. We show here that the shapes of voids as a probe can be of use for future surveys to pin down the equation of state of the dark energy, i.e. the ratio of its pressure to its energy

  16. [Environmental Hazards Assessment Program annual report, June 1992--June 1993]. Selected topics in risk analysis

    SciTech Connect

    Voit, E.O.

    1993-12-01

    It is becoming increasingly clear that human health is intricately related to our chemical and physical surroundings. Recognizing the interdependence between health and environment, the Medical University of South Carolina has begun to implement a graduate program in Environmental Risk Assessment. While the infrastructure for such a program had been in place for quite a while, providing education in biostatistics, epidemiology, and mathematical modeling, specific courses in risk assessment were not available. To expedite the educational process in this area, the Department of Biometry and Epidemiology offered the course Special Topics in Risk Analysis in the Spring semester of 1993. This course was intended as an introduction for graduate students, but one faculty and one postdoctoral fellow also enrolled. The course was organized in the form of a seminar, with students or faculty presenting selected materials from the literature that covered some of the central issues in risk analysis. The presentations were subsequently written up as reports and revised according to suggestions by the instructor. This technical report comprises the presentations and reflects what has been learned in the course Special Topics in Risk Analysis. It also may serve as an easy to read introduction to the complex area of risk analysis. By the very nature of the course and this report, most of the presented material is not original. It does not necessarily reflect the authors` or the editor`s opinion and is not intended for citation. Nonetheless, the students and the instructor have paid attention to citing relevant literature in order to enable the reader to trace ideas back to the original sources. As an Appendix, this volume contains the course syllabus as well as hand-out material that the students prepared independently and that has not been edited or revised.

  17. Finding scientific topics

    PubMed Central

    Griffiths, Thomas L.; Steyvers, Mark

    2004-01-01

    A first step in identifying the content of a document is determining which topics that document addresses. We describe a generative model for documents, introduced by Blei, Ng, and Jordan [Blei, D. M., Ng, A. Y. & Jordan, M. I. (2003) J. Machine Learn. Res. 3, 993-1022], in which each document is generated by choosing a distribution over topics and then choosing each word in the document from a topic selected according to this distribution. We then present a Markov chain Monte Carlo algorithm for inference in this model. We use this algorithm to analyze abstracts from PNAS by using Bayesian model selection to establish the number of topics. We show that the extracted topics capture meaningful structure in the data, consistent with the class designations provided by the authors of the articles, and outline further applications of this analysis, including identifying “hot topics” by examining temporal dynamics and tagging abstracts to illustrate semantic content. PMID:14872004

  18. PREFACE: Selected papers from the Fourth Topical Conference on Nanoscale Science and Engineering of the American Institute of Chemical Engineers

    NASA Astrophysics Data System (ADS)

    Wong, Michael S.; Lee, Gil U.

    2005-07-01

    systems and tissue engineering; nanotechnology for drug delivery and imaging; bionanotechnology in cancer and cardiovascular disease; nanostructured biomaterials; nanotechnology in bioengineering; nanofabrication of biosensing devices. We are pleased to present a selection of research papers in this special issue of Nanotechnology on behalf of the Nanoscale Science and Engineering Forum (NSEF). NSEF was established in 2001 as a new division of AIChE to promote nanotechnology efforts in chemical engineering. The chemical engineering discipline deals with the production and processing of chemicals and materials, and does so through a fundamental understanding of the core issues of transport, thermodynamics, and kinetics that exist at multiple length scales. Thus, it should come as no surprise that chemical engineers have been pursuing nanotechnology research for the last fifty years. For example, fuel production has benefited immensely from improved catalysts in which their pore structure is controlled with nanoscale precision, and polymer properties have been improved by controlling the polymer supramolecular structure at the nanometre scale. Chemical engineering will continue to make important contributions to nanotechnology, and will play a critical role in the transition from basic science and engineering research to commercial applications. We would like to thank all of the authors who contributed to this special issue; the three NSEF poster presentation award winners for their papers (Sureshkumar, Sunkara, and Rinaldi groups); Dr Nina Couzin, Publisher of Nanotechnology, for her support and enthusiasm for this project; Drs Sharon Glotzer and Dan Coy who chaired the topical conference; and Drs Meyya Meyyappan and Brett Cruden (NASA Ames Research Center) for their assistance in the initial planning stages. We also take this opportunity to thank the many people and organizations who have supported the 2004 topical conference along the way, which include all the session

  19. Louisiana Parish School Board Members, 1977: Profile and Opinions on Selected Topics. Research Report, Vol. 8, No. 2.

    ERIC Educational Resources Information Center

    Blackmon, C. Robert; Jones, Sue C.

    The purpose of this study was to construct a profile of the characteristics of the 684 Louisiana public school board members serving in 1976 and to report on their opinions on selected education topics. A total of 341 board members responded to the instrument constructed and mailed by the researchers. Among the results is the finding that the…

  20. Preface: Special Topic Section on Advanced Electronic Structure Methods for Solids and Surfaces

    SciTech Connect

    Michaelides, Angelos; Martinez, Todd J.; Alavi, Ali; Kresse, Georg

    2015-09-14

    This Special Topic section on Advanced Electronic Structure Methods for Solids and Surfaces contains a collection of research papers that showcase recent advances in the high accuracy prediction of materials and surface properties. It provides a timely snapshot of a growing field that is of broad importance to chemistry, physics, and materials science.

  1. The Effect of Topical Structure Analysis Instruction on University Students' Writing Quality

    ERIC Educational Resources Information Center

    Liangprayoon, Somlak; Chaya, Walaiporn; Thep-ackraphong, Tipa

    2013-01-01

    Coherence is considered one of the characteristics of effective writing. Topical structure analysis (TSA) has been taught to students as a revision strategy to raise their awareness of importance of textual coherence and helps them clearly understand its concept. This study aimed to investigate the effectiveness of TSA instruction in improving…

  2. Influence of Professional Preparation and Class Structure on Sexuality Topics Taught in Middle and High Schools

    ERIC Educational Resources Information Center

    Rhodes, Darson L.; Kirchofer, Gregg; Hammig, Bart J.; Ogletree, Roberta J.

    2013-01-01

    Background: This study examined the impact of professional preparation and class structure on sexuality topics taught and use of practice-based instructional strategies in US middle and high school health classes. Methods: Data from the classroom-level file of the 2006 School Health Policies and Programs were used. A series of multivariable…

  3. Resin selection criteria for tough composite structures

    NASA Technical Reports Server (NTRS)

    Chamis, C. C.; Smith, G. T.

    1983-01-01

    Resin selection criteria are derived using a structured methodology consisting of an upward integrated mechanistic theory and its inverse (top-down structured theory). These criteria are expressed in a "criteria selection space" which are used to identify resin bulk properties for improved composite "toughness". The resin selection criteria correlate with a variety of experimental data including laminate strength, elevated temperature effects and impact resistance.

  4. A Summary of Information on the Behavior of the Yakima Fold Belt as a Structural Entity -- Topical Report

    SciTech Connect

    Last, George V.; Winsor, Kelsey; Unwin, Stephen D.

    2012-08-01

    This document is one in a series of topical reports compiled by the Pacific Northwest National Laboratory to summarize technical information on selected topics important to the performance of a probabilistic seismic hazard analysis (PSHA) of the Hanford Site. The purpose of this report is to summarize available data and analyses relevant to the Yakima Fold Belt (YFB) that may bear on the question of whether or not the YFB behaves as a single seismotectonic province in which activity along one fold structure is representative of behavior along all other fold structures. This topic has met with a fairly high level of contention in the expert community and has the potential to result in significant impacts on an evaluation of seismic hazard at the Hanford Site. This report defines the relevant alternative conceptual models relevant to this technical issue and the arguments and data that support those models. It provides a brief description of the technical issue and principal uncertainties; a general overview on the nature of the technical issue, along with alternative conceptual models, supporting arguments and information, and uncertainties; and finally, it suggests some possible approaches for reducing uncertainties regarding this issue.

  5. Advanced turbine systems program conceptual design and product development. Task 3 -- System selection; Topical report

    SciTech Connect

    White, D.J.

    1994-07-01

    Solar Turbines Incorporated has elected to pursue an intercooled and recuperated (ICR) gas turbine system to exceed the goals of the DOE Advanced Turbine Systems (ATS) program, which are to develop and commercialize an industrial gas turbine system that operates at thermal efficiencies at least 15% higher than 1991 products, and with emissions not exceeding eight ppmv NOx and 20 ppmv CO and UHC. Solar`s goal is to develop a commercially viable industrial system (3--20 MW) driven by a gas turbine engine with a thermal efficiency of 50% (ATS50), with the flexibility to meet the differing operational requirements of various markets. Dispersed power generation is currently considered to be the primary future target market for the ICR in the 5--15 MW size class. The ICR integrated system approach provides an ideal candidate for the assumed dispersed power market, with its small footprint, easy transportability, and environmental friendliness. In comparison with other systems that use water or toxic chemicals such as ammonia for NOx control, the ICR has no consumables other than fuel and air. The low pressure ratio of the gas turbine engine also is favorable in that less parasitic power is needed to pump the natural gas into the combustor than for simple-cycle machines. Solar has narrowed the ICR configuration to two basic approaches, a 1-spool, and a 2-spool version of the ATS50. The 1-spool engine will have a lower first-cost but lower part-power efficiencies. The 2-spool ATS may not only have better part-power efficiency, its efficiency will also be less sensitive to reduced turbine rotor inlet temperature levels. Thus hot-end parts life can be increased with only small sacrifices in efficiency. The flexibility of the 2-spool arrangement in meeting customer needs is its major advantage over the 1-spool. This Task 3 Topical Report is intended to present Solar`s preliminary system selection based upon the initial trade-off studies performed to date.

  6. Visual Orientation Selectivity Based Structure Description.

    PubMed

    Wu, Jinjian; Lin, Weisi; Shi, Guangming; Zhang, Yazhong; Dong, Weisheng; Chen, Zhibo

    2015-11-01

    The human visual system is highly adaptive to extract structure information for scene perception, and structure character is widely used in perception-oriented image processing works. However, the existing structure descriptors mainly describe the luminance contrast of a local region, but cannot effectively represent the spatial correlation of structure. In this paper, we introduce a novel structure descriptor according to the orientation selectivity mechanism in the primary visual cortex. Research on cognitive neuroscience indicate that the arrangement of excitatory and inhibitory cortex cells arise orientation selectivity in a local receptive field, within which the primary visual cortex performs visual information extraction for scene understanding. Inspired by the orientation selectivity mechanism, we compute the correlations among pixels in a local region based on the similarities of their preferred orientation. By imitating the arrangement of the excitatory/inhibitory cells, the correlations between a central pixel and its local neighbors are binarized, and the spatial correlation is represented with a set of binary values, which is named the orientation selectivity-based pattern. Then, taking both the gradient magnitude and the orientation selectivity-based pattern into account, a rotation invariant structure descriptor is introduced. The proposed structure descriptor is applied in texture classification and reduced reference image quality assessment, as two different application domains to verify its generality and robustness. Experimental results demonstrate that the orientation selectivity-based structure descriptor is robust to disturbance, and can effectively represent the structure degradation caused by different types of distortion. PMID:26219097

  7. Structure biology of selective autophagy receptors

    PubMed Central

    Kim, Byeong-Won; Kwon, Do Hoon; Song, Hyun Kyu

    2016-01-01

    Autophagy is a process tightly regulated by various autophagy-related proteins. It is generally classified into non-selective and selective autophagy. Whereas non-selective autophagy is triggered when the cell is under starvation, selective autophagy is involved in eliminating dysfunctional organelles, misfolded and/or ubiquitylated proteins, and intracellular pathogens. These components are recognized by autophagy receptors and delivered to phagophores. Several selective autophagy receptors have been identified and characterized. They usually have some common domains, such as motif, a specific cargo interacting (ubiquitin-dependent or ubiquitin-independent) domain. Recently, structural data of these autophagy receptors has been described, which provides an insight of their function in the selective autophagic process. In this review, we summarize the most up-to-date findings about the structure-function of autophagy receptors that regulates selective autophagy. [BMB Reports 2016; 49(2): 73-80] PMID:26698872

  8. Excerpts on Selected Topics in Collective Bargaining Agreements and a Brief Review of the Status of Collective Bargaining in Community Colleges 1972 to 1975; an ERIC Brief.

    ERIC Educational Resources Information Center

    Lombardi, John, Comp.

    To acquaint the faculty and administrators with the scope and breadth of community college collective bargaining agreements, excerpts of selected topics are reproduced in this document without comment. On each topic two or three excerpts from different agreements are reproduced. The following topics are treated: (1) recognition of the employee…

  9. Selected Topics in Overset Technology Development and Applications At NASA Ames Research Center

    NASA Technical Reports Server (NTRS)

    Chan, William M.; Kwak, Dochan (Technical Monitor)

    2002-01-01

    This paper presents a general overview of overset technology development and applications at NASA Ames Research Center. The topics include: 1) Overview of overset activities at NASA Ames; 2) Recent developments in Chimera Grid Tools; 3) A general framework for multiple component dynamics; 4) A general script module for automating liquid rocket sub-systems simulations; and 5) Critical future work.

  10. Selected Price Topical Papers for Career Education: Working Paper No. 8.

    ERIC Educational Resources Information Center

    McKay, Donald J., Ed.

    Presented are 15 papers on topics relevant to Project PRICE (Programing Retarded in Career Education), a project designed to develop a methodology by which school districts can educate school, community, and family personnel to provide more relevant instruction and supportive services to retarded students. The following titles and entries are…

  11. PREFACE: Topics in the application of scattering methods to investigate the structure and dynamics of soft condensed matter

    NASA Astrophysics Data System (ADS)

    Chen, Sow-Hsin; Baglioni, Piero

    2006-09-01

    This special issue of Journal of Physics: Condensed Matter gathers together a series of contributions presented at the workshop entitled `Topics in the Application of Scattering Methods to Investigate the Structure and Dynamics of Soft Condensed Matter' held at Pensione Bencista, Fiesole, Italy, a wonderful Italian jewel tucked high in the hills above Florence. This immaculate 14th century villa is a feast for the eyes with antiques and original artwork everywhere you turn, and a stunning view of Florence, overlooking numerous villas and groves of olive trees. The meeting consisted of about 40 invited talks delivered by a selected group of prominent physicists and chemists from the USA, Mexico, Europe and Asia working in the fields of complex and glassy liquids. The topics covered by the talks included: simulations on the liquid-liquid transition phenomenon dynamic crossover in deeply supercooled confined water thermodynamics and dynamics of complex fluids dynamics of interfacial water structural arrest transitions in colloidal systems structure and dynamics in complex systems structure of supramolecular assemblies The choice of topics is obviously heavily biased toward the current interests of the two organizers of the workshop, in view of the fact that one of the incentives for organizing the meeting was to celebrate Sow-Hsin Chen’s life-long scientific activities on the occasion of his 70th birthday. The 21 articles presented in this issue are a state-of-the-art description of the different aspects reported at the workshop from all points of view---experimental, theoretical and numerical. The interdisciplinary nature of the talks should make this special issue of interest to a broad community of scientists involved in the study of the properties of complex fluids, soft condensed matter and disordered glassy systems. We are grateful to the Consorzio per lo Sviluppo dei Sistemi a Grande Interfase (CSGI), Florence, Italy and to the Materials Science Program of

  12. Orientation selectivity based structure for texture classification

    NASA Astrophysics Data System (ADS)

    Wu, Jinjian; Lin, Weisi; Shi, Guangming; Zhang, Yazhong; Lu, Liu

    2014-10-01

    Local structure, e.g., local binary pattern (LBP), is widely used in texture classification. However, LBP is too sensitive to disturbance. In this paper, we introduce a novel structure for texture classification. Researches on cognitive neuroscience indicate that the primary visual cortex presents remarkable orientation selectivity for visual information extraction. Inspired by this, we investigate the orientation similarities among neighbor pixels, and propose an orientation selectivity based pattern for local structure description. Experimental results on texture classification demonstrate that the proposed structure descriptor is quite robust to disturbance.

  13. The skin health and beauty pyramid: a clinically based guide to selecting topical skincare products.

    PubMed

    Mayoral, Flor A; Kenner, Julie R; Draelos, Zoe Diana

    2014-04-01

    The use of cosmeceuticals by patients is now commonplace. Without consultation and direction from an informed clinician, marketing pressures can lead consumers to make poor product choices that can result in wasted money and unsatisfactory outcomes. Skin professionals need a scientifically based, succinct tool to guide their patients toward best topical skincare practices. The Skin Health and Beauty Pyramid is an educational framework and product guide created from extensive scientific literature and study review on ingredients, formulations and technologies affecting skin biology. This clinical tool can simplify product choices for physicians and clinicians in the process of professionally guiding patients toward the optimal use of topical products to achieve best outcomes for skin health and beauty. PMID:24719060

  14. Selected Research and Development Topics on Aerospace Communications at NASA Glenn Research Center

    NASA Technical Reports Server (NTRS)

    Miranda, Felix A.; Romanofsky, Robert R.; Nessel, James A.

    2014-01-01

    This presentation discusses some of the efforts on communications RD that have been performed or are currently underway at NASA Glenn Research Center. The primary purpose of this presentation is to outline some RD topics to serve as talking points for a Technical Interchange Meeting with the Ohio State University. The meeting is scheduled to take place at The ElectroScience Laboratory of the Ohio State University on February 24, 2014.

  15. Photocarcinogenicity of selected topically applied dermatological drugs: calcineurin inhibitors, corticosteroids, and vitamin D analogs.

    PubMed

    Lerche, Catharina M; Wulf, Hans Christian

    2010-08-31

    Topical therapies constitute the mainstay of dermatological treatments for skin disorders, such as atopic dermatitis, contact dermatitis, psoriasis, or acne. Since some of these diseases are often chronic, treatment duration may last for years and may even last the patient's entire lifetime. Obviously, such long-term therapy may raise safety concerns, which also include the potential photocarcinogenic effect. Most patients are exposed to ultraviolet radiation (UVR) during leisure, work, vacations, or in tanning beds. Additionally, the patients may receive UVR via UVB phototherapy or psoralens plus UVA radiation (PUVA). The use of immunosuppressant's, such as corticosteroids and calcineurin inhibitors, has markedly increased. Patients with skin diseases have benefited from both systemic and topical treatment of both new and established drugs. The issue of a black box warning by the US Food and Drug Administration has increased concerns about photocarcinogenesis, which raises the question: "Are these drugs safe?" This review focuses on the mechanism of action and photocarcinogenic potential of commonly used topical treatments, such as corticosteroids, calcineurin inhibitors, and vitamin D analogs. PMID:25386250

  16. The transfer of drugs and therapeutics into human breast milk: an update on selected topics.

    PubMed

    Sachs, Hari Cheryl

    2013-09-01

    Many mothers are inappropriately advised to discontinue breastfeeding or avoid taking essential medications because of fears of adverse effects on their infants. This cautious approach may be unnecessary in many cases, because only a small proportion of medications are contraindicated in breastfeeding mothers or associated with adverse effects on their infants. Information to inform physicians about the extent of excretion for a particular drug into human milk is needed but may not be available. Previous statements on this topic from the American Academy of Pediatrics provided physicians with data concerning the known excretion of specific medications into breast milk. More current and comprehensive information is now available on the Internet, as well as an application for mobile devices, at LactMed (http://toxnet.nlm.nih.gov). Therefore, with the exception of radioactive compounds requiring temporary cessation of breastfeeding, the reader will be referred to LactMed to obtain the most current data on an individual medication. This report discusses several topics of interest surrounding lactation, such as the use of psychotropic therapies, drugs to treat substance abuse, narcotics, galactagogues, and herbal products, as well as immunization of breastfeeding women. A discussion regarding the global implications of maternal medications and lactation in the developing world is beyond the scope of this report. The World Health Organization offers several programs and resources that address the importance of breastfeeding (see http://www.who.int/topics/breastfeeding/en/). PMID:23979084

  17. Emergence of social structures via preferential selection

    NASA Astrophysics Data System (ADS)

    Lipowski, Adam; Lipowska, Dorota; Ferreira, Antonio Luis

    2014-09-01

    We examine a weighted-network multiagent model with preferential selection such that agents choose partners with probability p (w), where w is the number of their past selections. When p (w) increases sublinearly with the number of past selections [p(w)˜wα,α<1], agents develop a uniform preference for all other agents. At α =1, this state loses stability and more complex structures form. For a superlinear increase (α>1), strong heterogeneities emerge and agents make selections mainly within small and sometimes asymmetric clusters. Even in a few-agent case, the formation of such clusters resembles phase transitions with spontaneous symmetry breaking.

  18. Material Selection for Cryogenic Support Structures

    NASA Astrophysics Data System (ADS)

    Kramer, Erik; Kellaris, Nicholas; Daal, Miguel; Sadoulet, Bernard; Golwala, Sunil; Hollister, Matthew

    2014-09-01

    Design specifications for the support structures of low temperature instrumentation often call for low thermal conductivity between temperature stages, high stiffness, and specific load bearing capabilities. While overall geometric design plays an important role in both overall stiffness and heat conduction between stages, material selection can affect a structure's properties significantly. In this contribution, we suggest and compare several alternative materials to the current standard materials for building cryogenic support structures.

  19. Preface to Special Topic: Selected Papers from the 5th International Conference on Optofluidics.

    PubMed

    Fan, Shih-Kang; Yang, Zhenchuan

    2016-01-01

    The 5th International Conference on Optofluidics (Optofluidics 2015) was held in Taipei, Taiwan, July 26-29, 2015. The aim of this conference was to provide a forum to promote scientific exchange and to foster closer networks and collaborative ties between leading international researchers in optics and micro/nanofluidics across various disciplines. The scope of Optofluidics 2015 was deliberately broad and interdisciplinary, encompassing the latest advances and the most innovative developments in micro/nanoscale science and technology. Topics ranged from fundamental research to its applications in chemistry, physics, biology, materials, and medicine. PMID:27076863

  20. Preface to Special Topic: Selected Papers from the 5th International Conference on Optofluidics

    PubMed Central

    Fan, Shih-Kang; Yang, Zhenchuan

    2016-01-01

    The 5th International Conference on Optofluidics (Optofluidics 2015) was held in Taipei, Taiwan, July 26–29, 2015. The aim of this conference was to provide a forum to promote scientific exchange and to foster closer networks and collaborative ties between leading international researchers in optics and micro/nanofluidics across various disciplines. The scope of Optofluidics 2015 was deliberately broad and interdisciplinary, encompassing the latest advances and the most innovative developments in micro/nanoscale science and technology. Topics ranged from fundamental research to its applications in chemistry, physics, biology, materials, and medicine. PMID:27076863

  1. Selecting their Own Research Topic: An Effective Means of Engaging Undergraduates in Geoscience Careers

    NASA Astrophysics Data System (ADS)

    Sloan, V.; Haacker-Santos, R.

    2012-12-01

    Research experiences have been shown to successfully help draw undergraduates into STEM fields. In the SOARS and RESESS summer internship programs, which focus on the atmospheric and Earth sciences respectively, we attempt to match each intern with a project that is of specific interest to them, and to place the student with a science mentor with that expertise. Initially interns are solicited before the summer on their preferred topics of interest by having applicants or reapplicants choose fields of study from a list of topics. Follow-up conversations help to better define their area of interest. We then match those with the projects that have been proposed by prospective mentors, or seek scientists in the community who do research in that subdiscipline. Mentors also evaluate the intern's course background to determine if they have the foundation necessary for that work. Interns report that the opportunity to work on a topic that they perceive as interesting is vital to their engagement in the research. One intern wrote, "One of the most important components of internships like this is definitely letting the students somewhat chose their project. I think that a really good way to turn students OFF from research is by having them spend a summer researching something they are not even close to interested in." Another commented, "I really appreciated being matched with a project in my interest area. I think that's really important, even if it just teaches you that you might want to work in a different field than you initially thought." Being immersed in such a research group or lab provides interns with a rich opportunity to learn relevant content and skills, and to start developing a professional support network. Interns continue to engage with experts in their field of interest when they present at at scientifically relevant meeting sessions during the following academic year. Many of our interns go on to study the same subdiscipline of atmospheric or Earth

  2. Selected topics in particle accelerators: Proceedings of the CAP meetings. Volume 4

    SciTech Connect

    Parsa, Z.

    1995-10-01

    This Report includes copies of transparencies and notes from the presentations made at the Center for Accelerator Physics at Brookhaven National Laboratory. Editing and changes to the authors` contributions in this Report were made only to fulfill the publication requirements. This volume includes notes and transparencies on eight presentations: ``Application of Accelerator-Driven Spallation Targets - Including Tritium Production and Nuclear Waste Transmutation``, ``BNL 5 MW Pulsed Spallation Neutron Source Study``, ``Designing and Understanding of Magnets with the Help of Conformal Mapping``, ``Laser - Electron Beam Scattering Coherent Compton X-Ray Sources``, ``The LHC Project``, ``Optimization of the Photocathode-Linac Separation for the ATF [Accelerator Test Facility] Injection System``, ``On CEBAF Commissioning: First Results``, and ``The Proposed Booster Application Facility at BNL``. An Appendix lists dates, topics, and speakers from October 1989 to December 1994.

  3. Analysis of multiple instructional techniques on the understanding and retention of select mechanical topics

    NASA Astrophysics Data System (ADS)

    Fetsco, Sara Elizabeth

    There are several topics that introductory physics students typically have difficulty understanding. The purpose of this thesis is to investigate if multiple instructional techniques will help students to better understand and retain the material. The three units analyzed in this study are graphing motion, projectile motion, and conservation of momentum. For each unit students were taught using new or altered instructional methods including online laboratory simulations, inquiry labs, and interactive demonstrations. Additionally, traditional instructional methods such as lecture and problem sets were retained. Effectiveness was measured through pre- and post-tests and student opinion surveys. Results suggest that incorporating multiple instructional techniques into teaching will improve student understanding and retention. Students stated that they learned well from all of the instructional methods used except the online simulations.

  4. Students Fail to Transfer Knowledge of Chromosome Structure to Topics Pertaining to Cell Division

    PubMed Central

    Newman, Dina L.; Catavero, Christina M.; Wright, L. Kate

    2012-01-01

    Cellular processes that rely on knowledge of molecular behavior are difficult for students to comprehend. For example, thorough understanding of meiosis requires students to integrate several complex concepts related to chromosome structure and function. Using a grounded theory approach, we have unified classroom observations, assessment data, and in-depth interviews under the theory of knowledge transfer to explain student difficulties with concepts related to chromosomal behavior. In this paper, we show that students typically understand basic chromosome structure but do not activate cognitive resources that would allow them to explain macromolecular phenomena (e.g., homologous pairing during meiosis). To improve understanding of topics related to genetic information flow, we suggest that instructors use pedagogies and activities that prime students for making connections between chromosome structure and cellular processes. PMID:23222838

  5. Selective methane oxidation over promoted oxide catalysts. Topical report, September 8, 1992--September 7, 1996

    SciTech Connect

    Klier, K.; Herman, R.G.

    1996-12-31

    The objective of this research was to selectively oxidize methane to C{sub 2} hydrocarbons and to oxygenates, in particular formaldehyde and methanol, in high space time yields using air at the oxidant under milder reaction conditions that heretofore employed over industrially practical oxide catalysts. The research carried out under this US DOE-METC contract was divided into the following three tasks: Task 1, maximizing selective methane oxidation to C{sub 2}{sup +} products over promoted SrO/La{sub 2}O{sub 3} catalysts; Task 2, selective methane oxidation to oxygenates; and Task 3, catalyst characterization and optimization. Principal accomplishments include the following: the 1 wt% SO{sub 4}{sup 2{minus}}/SrO/La{sub 2}O{sub 3} promoted catalyst developed here produced over 2 kg of C{sub 2} hydrocarbons/kg catalyst/hr at 550 C; V{sub 2}O{sub 5}/SiO{sub 2} catalysts have been prepared that produce up to 1.5 kg formaldehyde/kg catalyst/hr at 630 C with low CO{sub 2} selectivities; and a novel dual bed catalyst system has been designed and utilized to produce over 100 g methanol/kg catalyst/hr at 600 C with the presence of steam in the reactant mixture.

  6. Selected Topics from LVCSR Research for Asian Languages at Tokyo Tech

    NASA Astrophysics Data System (ADS)

    Furui, Sadaoki

    This paper presents our recent work in regard to building Large Vocabulary Continuous Speech Recognition (LVCSR) systems for the Thai, Indonesian, and Chinese languages. For Thai, since there is no word boundary in the written form, we have proposed a new method for automatically creating word-like units from a text corpus, and applied topic and speaking style adaptation to the language model to recognize spoken-style utterances. For Indonesian, we have applied proper noun-specific adaptation to acoustic modeling, and rule-based English-to-Indonesian phoneme mapping to solve the problem of large variation in proper noun and English word pronunciation in a spoken-query information retrieval system. In spoken Chinese, long organization names are frequently abbreviated, and abbreviated utterances cannot be recognized if the abbreviations are not included in the dictionary. We have proposed a new method for automatically generating Chinese abbreviations, and by expanding the vocabulary using the generated abbreviations, we have significantly improved the performance of spoken query-based search.

  7. Selected Topics on the Synthesis, Properties and Applications of Multiwalled Carbon Nanotubes

    PubMed Central

    Stoner, B.R.; Brown, B.; Glass, J.T.

    2014-01-01

    Summary In summary, MWCNTs have been examined for a variety of electronic applications due to their unique structure and chemistry. Electrodes for field emission, energy and sensor applications hold particular interest. MWCNTs provide a very high surface area, relatively easy methods of surface modification, controllable and high concentration of reactive surface sites, and high specific capacitance. Combining MWCNTs with graphene structures, oxide and metal nanoparticles and certain polymers extends their performance and functionality. Such hybrid structures have been produced in situ during CNT growth and in two-step processes. Excellent progress on understanding the mechanisms of CNT growth has enabled numerous growth methods to all yield MWCNT structures in a variety of morphologies. PMID:24910503

  8. Development of BEACON technology: Hydrogen catalyst selection and preparation: Topical report

    SciTech Connect

    Not Available

    1983-10-01

    The BEACON process involves the catalytic deposition of a highly reactive form of carbon from a gas stream which contains carbon monoxide. The carbon-depleted gas is combusted with air to produce power, and the carbon is reacted with steam to produce methane or hydrogen. Bench scale development of the methane process was completed during the second quarter 1983 and the results reported to DOE. Bench scale development of the hydrogen process is currently underway. This document summarizes the effort expended in the selection and preparation of the primary and back-up hydrogen production catalysts to be used in multi-cycle testing at bench scale. The effort comprised the Task 1 experimentation of the current BEACON program and was six weeks in duration. From 20 catalysts screened at laboratory scale as candidates for hydrogen production from BEACON carbon, two were selected as promising for exhibiting good performance (activity and selectivity) at reaction pressures above ambient. These two catalysts, No. 6 and No. 11, were subjected to extensive carbon deposition-steaming testing at 50, 75 and 100 psig (3 to 5 cycles at each pressure); 10 to 20 gram batches of solids were used in these tests. Performance comparisons led to the selection of Catalyst No. 11 as the primary catalyst for the hydrogen process. Catalyst No. 6 performed well enough at pressures up to 50 psig to be considered as a potential replacement to Catalyst No. 11 should the latter fail multi-cycle testing (long-term activity tests at elevated pressures). The multi-cycle testing (a minimum operation of 250 hours of simultaneous carbon deposition and steaming to hydrogen) will be performed in the existing Tandem Reactor apparatus under Task 2 of this program. 2 figs., 7 tabs.

  9. Gas Research Institute`s appalachian basin research: Selected bibliography. Topical report, July 1995

    SciTech Connect

    Picciano, L.

    1995-07-01

    The Appalachian Basin citations listed in this bibliography present select research reports that provide an overview of research and development (R&D) efforts related to the basin. The bibliography is organized in three sections, one for each of the following unconventional gas resources: coalbed methane, gas shales, and tight gas sands. Citations are further divided into geology and engineering subsections. The citations are only for those reports resulting directly from GRI`s research investment or reviews that extensively used GRI results.

  10. Structural context shapes the aquaporin selectivity filter

    PubMed Central

    Savage, David F.; O’Connell, Joseph D.; Miercke, Larry J. W.; Finer-Moore, Janet; Stroud, Robert M.

    2010-01-01

    Aquaporins are transmembrane channels that facilitate the permeation of water and small, uncharged amphipathic molecules across cellular membranes. One distinct aquaporin subfamily contains pure water channels, whereas a second subfamily contains channels that conduct small alditols such as glycerol, in addition to water. Distinction between these substrates is central to aquaporin function, though the contributions of protein structural motifs required for selectivity are not yet fully characterized. To address this question, we sequentially engineered three signature amino acids of the glycerol-conducting subfamily into the Escherichia coli water channel aquaporin Z (AqpZ). Functional analysis of these mutant channels showed a decrease in water permeability but not the expected increase in glycerol conduction. Using X-ray crystallography, we determined the atomic resolution structures of the mutant channels. The structures revealed a channel surprisingly similar in size to the wild-type AqpZ pore. Comparison with measured rates of transport showed that, as the size of the selectivity filter region of the channel approaches that of water, channel hydrophilicity dominated water conduction energetics. In contrast, the major determinant of selectivity for larger amphipathic molecules such as glycerol was channel cross-section size. Finally, we find that, although the selectivity filter region is indeed central to substrate transport, other structural elements that do not directly interact with the substrates, such as the loop connecting helices M6 and M7, and the C loop between helices C4 and C5, play an essential role in facilitating selectivity. PMID:20855585

  11. The selection of sun-blocking topical agents to protect the skin.

    PubMed

    Tipton, J B

    1978-08-01

    A simple method, based on scientific evidence, for the selection of a proper sun protective agent has been presented. To make it even easier, the surgeon need only look for a product containing both PABA and titanium dioxide. The author is aware there may be many other fine products available but not mentioned here, and some of those mentioned here serve the purpose for which they were designed but may not do all the things the plastic surgeon desires. In any event, the statements made herein should not be construed as an endorsement of one product over another. PMID:674411

  12. On the structure selectivity of clathrate hydrates.

    PubMed

    Matsumoto, Masakazu; Tanaka, Hideki

    2011-06-30

    We propose a strategic method to search for a new clathrate hydrate by investigating the selectivity of its crystalline structure, which has been expected to depend mostly on the guest species and less on the thermodynamic conditions. Relative stability among various morphologies is examined in terms of the chemical potential of water of clathrate hydrates in equilibrium with guest gases. This evaluation is performed by calculating the free energy of cage occupancy according to the standard statistical mechanical theory with the aid of the Yarmolyuk and Kripyakevich's rule on the Frank-Kasper type alloys to estimate the numbers of cages of various types. Thus, a comprehensive interpretation of the selectivity of crystalline structures is successfully made. We explain why two major structures are stable in most of the thermodynamic conditions and establish a relation between polymorphism of clathrate hydrate and the guest size and other parameters, thereby suggesting a way to find a new clathrate hydrate by appropriate choice of the guest species and/or the thermodynamic properties. It is found that there is a small room in the above parameter space for the other structure than the major two to be the most stable, including a new structure. In addition, simple but thorough elucidation is given for preferential formation of TS-I structure in bromine hydrate. PMID:21619053

  13. Selected topics on the interaction between cirrus clouds and embedded contrails

    NASA Astrophysics Data System (ADS)

    Gierens, K.

    2012-12-01

    Persistent contrails and natural cirrus clouds often coexist in the upper troposphere and contrails can be embedded within cirrus clouds. The present paper deals with some questions regarding the interaction of cirrus clouds and embedded contrails. I have selected only questions that can be answered by analytical means. I find that (1) the emission index for water vapour is only slightly changed when an aircraft crosses a cirrus cloud, (2) that contrail formation is not affected by an ambient cirrus, (3) that cirrus ice crystals entrained into the trailing wing tip vortex do not efficiently retard the sublimation of contrail ice crystals, and (4) that cirrus can start to dissolve an embedded contrail after a couple of hours by aggregation.

  14. Structure and selectivity in bestrophin ion channels

    DOE PAGESBeta

    Yang, Tingting; Liu, Qun; Kloss, Brian; Bruni, Renato; Kalathur, Ravi C.; Guo, Youzhong; Kloppmann, Edda; Rost, Burkhard; Colecraft, Henry M.; Hendrickson, Wayne A.

    2014-09-25

    Human bestrophin 1 (hBest1) is a calcium-activated chloride channel from the retinal pigment epithelium, where it can suffer mutations associated with vitelliform macular degeneration, or Best disease. We describe the structure of a bacterial homolog (KpBest) of hBest1 and functional characterizations of both channels. KpBest is a pentamer that forms a five-helix transmembrane pore, closed by three rings of conserved hydrophobic residues, and has a cytoplasmic cavern with a restricted exit. From electrophysiological analysis of structure-inspired mutations in KpBest and hBest1, we find a subtle control of ion selectivity in the bestrophins, including reversal of anion/cation selectivity, and dramatic activationmore » by mutations at the exit restriction. Lastly, a homology model of hBest1 shows the locations of disease-causing mutations and suggests possible roles in regulation.« less

  15. Structure and selectivity in bestrophin ion channels

    SciTech Connect

    Yang, Tingting; Liu, Qun; Kloss, Brian; Bruni, Renato; Kalathur, Ravi C.; Guo, Youzhong; Kloppmann, Edda; Rost, Burkhard; Colecraft, Henry M.; Hendrickson, Wayne A.

    2014-09-25

    Human bestrophin 1 (hBest1) is a calcium-activated chloride channel from the retinal pigment epithelium, where it can suffer mutations associated with vitelliform macular degeneration, or Best disease. We describe the structure of a bacterial homolog (KpBest) of hBest1 and functional characterizations of both channels. KpBest is a pentamer that forms a five-helix transmembrane pore, closed by three rings of conserved hydrophobic residues, and has a cytoplasmic cavern with a restricted exit. From electrophysiological analysis of structure-inspired mutations in KpBest and hBest1, we find a subtle control of ion selectivity in the bestrophins, including reversal of anion/cation selectivity, and dramatic activation by mutations at the exit restriction. Lastly, a homology model of hBest1 shows the locations of disease-causing mutations and suggests possible roles in regulation.

  16. The Influence of Topical Prostaglandin Analogues in Inflammation After Selective Laser Trabeculoplasty Treatment

    PubMed Central

    Chen, Enping

    2012-01-01

    Abstract Purpose Reducing intraocular pressure (IOP) seems to be the only treatment that slows progression in glaucoma. The IOP can be decreased by pharmaceutical treatment, laser [selective laser trabeculoplasty (SLT)] treatment, or surgery. Prostaglandin analogues have been postulated to share action mechanisms with SLT and to possibly diminish the effects of SLT treatment. The aim of the current study was to investigate the effects of prostaglandin analogues in inflammation and IOP reduction after SLT treatment. Methods Prospective nonrandomized study. One hundred and eighteen patients were included in the study. Inclusion criteria: Glaucoma (open-angle or pseudoexfoliation glaucoma) patients who will be treated with SLT. Inflammation was measured with a laser flare meter (Kowa FM-500). Measurements were made before SLT and then 2 h, 1 week, and 1 month after SLT treatment. IOP was also checked at the same time intervals. The SLT treatment was performed over 90°. All patients were divided into two groups: those receiving prostaglandins analogues and those treated with nonprostaglandin analogues. Results Inflammation before and after SLT showed no significant difference between the groups at all the time intervals studied (t-test, before: P=0.16; 2 h: P=0.14; 1 week: P=0.12; and 1 month: P=0.36). IOP reduction showed no significant difference between the groups (t-test, P=0.31). Conclusions SLT treatment effects do not seem to be influenced by the use of prostaglandin analogues. PMID:22087857

  17. In-Depth Analysis of Selected Topics Related to the Quality Assessment of E-Commerce Systems

    NASA Astrophysics Data System (ADS)

    Stefani, Antonia; Stavrinoudis, Dimitris; Xenos, Michalis

    This paper provides an in-depth analysis of selected important topics related to the quality assessment of e-commerce systems. It briefly introduces to the reader a quality assessment model based on Bayesian Networks and presents in detail the practical application of this model, highlighting practical issues related to the involvement of human subjects, conflict resolution, and calibration of the measurement instruments. Furthermore, the paper presents the application process of the model for the quality assessment of various e-commerce systems; it also discusses in detail how particular features (data) of the assessed e-commerce systems can be identified and, using the described automated assessment process, lead to higher abstraction information (desiderata) regarding the quality of the assessed e-commerce systems.

  18. EDITORIAL: Selected Papers from OMS'07, the 2nd Topical Meeting of the European Optical Society on Optical Microsystems (OMS)

    NASA Astrophysics Data System (ADS)

    Rendina, Ivo; Fazio, Eugenio; Ferraro, Pietro

    2008-06-01

    OMS'07 was the 2nd Topical Meeting of the European Optical Society (EOS) on Optical Microsystems (OMS). It was organized by the EOS in the frame of its international topical meeting activity, and after the success of the inaugural meeting was once again held in Italy, 30 September to 3 October 2007, amidst the wonderful scenery of the Island of Capri. The local organizing committee was composed of researchers from `La Sapienza' University in Rome and the National Council of Research (CNR) in Naples, Italy. A selected group of leading scientists in the field formed the international scientific committee. The conference was fully dedicated to the most recent advancements carried out in the field of optical microsystems. More then 150 scientists coming from five continents attended the conference and more than 100 papers were presented, organized into the following sessions: Photonic cystals and metamaterials Optofluidic microsystems and devices Optical microsystems and devices New characterization methods for materials and devices Application of optical systems Optical sources and photodetectors Optical resonators Nonlinear optic devices Micro-optical devices. Four keynote lecturers were invited for the Plenary sessions: Federico Capasso, Harvard University, USA; Bahram Javidi, University of Connecticut, USA (Distinguished Lecturer, Emeritus of LEOS--IEEE Society); Demetri Psaltis, EPFL, Lausanne, Switzerland; Ammon Yariv, California Institute of Technology, USA. Furthermore, 21 invited speakers opened each session of the conference with their talks. In addition a special session was organized to celebrate eighty years of the Isituto Nazionale di Ottica Applicata (INOA) of CNR. The special invited speaker for this session was Professor Theodor W Hänsch (Nobel Prize in Physics, 2005), who gave a lecture entitled `What can we do with optical frequency combs?' In this special issue of Journal of Optics A: Pure and Applied Optics, a selection of the most interesting

  19. Structured Correspondence Topic Models for Mining Captioned Figures in Biological Literature.

    PubMed

    Ahmed, Amr; Xing, Eric P; Cohen, William W; Murphy, Robert F

    2009-01-01

    A major source of information (often the most crucial and informative part) in scholarly articles from scientific journals, proceedings and books are the figures that directly provide images and other graphical illustrations of key experimental results and other scientific contents. In biological articles, a typical figure often comprises multiple panels, accompanied by either scoped or global captioned text. Moreover, the text in the caption contains important semantic entities such as protein names, gene ontology, tissues labels, etc., relevant to the images in the figure. Due to the avalanche of biological literature in recent years, and increasing popularity of various bio-imaging techniques, automatic retrieval and summarization of biological information from literature figures has emerged as a major unsolved challenge in computational knowledge extraction and management in the life science. We present a new structured probabilistic topic model built on a realistic figure generation scheme to model the structurally annotated biological figures, and we derive an efficient inference algorithm based on collapsed Gibbs sampling for information retrieval and visualization. The resulting program constitutes one of the key IR engines in our SLIF system that has recently entered the final round (4 out 70 competing systems) of the Elsevier Grand Challenge on Knowledge Enhancement in the Life Science. Here we present various evaluations on a number of data mining tasks to illustrate our method. PMID:25485170

  20. Acne Treatment Based on Selective Photothermolysis of Sebaceous Follicles with Topically Delivered Light-Absorbing Gold Microparticles.

    PubMed

    Paithankar, Dilip Y; Sakamoto, Fernanda H; Farinelli, William A; Kositratna, Garuna; Blomgren, Richard D; Meyer, Todd J; Faupel, Linda J; Kauvar, Arielle N B; Lloyd, Jenifer R; Cheung, Wang L; Owczarek, Witold D; Suwalska, Anna M; Kochanska, Katarzyna B; Nawrocka, Agnieszka K; Paluchowska, Elwira B; Podolec, Katarzyna M; Pirowska, Magdalena M; Wojas-Pelc, Anna B; Anderson, R Rox

    2015-07-01

    The pathophysiology of acne vulgaris depends on active sebaceous glands, implying that selective destruction of sebaceous glands could be an effective treatment. We hypothesized that light-absorbing microparticles could be delivered into sebaceous glands, enabling local injury by optical pulses. A suspension of topically applied gold-coated silica microparticles exhibiting plasmon resonance with strong absorption at 800 nm was delivered into human pre-auricular and swine sebaceous glands in vivo, using mechanical vibration. After exposure to 10-50 J cm(-2), 30 milliseconds, 800 nm diode laser pulses, microscopy revealed preferential thermal injury to sebaceous follicles and glands, consistent with predictions from a computational model. Inflammation was mild; gold particles were not retained in swine skin 1 month after treatment, and uptake in other organs was negligible. Two independent prospective randomized controlled clinical trials were performed for treatment of moderate-to-severe facial acne, using unblinded and blinded assessments of disease severity. Each trial showed clinically and statistically significant improvement of inflammatory acne following three treatments given 1-2 weeks apart. In Trial 2, inflammatory lesions were significantly reduced at 12 weeks (P=0.015) and 16 weeks (P=0.04) compared with sham treatments. Optical microparticles enable selective photothermolysis of sebaceous glands. This appears to be a well-tolerated, effective treatment for acne vulgaris. PMID:25748556

  1. Acne Treatment Based on Selective Photothermolysis of Sebaceous Follicles with Topically Delivered Light-Absorbing Gold Microparticles

    PubMed Central

    Paithankar, Dilip Y; Sakamoto, Fernanda H; Farinelli, William A; Kositratna, Garuna; Blomgren, Richard D; Meyer, Todd J; Faupel, Linda J; Kauvar, Arielle N B; Lloyd, Jenifer R; Cheung, Wang L; Owczarek, Witold D; Suwalska, Anna M; Kochanska, Katarzyna B; Nawrocka, Agnieszka K; Paluchowska, Elwira B; Podolec, Katarzyna M; Pirowska, Magdalena M; Wojas-Pelc, Anna B; Anderson, R Rox

    2015-01-01

    The pathophysiology of acne vulgaris depends on active sebaceous glands, implying that selective destruction of sebaceous glands could be an effective treatment. We hypothesized that light-absorbing microparticles could be delivered into sebaceous glands, enabling local injury by optical pulses. A suspension of topically applied gold-coated silica microparticles exhibiting plasmon resonance with strong absorption at 800 nm was delivered into human pre-auricular and swine sebaceous glands in vivo, using mechanical vibration. After exposure to 10–50 J cm−2, 30 milliseconds, 800 nm diode laser pulses, microscopy revealed preferential thermal injury to sebaceous follicles and glands, consistent with predictions from a computational model. Inflammation was mild; gold particles were not retained in swine skin 1 month after treatment, and uptake in other organs was negligible. Two independent prospective randomized controlled clinical trials were performed for treatment of moderate-to-severe facial acne, using unblinded and blinded assessments of disease severity. Each trial showed clinically and statistically significant improvement of inflammatory acne following three treatments given 1–2 weeks apart. In Trial 2, inflammatory lesions were significantly reduced at 12 weeks (P=0.015) and 16 weeks (P=0.04) compared with sham treatments. Optical microparticles enable selective photothermolysis of sebaceous glands. This appears to be a well-tolerated, effective treatment for acne vulgaris. PMID:25748556

  2. Modeling the Relationships among Topical Knowledge, Anxiety, and Integrated Speaking Test Performance: A Structural Equation Modeling Approach

    ERIC Educational Resources Information Center

    Huang, Heng-Tsung Danny

    2010-01-01

    Thus far, few research studies have examined the practice of integrated speaking test tasks in the field of second/foreign language oral assessment. This dissertation utilized structural equation modeling (SEM) and qualitative techniques to explore the relationships among topical knowledge, anxiety, and integrated speaking test performance and to…

  3. Freshman Health Topics

    ERIC Educational Resources Information Center

    Hovde, Karen

    2011-01-01

    This article examines a cluster of health topics that are frequently selected by students in lower division classes. Topics address issues relating to addictive substances, including alcohol and tobacco, eating disorders, obesity, and dieting. Analysis of the topics examines their interrelationships and organization in the reference literature.…

  4. Lexical and Syntactic Influences on Structural Selection in Language Production

    ERIC Educational Resources Information Center

    Frazer, Alexandra Kate

    2016-01-01

    We still know surprisingly little about how grammatical structures are selected for use in sentence production. A major debate concerns whether structural selection is competitive or noncompetitive. Competitive accounts propose that alternative structures or structural components actively suppress one another's activation until one option reaches…

  5. Effect of parental selection of healthy behavior topic during well child visit on plan to change childs eating or physical activity behavior

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Current recommendations direct pediatricians to address obesity and obesity prevention routinely during well child visits and to tailor their counseling, but clinicians may feel ineffective because of time constraints and lack of parent interest. To prompt parents to select a healthy lifestyle topic...

  6. How selection structures species abundance distributions

    PubMed Central

    Magurran, Anne E.; Henderson, Peter A.

    2012-01-01

    How do species divide resources to produce the characteristic species abundance distributions seen in nature? One way to resolve this problem is to examine how the biomass (or capacity) of the spatial guilds that combine to produce an abundance distribution is allocated among species. Here we argue that selection on body size varies across guilds occupying spatially distinct habitats. Using an exceptionally well-characterized estuarine fish community, we show that biomass is concentrated in large bodied species in guilds where habitat structure provides protection from predators, but not in those guilds associated with open habitats and where safety in numbers is a mechanism for reducing predation risk. We further demonstrate that while there is temporal turnover in the abundances and identities of species that comprise these guilds, guild rank order is conserved across our 30-year time series. These results demonstrate that ecological communities are not randomly assembled but can be decomposed into guilds where capacity is predictably allocated among species. PMID:22787020

  7. The Structure of Scientific Arguments by Secondary Science Teachers: Comparison of Experimental and Historical Science Topics

    ERIC Educational Resources Information Center

    Gray, Ron; Kang, Nam-Hwa

    2014-01-01

    Just as scientific knowledge is constructed using distinct modes of inquiry (e.g. experimental or historical), arguments constructed during science instruction may vary depending on the mode of inquiry underlying the topic. The purpose of this study was to examine whether and how secondary science teachers construct scientific arguments during…

  8. Selective induction of apoptosis in the hamster flank sebaceous gland organ by a topical liposome 5-alpha-reductase inhibitor: a treatment strategy for acne.

    PubMed

    Li, Lingna; Tang, Li; Baranov, Eugene; Yang, Meng; Amoh, Yasuyuki; Katsuoka, Kensei; Hoffman, Robert M

    2010-02-01

    Acne is a very widespread cosmesis problem. Isotretinoin, a synthetic oral retinoid is used to treat acne, which is androgen dependent. Numerous side-effects occur from this treatment. 5-alpha-Reductase plays a critical role in normal and pathological androgen-dependent processes. We have taken the approach to develop a selective, effective, topically-applied 5-alpha-reductase inhibitor to modify unwanted or pathological processes in the pilosebaceous unit such as acne. Toward this goal, we have previously developed a selective liposome hair follicle targeting system. We demonstrate in this report that the 5-alpha-reductase inhibitor N,N-diethyl-4-methyl-3-oxo-4-aza-5alpha-androstane-17beta-carboxamide (4-MA) incorporated into liposomes induces apoptosis and inhibits growth of the dihydrotestosterone (DHT)-dependent hamster flank organ sebaceous gland. We have compared topical application of liposome 4-MA and solvent-formulated 4-MA and observed selective efficacy of topical application of liposome 4-MA by the reduction of size and induction of apoptosis only in the treated hamster flank organ. Apoptosis induced by liposome 4-MA in the treated flank organ sebaceous gland cells was observed both by assays for DNA fragments (transferase deoxytidyl uridine end labeling) and by observation of condensed and fragmented nuclei. When 4-MA was topically applied formulated in ethanol and glycerol without liposomes, the selective efficacy was lost. Liposome 4-MA did not significantly affect prostate weight, testosterone/DHT ratios or bodyweight gain compared to controls indicating safety as well as efficacy of topical application of liposome 4-MA for pathological processes such as acne. PMID:20175850

  9. Succinyl hydroxamates as potent and selective non-peptidic inhibitors of procollagen C-proteinase: design, synthesis, and evaluation as topically applied, dermal anti-scarring agents.

    PubMed

    Bailey, Simon; Fish, Paul V; Billotte, Stephane; Bordner, Jon; Greiling, Doris; James, Kim; McElroy, Andrew; Mills, James E; Reed, Charlotte; Webster, Robert

    2008-12-15

    Succinyl hydroxamates 1 and 2 are disclosed as novel series of potent and selective inhibitors of procollagen C-proteinase (PCP) which may have potential as anti-fibrotic agents. Carboxamide 7 demonstrated good PCP inhibition and had excellent selectivity over MMPs involved in wound healing. In addition, 7 was effective in a cell-based model of collagen deposition (fibroplasia model) and was very effective at penetrating human skin in vitro. Compound 7 (UK-383,367) was selected as a candidate for evaluation in clinical studies as a topically applied, dermal anti-scarring agent. PMID:18945617

  10. Structural selectivity of human SGLT inhibitors

    PubMed Central

    Hummel, Charles S.; Lu, Chuan; Liu, Jie; Ghezzi, Chiari; Hirayama, Bruce A.; Loo, Donald D. F.; Kepe, Vladimir; Barrio, Jorge R.

    2012-01-01

    Human Na+-d-glucose cotransporter (hSGLT) inhibitors constitute the newest class of diabetes drugs, blocking up to 50% of renal glucose reabsorption in vivo. These drugs have potential for widespread use in the diabetes epidemic, but how they work at a molecular level is poorly understood. Here, we use electrophysiological methods to assess how they block Na+-d-glucose cotransporter SGLT1 and SGLT2 expressed in human embryonic kidney 293T (HEK-293T) cells and compared them to the classic SGLT inhibitor phlorizin. Dapagliflozin [(1S)-1,5,5-anhydro-1-C-{4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl}-d-glucitol], two structural analogs, and the aglycones of phlorizin and dapagliflozin were investigated in detail. Dapagliflozin and fluoro-dapagliflozin [(1S)-1,5-anhydro-1-C-{4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl}-4-F-4-deoxy-d-glucitol] blocked glucose transport and glucose-coupled currents with ≈100-fold specificity for hSGLT2 (Ki = 6 nM) over hSGLT1 (Ki = 400 nM). As galactose is a poor substrate for SGLT2, it was surprising that galacto-dapagliflozin [(1S)-1,5-anhydro-1-C-{4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl}-d-galactitol] was a selective inhibitor of hSGLT2, but was less potent than dapagliflozin for both transporters (hSGLT2 Ki = 25 nM, hSGLT1 Ki = 25,000 nM). Phlorizin and galacto-dapagliflozin rapidly dissociated from SGLT2 [half-time off rate (t1/2,Off) ≈ 20–30 s], while dapagliflozin and fluoro-dapagliflozin dissociated from hSGLT2 at a rate 10-fold slower (t1/2,Off ≥ 180 s). Phlorizin was unable to exchange with dapagliflozin bound to hSGLT2. In contrast, dapagliflozin, fluoro-dapagliflozin, and galacto-dapagliflozin dissociated quickly from hSGLT1 (t1/2,Off = 1–2 s), and phlorizin readily exchanged with dapagliflozin bound to hSGLT1. The aglycones of phlorizin and dapagliflozin were poor inhibitors of both hSGLT2 and hSGLT1 with Ki values > 100 μM. These results show that inhibitor binding to SGLTs is composed of two synergistic forces

  11. Glass science tutorial lecture {number_sign}6: The melting of silicate glasses, a review of selected topics

    SciTech Connect

    Swarts, E.L.

    1995-03-01

    This report summarizes a two-day lecture given at Westinghouse Hanford Company in March, 1995 and includes the data used in the presentation. Topics included the special needs of a low-level waste vitrification process, glass melting, mechanisms of the formation of foam, glass refining (bubble removal), and homogenization (reduction of chemical heterogeneity to acceptable levels). 96 refs.

  12. A Curriculum Activities Guide to Selected Environmental Topics for Use With Elementary and Junior High School Students.

    ERIC Educational Resources Information Center

    Sexton, Alan D., Ed.

    This guide contains learning activities in environmental education developed by teachers and intended for use at the elementary or junior high school levels. Topics covered include: water, esthetics, air, soil and sediment, solid waste, energy, noise, population, and transportation. Generally, each activity contains an introduction, a listing of…

  13. Structured variable selection with q-values

    Technology Transfer Automated Retrieval System (TEKTRAN)

    When some of the regressors can act on both the response and other explanatory variables, the already challenging problem of selecting variables when the number of covariates exceeds the sample size becomes more difficult. A motivating example is a metabolic study in mice that has diet groups and gu...

  14. Structural Implications for Selective Targeting of PARPs

    PubMed Central

    Steffen, Jamin D.; Brody, Jonathan R.; Armen, Roger S.; Pascal, John M.

    2013-01-01

    Poly(ADP-ribose) polymerases (PARPs) are a family of enzymes that use NAD+ as a substrate to synthesize polymers of ADP-ribose (PAR) as post-translational modifications of proteins. PARPs have important cellular roles that include preserving genomic integrity, telomere maintenance, transcriptional regulation, and cell fate determination. The diverse biological roles of PARPs have made them attractive therapeutic targets, which have fueled the pursuit of small molecule PARP inhibitors. The design of PARP inhibitors has matured over the past several years resulting in several lead candidates in clinical trials. PARP inhibitors are mainly used in clinical trials to treat cancer, particularly as sensitizing agents in combination with traditional chemotherapy to reduce side effects. An exciting aspect of PARP inhibitors is that they are also used to selectivity kill tumors with deficiencies in DNA repair proteins (e.g., BRCA1/2) through an approach termed “synthetic lethality.” In the midst of the tremendous efforts that have brought PARP inhibitors to the forefront of modern chemotherapy, most clinically used PARP inhibitors bind to conserved regions that permits cross-selectivity with other PARPs containing homologous catalytic domains. Thus, the differences between therapeutic effects and adverse effects stemming from pan-PARP inhibition compared to selective inhibition are not well understood. In this review, we discuss current literature that has found ways to gain selectivity for one PARP over another. We furthermore provide insights into targeting other domains that make up PARPs, and how new classes of drugs that target these domains could provide a high degree of selectivity by affecting specific cellular functions. A clear understanding of the inhibition profiles of PARP inhibitors will not only enhance our understanding of the biology of individual PARPs, but may provide improved therapeutic options for patients. PMID:24392349

  15. The perfidious effect of topical placebo: calibration of Staphylococcus aureus ventilator-associated pneumonia incidence within selective digestive decontamination studies versus the broader evidence base.

    PubMed

    Hurley, James C

    2013-09-01

    Among various methods for preventing ventilator-associated pneumonia (VAP), the evidence base for selective digestive decontamination (SDD) appears most compelling. However, the extent of Staphylococcus aureus emergence with SDD use remains uncertain. Groups from 37 observational studies and component (control and intervention) groups from 58 studies of SDD and other methods of VAP prevention were sourced exclusively from 10 systematic reviews. S. aureus as a proportion of VAP isolates (S. aureus isolate proportion [S. aureus IP]) among component groups was calibrated versus that among observational groups (the benchmark). The influence of topical placebo used for blinding purposes and other group-level factors was estimated using generalized estimating equation methods (GEE). The mean S. aureus IP is 22% (95% confidence interval [CI], 19 to 25) for 37 observational groups versus 32% (24 to 41) and 20% (15 to 25) for 22 control groups from the SDD evidence base which did versus did not receive topical placebo, respectively. In GEE models including all 148 observational and component groups, membership of a control (P = 0.03) or intervention (P < 0.001) group of an SDD study that used topical placebo was associated with higher S. aureus IP, whereas, in contrast, membership of these groups was without effect on Pseudomonas aeruginosa. Topical placebo is implicated as a vehicle for selective cross-infection with S. aureus within the specific context of the SDD evidence base. This effect of topical placebo is perfidious; it could contribute to the higher VAP incidence and inflate the apparent "effectiveness" of SDD. The SDD evidence base requires reappraisal. PMID:23836178

  16. A pilot study on the incidence of severe photosensitivity reactions leading to hospitalization linked to topical ketoprofen and other medications in selected European regions.

    PubMed

    Cazzaniga, Simone; Naldi, Luigi; Lecchi, Silvia; Kürzinger, Marie-Laure; Auclert, Laurent; Gori, Mario; Chosidow, Olivier; Hercogova, Jana

    2016-06-01

    The aim of this study was to assess the prevalence of exposure to topical nonsteroidal anti-inflammatory drugs (NSAIDs), particularly ketoprofen, in a convenience sample of the population, to obtain estimates of the incidence of severe photosensitivity leading to hospitalization, and to assess causative factors in three catchment areas: the Paris metropolitan area, the Lombardy region (Italy) and the Prague area. All cases of severe photosensitivity not explained by underlying conditions and admitted to hospitals in the selected areas were included in the study. Controls were patients consecutively admitted to hospitals, in the same areas, for an acute condition or for an elective procedure not suspected of being related to medication use. From October 2012 to September 2013, 920 controls were recruited (median age 44 years, 50.8% females); 8 severe photosensitivity cases were reported in the population aged 18-74 years of the 3 geographical areas during the 1-year surveillance period, corresponding to an incidence rate of 4.81 cases per 10 million person-years (95% confidence interval - CI, 2.07-9.48). Six controls reported 1-month exposure to topical ketoprofen, with an estimated prevalence of 0.65% (95% CI, 0.24-1.42). The population attributable risk for severe photosensitivity reactions linked to ketoprofen was 11.92% (95% CI, -0.12-52.99). This study was conducted in selected European areas and showed that the incidence of severe photosensitivity reactions leading to hospitalization as well as the exposure rate to topical ketoprofen were low. Among topical NSAIDs, topical ketoprofen was the leading cause of photosensitivity reactions but accounted for a limited number of hospitalized cases. Probably most of the relevant reactions were managed in the outpatient setting and a community based case-control study is advisable. PMID:27433339

  17. Selection of Cooperation in Spatially Structured Populations

    NASA Astrophysics Data System (ADS)

    Yang, Hyunmo; Ghim, Cheol-Min

    The social dilemma games give rise to an emergence of cooperation in which altruistic individuals survive the natural selection at higher rate than random chance. We try to extend our understanding of this spatial reciprocity by including the impact of degree-degree correlation on the propensity toward prosocial behaviour in an otherwise well-mixed population. In a stochastic death-birth process with weak selection, we find that the disassortative degree mixing, or negative correlation between the degrees of neighbouring nodes significantly promotes the fixation of cooperators whereas the assortative mixing acts to suppress it. This is consistent with the fact that the spatial heterogeneity weakens the average tendency of a population to cooperate, which we describe in a unified scheme of the effective isothermality in coarse-grained networks. We also discuss the individual-level incentives that indirectly foster restructuring the social networks toward the more cooperative topologies.

  18. Target Selection and Determination of Function in Structural Genomics

    PubMed Central

    Watson, James D.; Todd, Annabel E.; Bray, James; Laskowski, Roman A.; Edwards, Aled; Joachimiak, Andrzej; Orengo, Christine A.; Thornton, Janet M.

    2011-01-01

    Summary The first crucial step in any structural genomics project is the selection and prioritization of target proteins for structure determination. There may be a number of selection criteria to be satisfied, including that the proteins have novel folds, that they be representatives of large families for which no structure is known, and so on. The better the selection at this stage, the greater is the value of the structures obtained at the end of the experimental process. This value can be further enhanced once the protein structures have been solved if the functions of the given proteins can also be determined. Here we describe the methods used at either end of the experimental process: firstly, sensitive sequence comparison techniques for selecting a high-quality list of target proteins, and secondly the various computational methods that can be applied to the eventual 3D structures to determine the most likely biochemical function of the proteins in question. PMID:12880206

  19. Ciclopirox Topical

    MedlinePlus

    ... ciclopirox topical solution.Ciclopirox topical solution may catch fire. Do not use this medication near heat or ... have ever had any disease that affects your immune system, such as human immunodeficiency virus (HIV) or ...

  20. Testosterone Topical

    MedlinePlus

    ... in which the body does not produce enough natural testosterone). Testosterone is used only for men with ... topical may control your symptoms but will not cure your condition. Continue to use testosterone topical even ...

  1. Structures and Functions of Selective Attention.

    ERIC Educational Resources Information Center

    Posner, Michael I.

    While neuropsychology relates the neural structures damaged in traumatic brain injury with their cognitive functions in daily life, this report reviews evidence that elementary operations of cognition as defined by cognitive studies are the level at which the brain localizes its computations. Orienting of visual attention is used as a model task.…

  2. Preface to Special Topic: Invited Papers of the 3rd International Conference on Ultrafast Structural Dynamics

    PubMed Central

    Johnson, S. L.

    2016-01-01

    The ability to visualize the real-time dynamics of atomic, magnetic, and electronic structure is widely recognized in many fields as a key element underpinning many important processes in chemistry, materials science, and biology. The need for an improved understanding of such processes becomes acute as energy conversion processes on fast time scales become increasingly relevant to problems in science and technology. This special issue, containing invited papers from participants at the 3rd International Conference on Ultrafast Structural Dynamics held June 10–12, 2015 in Zurich, Switzerland, discusses several recent developments in this area. PMID:27191008

  3. Preface to Special Topic: Invited Papers of the 3rd International Conference on Ultrafast Structural Dynamics.

    PubMed

    Johnson, S L

    2016-03-01

    The ability to visualize the real-time dynamics of atomic, magnetic, and electronic structure is widely recognized in many fields as a key element underpinning many important processes in chemistry, materials science, and biology. The need for an improved understanding of such processes becomes acute as energy conversion processes on fast time scales become increasingly relevant to problems in science and technology. This special issue, containing invited papers from participants at the 3rd International Conference on Ultrafast Structural Dynamics held June 10-12, 2015 in Zurich, Switzerland, discusses several recent developments in this area. PMID:27191008

  4. Students Fail to Transfer Knowledge of Chromosome Structure to Topics Pertaining to Cell Division

    ERIC Educational Resources Information Center

    Newman, Dina L.; Catavero, Christina M.; Wright, L. Kate

    2012-01-01

    Cellular processes that rely on knowledge of molecular behavior are difficult for students to comprehend. For example, thorough understanding of meiosis requires students to integrate several complex concepts related to chromosome structure and function. Using a grounded theory approach, we have unified classroom observations, assessment data, and…

  5. Selection process for trade study: Graphite Composite Primary Structure (GCPS)

    NASA Technical Reports Server (NTRS)

    Greenberg, H. S.

    1994-01-01

    This TA 2 document describes the selection process that will be used to identify the most suitable structural configuration for an SSTO winged vehicle capable of delivering 25,000 lbs to a 220 nm circular orbit at 51.6 degree inclination. The most suitable unpressurized graphite composite structures and material selections is within this configuration and will be the prototype design for subsequent design and analysis and the basis for the design and fabrication of payload bay, wing, and thrust structure full scale test articles representing segments of the prototype structures. The selection process for this TA 2 trade study is the same as that for the TA 1 trade study. As the trade study progresses additional insight may result in modifications to the selection criteria within this process. Such modifications will result in an update of this document as appropriate.

  6. A Structured Interview for the Selection of Physician's Assistant Students.

    ERIC Educational Resources Information Center

    Niebuhr, Bruce R.; And Others

    To improve the reliability of selection interviews, the faculty of the University of Texas Medical Branch physician's assistant program developed a structured fourteen-category interview. The thirty-minute interview was used to select from 94 applicants; each applicant was interviewed three times and independently rated on a five-point scale of…

  7. TOPICAL REVIEW Elasto-capillarity: deforming an elastic structure with a liquid droplet

    NASA Astrophysics Data System (ADS)

    Roman, B.; Bico, J.

    2010-12-01

    Although negligible at macroscopic scales, capillary forces become dominant as the sub-millimetric scales of micro-electro-mechanical systems (MEMS) are considered. We review various situations, not limited to micro-technologies, where capillary forces are able to deform elastic structures. In particular, we define the different length scales that are relevant for 'elasto-capillary' problems. We focus on the case of slender structures (lamellae, rods and sheets) and describe the size of a bundle of wet hair, the condition for a flexible rod to pierce a liquid interface or the fate of a liquid droplet deposited on a flexible thin sheet. These results can be generalized to similar situations involving adhesion or fracture energy, which widens the scope of possible applications from biological systems, to stiction issues in micro-fabrication processes, the manufacturing of 3D microstructures or the formation of blisters in thin film coatings.

  8. Early Childhood Education: Organization of Reference Topics for Use in Undergraduate Courses. ERIC 1967-Spring 1973. (A Selective Listing).

    ERIC Educational Resources Information Center

    Wallat, Cynthia, Comp.

    This selective bibliography cites references pertaining to early childhood education from "Research in Education" (RIE) and "Current Index to Journals in Education" (CIJE). The bibliography is divided into three sections. The first two sections contain references from RIE and CIJE from spring 1967 through spring 1973; the last section updates the…

  9. TOPICAL REVIEW: Trends in the electronic structure of dilute nitride alloys

    NASA Astrophysics Data System (ADS)

    O'Reilly, E. P.; Lindsay, A.; Klar, P. J.; Polimeni, A.; Capizzi, M.

    2009-03-01

    The band-anticrossing (BAC) model has been widely applied to analyse the electronic structure of dilute nitride III-V-N alloys such as GaNxAs1-x. The BAC model describes the strong band gap bowing observed at low N composition in GaNxAs1-x in terms of an interaction between the GaAs host matrix conduction band edge and a higher lying band of localized N resonant states. In practice, replacing As by N introduces a range of N-related defect levels, associated with isolated N atoms, N-N pairs and larger clusters of N atoms. We show that the effect of such defect levels on the alloy conduction band structure is strongly dependent on the relative energy of the defect levels and the host conduction band edge. We first consider GaNxAs1-x, where we show that the unexpectedly large electron effective mass and gyromagnetic ratio, and their non-monotonic variation with x, are due to hybridization between the conduction band edge and specific nitrogen states close to the band edge. The N-related defect levels lie below the conduction band edge in GaNxP1-x. We must therefore explicitly treat the interaction between the higher lying GaP host Γ conduction band minimum and defect states associated with a random distribution of N atoms in order to obtain a good description of the lowest conduction states in disordered GaPN alloys. Turning to other alloys, N-related defect levels should generally lie well above the conduction band minimum in InNSb, with the band dispersion of InNSb then well described by a two-level BAC model. Both InP and InAs are intermediate between InSb and GaAs. By contrast, we calculate that N-related defect levels lie close to the conduction band minimum in GaNSb, and will therefore strongly perturb the lowest conduction states in this alloy. Overall, we conclude that the BAC model provides a good qualitative explanation of the electronic properties of dilute nitride alloys, but that it is in many cases necessary to include the details of the distribution of

  10. REVIEWS OF TOPICAL PROBLEMS: Supermolecular liquid-crystalline structures in solutions of amphiphilic molecules

    NASA Astrophysics Data System (ADS)

    Vedenov, A. A.; Levchenko, E. B.

    1983-09-01

    This paper reviews the physical properties of liquid-crystalline phases arising in solutions containing molecules of amphiphilic substances. The basic characteristics of micelle formation in dilute solutions, models of sphere-disk or sphere-cylinder structural transformations, as well as phase transitions related to the appearance of lyotropic mesophases in the system, including nematic, lamellar, hexagonal, and others, are examined. The results of experimental and theoretical investigation of "solvation" forces acting between micelles in the solvent, as well as recently studied models of swelling of lamellar phases are presented. The phenomena occurring near the inversion point of microemulsions in amphiphile-oil-water systems are examined briefly. The role of liquid-crystalline ordering in some biological systems is discussed.

  11. Selective reinforcement of wing structure for flutter prevention.

    NASA Technical Reports Server (NTRS)

    Cooper, P. A.; Stroud, W. J.

    1972-01-01

    The results of an analytical study are presented on the use of boron polyimide filamentary composite material for the purpose of increasing the flutter speed of a simple titanium full depth sandwich wing structure designed for strength. The results clearly demonstrate that selective reinforcement of wing surfaces, using judiciously placed filamentary composites, promises sizable mass savings in the design of advanced aircraft structures.

  12. Multi-Topic Tracking Model for dynamic social network

    NASA Astrophysics Data System (ADS)

    Li, Yuhua; Liu, Changzheng; Zhao, Ming; Li, Ruixuan; Xiao, Hailing; Wang, Kai; Zhang, Jun

    2016-07-01

    The topic tracking problem has attracted much attention in the last decades. However, existing approaches rarely consider network structures and textual topics together. In this paper, we propose a novel statistical model based on dynamic bayesian network, namely Multi-Topic Tracking Model for Dynamic Social Network (MTTD). It takes influence phenomenon, selection phenomenon, document generative process and the evolution of textual topics into account. Specifically, in our MTTD model, Gibbs Random Field is defined to model the influence of historical status of users in the network and the interdependency between them in order to consider the influence phenomenon. To address the selection phenomenon, a stochastic block model is used to model the link generation process based on the users' interests to topics. Probabilistic Latent Semantic Analysis (PLSA) is used to describe the document generative process according to the users' interests. Finally, the dependence on the historical topic status is also considered to ensure the continuity of the topic itself in topic evolution model. Expectation Maximization (EM) algorithm is utilized to estimate parameters in the proposed MTTD model. Empirical experiments on real datasets show that the MTTD model performs better than Popular Event Tracking (PET) and Dynamic Topic Model (DTM) in generalization performance, topic interpretability performance, topic content evolution and topic popularity evolution performance.

  13. Inferring Selection Intensity and Allele Age from Multilocus Haplotype Structure

    PubMed Central

    Chen, Hua; Slatkin, Montgomery

    2013-01-01

    It is a challenging task to infer selection intensity and allele age from population genetic data. Here we present a method that can efficiently estimate selection intensity and allele age from the multilocus haplotype structure in the vicinity of a segregating mutant under positive selection. We use a structured-coalescent approach to model the effect of directional selection on the gene genealogies of neutral markers linked to the selected mutant. The frequency trajectory of the selected allele follows the Wright-Fisher model. Given the position of the selected mutant, we propose a simplified multilocus haplotype model that can efficiently model the dynamics of the ancestral haplotypes under the joint influence of selection and recombination. This model approximates the ancestral genealogies of the sample, which reduces the number of states from an exponential function of the number of single-nucleotide polymorphism loci to a quadratic function. That allows parameter inference from data covering DNA regions as large as several hundred kilo-bases. Importance sampling algorithms are adopted to evaluate the probability of a sample by exploring the space of both allele frequency trajectories of the selected mutation and gene genealogies of the linked sites. We demonstrate by simulation that the method can accurately estimate selection intensity for moderate and strong positive selection. We apply the method to a data set of the G6PD gene in an African population and obtain an estimate of 0.0456 (95% confidence interval 0.0144−0.0769) for the selection intensity. The proposed method is novel in jointly modeling the multilocus haplotype pattern caused by recombination and mutation, allowing the analysis of haplotype data in recombining regions. Moreover, the method is applicable to data from populations under exponential growth and a variety of other demographic histories. PMID:23797107

  14. Selecting Earthquake Records for Nonlinear Dynamic Analysis of Structures

    SciTech Connect

    Rodriguez, Mario E.

    2008-07-08

    An area in earthquake risk reduction that needs an urgent examination is the selection of earthquake records for nonlinear dynamic analysis of structures. An often-mentioned shortcoming from results of nonlinear dynamic analyses of structures is that these results are limited to the type of records that these analyses use as input data. This paper proposes a procedure for selecting earthquake records for nonlinear dynamic analysis of structures. This procedure uses a seismic damage index evaluated using the hysteretic energy dissipated by a Single Degree of Freedom System (SDOF) representing a multi-degree-of freedom structure responding to an earthquake record, and the plastic work capacity of the system at collapse. The type of structural system is considered using simple parameters. The proposed method is based on the evaluation of the damage index for a suite of earthquake records and a selected type of structural system. A set of 10 strong ground motion records is analyzed to show an application of the proposed procedure for selecting earthquake records for structural design.

  15. TOPICAL REVIEW: Fabrication of micro- and nano-structured materials using mask-less processes

    NASA Astrophysics Data System (ADS)

    Roy, Sudipta

    2007-11-01

    Micro- and nano-scale devices are used in electronics, micro-electro- mechanical, bio-analytical and medical components. An essential step for the fabrication of such small scale devices is photolithography. Photolithography requires a master mask to transfer micrometre or sub-micrometre scale patterns onto a substrate. The requirement of a physical, rigid mask can impede progress in applications which require rapid prototyping, flexible substrates, multiple alignment and 3D fabrication. Alternative technologies, which do not require the use of a physical mask, are suitable for these applications. In this paper mask-less methods of micro- and nano-scale fabrication have been discussed. The most common technique, which is the laser direct imaging (LDI), technique has been applied to fabricate micrometre scale structures on printed circuit boards, glass and epoxy. LDI can be combined with chemical methods to deposit metals, inorganic materials as well as some organic entities at the micrometre scale. Inkjet technology can be used to fabricate micrometre patterns of etch resists, organic transistors as well as arrays for bioanalysis. Electrohydrodynamic atomisation is used to fabricate micrometre scale ceramic features. Electrochemical methodologies offer a variety of technical solutions for micro- and nano-fabrication owing to the fact that electron charge transfer can be constrained to a solid liquid interface. Electrochemical printing is an adaptation of inkjet printing which can be used for rapid prototyping of metallic circuits. Micro-machining using nano-second voltage pulses have been used to fabricate high precision features on metals and semiconductors. Optimisation of reactor, electrochemistry and fluid flow (EnFACE) has also been employed to transfer micrometre scale patterns on a copper substrate. Nano-scale features have been fabricated by using specialised tools such as scanning tunnelling microscopy, atomic force microscopy and focused ion beam. The

  16. Selected topics in point-of-care testing. Urinalysis, pregnancy testing, microbiology, fecal occult blood, and other tests.

    PubMed

    Lee-Lewandrowski, E; Lewandrowski, K

    2001-06-01

    The menu of tests available at the point of care continues to expand. Many of these tests present unique opportunities to deploy point-of-care technologies in the home, outpatient, and hospital settings. The future will inevitably create new applications for POCT. The success of these efforts will be in part determined by how technologies for specific applications are selected and by the ability to manage new point-of-care tests as part of an organizational point-of-care program. The possibilities to improve patient care are obvious, provided adequate attention is paid to ensuring quality testing and to managing patient data from these novel technologies. PMID:11396091

  17. Materials research at selected Japanese laboratories. Based on a 1992 visit: Overview, summary of highlights, notes on laboratories and topics

    SciTech Connect

    Not Available

    1994-02-01

    I visited Japan from June 29 to August 1, 1992. The purpose of this visit was to assess the status of materials science research at selected governmental, university and industrial laboratories and to established acquaintances with Japanese researchers. The areas of research covered by these visits included ceramics, oxide superconductors, intermetallics alloys, superhard materials and diamond films, high-temperature materials and properties, mechanical properties, fracture, creep, fatigue, defects, materials for nuclear reactor applications and irradiation effects, high pressure synthesis, self-propagating high temperature synthesis, microanalysis, magnetic properties and magnetic facilities, and surface science.

  18. Tracking topic birth and death in LDA.

    SciTech Connect

    Wilson, Andrew T.; Robinson, David Gerald

    2011-09-01

    Most topic modeling algorithms that address the evolution of documents over time use the same number of topics at all times. This obscures the common occurrence in the data where new subjects arise and old ones diminish or disappear entirely. We propose an algorithm to model the birth and death of topics within an LDA-like framework. The user selects an initial number of topics, after which new topics are created and retired without further supervision. Our approach also accommodates many of the acceleration and parallelization schemes developed in recent years for standard LDA. In recent years, topic modeling algorithms such as latent semantic analysis (LSA)[17], latent Dirichlet allocation (LDA)[10] and their descendants have offered a powerful way to explore and interrogate corpora far too large for any human to grasp without assistance. Using such algorithms we are able to search for similar documents, model and track the volume of topics over time, search for correlated topics or model them with a hierarchy. Most of these algorithms are intended for use with static corpora where the number of documents and the size of the vocabulary are known in advance. Moreover, almost all current topic modeling algorithms fix the number of topics as one of the input parameters and keep it fixed across the entire corpus. While this is appropriate for static corpora, it becomes a serious handicap when analyzing time-varying data sets where topics come and go as a matter of course. This is doubly true for online algorithms that may not have the option of revising earlier results in light of new data. To be sure, these algorithms will account for changing data one way or another, but without the ability to adapt to structural changes such as entirely new topics they may do so in counterintuitive ways.

  19. Seismic design technology for breeder reactor structures. Volume 2. Special topics in soil/structure interaction analyses

    SciTech Connect

    Reddy, D.P.

    1983-04-01

    This volume is divided into six chapters: definition of seismic input ground motion, review of state-of-the-art procedures, analysis guidelines, rock/structure interaction analysis example, comparison of two- and three-dimensional analyses, and comparison of analyses using FLUSH and TRI/SAC Codes. (DLC)

  20. Computational approaches to selecting and optimising targets for structural biology.

    PubMed

    Overton, Ian M; Barton, Geoffrey J

    2011-09-01

    Selection of protein targets for study is central to structural biology and may be influenced by numerous factors. A key aim is to maximise returns for effort invested by identifying proteins with the balance of biophysical properties that are conducive to success at all stages (e.g. solubility, crystallisation) in the route towards a high resolution structural model. Selected targets can be optimised through construct design (e.g. to minimise protein disorder), switching to a homologous protein, and selection of experimental methodology (e.g. choice of expression system) to prime for efficient progress through the structural proteomics pipeline. Here we discuss computational techniques in target selection and optimisation, with more detailed focus on tools developed within the Scottish Structural Proteomics Facility (SSPF); namely XANNpred, ParCrys, OB-Score (target selection) and TarO (target optimisation). TarO runs a large number of algorithms, searching for homologues and annotating the pool of possible alternative targets. This pool of putative homologues is presented in a ranked, tabulated format and results are also visualised as an automatically generated and annotated multiple sequence alignment. The target selection algorithms each predict the propensity of a selected protein target to progress through the experimental stages leading to diffracting crystals. This single predictor approach has advantages for target selection, when compared with an approach using two or more predictors that each predict for success at a single experimental stage. The tools described here helped SSPF achieve a high (21%) success rate in progressing cloned targets to diffraction-quality crystals. PMID:21906678

  1. Estradiol Topical

    MedlinePlus

    ... a medication that is applied topically to the vagina. Estradiol is in a class of medications called ... swelling, redness, burning, irritation, or itching of the vagina vaginal discharge Some side effects can be serious. ...

  2. Mometasone Topical

    MedlinePlus

    Mometasone comes as a topical cream, ointment, and lotion. It usually is applied externally once a day. ... affected skin areas once daily.To apply the lotion, place a few drops on the affected areas ...

  3. Fluorouracil Topical

    MedlinePlus

    ... caused by years of too much exposure to sunlight). Fluorouracil cream and topical solution are also used ... plan to avoid unnecessary or prolonged exposure to sunlight and UV light (such as tanning booths) and ...

  4. Bexarotene Topical

    MedlinePlus

    ... talking to your doctor.Bexarotene gel may catch fire. Do not use this medication near a source ... sunlamps and to wear protective clothing, sunglasses, and sunscreen. Topical bexarotene may make your skin sensitive to ...

  5. Fluorouracil Topical

    MedlinePlus

    ... topical solution are used to treat actinic or solar keratoses (scaly or crusted lesions [skin areas] caused ... you are using fluorouracil to treat actinic or solar keratoses, you should continue using it until the ...

  6. The Structure of Linkage Disequilibrium Around a Selective Sweep

    PubMed Central

    McVean, Gil

    2007-01-01

    The fixation of advantageous mutations by natural selection has a profound impact on patterns of linked neutral variation. While it has long been appreciated that such selective sweeps influence the frequency spectrum of nearby polymorphism, it has only recently become clear that they also have dramatic effects on local linkage disequilibrium. By extending previous results on the relationship between genealogical structure and linkage disequilibrium, I obtain simple expressions for the influence of a selective sweep on patterns of allelic association. I show that sweeps can increase, decrease, or even eliminate linkage disequilibrium (LD) entirely depending on the relative position of the selected and neutral loci. I also show the importance of the age of the neutral mutations in predicting their degree of association and describe the consequences of such results for the interpretation of empirical data. In particular, I demonstrate that while selective sweeps can eliminate LD, they generate patterns of genetic variation very different from those expected from recombination hotspots. PMID:17194788

  7. New Insight into Carbon Nanotube Electronic Structure Selectivity

    SciTech Connect

    Sumpter, Bobby G; Meunier, Vincent; Jiang, Deen

    2009-01-01

    The fundamental role of aryl diazonium salts for post synthesis selectivity of carbon nanotubes is investigated using extensive electronic structure calculations. The resulting understanding for diazonium salt based selective separation of conducting and semiconducting carbon nanotubes shows how the primary contributions come from the interplay between the intrinsic electronic structure of the carbon nanotubes and that of the anion of the salt. We demonstrate how the electronic transport properties change upon the formation of charge transfer complexes and upon their conversion into covalently attached functional groups. Our results are found to correlate well with experiments and provide for the first time an atomistic description for diazonium salt based chemical separation of carbon nanotubes

  8. Future high intensity ISOL facilities: Selected current R&D topics and possible synergies with other projects

    NASA Astrophysics Data System (ADS)

    Mueller, Alex C.

    2003-05-01

    The long-term future of ISOL facilities will be governed by the quest for ever increasing secondary beam intensities. One important aspect concerns a new generation of high-power driver accelerators which aim at multi-megawatt beam powers, used in a two-step production scheme for fission products. Within the EURISOL study, e.g. a 1 GeV, 5 mA proton has been investigated in some detail. It would be upgradeable in energy and also have, up to a certain extend, the capability for heavy-ion acceleration. The required R&D programme was assessed, and found to be in the mainstream of today's accelerator development which addresses also other projects like accelerator-driven transmutation of nuclear waste, neutrino beams, …. The concomitant development of high-power spallation targets and the secondary uranium targets is the second issue where a lot of R&D effort is done by several communities. Linked to this are also the studies in which photo-fission is used as a "low-cost" option for a dedicated region of the nuclear chart. The present paper will introduce in this general context, and discuss (selected) relevant new experimental results which are obtained in linac in particular.

  9. Structural features for functional selectivity at serotonin receptors.

    PubMed

    Wacker, Daniel; Wang, Chong; Katritch, Vsevolod; Han, Gye Won; Huang, Xi-Ping; Vardy, Eyal; McCorvy, John D; Jiang, Yi; Chu, Meihua; Siu, Fai Yiu; Liu, Wei; Xu, H Eric; Cherezov, Vadim; Roth, Bryan L; Stevens, Raymond C

    2013-05-01

    Drugs active at G protein-coupled receptors (GPCRs) can differentially modulate either canonical or noncanonical signaling pathways via a phenomenon known as functional selectivity or biased signaling. We report biochemical studies showing that the hallucinogen lysergic acid diethylamide, its precursor ergotamine (ERG), and related ergolines display strong functional selectivity for β-arrestin signaling at the 5-HT2B 5-hydroxytryptamine (5-HT) receptor, whereas they are relatively unbiased at the 5-HT1B receptor. To investigate the structural basis for biased signaling, we determined the crystal structure of the human 5-HT2B receptor bound to ERG and compared it with the 5-HT1B/ERG structure. Given the relatively poor understanding of GPCR structure and function to date, insight into different GPCR signaling pathways is important to better understand both adverse and favorable therapeutic activities. PMID:23519215

  10. LIFE Materials: Topical Assessment Report for LIFE Volume 1 TOPIC: Solid First Wall and Structural Components TASK: Radiation Effects on First Wall

    SciTech Connect

    Caro, A

    2008-11-26

    This report consists of the following chapters: CHAPTER A: LIFE Requirements for Materials. Part 1: The structure of the First Wall--Basic requirements; A qualitative view of the challenge; The candidate materials; and Base-line material's properties. CHAPTER B: Summary of Existing Knowledge--Brief historical introduction; Design window; The temperature window; Evolution of the design window with damage; Damage calculations; He and H production; Swelling resistance; Incubation dose for swelling; Design criterion No. 1, Strength; Design criterion No. 2, Corrosion resistance; Design criterion No. 3, Creep resistance; Design criterion No. 4, Radiation induced embrittlement; and Conclusions. CHAPTER C: Identification of Gaps in Knowledge & Vulnerabilities. CHAPTER D: Strategy and Future Work.

  11. The frequency selectivity of double H-shaped metallic structures

    NASA Astrophysics Data System (ADS)

    Bu, Xiaoxia; Zhao, Guozhong

    2013-12-01

    This paper presents the design and numerical simulation of the double H-shaped metallic periodic structure based on finite difference time domain (FDTD) method in terahertz frequency range. The double H-shaped structure unit cell consists of two H structures overlapped in the same plane. Numerical simulation results show that the double H-shaped structure results in a distinct and strong transmission trap in 0.2~3.0THz range. The position and the full wave at half maximum (FWHM) of transmission trap are changed with different structure size. The surface current distribution of structure is numerical simulated, which clarifies the frequency selection mechanism of the transmission spectra.

  12. Interest area selection for navigation based on structured edge detection

    NASA Astrophysics Data System (ADS)

    Sun, Xiao; Shang, Ke; Li, ShaoJun; Dou, Hao; Tian, JinWen; Ming, Delie

    2015-12-01

    The scene matching based navigation is an important precision navigation technology for unmanned aerial vehicles (UAV). Selection of interest area where reference image is made has an important influence on the precision of matching result besides the performance of match algorithm. In this paper, a method to select interest area based on structured edge detection is proposed. We use a data driven approach that classifies each pixel with a typical structured edge label. We propose a method that combines these labels into a feature measuring suitable to match of a region. Then a SVM classifier is trained to classify the features and get the final result of the selection of interest area. The experimental result shows that the proposed method is valid and effective.

  13. Spotlight Topics

    NASA Astrophysics Data System (ADS)

    A Spotlight Topic consists of a set of two or more review articles focused on a specific subject in surface science. The topics are recommended by the Board of Editors. A topic may be chosen because it is particularly new or fast-breaking, thus deserving introduction to the general readership. Or, it may be because a topic is especially controversial or confusing, requiring clarification by experts. Each review will give a critical assessment rather than an encyclopedic report. While our editors always will insist on fairness and accuracy, any review which forwards an opinion is bound to be somewhat subjective. Therefore, it is the editors' wish that the set of reviews written by different authors on the same subject matter will provide a broad and balanced viewpoint. It is often the case that an author who is an expert in a technique or method may be especially enthusiastic or critical about this technique or method. A companion review in the set may provide a different viewpoint. We are hopeful that the reader, after studying these reviews and checking some of the key references, will obtain an informed opinion of the subject. We think the set of reviews in a spotlight area will considerably shorten the ``learning time'' that a nonexpert would otherwise need to become knowledgeable about a subject. In this issue, we feature a spotlight topic on oxide surfaces. The set contains an overview article by Jacques Jupille, and four articles written by G. Pacchioni, F. Cosandey and T. E. Madey, B. G. Daniels, R. Lindsay and G. Thornton, and C. Noguera respectively. Of these, the article by Pacchioni has already appeared in SRL 7, 277 (2000). The other three articles appear in this issue. A reader who wishes to suggest a spotlight topic or recommend authors to write such reviews should contact the Editor-in-Chief. We would like to hear from you.

  14. Item Selection, Evaluation, and Simple Structure in Personality Data

    PubMed Central

    Pettersson, Erik; Turkheimer, Eric

    2010-01-01

    We report an investigation of the genesis and interpretation of simple structure in personality data using two very different self-reported data sets. The first consists of a set of relatively unselected lexical descriptors, whereas the second is based on responses to a carefully constructed instrument. In both data sets, we explore the degree of simple structure by comparing factor solutions to solutions from simulated data constructed to have either strong or weak simple structure. The analysis demonstrates that there is little evidence of simple structure in the unselected items, and a moderate degree among the selected items. In both instruments, however, much of the simple structure that could be observed originated in a strong dimension of positive vs. negative evaluation. PMID:20694168

  15. Instant fabrication and selection of folded structures using drop impact

    PubMed Central

    Antkowiak, Arnaud; Audoly, Basile; Josserand, Christophe; Neukirch, Sébastien; Rivetti, Marco

    2011-01-01

    A drop impacting a target cutout in a thin polymer film is wrapped by the film in a dynamic sequence involving both capillary forces and inertia. Different 3D structures can be produced from a given target by slightly varying the impact parameters. A simplified model for a nonlinear dynamic Elastica coupled with a drop successfully explains this shape selection and yields detailed quantitative agreement with experiments. This first venture into the largely unexplored dynamics of elastocapillary assemblies opens up the perspective of mass production of 3D packages with individual shape selection. PMID:21670249

  16. Select topics in neurocritical care.

    PubMed

    Noto, Anthony; Marcolini, Evie

    2014-11-01

    Neurocritical care aims to improve outcomes in patients with life-threatening neurologic illness. The scope of neurocritical care extends beyond the more commonly encountered and important field of cerebrovascular disease, as described previously. This article focuses on neuromuscular, neuroinfectious, and neuroimmunologic conditions that are significant causes of morbidity and mortality in the acutely neurologically ill patient. As understanding continues to increase regarding the physiology of these conditions and the best treatment, rapid identification, triage, and treatment of these patients in the emergency department is paramount. PMID:25441043

  17. Selected topics in nuclear astrophysics

    SciTech Connect

    Martinez-Pinedo, Gabriel

    2013-06-10

    In this lectures after a brief introduction to stellar reaction rates and its implementation in nuclear networks, I discuss the nuclear physics aspects of core collapse supernova and explosive nucleosynthesis and their significance for the production of heavy elements by the rapid neutron capture process and potentially also by the recently discovered {nu}p process.

  18. Structural basis for selective activation of ABA receptors

    SciTech Connect

    Peterson, Francis C.; Burgie, E. Sethe; Park, Sang-Youl; Jensen, Davin R.; Weiner, Joshua J.; Bingman, Craig A.; Chang, Chia-En A.; Cutler, Sean R.; Phillips, Jr., George N.; Volkman, Brian F.

    2010-11-01

    Changing environmental conditions and lessening fresh water supplies have sparked intense interest in understanding and manipulating abscisic acid (ABA) signaling, which controls adaptive responses to drought and other abiotic stressors. We recently discovered a selective ABA agonist, pyrabactin, and used it to discover its primary target PYR1, the founding member of the PYR/PYL family of soluble ABA receptors. To understand pyrabactin's selectivity, we have taken a combined structural, chemical and genetic approach. We show that subtle differences between receptor binding pockets control ligand orientation between productive and nonproductive modes. Nonproductive binding occurs without gate closure and prevents receptor activation. Observations in solution show that these orientations are in rapid equilibrium that can be shifted by mutations to control maximal agonist activity. Our results provide a robust framework for the design of new agonists and reveal a new mechanism for agonist selectivity.

  19. Selection of active member locations in adaptive structures

    NASA Technical Reports Server (NTRS)

    Chen, G.-S.; Bruno, R.; Salama, M.

    1989-01-01

    The effective use of multiple passive and active members in adaptive structures necessitates that these members be optimally distributed throughout the structure. In truss structures, the problem falls into the class of combinatorial optimization for which the solution becomes exceedingly intractable as the problem size increases. This is overcome by using the simulated annealing algorithm to obtain near optimal locations for passive and/or active members. The maximization of the rate of energy dissipation over a finite time period as the measure of optimality is adopted. The selection of optimal locations for both passive and active members is consistently treated through the use of the energy dissipation rate criterion within the simulated annealing algorithm. Numerical examples are used to illustrate the effectiveness of the methodology for large truss structures.

  20. Performance of structured lipids incorporating selected phenolic and ascorbic acids.

    PubMed

    Gruczynska, Eliza; Przybylski, Roman; Aladedunye, Felix

    2015-04-15

    Conditions applied during frying require antioxidant which is stable at these conditions and provides protection for frying oil and fried food. Novel structured lipids containing nutraceuticals and antioxidants were formed by enzymatic transesterification, exploring canola oil and naturally occurring antioxidants such as ascorbic and selected phenolic acids as substrates. Lipozyme RM IM lipase from Rhizomucor miehei was used as biocatalyst. Frying performance and oxidative stability of the final transesterification products were evaluated. The novel lipids showed significantly improved frying performance compared to canola oil. Oxidative stability assessment of the structured lipids showed significant improvement in resistance to oxidative deterioration compared to original canola oil. Interestingly, the presence of ascorbic acid in an acylglycerol structure protected α-tocopherol against thermal degradation, which was not observed for the phenolic acids. Developed structured lipids containing nutraceuticals and antioxidants may directly affect nutritional properties of lipids also offering nutraceutical ingredients for food formulation. PMID:25466089

  1. Generating Topic Headings during Reading of Screen-Based Text Facilitates Learning of Structural Knowledge and Impairs Learning of Lower-Level Knowledge

    ERIC Educational Resources Information Center

    Clariana, Roy B.; Marker, Anthony W.

    2007-01-01

    This investigation considers the effects of learner-generated headings on memory. Participants (N = 63) completed a computer-based lesson with or without learner-generated text topic headings. Posttests included a cued recall test of factual knowledge and a sorting task measure of structural knowledge. A significant disordinal interaction was…

  2. Evaluation of hydroxyimine as cytochrome P450-selective prodrug structure.

    PubMed

    Kumpulainen, Hanna; Mähönen, Niina; Laitinen, Marja-Leena; Jaurakkajärvi, Marja; Raunio, Hannu; Juvonen, Risto O; Vepsäläinen, Jouko; Järvinen, Tomi; Rautio, Jarkko

    2006-02-01

    Hydroxyimine derivatives of ketoprofen (1) and nabumetone (2) were synthesized and evaluated in vitro and in vivo as cytochrome P450-selective intermediate prodrug structures of ketones. 2 released nabumetone in vitro in the presence of isolated rat and human liver microsomes and in different recombinant human CYP isoforms. Bioconversion of 2 to both nabumetone and its active metabolite, 6-methoxy-2-naphthylacetic acid (6-MNA), was further confirmed in rats in vivo. Results indicate that hydroxyimine is a useful intermediate prodrug structure for ketone drugs. PMID:16451086

  3. Wireless structural sensor made with frequency selective surface antenna

    NASA Astrophysics Data System (ADS)

    Jang, Sang-Dong; Kim, Jaehwan

    2012-04-01

    Nondestructive Structural health monitoring (SHM) system using wireless sensor network is the one of important issue for aerospace and civil engineering. Chipless passive wireless sensor system is one of novel methods for SHM which uses the electromagnetic wave characteristic change by geometrical change of electromagnetic resonators or impedance change of functional material sensing part without RFID chip. In this paper, the chipless passive wireless SHM sensor using frequency selective surface (FSS) is investigated. Electromagnetic characteristic change of FSS by mechanical strain or structural damage is investigated by simulation and experiment.

  4. ASH structure alignment package: Sensitivity and selectivity in domain classification

    PubMed Central

    Standley, Daron M; Toh, Hiroyuki; Nakamura, Haruki

    2007-01-01

    Background Structure alignment methods offer the possibility of measuring distant evolutionary relationships between proteins that are not visible by sequence-based analysis. However, the question of how structural differences and similarities ought to be quantified in this regard remains open. In this study we construct a training set of sequence-unique CATH and SCOP domains, from which we develop a scoring function that can reliably identify domains with the same CATH topology and SCOP fold classification. The score is implemented in the ASH structure alignment package, for which the source code and a web service are freely available from the PDBj website . Results The new ASH score shows increased selectivity and sensitivity compared with values reported for several popular programs using the same test set of 4,298,905 structure pairs, yielding an area of .96 under the receiver operating characteristic (ROC) curve. In addition, weak sequence homologies between similar domains are revealed that could not be detected by BLAST sequence alignment. Also, a subset of domain pairs is identified that exhibit high similarity, even though their CATH and SCOP classification differs. Finally, we show that the ranking of alignment programs based solely on geometric measures depends on the choice of the quality measure. Conclusion ASH shows high selectivity and sensitivity with regard to domain classification, an important step in defining distantly related protein sequence families. Moreover, the CPU cost per alignment is competitive with the fastest programs, making ASH a practical option for large-scale structure classification studies. PMID:17407606

  5. Topical anesthesia.

    PubMed

    Kumar, Mritunjay; Chawla, Rajiv; Goyal, Manish

    2015-01-01

    Topical anesthetics are being widely used in numerous medical and surgical sub-specialties such as anesthesia, ophthalmology, otorhinolaryngology, dentistry, urology, and aesthetic surgery. They cause superficial loss of pain sensation after direct application. Their delivery and effectiveness can be enhanced by using free bases; by increasing the drug concentration, lowering the melting point; by using physical and chemical permeation enhancers and lipid delivery vesicles. Various topical anesthetic agents available for use are eutectic mixture of local anesthetics, ELA-max, lidocaine, epinephrine, tetracaine, bupivanor, 4% tetracaine, benzocaine, proparacaine, Betacaine-LA, topicaine, lidoderm, S-caine patch™ and local anesthetic peel. While using them, careful attention must be paid to their pharmacology, area and duration of application, age and weight of the patients and possible side-effects. PMID:26702198

  6. Topical anesthesia

    PubMed Central

    Kumar, Mritunjay; Chawla, Rajiv; Goyal, Manish

    2015-01-01

    Topical anesthetics are being widely used in numerous medical and surgical sub-specialties such as anesthesia, ophthalmology, otorhinolaryngology, dentistry, urology, and aesthetic surgery. They cause superficial loss of pain sensation after direct application. Their delivery and effectiveness can be enhanced by using free bases; by increasing the drug concentration, lowering the melting point; by using physical and chemical permeation enhancers and lipid delivery vesicles. Various topical anesthetic agents available for use are eutectic mixture of local anesthetics, ELA-max, lidocaine, epinephrine, tetracaine, bupivanor, 4% tetracaine, benzocaine, proparacaine, Betacaine-LA, topicaine, lidoderm, S-caine patch™ and local anesthetic peel. While using them, careful attention must be paid to their pharmacology, area and duration of application, age and weight of the patients and possible side-effects. PMID:26702198

  7. Structural foundations of optogenetics: Determinants of channelrhodopsin ion selectivity.

    PubMed

    Berndt, Andre; Lee, Soo Yeun; Wietek, Jonas; Ramakrishnan, Charu; Steinberg, Elizabeth E; Rashid, Asim J; Kim, Hoseok; Park, Sungmo; Santoro, Adam; Frankland, Paul W; Iyer, Shrivats M; Pak, Sally; Ährlund-Richter, Sofie; Delp, Scott L; Malenka, Robert C; Josselyn, Sheena A; Carlén, Marie; Hegemann, Peter; Deisseroth, Karl

    2016-01-26

    The structure-guided design of chloride-conducting channelrhodopsins has illuminated mechanisms underlying ion selectivity of this remarkable family of light-activated ion channels. The first generation of chloride-conducting channelrhodopsins, guided in part by development of a structure-informed electrostatic model for pore selectivity, included both the introduction of amino acids with positively charged side chains into the ion conduction pathway and the removal of residues hypothesized to support negatively charged binding sites for cations. Engineered channels indeed became chloride selective, reversing near -65 mV and enabling a new kind of optogenetic inhibition; however, these first-generation chloride-conducting channels displayed small photocurrents and were not tested for optogenetic inhibition of behavior. Here we report the validation and further development of the channelrhodopsin pore model via crystal structure-guided engineering of next-generation light-activated chloride channels (iC++) and a bistable variant (SwiChR++) with net photocurrents increased more than 15-fold under physiological conditions, reversal potential further decreased by another ∼ 15 mV, inhibition of spiking faithfully tracking chloride gradients and intrinsic cell properties, strong expression in vivo, and the initial microbial opsin channel-inhibitor-based control of freely moving behavior. We further show that inhibition by light-gated chloride channels is mediated mainly by shunting effects, which exert optogenetic control much more efficiently than the hyperpolarization induced by light-activated chloride pumps. The design and functional features of these next-generation chloride-conducting channelrhodopsins provide both chronic and acute timescale tools for reversible optogenetic inhibition, confirm fundamental predictions of the ion selectivity model, and further elucidate electrostatic and steric structure-function relationships of the light-gated pore. PMID

  8. Topical Research: Africa.

    ERIC Educational Resources Information Center

    Lynn, Karen

    This lesson plan can be used in social studies, language arts, or library research. The instructional objective is for students to select a topic of study relating to Africa, write a thesis statement, collect information from media sources, and develop a conclusion. The teacher may assign the lesson for written or oral evaluation. The teacher…

  9. Inexpensive Method for Selecting Receptor Structures for Virtual Screening.

    PubMed

    Huang, Zunnan; Wong, Chung F

    2016-01-25

    This article introduces a screening performance index (SPI) to help select from a number of experimental structures one or a few that are more likely to identify more actives among its top hits from virtual screening of a compound library. It achieved this by docking only known actives to the experimental structures without considering a large number of decoys to reduce computational costs. The SPI is calculated by using the docking energies of the actives to all the receptor structures. We evaluated the performance of the SPI by applying it to study eight protein systems: fatty acid binding protein adipocyte FABP4, serine/threonine-protein kinase BRAF, beta-1 adrenergic receptor ADRB1, TGF-beta receptor type I TGFR1, adenosylhomocysteinase SAHH, thyroid hormone receptor beta-1 THB, phospholipase A2 group IIA PA2GA, and cytochrome P450 3a4 CP3A4. We found that the SPI agreed with the results from other popular performance metrics such as Boltzmann-Enhanced Discrimination Receiver Operator Characteristics (BEDROC), Robust Initial Enhancement (RIE), Area Under Accumulation Curve (AUAC), and Enrichment Factor (EF) but is less expensive to calculate. SPI also performed better than the best docking energy, the molecular volume of the bound ligand, and the resolution of crystal structure in selecting good receptor structures for virtual screening. The implications of these findings were further discussed in the context of ensemble docking, in situations when no experimental structure for the targeted protein was available, or under circumstances when quick choices of receptor structures need to be made before quantitative indexes such as the SPI and BEDROC can be calculated. PMID:26651874

  10. Structural foundations of optogenetics: Determinants of channelrhodopsin ion selectivity

    PubMed Central

    Berndt, Andre; Lee, Soo Yeun; Wietek, Jonas; Ramakrishnan, Charu; Steinberg, Elizabeth E.; Rashid, Asim J.; Kim, Hoseok; Park, Sungmo; Santoro, Adam; Frankland, Paul W.; Iyer, Shrivats M.; Pak, Sally; Ährlund-Richter, Sofie; Delp, Scott L.; Malenka, Robert C.; Josselyn, Sheena A.; Carlén, Marie; Hegemann, Peter; Deisseroth, Karl

    2016-01-01

    The structure-guided design of chloride-conducting channelrhodopsins has illuminated mechanisms underlying ion selectivity of this remarkable family of light-activated ion channels. The first generation of chloride-conducting channelrhodopsins, guided in part by development of a structure-informed electrostatic model for pore selectivity, included both the introduction of amino acids with positively charged side chains into the ion conduction pathway and the removal of residues hypothesized to support negatively charged binding sites for cations. Engineered channels indeed became chloride selective, reversing near −65 mV and enabling a new kind of optogenetic inhibition; however, these first-generation chloride-conducting channels displayed small photocurrents and were not tested for optogenetic inhibition of behavior. Here we report the validation and further development of the channelrhodopsin pore model via crystal structure-guided engineering of next-generation light-activated chloride channels (iC++) and a bistable variant (SwiChR++) with net photocurrents increased more than 15-fold under physiological conditions, reversal potential further decreased by another ∼15 mV, inhibition of spiking faithfully tracking chloride gradients and intrinsic cell properties, strong expression in vivo, and the initial microbial opsin channel-inhibitor–based control of freely moving behavior. We further show that inhibition by light-gated chloride channels is mediated mainly by shunting effects, which exert optogenetic control much more efficiently than the hyperpolarization induced by light-activated chloride pumps. The design and functional features of these next-generation chloride-conducting channelrhodopsins provide both chronic and acute timescale tools for reversible optogenetic inhibition, confirm fundamental predictions of the ion selectivity model, and further elucidate electrostatic and steric structure–function relationships of the light-gated pore. PMID

  11. Topical Steroids.

    PubMed

    Oakley, Gretchen M; Harvey, Richard J

    2016-01-01

    Chronic rhinosinusitis with nasal polyps (CRSwNP) is an inflammatory condition with heterogeneous pathophysiology. A cornerstone of the management of this condition is the use of anti-inflammatory agents. Corticosteroids are very effective and the most commonly used, but other drugs with immunodulatory activity such as anti-IL5, doxycycline (Th2), and macrolides (anti-neutrophilic/IL8) have been shown to have efficacy. Although systemic corticosteroids have shown benefit in managing this condition, the frequency of use often required in this condition is associated with significant adverse effects. Topical corticosteroids, particularly when utilized after endoscopic sinus surgery and delivered in a high volume, high pressure manner, provide the desired anti-inflammatory effects with nearly negligible systemic absorption. Studies assessing the long-term use of second generation topical corticosteroids have demonstrated no significant effects on cortisol levels, growth rate, intraocular pressures or lens opacification, or local mucosal atrophy. Patients who often respond most favorably to corticosteroid treatment are those with a Th2-mediated, highly eosinophilic CRSwNP. However, there is a subset of patients who are steroid resistant. In the case of a predominantly neutrophilic CRSwNP, it is important to be aware that patients may respond well to the use of macrolide therapy. Additionally, the use of verapamil has shown promise in increasing steroid responsiveness in a difficult to treat group of patients with steroid resistance. Topical corticosteroids play a key role in the long term management of this complicated inflammatory condition by providing the much needed pharmacologic local control with minimal systemic adverse effects. PMID:27466854

  12. Composite Payload Fairing Structural Architecture Assessment and Selection

    NASA Technical Reports Server (NTRS)

    Krivanek, Thomas M.; Yount, Bryan C.

    2012-01-01

    This paper provides a summary of the structural architecture assessments conducted and a recommendation for an affordable high performance composite structural concept to use on the next generation heavy-lift launch vehicle, the Space Launch System (SLS). The Structural Concepts Element of the Advanced Composites Technology (ACT) project and its follow on the Lightweight Spacecraft Structures and Materials (LSSM) project was tasked with evaluating a number of composite construction technologies for specific Ares V components: the Payload Shroud, the Interstage, and the Core Stage Intertank. Team studies strived to address the structural challenges, risks and needs for each of these vehicle components. Leveraging off of this work, the subsequent Composites for Exploration (CoEx) effort is focused on providing a composite structural concept to support the Payload Fairing for SLS. This paper documents the evaluation and down selection of composite construction technologies and evolution to the SLS Payload Fairing. Development of the evaluation criteria (also referred to as Figures of Merit or FOMs), their relative importance, and association to vehicle requirements are presented. A summary of the evaluation results, and a recommendation of the composite concept to baseline in the Composites for Exploration (CoEx) project is presented. The recommendation for the SLS Fairing is a Honeycomb Sandwich architecture based primarily on affordability and performance with two promising alternatives, Hat stiffened and Fiber Reinforced Foam (FRF) identified for eventual program block upgrade.

  13. In vitro spectrum of pexiganan activity; bactericidal action and resistance selection tested against pathogens with elevated MIC values to topical agents.

    PubMed

    Flamm, Robert K; Rhomberg, Paul R; Farrell, David J; Jones, Ronald N

    2016-09-01

    Pexiganan, in Phase 3 clinical development for topical use, exhibited bactericidal activity in vitro against Gram-positive and -negative isolates and was also shown to have a low potential for resistance development in broth serial passage experiments. Susceptibility studies were performed against bacterial isolates (110 total from 2004 to 2013; primarily from skin and soft tissue infections) selected for elevated MIC values (non-wildtype [WT] distributions) to bacitracin, polymyxin B, neomycin, mupirocin, retapamulin, fusidic acid, or gentamicin. A narrow range of pexiganan MIC values (4-32 μg/mL) against Staphylococcus aureus was observed (MIC50 and MIC90 values, 16 μg/mL) with a pexiganan mode and MIC50 value for the subsets of isolates with non-WT MIC values to bacitracin and neomycin (n = 14), fusidic acid (n = 11), mupirocin (n = 12) and retapamulin (n = 11) at 16 μg/mL. For coagulase-negative staphylococci (CoNS), the pexiganan mode and MIC50 values were 4 μg/mL. The pexiganan mode and MIC50 for each non-WT CoNS subset was also 4 μg/mL. Pexiganan MIC values for Enterococcus faecium was 8 μg/mL, but E. faecalis isolates exhibited MIC values that ranged from 128-256 μg/mL. Pexiganan was active against β-hemolytic streptococci including non-WT subsets (MIC range, 4-64 μg/mL). MIC values for pexiganan varied by species for viridans group streptococci, with highest values occurring for Streptococcus oralis. The broad bactericidal spectrum of pexiganan activity and low potential for resistance selection offers the possibility that this experimental agent may be able to play an important role in the current environment of emerging multi-drug resistant pathogens. PMID:27352729

  14. Optimization of aerospace structures

    NASA Technical Reports Server (NTRS)

    Keith, Theo G., Jr.; Patnaik, Surya N.

    1994-01-01

    Research carried out is grouped under two topics: (1) Design Optimization, and (2) Integrated Force Method of Analysis. Design Optimization Research Topics are singularity alleviation enhances structural optimization methods, computer based design capability extended through substructure synthesis, and optimality criteria provides optimum design for a select class of structural problems. Integrated Force Method of Analysis Research Topics are boundary compatibility formulation improves stress analysis of shell structures. Brief descriptions of the four topics are appended.

  15. Structural principles of nucleoside selectivity in a 2'-deoxyguanosine riboswitch.

    PubMed

    Pikovskaya, Olga; Polonskaia, Anna; Patel, Dinshaw J; Serganov, Alexander

    2011-10-01

    Purine riboswitches have an essential role in genetic regulation of bacterial metabolism. This family includes the 2'-deoxyguanosine (dG) riboswitch, which is involved in feedback control of deoxyguanosine biosynthesis. To understand the principles that define dG selectivity, we determined crystal structures of the natural Mesoplasma florum riboswitch bound to cognate dG as well as to noncognate guanosine, deoxyguanosine monophosphate and guanosine monophosphate. Comparison with related purine riboswitch structures reveals that the dG riboswitch achieves its specificity through modification of key interactions involving the nucleobase and rearrangement of the ligand-binding pocket to accommodate the additional sugar moiety. In addition, we observe new conformational changes beyond the junctional binding pocket extending as far as peripheral loop-loop interactions. It appears that re-engineering riboswitch scaffolds will require consideration of selectivity features dispersed throughout the riboswitch tertiary fold, and structure-guided drug design efforts targeted to junctional RNA scaffolds need to be addressed within such an expanded framework. PMID:21841796

  16. Cre recombinase expression or topical tamoxifen treatment do not affect retinal structure and function, neuronal vulnerability or glial reactivity in the mouse eye.

    PubMed

    Boneva, S K; Groß, T R; Schlecht, A; Schmitt, S I; Sippl, C; Jägle, H; Volz, C; Neueder, A; Tamm, E R; Braunger, B M

    2016-06-14

    Mice with a constitutive or tamoxifen-induced Cre recombinase (Cre) expression are frequently used research tools to allow the conditional deletion of target genes via the Cre-loxP system. Here we analyzed for the first time in a comprehensive and comparative way, whether retinal Cre expression or topical tamoxifen treatment itself would cause structural or functional changes, including changes in the expression profiles of molecular markers, glial reactivity and photoreceptor vulnerability. To this end, we characterized the transgenic α-Cre, Lmop-Cre and the tamoxifen-inducible CAGG-CreER™ mouse lines, all having robust Cre expression in the neuronal retina. In addition, we characterized the effects of topical tamoxifen treatment itself in wildtype mice. We performed morphometric analyses, immunohistochemical staining, in vivo ERG and angiography analyses and realtime RT-PCR analyses. Furthermore, the influence of Cre recombinase or topical tamoxifen exposure on neuronal vulnerability was studied by using light damage as a model for photoreceptor degeneration. Taken together, neither the expression of Cre, nor topical tamoxifen treatment caused detectable changes in retinal structure and function, the expression profiles of investigated molecular markers, glial reactivity and photoreceptor vulnerability. We conclude that the Cre-loxP system and its induction through tamoxifen is a safe and reliable method to delete desired target genes in the neural retina. PMID:27026593

  17. Identifying Computer-Supported Collaborative Learning (CSCL) Research in Selected Journals Published from 2003 to 2012: A Content Analysis of Research Topics and Issues

    ERIC Educational Resources Information Center

    Zheng, Lanqin; Huang, Ronghuai; Yu, Junhui

    2014-01-01

    This study aims to identity the emerging research trends in the field of computed-supported collaborative learning (CSCL) so as to provide insights for researchers and educators into research topics and issues for further exploration. This paper analyzed the research topics, methods and technology adoption of CSCL from 2003 to 2012. A total of 706…

  18. Transmission properties of frequency selective structures with air gaps

    NASA Astrophysics Data System (ADS)

    Meng, Zhi-Jun; Wang, Li-Feng; Lü, Ming-Yun; Wu, Zhe

    2010-12-01

    The transmission properties of compound frequency selective structures with dielectric slab and air gaps were investigated by computation and experimentation. Mechanism analyses were also carried out. Results show that the air gaps have a distinct influence on the transmission properties. Resonant frequency of the structure would increase rapidly when the air gap appears. After the gap gets larger to a specific value, generally 1/5 wavelength corresponding to the resonant frequency, the transmission properties would change periodically with the gap thickness. The change of transmission properties in one period has a close relationship with the dielectric thickness. These results provide a new method for designing a bandpass radome of large incidence angle and low loss with the concept of stealth shield radome.

  19. Structural adaptations to diverse fighting styles in sexually selected weapons

    PubMed Central

    McCullough, Erin L.; Tobalske, Bret W.; Emlen, Douglas J.

    2014-01-01

    The shapes of sexually selected weapons differ widely among species, but the drivers of this diversity remain poorly understood. Existing explanations suggest weapon shapes reflect structural adaptations to different fighting styles, yet explicit tests of this hypothesis are lacking. We constructed finite element models of the horns of different rhinoceros beetle species to test whether functional specializations for increased performance under species-specific fighting styles could have contributed to the diversification of weapon form. We find that horns are both stronger and stiffer in response to species-typical fighting loads and that they perform more poorly under atypical fighting loads, which suggests weapons are structurally adapted to meet the functional demands of fighting. Our research establishes a critical link between weapon form and function, revealing one way male–male competition can drive the diversification of animal weapons. PMID:25201949

  20. Structural basis for selective inhibition of purine nucleoside phosphorylase from Schistosoma mansoni: kinetic and structural studies.

    PubMed

    Castilho, Marcelo S; Postigo, Matheus P; Pereira, Humberto M; Oliva, Glaucius; Andricopulo, Adriano D

    2010-02-15

    Selectivity plays a crucial role in the design of enzyme inhibitors as novel antiparasitic agents, particularly in cases where the target enzyme is also present in the human host. Purine nucleoside phosphorylase from Schistosoma mansoni (SmPNP) is an attractive target for the discovery of potential antischistosomal agents. In the present work, kinetic studies were carried out in order to determine the inhibitory potency, mode of action and enzyme selectivity of a series of inhibitors of SmPNP. In addition, crystallographic studies provided important structural insights for rational inhibitor design, revealing consistent structural differences in the binding mode of the inhibitors in the active sites of the SmPNP and human PNP (HsPNP) structures. The molecular information gathered in this work should be useful for future medicinal chemistry efforts in the design of new inhibitors of SmPNP having increased affinity and selectivity. PMID:20129792

  1. Composite Interstage Structural Concept Down Select Process and Results

    NASA Technical Reports Server (NTRS)

    Sleight, David W.; Kosareo, Daniel N.; Thoma, Scott D.

    2012-01-01

    NASA's Advanced Composites Technologies (ACT) project evaluated several composite construction options for the Ares V Interstage to support the Constellation Program's goal of reducing the mass of vehicle dry structures. In Phase 1 of the project, eight candidate construction concepts were evaluated for the Ares V Interstage design. Trade studies were performed using finite element analyses to determine weight estimates for the construction concepts. An evaluation process was then used to down select the construction concepts down to two concepts for further consideration in Phase 2 of the project. In Phase 2 of the project, additional trade studies were performed using detailed finite element analyses of the Interstage and a final down select process was used to choose the recommended Interstage construction concept. The results of the study showed that a honeycomb sandwich design was the most favorable Interstage construction concept based on advantages in manufacturing cost. Details of the Phase 1 and Phase 2 trade studies and down select process with final results are presented in the paper.

  2. TOPICAL REVIEW: Highly charged ions

    NASA Astrophysics Data System (ADS)

    Gillaspy, J. D.

    2001-10-01

    This paper reviews some of the fundamental properties of highly charged ions, the methods of producing them (with particular emphasis on table-top devices), and their use as a tool for both basic science and applied technology. Topics discussed include: charge dependence and scaling laws along isoelectronic or isonuclear sequences (for wavefunction size or Bohr radius, ionization energy, dipole transition energy, relativistic fine structure, hyperfine structure, Zeeman effect, Stark effect, line intensities, linewidths, strength of parity violation, etc), changes in angular momentum coupling schemes, selection rules, interactions with surfaces, electron-impact ionization, the electron beam ion trap (EBIT), ion accelerators, atomic reference data, cosmic chronometers, laboratory x-ray astrophysics, vacuum polarization, solar flares, ion implantation, ion lithography, ion microprobes (SIMS and x-ray microscope), nuclear fusion diagnostics, nanotechnology, quantum computing, cancer therapy and biotechnology.

  3. [Topical contraceptives].

    PubMed

    Alipov, V I; Korkhov, V V

    1982-02-01

    Recently there has been little interest in topical contraceptives. The most popular are the cervical cap and the diaphragm. Other types of mechanical contraceptive devices are being investigated. Standley and Kessler have developed a device for introduction into the cervical canal with a reservoir of spermatocide, it does not block the flow of blood during menstruation. New models of vaginal rings are also being developed which are simple enough for self-insertion and also contain a reservoir of spermatocide. Work is being done on spermatocide-containing sponges in many countries. Another project being investigated is the possibility of using natural proteins, collagens, and other substances which absorb spermatozoids. The ancients used various vaginal suppositories to kill spermatozoids; in the late 19th century quinine sulfate was used for this, and a variety of substances have been used recently. These spermicidal creams also have the advantage of acting as anti-infectious agents in many cases. But they do have some negative effects. They are about 85% effective, are local irritants, and some cause discomfort during intercourse. And it is possible that some are resorbed by the body and act on the liver and other organs. Vaginal globules and suppositories are also popular. The "Kontraceptin-T" brand contains quinosol, boric acid, and tannin. There are also foaming tablets which are mixed with water and then introduced. New locally-active chemical substances are being developed in Japan, West Germany, and the USSR. Kontraceptin-E contains paranonyl-phenoxypolyethylene glycol and sodium dioctylsulfosuccinate. The "Norforks" and other preparations contain mercurial compounds which may turn out to be harmful. The future promises the development of products which will act to prevent fertilization by acting on the hyaluronidase and the acrosine of the spermatozoid, thus preventing it from penetrating the ovum. It would be best to find enzyme inhibitors which are

  4. Current perspectives on the pediatric hip: selected topics in hip dysplasia, Perthes disease, and chondrolysis: synopsis of the hip subspecialty session at the POSNA Annual Meeting, May 1, 2013, Toronto.

    PubMed

    Millis, Michael B; Zaltz, Ira

    2014-01-01

    The following are proceedings from the Hip Breakout Session held at the 2013 annual meeting of the Pediatric Orthopaedic Society of North America in Toronto, Canada. The organizer's goal of the meeting was to gather experts with years of clinical experience to discuss topics based upon both experience and current clinical evidence. The topics that were selected represented the most commonly encountered pathology where there are wide variations of clinical practice. The invited speakers were asked to summarize both their clinical experience and the current scientific evidence and to summarize areas that require further scientific investigation. PMID:25207735

  5. Composite Load Spectra for Select Space Propulsion Structural Components

    NASA Technical Reports Server (NTRS)

    Ho, Hing W.; Newell, James F.

    1994-01-01

    Generic load models are described with multiple levels of progressive sophistication to simulate the composite (combined) load spectra (CLS) that are induced in space propulsion system components, representative of Space Shuttle Main Engines (SSME), such as transfer ducts, turbine blades and liquid oxygen (LOX) posts. These generic (coupled) models combine the deterministic models for composite load dynamic, acoustic, high-pressure and high rotational speed, etc., load simulation using statistically varying coefficients. These coefficients are then determined using advanced probabilistic simulation methods with and without strategically selected experimental data. The entire simulation process is included in a CLS computer code. Applications of the computer code to various components in conjunction with the PSAM (Probabilistic Structural Analysis Method) to perform probabilistic load evaluation and life prediction evaluations are also described to illustrate the effectiveness of the coupled model approach.

  6. Population structure, migration, and diversifying selection in the Netherlands

    PubMed Central

    Abdellaoui, Abdel; Hottenga, Jouke-Jan; Knijff, Peter de; Nivard, Michel G; Xiao, Xiangjun; Scheet, Paul; Brooks, Andrew; Ehli, Erik A; Hu, Yueshan; Davies, Gareth E; Hudziak, James J; Sullivan, Patrick F; van Beijsterveldt, Toos; Willemsen, Gonneke; de Geus, Eco J; Penninx, Brenda W J H; Boomsma, Dorret I

    2013-01-01

    Genetic variation in a population can be summarized through principal component analysis (PCA) on genome-wide data. PCs derived from such analyses are valuable for genetic association studies, where they can correct for population stratification. We investigated how to capture the genetic population structure in a well-characterized sample from the Netherlands and in a worldwide data set and examined whether (1) removing long-range linkage disequilibrium (LD) regions and LD-based SNP pruning significantly improves correlations between PCs and geography and (2) whether genetic differentiation may have been influenced by migration and/or selection. In the Netherlands, three PCs showed significant correlations with geography, distinguishing between: (1) North and South; (2) East and West; and (3) the middle-band and the rest of the country. The third PC only emerged with minimized LD, which also significantly increased correlations with geography for the other two PCs. In addition to geography, the Dutch North–South PC showed correlations with genome-wide homozygosity (r=0.245), which may reflect a serial-founder effect due to northwards migration, and also with height (♂: r=0.142, ♀: r=0.153). The divergence between subpopulations identified by PCs is partly driven by selection pressures. The first three PCs showed significant signals for diversifying selection (545 SNPs - the majority within 184 genes). The strongest signal was observed between North and South for the functional SNP in HERC2 that determines human blue/brown eye color. Thus, this study demonstrates how to increase ancestry signals in a relatively homogeneous population and how those signals can reveal evolutionary history. PMID:23531865

  7. Population structure, migration, and diversifying selection in the Netherlands.

    PubMed

    Abdellaoui, Abdel; Hottenga, Jouke-Jan; de Knijff, Peter; Nivard, Michel G; Xiao, Xiangjun; Scheet, Paul; Brooks, Andrew; Ehli, Erik A; Hu, Yueshan; Davies, Gareth E; Hudziak, James J; Sullivan, Patrick F; van Beijsterveldt, Toos; Willemsen, Gonneke; de Geus, Eco J; Penninx, Brenda W J H; Boomsma, Dorret I

    2013-11-01

    Genetic variation in a population can be summarized through principal component analysis (PCA) on genome-wide data. PCs derived from such analyses are valuable for genetic association studies, where they can correct for population stratification. We investigated how to capture the genetic population structure in a well-characterized sample from the Netherlands and in a worldwide data set and examined whether (1) removing long-range linkage disequilibrium (LD) regions and LD-based SNP pruning significantly improves correlations between PCs and geography and (2) whether genetic differentiation may have been influenced by migration and/or selection. In the Netherlands, three PCs showed significant correlations with geography, distinguishing between: (1) North and South; (2) East and West; and (3) the middle-band and the rest of the country. The third PC only emerged with minimized LD, which also significantly increased correlations with geography for the other two PCs. In addition to geography, the Dutch North-South PC showed correlations with genome-wide homozygosity (r=0.245), which may reflect a serial-founder effect due to northwards migration, and also with height (♂: r=0.142, ♀: r=0.153). The divergence between subpopulations identified by PCs is partly driven by selection pressures. The first three PCs showed significant signals for diversifying selection (545 SNPs - the majority within 184 genes). The strongest signal was observed between North and South for the functional SNP in HERC2 that determines human blue/brown eye color. Thus, this study demonstrates how to increase ancestry signals in a relatively homogeneous population and how those signals can reveal evolutionary history. PMID:23531865

  8. Structures of Potent Selective Peptide Mimetics Bound to Carboxypeptidase B

    SciTech Connect

    Adler, M.; Buckman, B.; Bryant, J.; Chang, Z.; Chu, K.; Emayan, K.; Hrvatin, P.; Islam, I.; Morser, J.; Sukovich, D.; West, C.; Yuan, S.; Whitlow, M.

    2009-05-11

    This article reports the crystal structures of inhibitors of the functional form of thrombin-activatable fibrinolysis inhibitor (TAFIa). In vivo experiments indicate that selective inhibitors of TAFIa would be useful in the treatment of heart attacks. Since TAFIa rapidly degrades in solution, the homologous protein porcine pancreatic carboxypeptidase B (pp-CpB) was used in these crystallography studies. Both TAFIa and pp-CpB are zinc-based exopeptidases that are specific for basic residues. The final development candidate, BX 528, is a potent inhibitor of TAFIa (2 nM) and has almost no measurable effect on the major selectivity target, carboxypeptidase N. BX 528 was designed to mimic the tripeptide Phe-Val-Lys. A sulfonamide replaces the Phe-Val amide bond and a phosphinate connects the Val and Lys groups. The phosphinate also chelates the active-site zinc. The electrostatic interactions with the protein mimic those of the natural substrate. The primary amine in BX 528 forms a salt bridge to Asp255 at the base of the S1 pocket. The carboxylic acid interacts with Arg145 and the sulfonamide is hydrogen bonded to Arg71. Isopropyl and phenyl groups replace the side chains of Val and Phe, respectively. A series of structures are presented here that illustrate the evolution of BX 528 from thiol-based inhibitors that mimic a free C-terminal arginine. The first step in development was the replacement of the thiol with a phosphinate. This caused a precipitous drop in binding affinity. Potency was reclaimed by extending the inhibitors into the downstream binding sites for the natural substrate.

  9. CHF6001 I: a novel highly potent and selective phosphodiesterase 4 inhibitor with robust anti-inflammatory activity and suitable for topical pulmonary administration.

    PubMed

    Moretto, Nadia; Caruso, Paola; Bosco, Raffaella; Marchini, Gessica; Pastore, Fiorella; Armani, Elisabetta; Amari, Gabriele; Rizzi, Andrea; Ghidini, Eleonora; De Fanti, Renato; Capaldi, Carmelida; Carzaniga, Laura; Hirsch, Emilio; Buccellati, Carola; Sala, Angelo; Carnini, Chiara; Patacchini, Riccardo; Delcanale, Maurizio; Civelli, Maurizio; Villetti, Gino; Facchinetti, Fabrizio

    2015-03-01

    This study examined the pharmacologic characterization of CHF6001 [(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(3-(cyclopropylmethoxy)-4-(methylsulfonamido)benzoyloxy)ethyl)pyridine 1-oxide], a novel phosphodiesterase (PDE)4 inhibitor designed for treating pulmonary inflammatory diseases via inhaled administration. CHF6001 was 7- and 923-fold more potent than roflumilast and cilomilast, respectively, in inhibiting PDE4 enzymatic activity (IC50 = 0.026 ± 0.006 nM). CHF6001 inhibited PDE4 isoforms A-D with equal potency, showed an elevated ratio of high-affinity rolipram binding site versus low-affinity rolipram binding site (i.e., >40) and displayed >20,000-fold selectivity versus PDE4 compared with a panel of PDEs. CHF6001 effectively inhibited (subnanomolar IC50 values) the release of tumor necrosis factor-α from human peripheral blood mononuclear cells, human acute monocytic leukemia cell line macrophages (THP-1), and rodent macrophages (RAW264.7 and NR8383). Moreover, CHF6001 potently inhibited the activation of oxidative burst in neutrophils and eosinophils, neutrophil chemotaxis, and the release of interferon-γ from CD4(+) T cells. In all these functional assays, CHF6001 was more potent than previously described PDE4 inhibitors, including roflumilast, UK-500,001 [2-(3,4-difluorophenoxy)-5-fluoro-N-((1S,4S)-4-(2-hydroxy-5-methylbenzamido)cyclohexyl)nicotinamide], and cilomilast, and it was comparable to GSK256066 [6-((3-(dimethylcarbamoyl)phenyl)sulfonyl)-4-((3-methoxyphenyl)amino)-8-methylquinoline-3-carboxamide]. When administered intratracheally to rats as a micronized dry powder, CHF6001 inhibited liposaccharide-induced pulmonary neutrophilia (ED50 = 0.205 μmol/kg) and leukocyte infiltration (ED50 = 0.188 μmol/kg) with an efficacy comparable to a high dose of budesonide (1 μmol/kg i.p.). In sum, CHF6001 has the potential to be an effective topical treatment of conditions associated with pulmonary inflammation, including

  10. High Temperature Irradiation Effects in Selected Generation IV Structural Alloys

    SciTech Connect

    Nanstad, Randy K; McClintock, David A; Hoelzer, David T; Tan, Lizhen; Allen, Todd R.

    2009-01-01

    In the Generation IV Materials Program cross-cutting task, irradiation and testing were carried out to address the issue of high temperature irradiation effects with selected current and potential candidate metallic alloys. The materials tested were (1) a high-nickel iron-base alloy (Alloy 800H); (2) a nickel-base alloy (Alloy 617); (3) two advanced nano-structured ferritic alloys (designated 14YWT and 14WT); and (4) a commercial ferritic-martensitic steel (annealed 9Cr-1MoV). Small tensile specimens were irradiated in rabbit capsules in the High-Flux Isotope Reactor at temperatures from about 550 to 700 C and to irradiation doses in the range 1.2 to 1.6 dpa. The Alloy 800H and Alloy 617 exhibited significant hardening after irradiation at 580 C; some hardening occurred at 660 C as well, but the 800H showed extremely low tensile elongations when tested at 700 C. Notably, the grain boundary engineered 800H exhibited even greater hardening at 580 C and retained a high amount of ductility. Irradiation effects on the two nano-structured ferritic alloys and the annealed 9Cr-1MoV were relatively slight at this low dose.

  11. Structural considerations on the selectivity of an immunoassay for sulfamethoxazole.

    PubMed

    Hoffmann, Holger; Baldofski, Stefanie; Hoffmann, Kristin; Flemig, Sabine; Silva, Carla Patrícia; Esteves, Valdemar I; Emmerling, Franziska; Panne, Ulrich; Schneider, Rudolf J

    2016-09-01

    Sulfamethoxazole (SMX), a sulfonamide, is a widely used bacteriostatic antibiotic and therefore a promising marker for the entry of anthropogenic pollution in the environment. SMX is frequently found in wastewater and surface water. This study presents the production of high affinity and selective polyclonal antibodies for SMX and the development and evaluation of a direct competitive enzyme-linked immunosorbent assay (ELISA) for the quantification of SMX in environmental water samples. The crystal structures of the cross-reacting compounds sulfamethizole, N(4)-acetyl-SMX and succinimidyl-SMX were determined by x-ray diffraction aiming to explain their high cross-reactivity. These crystal structures are described for the first time. The quantification range of the ELISA is 0.82-63µg/L. To verify our results, the SMX concentration in 20 environmental samples, including wastewater and surface water, was determined by ELISA and tandem mass spectrometry (MS/MS). A good agreement of the measured SMX concentrations was found with average recoveries of 97-113% for the results of ELISA compared to LC-MS/MS. PMID:27343596

  12. Structure-guided development of heterodimer-selective GPCR ligands

    PubMed Central

    Hübner, Harald; Schellhorn, Tamara; Gienger, Marie; Schaab, Carolin; Kaindl, Jonas; Leeb, Laurin; Clark, Timothy; Möller, Dorothee; Gmeiner, Peter

    2016-01-01

    Crystal structures of G protein-coupled receptor (GPCR) ligand complexes allow a rational design of novel molecular probes and drugs. Here we report the structure-guided design, chemical synthesis and biological investigations of bivalent ligands for dopamine D2 receptor/neurotensin NTS1 receptor (D2R/NTS1R) heterodimers. The compounds of types 1–3 consist of three different D2R pharmacophores bound to an affinity-generating lipophilic appendage, a polyethylene glycol-based linker and the NTS1R agonist NT(8-13). The bivalent ligands show binding affinity in the picomolar range for cells coexpressing both GPCRs and unprecedented selectivity (up to three orders of magnitude), compared with cells that only express D2Rs. A functional switch is observed for the bivalent ligands 3b,c inhibiting cAMP formation in cells singly expressing D2Rs but stimulating cAMP accumulation in D2R/NTS1R-coexpressing cells. Moreover, the newly synthesized bivalent ligands show a strong, predominantly NTS1R-mediated β-arrestin-2 recruitment at the D2R/NTS1R-coexpressing cells. PMID:27457610

  13. Structural deterministic safety factors selection criteria and verification

    NASA Technical Reports Server (NTRS)

    Verderaime, V.

    1992-01-01

    Though current deterministic safety factors are arbitrarily and unaccountably specified, its ratio is rooted in resistive and applied stress probability distributions. This study approached the deterministic method from a probabilistic concept leading to a more systematic and coherent philosophy and criterion for designing more uniform and reliable high-performance structures. The deterministic method was noted to consist of three safety factors: a standard deviation multiplier of the applied stress distribution; a K-factor for the A- or B-basis material ultimate stress; and the conventional safety factor to ensure that the applied stress does not operate in the inelastic zone of metallic materials. The conventional safety factor is specifically defined as the ratio of ultimate-to-yield stresses. A deterministic safety index of the combined safety factors was derived from which the corresponding reliability proved the deterministic method is not reliability sensitive. The bases for selecting safety factors are presented and verification requirements are discussed. The suggested deterministic approach is applicable to all NASA, DOD, and commercial high-performance structures under static stresses.

  14. Terahertz wave filter based on frequency-selective surface structure

    NASA Astrophysics Data System (ADS)

    Sun, Chao; Li, Jiu-sheng

    2011-11-01

    Terahertz radiations, which refer to the frequencies from 100GHz to 10THz, lie in the frequency gap between the infrared and microwave, have received considerable attention during the past decades. Due to their special prosperties, THz radiations have been applied in many fields such as gases, semiconductors, explosives materials, and environment pollutants. The technique is based on recording the time dependence of the electric field of a short electromagnetic pulse transmitted through a sample. The ratio of the Fourier transforms of the data recorded with and without the sample yields the complex transmission coefficient of the sample in the frequency domain. The absorption coefficient and the refractive index of the material studied are directly related to the amplitude and phase respectively of the transmitted field. Terahertz wave filter, a frequency-selective surface structure, has been characterized by terahertz time-domain spectroscopy in the region from 0.1 to 3THz. We have compared THz-TDS measurement and calculation results of the mode-matching theory of the terahertz wave filter, and find that the two data sets agree very closely. The peak of the transmittance of about 90.5%occurs at 0.45THz for the first case and the peak of the transmittance of about 89.4% occurs at 0.79THz for the second case.

  15. Terahertz wave filter based on frequency-selective surface structure

    NASA Astrophysics Data System (ADS)

    Sun, Chao; Li, Jiu-sheng

    2012-03-01

    Terahertz radiations, which refer to the frequencies from 100GHz to 10THz, lie in the frequency gap between the infrared and microwave, have received considerable attention during the past decades. Due to their special prosperties, THz radiations have been applied in many fields such as gases, semiconductors, explosives materials, and environment pollutants. The technique is based on recording the time dependence of the electric field of a short electromagnetic pulse transmitted through a sample. The ratio of the Fourier transforms of the data recorded with and without the sample yields the complex transmission coefficient of the sample in the frequency domain. The absorption coefficient and the refractive index of the material studied are directly related to the amplitude and phase respectively of the transmitted field. Terahertz wave filter, a frequency-selective surface structure, has been characterized by terahertz time-domain spectroscopy in the region from 0.1 to 3THz. We have compared THz-TDS measurement and calculation results of the mode-matching theory of the terahertz wave filter, and find that the two data sets agree very closely. The peak of the transmittance of about 90.5%occurs at 0.45THz for the first case and the peak of the transmittance of about 89.4% occurs at 0.79THz for the second case.

  16. Antimicrobial Activity of Xanthohumol and Its Selected Structural Analogues.

    PubMed

    Stompor, Monika; Żarowska, Barbara

    2016-01-01

    The objective of this study was to evaluate the antimicrobial activity of structural analogues of xanthohumol 1, a flavonoid compound found in hops (Humulus lupulus). The agar-diffusion method using filter paper disks was applied. Biological tests performed for selected strains of Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria, fungi (Alternaria sp.), and yeasts (Rhodotorula rubra, Candida albicans) revealed that compounds with at least one hydroxyl group-all of them have it at the C-4 position-demonstrated good activity. Our research showed that the strain S. aureus was more sensitive to chalcones than to the isomers in which the heterocyclic ring C is closed (flavanones). The strain R. rubra was moderately sensitive to only one compound: 4-hydroxy-4'-methoxychalcone 8. Loss of the hydroxyl group in the B-ring of 4'-methoxychalcones or its replacement by a halogen atom (-Cl, -Br), nitro group (-NO₂), ethoxy group (-OCH₂CH₃), or aliphatic substituent (-CH₃, -CH₂CH₃) resulted in the loss of antimicrobial activity towards both R. rubra yeast and S. aureus bacteria. Xanthohumol 1, naringenin 5, and chalconaringenin 7 inhibited growth of S. aureus, whereas 4-hydroxy-4'-methoxychalcone 8 was active towards two strains: S. aureus and R. rubra. PMID:27187329

  17. Electronic structure and physicochemical properties of selected penicillins

    NASA Astrophysics Data System (ADS)

    Soriano-Correa, Catalina; Ruiz, Juan F. Sánchez; Raya, A.; Esquivel, Rodolfo O.

    Traditionally, penicillins have been used as antibacterial agents due to their characteristics and widespread applications with few collateral effects, which have motivated several theoretical and experimental studies. Despite the latter, their mechanism of biological action has not been completely elucidated. We present a theoretical study at the Hartree-Fock and density functional theory (DFT) levels of theory of a selected group of penicillins such as the penicillin-G, amoxicillin, ampicillin, dicloxacillin, and carbenicillin molecules, to systematically determine the electron structure of full ?-lactam antibiotics. Our results allow us to analyze the electronic properties of the pharmacophore group, the aminoacyl side-chain, and the influence of the substituents (R and X) attached to the aminoacyl side-chain at 6? (in contrast with previous studies focused at the 3? substituents), and to corroborate the results of previous studies performed at the semiempirical level, solely on the ?-lactam ring of penicillins. Besides, several density descriptors are determined with the purpose of analyzing their link to the antibacterial activity of these penicillin compounds. Our results for the atomic charges (fitted to the electrostatic potential), the bond orders, and several global reactivity descriptors, such as the dipole moments, ionization potential, hardness, and the electrophilicity index, led us to characterize: the active sites, the effect of the electron-attracting substituent properties and their physicochemical features, which altogether, might be important to understand the biological activity of these type of molecules.

  18. Correlations between surface structure and catalytic activity/selectivity

    SciTech Connect

    Goodman, D.W.

    1992-10-01

    Objective is to address the keys to understanding the relation between surface structure and catalytic activity/selectivity. Of concern are questions related to enhanced catalytic properties of mixed-metal catalysts and critical active site requirements for molecular synthesis and rearrangement. The experimental approach utilizes a microcatalytic reactor contiguous to a surface analysis system, an arrangement which allows in vacuo transfer of the catalyst from one chamber to the other. Surface techniques being used include Auger (AES), UV and X-ray photoemission spectroscopy (UPS and XPS), temperature programmed desorption (TPD), low energy electron diffraction (LEED), high resolution electron energy loss spectroscopy (HREELS) and infrared reflection-absorption spectroscopy (IRAS). Our research program builds upon our previous experience relating the results of single crystal kinetic measurements with the results obtained with supported analogs. As well we are exploiting our recent work on the preparation, the characterization, and the determination of the catalytic properties of ultra-thin metal and metal oxide films. The program is proceeding toward the study of the unique catalytic properties of ultrathin metal films; the investigation of the critical ensemble size requirements for principal catalytic reaction types; and the modelling of supported catalysts using ultra-thin planar oxide surfaces.

  19. Structural aspects of host molecules acting as ionophores in ion-selective electrodes

    NASA Astrophysics Data System (ADS)

    Bocheńska, Maria

    1998-09-01

    Structural aspects of ligand molecules acting as neutral ionophores in ion-selective membrane electrodes are discussed and examples of Li-selective ionophores are presented. The relationship between the structure of ionophore and its complex determined by X-ray and NMR study and the selectivity of ISE was determined.

  20. Topic Model for Graph Mining.

    PubMed

    Xuan, Junyu; Lu, Jie; Zhang, Guangquan; Luo, Xiangfeng

    2015-12-01

    Graph mining has been a popular research area because of its numerous application scenarios. Many unstructured and structured data can be represented as graphs, such as, documents, chemical molecular structures, and images. However, an issue in relation to current research on graphs is that they cannot adequately discover the topics hidden in graph-structured data which can be beneficial for both the unsupervised learning and supervised learning of the graphs. Although topic models have proved to be very successful in discovering latent topics, the standard topic models cannot be directly applied to graph-structured data due to the "bag-of-word" assumption. In this paper, an innovative graph topic model (GTM) is proposed to address this issue, which uses Bernoulli distributions to model the edges between nodes in a graph. It can, therefore, make the edges in a graph contribute to latent topic discovery and further improve the accuracy of the supervised and unsupervised learning of graphs. The experimental results on two different types of graph datasets show that the proposed GTM outperforms the latent Dirichlet allocation on classification by using the unveiled topics of these two models to represent graphs. PMID:25616091

  1. Composite load spectra for select space propulsion structural components

    NASA Technical Reports Server (NTRS)

    Newell, J. F.; Ho, H. W.; Kurth, R. E.

    1991-01-01

    The work performed to develop composite load spectra (CLS) for the Space Shuttle Main Engine (SSME) using probabilistic methods. The three methods were implemented to be the engine system influence model. RASCAL was chosen to be the principal method as most component load models were implemented with the method. Validation of RASCAL was performed. High accuracy comparable to the Monte Carlo method can be obtained if a large enough bin size is used. Generic probabilistic models were developed and implemented for load calculations using the probabilistic methods discussed above. Each engine mission, either a real fighter or a test, has three mission phases: the engine start transient phase, the steady state phase, and the engine cut off transient phase. Power level and engine operating inlet conditions change during a mission. The load calculation module provides the steady-state and quasi-steady state calculation procedures with duty-cycle-data option. The quasi-steady state procedure is for engine transient phase calculations. In addition, a few generic probabilistic load models were also developed for specific conditions. These include the fixed transient spike model, the poison arrival transient spike model, and the rare event model. These generic probabilistic load models provide sufficient latitude for simulating loads with specific conditions. For SSME components, turbine blades, transfer ducts, LOX post, and the high pressure oxidizer turbopump (HPOTP) discharge duct were selected for application of the CLS program. They include static pressure loads and dynamic pressure loads for all four components, centrifugal force for the turbine blade, temperatures of thermal loads for all four components, and structural vibration loads for the ducts and LOX posts.

  2. Topical delivery of hexamidine.

    PubMed

    Parisi, Nicola; Paz-Alvarez, Miguel; Matts, Paul J; Lever, Rebecca; Hadgraft, Jonathan; Lane, Majella E

    2016-06-15

    Hexamidine diisethionate (HEX D) has been used for its biocidal actions in topical preparations since the 1950s. Recent data also suggest that it plays a beneficial role in skin homeostasis. To date, the extent to which this compound penetrates the epidermis has not been reported nor how its topical delivery may be modulated. In the present work we set out to characterise the interaction of HEX D with the skin and to develop a range of simple formulations for topical targeting of the active. A further objective was to compare the skin penetration of HEX D with its corresponding dihydrochloride salt (HEX H) as the latter has more favourable physicochemical properties for skin uptake. Candidate vehicles were evaluated by in vitro Franz cell permeation studies using porcine skin. Initially, neat solvents were investigated and subsequently binary systems were examined. The solvents and chemical penetration enhancers investigated included glycerol, dimethyl isosorbide (DMI), isopropyl alcohol (IPA), 1,2-pentanol (1,2-PENT), polyethylene glycol (PEG) 200, propylene glycol (PG), propylene glycol monolaurate (PGML) and Transcutol(®)P (TC). Of a total of 30 binary solvent systems evaluated only 10 delivered higher amounts of active into the skin compared with the neat solvents. In terms of topical efficacy, formulations containing PGML far surpassed all other solvents or binary combinations. More than 70% of HEX H was extracted from the skin following application in PG:PGML (50:50). Interestingly, the same vehicle effectively promoted skin penetration of HEX D but demonstrated significantly lower uptake into and through the skin (30%). The findings confirm the unpredictable nature of excipients on delivery of actives with reference to skin even where there are minor differences in molecular structures. We also believe that they underline the ongoing necessity for fundamental studies on the interaction of topical excipients with the skin. PMID:27130367

  3. Interface Pattern Selection Criterion for Cellular Structures in Directional Solidification

    NASA Technical Reports Server (NTRS)

    Trivedi, R.; Tewari, S. N.; Kurtze, D.

    1999-01-01

    The aim of this investigation is to establish key scientific concepts that govern the selection of cellular and dendritic patterns during the directional solidification of alloys. We shall first address scientific concepts that are crucial in the selection of interface patterns. Next, the results of ground-based experimental studies in the Al-4.0 wt % Cu system will be described. Both experimental studies and theoretical calculations will be presented to establish the need for microgravity experiments.

  4. Selective formation of turbulent structures in magnetized cylindrical plasmas

    SciTech Connect

    Kasuya, Naohiro; Itoh, Kimitaka; Yagi, Masatoshi; Itoh, Sanae-I

    2008-05-15

    The mechanism of nonlinear structural formation has been studied with a three-field reduced fluid model, which is extended to describe the resistive drift wave turbulence in magnetized cylindrical plasmas. In this model, ion-neutral collisions strongly stabilize the resistive drift wave, and the formed structure depends on the collision frequency. If the collision frequency is small, modulational coupling of unstable modes generates a zonal flow. On the other hand, if the collision frequency is large, a streamer, which is a localized vortex in the azimuthal direction, is formed. The structure is generated by nonlinear wave coupling and is sustained for a much longer duration than the drift wave oscillation period. This is a minimal model for analyzing the turbulent structural formation mechanism by mode coupling in cylindrical plasmas, and the competitive nature of structural formation is revealed. These turbulent structures affect particle transport.

  5. PREFACE: CEWQO Topical Issue CEWQO Topical Issue

    NASA Astrophysics Data System (ADS)

    Bozic, Mirjana; Man'ko, Margarita

    2009-09-01

    This topical issue of Physica Scripta collects selected peer-reviewed contributions based on invited and contributed talks and posters presented at the 15th Central European Workshop on Quantum Optics (CEWQO) which took place in Belgrade 29 May-3 June 2008 (http://cewqo08.phy.bg.ac.yu). On behalf of the whole community took place in Belgrade 29 May-3 June 2008 (http://cewqo08.phy.bg.ac.yu, cewqo08.phy.bg.ac.yu). On behalf of the whole community of the workshop, we thank the referees for their careful reading and useful suggestions which helped to improve all of the submitted papers. A brief description of CEWQO The Central European Workshop on Quantum Optics is a series of conferences started informally in Budapest in 1992. Sometimes small events transform into important conferences, as in the case of CEWQO. Professor Jozsef Janszky, from the Research Institute of Solid State Physics and Optics, is the founder of this series. Margarita Man'ko obtained the following information from Jozsef Janszky during her visit to Budapest, within the framework of cooperation between the Russian and Hungarian Academies of Sciences in 2005. He organized a small workshop on quantum optics in Budapest in 1992 with John Klauder as a main speaker. Then, bearing in mind that a year before Janszky himself was invited by Vladimir Buzek to give a seminar on the same topic in Bratislava, he decided to assign the name 'Central European Workshop on Quantum Optics', considering the seminar in Bratislava to be the first workshop and the one in Budapest the second. The third formal workshop took place in Bratislava in 1993 organized by Vladimir Buzek, then in 1994 (Budapest, by Jozsef Janszky), 1995 and 1996 (Budmerice, Slovakia, by Vladimir Buzek), 1997 (Prague, by Igor Jex), 1999 (Olomouc, Czech Republic, by Zdenek Hradil), 2000 (Balatonfüred, Hungary, by Jozsef Janszky ), 2001 (Prague, by Igor Jex), 2002 (Szeged, Hungary, by Mihaly Benedict), 2003 (Rostock,Germany, by Werner Vogel and

  6. EDITORIAL: Special section: Selected papers from OMS'05, the 1st Topical Meeting of the European Optical Society on Optical Microsystems (OMS)

    NASA Astrophysics Data System (ADS)

    Rendina, Ivo; Fazio, Eugenio; Ferraro, Pietro

    2006-07-01

    OMS'05 is the first international conference wholly dedicated to optical microsystems. It was organized by the European Optical Society (EOS) in the frame of its international topical meeting activity and was held in Italy, September 2005, amidst the wonderful scenery of the Island of Capri. A possible definition of an optical microsystem is a complex system, able to perform one or more sensing and actuation functions, where optical devices are integrated in a smart way with electronic, mechanical and sensing components by taking advantage of the progress in micro- and nano-technologies. The increasing interest in this field arises from the expected applications that would significantly improve the quality of life. The list of possibilities offered by the optical microsystem enabling technologies is very long and seems to increase day by day. We are not only thinking about the next generation of optical telecommunication networks and computers, but also about low-cost, compact microsystems for environmental monitoring, in order to improve safety in the avionic and automotive fields, medical diagnostics and proteomic/genomic studies, or just finding general applications in several industrial fields. The goal of the conference was to involve scientists and young researchers from the main public and private laboratories, giving them the opportunity to present new scientific results and compare their know-how in the exciting and emerging field of optical microsystems. We believe that we succeeded in this. More than 200 scientists from all over the world attended the conference. We had more than 100 oral presentations and approximately 20 from the keynote lectures and invited speeches. It was an opportunity to define the most recent progress carried out in the field and to outline the possible road-map leading to the expected results in the industrial and social fields. We strongly believe that research and technology are closely interconnected at present and cannot

  7. Structural determinants of the alpha2 adrenoceptor subtype selectivity

    PubMed Central

    Ostopovici-Halip, Liliana; Curpăn, Ramona; Mracec, Maria; Bologa, Cristian G.

    2012-01-01

    Alpha2-adrenergic receptor (α2-AR) subtypes, acting mainly on the central nervous and cardiovascular systems, represent important targets for drug design, confirmed by the high number of studies published so far. Presently, only few α2-AR subtype selective compounds are known. Using homology modeling and ligand docking, the present study analyzes the similarities and differences between binding sites, and between extracellular loops of the three subtypes of α2-AR. Several α2-AR subtype selective ligands were docked in the active sites of the three α2-AR subtypes, key interactions between ligands and receptors were mapped, and the predicted results were compared to experimental results. Binding site analysis reveals a strong identity between important amino acid residues in each receptor, the very few differences being the key towards modulating selectivity of α2-AR ligands. The observed differences between binding site residues provide an excellent starting point for virtual screening of chemical databases in order to identify potentially selective ligands for α2-ARs. PMID:21602069

  8. Training set optimization under population structure in genomic selection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The optimization of the training set (TRS) in genomic selection (GS) has received much interest in both animal and plant breeding, because it is critical to the accuracy of the prediction models. In this study, five different TRS sampling algorithms, stratified sampling, mean of the Coefficient of D...

  9. Reconsidering the logical structure of the theory of natural selection

    PubMed Central

    Hunt, Tam

    2014-01-01

    Natural selection has been criticized as a tautology. This would be a major problem for evolutionary biology, if true, because tautological statements can't be falsified and, therefore, can't be scientific. There is merit to this critique insofar as the theory of natural selection is indeed generally described in a tautological manner. However, natural selection can be described non-tautologically if we’re careful. Natural selection should be defined as the theory that attempts to predict and retrodict evolutionary change through environmental forces acting upon organisms. However, this re-framing comes at a cost: it reveals, based on our current knowledge of evolutionary forces, the lack of ability to make accurate predictions about expected changes except in the most simple of circumstances. I suggest that evolutionary biologists should work to develop “principles of evolution,” based on an expanded and more focused research program designed to identify common trends in evolution, which will ultimately allow us to make more accurate predictions and retrodictions about evolution. PMID:26478764

  10. Training set optimization under population structure in genomic selection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The optimization of the training set (TRS) in genomic selection has received much interest in both animal and plant breeding, because it is critical to the accuracy of the prediction models. In this study, five different TRS sampling algorithms, stratified sampling, mean of the coefficient of determ...

  11. Application of composites to the selective reinforcement of metallic aerospace structures. [application of structural design criteria for weight reduction

    NASA Technical Reports Server (NTRS)

    Brooks, W. A., Jr.; Mathauser, E. E.; Pride, R. A.

    1972-01-01

    The use of composite materials to selectively reinforce metallic structures provides a low-cost way to reduce weight and a means of minimizing the risks usually associated with the introduction of new materials. An overview is presented of the NASA Langley Research Center programs to identify the advantages and to develop the potential of the selective reinforcement approach to the use of composites. These programs have shown that selective reinforcement provides excellent strength and stiffness improvements to metallic structures. Significant weight savings can be obtained in a cost effective manner. Flight service programs which have been initiated to validate further the merits of selective reinforcement are described.

  12. Changing Structure of the Electric Power Industry: Selected Issues, 1998

    EIA Publications

    1998-01-01

    Provides an analytical assessment of the changes taking place in the electric power industry, including market structure, consumer choice, and ratesetting and transition costs. Also presents federal and state initiatives in promoting competition.

  13. Probabilistic structural analysis methods for select space propulsion system components

    NASA Technical Reports Server (NTRS)

    Millwater, H. R.; Cruse, T. A.

    1989-01-01

    The Probabilistic Structural Analysis Methods (PSAM) project developed at the Southwest Research Institute integrates state-of-the-art structural analysis techniques with probability theory for the design and analysis of complex large-scale engineering structures. An advanced efficient software system (NESSUS) capable of performing complex probabilistic analysis has been developed. NESSUS contains a number of software components to perform probabilistic analysis of structures. These components include: an expert system, a probabilistic finite element code, a probabilistic boundary element code and a fast probability integrator. The NESSUS software system is shown. An expert system is included to capture and utilize PSAM knowledge and experience. NESSUS/EXPERT is an interactive menu-driven expert system that provides information to assist in the use of the probabilistic finite element code NESSUS/FEM and the fast probability integrator (FPI). The expert system menu structure is summarized. The NESSUS system contains a state-of-the-art nonlinear probabilistic finite element code, NESSUS/FEM, to determine the structural response and sensitivities. A broad range of analysis capabilities and an extensive element library is present.

  14. Resources for Topics in Nursing.

    ERIC Educational Resources Information Center

    Riordan, Dale B.

    This guide is intended to help the user become familiar with a selected group of reference tools and resources which are useful in nursing education and practice. It is important for students to use the correct medical or scientific terminology, understand the scope of a topic, and then utilize the tools necessary to research subjects of interest.…

  15. Helping Kids Choose a Topic.

    ERIC Educational Resources Information Center

    Bunce-Crim, Marna

    1991-01-01

    Thinking about how published authors get their ideas for stories is one way for children to generate their own story ideas. The article discusses how elementary teachers can use storytelling, reading, examining picture books, and learning writing techniques to help their students select a topic. (SM)

  16. Prediction of formulation effects on dermal absorption of topically applied ectoparasiticides dosed in vitro on canine and porcine skin using a mixture-adjusted quantitative structure permeability relationship.

    PubMed

    Riviere, J E; Brooks, J D; Collard, W T; Deng, J; de Rose, G; Mahabir, S P; Merritt, D A; Marchiondo, A A

    2014-10-01

    Topical application of ectoparasiticides for flea and tick control is a major focus for product development in animal health. The objective of this work was to develop a quantitative structure permeability relationship (QSPeR) model sensitive to formulation effects for predicting absorption and skin deposition of five topically applied drugs administered in six vehicle combinations to porcine and canine skin in vitro. Saturated solutions (20 μL) of (14) C-labeled demiditraz, fipronil, permethrin, imidacloprid, or sisapronil were administered in single or binary (50:50 v/v) combinations of water, ethanol, and transcutol (6 formulations, n = 4-5 replicates per treatment) nonoccluded to 0.64 cm(2) disks of dermatomed pig or dog skin mounted in flow-through diffusion cells. Perfusate flux over 24 h and skin deposition at termination were determined. Permeability (logKp), absorption, and penetration endpoints were modeled using a four-term Abrahams and Martin (hydrogen-bond donor acidity and basicity, dipolarity/polarizability, and excess molar refractivity) linear free energy QSPeR equation with a mixture factor added to compensate for formulation ingredient interactions. Goodness of fit was judged by r(2) , cross-validation coefficient, coefficients (q(2) s), and Williams Plot to visualize the applicability domain. Formulation composition was the primary determinant of permeation. Compounds generally penetrated dog skin better than porcine skin. The vast majority of permeated penetrant was deposited within the dosed skin relative to transdermal flux, an attribute for ectoparasiticides. The best QSPeR logKp model for pig skin permeation (r(2) = 0.86, q(2) s = 0.85) included log octanol/water partition coefficient as the mixture factor, while for dogs (r(2) = 0.91, q(2) s = 0.90), it was log water solubility. These studies clearly showed that the permeation of topical ectoparasiticides could be well predicted using QSPeR models that account for both the physical

  17. PREFACE: CEWQO Topical Issue CEWQO Topical Issue

    NASA Astrophysics Data System (ADS)

    Bozic, Mirjana; Man'ko, Margarita

    2009-09-01

    This topical issue of Physica Scripta collects selected peer-reviewed contributions based on invited and contributed talks and posters presented at the 15th Central European Workshop on Quantum Optics (CEWQO) which took place in Belgrade 29 May-3 June 2008 (http://cewqo08.phy.bg.ac.yu). On behalf of the whole community took place in Belgrade 29 May-3 June 2008 (http://cewqo08.phy.bg.ac.yu, cewqo08.phy.bg.ac.yu). On behalf of the whole community of the workshop, we thank the referees for their careful reading and useful suggestions which helped to improve all of the submitted papers. A brief description of CEWQO The Central European Workshop on Quantum Optics is a series of conferences started informally in Budapest in 1992. Sometimes small events transform into important conferences, as in the case of CEWQO. Professor Jozsef Janszky, from the Research Institute of Solid State Physics and Optics, is the founder of this series. Margarita Man'ko obtained the following information from Jozsef Janszky during her visit to Budapest, within the framework of cooperation between the Russian and Hungarian Academies of Sciences in 2005. He organized a small workshop on quantum optics in Budapest in 1992 with John Klauder as a main speaker. Then, bearing in mind that a year before Janszky himself was invited by Vladimir Buzek to give a seminar on the same topic in Bratislava, he decided to assign the name 'Central European Workshop on Quantum Optics', considering the seminar in Bratislava to be the first workshop and the one in Budapest the second. The third formal workshop took place in Bratislava in 1993 organized by Vladimir Buzek, then in 1994 (Budapest, by Jozsef Janszky), 1995 and 1996 (Budmerice, Slovakia, by Vladimir Buzek), 1997 (Prague, by Igor Jex), 1999 (Olomouc, Czech Republic, by Zdenek Hradil), 2000 (Balatonfüred, Hungary, by Jozsef Janszky ), 2001 (Prague, by Igor Jex), 2002 (Szeged, Hungary, by Mihaly Benedict), 2003 (Rostock,Germany, by Werner Vogel and

  18. Topical Products for the Aging Face.

    PubMed

    McCook, John P

    2016-07-01

    This article focuses on nonprescription home-use topical treatment technologies for the aging face and is intended to serve as a guide for the core cosmeceutical technologies currently used and to help educate and assist the selection of topical antiaging products by the professional staff and their patients. Antiaging topical treatments for patient home use should be nonirritating, compatible with the patient skin type, effective, and complementary to surgical and minimally invasive office procedures, and aesthetically elegant. New topical antiaging technologies, formulated as monotherapy or as combinations with well-known cosmeceuticals, should present adequate clinical studies to support their selection for use. PMID:27363774

  19. Hypersensitivity to topical corticosteroids.

    PubMed

    Wilkinson, S M

    1994-01-01

    Contact hypersensitivity from topical corticosteroids is becoming increasingly recognized; it is present in 2-5% of the patients attending contact dermatitis clinics. The use of a corticosteroid series containing tixocortal pivalate 1% (petrolatum), to detect hypersensitivity to hydrocortisone, and other steroids 1% (ethanol), depending on local corticosteroid usage, detects the majority of cases of corticosteroid hypersensitivity. In selected cases, the use of intradermal tests further improves the diagnosis of corticosteroid hypersensitivity. Corticosteroid hypersensitivity occurs most frequently among patients with stasis dermatitis. However, corticosteroid hypersensitivity is also common in other types of dermatitis, occurring as frequently as hypersensitivity to several allergens (e.g. wool alcohols and colophony) in the European standard battery. Although hypersensitivity has mainly been reported with corticosteroids applied to the skin, reactions may also occur on mucosal surfaces, following systemic administration and with sex steroids. PMID:8313630

  20. Method of forming silicon structures with selectable optical characteristics

    NASA Technical Reports Server (NTRS)

    Fathauer, Robert W. (Inventor); Schowalter, Leo (Inventor)

    1993-01-01

    Silicon and metal are coevaporated onto a silicon substrate in a molecular beam epitaxy system with a larger than stoichiometric amount of silicon so as to epitaxially grow particles of metal silicide embedded in a matrix of single crystal epitaxially grown silicon. The particles interact with incident photons by resonant optical absorption at the surface plasmon resonance frequency. Controlling the substrate temperature and deposition rate and time allows the aspect ratio of the particles to be tailored to desired wavelength photons and polarizations. The plasmon energy may decay as excited charge carriers or phonons, either of which can be monitored to indicate the amount of incident radiation at the selected frequency and polarization.

  1. Lactobionic acid as antioxidant and moisturizing active in alkyl polyglucoside-based topical emulsions: the colloidal structure, stability and efficacy evaluation.

    PubMed

    Tasic-Kostov, M; Pavlovic, D; Lukic, M; Jaksic, I; Arsic, I; Savic, S

    2012-10-01

    Cosmeceutical antioxidants may protect the skin against oxidative injury, involved in the pathogenesis of many skin disorders. However, an unsuitable topical delivery system with compromising safety profile can affect the efficacy of an antioxidant active. This study investigated the antioxidant potential of lactobionic acid (LA), a newer cosmeceutical active, per se (in solution) and incorporated into natural alkyl polyglucoside (APG) emulsifier-based system using 1,1-diphenyl-2-picrylhydrazyl free radical scavenging and lipid peroxidation inhibition assays. The α-tocopherol was used as a reference compound. The physical stability (using rheology, polarization microscopy, pH and conductivity measurements) of an Alkyl glucoside-based emulsion was evaluated with and without the active (LA); colloidal structure was assessed using polarization and transmission electron microscopy, rheology, thermal and texture analysis. Additionally, the safety profile and moisturizing potential were investigated using the methods of skin bioengineering. Good physical stability and applicative characteristics were obtained although LA strongly influenced the colloidal structure of the vehicle. LA per se and in APG-based emulsion showed satisfying antioxidant activity that promotes it as mild multifunctional cosmeceutical efficient in the treatment and prevention of the photoaged skin. Employed assays were shown as suitable for the antioxidant activity evaluation of LA in APG-based emulsions, but not for α-tocopherol in the same vehicle. PMID:22691034

  2. The Economics of Structured Continuing Education in Selected Professional Journals.

    ERIC Educational Resources Information Center

    Sasmor, James C.

    A study determined what business administration considerations were elements in the managerial decision making process to include structured continuing education in a professional journal and what the positive or negative results have been in terms of operating benefits and profits. An initial literature review showed the need for exploratory…

  3. Belief Structures about People Held by Selected Graduate Students.

    ERIC Educational Resources Information Center

    Dole, Arthur A.; And Others

    Wrightsman has established that assumptions about human nature distinguish religious, occupational, political, gender, and other groups, and that they predict behavior in structured situations. Hjelle and Ziegler proposed a set of nine basic bipolar assumptions about the nature of people: freedom-determinism; rationality-irrationality;…

  4. Structural Insight into Substrate Selectivity of Erwinia chrysanthemil-Asparaginase

    PubMed Central

    2016-01-01

    l-Asparaginases of bacterial origin are a mainstay of acute lymphoblastic leukemia treatment. The mechanism of action of these enzyme drugs is associated with their capacity to deplete the amino acid l-asparagine from the blood. However, clinical use of bacterial l-asparaginases is complicated by their dual l-asparaginase and l-glutaminase activities. The latter, even though representing only ∼10% of the overall activity, is partially responsible for the observed toxic side effects. Hence, l-asparaginases devoid of l-glutaminase activity hold potential as safer drugs. Understanding the key determinants of l-asparaginase substrate specificity is a prerequisite step toward the development of enzyme variants with reduced toxicity. Here we present crystal structures of the Erwinia chrysanthemil-asparaginase in complex with l-aspartic acid and with l-glutamic acid. These structures reveal two enzyme conformations—open and closed—corresponding to the inactive and active states, respectively. The binding of ligands induces the positioning of the catalytic Thr15 into its active conformation, which in turn allows for the ordering and closure of the flexible N-terminal loop. Notably, l-aspartic acid is more efficient than l-glutamic acid in inducing the active positioning of Thr15. Structural elements explaining the preference of the enzyme for l-asparagine over l-glutamine are discussed with guidance to the future development of more specific l-asparaginases. PMID:26855287

  5. Microbial utilization and selectivity of pectin fractions with various structures.

    PubMed

    Onumpai, Chatchaya; Kolida, Sofia; Bonnin, Estelle; Rastall, Robert A

    2011-08-15

    To evaluate the fermentation properties of oligosaccharides derived from pectins and their parent polysaccharides, a 5-ml-working-volume, pH- and temperature-controlled fermentor was tested. Six pectic oligosaccharides representing specific substructures found within pectins were prepared. These consisted of oligogalacturonides (average degrees of polymerization [DP] of 5 and 9), methylated oligogalacturonides (average DP of 5), oligorhamnogalacturonides (average DP of 10 as a disaccharide unit of galacturonic acid and rhamnose), oligogalactosides (average DP of 5), and oligoarabinosides (average DP of 6). The influence of these carbohydrates on the human fecal microbiota was evaluated. Use of neutral sugar fractions resulted in an increase in Bifidobacterium populations and gave higher organic acid yields. The Bacteroides-Prevotella group significantly increased on all oligosaccharides except oligogalacturonides with an average DP of 5. The most selective substrates for bifidobacteria were arabinan, galactan, oligoarabinosides, and oligogalactosides. PMID:21724897

  6. Restoration of Retinal Structure and Function after Selective Photocoagulation

    PubMed Central

    Jones, Bryan W.; Huie, Philip; Paulus, Yannis M.; Lavinsky, Daniel; Leung, Loh-Shan S.; Nomoto, Hiroyuki; Beier, Corinne; Marc, Robert E.; Palanker, Daniel

    2013-01-01

    CNS neurons change their connectivity to accommodate a changing environment, form memories, or respond to injury. Plasticity in the adult mammalian retina after injury or disease was thought to be limited to restructuring resulting in abnormal retinal anatomy and function. Here we report that neurons in the mammalian retina change their connectivity and restore normal retinal anatomy and function after injury. Patches of photoreceptors in the rabbit retina were destroyed by selective laser photocoagulation, leaving retinal inner neurons (bipolar, amacrine, horizontal, ganglion cells) intact. Photoreceptors located outside of the damaged zone migrated to make new functional connections with deafferented bipolar cells located inside the lesion. The new connections restored ON and OFF responses in deafferented ganglion cells. This finding extends the previously perceived limits of restorative plasticity in the adult retina and allows for new approaches to retinal laser therapy free of current detrimental side effects such as scotomata and scarring. PMID:23595739

  7. Composite load spectra for select space propulsion structural components

    NASA Technical Reports Server (NTRS)

    Newell, J. F.; Kurth, R. E.; Ho, H.

    1991-01-01

    The objective of this program is to develop generic load models with multiple levels of progressive sophistication to simulate the composite (combined) load spectra that are induced in space propulsion system components, representative of Space Shuttle Main Engines (SSME), such as transfer ducts, turbine blades, and liquid oxygen posts and system ducting. The first approach will consist of using state of the art probabilistic methods to describe the individual loading conditions and combinations of these loading conditions to synthesize the composite load spectra simulation. The second approach will consist of developing coupled models for composite load spectra simulation which combine the deterministic models for composite load dynamic, acoustic, high pressure, and high rotational speed, etc., load simulation using statistically varying coefficients. These coefficients will then be determined using advanced probabilistic simulation methods with and without strategically selected experimental data.

  8. Instructional Complements for Undergraduate World History or Western Civilization Courses: Selected Topics in the Ancient, Medieval, and Modern History of India: A Curriculum Supplement.

    ERIC Educational Resources Information Center

    Wiley, Wayne Hamilton

    This curriculum supplement on India consists of three modules that have been used with undergraduates in introductory world civilization courses. Module 1, "Ancient Period: Hinduism and the Caste System in India: Origin, Development, and Social Functions" discusses the religious doctrines of Hinduism, the caste system, and its structure. The…

  9. Effect of parental selection of healthy behavior topic on immediate and delayed plan to change child’s eating or physical activity behavior

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recommendations direct pediatricians to address obesity and obesity prevention routinely during well child visits and to tailor their counseling, but clinicians feel ineffective because of time constraints and lack of parent interest. This intervention was designed to maintain the structure of the o...

  10. Considering Future Potential Regarding Structural Diversity in Selection of Forest Reserves.

    PubMed

    Lundström, Johanna; Öhman, Karin; Rönnqvist, Mikael; Gustafsson, Lena

    2016-01-01

    A rich structural diversity in forests promotes biodiversity. Forests are dynamic and therefore it is crucial to consider future structural potential when selecting reserves, to make robust conservation decisions. We analyzed forests in boreal Sweden based on 17,599 National Forest Inventory (NFI) plots with the main aim to understand how effectiveness of reserves depends on the time dimension in the selection process, specifically by considering future structural diversity. In the study both the economic value and future values of 15 structural variables were simulated during a 100 year period. To get a net present structural value (NPSV), a single value covering both current and future values, we used four discounting alternatives: (1) only considering present values, (2) giving equal importance to values in each of the 100 years within the planning horizon, (3) applying an annual discount rate considering the risk that values could be lost, and (4) only considering the values in year 100. The four alternatives were evaluated in a reserve selection model under budget-constrained and area-constrained selections. When selecting young forests higher structural richness could be reached at a quarter of the cost over almost twice the area in a budget-constrained selection compared to an area-constrained selection. Our results point to the importance of considering future structural diversity in the selection of forest reserves and not as is done currently to base the selection on existing values. Targeting future values increases structural diversity and implies a relatively lower cost. Further, our results show that a re-orientation from old to young forests would imply savings while offering a more extensive reserve network with high structural qualities in the future. However, caution must be raised against a drastic reorientation of the current old-forest strategy since remnants of ancient forests will need to be prioritized due to their role for disturbance

  11. Considering Future Potential Regarding Structural Diversity in Selection of Forest Reserves

    PubMed Central

    Lundström, Johanna; Öhman, Karin; Rönnqvist, Mikael; Gustafsson, Lena

    2016-01-01

    A rich structural diversity in forests promotes biodiversity. Forests are dynamic and therefore it is crucial to consider future structural potential when selecting reserves, to make robust conservation decisions. We analyzed forests in boreal Sweden based on 17,599 National Forest Inventory (NFI) plots with the main aim to understand how effectiveness of reserves depends on the time dimension in the selection process, specifically by considering future structural diversity. In the study both the economic value and future values of 15 structural variables were simulated during a 100 year period. To get a net present structural value (NPSV), a single value covering both current and future values, we used four discounting alternatives: (1) only considering present values, (2) giving equal importance to values in each of the 100 years within the planning horizon, (3) applying an annual discount rate considering the risk that values could be lost, and (4) only considering the values in year 100. The four alternatives were evaluated in a reserve selection model under budget-constrained and area-constrained selections. When selecting young forests higher structural richness could be reached at a quarter of the cost over almost twice the area in a budget-constrained selection compared to an area-constrained selection. Our results point to the importance of considering future structural diversity in the selection of forest reserves and not as is done currently to base the selection on existing values. Targeting future values increases structural diversity and implies a relatively lower cost. Further, our results show that a re-orientation from old to young forests would imply savings while offering a more extensive reserve network with high structural qualities in the future. However, caution must be raised against a drastic reorientation of the current old-forest strategy since remnants of ancient forests will need to be prioritized due to their role for disturbance

  12. Structural and optical studies on selected web spinning spider silks.

    PubMed

    Karthikeyani, R; Divya, A; Mathavan, T; Asath, R Mohamed; Benial, A Milton Franklin; Muthuchelian, K

    2017-01-01

    This study investigates the structural and optical properties in the cribellate silk of the sheet web spider Stegodyphus sarasinorum Karsch (Eresidae) and the combined dragline, viscid silk of the orb-web spiders Argiope pulchella Thorell (Araneidae) and Nephila pilipes Fabricius (Nephilidae). X-ray diffraction (XRD), Fourier transform infra-red (FTIR), Ultraviolet-visible (UV-Vis) and fluorescence spectroscopic techniques were used to study these three spider silk species. X-ray diffraction data are consistent with the amorphous polymer network which is arising from the interaction of larger side chain amino acid contributions due to the poly-glycine rich sequences known to be present in the proteins of cribellate silk. The same amorphous polymer networks have been determined from the combined dragline and viscid silk of orb-web spiders. From FTIR spectra the results demonstrate that, cribellate silk of Stegodyphus sarasinorum, combined dragline viscid silk of Argiope pulchella and Nephila pilipes spider silks are showing protein peaks in the amide I, II and III regions. Further they proved that the functional groups present in the protein moieties are attributed to α-helical and side chain amino acid contributions. The optical properties of the obtained spider silks such as extinction coefficients, refractive index, real and imaginary dielectric constants and optical conductance were studied extensively from UV-Vis analysis. The important fluorescent amino acid tyrosine is present in the protein folding was investigated by using fluorescence spectroscopy. This research would explore the protein moieties present in the spider silks which were found to be associated with α-helix and side chain amino acid contributions than with β-sheet secondary structure and also the optical relationship between the three different spider silks are investigated. Successful spectroscopic knowledge of the internal protein structure and optical properties of the spider silks could

  13. Coexistence of structured populations with size-based prey selection.

    PubMed

    Hartvig, Martin; Andersen, Ken Haste

    2013-11-01

    Species with a large adult-offspring size ratio and a preferred predator-prey mass ratio undergo ontogenetic trophic niche shift(s) throughout life. Trophic interactions between such species vary throughout life, resulting in different species-level interaction motifs depending on the maximum adult sizes and population size distributions. We explore the assembly and potential for coexistence of small communities where all species experience ontogenetic trophic niche shifts. The life-history of each species is described by a physiologically structured model and species identity is characterised by the trait: size at maturation. We show that a single species can exist in two different states: a 'resource driven state' and a 'cannibalistic state' with a large scope for emergent Allee effects and bistable states. Two species can coexist in two different configurations: in a 'competitive coexistence' state when the ratio between sizes at maturation of the two species is less than a predator-prey mass ratio and the resource level is low to intermediate, or in a 'trophic ladder' state if the ratio of sizes at maturation is larger than the predator-prey mass ratio at all resource levels. While there is a large scope for coexistence of two species, the scope for coexistence of three species is limited and we conclude that further trait differentiation is required for coexistence of more species-rich size-structured communities. PMID:23927897

  14. Selective visualization of gene structure with ultraviolet light

    SciTech Connect

    Wang, Z.; Becker, M.M.

    1988-02-01

    The ability of the ultraviolet (UV) footprinting technique to detect chromatin has been investigated in vitro. Two basic types of chromatin, a phased nucleosome and a phased nucleosome containing a phased H1 protein, have been reconstituted onto a cloned 5S ribosomal RNA gene from sea urchin. The histone-DNA interactions in each complex have been probed with exonuclease III, DNase I, dimethyl sulfate, and UV light. Whereas DNase I and exonuclease III readily detect interactions between histones and DNA, UV light and dimethyl sulfate do not. In contrast to histone-DNA interactions, we demonstrate that intimate sequence-specific contacts between the same sea urchin 5S DNA and the Xenopus laevis transcription factor IIIA (TFIIIA) are readily detected with UV light. Since the sensitivity of UV light for TFIIIA contacts is similar to its sensitivity for other regulatory protein-DNA contacts, these studies demonstrate the feasibility of using UV light to selectively visualize regulatory protein-DNA interactions in vivo with little or no interference from histone-DNA interactions.

  15. Structural Dynamics of GaN Microcrystals in Evolutionary Selection Selective Area Growth probed by X-ray Microdiffraction

    PubMed Central

    Kachkanov, V.; Leung, B.; Song, J.; Zhang, Y.; Tsai, M.-C.; Yuan, G.; Han, J.; O'Donnell, K. P.

    2014-01-01

    A method to grow high quality, single crystalline semiconductor material irrespective of the substrate would allow a cost-effective improvement to functionality and performance of optoelectronic devices. Recently, a novel type of substrate-insensitive growth process called Evolutionary Selection Selective Area Growth (ES-SAG) has been proposed. Here we report the use of X-ray microdiffraction to study the structural properties of GaN microcrystals grown by ES-SAG. Utilizing high resolution in both direct and reciprocal spaces, we have unraveled structural dynamics of GaN microcrystals in growth structures of different dimensions. It has been found that the geometric proportions of the growth constrictions play an important role: 2.6 μm and 4.5 μm wide growth tunnels favor the evolutionary selection mechanism, contrary to the case of 8.6 μm growth tunnels. It was also found that GaN microcrystal ensembles are dominated by slight tensile strain irrespective of growth tunnel shape. PMID:24722064

  16. Composite load spectra for select space propulsion structural components

    NASA Technical Reports Server (NTRS)

    Newell, J. F.; Kurth, R. E.; Ho, H.

    1991-01-01

    The objective of this program is to develop generic load models with multiple levels of progressive sophistication to simulate the composite load spectra that are induced in space propulsion system components, representative of Space Shuttle Main Engines (SSME), such as transfer ducts, turbine blades, and liquid oxygen (LOX) posts and system ducting. These models will be developed using two independent approaches. The first approach consists of using state-of-the-art probabilistic methods to describe the individual loading conditions and combinations of these loading conditions to synthesize the composite load spectra simulation. The methodology required to combine the various individual load simulation models (hot-gas dynamic, vibrations, instantaneous position, centrifugal field, etc.) into composite load spectra simulation models will be developed under this program. A computer code incorporating the various individual and composite load spectra models will be developed to construct the specific load model desired. The second approach, which is covered under the options portion of the contract, will consist of developing coupled models for composite load spectra simulation which combine the (deterministic) models for composite load dynamic, acoustic, high-pressure and high rotational speed, etc., load simulation using statistically varying coefficients. These coefficients will then be determined using advanced probabilistic simulation methods with and without strategically selected experimental data. This report covers the efforts of the third year of the contract. The overall program status is that the turbine blade loads have been completed and implemented. The transfer duct loads are defined and are being implemented. The thermal loads for all components are defined and coding is being developed. A dynamic pressure load model is under development. The parallel work on the probabilistic methodology is essentially completed. The overall effort is being

  17. Haloprogin: a Topical Antifungal Agent

    PubMed Central

    Harrison, E. F.; Zwadyk, P.; Bequette, R. J.; Hamlow, E. E.; Tavormina, P. A.; Zygmunt, W. A.

    1970-01-01

    Haloprogin was shown to be a highly effective agent for the treatment of experimentally induced topical mycotic infections in guinea pigs. Its in vitro spectrum of activity also includes yeasts, yeastlike fungi (Candida species), and certain gram-positive bacteria. The in vitro and in vivo antifungal activity of haloprogin against dermatophytes was equal to that observed with tolnaftate. The striking differences between the two agents were the marked antimonilial and selective antibacterial activities shown by haloprogin, contrasted with the negligible activities found with tolnaftate. Addition of serum decreased the in vitro antifungal activity of haloprogin to a greater extent than that of tolnaftate; however, diminished antifungal activity was not observed when haloprogin was applied topically to experimental dermatophytic infections. Based on its broad spectrum of antimicrobial activity, haloprogin may prove to be a superior topical agent in the treatment of dermatophytic and monilial infections in man. PMID:5422306

  18. Selective Reinforcement to Enhance the Structural Performance of Metallic Compression Panels

    NASA Technical Reports Server (NTRS)

    Farley, Gary L.

    2004-01-01

    An experimental and analytical investigation of the influence of selective reinforcement on metallic panels with cutouts was conducted. Selective reinforcement was shown to be a weight effective concept for increasing structural performance of panels with cutouts designed to carry loads into the post-buckled regime. For instance, a selectively reinforced aluminum panel under shear load exhibited a 68 percent increase in specific-buckling load as compared to a geometrically comparable unreinforced aluminum panel. In comparison, a quasi-isotropic carbon-fiber-reinforced-polymer composite panel only produced a 45 percent higher specific-buckling load than the same unreinforced aluminum panel. Selective reinforcement offers the potential to tailor structural response through local strengthening and stiffening the structure for a broad range of structural application.

  19. Selective exchange of divalent transition metal ions in cryptomelane-type manganic acid with tunnel structure

    SciTech Connect

    Tsuji, M. ); Komarneni, S. )

    1993-03-01

    The ion-exchange selectivity of divalent transition metal ions on cryptomelane-type manganic acid (CMA) with tunnel structure has been studied using the distribution coefficients ([ital K][sub [ital d

  20. Comparative topical anti-inflammatory activity of cannabinoids and cannabivarins.

    PubMed

    Tubaro, Aurelia; Giangaspero, Anna; Sosa, Silvio; Negri, Roberto; Grassi, Gianpaolo; Casano, Salvatore; Della Loggia, Roberto; Appendino, Giovanni

    2010-10-01

    A selection of seven phytocannabinoids representative of the major structural types of classic cannabinoids and their corresponding cannabivarins was investigated for in vivo topical anti-inflammatory activity in the Croton oil mouse ear dermatitis assay. Differences in the terpenoid moiety were far more important for anti-inflammatory activity than those at the C-3 alkyl residue, suggesting the involvement not only of cannabinoid receptors, but also of other inflammatory end-points targeted by phytocannabinoids. PMID:20450962

  1. The Structure of Genealogies in the Presence of Purifying Selection: A Fitness-Class Coalescent

    PubMed Central

    Walczak, Aleksandra M.; Nicolaisen, Lauren E.; Plotkin, Joshua B.; Desai, Michael M.

    2012-01-01

    Compared to a neutral model, purifying selection distorts the structure of genealogies and hence alters the patterns of sampled genetic variation. Although these distortions may be common in nature, our understanding of how we expect purifying selection to affect patterns of molecular variation remains incomplete. Genealogical approaches such as coalescent theory have proven difficult to generalize to situations involving selection at many linked sites, unless selection pressures are extremely strong. Here, we introduce an effective coalescent theory (a “fitness-class coalescent”) to describe the structure of genealogies in the presence of purifying selection at many linked sites. We use this effective theory to calculate several simple statistics describing the expected patterns of variation in sequence data, both at the sites under selection and at linked neutral sites. Our analysis combines a description of the allele frequency spectrum in the presence of purifying selection with the structured coalescent approach of Kaplan et al. (1988), to trace the ancestry of individuals through the distribution of fitnesses within the population. We also derive our results using a more direct extension of the structured coalescent approach of Hudson and Kaplan (1994). We find that purifying selection leads to patterns of genetic variation that are related but not identical to a neutrally evolving population in which population size has varied in a specific way in the past. PMID:22135349

  2. Seven topics in perturbative QCD

    SciTech Connect

    Buras, A.J.

    1980-09-01

    The following topics of perturbative QCD are discussed: (1) deep inelastic scattering; (2) higher order corrections to e/sup +/e/sup -/ annihilation, to photon structure functions and to quarkonia decays; (3) higher order corrections to fragmentation functions and to various semi-inclusive processes; (4) higher twist contributions; (5) exclusive processes; (6) transverse momentum effects; (7) jet and photon physics.

  3. TOPICAL REVIEW: Black silicon method X: a review on high speed and selective plasma etching of silicon with profile control: an in-depth comparison between Bosch and cryostat DRIE processes as a roadmap to next generation equipment

    NASA Astrophysics Data System (ADS)

    Jansen, H V; de Boer, M J; Unnikrishnan, S; Louwerse, M C; Elwenspoek, M C

    2009-03-01

    An intensive study has been performed to understand and tune deep reactive ion etch (DRIE) processes for optimum results with respect to the silicon etch rate, etch profile and mask etch selectivity (in order of priority) using state-of-the-art dual power source DRIE equipment. The research compares pulsed-mode DRIE processes (e.g. Bosch technique) and mixed-mode DRIE processes (e.g. cryostat technique). In both techniques, an inhibitor is added to fluorine-based plasma to achieve directional etching, which is formed out of an oxide-forming (O2) or a fluorocarbon (FC) gas (C4F8 or CHF3). The inhibitor can be introduced together with the etch gas, which is named a mixed-mode DRIE process, or the inhibitor can be added in a time-multiplexed manner, which will be termed a pulsed-mode DRIE process. Next, the most convenient mode of operation found in this study is highlighted including some remarks to ensure proper etching (i.e. step synchronization in pulsed-mode operation and heat control of the wafer). First of all, for the fabrication of directional profiles, pulsed-mode DRIE is far easier to handle, is more robust with respect to the pattern layout and has the potential of achieving much higher mask etch selectivity, whereas in a mixed-mode the etch rate is higher and sidewall scalloping is prohibited. It is found that both pulsed-mode CHF3 and C4F8 are perfectly suited to perform high speed directional etching, although they have the drawback of leaving the FC residue at the sidewalls of etched structures. They show an identical result when the flow of CHF3 is roughly 30 times the flow of C4F8, and the amount of gas needed for a comparable result decreases rapidly while lowering the temperature from room down to cryogenic (and increasing the etch rate). Moreover, lowering the temperature lowers the mask erosion rate substantially (and so the mask selectivity improves). The pulsed-mode O2 is FC-free but shows only tolerable anisotropic results at -120 °C. The

  4. Improving a consensus approach for protein structure selection by removing redundancy.

    PubMed

    Wang, Qingguo; Shang, Yi; Xu, Dong

    2011-01-01

    In protein tertiary structure prediction, a crucial step is to select near-native structures from a large number of predicted structural models. Over the years, extensive research has been conducted for the protein structure selection problem with most approaches focusing on developing more accurate energy or scoring functions. Despite significant advances in this area, the discerning power of current approaches is still unsatisfactory. In this paper, we propose a novel consensus-based algorithm for the selection of predicted protein structures. Given a set of predicted models, our method first removes redundant structures to derive a subset of reference models. Then, a structure is ranked based on its average pairwise similarity to the reference models. Using the CASP8 data set containing a large collection of predicted models for 122 targets, we compared our method with the best CASP8 quality assessment (QA) servers, which are all consensus based, and showed that our QA scores correlate better with the GDT-TSs than those of the CASP8 QA servers. We also compared our method with the state-of-the-art scoring functions and showed its improved performance for near-native model selection. The GDT-TSs of the top models picked by our method are on average more than 8 percent better than the ones selected by the best performing scoring function. PMID:21519117

  5. The structure of XIAP BIR2: understanding the selectivity of the BIR domains

    SciTech Connect

    Lukacs, Christine Belunis, Charles; Crowther, Robert; Danho, Waleed; Gao, Lin; Goggin, Barry; Janson, Cheryl A.; Li, Shirley; Remiszewski, Stacy; Schutt, Andrew; Thakur, Manish K.; Singh, Saroj K.; Swaminathan, Srinivasan; Pandey, Rajat; Tyagi, Rajiv; Gosu, Ramachandraiah; Kamath, Ajith V.; Kuglstatter, Andreas

    2013-09-01

    The high-resolution crystal structures of apo and peptide-bound XIAP BIR2 are presented and compared with BIR3 structures to understand their selectivity. This crystal system can be used to determine the structures of BIR2–inhibitor complexes. XIAP, a member of the inhibitor of apoptosis family of proteins, is a critical regulator of apoptosis. Inhibition of the BIR domain–caspase interaction is a promising approach towards treating cancer. Previous work has been directed towards inhibiting the BIR3–caspase-9 interaction, which blocks the intrinsic apoptotic pathway; selectively inhibiting the BIR2–caspase-3 interaction would also block the extrinsic pathway. The BIR2 domain of XIAP has successfully been crystallized; peptides and small-molecule inhibitors can be soaked into these crystals, which diffract to high resolution. Here, the BIR2 apo crystal structure and the structures of five BIR2–tetrapeptide complexes are described. The structural flexibility observed on comparing these structures, along with a comparison with XIAP BIR3, affords an understanding of the structural elements that drive selectivity between BIR2 and BIR3 and which can be used to design BIR2-selective inhibitors.

  6. The Acceptance of Universalism: The Importance of Selected Aspects of School Structure.

    ERIC Educational Resources Information Center

    Martin, Robert A.

    This report describes a study that investigated empirically the relationships between selected aspects of the organizational structure of elementary schools and the extent to which students endorsed the norm of universalism. Four aspects of structure were studied: degree of departmentalization, school enrollment, student-teacher ratio, and extent…

  7. Discovery and Structure-Activity Relationships of a Highly Selective Butyrylcholinesterase Inhibitor by Structure-Based Virtual Screening.

    PubMed

    Dighe, Satish N; Deora, Girdhar Singh; De la Mora, Eugenio; Nachon, Florian; Chan, Stephen; Parat, Marie-Odile; Brazzolotto, Xavier; Ross, Benjamin P

    2016-08-25

    Structure-based virtual screening of two libraries containing 567 981 molecules was used to discover novel, selective BuChE inhibitors, which are potentially superior symptomatic treatments in late-stage Alzheimer's disease. Compound 16 was identified as a highly selective submicromolar inhibitor of BuChE (huBuChE IC50 = 0.443 μM) with high permeability in the PAMPA-BBB model. The X-ray crystal structure of huBuChE in complex with 16 revealed the atomic-level interactions and offers opportunities for further development of the series. PMID:27405689

  8. The Structural Basis of Cryptosporidium-Specific IMP Dehydrogenase Inhibitor Selectivity

    SciTech Connect

    MacPherson, Iain S.; Kirubakaran, Sivapriya; Gorla, Suresh Kumar; Riera, Thomas V.; D’Aquino, J. Alejandro; Zhang, Minjia; Cuny, Gregory D.; Hedstrom, Lizbeth

    2010-03-29

    Cryptosporidium parvum is a potential biowarfare agent, an important AIDS pathogen, and a major cause of diarrhea and malnutrition. No vaccines or effective drug treatment exist to combat Cryptosporidium infection. This parasite relies on inosine 5{prime}-monophosphate dehydrogenase (IMPDH) to obtain guanine nucleotides, and inhibition of this enzyme blocks parasite proliferation. Here, we report the first crystal structures of CpIMPDH. These structures reveal the structural basis of inhibitor selectivity and suggest a strategy for further optimization. Using this information, we have synthesized low-nanomolar inhibitors that display 10{sup 3} selectivity for the parasite enzyme over human IMPDH2.

  9. Identifying Topics in Microblogs Using Wikipedia.

    PubMed

    Yıldırım, Ahmet; Üsküdarlı, Suzan; Özgür, Arzucan

    2016-01-01

    Twitter is an extremely high volume platform for user generated contributions regarding any topic. The wealth of content created at real-time in massive quantities calls for automated approaches to identify the topics of the contributions. Such topics can be utilized in numerous ways, such as public opinion mining, marketing, entertainment, and disaster management. Towards this end, approaches to relate single or partial posts to knowledge base items have been proposed. However, in microblogging systems like Twitter, topics emerge from the culmination of a large number of contributions. Therefore, identifying topics based on collections of posts, where individual posts contribute to some aspect of the greater topic is necessary. Models, such as Latent Dirichlet Allocation (LDA), propose algorithms for relating collections of posts to sets of keywords that represent underlying topics. In these approaches, figuring out what the specific topic(s) the keyword sets represent remains as a separate task. Another issue in topic detection is the scope, which is often limited to specific domain, such as health. This work proposes an approach for identifying domain-independent specific topics related to sets of posts. In this approach, individual posts are processed and then aggregated to identify key tokens, which are then mapped to specific topics. Wikipedia article titles are selected to represent topics, since they are up to date, user-generated, sophisticated articles that span topics of human interest. This paper describes the proposed approach, a prototype implementation, and a case study based on data gathered during the heavily contributed periods corresponding to the four US election debates in 2012. The manually evaluated results (0.96 precision) and other observations from the study are discussed in detail. PMID:26991442

  10. Identifying Topics in Microblogs Using Wikipedia

    PubMed Central

    Yıldırım, Ahmet; Üsküdarlı, Suzan; Özgür, Arzucan

    2016-01-01

    Twitter is an extremely high volume platform for user generated contributions regarding any topic. The wealth of content created at real-time in massive quantities calls for automated approaches to identify the topics of the contributions. Such topics can be utilized in numerous ways, such as public opinion mining, marketing, entertainment, and disaster management. Towards this end, approaches to relate single or partial posts to knowledge base items have been proposed. However, in microblogging systems like Twitter, topics emerge from the culmination of a large number of contributions. Therefore, identifying topics based on collections of posts, where individual posts contribute to some aspect of the greater topic is necessary. Models, such as Latent Dirichlet Allocation (LDA), propose algorithms for relating collections of posts to sets of keywords that represent underlying topics. In these approaches, figuring out what the specific topic(s) the keyword sets represent remains as a separate task. Another issue in topic detection is the scope, which is often limited to specific domain, such as health. This work proposes an approach for identifying domain-independent specific topics related to sets of posts. In this approach, individual posts are processed and then aggregated to identify key tokens, which are then mapped to specific topics. Wikipedia article titles are selected to represent topics, since they are up to date, user-generated, sophisticated articles that span topics of human interest. This paper describes the proposed approach, a prototype implementation, and a case study based on data gathered during the heavily contributed periods corresponding to the four US election debates in 2012. The manually evaluated results (0.96 precision) and other observations from the study are discussed in detail. PMID:26991442

  11. Microphase separated structures of block copolymer thin film with non-volatile selective solvent

    NASA Astrophysics Data System (ADS)

    Yamamoto, Katsuhiro; Umegaki, Naoya; Matsutani, Taito; Takagi, Hideaki; Ito, Eri; Sakurai, Shinichi

    2010-11-01

    Microphase separated structures of block copolymer, polystyrene-b-polyisoprene (PS-b-PI, phiPS = 14%) including non-volatile selective solvent thin films were investigated using grazing incidence small angle X-ray scattering technique. The diethyl phthalate (DEP) was used as a non-volatile selective solvent which solves PS only. The DEP swelled PS phase selectively and the microphase separated structure transited from the PS spherical domain to the lamellar domain with an increase in DEP content in the bulk state. Similarly, the phase separated structure in the thin film prepared by spin cast on a silicon wafer from the mixture of toluene/DEP and block copolymer changed according to the initial DPE concentration. However, the morphologies developed in the thin film were shifted to the structures at lower DEP concentration than that expected from the initial concentration. Moreover, the cylindrical and lamellar domains were aligned parallel and perpendicularly to the substrate, respectively.

  12. IT vendor selection model by using structural equation model & analytical hierarchy process

    NASA Astrophysics Data System (ADS)

    Maitra, Sarit; Dominic, P. D. D.

    2012-11-01

    Selecting and evaluating the right vendors is imperative for an organization's global marketplace competitiveness. Improper selection and evaluation of potential vendors can dwarf an organization's supply chain performance. Numerous studies have demonstrated that firms consider multiple criteria when selecting key vendors. This research intends to develop a new hybrid model for vendor selection process with better decision making. The new proposed model provides a suitable tool for assisting decision makers and managers to make the right decisions and select the most suitable vendor. This paper proposes a Hybrid model based on Structural Equation Model (SEM) and Analytical Hierarchy Process (AHP) for long-term strategic vendor selection problems. The five steps framework of the model has been designed after the thorough literature study. The proposed hybrid model will be applied using a real life case study to assess its effectiveness. In addition, What-if analysis technique will be used for model validation purpose.

  13. ACEE Composite Structures Technology: Review of selected NASA research on composite materials and structures

    NASA Technical Reports Server (NTRS)

    1984-01-01

    The NASA Aircraft Energy Efficiency (ACEE) Composite Primary Aircraft Structures Program was designed to develop technology for advanced composites in commercial aircraft. Research on composite materials, aircraft structures, and aircraft design is presented herein. The following parameters of composite materials were addressed: residual strength, damage tolerance, toughness, tensile strength, impact resistance, buckling, and noise transmission within composite materials structures.

  14. Profile comparison revealed deviation from structural constraint at the positively selected sites.

    PubMed

    Oda, Hiroyuki; Ota, Motonori; Toh, Hiroyuki

    2016-09-01

    The amino acid substitutions at a site are affected by mixture of various constraints. It is also known that the amino acid substitutions are accelerated at sites under positive selection. However, the relationship between the substitutions at positively selected sites and the constraints has not been thoroughly examined. The advances in computational biology have enabled us to divide the mixture of the constraints into the structural constraint and the remainings by using the amino acid sequences and the tertiary structures, which is expressed as the deviation of the mixture of constraints from the structural constraint. Here, two types of profiles, or matrices with the size of 20 x (site length), are compared. One of the profiles represents the mixture of constraints, and is generated from a multiple amino acid sequence alignment, whereas the other is designed to represent the structural constraints. We applied the profile comparison method to proteins under positive selection to examine the relationship between the positive selection and constraints. The results suggested that the constraint at a site under positive selection tends to be deviated from the structural constraint at the site. PMID:27443483

  15. A hidden Markov model for investigating recent positive selection through haplotype structure.

    PubMed

    Chen, Hua; Hey, Jody; Slatkin, Montgomery

    2015-02-01

    Recent positive selection can increase the frequency of an advantageous mutant rapidly enough that a relatively long ancestral haplotype will be remained intact around it. We present a hidden Markov model (HMM) to identify such haplotype structures. With HMM identified haplotype structures, a population genetic model for the extent of ancestral haplotypes is then adopted for parameter inference of the selection intensity and the allele age. Simulations show that this method can detect selection under a wide range of conditions and has higher power than the existing frequency spectrum-based method. In addition, it provides good estimate of the selection coefficients and allele ages for strong selection. The method analyzes large data sets in a reasonable amount of running time. This method is applied to HapMap III data for a genome scan, and identifies a list of candidate regions putatively under recent positive selection. It is also applied to several genes known to be under recent positive selection, including the LCT, KITLG and TYRP1 genes in Northern Europeans, and OCA2 in East Asians, to estimate their allele ages and selection coefficients. PMID:25446961

  16. A Hidden Markov Model for Investigating Recent Positive Selection through Haplotype Structure

    PubMed Central

    Hey, Jody; Slatkin, Montgomery

    2014-01-01

    Recent positive selection can increase the frequency of an advantageous mutant rapidly enough that a relatively long ancestral haplotype will be remained intact around it. We present a hidden Markov model (HMM) to identify such haplotype structures. With HMM identified haplotype structures, a population genetic model for the extent of ancestral haplotypes is then adopted for parameter inference of the selection intensity and the allele age. Simulations show that this method can detect selection under a wide range of conditions and has higher power than the existing frequency spectrum-based method. In addition, it provides good estimate of the selection coefficients and allele ages for strong selection. The method analyzes large data sets in a reasonable amount of running time. This method is applied to HapMap III data for a genome scan, and identifies a list of candidate regions putatively under recent positive selection. It is also applied to several genes known to be under recent positive selection, including the LCT, KITLG and TYRP1 genes in Northern Europeans, and OCA2 in East Asians, to estimate their allele ages and selection coefficients. PMID:25446961

  17. Structured Practice in Preparing School Personnel; A Guide to Selected Documents in the ERIC Collection, 1966-1968.

    ERIC Educational Resources Information Center

    Ross, Marlene

    One hundred books, articles, and papers published between 1959 and 1968 are listed in this annotated bibliography of selected documents on teacher education in the Educational Resources Information Center (ERIC) collection. Summaries of topics with references to document numbers are included in Part 1, and abstracts to which the summaries are…

  18. Selected Topics in Peace Corps Training.

    ERIC Educational Resources Information Center

    Hubchen, Jonathan

    Steps to alleviate the problems in achieving successful technical and cross-cultural training for United States Peace Corps volunteers are discussed. Historically, training was conducted at American universities or centers in Puerto Rico, Hawaii, or the Virgin Islands, but by the mid-1970s, in response to criticism that this provided inadequate…

  19. Selected topics related to occupational exposures.

    PubMed

    Leikin, J B; Davis, A; Klodd, D A; Thunder, T; Kelafant, G A; Paquette, D L; Rothe, M J; Rubin, R

    2000-04-01

    The auditory and nonauditory effects of noise can be quite profound, affecting approximately 15 to 20 million Americans. As with most occupational toxins, recognition and careful assessment of noise exposure are the foundation on which preventive measures and treatment are based. Dosimeters can measure noise exposure over specific time periods. Pure tone air conduction audiometric monitoring should be performed on an annual basis in workers at risk for significant noise exposure. Occupational infectious disease involves far more than hepatitis and tuberculosis. Periodic fever, dermatologic manifestations and other symptoms peculiar to a specific disease may be important clues to an occupationally related exposure. Whereas strict attention to hand washing and isolation are cornerstones of prevention, use of protective gear is mandated in certain situations. Zoonotic disease, agriculture exposure, water transmission, and biologic contaminants in buildings can be important but subtle exposures sources. Recognition of these infections often depends on the alertness of the primary care giver. PMID:10830610

  20. School Chemistry, Trends in Reform, Selected Topics.

    ERIC Educational Resources Information Center

    Chisman, D. G.

    Trends, from 1960 to 1963, in the teaching of chemistry in secondary schools in Austria, Belgium, Denmark, France, Germany, Greece, Ireland, Italy, Netherlands, Norway, Spain, Switzerland, Turkey, United Kingdom, and the United States of America are outlined in the first part of this report of a 1963 working session on the teaching of school…

  1. Application of value-focused thinking on the environmental selection of wall structures.

    PubMed

    Hassan, O A B

    2004-02-01

    The decision of selecting building structures with respect to the environmental demand is an issue commonly addressed in environmental management. In this paper, the importance of considering the decision analysis technique value-focused thinking in the environmental selection of wall structures is investigated. In this context, a qualitative value model is developed in which the external and internal environmental factors are considered. The model is applied on a case study in which a decision should be made on three categories of exterior wall structures: wood, masonry and concrete. It is found that the wall structure made of wood is the most compatible option with respect to the external and internal environmental requirements of building structures. PMID:15160743

  2. Salicylic Acid Topical

    MedlinePlus

    Propa pH® Peel-Off Acne Mask ... pimples and skin blemishes in people who have acne. Topical salicylic acid is also used to treat ... medications called keratolytic agents. Topical salicylic acid treats acne by reducing swelling and redness and unplugging blocked ...

  3. Health Topic XML File Description

    MedlinePlus

    ... has its own topic> element. This topic title is the value of the element. The attributes ... topic pages and other pages. Example: topic title="Abdominal Pain" url="https://www.nlm.nih.gov/ ...

  4. Selection of optimal artificial boundary condition (ABC) frequencies for structural damage identification

    NASA Astrophysics Data System (ADS)

    Mao, Lei; Lu, Yong

    2016-07-01

    In this paper, the sensitivities of artificial boundary condition (ABC) frequencies to the damages are investigated, and the optimal sensors are selected to provide the reliable structural damage identification. The sensitivity expressions for one-pin and two-pin ABC frequencies, which are the natural frequencies from structures with one and two additional constraints to its original boundary condition, respectively, are proposed. Based on the expressions, the contributions of the underlying mode shapes in the ABC frequencies can be calculated and used to select more sensitive ABC frequencies. Selection criteria are then defined for different conditions, and their performance in structural damage identification is examined with numerical studies. From the findings, conclusions are given.

  5. Topic Maps e-Learning Portal Development

    ERIC Educational Resources Information Center

    Olsevicova, Kamila

    2006-01-01

    Topic Maps, ISO/IEC 13250 standard, are designed to facilitate the organization and navigation of large collections of information objects by creating meta-level perspectives of their underlying concepts and relationships. The underlying structure of concepts and relations is expressed by domain ontologies. The Topics Maps technology can become…

  6. Probabilistic Structural Analysis Methods (PSAM) for select space propulsion system structural components

    NASA Technical Reports Server (NTRS)

    Cruse, T. A.

    1987-01-01

    The objective is the development of several modular structural analysis packages capable of predicting the probabilistic response distribution for key structural variables such as maximum stress, natural frequencies, transient response, etc. The structural analysis packages are to include stochastic modeling of loads, material properties, geometry (tolerances), and boundary conditions. The solution is to be in terms of the cumulative probability of exceedance distribution (CDF) and confidence bounds. Two methods of probability modeling are to be included as well as three types of structural models - probabilistic finite-element method (PFEM); probabilistic approximate analysis methods (PAAM); and probabilistic boundary element methods (PBEM). The purpose in doing probabilistic structural analysis is to provide the designer with a more realistic ability to assess the importance of uncertainty in the response of a high performance structure. Probabilistic Structural Analysis Method (PSAM) tools will estimate structural safety and reliability, while providing the engineer with information on the confidence that should be given to the predicted behavior. Perhaps most critically, the PSAM results will directly provide information on the sensitivity of the design response to those variables which are seen to be uncertain.

  7. Probabilistic Structural Analysis Methods for select space propulsion system structural components (PSAM)

    NASA Technical Reports Server (NTRS)

    Cruse, T. A.; Burnside, O. H.; Wu, Y.-T.; Polch, E. Z.; Dias, J. B.

    1988-01-01

    The objective is the development of several modular structural analysis packages capable of predicting the probabilistic response distribution for key structural variables such as maximum stress, natural frequencies, transient response, etc. The structural analysis packages are to include stochastic modeling of loads, material properties, geometry (tolerances), and boundary conditions. The solution is to be in terms of the cumulative probability of exceedance distribution (CDF) and confidence bounds. Two methods of probability modeling are to be included as well as three types of structural models - probabilistic finite-element method (PFEM); probabilistic approximate analysis methods (PAAM); and probabilistic boundary element methods (PBEM). The purpose in doing probabilistic structural analysis is to provide the designer with a more realistic ability to assess the importance of uncertainty in the response of a high performance structure. Probabilistic Structural Analysis Method (PSAM) tools will estimate structural safety and reliability, while providing the engineer with information on the confidence that should be given to the predicted behavior. Perhaps most critically, the PSAM results will directly provide information on the sensitivity of the design response to those variables which are seen to be uncertain.

  8. Cation Selectivity in Biological Cation Channels Using Experimental Structural Information and Statistical Mechanical Simulation.

    PubMed

    Finnerty, Justin John; Peyser, Alexander; Carloni, Paolo

    2015-01-01

    Cation selective channels constitute the gate for ion currents through the cell membrane. Here we present an improved statistical mechanical model based on atomistic structural information, cation hydration state and without tuned parameters that reproduces the selectivity of biological Na+ and Ca2+ ion channels. The importance of the inclusion of step-wise cation hydration in these results confirms the essential role partial dehydration plays in the bacterial Na+ channels. The model, proven reliable against experimental data, could be straightforwardly used for designing Na+ and Ca2+ selective nanopores. PMID:26460827

  9. Selective Adsorption of CO2 from Light Gas Mixtures Using a Structurally Dynamic Porous Coordination Polymer**

    SciTech Connect

    Kristi L. Kauffman, Jeffrey T. Culp, Andrew J. Allen, Laura Espinal, Winnie Wong-Ng, Thomas D. Brown, Angela Goodman, Mark P. Bernardo, Russel J. Pancoast, Danielle Chirdon, Christopher Matranga*

    2010-01-01

    The selective adsorption of CO{sub 2} from mixtures with N{sub 2}, CH{sub 4}, and N{sub 2}O in a dynamic porous coordination polymer (see monomer structure) was evaluated by ATR-FTIR spectroscopy, GC, and SANS. All three techniques indicate highly selective adsorption of CO{sub 2} from CO{sub 2}/CH{sub 4} and CO{sub 2}/N{sub 2} mixtures at 30 C, with no selectivity observed for the CO{sub 2}/N{sub 2}O system.

  10. Cation Selectivity in Biological Cation Channels Using Experimental Structural Information and Statistical Mechanical Simulation

    PubMed Central

    Finnerty, Justin John

    2015-01-01

    Cation selective channels constitute the gate for ion currents through the cell membrane. Here we present an improved statistical mechanical model based on atomistic structural information, cation hydration state and without tuned parameters that reproduces the selectivity of biological Na+ and Ca2+ ion channels. The importance of the inclusion of step-wise cation hydration in these results confirms the essential role partial dehydration plays in the bacterial Na+ channels. The model, proven reliable against experimental data, could be straightforwardly used for designing Na+ and Ca2+ selective nanopores. PMID:26460827

  11. Formal selection rules for Brillouin scattering in integrated waveguides and structured fibers.

    PubMed

    Wolff, C; Steel, M J; Poulton, C G

    2014-12-29

    We derive formal selection rules for Stimulated Brillouin Scattering (SBS) in structured waveguides. Using a group-theoretical approach, we show how the waveguide symmetry determines which optical and acoustic modes interact for both forward and backward SBS. We present a general framework for determining this interaction and give important examples for SBS in waveguides with rectangular, triangular and hexagonal symmetry. The important role played by degeneracy of the optical modes is illustrated. These selection rules are important for SBS-based device design and for a full understanding the physics of SBS in structured waveguides. PMID:25607211

  12. Structural basis for ion selectivity revealed by high-resolution crystal structure of Mg2+ channel MgtE

    PubMed Central

    Takeda, Hironori; Hattori, Motoyuki; Nishizawa, Tomohiro; Yamashita, Keitaro; Shah, Syed T. A.; Caffrey, Martin; Maturana, Andrés D.; Ishitani, Ryuichiro; Nureki, Osamu

    2014-01-01

    Magnesium is the most abundant divalent cation in living cells and is crucial to several biological processes. MgtE is a Mg2+ channel distributed in all domains of life that contributes to the maintenance of cellular Mg2+ homeostasis. Here we report the high-resolution crystal structures of the transmembrane domain of MgtE, bound to Mg2+, Mn2+ and Ca2+. The high-resolution Mg2+-bound crystal structure clearly visualized the hydrated Mg2+ ion within its selectivity filter. Based on those structures and biochemical analyses, we propose a cation selectivity mechanism for MgtE in which the geometry of the hydration shell of the fully hydrated Mg2+ ion is recognized by the side-chain carboxylate groups in the selectivity filter. This is in contrast to the K+-selective filter of KcsA, which recognizes a dehydrated K+ ion. Our results further revealed a cation-binding site on the periplasmic side, which regulate channel opening and prevents conduction of near-cognate cations. PMID:25367295

  13. Structures of the Four Subfamilies of Phosphodiesterase-4 Provide Insight into the Selectivity of Their Inhibitors

    SciTech Connect

    Wang, H.; Peng, M; Chen , Y; Geng, J; Robinson, H; Houslay , M; Cai, J; Ke, H

    2007-01-01

    PDE4 (phosphodiesterase-4)-selective inhibitors have attracted much attention as potential therapeutics for the treatment of both depression and major inflammatory diseases, but their practical application has been compromised by side effects. A possible cause for the side effects is that current PDE4-selective inhibitors similarly inhibit isoforms from all four PDE4 subfamilies. The development of PDE4 subfamily-selective inhibitors has been hampered by a lack of structural information. In the present study, we rectify this by providing the crystal structures of the catalytic domains of PDE4A, PDE4B and PDE4D in complex with the PDE4 inhibitor NVP 4-[8-(3-nitrophenyl)-[1,7]naphthyridin-6-yl]benzoic acid as well as the unliganded PDE4C structure. NVP binds in the same conformation to the deep cAMP substrate pocket and interacts with the same residues in each instance. However, detailed structural comparison reveals significant conformational differences. Although the active sites of PDE4B and PDE4D are mostly comparable, PDE4A shows significant displacements of the residues next to the invariant glutamine residue that is critical for substrate and inhibitor binding. PDE4C appears to be more distal from other PDE4 subfamilies, with certain key residues being disordered. Our analyses provide the first structural basis for the development of PDE4 subfamily-selective inhibitors.

  14. Broadband frequency-selective spoof surface plasmon polaritons on ultrathin metallic structure.

    PubMed

    Yin, Jia Yuan; Ren, Jian; Zhang, Hao Chi; Pan, Bai Cao; Cui, Tie Jun

    2015-01-01

    We propose an ultrathin metallic structure to produce frequency-selective spoof surface plasmon polaritons (SPPs) in the microwave and terahertz frequencies. Designed on a thin dielectric substrate, the ultrathin metallic structure is composed of two oppositely oriented single-side corrugated strips, which are coupled to two double-side corrugated strips. The structure is fed by a traditional coplanar waveguide (CPW). To make a smooth conversion between the spatial modes in CPW and SPP modes, two transition sections are also designed. We fabricate and measure the frequency-selective spoof SPP structure in microwave frequencies. The measurement results show that the reflection coefficient is less than -10 dB with the transmission loss around 1.5 dB in the selective frequency band from 7 to 10 GHz, which are in good agreements with numerical simulations. The proposed structure can be used as an SPP filter with good performance of low loss, high transmission, and wide bandwidth in the selective frequency band. PMID:25641730

  15. Optimal sequence selection in proteins of known structure by simulated evolution.

    PubMed Central

    Hellinga, H W; Richards, F M

    1994-01-01

    Rational design of protein structure requires the identification of optimal sequences to carry out a particular function within a given backbone structure. A general solution to this problem requires that a potential function describing the energy of the system as a function of its atomic coordinates be minimized simultaneously over all available sequences and their three-dimensional atomic configurations. Here we present a method that explicitly minimizes a semiempirical potential function simultaneously in these two spaces, using a simulated annealing approach. The method takes the fixed three-dimensional coordinates of a protein backbone and stochastically generates possible sequences through the introduction of random mutations. The corresponding three-dimensional coordinates are constructed for each sequence by "redecorating" the backbone coordinates of the original structure with the corresponding side chains. These are then allowed to vary in their structure by random rotations around free torsional angles to generate a stochastic walk in configurational space. We have named this method protein simulated evolution, because, in loose analogy with natural selection, it randomly selects for allowed solutions in the sequence of a protein subject to the "selective pressure" of a potential function. Energies predicted by this method for sequences of a small group of residues in the hydrophobic core of the phage lambda cI repressor correlate well with experimentally determined biological activities. This "genetic selection by computer" approach has potential applications in protein engineering, rational protein design, and structure-based drug discovery. PMID:8016069

  16. Broadband Frequency-Selective Spoof Surface Plasmon Polaritons on Ultrathin Metallic Structure

    PubMed Central

    Yin, Jia Yuan; Ren, Jian; Zhang, Hao Chi; Pan, Bai Cao; Cui, Tie Jun

    2015-01-01

    We propose an ultrathin metallic structure to produce frequency-selective spoof surface plasmon polaritons (SPPs) in the microwave and terahertz frequencies. Designed on a thin dielectric substrate, the ultrathin metallic structure is composed of two oppositely oriented single-side corrugated strips, which are coupled to two double-side corrugated strips. The structure is fed by a traditional coplanar waveguide (CPW). To make a smooth conversion between the spatial modes in CPW and SPP modes, two transition sections are also designed. We fabricate and measure the frequency-selective spoof SPP structure in microwave frequencies. The measurement results show that the reflection coefficient is less than -10 dB with the transmission loss around 1.5 dB in the selective frequency band from 7 to 10 GHz, which are in good agreements with numerical simulations. The proposed structure can be used as an SPP filter with good performance of low loss, high transmission, and wide bandwidth in the selective frequency band. PMID:25641730

  17. Usage-Oriented Topic Maps Building Approach

    NASA Astrophysics Data System (ADS)

    Ellouze, Nebrasse; Lammari, Nadira; Métais, Elisabeth; Ben Ahmed, Mohamed

    In this paper, we present a collaborative and incremental construction approach of multilingual Topic Maps based on enrichment and merging techniques. In recent years, several Topic Map building approaches have been proposed endowed with different characteristics. Generally, they are dedicated to particular data types like text, semi-structured data, relational data, etc. We note also that most of these approaches take as input monolingual documents to build the Topic Map. The problem is that the large majority of resources available today are written in various languages, and these resources could be relevant even to non-native speakers. Thus, our work is driven towards a collaborative and incremental method for Topic Map construction from textual documents available in different languages. To enrich the Topic Map, we take as input a domain thesaurus and we propose also to explore the Topic Map usage which means available potential questions related to the source documents.

  18. Topical diclofenac solution.

    PubMed

    Moen, Marit D

    2009-01-01

    Topical diclofenac solution (Pennsaid) is a liquid formulation containing the NSAID diclofenac sodium (1.5% w/w). The solution base contains 45% w/w dimethyl sulfoxide (DMSO) to enhance the absorption of diclofenac through the skin. Topical diclofenac solution is applied directly to the knee for treatment of symptoms associated with osteoarthritis of the knee. In well designed 4- to 12-week trials in patients with primary osteoarthritis of the knee, topical diclofenac solution (40 drops four times daily) was significantly more effective than placebo or vehicle control (carrier solution without diclofenac) for improving Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index pain and physical function, and improving patient global assessment (PGA) and/or patient overall health assessment scores from baseline to the final assessments. Topical diclofenac solution (50 drops three times daily) was as effective as oral diclofenac 150 mg/day for improving WOMAC pain and physical function and PGA scores in a 12-week double-blind study in patients with osteoarthritis of the knee. Topical diclofenac solution was generally well tolerated. The most common treatment-emergent adverse event experienced by topical diclofenac solution recipients was dry skin at the application site. Gastrointestinal adverse events and abnormal laboratory parameters were less common with topical diclofenac solution than with oral diclofenac. PMID:19943711

  19. Structural optimization and structure-functional selectivity relationship studies of G protein-biased EP2 receptor agonists.

    PubMed

    Ogawa, Seiji; Watanabe, Toshihide; Moriyuki, Kazumi; Goto, Yoshikazu; Yamane, Shinsaku; Watanabe, Akio; Tsuboi, Kazuma; Kinoshita, Atsushi; Okada, Takuya; Takeda, Hiroyuki; Tani, Kousuke; Maruyama, Toru

    2016-05-15

    The modification of the novel G protein-biased EP2 agonist 1 has been investigated to improve its G protein activity and develop a better understanding of its structure-functional selectivity relationship (SFSR). The optimization of the substituents on the phenyl ring of 1, followed by the inversion of the hydroxyl group on the cyclopentane moiety led to compound 9, which showed a 100-fold increase in its G protein activity compared with 1 without any increase in β-arrestin recruitment. Furthermore, SFSR studies revealed that the combination of meta and para substituents on the phenyl moiety was crucial to the functional selectivity. PMID:27055938

  20. Sentence processing selectivity in Broca’s area: evident for structure but not syntactic movement

    PubMed Central

    Almeida, Diogo; Sprouse, Jon; Hickok, Gregory

    2016-01-01

    The role of Broca’s area in sentence processing is hotly debated. Prominent hypotheses include that Broca’s area supports sentence comprehension via syntax-specific processes (“syntactic movement” in particular), hierarchical structure building or working memory. In the present fMRI study we adopt a within subject, across task approach using targeted sentence-level contrasts and non-sentential comparison tasks to address these hypotheses regarding the role of Broca’s area in sentence processing. For clarity, we have presented findings as three experiments: (i) Experiment 1 examines selectivity for a particular type of sentence construction, namely those containing syntactic movement. Standard syntactic movement distance effects in Broca’s area were replicated but no difference was found between movement and non-movement sentences in Broca’s area at the group level or consistently in individual subjects. (ii) Experiment 2 examines selectivity for sentences versus non-sentences, to assess claims regarding the role of Broca’s area in hierarchical structure building. Group and individual results differ, but both identify subregions of Broca’s area that are selective for sentence structure. (iii) Experiment 3 assesses whether activations in Broca’s area are selective for sentences when contrasted with simple subvocal articulation. Group results suggest shared resources for sentence processing and articulation in Broca’s area, but individual subject analyses contradict this finding. We conclude that Broca’s area is not selectively involved in processing syntactic movement, but that subregions are selectively responsive to sentence structure. Our findings also reinforce Fedorenko & Kanwishser’s call for the use of more individual subject analyses in functional imaging studies of sentence processing in Broca’s area, as group findings can obscure selective response patterns. PMID:27135039

  1. Individual fitness and phenotypic selection in age-structured populations with constant growth rates

    PubMed Central

    Moorad, Jacob A.

    2013-01-01

    Powerful multiple regression-based approaches are commonly used to measure the strength of phenotypic selection, which is the statistical association between individual fitness and trait values. Age structure and overlapping generations complicate determinations of individual fitness, contributing to the popularity of alternative methods for measuring natural selection that do not depend upon such measures. The application of regression-based techniques for measuring selection in these situations requires a demographically appropriate, conceptually sound, and observable measure of individual fitness. It has been suggested that Fisher’s reproductive value applied to an individual at its birth is such a definition. Here I offer support for this assertion by showing that multiple regression applied to this measure and vital rates (age-specific survival and fertility rates) yields the same selection gradients for vital rates as those inferred from Hamilton’s classical results. I discuss how multiple regressions, applied to individual reproductive value at birth, can be used efficiently to estimate measures of phenotypic selection that are problematic for sensitivity analyses. These include nonlinear selection, components of the opportunity for selection, and multi-level selection. PMID:24933826

  2. Artificial selection for structural color on butterfly wings and comparison with natural evolution

    PubMed Central

    Wasik, Bethany R.; Liew, Seng Fatt; Lilien, David A.; Dinwiddie, April J.; Noh, Heeso; Cao, Hui; Monteiro, Antónia

    2014-01-01

    Brilliant animal colors often are produced from light interacting with intricate nano-morphologies present in biological materials such as butterfly wing scales. Surveys across widely divergent butterfly species have identified multiple mechanisms of structural color production; however, little is known about how these colors evolved. Here, we examine how closely related species and populations of Bicyclus butterflies have evolved violet structural color from brown-pigmented ancestors with UV structural color. We used artificial selection on a laboratory model butterfly, B. anynana, to evolve violet scales from UV brown scales and compared the mechanism of violet color production with that of two other Bicyclus species, Bicyclus sambulos and Bicyclus medontias, which have evolved violet/blue scales independently via natural selection. The UV reflectance peak of B. anynana brown scales shifted to violet over six generations of artificial selection (i.e., in less than 1 y) as the result of an increase in the thickness of the lower lamina in ground scales. Similar scale structures and the same mechanism for producing violet/blue structural colors were found in the other Bicyclus species. This work shows that populations harbor large amounts of standing genetic variation that can lead to rapid evolution of scales’ structural color via slight modifications to the scales’ physical dimensions. PMID:25092295

  3. Environmental Topics for Introductory Physics Courses

    ERIC Educational Resources Information Center

    Hodges, Laurent

    1974-01-01

    Presents selected environmental references with comparatively detailed descriptions for the purpose of helping high school and college physics teachers in selecting materials for their course. The topics include thermal pollution, space heating and cooling, atmospheric temperature distribution, radiation balance of the earth, sound and noises, and…

  4. Structural insights into human heme oxygenase-1 inhibition by potent and selective azole-based compounds

    PubMed Central

    Rahman, Mona N.; Vukomanovic, Dragic; Vlahakis, Jason Z.; Szarek, Walter A.; Nakatsu, Kanji; Jia, Zongchao

    2013-01-01

    The development of heme oxygenase (HO) inhibitors, especially those that are isozyme-selective, promises powerful pharmacological tools to elucidate the regulatory characteristics of the HO system. It is already known that HO has cytoprotective properties and may play a role in several disease states, making it an enticing therapeutic target. Traditionally, the metalloporphyrins have been used as competitive HO inhibitors owing to their structural similarity with the substrate, heme. However, given heme's important role in several other proteins (e.g. cytochromes P450, nitric oxide synthase), non-selectivity is an unfortunate side-effect. Reports that azalanstat and other non-porphyrin molecules inhibited HO led to a multi-faceted effort to develop novel compounds as potent, selective inhibitors of HO. This resulted in the creation of non-competitive inhibitors with selectivity for HO, including a subset with isozyme selectivity for HO-1. Using X-ray crystallography, the structures of several complexes of HO-1 with novel inhibitors have been elucidated, which provided insightful information regarding the salient features required for inhibitor binding. This included the structural basis for non-competitive inhibition, flexibility and adaptability of the inhibitor binding pocket, and multiple, potential interaction subsites, all of which can be exploited in future drug-design strategies. PMID:23097500

  5. Structural basis for the design of selective phosphodiesterase 4B inhibitors.

    PubMed

    Fox, David; Burgin, Alex B; Gurney, Mark E

    2014-03-01

    Phosphodiesterase-4B (PDE4B) regulates the pro-inflammatory Toll Receptor -Tumor Necrosis Factor α (TNFα) pathway in monocytes, macrophages and microglial cells. As such, it is an important, although under-exploited molecular target for anti-inflammatory drugs. This is due in part to the difficulty of developing selective PDE4B inhibitors as the amino acid sequence of the PDE4 active site is identical in all PDE4 subtypes (PDE4A-D). We show that highly selective PDE4B inhibitors can be designed by exploiting sequence differences outside the active site. Specifically, PDE4B selectivity can be achieved by capture of a C-terminal regulatory helix, now termed CR3 (Control Region 3), across the active site in a conformation that closes access by cAMP. PDE4B selectivity is driven by a single amino acid polymorphism in CR3 (Leu674 in PDE4B1 versus Gln594 in PDE4D). The reciprocal mutations in PDE4B and PDE4D cause a 70-80 fold shift in selectivity. Our structural studies show that CR3 is flexible and can adopt multiple orientations and multiple registries in the closed conformation. The new co-crystal structure with bound ligand provides a guide map for the design of PDE4B selective anti-inflammatory drugs. PMID:24361374

  6. Genome Scan for Selection in Structured Layer Chicken Populations Exploiting Linkage Disequilibrium Information

    PubMed Central

    Gholami, Mahmood; Reimer, Christian; Erbe, Malena; Preisinger, Rudolf; Weigend, Annett; Weigend, Steffen; Servin, Bertrand; Simianer, Henner

    2015-01-01

    An increasing interest is being placed in the detection of genes, or genomic regions, that have been targeted by selection because identifying signatures of selection can lead to a better understanding of genotype-phenotype relationships. A common strategy for the detection of selection signatures is to compare samples from distinct populations and to search for genomic regions with outstanding genetic differentiation. The aim of this study was to detect selective signatures in layer chicken populations using a recently proposed approach, hapFLK, which exploits linkage disequilibrium information while accounting appropriately for the hierarchical structure of populations. We performed the analysis on 70 individuals from three commercial layer breeds (White Leghorn, White Rock and Rhode Island Red), genotyped for approximately 1 million SNPs. We found a total of 41 and 107 regions with outstanding differentiation or similarity using hapFLK and its single SNP counterpart FLK respectively. Annotation of selection signature regions revealed various genes and QTL corresponding to productions traits, for which layer breeds were selected. A number of the detected genes were associated with growth and carcass traits, including IGF-1R, AGRP and STAT5B. We also annotated an interesting gene associated with the dark brown feather color mutational phenotype in chickens (SOX10). We compared FST, FLK and hapFLK and demonstrated that exploiting linkage disequilibrium information and accounting for hierarchical population structure decreased the false detection rate. PMID:26151449

  7. Women's Health Topics

    MedlinePlus

    ... Women's Health 10903 New Hampshire Avenue WO32-2333 Silver Spring, MD 20993 More in Women's Health Topics ... Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993 1-888-INFO-FDA (1- ...

  8. Diclofenac Topical (osteoarthritis pain)

    MedlinePlus

    ... growths on the skin caused by too much sun exposure). This monograph only gives information about diclofenac gel ( ... you should know that you should not apply sunscreens, cosmetics, lotions, moisturizers, insect repellents, or other topical ...

  9. A Study of the Structure and Content of Principal Selection Interviews in Pennsylvania

    ERIC Educational Resources Information Center

    Weber, Elizabeth A.

    2012-01-01

    The principal plays a key role in student success. The employment interview is a critical element in the principal selection process. This study examined the interview structure and the content of the interview questions that districts used in their principal search for the 2011-2012 school year. The research-based practices for interview…

  10. Structural and Thermodynamic Properties of Selective Ion Binding in a K+ Channel

    SciTech Connect

    Lockless,S.; Zhou, M.; MacKinnon, R.

    2007-01-01

    Thermodynamic measurements of ion binding to the Streptomyces lividans K+ channel were carried out using isothermal titration calorimetry, whereas atomic structures of ion-bound and ion-free conformations of the channel were characterized by x-ray crystallography. Here we use these assays to show that the ion radius dependence of selectivity stems from the channel's recognition of ion size (i.e., volume) rather than charge density. Ion size recognition is a function of the channel's ability to adopt a very specific conductive structure with larger ions (K+, Rb+, Cs+, and Ba2+) bound and not with smaller ions (Na+, Mg2+, and Ca2+). The formation of the conductive structure involves selectivity filter atoms that are in direct contact with bound ions as well as protein atoms surrounding the selectivity filter up to a distance of 15 Angstroms from the ions. We conclude that ion selectivity in a K+ channel is a property of size-matched ion binding sites created by the protein structure.

  11. Structural and Thermodynamic Properties of Selective Ion Binding in a K+ Channel

    PubMed Central

    Lockless, Steve W; Zhou, Ming; MacKinnon, Roderick

    2007-01-01

    Thermodynamic measurements of ion binding to the Streptomyces lividans K+ channel were carried out using isothermal titration calorimetry, whereas atomic structures of ion-bound and ion-free conformations of the channel were characterized by x-ray crystallography. Here we use these assays to show that the ion radius dependence of selectivity stems from the channel's recognition of ion size (i.e., volume) rather than charge density. Ion size recognition is a function of the channel's ability to adopt a very specific conductive structure with larger ions (K+, Rb+, Cs+, and Ba2+) bound and not with smaller ions (Na+, Mg2+, and Ca2+). The formation of the conductive structure involves selectivity filter atoms that are in direct contact with bound ions as well as protein atoms surrounding the selectivity filter up to a distance of 15 Å from the ions. We conclude that ion selectivity in a K+ channel is a property of size-matched ion binding sites created by the protein structure. PMID:17472437

  12. Multiple-grid frequency-selective surfaces as periodically loaded structures

    NASA Astrophysics Data System (ADS)

    Orta, R.; Tascone, R.; Zich, R.

    1988-04-01

    An novel approach to the analysis of multiple-grid frequency-selective surfaces (FSS) is presented. In this case, the multiple grid FSS is thought of as a periodically loaded structure where the unit cell consists of a grid with its adjacent layers. The Bloch wave passband and stopband are used to create the transmission and reflection bands.

  13. Biochemical And Structural Evaluation of Highly Selective 2-Arylbenzoxazole-Based Transthyretin Amyloidogenesis Inhibitors

    SciTech Connect

    Johnson, S.M.; Connelly, S.; Wilson, I.A.; Kelly, J.W.

    2009-05-18

    To develop potent transthyretin (TTR) amyloidogenesis inhibitors that also display high binding selectivity in blood, it proves useful to systematically optimize each of the three substructural elements that comprise a typical inhibitor: the two aryl rings and the linker joining them. In the first study, described herein, structural modifications to one aryl ring were evaluated by screening a library of 2-arylbenzoxazoles bearing thyroid hormone-like aryl substituents on the 2-aryl ring. Several potent and highly selective amyloidogenesis inhibitors were identified that exhibit minimal thyroid hormone nuclear receptor and COX-1 binding. High resolution crystal structures (1.3-1.5 A) of three inhibitors (2f, 4f, and 4d) in complex with TTR were obtained to characterize their binding orientation. Collectively, the results demonstrate that thyroid hormone-like substitution patterns on one aryl ring lead to potent and highly selective TTR amyloidogenesis inhibitors that lack undesirable thyroid hormone receptor or COX-1 binding.

  14. Structural Basis for Binding and Selectivity of Antimalarial and Anticancer Ethylenediamine Inhibitors to Protein Farnesyltransferase

    SciTech Connect

    Hast, Michael A.; Fletcher, Steven; Cummings, Christopher G.; Pusateri, Erin E.; Blaskovich, Michelle A.; Rivas, Kasey; Gelb, Michael H.; Voorhis, Wesley C.Van; Sebti, Said M.; Hamilton, Andrew D.; Beese, Lorena S. ); ); ); )

    2009-03-20

    Protein farnesyltransferase (FTase) catalyzes an essential posttranslational lipid modification of more than 60 proteins involved in intracellular signal transduction networks. FTase inhibitors have emerged as a significant target for development of anticancer therapeutics and, more recently, for the treatment of parasitic diseases caused by protozoan pathogens, including malaria (Plasmodium falciparum). We present the X-ray crystallographic structures of complexes of mammalian FTase with five inhibitors based on an ethylenediamine scaffold, two of which exhibit over 1000-fold selective inhibition of P. falciparum FTase. These structures reveal the dominant determinants in both the inhibitor and enzyme that control binding and selectivity. Comparison to a homology model constructed for the P. falciparum FTase suggests opportunities for further improving selectivity of a new generation of antimalarial inhibitors.

  15. 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

  16. An Innovative Structural Mode Selection Methodology: Application for the X-33 Launch Vehicle Finite Element Model

    NASA Technical Reports Server (NTRS)

    Hidalgo, Homero, Jr.

    2000-01-01

    An innovative methodology for determining structural target mode selection and mode selection based on a specific criterion is presented. An effective approach to single out modes which interact with specific locations on a structure has been developed for the X-33 Launch Vehicle Finite Element Model (FEM). We presented Root-Sum-Square (RSS) displacement method computes resultant modal displacement for each mode at selected degrees of freedom (DOF) and sorts to locate modes with highest values. This method was used to determine modes, which most influenced specific locations/points on the X-33 flight vehicle such as avionics control components, aero-surface control actuators, propellant valve and engine points for use in flight control stability analysis and for flight POGO stability analysis. Additionally, the modal RSS method allows for primary or global target vehicle modes to also be identified in an accurate and efficient manner.

  17. A qualitative model structure sensitivity analysis method to support model selection

    NASA Astrophysics Data System (ADS)

    Van Hoey, S.; Seuntjens, P.; van der Kwast, J.; Nopens, I.

    2014-11-01

    The selection and identification of a suitable hydrological model structure is a more challenging task than fitting parameters of a fixed model structure to reproduce a measured hydrograph. The suitable model structure is highly dependent on various criteria, i.e. the modeling objective, the characteristics and the scale of the system under investigation and the available data. Flexible environments for model building are available, but need to be assisted by proper diagnostic tools for model structure selection. This paper introduces a qualitative method for model component sensitivity analysis. Traditionally, model sensitivity is evaluated for model parameters. In this paper, the concept is translated into an evaluation of model structure sensitivity. Similarly to the one-factor-at-a-time (OAT) methods for parameter sensitivity, this method varies the model structure components one at a time and evaluates the change in sensitivity towards the output variables. As such, the effect of model component variations can be evaluated towards different objective functions or output variables. The methodology is presented for a simple lumped hydrological model environment, introducing different possible model building variations. By comparing the effect of changes in model structure for different model objectives, model selection can be better evaluated. Based on the presented component sensitivity analysis of a case study, some suggestions with regard to model selection are formulated for the system under study: (1) a non-linear storage component is recommended, since it ensures more sensitive (identifiable) parameters for this component and less parameter interaction; (2) interflow is mainly important for the low flow criteria; (3) excess infiltration process is most influencing when focussing on the lower flows; (4) a more simple routing component is advisable; and (5) baseflow parameters have in general low sensitivity values, except for the low flow criteria.

  18. Much Needed Structure [Structured Decision-Making with DMRCS. Define-Measure-Reduce-Combine-Select

    DOE PAGESBeta

    Anderson-Cook, Christine M.; Lu, Lu

    2015-10-01

    We have described a new DMRCS process for structured decision making, which mirrors the approach of the DMAIC process which has become so popular within Lean Six Sigma. By dividing a complex often unstructured process into distinct steps, we hope to have made the task of balancing multiple competing objectives less daunting.

  19. Selective logging: does the imprint remain on tree structure and composition after 45 years?

    PubMed

    Osazuwa-Peters, Oyomoare L; Chapman, Colin A; Zanne, Amy E

    2015-01-01

    Selective logging of tropical forests is increasing in extent and intensity. The duration over which impacts of selective logging persist, however, remains an unresolved question, particularly for African forests. Here, we investigate the extent to which a past selective logging event continues to leave its imprint on different components of an East African forest 45 years later. We inventoried 2358 stems ≥10 cm in diameter in 26 plots (200 m × 10 m) within a 5.2 ha area in Kibale National Park, Uganda, in logged and unlogged forest. In these surveys, we characterized the forest light environment, taxonomic composition, functional trait composition using three traits (wood density, maximum height and maximum diameter) and forest structure based on three measures (stem density, total basal area and total above-ground biomass). In comparison to unlogged forests, selectively logged forest plots in Kibale National Park on average had higher light levels, different structure characterized by lower stem density, lower total basal area and lower above-ground biomass, and a distinct taxonomic composition driven primarily by changes in the relative abundance of species. Conversely, selectively logged forest plots were like unlogged plots in functional composition, having similar community-weighted mean values for wood density, maximum height and maximum diameter. This similarity in functional composition irrespective of logging history may be due to functional recovery of logged forest or background changes in functional attributes of unlogged forest. Despite the passage of 45 years, the legacy of selective logging on the tree community in Kibale National Park is still evident, as indicated by distinct taxonomic and structural composition and reduced carbon storage in logged forest compared with unlogged forest. The effects of selective logging are exerted via influences on tree demography rather than functional trait composition. PMID:27293697

  20. A Method for Selecting Structure-switching Aptamers Applied to a Colorimetric Gold Nanoparticle Assay

    PubMed Central

    Martin, Jennifer A.; Smith, Joshua E.; Warren, Mercedes; Chávez, Jorge L.; Hagen, Joshua A.; Kelley-Loughnane, Nancy

    2015-01-01

    Small molecules provide rich targets for biosensing applications due to their physiological implications as biomarkers of various aspects of human health and performance. Nucleic acid aptamers have been increasingly applied as recognition elements on biosensor platforms, but selecting aptamers toward small molecule targets requires special design considerations. This work describes modification and critical steps of a method designed to select structure-switching aptamers to small molecule targets. Binding sequences from a DNA library hybridized to complementary DNA capture probes on magnetic beads are separated from nonbinders via a target-induced change in conformation. This method is advantageous because sequences binding the support matrix (beads) will not be further amplified, and it does not require immobilization of the target molecule. However, the melting temperature of the capture probe and library is kept at or slightly above RT, such that sequences that dehybridize based on thermodynamics will also be present in the supernatant solution. This effectively limits the partitioning efficiency (ability to separate target binding sequences from nonbinders), and therefore many selection rounds will be required to remove background sequences. The reported method differs from previous structure-switching aptamer selections due to implementation of negative selection steps, simplified enrichment monitoring, and extension of the length of the capture probe following selection enrichment to provide enhanced stringency. The selected structure-switching aptamers are advantageous in a gold nanoparticle assay platform that reports the presence of a target molecule by the conformational change of the aptamer. The gold nanoparticle assay was applied because it provides a simple, rapid colorimetric readout that is beneficial in a clinical or deployed environment. Design and optimization considerations are presented for the assay as proof-of-principle work in buffer to

  1. TOPICAL TREATMENT OF MELASMA

    PubMed Central

    Bandyopadhyay, Debabrata

    2009-01-01

    Melasma is a common hypermelanotic disorder affecting the face that is associated with considerable psychological impacts. The management of melasma is challenging and requires a long-term treatment plan. In addition to avoidance of aggravating factors like oral pills and ultraviolet exposure, topical therapy has remained the mainstay of treatment. Multiple options for topical treatment are available, of which hydroquinone (HQ) is the most commonly prescribed agent. Besides HQ, other topical agents for which varying degrees of evidence for clinical efficacy exist include azelaic acid, kojic acid, retinoids, topical steroids, glycolic acid, mequinol, and arbutin. Topical medications modify various stages of melanogenesis, the most common mode of action being inhibition of the enzyme, tyrosinase. Combination therapy is the preferred mode of treatment for the synergism and reduction of untoward effects. The most popular combination consists of HQ, a topical steroid, and retinoic acid. Prolonged HQ usage may lead to untoward effects like depigmentation and exogenous ochronosis. The search for safer alternatives has given rise to the development of many newer agents, several of them from natural sources. Well-designed controlled clinical trials are needed to clarify their role in the routine management of melasma. PMID:20101327

  2. Structure-Guided Design of Group I Selective p21-Activated Kinase Inhibitors.

    PubMed

    Crawford, James J; Lee, Wendy; Aliagas, Ignacio; Mathieu, Simon; Hoeflich, Klaus P; Zhou, Wei; Wang, Weiru; Rouge, Lionel; Murray, Lesley; La, Hank; Liu, Ning; Fan, Peter W; Cheong, Jonathan; Heise, Christopher E; Ramaswamy, Sreemathy; Mintzer, Robert; Liu, Yanzhou; Chao, Qi; Rudolph, Joachim

    2015-06-25

    The p21-activated kinases (PAKs) play important roles in cytoskeletal organization, cellular morphogenesis, and survival and have generated significant attention as potential therapeutic targets for cancer. Following a high-throughput screen, we identified an aminopyrazole scaffold-based series that was optimized to yield group I selective PAK inhibitors. A structure-based design effort aimed at targeting the ribose pocket for both potency and selectivity led to much-improved group I vs II selectivity. Early lead compounds contained a basic primary amine, which was found to be a major metabolic soft spot with in vivo clearance proceeding predominantly via N-acetylation. We succeeded in identifying replacements with improved metabolic stability, leading to compounds with lower in vivo rodent clearance and excellent group I PAK selectivity. PMID:26030457

  3. Differential visualisation of a spectrally selective structure of strongly scattering objects

    SciTech Connect

    Kuratov, A S; Rudenko, V N; Shuvalov, V V

    2014-07-31

    We describe a modification of the algorithm for the fast approximate solution of the diffuse optical tomography inverse problem. In this modification the amount of a priori (auxiliary) information necessary for the visualisation of the internal structure of the object is reduced by using a differential measurement scheme. The experiment is performed at two different wavelengths, and some a priori information, necessary to reconstruct only the spectrally selective component of the internal structure (the difference structure of the spatial distributions of the extinction coefficient at the wavelength employed), is replaced by the data of one of these measurements. (laser biophotonics)

  4. Structural Basis for the Potent and Selective Inhibition of Casein Kinase 1 Epsilon

    SciTech Connect

    Long, Alexander M.; Zhao, Huilin; Huang, Xin

    2012-10-29

    Casein kinase 1 epsilon (CK1ε) and its closest homologue CK1δ are key regulators of diverse cellular processes. We report two crystal structures of PF4800567, a potent and selective inhibitor of CK1ε, bound to the kinase domains of human CK1ε and CK1δ as well as one apo CK1ε crystal structure. These structures provide a molecular basis for the strong and specific inhibitor interactions with CK1ε and suggest clues for further development of CK1δ inhibitors.

  5. 3D printing of weft knitted textile based structures by selective laser sintering of nylon powder

    NASA Astrophysics Data System (ADS)

    Beecroft, M.

    2016-07-01

    3D printing is a form of additive manufacturing whereby the building up of layers of material creates objects. The selective laser sintering process (SLS) uses a laser beam to sinter powdered material to create objects. This paper builds upon previous research into 3D printed textile based material exploring the use of SLS using nylon powder to create flexible weft knitted structures. The results show the potential to print flexible textile based structures that exhibit the properties of traditional knitted textile structures along with the mechanical properties of the material used, whilst describing the challenges regarding fineness of printing resolution. The conclusion highlights the potential future development and application of such pieces.

  6. A determinant-based criterion for working correlation structure selection in generalized estimating equations.

    PubMed

    Jaman, Ajmery; Latif, Mahbub A H M; Bari, Wasimul; Wahed, Abdus S

    2016-05-20

    In generalized estimating equations (GEE), the correlation between the repeated observations on a subject is specified with a working correlation matrix. Correct specification of the working correlation structure ensures efficient estimators of the regression coefficients. Among the criteria used, in practice, for selecting working correlation structure, Rotnitzky-Jewell, Quasi Information Criterion (QIC) and Correlation Information Criterion (CIC) are based on the fact that if the assumed working correlation structure is correct then the model-based (naive) and the sandwich (robust) covariance estimators of the regression coefficient estimators should be close to each other. The sandwich covariance estimator, used in defining the Rotnitzky-Jewell, QIC and CIC criteria, is biased downward and has a larger variability than the corresponding model-based covariance estimator. Motivated by this fact, a new criterion is proposed in this paper based on the bias-corrected sandwich covariance estimator for selecting an appropriate working correlation structure in GEE. A comparison of the proposed and the competing criteria is shown using simulation studies with correlated binary responses. The results revealed that the proposed criterion generally performs better than the competing criteria. An example of selecting the appropriate working correlation structure has also been shown using the data from Madras Schizophrenia Study. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26626276

  7. The effect of host structure on the selectivity and mechanism of supramolecular catalysis of Prins cyclizations

    DOE PAGESBeta

    Hart-Cooper, William M.; Zhao, Chen; Triano, Rebecca M.; Yaghoubi, Parastou; Ozores, Haxel Lionel; Burford, Kristen N.; Toste, F. Dean; Bergman, Robert G.; Raymond, Kenneth N.

    2014-11-28

    The effect of host structure on the selectivity and mechanism of intramolecular Prins reactions is evaluated using K12Ga4L6 tetrahedral catalysts. The host structure was varied by modifying the structure of the chelating moieties and the size of the aromatic spacers. While variation in chelator substituents was generally observed to affect changes in rate but not selectivity, changing the host spacer afforded differences in efficiency and product diastereoselectivity. An extremely high number of turnovers (up to 840) was observed. Maximum rate accelerations were measured to be on the order of 105, which numbers among the largest magnitudes of transition state stabilizationmore » measured with a synthetic host-catalyst. Host/guest size effects were observed to play an important role in host-mediated enantioselectivity.« less

  8. Strategy of manufacturing components with designed internal structure by selective laser melting of metallic powder

    NASA Astrophysics Data System (ADS)

    Yadroitsev, I.; Thivillon, L.; Bertrand, Ph.; Smurov, I.

    2007-12-01

    Application of selective laser melting for manufacturing three-dimensional objects represents one of the promising directions to solve challenging industrial problems. This approach permits to extend dramatically the freedom of design and manufacture by allowing, for example, to create an object with desired shape and internal structure in a single fabrication step. The design of the part can be tailored to meet specific functions and properties (e.g. physical, mechanical, chemical, biological, etc.) using different materials. Metallic objects were manufactured by Phenix PM 100 machine from Inconel 625 powder. The objective was to analyze the influence of the manufacturing strategy on the internal structure and mechanical properties of the components manufactured by selective laser melting technology. Anisotropy of the internal structure and mechanical properties of the fabricated objects were studied.

  9. Selectivity control of photosensitivity of Ag-GaP and Ag- AlGaN structures

    NASA Astrophysics Data System (ADS)

    Lamkin, I. A.; Tarasov, S. A.; Solomonov, A. V.; Andreev, M. Y.; Kurin, S. Yu

    2015-12-01

    Design, growth and studies of photosensitive structures based on Ag-GaP and Ag- AlxGa1-xN contacts are reported. Methods for structure selectivity control, which allow changing the sensitivity spectrum half-width in a range of 11-210 nm were worked out. By varying the metal layer thickness, a set of Ag-GaP short-wavelength photodetectors (PD) was fabricated. The set includes PDs from broadband (spectrum half-width Δλ=210 nm, sensitivity SI = 0,19 A/W) to visible-blind (Δλ=15 nm, SI = 0,034 A/W). The use of Ag-AlxGa1-xN structures provided increased sensitivity (SI = 0,071 A/W) and Δλ reduced to 11 nm due to special selection of solid solution composition.

  10. Fabrication and atomic structure of size-selected, layered MoS2 clusters for catalysis.

    PubMed

    Cuddy, Martin J; Arkill, Kenton P; Wang, Zhi Wei; Komsa, Hannu-Pekka; Krasheninnikov, Arkady V; Palmer, Richard E

    2014-11-01

    Well defined MoS2 nanoparticles having a layered structure and abundant edges would be of considerable interest for applications including photocatalysis. We report the atomic structure of MoS2 size-selected clusters with mass in a range all the way from 50 to ∼2000 MoS2 units. The clusters were prepared by magnetron sputtering and gas condensation prior to size selection and soft landing on carbon supports. Aberration-corrected scanning transmission electron microscopy (STEM) in high-angle annular dark-field (HAADF) mode reveals a layered structure and Mo-Mo spacing similar to the bulk material. The mean number of layers in these lamellar clusters increases from one to three with increasing mass, consistent with density functional theory calculations of the balance between edge energies and interlayer binding. PMID:25226541

  11. Selective Sequence for the Peptide-Triggered Phase Transition of Lyotropic Liquid-Crystalline Structures.

    PubMed

    Liu, Qingtao; Dong, Yao-Da; Boyd, Ben J

    2016-05-24

    A novel concept of using mixed lipids to construct selective peptide-sequence-sensing lyotropic liquid-crystalline (LLC) dispersion systems was investigated. The LLC systems were constructed using a mixture of phytantriol, a lipid that forms lyotropic liquid-crystalline phases, and a novel synthesized peptide-lipid (peplipid) for sensing a target peptide with the RARAR sequence. The internal structure of the dispersed LLC particles was converted from the lamellar structure (liposomes) to the inverse bicontinuous cubic phase (cubosomes) in the presence of the target peptide. The addition of common human proteins did not induce any structural change, indicating a high selectivity of interaction with the target peptide. The concept has potential for the design of targeted controlled release drug delivery agents. PMID:27148806

  12. The effect of host structure on the selectivity and mechanism of supramolecular catalysis of Prins cyclizations

    SciTech Connect

    Hart-Cooper, William M.; Zhao, Chen; Triano, Rebecca M.; Yaghoubi, Parastou; Ozores, Haxel Lionel; Burford, Kristen N.; Toste, F. Dean; Bergman, Robert G.; Raymond, Kenneth N.

    2014-11-28

    The effect of host structure on the selectivity and mechanism of intramolecular Prins reactions is evaluated using K12Ga4L6 tetrahedral catalysts. The host structure was varied by modifying the structure of the chelating moieties and the size of the aromatic spacers. While variation in chelator substituents was generally observed to affect changes in rate but not selectivity, changing the host spacer afforded differences in efficiency and product diastereoselectivity. An extremely high number of turnovers (up to 840) was observed. Maximum rate accelerations were measured to be on the order of 105, which numbers among the largest magnitudes of transition state stabilization measured with a synthetic host-catalyst. Host/guest size effects were observed to play an important role in host-mediated enantioselectivity.

  13. Structural inheritance and selective reactivation in the central Andes: Cenozoic deformation guided by pre-Andean structures in southern Peru

    NASA Astrophysics Data System (ADS)

    Perez, Nicholas D.; Horton, Brian K.; Carlotto, Victor

    2016-03-01

    Structural, stratigraphic, and geochronologic constraints from the Eastern Cordillera in the central Andean plateau of southern Peru (14-15°S) demonstrate the existence and position of major pre-Andean structures that controlled the accumulation of Triassic synrift fill and guided subsequent Cenozoic deformation. The timing of initial clastic deposition of the Triassic Mitu Group is here constrained to ~ 242-233 Ma on the basis of detrital and volcanic zircon U-Pb geochronology. Regionally distinct provenance variations, as provided by U-Pb age populations from localized synrift accumulations, demonstrate Triassic erosion of multiple diagnostic sources from diverse rift-flank uplifts. Stratigraphic correlations suggest synchronous initiation of extensional basins containing the Mitu Group, in contrast with previous interpretations of southward rift propagation. Triassic motion along the NE-dipping San Anton normal fault accommodated up to 7 km of throw and hanging-wall deposition of a synrift Mitu succession > 2.5 km thick. The contrasting orientation of a non-reactivated Triassic normal fault suggests selective inversion of individual structures in the Eastern Cordillera was dependent on fault dip and strike. Selective preservation of a ~ 4 km thick succession of Carboniferous-Permian strata in the down-dropped San Anton hanging wall, beneath the synrift Mitu Group, suggests large-scale erosional removal in the uplifted footwall. Field and map observations identify additional pre-Andean thrust faults and folds attributed to poorly understood Paleozoic orogenic events preserved in the San Anton hanging wall. Selective thrust reactivation of normal and reverse faults during later compression largely guided Cenozoic deformation in the Eastern Cordillera. The resulting structural compartmentalization and across-strike variations in kinematics and deformation style highlight the influence of inherited Paleozoic structures and Triassic normal faults on the long

  14. Probabilistic Structural Analysis Methods (PSAM) for select space propulsion system components, part 2

    NASA Technical Reports Server (NTRS)

    1991-01-01

    The technical effort and computer code enhancements performed during the sixth year of the Probabilistic Structural Analysis Methods program are summarized. Various capabilities are described to probabilistically combine structural response and structural resistance to compute component reliability. A library of structural resistance models is implemented in the Numerical Evaluations of Stochastic Structures Under Stress (NESSUS) code that included fatigue, fracture, creep, multi-factor interaction, and other important effects. In addition, a user interface was developed for user-defined resistance models. An accurate and efficient reliability method was developed and was successfully implemented in the NESSUS code to compute component reliability based on user-selected response and resistance models. A risk module was developed to compute component risk with respect to cost, performance, or user-defined criteria. The new component risk assessment capabilities were validated and demonstrated using several examples. Various supporting methodologies were also developed in support of component risk assessment.

  15. Selection for territory acquisition is modulated by social network structure in a wild songbird

    PubMed Central

    Farine, D R; Sheldon, B C

    2015-01-01

    The social environment may be a key mediator of selection that operates on animals. In many cases, individuals may experience selection not only as a function of their phenotype, but also as a function of the interaction between their phenotype and the phenotypes of the conspecifics they associate with. For example, when animals settle after dispersal, individuals may benefit from arriving early, but, in many cases, these benefits will be affected by the arrival times of other individuals in their local environment. We integrated a recently described method for calculating assortativity on weighted networks, which is the correlation between an individual's phenotype and that of its associates, into an existing framework for measuring the magnitude of social selection operating on phenotypes. We applied this approach to large-scale data on social network structure and the timing of arrival into the breeding area over three years. We found that late-arriving individuals had a reduced probability of breeding. However, the probability of breeding was also influenced by individuals’ social networks. Associating with late-arriving conspecifics increased the probability of successfully acquiring a breeding territory. Hence, social selection could offset the effects of nonsocial selection. Given parallel theoretical developments of the importance of local network structure on population processes, and increasing data being collected on social networks in free-living populations, the integration of these concepts could yield significant insights into social evolution. PMID:25611344

  16. Selection for territory acquisition is modulated by social network structure in a wild songbird.

    PubMed

    Farine, D R; Sheldon, B C

    2015-03-01

    The social environment may be a key mediator of selection that operates on animals. In many cases, individuals may experience selection not only as a function of their phenotype, but also as a function of the interaction between their phenotype and the phenotypes of the conspecifics they associate with. For example, when animals settle after dispersal, individuals may benefit from arriving early, but, in many cases, these benefits will be affected by the arrival times of other individuals in their local environment. We integrated a recently described method for calculating assortativity on weighted networks, which is the correlation between an individual's phenotype and that of its associates, into an existing framework for measuring the magnitude of social selection operating on phenotypes. We applied this approach to large-scale data on social network structure and the timing of arrival into the breeding area over three years. We found that late-arriving individuals had a reduced probability of breeding. However, the probability of breeding was also influenced by individuals' social networks. Associating with late-arriving conspecifics increased the probability of successfully acquiring a breeding territory. Hence, social selection could offset the effects of nonsocial selection. Given parallel theoretical developments of the importance of local network structure on population processes, and increasing data being collected on social networks in free-living populations, the integration of these concepts could yield significant insights into social evolution. PMID:25611344

  17. Major research topics in combustion

    SciTech Connect

    Hussaini, M.Y.; Kumar, A.; Voigt, R.G.

    1992-01-01

    The Institute for Computer Applications in Science and Engineering (ICASE) and NASA Langley Research Center (LaRC) hosted a workshop on October 2--4, 1989 to discuss some combustion problems of technological interest to LaRC and to foster interaction with the academic community in these research areas. The topics chosen for this purpose were flame structure, flame holding/extinction, chemical kinetics, turbulence-kinetics interaction, transition to detonation, and reacting free shear layers. This document contains the papers and edited versions of general discussions on these topics. The lead paper set the stage for the meeting by discussing the status and issues of supersonic combustion relevant to the scramjet engine. Experts were then called upon to review the current knowledge in the aforementioned areas, to focus on how this knowledge can be extended and applied to high-speed combustion, and to suggest future directions of research in these areas.

  18. Lack of Spatial Immunogenetic Structure among Wolverine (Gulo gulo) Populations Suggestive of Broad Scale Balancing Selection

    PubMed Central

    Rico, Yessica; Morris-Pocock, James; Zigouris, Joanna; Nocera, Joseph J.; Kyle, Christopher J.

    2015-01-01

    Elucidating the adaptive genetic potential of wildlife populations to environmental selective pressures is fundamental for species conservation. Genes of the major histocompatibility complex (MHC) are highly polymorphic, and play a key role in the adaptive immune response against pathogens. MHC polymorphism has been linked to balancing selection or heterogeneous selection promoting local adaptation. However, spatial patterns of MHC polymorphism are also influenced by gene flow and drift. Wolverines are highly vagile, inhabiting varied ecoregions that include boreal forest, taiga, tundra, and high alpine ecosystems. Here, we investigated the immunogenetic variation of wolverines in Canada as a surrogate for identifying local adaptation by contrasting the genetic structure at MHC relative to the structure at 11 neutral microsatellites to account for gene flow and drift. Evidence of historical positive selection was detected at MHC using maximum likelihood codon-based methods. Bayesian and multivariate cluster analyses revealed weaker population genetic differentiation at MHC relative to the increasing microsatellite genetic structure towards the eastern wolverine distribution. Mantel correlations of MHC against geographical distances showed no pattern of isolation by distance (IBD: r = -0.03, p = 0.9), whereas for microsatellites we found a relatively strong and significant IBD (r = 0.54, p = 0.01). Moreover, we found a significant correlation between microsatellite allelic richness and the mean number of MHC alleles, but we did not observe low MHC diversity in small populations. Overall these results suggest that MHC polymorphism has been influenced primarily by balancing selection and to a lesser extent by neutral processes such as genetic drift, with no clear evidence for local adaptation. This study contributes to our understanding of how vulnerable populations of wolverines may respond to selective pressures across their range. PMID:26448462

  19. Lack of Spatial Immunogenetic Structure among Wolverine (Gulo gulo) Populations Suggestive of Broad Scale Balancing Selection.

    PubMed

    Rico, Yessica; Morris-Pocock, James; Zigouris, Joanna; Nocera, Joseph J; Kyle, Christopher J

    2015-01-01

    Elucidating the adaptive genetic potential of wildlife populations to environmental selective pressures is fundamental for species conservation. Genes of the major histocompatibility complex (MHC) are highly polymorphic, and play a key role in the adaptive immune response against pathogens. MHC polymorphism has been linked to balancing selection or heterogeneous selection promoting local adaptation. However, spatial patterns of MHC polymorphism are also influenced by gene flow and drift. Wolverines are highly vagile, inhabiting varied ecoregions that include boreal forest, taiga, tundra, and high alpine ecosystems. Here, we investigated the immunogenetic variation of wolverines in Canada as a surrogate for identifying local adaptation by contrasting the genetic structure at MHC relative to the structure at 11 neutral microsatellites to account for gene flow and drift. Evidence of historical positive selection was detected at MHC using maximum likelihood codon-based methods. Bayesian and multivariate cluster analyses revealed weaker population genetic differentiation at MHC relative to the increasing microsatellite genetic structure towards the eastern wolverine distribution. Mantel correlations of MHC against geographical distances showed no pattern of isolation by distance (IBD: r = -0.03, p = 0.9), whereas for microsatellites we found a relatively strong and significant IBD (r = 0.54, p = 0.01). Moreover, we found a significant correlation between microsatellite allelic richness and the mean number of MHC alleles, but we did not observe low MHC diversity in small populations. Overall these results suggest that MHC polymorphism has been influenced primarily by balancing selection and to a lesser extent by neutral processes such as genetic drift, with no clear evidence for local adaptation. This study contributes to our understanding of how vulnerable populations of wolverines may respond to selective pressures across their range. PMID:26448462

  20. IP Internal Movement and Topicalization

    ERIC Educational Resources Information Center

    Kuo, Pei-Jung

    2009-01-01

    In this dissertation, I investigate the phenomenon of internal topicalization cross-linguistically, using Chinese as a starting point. Internal topicalization refers to constructions in which a topic phrase is placed between the subject and the verb (in contrast to external topicalization, which involves a topic in the CP domain). I argue that…

  1. TOPICAL REVIEW: Nanoparticle catalysts

    NASA Astrophysics Data System (ADS)

    Moshfegh, A. Z.

    2009-12-01

    In this review, the importance of nanoparticles (NPs), with emphasis on their general and specific properties, especially the high surface-to-volume ratio (A/V), in many technological and industrial applications is studied. Some physical and chemical preparation methods for growing several metallic and binary alloy NP catalysts are reviewed. The growth and mechanism of catalytic reactions for synthesis of 1D nanostructures such as ZnO nanowires and multiwall carbon nanotubes (MWCNTs) are discussed. Gas-phase production with emphasis on dependence of catalytic activity and selectivity on size, shape and structure of NPs is also investigated. Application of NP catalysts in several technological processes including H2 production and storage as well as antibacterial effect, gas sensors and fuel cells is discussed. The mechanism of H2 production from catalytic photoelectrochemical and photocatalytic degradation reactions of some organic dyes is discussed. Finally, the future outlook of NP catalysts in various disciplines is presented.

  2. Physical Ingredients Controlling Stability and Structural Selection of Empty Viral Capsids.

    PubMed

    Aznar, María; Reguera, David

    2016-07-01

    One of the crucial steps in the viral replication cycle is the self-assembly of its protein shell. Typically, each native virus adopts a unique architecture, but the coat proteins of many viruses have the capability to self-assemble in vitro into different structures by changing the assembly conditions. However, the mechanisms determining which of the possible capsid shapes and structures is selected by a virus are still not well-known. We present a coarse-grained model to analyze and understand the physical mechanisms controlling the size and structure selection in the assembly of empty viral capsids. Using this model and Monte Carlo simulations, we have characterized the phase diagram and stability of T = 1,3,4,7 and snub cube shells. In addition, we have studied the tolerance of different shells to changes in physical parameters related to ambient conditions, identifying possible strategies to induce misassembly or failure. Finally, we discuss the factors that select the shape of a capsid as spherical, faceted, elongated, or decapsidated. Our model sheds important light on the ingredients that control the assembly and stability of viral shells. This knowledge is essential to get capsids with well-defined size and structure that could be used for promising applications in medicine or bionanotechnology. PMID:27114062

  3. Selecting Optimum Eukaryotic Integral Membrane Proteins for Structure Determination by Rapid Expression and Solubilization Screening

    PubMed Central

    Li, Min; Hays, Franklin A.; Roe-Zurz, Zygy; Vuong, Linda; Kelly, Libusha; Ho, Chi-Min; Robbins, Renée M.; Pieper, Ursula; O’Connell, Joseph D.; Miercke, Larry J. W.; Giacomini, Kathleen M.; Sali, Andrej; Stroud, Robert M.

    2009-01-01

    A medium throughput approach is used to rapidly identify membrane proteins from a eukaryotic organism that are most amenable to expression in amounts and quality adequate to support structure determination. The goal was to expand knowledge of new membrane protein structures based on proteome-wide coverage. In the first phase membrane proteins from the budding yeast Saccharomyces cerevisiae were selected for homologous expression in S. cerevisiae, a system that can be adapted to expression of membrane proteins from other eukaryotes. We performed medium-scale expression and solubilization tests on 351 rationally selected membrane proteins from the budding yeast Saccharomyces cerevisiae. These targets are inclusive of all annotated and unannotated membrane protein families within the organism’s membrane proteome. 272 targets were expressed and of these 234 solubilized in the detergent n-dodecyl-β-D-maltopyranoside. Furthermore, we report the identity of a subset of targets that were purified to homogeneity to facilitate structure determinations. The extensibility of this approach is demonstrated with the expression of ten human integral membrane proteins from the solute carrier superfamily (SLC). This discovery-oriented pipeline provides an efficient way to select proteins from particular membrane protein classes, families, or organisms that may be more suited to structure analysis than others. PMID:19061901

  4. Effects of Sample Selection Bias on the Accuracy of Population Structure and Ancestry Inference

    PubMed Central

    Shringarpure, Suyash; Xing, Eric P.

    2014-01-01

    Population stratification is an important task in genetic analyses. It provides information about the ancestry of individuals and can be an important confounder in genome-wide association studies. Public genotyping projects have made a large number of datasets available for study. However, practical constraints dictate that of a geographical/ethnic population, only a small number of individuals are genotyped. The resulting data are a sample from the entire population. If the distribution of sample sizes is not representative of the populations being sampled, the accuracy of population stratification analyses of the data could be affected. We attempt to understand the effect of biased sampling on the accuracy of population structure analysis and individual ancestry recovery. We examined two commonly used methods for analyses of such datasets, ADMIXTURE and EIGENSOFT, and found that the accuracy of recovery of population structure is affected to a large extent by the sample used for analysis and how representative it is of the underlying populations. Using simulated data and real genotype data from cattle, we show that sample selection bias can affect the results of population structure analyses. We develop a mathematical framework for sample selection bias in models for population structure and also proposed a correction for sample selection bias using auxiliary information about the sample. We demonstrate that such a correction is effective in practice using simulated and real data. PMID:24637351

  5. Crystal structure of PTP1B complexed with a potent and selective bidentate inhibitor.

    PubMed

    Sun, Jin-Peng; Fedorov, Alexander A; Lee, Seung-Yub; Guo, Xiao-Ling; Shen, Kui; Lawrence, David S; Almo, Steven C; Zhang, Zhong-Yin

    2003-04-01

    Protein-tyrosine phosphatase 1B (PTP1B) has been implicated as an important regulator in several signaling pathways including those initiated by insulin and leptin. Potent and specific PTP1B inhibitors could serve as useful tools in elucidating the physiological functions of PTP1B and may constitute valuable therapeutics in the treatment of several human diseases. We have determined the crystal structure of PTP1B in complex with compound 2, the most potent and selective PTP1B inhibitor reported to date. The structure at 2.15-A resolution reveals that compound 2 simultaneously binds to the active site and a unique proximal noncatalytic site formed by Lys-41, Arg-47, and Asp-48. The structural data are further corroborated by results from kinetic analyses of the interactions of PTP1B and its site-directed mutants with compound 2 and several of its variants. Although many of the residues important for interactions between PTP1B and compound 2 are not unique to PTP1B, the combinations of all contact residues differ between PTP isozymes, which provide a structural basis for potent and selective PTP1B inhibition. Our data further suggest that potent, yet highly selective, PTP1B inhibitory agents can be acquired by targeting the area defined by residues Lys-41, Arg-47, and Asp-48, in addition to the previously identified second aryl phosphate-binding pocket. PMID:12547827

  6. Topical antibiotics in dermatology.

    PubMed

    Hirschmann, J V

    1988-11-01

    Topical antibiotics are safe and effective in certain conditions, primarily acne, rosacea, and nasal carriage of Staphylococcus aureus. They are useful in impetigo only when it is of limited extent. Their efficacy in other pyodermas is unclear, although mupirocin is probably effective in many cases. In "infected eczema" that does not require systemic therapy they seem to add little to what topical corticosteroids alone achieve. They are ineffective in reducing the incidence of significant infection with indwelling intravenous catheters. They are safe preparations, but extensive use, especially in closed populations, may encourage the emergence of resistant bacteria. PMID:2972259

  7. Topical Therapies for Pruritus

    PubMed Central

    Elmariah, Sarina B.; Lerner, Ethan A.

    2011-01-01

    Itch, or pruritus, is the predominant symptom associated with acute and chronic cutaneous disease and in some cases, may be debilitating. To date, there is no single universally effective anti-itch treatment. As the pathophysiology of itch in most cutaneous or systemic disorders remains unclear, anti-pruritic therapy is often directed against a variety of targets, including the epidermal barrier, immune system, or the nervous system. Topical therapy is the mainstay of dermatologic management of acute or localized itch or in patients with contraindications to systemic therapies. This review will summarize current topical therapies to treat pruritus and discuss potential future therapies. PMID:21767774

  8. Survey of social health insurance structure in selected countries; providing framework for basic health insurance in Iran

    PubMed Central

    Mohammadi, Effat; Raissi, Ahmad Reza; Barooni, Mohsen; Ferdoosi, Massoud; Nuhi, Mojtaba

    2014-01-01

    Introduction and Objectives: Health system reforms are the most strategic issue that has been seriously considered in healthcare systems in order to reduce costs and increase efficiency and effectiveness. The costs of health system finance in our country, lack of universal coverage in health insurance, and related issues necessitate reforms in our health system financing. The aim of this research was to prepare a structure of framework for social health insurance in Iran and conducting a comparative study in selected countries with social health insurance. Materials and Methods: This comparative descriptive study was conducted in three phases. The first phase of the study examined the structure of health social insurance in four countries – Germany, South Korea, Egypt, and Australia. The second phase was to develop an initial model, which was designed to determine the shared and distinguishing points of the investigated structures, for health insurance in Iran. The third phase was to validate the final research model. The developed model by the Delphi method was given to 20 professionals in financing of the health system, health economics and management of healthcare services. Their comments were collected in two stages and its validity was confirmed. Findings: The study of the structure of health insurance in the selected countries shows that health social insurance in different countries have different structures. Based on the findings of the present study, the current situation of the health system, and the conducted surveys, the following framework is suitable for the health social insurance system in Iran. The Health Social Insurance Organization has a unique service by having five funds of governmental employees, companies and NGOs, self-insured, villagers, and others, which serves as a nongovernmental organization under the supervision of public law and by decision- and policy-making of the Health Insurance Supreme Council. Membership in this organization

  9. In search of potent and selective inhibitors of neuronal nitric oxide synthase with more simple structures

    PubMed Central

    Jing, Qing; Li, Huiying; Fang, Jianguo; Roman, Linda J.; Martásek, Pavel; Poulos, Thomas L.; Silverman, Richard B.

    2013-01-01

    In certain neurodegenerative diseases damaging levels of nitric oxide (NO) are produced by neuronal nitric oxide synthase (nNOS). It, therefore, is important to develop inhibitors selective for nNOS that do not interfere with other NOS isoforms, especially endothelial NOS (eNOS), which is critical for proper functioning of the cardiovascular system. While we have been successful in developing potent and isoform-selective inhibitors, such as lead compounds 1 and 2, the ease of synthesis and bioavailability have been problematic. Here we describe a new series of compounds including crystal structures of NOS-inhibitor complexes that integrate the advantages of easy synthesis and good biological properties compared to the lead compounds. These results provide the basis for additional structure–activity relationship (SAR) studies to guide further improvement of isozyme selective inhibitors. PMID:23867386

  10. Electrofluidics fabricated by space-selective metallization in glass microfluidic structures using femtosecond laser direct writing.

    PubMed

    Xu, Jian; Wu, Dong; Hanada, Yasutaka; Chen, Chi; Wu, Sizhu; Cheng, Ya; Sugioka, Koji; Midorikawa, Katsumi

    2013-12-01

    Space-selective metallization of the inside of glass microfluidic structures using femtosecond laser direct-write ablation followed by electroless plating is demonstrated. Femtosecond laser direct writing followed by thermal treatment and successive chemical etching allows us to fabricate three-dimensional microfluidic structures inside photosensitive glass. Then, femtosecond laser ablation followed by electroless metal plating enables flexible deposition of patterned metal films on desired locations of not only the top and bottom walls but also the sidewalls of fabricated microfluidic structures. A volume writing scheme for femtosecond laser irradiation inducing homogeneous ablation on the sidewalls of microfluidic structures is proposed for sidewall metallization. The developed technique is used to fabricate electrofluidics in which microelectric components are integrated into glass microchannels. The fabricated electrofluidics are applied to control the temperature of liquid samples in the microchannels for the enhancement of chemical reactions and to manipulate the movement of biological samples in the microscale space. PMID:24104603

  11. Structure-dependent water transport across nanopores of carbon nanotubes: toward selective gating upon temperature regulation.

    PubMed

    Zhao, Kuiwen; Wu, Huiying

    2015-04-28

    Determining water structure in nanopores and its influence on water transport behaviour is of great importance for understanding and regulating the transport across nanopores. Here we report an ultrafast-slow flow transition phenomenon for water transport across nanopores of carbon nanotubes owing to the change in water structure in nanopores induced by temperature. By performing extensive molecular dynamics simulations, we show the dependence of water transport behaviours on water structures. Our results indicate that owing to the change in water structure in nanopores, water flux across nanopores with certain pore sizes decreases sharply (nearly 3 orders of magnitude) with the decreasing temperature. This phenomenon is very sensitive to the pore size. The threshold temperatures for the occurrence of the ultrafast-slow flow transition for water transport are also determined for various pore sizes. These findings suggest a novel protocol for selective gating of water and proton conduction across nanopores and temperature-controlled drug release. PMID:25805425

  12. Small Angle X-ray Scattering in Structural Investigation of Selected Biological Systems

    SciTech Connect

    Kozak, Maciej

    2007-11-26

    Small angle X-ray scattering method (SAXS) is a technique complementary to the protein crystallography, allowing determination of the structural parameters such as the radius of gyration or the maximum size characterizing the macromolecules, and providing information on the conformational changes taking place in solution. The use of SAXS method enables a comparison of the protein crystal structure with the data collected in solution. Recent development of the measurement techniques (mainly those based on synchrotron radiation) and calculation methods has permitted introduction of advanced techniques also in the field of structural analysis of biomolecules (e.g. for determination of the shape of the protein molecule in solution). The paper presents a few selected methods of structural analysis of biological systems based on the SAXS data and illustrates their performance on the example of xylanase from Trichoderma longibrachiatum and a model phospholipid system.

  13. The crystal structure of a bimorphinan with highly selective kappa opioid receptor antagonist activity

    NASA Astrophysics Data System (ADS)

    Urbańczyk-Lipkowska, Zofia; Etter, Margaret C.; Lipkowski, Andrzej W.; Portoghese, Philip S.

    1987-07-01

    The crystal structure of the dihydrobromide heptahydrate of nor-binaltorphimine (17, 17'-bis(cyclopropylmethyl)-6,6',7,7'-tetrahydro-4,5α: 4',5'α-diepoxy-6,6'-imino[7,7' bimorphinan]-3,3',14,14'-tetraol)is presented. This structure is the first reported structure of a rigid bivalent opioid ligand. Two morphinan pharmacophores are connected by a rigid spacer, the pyrrole ring. The nor-binaltorphimine structure itself shows unique, high selectivity as a kappa opioid receptor antagonist. Crystal data: P3 2, Z = 3, a = b = 20.223 (4), c = 9.541(7) Å, α = β = 90°, γ = 120°; R = 0.079 (1765 reflections, Fobs > 1σ( F)).

  14. Structural and functional implications of positive selection at the primate angiogenin gene

    PubMed Central

    Osorio, Daniel S; Antunes, Agostinho; Ramos, Maria J

    2007-01-01

    Background Angiogenesis, the formation of new blood vessels, is a primordial process in development and its dysregulation has a central role in the pathogenesis of many diseases. Angiogenin (ANG), a peculiar member of the RNase A superfamily, is a potent inducer of angiogenesis involved in many different types of cancer, amyotrophic lateral sclerosis and also with a possible role in the innate immune defense. The evolutionary path of this family has been a highly dynamic one, where positive selection has played a strong role. In this work we used a combined gene and protein level approach to determine the main sites under diversifying selection on the primate ANG gene and analyze its structural and functional implications. Results We obtained evidence for positive selection in the primate ANG gene. Site specific analysis pointed out 15 sites under positive selection, most of which also exhibited drastic changes in amino acid properties. The mapping of these sites in the ANG 3D-structure described five clusters, four of which were located in functional regions: two in the active site region, one in the nucleolar location signal and one in the cell-binding site. Eight of the 15 sites under selection in the primate ANG gene were highly or moderately conserved in the RNase A family, suggesting a directed event and not a simple consequence of local structural or functional permissiveness. Moreover, 11 sites were exposed to the surface of the protein indicating that they may influence the interactions performed by ANG. Conclusion Using a maximum likelihood gene level analysis we identified 15 sites under positive selection in the primate ANG genes, that were further corroborated through a protein level analysis of radical changes in amino acid properties. These sites mapped onto the main functional regions of the ANG protein. The fact that evidence for positive selection is present in all ANG regions required for angiogenesis may be a good indication that angiogenesis is

  15. Structural Bioinformatics-Based Prediction of Exceptional Selectivity of p38 MAP Kinase Inhibitor PH-797804

    SciTech Connect

    Xing, Li; Shieh, Huey S.; Selness, Shaun R.; Devraj, Rajesh V.; Walker, John K.; Devadas, Balekudru; Hope, Heidi R.; Compton, Robert P.; Schindler, John F.; Hirsch, Jeffrey L.; Benson, Alan G.; Kurumbail, Ravi G.; Stegeman, Roderick A.; Williams, Jennifer M.; Broadus, Richard M.; Walden, Zara; Monahan, Joseph B.; Pfizer

    2009-07-24

    PH-797804 is a diarylpyridinone inhibitor of p38{alpha} mitogen-activated protein (MAP) kinase derived from a racemic mixture as the more potent atropisomer (aS), first proposed by molecular modeling and subsequently confirmed by experiments. On the basis of structural comparison with a different biaryl pyrazole template and supported by dozens of high-resolution crystal structures of p38{alpha} inhibitor complexes, PH-797804 is predicted to possess a high level of specificity across the broad human kinase genome. We used a structural bioinformatics approach to identify two selectivity elements encoded by the TXXXG sequence motif on the p38{alpha} kinase hinge: (i) Thr106 that serves as the gatekeeper to the buried hydrophobic pocket occupied by 2,4-difluorophenyl of PH-797804 and (ii) the bidentate hydrogen bonds formed by the pyridinone moiety with the kinase hinge requiring an induced 180{sup o} rotation of the Met109-Gly110 peptide bond. The peptide flip occurs in p38{alpha} kinase due to the critical glycine residue marked by its conformational flexibility. Kinome-wide sequence mining revealed rare presentation of the selectivity motif. Corroboratively, PH-797804 exhibited exceptionally high specificity against MAP kinases and the related kinases. No cross-reactivity was observed in large panels of kinase screens (selectivity ratio of >500-fold). In cellular assays, PH-797804 demonstrated superior potency and selectivity consistent with the biochemical measurements. PH-797804 has met safety criteria in human phase I studies and is under clinical development for several inflammatory conditions. Understanding the rationale for selectivity at the molecular level helps elucidate the biological function and design of specific p38{alpha} kinase inhibitors.

  16. Selection of actuator locations for static shape control of large space structures by heuristic integer programing

    NASA Technical Reports Server (NTRS)

    Haftka, R. T.; Adelman, H. M.

    1984-01-01

    Orbiting spacecraft such as large space antennas have to maintain a highly accurate space to operate satisfactorily. Such structures require active and passive controls to mantain an accurate shape under a variety of disturbances. Methods for the optimum placement of control actuators for correcting static deformations are described. In particular, attention is focused on the case were control locations have to be selected from a large set of available sites, so that integer programing methods are called for. The effectiveness of three heuristic techniques for obtaining a near-optimal site selection is compared. In addition, efficient reanalysis techniques for the rapid assessment of control effectiveness are presented. Two examples are used to demonstrate the methods: a simple beam structure and a 55m space-truss-parabolic antenna.

  17. Selection of actuator locations for static shape control of large space structures by heuristic integer programing

    NASA Technical Reports Server (NTRS)

    Haftka, R. T.; Adelman, H. M.

    1985-01-01

    Orbiting spacecraft such as large space antennas have to maintain a highly accurate shape to operate satisfactorily. Such structures require active and passive controls to maintain an accurate shape under a variety of disturbances. Methods for the optimum placement of control actuators for correcting static deformations are described. In particular, attention is focused on the case were control locations have to be selected from a large set of available sites, so that integer programing methods are called for. The effectiveness of three heuristic techniques for obtaining a near-optimal site selection is compared. In addition, efficient reanalysis techniques for the rapid assessment of control effectiveness are presented. Two examples are used to demonstrate the methods: a simple beam structure and a 55m space-truss-parabolic antenna.

  18. Introduction of structural affinity handles as a tool in selective nucleic acid separations

    NASA Technical Reports Server (NTRS)

    Willson, III, Richard Coale (Inventor); Cano, Luis Antonio (Inventor)

    2011-01-01

    The method is used for separating nucleic acids and other similar constructs. It involves selective introduction, enhancement, or stabilization of affinity handles such as single-strandedness in the undesired (or desired) nucleic acids as compared to the usual structure (e.g., double-strandedness) of the desired (or undesired) nucleic acids. The undesired (or desired) nucleic acids are separated from the desired (or undesired) nucleic acids due to capture by methods including but not limited to immobilized metal affinity chromatography, immobilized single-stranded DNA binding (SSB) protein, and immobilized oligonucleotides. The invention is useful to: remove contaminating genomic DNA from plasmid DNA; remove genomic DNA from plasmids, BACs, and similar constructs; selectively separate oligonucleotides and similar DNA fragments from their partner strands; purification of aptamers, (deoxy)-ribozymes and other highly structured nucleic acids; Separation of restriction fragments without using agarose gels; manufacture recombinant Taq polymerase or similar products that are sensitive to host genomic DNA contamination; and other applications.

  19. Structure-based design of 2-aminopyridine oxazolidinones as potent and selective tankyrase inhibitors.

    PubMed

    Huang, Hongbing; Guzman-Perez, Angel; Acquaviva, Lisa; Berry, Virginia; Bregman, Howard; Dovey, Jennifer; Gunaydin, Hakan; Huang, Xin; Huang, Liyue; Saffran, Doug; Serafino, Randy; Schneider, Steve; Wilson, Cindy; DiMauro, Erin F

    2013-12-12

    Aberrant activation of the Wnt pathway has been implicated in the development and formation of many cancers. TNKS inhibition has been shown to antagonize Wnt signaling via Axin stabilization in APC mutant colon cancer cell lines. We employed structure-based design to identify a series of 2-aminopyridine oxazolidinones as potent and selective TNKS inhibitors. These compounds exhibited good enzyme and cell potency as well as selectivity over other PARP isoforms. Co-crystal structures of these 2-aminopyridine oxazolidinones complexed to TNKS reveal an induced-pocket binding mode that does not involve interactions with the nicotinamide binding pocket. Oral dosing of lead compounds 3 and 4 resulted in significant effects on several Wnt-pathway biomarkers in a three day DLD-1 mouse tumor PD model. PMID:24900633

  20. Two-photon polarization-selective etching of emergent nano-structures on diamond surfaces.

    PubMed

    Lehmann, A; Bradac, C; Mildren, R P

    2014-01-01

    Optical techniques have advanced considerably in recent years to enable processing of surfaces with a resolution less than the wavelength of light. Despite the highly selective nature of light-matter interactions, however, efforts to increase resolution to the scale of single atoms are hampered by rapid and efficient dissipation of the absorbed energy to the surrounding matrix. Here we show that two-photon surface excitation using ultraviolet light provides a method for selectively removing carbon from diamond surfaces. Polished surfaces etched by this method develop ultra-deep subwavelength structures with morphologies dependent on the polarization of the incident laser with respect to the crystal axes. As well as revealing a practical and versatile method for nano-patterning of diamond surfaces, we show that the results comprise mesoscopic evidence for bond scission via a highly localized optical interaction that may lead to the development of new optical approaches for ultra-nanoscale (<10 nm) surface structuring. PMID:24594857

  1. Spatial localization of the K+ channel selectivity filter by mutant cycle-based structure analysis.

    PubMed

    Ranganathan, R; Lewis, J H; MacKinnon, R

    1996-01-01

    The structurally well-characterized scorpion toxin Agitoxin2 inhibits ion permeation through Shaker K+ channels by binding to the external pore entryway. Scanning mutagenesis identified a set of inhibitor residues critical for making energetic contacts with the channel. Using thermodynamic mutant cycle analysis, we have mapped channel residues relative to the known inhibitor structure. This study constrains the position of multiple channel residues within the pore-forming loops; in one stretch, we have been able to map five out of seven contiguous residues to the inhibitor interaction surface, including those involved in ion selectivity. One interaction in particular, that of K27M on the inhibitor with Y445F on the channel, is unique in that it depends on the K+ ion concentration. These results reveal a shallow vestibule formed by the pore loops at the K+ channel entryway. The selectivity filter is located at the center of the vestibule close to (approximately 5 A) the extracellular solution. PMID:8562077

  2. Wave-plate structures, power selective optical filter devices, and optical systems using same

    DOEpatents

    Koplow, Jeffrey P.

    2012-07-03

    In an embodiment, an optical filter device includes an input polarizer for selectively transmitting an input signal. The device includes a wave-plate structure positioned to receive the input signal, which includes first and second substantially zero-order, zero-wave plates arranged in series with and oriented at an angle relative to each other. The first and second zero-wave plates are configured to alter a polarization state of the input signal passing in a manner that depends on the power of the input signal. Each zero-wave plate includes an entry and exit wave plate each having a fast axis, with the fast axes oriented substantially perpendicular to each other. Each entry wave plate is oriented relative to a transmission axis of the input polarizer at a respective angle. An output polarizer is positioned to receive a signal output from the wave-plate structure and selectively transmits the signal based on the polarization state.

  3. Crystal Structure of Oxidative Stress Sensor Keap1 in Complex with Selective Autophagy Substrate p62

    NASA Astrophysics Data System (ADS)

    Kurokawa, Hirofumi

    Keap1, an adaptor protein of cullin-RING ubiquitin ligase complex, represses cytoprotective transcription factor Nrf2 in an oxidative stress-dependent manner. The accumulation of selective autophagy substrate p62 also activates Nrf2 target genes, but the detailed mechanism has not been elucidated. Crystal structure of Keap1-p62 complex revealed the structural basis for the Nrf2 activation in which Keap1 is inactivated by p62. The accumulation of p62 is observed in hepatocellular carcinoma. The activation of Nrf2 target genes, including detoxifying enzymes and efflux transporters, by p62 may protect the cancer cells from anti-cancer drugs.

  4. Economic sensor/actuator selection and its application to flexible structure control

    NASA Astrophysics Data System (ADS)

    Skelton, Robert E.; Li, Faming

    2004-07-01

    A systematic design method is proposed for the selecting of actuators and sensors in the structural control in order to minimize the instrumental cost. With actuators and sensors placed at all the admissible locations initially, an iterative minimization algorithm is carried out to identify the sensor/actuator that requires the least precision. By deleting the roughest sensor/actuator each time till loss of feasibility, one can conclude simultaneously the necessary number and type of sensor/actuator, and the location and precision for each sensor/actuator. A tensegrity structure example has been solved as an application of the proposed algorithm.

  5. Model-based fault detection and identification with online aerodynamic model structure selection

    NASA Astrophysics Data System (ADS)

    Lombaerts, T.

    2013-12-01

    This publication describes a recursive algorithm for the approximation of time-varying nonlinear aerodynamic models by means of a joint adaptive selection of the model structure and parameter estimation. This procedure is called adaptive recursive orthogonal least squares (AROLS) and is an extension and modification of the previously developed ROLS procedure. This algorithm is particularly useful for model-based fault detection and identification (FDI) of aerospace systems. After the failure, a completely new aerodynamic model can be elaborated recursively with respect to structure as well as parameter values. The performance of the identification algorithm is demonstrated on a simulation data set.

  6. Feature selection and the information content of Thematic Mapper simulator data for forest structural assessment

    NASA Technical Reports Server (NTRS)

    Spanner, M. A.; Brass, J. A.; Peterson, D. L.

    1984-01-01

    An assessment is made of the information content of Thematic Mapper Simulator (TMS) data for the case of a forested region, in order to determine the sensitivity of such data to forest crown closure and tree size class. Principal components analysis and Monte Carlo simulation indicated that channels 4, 7, 5 and 3 were optimal for four-channel forest structure analysis. As the number of channels supplied to the Monte Carlo feature selection routine increased, classification accuracy increased. The greatest sensitivity to the forest structural parameters, which included succession within clearcuts as well as crown closure and size class, was obtained from the 7-channel TMS data.

  7. Selective COX-2 Inhibitors: A Review of Their Structure-Activity Relationships

    PubMed Central

    Zarghi, Afshin; Arfaei, Sara

    2011-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are the competitive inhibitors of cyclooxygenase (COX), the enzyme which mediates the bioconversion of arachidonic acid to inflammatory prostaglandins (PGs). Their use is associated with the side effects such as gastrointestinal and renal toxicity. The therapeutic anti-inflammatory action of NSAIDs is produced by the inhibition of COX-2, while the undesired side effects arise from inhibition of COX-1 activity. Thus, it was though that more selective COX-2 inhibitors would have reduced side effects. Based upon a number of selective COX-2 inhibitors (rofecoxib, celecoxib, valdecoxibetc.) were developed as safer NSAIDs with improved gastric safety profile. However, the recent market removal of some COXIBs such as rofecoxib due to its adverse cardiovascular side effects clearly encourages the researchers to explore and evaluate alternative templates with COX-2 inhibitory activity. Recognition of new avenues for selective COX-2 inhibitors in cancer chemotherapy and neurological diseases such as Parkinson and Alzheimer’s diseases still continues to attract investigations on the development of COX-2 inhibitors. This review highlights the various structural classes of selective COX-2 inhibitors with special emphasis on their structure-activity relationships. PMID:24250402

  8. Evolutionary ecology of plant-microbe interactions: soil microbial structure alters selection on plant traits.

    PubMed

    Lau, Jennifer A; Lennon, Jay T

    2011-10-01

    • Below-ground microbial communities influence plant diversity, plant productivity, and plant community composition. Given these strong ecological effects, are interactions with below-ground microbes also important for understanding natural selection on plant traits? • Here, we manipulated below-ground microbial communities and the soil moisture environment on replicated populations of Brassica rapa to examine how microbial community structure influences selection on plant traits and mediates plant responses to abiotic environmental stress. • In soils with experimentally simplified microbial communities, plants were smaller, had reduced chlorophyll content, produced fewer flowers, and were less fecund when compared with plant populations grown in association with more complex soil microbial communities. Selection on plant growth and phenological traits also was stronger when plants were grown in simplified, less diverse soil microbial communities, and these effects typically were consistent across soil moisture treatments. • Our results suggest that microbial community structure affects patterns of natural selection on plant traits. Thus, the below-ground microbial community can influence evolutionary processes, just as recent studies have demonstrated that microbial diversity can influence plant community and ecosystem processes. PMID:21658184

  9. Novel sst(4)-selective somatostatin (SRIF) agonists. 4. Three-dimensional consensus structure by NMR.

    PubMed

    Grace, Christy Rani R; Koerber, Steven C; Erchegyi, Judit; Reubi, Jean Claude; Rivier, Jean; Riek, Roland

    2003-12-18

    The three-dimensional NMR structures of eight cyclic octapeptide analogues of somatostatin (SRIF) are described. These analogues, with the basic sequence H-c[Cys(3)-Phe(6)-Xxx(7)-Yyy(8)-Lys(9)-Thr(10)-Zzz(11)-Cys(14)]-OH (the numbering refers to the position in native SRIF), with Xxx(7) being Phe/Ala/Tyr, Yyy(8) being Trp/DTrp/D-threo-beta-Me2Nal/L-threo-beta-Me2Nal, and Zzz(11) being Phe/Ala, exhibit potent and highly selective binding to human SRIF type 4 (sst(4)) receptors. The conformations reveal that the backbones of these analogues do not have the usual type-II' beta-turn reported in the literature for sst(2)-subtype-selective analogues. Instead, the structures contain a unique arrangement of side chains of Yyy(8), Lys(9), and Phe(6) or Phe(11). The conformational preferences and results from biological analyses of these analogues (parts 1-3 of this series, Rivier et al., Erchegyi et al., and Erchegyi et al., J. Med. Chem. 2003, preceding papers in this issue) allow a detailed study of the structure-activity relationship of SRIF. The proposed consensus structural motif at the binding pocket for the sst(4)-selective analogues requires a unique set of distances between an indole/2-naphthyl ring, a lysine side chain, and another aromatic ring. This motif is necessary and sufficient to explain the binding affinities of all of the analogues studied and is distinct from the existing model suggested for sst(2)/sst(5) selectivity. PMID:14667215

  10. Kinetic and structural studies of phosphodiesterase-8A and implication on the inhibitor selectivity

    PubMed Central

    Wang, Huanchen; Yan, Zier; Yang, Serena; Cai, Jiwen; Robinson, Howard; Ke, Hengming

    2009-01-01

    Cyclic nucleotide phosphodiesterase-8 (PDE8) is a family of cAMP-specific enzymes and plays important roles in many biological processes, including T-cell activation, testosterone production, adrenocortical hyperplasia, and thyroid function. However, no PDE8 selective inhibitors are available for trial treatment of human diseases. Here we report kinetic properties of the highly active PDE8A1 catalytic domain prepared from refolding and its crystal structures in the unliganded and 3-isobutyl-1-methylxanthine (IBMX) bound forms at 1.9 and 2.1 Å resolutions, respectively. The PDE8A1 catalytic domain has KM of 1.8 μM, Vmax of 6.1 μmol/min/mg, kcat of 4.0 s−1 for cAMP, and KM of 1.6 mM, Vmax of 2.5 μmol/min/mg, kcat of 1.6 s−1 for cGMP, thus indicating that the substrate specificity of PDE8 is dominated by KM. The structure of the PDE8A1 catalytic domain has similar topology as those of other PDE families, but contains two extra helices around Asn685-Thr710. Since this fragment is distant from the active site of the enzyme, its impact on the catalysis is unclear. The PDE8A1 catalytic domain is insensitive to the IBMX inhibition (IC50 = 700 μM). The unfavorable interaction of IBMX in the PDE8A1-IBMX structure suggests an important role of Tyr748 in the inhibitor binding. Indeed, the mutation of Tyr748 to phenylalanine increases the PDE8A1 sensitivity to several non-selective or family-selective PDE inhibitors. Thus, the structural and mutagenesis studies provide not only insight into the enzymatic properties, but also guidelines for design of PDE8 selective inhibitors. PMID:18983167

  11. Structural Characterization of Inhibitors with Selectivity against Members of a Homologous Enzyme Family

    SciTech Connect

    Pavlovsky, Alexander G.; Liu, Xuying; Faehnle, Christopher R.; Potente, Nina; Viola, Ronald E.

    2013-01-31

    The aspartate biosynthetic pathway provides essential metabolites for many important biological functions, including the production of four essential amino acids. As this critical pathway is only present in plants and microbes, any disruptions will be fatal to these organisms. An early pathway enzyme, L-aspartate-{beta}-semialdehyde dehydrogenase, produces a key intermediate at the first branch point of this pathway. Developing potent and selective inhibitors against several orthologs in the L-aspartate-{beta}-semialdehyde dehydrogenase family can serve as lead compounds for antibiotic development. Kinetic studies of two small molecule fragment libraries have identified inhibitors that show good selectivity against L-aspartate-{beta}-semialdehyde dehydrogenases from two different bacterial species, Streptococcus pneumoniae and Vibrio cholerae, despite the presence of an identical constellation of active site amino acids in this homologous enzyme family. Structural characterization of enzyme-inhibitor complexes have elucidated different modes of binding between these structurally related enzymes. This information provides the basis for a structure-guided approach to the development of more potent and more selective inhibitors.

  12. Structural Characterization of Inhibitors with Selectivity against Members of a Homologous Enzyme Family

    PubMed Central

    Pavlovsky, Alexander G.; Liu, Xuying; Faehnle, Christopher R.; Potente, Nina; Viola, Ronald E.

    2012-01-01

    The aspartate biosynthetic pathway provides essential metabolites for many important biological functions, including the production of four essential amino acids. Since this critical pathway is only present in plants and microbes any disruptions will be fatal to these organisms. An early pathway enzyme, L-aspartate-β-semialdehyde dehydrogenase (ASADH), produces a key intermediate at the first branch point of this pathway. Developing potent and selective inhibitors against several orthologs in the ASADH family can serve as lead compounds for antibiotic development. Kinetic studies of two small molecule fragment libraries have identified inhibitors that show good selectivity against ASADHs from two different bacterial species, Streptococcus pneumoniae and Vibrio cholerae, despite the presence of an identical constellation of active site amino acids in this homologous enzyme family. Structural characterization of enzyme-inhibitor complexes have elucidated different modes of binding between these structurally related enzymes. This information provides the basis for a structure guided approach to the development of more potent and more selective inhibitors. PMID:22039970

  13. Structural characterization of inhibitors with selectivity against members of a homologous enzyme family.

    PubMed

    Pavlovsky, Alexander G; Liu, Xuying; Faehnle, Christopher R; Potente, Nina; Viola, Ronald E

    2012-01-01

    The aspartate biosynthetic pathway provides essential metabolites for many important biological functions, including the production of four essential amino acids. As this critical pathway is only present in plants and microbes, any disruptions will be fatal to these organisms. An early pathway enzyme, l-aspartate-β-semialdehyde dehydrogenase, produces a key intermediate at the first branch point of this pathway. Developing potent and selective inhibitors against several orthologs in the l-aspartate-β-semialdehyde dehydrogenase family can serve as lead compounds for antibiotic development. Kinetic studies of two small molecule fragment libraries have identified inhibitors that show good selectivity against l-aspartate-β-semialdehyde dehydrogenases from two different bacterial species, Streptococcus pneumoniae and Vibrio cholerae, despite the presence of an identical constellation of active site amino acids in this homologous enzyme family. Structural characterization of enzyme-inhibitor complexes have elucidated different modes of binding between these structurally related enzymes. This information provides the basis for a structure-guided approach to the development of more potent and more selective inhibitors. PMID:22039970

  14. Crystal Structure of Checkpoint Kinase 2 in Complex with Nsc 109555, a Potent and Selective Inhibitor

    SciTech Connect

    Lountos, George T.; Tropea, Joseph E.; Zhang, Di; Jobson, Andrew G.; Pommier, Yves; Shoemaker, Robert H.; Waugh, David S.

    2009-03-05

    Checkpoint kinase 2 (Chk2), a ser/thr kinase involved in the ATM-Chk2 checkpoint pathway, is activated by genomic instability and DNA damage and results in either arrest of the cell cycle to allow DNA repair to occur or apoptosis if the DNA damage is severe. Drugs that specifically target Chk2 could be beneficial when administered in combination with current DNA-damaging agents used in cancer therapy. Recently, a novel inhibitor of Chk2, NSC 109555, was identified that exhibited high potency (IC{sub 50} = 240 nM) and selectivity. This compound represents a new chemotype and lead for the development of novel Chk2 inhibitors that could be used as therapeutic agents for the treatment of cancer. To facilitate the discovery of new analogs of NSC 109555 with even greater potency and selectivity, we have solved the crystal structure of this inhibitor in complex with the catalytic domain of Chk2. The structure confirms that the compound is an ATP-competitive inhibitor, as the electron density clearly reveals that it occupies the ATP-binding pocket. However, the mode of inhibition differs from that of the previously studied structure of Chk2 in complex with debromohymenialdisine, a compound that inhibits both Chk1 and Chk2. A unique hydrophobic pocket in Chk2, located very close to the bound inhibitor, presents an opportunity for the rational design of compounds with higher binding affinity and greater selectivity.

  15. Historical Topics in Algebra.

    ERIC Educational Resources Information Center

    National Council of Teachers of Mathematics, Inc., Reston, VA.

    This is a reprint of the historical capsules dealing with algebra from the 31st Yearbook of NCTM,"Historical Topics for the Mathematics Classroom." Included are such themes as the change from a geometric to an algebraic solution of problems, the development of algebraic symbolism, the algebraic contributions of different countries, the origin and…

  16. Topics for Mathematics Clubs.

    ERIC Educational Resources Information Center

    Dalton, LeRoy C., Ed.; Snyder, Henry D., Ed.

    The ten chapters in this booklet cover topics not ordinarily discussed in the classroom: Fibonacci sequences, projective geometry, groups, infinity and transfinite numbers, Pascal's Triangle, topology, experiments with natural numbers, non-Euclidean geometries, Boolean algebras, and the imaginary and the infinite in geometry. Each chapter is…

  17. Housing: Topic Paper F.

    ERIC Educational Resources Information Center

    National Council on the Handicapped, Washington, DC.

    This paper, one of a series of topic papers assessing federal laws and programs affecting persons with disabilities, addresses the issue of housing. Major federal responsibilities are to develop additional housing opportunities for persons with disabilities and to assure that currently available housing is equally open to individuals with…

  18. Topic: Mastery Learning.

    ERIC Educational Resources Information Center

    Killoran, James, Ed.

    1983-01-01

    This journal issue addresses the topic of mastery learning at both the elementary and secondary school levels. The first article, "The Theory and Practice of Mastery Learning" (Guskey), gives a definition of and information about the development, operation, and application of mastery learning, based on the theories of Benjamin Bloom. In addition,…

  19. Differential Topic Models.

    PubMed

    Chen, Changyou; Buntine, Wray; Ding, Nan; Xie, Lexing; Du, Lan

    2015-02-01

    In applications we may want to compare different document collections: they could have shared content but also different and unique aspects in particular collections. This task has been called comparative text mining or cross-collection modeling. We present a differential topic model for this application that models both topic differences and similarities. For this we use hierarchical Bayesian nonparametric models. Moreover, we found it was important to properly model power-law phenomena in topic-word distributions and thus we used the full Pitman-Yor process rather than just a Dirichlet process. Furthermore, we propose the transformed Pitman-Yor process (TPYP) to incorporate prior knowledge such as vocabulary variations in different collections into the model. To deal with the non-conjugate issue between model prior and likelihood in the TPYP, we thus propose an efficient sampling algorithm using a data augmentation technique based on the multinomial theorem. Experimental results show the model discovers interesting aspects of different collections. We also show the proposed MCMC based algorithm achieves a dramatically reduced test perplexity compared to some existing topic models. Finally, we show our model outperforms the state-of-the-art for document classification/ideology prediction on a number of text collections. PMID:26353238

  20. Structure-Based Evolution of Subtype-Selective Neurotensin Receptor Ligands

    PubMed Central

    Schaab, Carolin; Kling, Ralf Christian; Einsiedel, Jürgen; Hübner, Harald; Clark, Tim; Seebach, Dieter; Gmeiner, Peter

    2014-01-01

    Subtype-selective agonists of the neurotensin receptor NTS2 represent a promising option for the treatment of neuropathic pain, as NTS2 is involved in the mediation of μ-opioid-independent anti-nociceptive effects. Based on the crystal structure of the subtype NTS1 and previous structure–activity relationships (SARs) indicating a potential role for the sub-pocket around Tyr11 of NT(8–13) in subtype-specific ligand recognition, we have developed new NTS2-selective ligands. Starting from NT(8–13), we replaced the tyrosine unit by β2-amino acids (type 1), by heterocyclic tyrosine bioisosteres (type 2) and peptoid analogues (type 3). We were able to evolve an asymmetric synthesis of a 5-substituted azaindolylalanine and its application as a bioisostere of tyrosine capable of enhancing NTS2 selectivity. The S-configured test compound 2 a, [(S)-3-(pyrazolo[1,5-a]pyridine-5-yl)-propionyl11]NT(8–13), exhibits substantial NTS2 affinity (4.8 nm) and has a nearly 30-fold NTS2 selectivity over NTS1. The (R)-epimer 2 b showed lower NTS2 affinity but more than 600-fold selectivity over NTS1. PMID:25478316

  1. Intrinsic Selectivity and Structure Sensitivity of Rhodium Catalysts for C(2+) Oxygenate Production.

    PubMed

    Yang, Nuoya; Medford, Andrew J; Liu, Xinyan; Studt, Felix; Bligaard, Thomas; Bent, Stacey F; Nørskov, Jens K

    2016-03-23

    Synthesis gas (CO + H2) conversion is a promising route to converting coal, natural gas, or biomass into synthetic liquid fuels. Rhodium has long been studied as it is the only elemental catalyst that has demonstrated selectivity to ethanol and other C2+ oxygenates. However, the fundamentals of syngas conversion over rhodium are still debated. In this work a microkinetic model is developed for conversion of CO and H2 into methane, ethanol, and acetaldehyde on the Rh (211) and (111) surfaces, chosen to describe steps and close-packed facets on catalyst particles. The model is based on DFT calculations using the BEEF-vdW functional. The mean-field kinetic model includes lateral adsorbate-adsorbate interactions, and the BEEF-vdW error estimation ensemble is used to propagate error from the DFT calculations to the predicted rates. The model shows the Rh(211) surface to be ∼6 orders of magnitude more active than the Rh(111) surface, but highly selective toward methane, while the Rh(111) surface is intrinsically selective toward acetaldehyde. A variety of Rh/SiO2 catalysts are synthesized, tested for catalytic oxygenate production, and characterized using TEM. The experimental results indicate that the Rh(111) surface is intrinsically selective toward acetaldehyde, and a strong inverse correlation between catalytic activity and oxygenate selectivity is observed. Furthermore, iron impurities are shown to play a key role in modulating the selectivity of Rh/SiO2 catalysts toward ethanol. The experimental observations are consistent with the structure-sensitivity predicted from theory. This work provides an improved atomic-scale understanding and new insight into the mechanism, active site, and intrinsic selectivity of syngas conversion over rhodium catalysts and may also guide rational design of alloy catalysts made from more abundant elements. PMID:26958997

  2. Algorithm for selection of optimized EPR distance restraints for de novo protein structure determination

    PubMed Central

    Kazmier, Kelli; Alexander, Nathan S.; Meiler, Jens; Mchaourab, Hassane S.

    2010-01-01

    A hybrid protein structure determination approach combining sparse Electron Paramagnetic Resonance (EPR) distance restraints and Rosetta de novo protein folding has been previously demonstrated to yield high quality models (Alexander et al., 2008). However, widespread application of this methodology to proteins of unknown structures is hindered by the lack of a general strategy to place spin label pairs in the primary sequence. In this work, we report the development of an algorithm that optimally selects spin labeling positions for the purpose of distance measurements by EPR. For the α-helical subdomain of T4 lysozyme (T4L), simulated restraints that maximize sequence separation between the two spin labels while simultaneously ensuring pairwise connectivity of secondary structure elements yielded vastly improved models by Rosetta folding. 50% of all these models have the correct fold compared to only 21% and 8% correctly folded models when randomly placed restraints or no restraints are used, respectively. Moreover, the improvements in model quality require a limited number of optimized restraints, the number of which is determined by the pairwise connectivities of T4L α-helices. The predicted improvement in Rosetta model quality was verified by experimental determination of distances between spin labels pairs selected by the algorithm. Overall, our results reinforce the rationale for the combined use of sparse EPR distance restraints and de novo folding. By alleviating the experimental bottleneck associated with restraint selection, this algorithm sets the stage for extending computational structure determination to larger, traditionally elusive protein topologies of critical structural and biochemical importance. PMID:21074624

  3. Structural Basis for Selective Small Molecule Kinase Inhibition of Activated c-Met

    SciTech Connect

    Rickert, Keith W.; Patel, Sangita B.; Allison, Timothy J.; Byrne, Noel J.; Darke, Paul L.; Ford, Rachael E.; Guerin, David J.; Hall, Dawn L.; Kornienko, Maria; Lu, Jun; Munshi, Sanjeev K.; Reid, John C.; Shipman, Jennifer M.; Stanton, Elizabeth F.; Wilson, Kevin J.; Young, Jonathon R.; Soisson, Stephen M.; Lumb, Kevin J.

    2012-03-15

    The receptor tyrosine kinase c-Met is implicated in oncogenesis and is the target for several small molecule and biologic agents in clinical trials for the treatment of cancer. Binding of the hepatocyte growth factor to the cell surface receptor of c-Met induces activation via autophosphorylation of the kinase domain. Here we describe the structural basis of c-Met activation upon autophosphorylation and the selective small molecule inhibiton of autophosphorylated c-Met. MK-2461 is a potent c-Met inhibitor that is selective for the phosphorylated state of the enzyme. Compound 1 is an MK-2461 analog with a 20-fold enthalpy-driven preference for the autophosphorylated over unphosphorylated c-Met kinase domain. The crystal structure of the unbound kinase domain phosphorylated at Tyr-1234 and Tyr-1235 shows that activation loop phosphorylation leads to the ejection and disorder of the activation loop and rearrangement of helix {alpha}C and the G loop to generate a viable active site. Helix {alpha}C adopts a orientation different from that seen in activation loop mutants. The crystal structure of the complex formed by the autophosphorylated c-Met kinase domain and compound 1 reveals a significant induced fit conformational change of the G loop and ordering of the activation loop, explaining the selectivity of compound 1 for the autophosphorylated state. The results highlight the role of structural plasticity within the kinase domain in imparting the specificity of ligand binding and provide the framework for structure-guided design of activated c-Met inhibitors.

  4. Target Selection and Annotation for the Structural Genomics of the Amidohydrolase and Enolase Superfamilies

    SciTech Connect

    Pieper, U.; Chiang, R; Seffernick, J; Brown, S; Glasner, M; Kelly, L; Eswar, N; Sauder, M; Bonanno, J; et al,

    2009-01-01

    To study the substrate specificity of enzymes, we use the amidohydrolase and enolase superfamilies as model systems; members of these superfamilies share a common TIM barrel fold and catalyze a wide range of chemical reactions. Here, we describe a collaboration between the Enzyme Specificity Consortium (ENSPEC) and the New York SGX Research Center for Structural Genomics (NYSGXRC) that aims to maximize the structural coverage of the amidohydrolase and enolase superfamilies. Using sequence- and structure-based protein comparisons, we first selected 535 target proteins from a variety of genomes for high-throughput structure determination by X-ray crystallography; 63 of these targets were not previously annotated as superfamily members. To date, 20 unique amidohydrolase and 41 unique enolase structures have been determined, increasing the fraction of sequences in the two superfamilies that can be modeled based on at least 30% sequence identity from 45% to 73%. We present case studies of proteins related to uronate isomerase (an amidohydrolase superfamily member) and mandelate racemase (an enolase superfamily member), to illustrate how this structure-focused approach can be used to generate hypotheses about sequence-structure-function relationships.

  5. Selecting a Separable Parametric Spatiotemporal Covariance Structure for Longitudinal Imaging Data

    PubMed Central

    George, Brandon; Aban, Inmaculada

    2014-01-01

    Longitudinal imaging studies allow great insight into how the structure and function of a subject’s internal anatomy changes over time. Unfortunately, the analysis of longitudinal imaging data is complicated by inherent spatial and temporal correlation: the temporal from the repeated measures, and the spatial from the outcomes of interest being observed at multiple points in a patients body. We propose the use of a linear model with a separable parametric spatiotemporal error structure for the analysis of repeated imaging data. The model makes use of spatial (exponential, spherical, and Matérn) and temporal (compound symmetric, autoregressive-1, Toeplitz, and unstructured) parametric correlation functions. A simulation study, inspired by a longitudinal cardiac imaging study on mitral regurgitation patients, compared different information criteria for selecting a particular separable parametric spatiotemporal correlation structure as well as the effects on Type I and II error rates for inference on fixed effects when the specified model is incorrect. Information criteria were found to be highly accurate at choosing between separable parametric spatiotemporal correlation structures. Misspecification of the covariance structure was found to have the ability to inflate the Type I error or have an overly conservative test size, which corresponded to decreased power. An example with clinical data is given illustrating how the covariance structure procedure can be done in practice, as well as how covariance structure choice can change inferences about fixed effects. PMID:25293361

  6. CdWO{sub 4} polymorphs: Selective preparation, electronic structures, and photocatalytic activities

    SciTech Connect

    Yan, Tingjiang; Li, Liping; Tong, Wenming; Zheng, Jing; Wang, Yunjian; Li, Guangshe

    2011-02-15

    This work explored the selective synthesis of polymorphs of CdWO{sub 4} in either tetragonal or monoclinic phase by optimizing the experimental parameters. Systematic characterization indicated that both polymorphs possessed similar spherical morphologies but different structural building blocks. Electronic structures calculations for both polymorphs demonstrated the same constructions of conduction band or valence band, while the conduction band widths of both polymorphs were quite different. Both CdWO{sub 4} polymorphs exhibited good photocatalytic activity for degradation of methyl orange under UV light irradiation. When comparing to some other well-known tungstate oxide materials, the photocatalytic activity was found to follow such a consequence, monoclinic CdWO{sub 4{approx}}monoclinic ZnWO{sub 4}>tetragonal CdWO{sub 4}>tetragonal CaWO{sub 4}. The specific photocatalytic activity of monoclinic CdWO{sub 4} was even higher than that of commercial TiO{sub 2} photocatalyst (Degussa P25). The increased activity from the tetragonal CdWO{sub 4} to the monoclinic was consistent with the trend of the decreased symmetry, and this could be explained in terms of the geometric structures and electronic structures for both polymorphs. -- Graphical abstract: Monoclinic CdWO{sub 4} exhibited a much higher photocatalytic activity than the tetragonal form owing to the lower symmetry, more distorted geometric structure, and the dispersive band configuration. Display Omitted Research highlights: > Polymorphs of CdWO{sub 4} in either tetragonal or monoclinic phase were selectively synthesized. > Both polymorphs possessed similar spherical morphologies, while the relevant structural building blocks were different. > Photocatalytic activities of CdWO{sub 4} polymorphs depended strongly on the symmetry, geometric structure, as well as band configuration.

  7. Membrane proteins bind lipids selectively to modulate their structure and function

    PubMed Central

    Allison, Timothy M.; Ulmschneider, Martin B.; Degiacomi, Matteo T.; Baldwin, Andrew J.; Robinson, Carol V.

    2014-01-01

    Previous studies have established that the folding, structure and function of membrane proteins are influenced by their lipid environments1-7 and that lipids can bind to specific sites, for example in potassium channels8. Fundamental questions remain however regarding the extent of membrane protein selectivity toward lipids. Here we report a mass spectrometry (MS) approach designed to determine the selectivity of lipid binding to membrane protein complexes. We investigate the mechanosensitive channel of large conductance (MscL), aquaporin Z (AqpZ), and the ammonia channel (AmtB) using ion mobility MS (IM-MS), which reports gas-phase collision cross sections. We demonstrate that folded conformations of membrane protein complexes can exist in the gas-phase. By resolving lipid-bound states we then rank bound lipids based on their ability to resist gas phase unfolding and thereby stabilize membrane protein structure. Results show that lipids bind non-selectively and with high avidity to MscL, all imparting comparable stability, the highest-ranking lipid however is phosphatidylinositol phosphate, in line with its proposed functional role in mechanosensation9. AqpZ is also stabilized by many lipids with cardiolipin imparting the most significant resistance to unfolding. Subsequently, through functional assays, we discover that cardiolipin modulates AqpZ function. Analogous experiments identify AmtB as being highly selective for phosphatidylglycerol prompting us to obtain an X-ray structure in this lipid membrane-like environment. The 2.3Å resolution structure, when compared with others obtained without lipid bound, reveals distinct conformational changes that reposition AmtB residues to interact with the lipid bilayer. Overall our results demonstrate that resistance to unfolding correlates with specific lipid-binding events enabling distinction of lipids that merely bind from those that modulate membrane protein structure and/or function. We anticipate that these

  8. Target Selection and Deselection at the Berkeley StructuralGenomics Center

    SciTech Connect

    Chandonia, John-Marc; Kim, Sung-Hou; Brenner, Steven E.

    2005-03-22

    At the Berkeley Structural Genomics Center (BSGC), our goalis to obtain a near-complete structural complement of proteins in theminimal organisms Mycoplasma genitalium and M. pneumoniae, two closelyrelated pathogens. Current targets for structure determination have beenselected in six major stages, starting with those predicted to be mosttractable to high throughput study and likely to yield new structuralinformation. We report on the process used to select these proteins, aswell as our target deselection procedure. Target deselection reducesexperimental effort by eliminating targets similar to those recentlysolved by the structural biology community or other centers. We measurethe impact of the 69 structures solved at the BSGC as of July 2004 onstructure prediction coverage of the M. pneumoniae and M. genitaliumproteomes. The number of Mycoplasma proteins for which thefold couldfirst be reliably assigned based on structures solved at the BSGC (24 M.pneumoniae and 21 M. genitalium) is approximately 25 percent of the totalresulting from work at all structural genomics centers and the worldwidestructural biology community (94 M. pneumoniae and 86M. genitalium)during the same period. As the number of structures contributed by theBSGC during that period is less than 1 percent of the total worldwideoutput, the benefits of a focused target selection strategy are apparent.If the structures of all current targets were solved, the percentage ofM. pneumoniae proteins for which folds could be reliably assigned wouldincrease from approximately 57 percent (391 of 687) at present to around80 percent (550 of 687), and the percentage of the proteome that could beaccurately modeled would increase from around 37 percent (254 of 687) toabout 64 percent (438 of 687). In M. genitalium, the percentage of theproteome that could be structurally annotated based on structures of ourremaining targets would rise from 72 percent (348 of 486) to around 76percent (371 of 486), with the

  9. Structural and Biochemical Characterization of AidC, a Quorum-Quenching Lactonase with Atypical Selectivity.

    PubMed

    Mascarenhas, Romila; Thomas, Pei W; Wu, Chun-Xiang; Nocek, Boguslaw P; Hoang, Quyen Q; Liu, Dali; Fast, Walter

    2015-07-21

    Quorum-quenching catalysts are of interest for potential application as biochemical tools for interrogating interbacterial communication pathways, as antibiofouling agents, and as anti-infective agents in plants and animals. Herein, the structure and function of AidC, an N-acyl-l-homoserine lactone (AHL) lactonase from Chryseobacterium, is characterized. Steady-state kinetics show that zinc-supplemented AidC is the most efficient wild-type quorum-quenching enzymes characterized to date, with a kcat/KM value of approximately 2 × 10(6) M(-1) s(-1) for N-heptanoyl-l-homoserine lactone. The enzyme has stricter substrate selectivity and significantly lower KM values (ca. 50 μM for preferred substrates) compared to those of typical AHL lactonases (ca. >1 mM). X-ray crystal structures of AidC alone and with the product N-hexanoyl-l-homoserine were determined at resolutions of 1.09 and 1.67 Å, respectively. Each structure displays as a dimer, and dimeric oligiomerization was also observed in solution by size-exclusion chromatography coupled with multiangle light scattering. The structures reveal two atypical features as compared to previously characterized AHL lactonases: a "kinked" α-helix that forms part of a closed binding pocket that provides affinity and enforces selectivity for AHL substrates and an active-site His substitution that is usually found in a homologous family of phosphodiesterases. Implications for the catalytic mechanism of AHL lactonases are discussed. PMID:26115006

  10. Selection of optimal threshold to construct recurrence plot for structural operational vibration measurements

    NASA Astrophysics Data System (ADS)

    Yang, Dong; Ren, Wei-Xin; Hu, Yi-Ding; Li, Dan

    2015-08-01

    The structural health monitoring (SHM) involves the sampled operational vibration measurements over time so that the structural features can be extracted accordingly. The recurrence plot (RP) and corresponding recurrence quantification analysis (RQA) have become a useful tool in various fields due to its efficiency. The threshold selection is one of key issues to make sure that the constructed recurrence plot contains enough recurrence points. Different signals have in nature different threshold values. This paper is aiming at presenting an approach to determine the optimal threshold for the operational vibration measurements of civil engineering structures. The surrogate technique and Taguchi loss function are proposed to generate reliable data and to achieve the optimal discrimination power point where the threshold is optimum. The impact of selecting recurrence thresholds on different signals is discussed. It is demonstrated that the proposed method to identify the optimal threshold is applicable to the operational vibration measurements. The proposed method provides a way to find the optimal threshold for the best RP construction of structural vibration measurements under operational conditions.

  11. Voltage-Gated Potassium Channels: A Structural Examination of Selectivity and Gating.

    PubMed

    Kim, Dorothy M; Nimigean, Crina M

    2016-01-01

    Voltage-gated potassium channels play a fundamental role in the generation and propagation of the action potential. The discovery of these channels began with predictions made by early pioneers, and has culminated in their extensive functional and structural characterization by electrophysiological, spectroscopic, and crystallographic studies. With the aid of a variety of crystal structures of these channels, a highly detailed picture emerges of how the voltage-sensing domain reports changes in the membrane electric field and couples this to conformational changes in the activation gate. In addition, high-resolution structural and functional studies of K(+) channel pores, such as KcsA and MthK, offer a comprehensive picture on how selectivity is achieved in K(+) channels. Here, we illustrate the remarkable features of voltage-gated potassium channels and explain the mechanisms used by these machines with experimental data. PMID:27141052

  12. Surface-promoted aggregation of amphiphilic quadruplex ligands drives their selectivity for alternative DNA structures.

    PubMed

    Laguerre, Aurélien; Chang, Yi; Pirrotta, Marc; Desbois, Nicolas; Gros, Claude P; Lesniewska, Eric; Monchaud, David

    2015-07-01

    Scientists are currently truly committed to enhance the specificity of chemotherapeutics that target DNA. To this end, sequence-specific drugs have progressively given way to structure-specific therapeutics. However, while numerous strategies have been implemented to design high-affinity candidates, strategies devoted to the design of high-selectivity ligands are still rare. Here we report on such an approach via the study of an amphiphilic compound, TEGPy, that self-assembles at a liquid/solid interface to provide nanosized objects that are stable in water. The resulting aggregates, identified through atomic force microscopy measurements, were found to disassemble upon interaction with DNA in a structure-specific manner (quadruplex- versus duplex-DNA). Our results provide a fertile ground for devising new strategies aiming at concomitantly enhancing DNA structural specificity and the water-solubility of aggregation-prone ligands. PMID:26040925

  13. Evaluating supervised topic models in the presence of OCR errors

    NASA Astrophysics Data System (ADS)

    Walker, Daniel; Ringger, Eric; Seppi, Kevin

    2013-01-01

    Supervised topic models are promising tools for text analytics that simultaneously model topical patterns in document collections and relationships between those topics and document metadata, such as timestamps. We examine empirically the effect of OCR noise on the ability of supervised topic models to produce high quality output through a series of experiments in which we evaluate three supervised topic models and a naive baseline on synthetic OCR data having various levels of degradation and on real OCR data from two different decades. The evaluation includes experiments with and without feature selection. Our results suggest that supervised topic models are no better, or at least not much better in terms of their robustness to OCR errors, than unsupervised topic models and that feature selection has the mixed result of improving topic quality while harming metadata prediction quality. For users of topic modeling methods on OCR data, supervised topic models do not yet solve the problem of finding better topics than the original unsupervised topic models.

  14. Kinetic and Structural Studies of Phosphodiesterase-8A and Implication on the Inhibitor Selectivity

    SciTech Connect

    Wang, H.; Yan, Z; Yang, S; Cai, J; Robinson, H; Ke, H

    2008-01-01

    Cyclic nucleotide phosphodiesterase-8 (PDE8) is a family of cAMP-specific enzymes and plays important roles in many biological processes, including T-cell activation, testosterone production, adrenocortical hyperplasia, and thyroid function. However, no PDE8 selective inhibitors are available for trial treatment of human diseases. Here we report kinetic properties of the highly active PDE8A1 catalytic domain prepared from refolding and its crystal structures in the unliganded and 3-isobutyl-1-methylxanthine (IBMX) bound forms at 1.9 and 2.1 Angstroms resolutions, respectively. The PDE8A1 catalytic domain has a KM of 1.8 eM, Vmax of 6.1 emol/min/mg, a kcat of 4.0 s-1 for cAMP, and a KM of 1.6 mM, Vmax of 2.5 emol/min/mg, a kcat of 1.6 s-1 for cGMP, thus indicating that the substrate specificity of PDE8 is dominated by KM. The structure of the PDE8A1 catalytic domain has similar topology as those of other PDE families but contains two extra helices around Asn685-Thr710. Since this fragment is distant from the active site of the enzyme, its impact on the catalysis is unclear. The PDE8A1 catalytic domain is insensitive to the IBMX inhibition (IC50 = 700 eM). The unfavorable interaction of IBMX in the PDE8A1-IBMX structure suggests an important role of Tyr748 in the inhibitor binding. Indeed, the mutation of Tyr748 to phenylalanine increases the PDE8A1 sensitivity to several nonselective or family selective PDE inhibitors. Thus, the structural and mutagenesis studies provide not only insight into the enzymatic properties but also guidelines for design of PDE8 selective inhibitors.

  15. Structural requirements to obtain highly potent and selective 18 kDa Translocator Protein (TSPO) Ligands.

    PubMed

    Taliani, Sabrina; Pugliesi, Isabella; Da Settimo, Federico

    2011-01-01

    The (18 kDa) Translocator Protein (TSPO), was initially identified in 1977 as peripheral binding site for the benzodiazepine diazepam and named "Peripheral-type benzodiazepine receptor (PBR)". It is an evolutionarily well-conserved protein particularly located at the outer/inner mitochondrial membrane contact sites, in closely association with the 32 kDa voltage-dependent anion channel (VDAC) and the 30 kDa adenine nucleotide translocase (ANT), thus forming the mitochondrial permeability transition pore (MPTP). TSPO is ubiquitary expressed in peripheral tissues (steroid producing tissues, liver, heart, kidney, lung, immune system) and in lower levels in the central nervous system, where it is mainly located in glial cells, and in neurons. TSPO is involved in a variety of biological processes such as cholesterol transport, steroidogenesis, calcium homeostasis, lipid metabolism, mitochondrial oxidation, cell growth and differentiation, apoptosis induction, and regulation of immune functions. In the last decade, many studies have reported that TSPO basal expression is altered in a number of human pathologies, such as cancer and neurodegenerative disorders (Huntington's and Alzheimer's diseases), as well as in various forms of brain injury and inflammation and anxiety. Consequently, TSPO has not only been suggested as a promising drug target for a number of therapeutic applications (anticonvulsant, anxiolytic, immunomodulating, etc.), but also as valid diagnostic marker for related-disease state and progression, prompting the development of specific labelled ligands as powerful tools for imaging techniques. A number of structurally different classes of ligands have been reported, showing high affinity and selectivity towards TSPO. Indeed, most of these ligands have been designed starting from selective CBR ligands which were structurally modified in order to shift their affinity towards TSPO. Extensive structure-activity relationship studies were performed allowing to

  16. Structure and selectivity trends in crystalline urea-functionalized anion-binding capsules

    SciTech Connect

    Rajbanshi, Arbin; Custelcean, Radu

    2012-01-01

    A tripodal trisurea receptor (L1) persistently self-assembles with various divalent oxoanion salts M{sub n}X (M = Na, K, Mg, Ca, Cd; X = SO{sub 4}{sup 2-}, SO{sub 3}{sup 2-}, SeO{sub 4}{sup 2-}, CrO{sub 4}{sup 2-}) into isomorphous series of crystalline frameworks in three different compositions: MX(L1){sub 2}(H{sub 2}O){sub 6} (M = Mg, Ca, Cd) (1), Na{sub 2}X(L1){sub 2}(H{sub 2}O){sub 4} (2) and K{sub 2}X(L1){sub 2}(H{sub 2}O){sub 2} (3). Single-crystal X-ray structural analysis revealed that all three series of structures adopt a NaCl-type topology, consisting of alternating anionic X(L1){sub 2}{sup 2-} capsules and M(H{sub 2}O){sub 6}{sup 2+}, Na{sub 2}(H{sub 2}O){sub 4}{sup 2+} or K{sub 2}(H{sub 2}O){sub 2}{sup 2+} hydrated cations. The capsules provide a complementary environment to tetrahedral oxoanions via 12 hydrogen bonds from six urea groups lining the cavities of the capsules. The persistent formation of the capsules facilitated the investigation of structural trends and structure-selectivity relationships across series 1-3. First, it was found that the size of the capsules is relatively unresponsive to the change in the encapsulated anion, resulting in good shape and size recognition in the separation of anions by competitive crystallizations. Second, it was found that the size of the capsules varies linearly with the size of the external cation, which provides a way for tuning the anion encapsulation selectivity. However, no straightforward dependence was found between the size of the capsules and the relative selectivity for different-sized tetrahedral oxoanions in competitive crystallizations.

  17. Structural Heterogeneity in Transmembrane Amyloid Precursor Protein Homodimer Is a Consequence of Environmental Selection

    PubMed Central

    2015-01-01

    The 99 amino acid C-terminal fragment of amyloid precursor protein (C99), consisting of a single transmembrane (TM) helix, is known to form homodimers. Homodimers can be processed by γ-secretase to produce amyloid-β (Aβ) protein, which is implicated in Alzheimer’s disease (AD). While knowledge of the structure of C99 homodimers is of great importance, experimental NMR studies and simulations have produced varying structural models, including right-handed and left-handed coiled-coils. In order to investigate the structure of this critical protein complex, simulations of the C9915–55 homodimer in POPC membrane bilayer and DPC surfactant micelle environments were performed using a multiscale approach that blends atomistic and coarse-grained models. The C9915–55 homodimer adopts a dominant right-handed coiled-coil topology consisting of three characteristic structural states in a bilayer, only one of which is dominant in the micelle. Our structural study, which provides a self-consistent framework for understanding a number of experiments, shows that the energy landscape of the C99 homodimer supports a variety of slowly interconverting structural states. The relative importance of any given state can be modulated through environmental selection realized by altering the membrane or micelle characteristics. PMID:24926593

  18. Femtosecond laser structuring of silver-containing glass: Silver redistribution, selective etching, and surface topology engineering

    SciTech Connect

    Desmoulin, Jean-Charles; Petit, Yannick; Cardinal, Thierry; Canioni, Lionel; Dussauze, Marc; Lahaye, Michel; Gonzalez, Hernando Magallanes; Brasselet, Etienne

    2015-12-07

    Femtosecond direct laser writing in silver-containing phosphate glasses allows for the three-dimensional (3D) implementation of complex photonic structures. Sample translation along or perpendicular to the direction of the beam propagation has been performed, which led to the permanent formation of fluorescent structures, either corresponding to a tubular shape or to two parallel planes at the vicinity of the interaction voxel, respectively. These optical features are related to significant modifications of the local material chemistry. Indeed, silver depletion areas with a diameter below 200 nm were evidenced at the center of the photo-produced structures while photo-produced luminescence properties are attributed to the formation of silver clusters around the multiphoton interaction voxel. The laser-triggered oxidation-reduction processes and the associated photo-induced silver redistribution are proposed to be at the origin of the observed original 3D luminescent structures. Thanks to such material structuring, surface engineering has been also demonstrated. Selective surface chemical etching of the glass has been obtained subsequently to laser writing at the location of the photo-produced structures, revealing features with nanometric depth profiles and radial dimensions strongly related to the spatial distributions of the silver clusters.

  19. Femtosecond laser structuring of silver-containing glass: Silver redistribution, selective etching, and surface topology engineering

    NASA Astrophysics Data System (ADS)

    Desmoulin, Jean-Charles; Petit, Yannick; Canioni, Lionel; Dussauze, Marc; Lahaye, Michel; Gonzalez, Hernando Magallanes; Brasselet, Etienne; Cardinal, Thierry

    2015-12-01

    Femtosecond direct laser writing in silver-containing phosphate glasses allows for the three-dimensional (3D) implementation of complex photonic structures. Sample translation along or perpendicular to the direction of the beam propagation has been performed, which led to the permanent formation of fluorescent structures, either corresponding to a tubular shape or to two parallel planes at the vicinity of the interaction voxel, respectively. These optical features are related to significant modifications of the local material chemistry. Indeed, silver depletion areas with a diameter below 200 nm were evidenced at the center of the photo-produced structures while photo-produced luminescence properties are attributed to the formation of silver clusters around the multiphoton interaction voxel. The laser-triggered oxidation-reduction processes and the associated photo-induced silver redistribution are proposed to be at the origin of the observed original 3D luminescent structures. Thanks to such material structuring, surface engineering has been also demonstrated. Selective surface chemical etching of the glass has been obtained subsequently to laser writing at the location of the photo-produced structures, revealing features with nanometric depth profiles and radial dimensions strongly related to the spatial distributions of the silver clusters.

  20. The Structural Diversity of Carbohydrate Antigens of Selected Gram-Negative Marine Bacteria

    PubMed Central

    Nazarenko, Evgeny L.; Crawford, Russell J.; Ivanova, Elena P.

    2011-01-01

    Marine microorganisms have evolved for millions of years to survive in the environments characterized by one or more extreme physical or chemical parameters, e.g., high pressure, low temperature or high salinity. Marine bacteria have the ability to produce a range of biologically active molecules, such as antibiotics, toxins and antitoxins, antitumor and antimicrobial agents, and as a result, they have been a topic of research interest for many years. Among these biologically active molecules, the carbohydrate antigens, lipopolysaccharides (LPSs, O-antigens) found in cell walls of Gram-negative marine bacteria, show great potential as candidates in the development of drugs to prevent septic shock due to their low virulence. The structural diversity of LPSs is thought to be a reflection of the ability for these bacteria to adapt to an array of habitats, protecting the cell from being compromised by exposure to harsh environmental stress factors. Over the last few years, the variety of structures of core oligosaccharides and O-specific polysaccharides from LPSs of marine microrganisms has been discovered. In this review, we discuss the most recently encountered structures that have been identified from bacteria belonging to the genera Aeromonas, Alteromonas, Idiomarina, Microbulbifer, Pseudoalteromonas, Plesiomonas and Shewanella of the Gammaproteobacteria phylum; Sulfitobacter and Loktanella of the Alphaproteobactera phylum and to the genera Arenibacter, Cellulophaga, Chryseobacterium, Flavobacterium, Flexibacter of the Cytophaga-Flavobacterium-Bacteroides phylum. Particular attention is paid to the particular chemical features of the LPSs, such as the monosaccharide type, non-sugar substituents and phosphate groups, together with some of the typifying traits of LPSs obtained from marine bacteria. A possible correlation is then made between such features and the environmental adaptations undertaken by marine bacteria. PMID:22073003

  1. The structural diversity of carbohydrate antigens of selected gram-negative marine bacteria.

    PubMed

    Nazarenko, Evgeny L; Crawford, Russell J; Ivanova, Elena P

    2011-01-01

    Marine microorganisms have evolved for millions of years to survive in the environments characterized by one or more extreme physical or chemical parameters, e.g., high pressure, low temperature or high salinity. Marine bacteria have the ability to produce a range of biologically active molecules, such as antibiotics, toxins and antitoxins, antitumor and antimicrobial agents, and as a result, they have been a topic of research interest for many years. Among these biologically active molecules, the carbohydrate antigens, lipopolysaccharides (LPSs, O-antigens) found in cell walls of gram-negative marine bacteria, show great potential as candidates in the development of drugs to prevent septic shock due to their low virulence. The structural diversity of LPSs is thought to be a reflection of the ability for these bacteria to adapt to an array of habitats, protecting the cell from being compromised by exposure to harsh environmental stress factors. Over the last few years, the variety of structures of core oligosaccharides and O-specific polysaccharides from LPSs of marine microrganisms has been discovered. In this review, we discuss the most recently encountered structures that have been identified from bacteria belonging to the genera Aeromonas, Alteromonas, Idiomarina, Microbulbifer, Pseudoalteromonas, Plesiomonas and Shewanella of the Gammaproteobacteria phylum; Sulfitobacter and Loktanella of the Alphaproteobactera phylum and to the genera Arenibacter, Cellulophaga, Chryseobacterium, Flavobacterium, Flexibacter of the Cytophaga-Flavobacterium-Bacteroides phylum. Particular attention is paid to the particular chemical features of the LPSs, such as the monosaccharide type, non-sugar substituents and phosphate groups, together with some of the typifying traits of LPSs obtained from marine bacteria. A possible correlation is then made between such features and the environmental adaptations undertaken by marine bacteria. PMID:22073003

  2. Identification and Structure-Function Analysis of Subfamily Selective G Protein-Coupled Receptor Kinase Inhibitors

    SciTech Connect

    Homan, Kristoff T.; Larimore, Kelly M.; Elkins, Jonathan M.; Szklarz, Marta; Knapp, Stefan; Tesmer, John J.G.

    2015-02-13

    Selective inhibitors of individual subfamilies of G protein-coupled receptor kinases (GRKs) would serve as useful chemical probes as well as leads for therapeutic applications ranging from heart failure to Parkinson’s disease. To identify such inhibitors, differential scanning fluorimetry was used to screen a collection of known protein kinase inhibitors that could increase the melting points of the two most ubiquitously expressed GRKs: GRK2 and GRK5. Enzymatic assays on 14 of the most stabilizing hits revealed that three exhibit nanomolar potency of inhibition for individual GRKs, some of which exhibiting orders of magnitude selectivity. Most of the identified compounds can be clustered into two chemical classes: indazole/dihydropyrimidine-containing compounds that are selective for GRK2 and pyrrolopyrimidine-containing compounds that potently inhibit GRK1 and GRK5 but with more modest selectivity. The two most potent inhibitors representing each class, GSK180736A and GSK2163632A, were cocrystallized with GRK2 and GRK1, and their atomic structures were determined to 2.6 and 1.85 Å spacings, respectively. GSK180736A, developed as a Rho-associated, coiled-coil-containing protein kinase inhibitor, binds to GRK2 in a manner analogous to that of paroxetine, whereas GSK2163632A, developed as an insulin-like growth factor 1 receptor inhibitor, occupies a novel region of the GRK active site cleft that could likely be exploited to achieve more selectivity. However, neither compound inhibits GRKs more potently than their initial targets. This data provides the foundation for future efforts to rationally design even more potent and selective GRK inhibitors.

  3. Identification and structure-function analysis of subfamily selective G protein-coupled receptor kinase inhibitors.

    PubMed

    Homan, Kristoff T; Larimore, Kelly M; Elkins, Jonathan M; Szklarz, Marta; Knapp, Stefan; Tesmer, John J G

    2015-01-16

    Selective inhibitors of individual subfamilies of G protein-coupled receptor kinases (GRKs) would serve as useful chemical probes as well as leads for therapeutic applications ranging from heart failure to Parkinson's disease. To identify such inhibitors, differential scanning fluorimetry was used to screen a collection of known protein kinase inhibitors that could increase the melting points of the two most ubiquitously expressed GRKs: GRK2 and GRK5. Enzymatic assays on 14 of the most stabilizing hits revealed that three exhibit nanomolar potency of inhibition for individual GRKs, some of which exhibiting orders of magnitude selectivity. Most of the identified compounds can be clustered into two chemical classes: indazole/dihydropyrimidine-containing compounds that are selective for GRK2 and pyrrolopyrimidine-containing compounds that potently inhibit GRK1 and GRK5 but with more modest selectivity. The two most potent inhibitors representing each class, GSK180736A and GSK2163632A, were cocrystallized with GRK2 and GRK1, and their atomic structures were determined to 2.6 and 1.85 Å spacings, respectively. GSK180736A, developed as a Rho-associated, coiled-coil-containing protein kinase inhibitor, binds to GRK2 in a manner analogous to that of paroxetine, whereas GSK2163632A, developed as an insulin-like growth factor 1 receptor inhibitor, occupies a novel region of the GRK active site cleft that could likely be exploited to achieve more selectivity. However, neither compound inhibits GRKs more potently than their initial targets. This data provides the foundation for future efforts to rationally design even more potent and selective GRK inhibitors. PMID:25238254

  4. Topical retinoids for acne.

    PubMed

    Yeh, Lindsey; Bonati, Lauren Meshkov; Silverberg, Nanette B

    2016-06-01

    Topical retinoids are currently approved by the US Food and Drug Administration for the treatment of acne vulgaris in nonpregnant, nonlactating patients 12 years of age and older. Their efficacy, safety, and tolerability are well documented for inflammatory and noninflammatory acne with studies repeatedly demonstrating a decrease in the number of lesions, significant improvement in acne severity, improvement in the cosmetic appearance of acne, and the prevention of acne lesions through microcomedone formation. There is some variability between prescription retinoid products regarding efficacy, safety, and tolerability; with erythema, peeling, and dryness being common, potential side effects. Due to their efficacious and safe profile, topical retinoids remain the first-line treatment for acne vulgaris. PMID:27416308

  5. Highly selective nanocomposite sorbents for the specific recognition of S-ibuprofen from structurally related compounds

    NASA Astrophysics Data System (ADS)

    Sooraj, M. P.; Mathew, Beena

    2016-06-01

    The aim of the present work was to synthesize highly homogeneous synthetic recognition units for the selective and specific separation of S-ibuprofen from its closely related structural analogues using molecular imprinting technology. The molecular imprinted polymer wrapped on functionalized multiwalled carbon nanotubes (MWCNT-MIP) was synthesized using S-ibuprofen as the template in the imprinting process. The characterization of the products and intermediates were done by FT-IR spectroscopy, PXRD, TGA, SEM and TEM techniques. The high regression coefficient value for Langmuir adsorption isotherm ( R 2 = 0.999) showed the homogeneous imprint sites and surface adsorption nature of the prepared polymer sorbent. The nano-MIP followed a second-order kinetics ( R 2 = 0.999) with a rapid adsorption rate which also suggested the formation of recognition sites on the surface of MWCNT-MIP. MWCNT-MIP showed 83.6 % higher rebinding capacity than its non-imprinted counterpart. The higher relative selectivity coefficient ( k') of the imprinted sorbent towards S-ibuprofen than that for its structural analogues evidenced the capability of the nano-MIP to selectively and specifically rebind the template rather than its analogues.

  6. Structure-Based Design of β5c Selective Inhibitors of Human Constitutive Proteasomes.

    PubMed

    Xin, Bo-Tao; de Bruin, Gerjan; Huber, Eva M; Besse, Andrej; Florea, Bogdan I; Filippov, Dmitri V; van der Marel, Gijsbert A; Kisselev, Alexei F; van der Stelt, Mario; Driessen, Christoph; Groll, Michael; Overkleeft, Herman S

    2016-08-11

    This work reports the development of highly potent and selective inhibitors of the β5c catalytic activity of human constitutive proteasomes. The work describes the design principles, large hydrophobic P3 residue and small hydrophobic P1 residue, that led to the synthesis of a panel of peptide epoxyketones; their evaluation and the selection of the most promising compounds for further analyses. Structure-activity relationships detail how in a logical order the β1c/i, β2c/i, and β5i activities became resistant to inhibition as compounds were diversified stepwise. The most effective compounds were obtained as a mixture of cis- and trans-biscyclohexyl isomers, and enantioselective synthesis resolved this issue. Studies on yeast proteasome structures complexed with some of the compounds provide a rationale for the potency and specificity. Substitution of the N-terminus in the most potent compound for a more soluble equivalent led to a cell-permeable molecule that selectively and efficiently blocks β5c in cells expressing both constitutive proteasomes and immunoproteasomes. PMID:27438186

  7. Evolution of Protein Quaternary Structure in Response to Selective Pressure for Increased Thermostability.

    PubMed

    Fraser, Nicholas J; Liu, Jian-Wei; Mabbitt, Peter D; Correy, Galen J; Coppin, Chris W; Lethier, Mathilde; Perugini, Matthew A; Murphy, James M; Oakeshott, John G; Weik, Martin; Jackson, Colin J

    2016-06-01

    Oligomerization has been suggested to be an important mechanism for increasing or maintaining the thermostability of proteins. Although it is evident that protein-protein contacts can result in substantial stabilization in many extant proteins, evidence for evolutionary selection for oligomerization is largely indirect and little is understood of the early steps in the evolution of oligomers. A laboratory-directed evolution experiment that selected for increased thermostability in the αE7 carboxylesterase from the Australian sheep blowfly, Lucilia cuprina, resulted in a thermostable variant, LcαE7-4a, that displayed increased levels of dimeric and tetrameric quaternary structure. A trade-off between activity and thermostability was made during the evolution of thermostability, with the higher-order oligomeric species displaying the greatest thermostability and lowest catalytic activity. Analysis of monomeric and dimeric LcαE7-4a crystal structures revealed that only one of the oligomerization-inducing mutations was located at a potential protein-protein interface. This work demonstrates that by imposing a selective pressure demanding greater thermostability, mutations can lead to increased oligomerization and stabilization, providing support for the hypothesis that oligomerization is a viable evolutionary strategy for protein stabilization. PMID:27016206

  8. Highly selective nanocomposite sorbents for the specific recognition of S-ibuprofen from structurally related compounds

    NASA Astrophysics Data System (ADS)

    Sooraj, M. P.; Mathew, Beena

    2015-07-01

    The aim of the present work was to synthesize highly homogeneous synthetic recognition units for the selective and specific separation of S-ibuprofen from its closely related structural analogues using molecular imprinting technology. The molecular imprinted polymer wrapped on functionalized multiwalled carbon nanotubes (MWCNT-MIP) was synthesized using S-ibuprofen as the template in the imprinting process. The characterization of the products and intermediates were done by FT-IR spectroscopy, PXRD, TGA, SEM and TEM techniques. The high regression coefficient value for Langmuir adsorption isotherm (R 2 = 0.999) showed the homogeneous imprint sites and surface adsorption nature of the prepared polymer sorbent. The nano-MIP followed a second-order kinetics (R 2 = 0.999) with a rapid adsorption rate which also suggested the formation of recognition sites on the surface of MWCNT-MIP. MWCNT-MIP showed 83.6 % higher rebinding capacity than its non-imprinted counterpart. The higher relative selectivity coefficient (k') of the imprinted sorbent towards S-ibuprofen than that for its structural analogues evidenced the capability of the nano-MIP to selectively and specifically rebind the template rather than its analogues.

  9. Structure-based approach for the study of thyroid hormone receptor binding affinity and subtype selectivity.

    PubMed

    Wang, Fang-Fang; Yang, Wei; Shi, Yong-Hui; Cheng, Xiang-Rong; Le, Guo-Wei

    2016-10-01

    Thyroid hormone (TH) possesses the ability to lower cholesterol and improve cardiac performance, which have prompted the efforts to design analogs that can utilize the cholesterol-lowering property without adversely affecting heart function. In order to gain insights into the interaction mechanism for agonists at the active site of thyroid hormone receptor β (TRβ), quantitative structure-activity relationship (QSAR) models have been developed on TRβ agonists, significant statistical coefficients were obtained (CoMFA, R(2)cv, .732), (CoMSIA, R(2)cv, .853), indicating the internal consistency of the models, the obtained models were further validated using the test set, the acquired R(2)pred values .7054 and .7129 were in good agreement with the experimental results. The key amino acids affecting ligand binding were identified by molecular docking, and the detailed binding modes of the compounds with different activities were also determined. Furthermore, molecular dynamics (MD) simulations were conducted to assess the reliability of the derived models and the docking results. Moreover, TH exerts significant physiological effects through modulation of the two human thyroid hormone receptor subtypes. Because TRβ and TRα locate in different target cells, selective TR ligands would target specific tissues regulated by one receptor without affecting the other. Thus, the 3D information was analyzed to reveal the most relevant structural features involved in selectivity. The findings serve as the basis for further investigation into selective TRβ/TRα agonists. PMID:26510472

  10. Structural plasticity and dynamic selectivity of acid-sensing ion channel-spider toxin complexes

    SciTech Connect

    Baconguis, Isabelle; Gouaux, Eric

    2012-07-29

    Acid-sensing ion channels (ASICs) are voltage-independent, amiloride-sensitive channels involved in diverse physiological processes ranging from nociception to taste. Despite the importance of ASICs in physiology, we know little about the mechanism of channel activation. Here we show that psalmotoxin activates non-selective and Na+-selective currents in chicken ASIC1a at pH7.25 and 5.5, respectively. Crystal structures of ASIC1a–psalmotoxin complexes map the toxin binding site to the extracellular domain and show how toxin binding triggers an expansion of the extracellular vestibule and stabilization of the open channel pore. At pH7.25 the pore is approximately 10Å in diameter, whereas at pH5.5 the pore is largely hydrophobic and elliptical in cross-section with dimensions of approximately 5 by 7Å, consistent with a barrier mechanism for ion selectivity. These studies define mechanisms for activation of ASICs, illuminate the basis for dynamic ion selectivity and provide the blueprints for new therapeutic agents.

  11. Structure-Guided Evolution of Potent and Selective CHK1 Inhibitors through Scaffold Morphing

    PubMed Central

    2011-01-01

    Pyrazolopyridine inhibitors with low micromolar potency for CHK1 and good selectivity against CHK2 were previously identified by fragment-based screening. The optimization of the pyrazolopyridines to a series of potent and CHK1-selective isoquinolines demonstrates how fragment-growing and scaffold morphing strategies arising from a structure-based understanding of CHK1 inhibitor binding can be combined to successfully progress fragment-derived hit matter to compounds with activity in vivo. The challenges of improving CHK1 potency and selectivity, addressing synthetic tractability, and achieving novelty in the crowded kinase inhibitor chemical space were tackled by multiple scaffold morphing steps, which progressed through tricyclic pyrimido[2,3-b]azaindoles to N-(pyrazin-2-yl)pyrimidin-4-amines and ultimately to imidazo[4,5-c]pyridines and isoquinolines. A potent and highly selective isoquinoline CHK1 inhibitor (SAR-020106) was identified, which potentiated the efficacies of irinotecan and gemcitabine in SW620 human colon carcinoma xenografts in nude mice. PMID:22111927

  12. Implications of structural genomics target selection strategies: Pfam5000, whole genome, and random approaches

    SciTech Connect

    Chandonia, John-Marc; Brenner, Steven E.

    2004-07-14

    The structural genomics project is an international effort to determine the three-dimensional shapes of all important biological macromolecules, with a primary focus on proteins. Target proteins should be selected according to a strategy which is medically and biologically relevant, of good value, and tractable. As an option to consider, we present the Pfam5000 strategy, which involves selecting the 5000 most important families from the Pfam database as sources for targets. We compare the Pfam5000 strategy to several other proposed strategies that would require similar numbers of targets. These include including complete solution of several small to moderately sized bacterial proteomes, partial coverage of the human proteome, and random selection of approximately 5000 targets from sequenced genomes. We measure the impact that successful implementation of these strategies would have upon structural interpretation of the proteins in Swiss-Prot, TrEMBL, and 131 complete proteomes (including 10 of eukaryotes) from the Proteome Analysis database at EBI. Solving the structures of proteins from the 5000 largest Pfam families would allow accurate fold assignment for approximately 68 percent of all prokaryotic proteins (covering 59 percent of residues) and 61 percent of eukaryotic proteins (40 percent of residues). More fine-grained coverage which would allow accurate modeling of these proteins would require an order of magnitude more targets. The Pfam5000 strategy may be modified in several ways, for example to focus on larger families, bacterial sequences, or eukaryotic sequences; as long as secondary consideration is given to large families within Pfam, coverage results vary only slightly. In contrast, focusing structural genomics on a single tractable genome would have only a limited impact in structural knowledge of other proteomes: a significant fraction (about 30-40 percent of the proteins, and 40-60 percent of the residues) of each proteome is classified in small

  13. Hot topics in flavor physics at CDF

    SciTech Connect

    Jun, Soon Yung; /Carnegie Mellon U.

    2005-01-01

    Hot topics in flavor physics at CDF are reviewed. Selected results of top, beauty, charm physics and exotic states in about 200 pb{sup -1} data collected by the CDF II detector in p{bar p} collisions at {radical}s = 1.96 TeV at the Fermilab Tevatron are presented.

  14. Structure-Guided Design of Selective Epac1 and Epac2 Agonists

    PubMed Central

    Schwede, Frank; Bertinetti, Daniela; Langerijs, Carianne N.; Hadders, Michael A.; Wienk, Hans; Ellenbroek, Johanne H.; de Koning, Eelco J. P.; Bos, Johannes L.; Herberg, Friedrich W.; Genieser, Hans-Gottfried; Janssen, Richard A. J.; Rehmann, Holger

    2015-01-01

    The second messenger cAMP is known to augment glucose-induced insulin secretion. However, its downstream targets in pancreatic β-cells have not been unequivocally determined. Therefore, we designed cAMP analogues by a structure-guided approach that act as Epac2-selective agonists both in vitro and in vivo. These analogues activate Epac2 about two orders of magnitude more potently than cAMP. The high potency arises from increased affinity as well as increased maximal activation. Crystallographic studies demonstrate that this is due to unique interactions. At least one of the Epac2-specific agonists, Sp-8-BnT-cAMPS (S-220), enhances glucose-induced insulin secretion in human pancreatic cells. Selective targeting of Epac2 is thus proven possible and may be an option in diabetes treatment. PMID:25603503

  15. Rational selection of structurally diverse natural product scaffolds with favorable ADME properties for drug discovery.

    PubMed

    Samiulla, D S; Vaidyanathan, V V; Arun, P C; Balan, G; Blaze, M; Bondre, S; Chandrasekhar, G; Gadakh, A; Kumar, R; Kharvi, G; Kim, H O; Kumar, S; Malikayil, J A; Moger, M; Mone, M K; Nagarjuna, P; Ogbu, C; Pendhalkar, D; Rao, A V S Raja; Rao, G Venkateshwar; Sarma, V K; Shaik, S; Sharma, G V R; Singh, S; Sreedhar, C; Sonawane, R; Timmanna, U; Hardy, L W

    2005-01-01

    Natural product analogs are significant sources for therapeutic agents. To capitalize efficiently on the effective features of naturally occurring substances, a natural product-based library production platform has been devised at Aurigene for drug lead discovery. This approach combines the attractive biological and physicochemical properties of natural product scaffolds, provided by eons of natural selection, with the chemical diversity available from parallel synthetic methods. Virtual property analysis, using computational methods described here, guides the selection of a set of natural product scaffolds that are both structurally diverse and likely to have favorable pharmacokinetic properties. The experimental characterization of several in vitro ADME properties of twenty of these scaffolds, and of a small set of designed congeners based upon one scaffold, is also described. These data confirm that most of the scaffolds and the designed library members have properties favorable to their utilization for creating libraries of lead-like molecules. PMID:15789560

  16. A hybrid algorithm for selecting head-related transfer function based on similarity of anthropometric structures

    NASA Astrophysics Data System (ADS)

    Zeng, Xiang-Yang; Wang, Shu-Guang; Gao, Li-Ping

    2010-09-01

    As the basic data for virtual auditory technology, head-related transfer function (HRTF) has many applications in the areas of room acoustic modeling, spatial hearing and multimedia. How to individualize HRTF fast and effectively has become an opening problem at present. Based on the similarity and relativity of anthropometric structures, a hybrid HRTF customization algorithm, which has combined the method of principal component analysis (PCA), multiple linear regression (MLR) and database matching (DM), has been presented in this paper. The HRTFs selected by both the best match and the worst match have been applied into obtaining binaurally auralized sounds, which are then used for subjective listening experiments and the results are compared. For the area in the horizontal plane, the localization results have shown that the selection of HRTFs can enhance the localization accuracy and can also abate the problem of front-back confusion.

  17. Structural characterizations of nonpeptidic thiadiazole inhibitors of matrix metalloproteinases reveal the basis for stromelysin selectivity.

    PubMed Central

    Finzel, B. C.; Baldwin, E. T.; Bryant, G. L.; Hess, G. F.; Wilks, J. W.; Trepod, C. M.; Mott, J. E.; Marshall, V. P.; Petzold, G. L.; Poorman, R. A.; O'Sullivan, T. J.; Schostarez, H. J.; Mitchell, M. A.

    1998-01-01

    The binding of two 5-substituted-1,3,4-thiadiazole-2-thione inhibitors to the matrix metalloproteinase stromelysin (MMP-3) have been characterized by protein crystallography. Both inhibitors coordinate to the catalytic zinc cation via an exocyclic sulfur and lay in an unusual position across the unprimed (P1-P3) side of the proteinase active site. Nitrogen atoms in the thiadiazole moiety make specific hydrogen bond interactions with enzyme structural elements that are conserved across all enzymes in the matrix metalloproteinase class. Strong hydrophobic interactions between the inhibitors and the side chain of tyrosine-155 appear to be responsible for the very high selectivity of these inhibitors for stromelysin. In these enzyme/inhibitor complexes, the S1' enzyme subsite is unoccupied. A conformational rearrangement of the catalytic domain occurs that reveals an inherent flexibility of the substrate binding region leading to speculation about a possible mechanism for modulation of stromelysin activity and selectivity. PMID:9792098

  18. Electrically tunable selective reflection of light by heliconical cholesteric structures (Presentation Recording)

    NASA Astrophysics Data System (ADS)

    Lavrentovich, Oleg D.; Xiang, Jie; Shiyanovskii, Sergij V.; Li, Quan

    2015-10-01

    Cholesteric liquid crystals with helicoidal molecular architecture are known for their ability to selectively reflect light with the wavelength that is determined by the periodicity of molecular orientations. Resulting interference colors are highly saturated, they add like colored lights and produce a color gamut greater than that obtained with inks, dyes, and pigments. The periodicity of the helical structure and thus the wavelength of the reflected light can be controlled by chemical composition and sometimes by temperature, but tuning with the electric field has been so far elusive. Here we demonstrate that by using a cholesteric with oblique helicoidal (heliconical) structure, as opposed to the classic "right-angle" helicoid, one can vary the wavelength of selectively reflected light in a broad spectral range, by simply adjusting the electric field applied parallel to the helicoidal axis. The effect can enable many applications that require dynamically controlled transmission and reflection of light, from energy-saving smart windows to tunable organic lasers, and transparent "see-through" displays. Since the material is non-absorbing and transparent everywhere except the electrically preselected reflection band, the effect can be used in creating multilayered structures with a dynamic additive mixture of colors.

  19. Structural basis for selective targeting of leishmanial ribosomes: aminoglycoside derivatives as promising therapeutics

    PubMed Central

    Shalev, Moran; Rozenberg, Haim; Smolkin, Boris; Nasereddin, Abedelmajeed; Kopelyanskiy, Dmitry; Belakhov, Valery; Schrepfer, Thomas; Schacht, Jochen; Jaffe, Charles L.; Adir, Noam; Baasov, Timor

    2015-01-01

    Leishmaniasis comprises an array of diseases caused by pathogenic species of Leishmania, resulting in a spectrum of mild to life-threatening pathologies. Currently available therapies for leishmaniasis include a limited selection of drugs. This coupled with the rather fast emergence of parasite resistance, presents a dire public health concern. Paromomycin (PAR), a broad-spectrum aminoglycoside antibiotic, has been shown in recent years to be highly efficient in treating visceral leishmaniasis (VL)—the life-threatening form of the disease. While much focus has been given to exploration of PAR activities in bacteria, its mechanism of action in Leishmania has received relatively little scrutiny and has yet to be fully deciphered. In the present study we present an X-ray structure of PAR bound to rRNA model mimicking its leishmanial binding target, the ribosomal A-site. We also evaluate PAR inhibitory actions on leishmanial growth and ribosome function, as well as effects on auditory sensory cells, by comparing several structurally related natural and synthetic aminoglycoside derivatives. The results provide insights into the structural elements important for aminoglycoside inhibitory activities and selectivity for leishmanial cytosolic ribosomes, highlighting a novel synthetic derivative, compound 3, as a prospective therapeutic candidate for the treatment of VL. PMID:26264664

  20. Structural basis for selective targeting of leishmanial ribosomes: Aminoglycoside derivatives as promising therapeutics

    SciTech Connect

    Shalev, Moran; Rozenberg, Haim; Smolkin, Boris; Nasereddin, Abedelmajeed; Kopelyanskiy, Dmitry; Belakhov, Valery; Schrepfer, Thomas; Schacht, Jochen; Jaffe, Charles L.; Adir, Noam; Baasov, Timor

    2015-08-11

    Leishmaniasis comprises an array of diseases caused by pathogenic species of Leishmania, resulting in a spectrum of mild to life-threatening pathologies. Currently available therapies for leishmaniasis include a limited selection of drugs. This coupled with the rather fast emergence of parasite resistance, presents a dire public health concern. Paromomycin (PAR), a broad-spectrum aminoglycoside antibiotic, has been shown in recent years to be highly efficient in treating visceral leishmaniasis (VL)—the life-threatening form of the disease. While much focus has been given to exploration of PAR activities in bacteria, its mechanism of action in Leishmania has received relatively little scrutiny and has yet to be fully deciphered. In the present study we present an X-ray structure of PAR bound to rRNA model mimicking its leishmanial binding target, the ribosomal A-site. We evaluate PAR inhibitory actions on leishmanial growth and ribosome function, as well as effects on auditory sensory cells, by comparing several structurally related natural and synthetic aminoglycoside derivatives. The results provide insights into the structural elements important for aminoglycoside inhibitory activities and selectivity for leishmanial cytosolic ribosomes, highlighting a novel synthetic derivative, compound 3, as a prospective therapeutic candidate for the treatment of VL.

  1. Structural basis for selective targeting of leishmanial ribosomes: Aminoglycoside derivatives as promising therapeutics

    DOE PAGESBeta

    Shalev, Moran; Rozenberg, Haim; Smolkin, Boris; Nasereddin, Abedelmajeed; Kopelyanskiy, Dmitry; Belakhov, Valery; Schrepfer, Thomas; Schacht, Jochen; Jaffe, Charles L.; Adir, Noam; et al

    2015-08-11

    Leishmaniasis comprises an array of diseases caused by pathogenic species of Leishmania, resulting in a spectrum of mild to life-threatening pathologies. Currently available therapies for leishmaniasis include a limited selection of drugs. This coupled with the rather fast emergence of parasite resistance, presents a dire public health concern. Paromomycin (PAR), a broad-spectrum aminoglycoside antibiotic, has been shown in recent years to be highly efficient in treating visceral leishmaniasis (VL)—the life-threatening form of the disease. While much focus has been given to exploration of PAR activities in bacteria, its mechanism of action in Leishmania has received relatively little scrutiny and hasmore » yet to be fully deciphered. In the present study we present an X-ray structure of PAR bound to rRNA model mimicking its leishmanial binding target, the ribosomal A-site. We evaluate PAR inhibitory actions on leishmanial growth and ribosome function, as well as effects on auditory sensory cells, by comparing several structurally related natural and synthetic aminoglycoside derivatives. The results provide insights into the structural elements important for aminoglycoside inhibitory activities and selectivity for leishmanial cytosolic ribosomes, highlighting a novel synthetic derivative, compound 3, as a prospective therapeutic candidate for the treatment of VL.« less

  2. Structural basis for selective targeting of leishmanial ribosomes: aminoglycoside derivatives as promising therapeutics.

    PubMed

    Shalev, Moran; Rozenberg, Haim; Smolkin, Boris; Nasereddin, Abedelmajeed; Kopelyanskiy, Dmitry; Belakhov, Valery; Schrepfer, Thomas; Schacht, Jochen; Jaffe, Charles L; Adir, Noam; Baasov, Timor

    2015-09-30

    Leishmaniasis comprises an array of diseases caused by pathogenic species of Leishmania, resulting in a spectrum of mild to life-threatening pathologies. Currently available therapies for leishmaniasis include a limited selection of drugs. This coupled with the rather fast emergence of parasite resistance, presents a dire public health concern. Paromomycin (PAR), a broad-spectrum aminoglycoside antibiotic, has been shown in recent years to be highly efficient in treating visceral leishmaniasis (VL)-the life-threatening form of the disease. While much focus has been given to exploration of PAR activities in bacteria, its mechanism of action in Leishmania has received relatively little scrutiny and has yet to be fully deciphered. In the present study we present an X-ray structure of PAR bound to rRNA model mimicking its leishmanial binding target, the ribosomal A-site. We also evaluate PAR inhibitory actions on leishmanial growth and ribosome function, as well as effects on auditory sensory cells, by comparing several structurally related natural and synthetic aminoglycoside derivatives. The results provide insights into the structural elements important for aminoglycoside inhibitory activities and selectivity for leishmanial cytosolic ribosomes, highlighting a novel synthetic derivative, compound 3: , as a prospective therapeutic candidate for the treatment of VL. PMID:26264664

  3. Practical guidelines to select and scale earthquake records for nonlinear response history analysis of structures

    USGS Publications Warehouse

    Kalkan, Erol; Chopra, Anil K.

    2010-01-01

    Earthquake engineering practice is increasingly using nonlinear response history analysis (RHA) to demonstrate performance of structures. This rigorous method of analysis requires selection and scaling of ground motions appropriate to design hazard levels. Presented herein is a modal-pushover-based scaling (MPS) method to scale ground motions for use in nonlinear RHA of buildings and bridges. In the MPS method, the ground motions are scaled to match (to a specified tolerance) a target value of the inelastic deformation of the first-'mode' inelastic single-degree-of-freedom (SDF) system whose properties are determined by first-'mode' pushover analysis. Appropriate for first-?mode? dominated structures, this approach is extended for structures with significant contributions of higher modes by considering elastic deformation of second-'mode' SDF system in selecting a subset of the scaled ground motions. Based on results presented for two bridges, covering single- and multi-span 'ordinary standard' bridge types, and six buildings, covering low-, mid-, and tall building types in California, the accuracy and efficiency of the MPS procedure are established and its superiority over the ASCE/SEI 7-05 scaling procedure is demonstrated.

  4. Update on the Pfam5000 Strategy for Selection of StructuralGenomics Targets

    SciTech Connect

    Chandonia, John-Marc; Brenner, Steven E.

    2005-06-27

    Structural Genomics is an international effort to determine the three-dimensional shapes of all important biological macromolecules, with a primary focus on proteins. Target proteins should be selected according to a strategy that is medically and biologically relevant, of good financial value, and tractable. In 2003, we presented the ''Pfam5000'' strategy, which involves selecting the 5,000 most important families from the Pfam database as sources for targets. In this update, we show that although both the Pfam database and the number of sequenced genomes have increased in size, the expected benefits of the Pfam5000 strategy have not changed substantially. Solving the structures of proteins from the 5,000 largest Pfam families would allow accurate fold assignment for approximately 65 percent of all prokaryotic proteins (covering 54 percent of residues) and 63 percent of eukaryotic proteins (42 percent of residues). Fewer than 2,300 of the largest families on this list remain to be solved, making the project feasible in the next five years given the expected throughput to be achieved in the production phase of the Protein Structure Initiative.

  5. Search tool plug-in: imploements latent topic feedback

    SciTech Connect

    2011-09-23

    IRIS is a search tool plug-in that is used to implement latent topic feedback for enhancing text navigation. It accepts a list of returned documents from an information retrieval wywtem that is generated from keyword search queries. Data is pulled directly from a topic information database and processed by IRIS to determine the most prominent and relevant topics, along with topic-ngrams, associated with the list of returned documents. User selected topics are then used to expand the query and presumabley refine the search results.

  6. Search tool plug-in: imploements latent topic feedback

    Energy Science and Technology Software Center (ESTSC)

    2011-09-23

    IRIS is a search tool plug-in that is used to implement latent topic feedback for enhancing text navigation. It accepts a list of returned documents from an information retrieval wywtem that is generated from keyword search queries. Data is pulled directly from a topic information database and processed by IRIS to determine the most prominent and relevant topics, along with topic-ngrams, associated with the list of returned documents. User selected topics are then used tomore » expand the query and presumabley refine the search results.« less

  7. The solution structures of two soybean calmodulin isoforms provide a structural basis for their selective target activation properties.

    PubMed

    Ishida, Hiroaki; Huang, Hao; Yamniuk, Aaron P; Takaya, Yoshiaki; Vogel, Hans J

    2008-05-23

    The intracellular calcium ion is one of the most important secondary messengers in eukaryotic cells. Ca(2+) signals are translated into physiological responses by EF-hand calcium-binding proteins such as calmodulin (CaM). Multiple CaM isoforms occur in plant cells, whereas only a single CaM protein is found in animals. Soybean CaM isoform 1 (sCaM1) shares 90% amino acid sequence identity with animal CaM (aCaM), whereas sCaM4 is only 78% identical. These two sCaM isoforms have distinct target-enzyme activation properties and physiological functions. sCaM4 is highly expressed during the self-defense reaction of the plant and activates the enzyme nitric-oxide synthase (NOS), whereas sCaM1 is incapable of activating NOS. The mechanism of selective target activation by plant CaM isoforms is poorly understood. We have determined high resolution NMR solution structures of Ca(2+)-sCaM1 and -sCaM4. These were compared with previously determined Ca(2+)-aCaM structures. For the N-lobe of the protein, the solution structures of Ca(2+)-sCaM1, -sCaM4, and -aCaM all closely resemble each other. However, despite the high sequence identity with aCaM, the C-lobe of Ca(2+)-sCaM1 has a more open conformation and consequently a larger hydrophobic target-protein binding pocket than Ca(2+)-aCaM or -sCaM4, the presence of which was further confirmed through biophysical measurements. The single Val-144 --> Met substitution in the C-lobe of Ca(2+)-sCaM1, which restores its ability to activate NOS, alters the structure of the C-lobe to a more closed conformation resembling Ca(2+)-aCaM and -sCaM4. The relationships between the structural differences in the two Ca(2+)-sCaM isoforms and their selective target activation properties are discussed. PMID:18347016

  8. Population Structure, Genetic Variation, and Linkage Disequilibrium in Perennial Ryegrass Populations Divergently Selected for Freezing Tolerance

    PubMed Central

    Kovi, Mallikarjuna Rao; Fjellheim, Siri; Sandve, Simen R.; Larsen, Arild; Rudi, Heidi; Asp, Torben; Kent, Matthew Peter; Rognli, Odd Arne

    2015-01-01

    Low temperature is one of the abiotic stresses seriously affecting the growth of perennial ryegrass (Lolium perenne L.), and freezing tolerance is a complex trait of major agronomical importance in northern and central Europe. Understanding the genetic control of freezing tolerance would aid in the development of cultivars of perennial ryegrass with improved adaptation to frost. The plant material investigated in this study was an experimental synthetic population derived from pair-crosses among five European perennial ryegrass genotypes, representing adaptations to a range of climatic conditions across Europe. A total number of 80 individuals (24 of High frost [HF]; 29 of Low frost [LF], and 27 of Unselected [US]) from the second generation of the two divergently selected populations and an unselected (US) control population were genotyped using 278 genome-wide SNPs derived from perennial ryegrass transcriptome sequences. Our studies investigated the genetic diversity among the three experimental populations by analysis of molecular variance and population structure, and determined that the HF and LF populations are very divergent after selection for freezing tolerance, whereas the HF and US populations are more similar. Linkage disequilibrium (LD) decay varied across the seven chromosomes and the conspicuous pattern of LD between the HF and LF population confirmed their divergence in freezing tolerance. Furthermore, two Fst outlier methods; finite island model (fdist) by LOSITAN and hierarchical structure model using ARLEQUIN, both detected six loci under directional selection. These outlier loci are most probably linked to genes involved in freezing tolerance, cold adaptation, and abiotic stress. These six candidate loci under directional selection for freezing tolerance might be potential marker resources for breeding perennial ryegrass cultivars with improved freezing tolerance. PMID:26617611

  9. Structural insight into selectivity and resistance profiles of ROS1 tyrosine kinase inhibitors

    PubMed Central

    Davare, Monika A.; Vellore, Nadeem A.; Wagner, Jacob P.; Eide, Christopher A.; Goodman, James R.; Drilon, Alexander; Deininger, Michael W.; O’Hare, Thomas; Druker, Brian J.

    2015-01-01

    Oncogenic ROS1 fusion proteins are molecular drivers in multiple malignancies, including a subset of non-small cell lung cancer (NSCLC). The phylogenetic proximity of the ROS1 and anaplastic lymphoma kinase (ALK) catalytic domains led to the clinical repurposing of the Food and Drug Administration (FDA)-approved ALK inhibitor crizotinib as a ROS1 inhibitor. Despite the antitumor activity of crizotinib observed in both ROS1- and ALK-rearranged NSCLC patients, resistance due to acquisition of ROS1 or ALK kinase domain mutations has been observed clinically, spurring the development of second-generation inhibitors. Here, we profile the sensitivity and selectivity of seven ROS1 and/or ALK inhibitors at various levels of clinical development. In contrast to crizotinib’s dual ROS1/ALK activity, cabozantinib (XL-184) and its structural analog foretinib (XL-880) demonstrate a striking selectivity for ROS1 over ALK. Molecular dynamics simulation studies reveal structural features that distinguish the ROS1 and ALK kinase domains and contribute to differences in binding site and kinase selectivity of the inhibitors tested. Cell-based resistance profiling studies demonstrate that the ROS1-selective inhibitors retain efficacy against the recently reported CD74-ROS1G2032R mutant whereas the dual ROS1/ALK inhibitors are ineffective. Taken together, inhibitor profiling and stringent characterization of the structure–function differences between the ROS1 and ALK kinase domains will facilitate future rational drug design for ROS1- and ALK-driven NSCLC and other malignancies. PMID:26372962

  10. Widespread signatures of local mRNA folding structure selection in four Dengue virus serotypes

    PubMed Central

    2015-01-01

    Background It is known that mRNA folding can affect and regulate various gene expression steps both in living organisms and in viruses. Previous studies have recognized functional RNA structures in the genome of the Dengue virus. However, these studies usually focused either on the viral untranslated regions or on very specific and limited regions at the beginning of the coding sequences, in a limited number of strains, and without considering evolutionary selection. Results Here we performed the first large scale comprehensive genomics analysis of selection for local mRNA folding strength in the Dengue virus coding sequences, based on a total of 1,670 genomes and 4 serotypes. Our analysis identified clusters of positions along the coding regions that may undergo a conserved evolutionary selection for strong or weak local folding maintained across different viral variants. Specifically, 53-66 clusters for strong folding and 49-73 clusters for weak folding (depending on serotype) aggregated of positions with a significant conservation of folding energy signals (related to partially overlapping local genomic regions) were recognized. In addition, up to 7% of these positions were found to be conserved in more than 90% of the viral genomes. Although some of the identified positions undergo frequent synonymous / non-synonymous substitutions, the selection for folding strength therein is preserved, and thus cannot be trivially explained based on sequence conservation alone. Conclusions The fact that many of the positions with significant folding related signals are conserved among different Dengue variants suggests that a better understanding of the mRNA structures in the corresponding regions may promote the development of prospective anti- Dengue vaccination strategies. The comparative genomics approach described here can be employed in the future for detecting functional regions in other pathogens with very high mutations rates. PMID:26449467

  11. Effect of the aerated structure on selected properties of freeze-dried hydrocolloid gels

    NASA Astrophysics Data System (ADS)

    Ciurzyńska, Agnieszka; Lenart, Andrzej

    2016-01-01

    The ability to create diverse structures and studies on the effect of the aerated structure on selected properties with the use of freeze-dried gels may provide knowledge about the properties of dried foods. Such gels can be a basis for obtaining innovative food products. For the gel preparation, 3 types of hydrocolloids were used: low-methoxyl pectin, a mixture of xanthan gum and locust-bean gum, and a mixture of xanthan gum and guar gum. Gels were aerated for 3 and 7 min, frozen at a temperature of -45°C 2 h-1, and freeze-dried at a temperature of 30°C. For the samples obtained, structure, porosity, shrinkage, rehydration, and colour were investigated. It was shown that the type of the hydrocolloid and aeration time influence the structure of freeze-dried gels, which determines such properties of samples as porosity, shrinkage, density, rehydration, and colour. The bigger pores of low-methoxyl pectin gels undergo rehydration in the highest degree. The delicate and aerated structure of gels with the mixture of xanthan gum and locust-bean gum was damaged during freeze-drying and shrinkage exhibited the highest value. Small pores of samples with the mixture of xanthan gum and guar gum were responsible for the lower rehydration properties, but the highest porosity value contributed to the highest lightness value.

  12. sDFIRE: Sequence-specific statistical energy function for protein structure prediction by decoy selections.

    PubMed

    Hoque, Md Tamjidul; Yang, Yuedong; Mishra, Avdesh; Zhou, Yaoqi

    2016-05-01

    An important unsolved problem in molecular and structural biology is the protein folding and structure prediction problem. One major bottleneck for solving this is the lack of an accurate energy to discriminate near-native conformations against other possible conformations. Here we have developed sDFIRE energy function, which is an optimized linear combination of DFIRE (the Distance-scaled Finite Ideal gas Reference state based Energy), the orientation dependent (polar-polar and polar-nonpolar) statistical potentials, and the matching scores between predicted and model structural properties including predicted main-chain torsion angles and solvent accessible surface area. The weights for these scoring terms are optimized by three widely used decoy sets consisting of a total of 134 proteins. Independent tests on CASP8 and CASP9 decoy sets indicate that sDFIRE outperforms other state-of-the-art energy functions in selecting near native structures and in the Pearson's correlation coefficient between the energy score and structural accuracy of the model (measured by TM-score). © 2016 Wiley Periodicals, Inc. PMID:26849026

  13. Theoretical Studies on Structures, Properties and Dominant Debromination Pathways for Selected Polybrominated Diphenyl Ethers

    PubMed Central

    Li, Lingyun; Hu, Jiwei; Shi, Xuedan; Ruan, Wenqian; Luo, Jin; Wei, Xionghui

    2016-01-01

    The B3LYP/6-311+G(d)-SDD method, which considers the relativistic effect of bromine, was adopted for the calculations of the selected polybrominated diphenyl ethers (PBDEs) in the present study, in which the B3LYP/6-311+G(d) method was also applied. The calculated values and experimental data for structural parameters of the selected PBDEs were compared to find the suitable theoretical methods for their structural optimization. The results show that the B3LYP/6-311+G(d) method can give the better results (with the root mean square errors (RMSEs) of 0.0268 for the C–Br bond and 0.0161 for the C–O bond) than the B3LYP/6-311+G(d)-SDD method. Then, the B3LYP/6-311+G(d) method was applied to predict the structures for the other selected PBDEs (both neutral and anionic species). The lowest unoccupied molecular orbital (LUMO) and the electron affinity are of a close relationship. The electron affinities (vertical electron affinity and adiabatic electron affinity) were discussed to study their electron capture abilities. To better estimate the conversion of configuration for PBDEs, the configuration transition states for BDE-5, BDE-22 and BDE-47 were calculated at the B3LYP/ 6-311+G(d) level in both gas phase and solution. The possible debromination pathway for BDE-22 were also studied, which have bromine substituents on two phenyl rings and the bromine on meta-position prefers to depart from the phenyl ring. The reaction profile of the electron-induced reductive debromination for BDE-22 were also shown in order to study its degradation mechanism. PMID:27322242

  14. Theoretical Studies on Structures, Properties and Dominant Debromination Pathways for Selected Polybrominated Diphenyl Ethers.

    PubMed

    Li, Lingyun; Hu, Jiwei; Shi, Xuedan; Ruan, Wenqian; Luo, Jin; Wei, Xionghui

    2016-01-01

    The B3LYP/6-311+G(d)-SDD method, which considers the relativistic effect of bromine, was adopted for the calculations of the selected polybrominated diphenyl ethers (PBDEs) in the present study, in which the B3LYP/6-311+G(d) method was also applied. The calculated values and experimental data for structural parameters of the selected PBDEs were compared to find the suitable theoretical methods for their structural optimization. The results show that the B3LYP/6-311+G(d) method can give the better results (with the root mean square errors (RMSEs) of 0.0268 for the C-Br bond and 0.0161 for the C-O bond) than the B3LYP/6-311+G(d)-SDD method. Then, the B3LYP/6-311+G(d) method was applied to predict the structures for the other selected PBDEs (both neutral and anionic species). The lowest unoccupied molecular orbital (LUMO) and the electron affinity are of a close relationship. The electron affinities (vertical electron affinity and adiabatic electron affinity) were discussed to study their electron capture abilities. To better estimate the conversion of configuration for PBDEs, the configuration transition states for BDE-5, BDE-22 and BDE-47 were calculated at the B3LYP/ 6-311+G(d) level in both gas phase and solution. The possible debromination pathway for BDE-22 were also studied, which have bromine substituents on two phenyl rings and the bromine on meta-position prefers to depart from the phenyl ring. The reaction profile of the electron-induced reductive debromination for BDE-22 were also shown in order to study its degradation mechanism. PMID:27322242

  15. Impedance-based structural health monitoring using neural networks for autonomous frequency range selection

    NASA Astrophysics Data System (ADS)

    Min, Jiyoung; Park, Seunghee; Yun, Chung-Bang

    2010-12-01

    The impedance-based structural health monitoring (SHM) method has come to the forefront in the SHM community due to its practical potential for real applications. In the impedance-based SHM method, the selection of optimal frequency ranges plays an important role in improving the sensitivity of damage detection, since an improper frequency range can lead to erroneous damage detection results and provide false positive damage alarms. To tackle this issue, this paper proposes an innovative technique for autonomous selection of damage-sensitive frequency ranges using artificial neural networks (ANNs). First, the impedance signals are obtained in a wide frequency band, and the signals are split into multiple sub-ranges of this wide band. Then, the predefined damage index is evaluated for each sub-range by comparing impedance signals between the intact and the concurrent cases. Here, the cross correlation coefficients (CCs) are used as the predefined damage index. The ANN is constructed and trained using all CC values at multiple frequency ranges as multi-inputs and the real damage severity as the single output for various preselected damage scenarios, so that subsequent damage estimations may be carried out by selecting the governing frequency ranges autonomously. The performance of the proposed approach has been examined via a series of experimental studies to detect loose bolts and cracks induced on real steel bridge and building structures. It is found that the proposed approach autonomously determines the damage-sensitive frequency ranges and can be used for effective evaluation of damage severity in a wide variety of damage cases in real structures.

  16. Selective extraction, structural characterisation and antifungal activity assessment of napins from an industrial rapeseed meal.

    PubMed

    Nioi, Claudia; Kapel, Romain; Rondags, Emmanuel; Marc, Ivan

    2012-10-15

    This article reports an extraction-purification of napins from an industrial rapeseed meal and the assessment of their antimicrobial activity against Fusarium langsethiae. The best extraction conditions are observed at pH 2, 12% (w/w) of rapeseed meal after 15 min of extraction in water at room temperature. Under these conditions the extraction is highly selective, allowing a simple purification process (ammonium sulfate precipitation followed by desalting size exclusion chromatography) to get purified napins. These napins possessed significant anti-Fusarium activity (IC(50)=70 μM) and a compact secondary structure rich in α-helix, which may explain this bioactivity. PMID:23442668

  17. Structure of ring-shaped Aβ42 oligomers determined by conformational selection

    NASA Astrophysics Data System (ADS)

    Tran, Linh; Basdevant, Nathalie; Prévost, Chantal; Ha-Duong, Tâp

    2016-02-01

    The oligomerization of amyloid beta (Aβ) peptides into soluble non-fibrillar species plays a critical role in the pathogenesis of Alzheimer’s disease. However, it has been challenging to characterize the tertiary and quaternary structures of Aβ peptides due to their disordered nature and high aggregation propensity. In this work, replica exchange molecular dynamics simulations were used to explore the conformational space of Aβ42 monomer. Among the most populated transient states, we identified a particular conformation which was able to generate ring-shaped pentamers and hexamers, when docked onto itself. The structures of these aggregates were stable during microsecond all-atom MD simulations in explicit solvent. In addition to high resolution models of these oligomers, this study provides support for the conformational selection mechanism of Aβ peptide self-assembly.

  18. Analysis of cholinesterase inactivation and reactivation by systematic structural modification and enantiomeric selectivity.

    PubMed

    Taylor, P; Wong, L; Radić, Z; Tsigelny, I; Brüggemann, R; Hosea, N A; Berman, H A

    1999-05-14

    We show here with a congeneric series of Rp- and Sp-alkoxymethyl phosphonothiolates of known absolute stereochemistry that chiral selectivity in their reaction with acetylcholinesterase can be described in terms of discrete orientational and steric requirements. Stereoselectivity depends on acyl pocket dimensions, which govern leaving group orientation and a productive association of the phosphonyl oxygen in the oxyanion hole. Overall geometry is consistent with a pentavalent intermediate where the attacking serine and leaving group are at apical positions. Oxime reactivation of the phosphonylated enzyme occurs through a similar associative intermediate presumably forming an oxime phosphonate. The oximes of differing structure show distinct angles of attacking the phosphate where the attack angles and access to the phosphorus are constrained in the sterically impacted gorge. Hence, efficacy of oxime reactivation is dependent on both oxime and conjugated phosphonate structures. PMID:10421434

  19. Structure of ring-shaped Aβ42 oligomers determined by conformational selection

    PubMed Central

    Tran, Linh; Basdevant, Nathalie; Prévost, Chantal; Ha-Duong, Tâp

    2016-01-01

    The oligomerization of amyloid beta (Aβ) peptides into soluble non-fibrillar species plays a critical role in the pathogenesis of Alzheimer’s disease. However, it has been challenging to characterize the tertiary and quaternary structures of Aβ peptides due to their disordered nature and high aggregation propensity. In this work, replica exchange molecular dynamics simulations were used to explore the conformational space of Aβ42 monomer. Among the most populated transient states, we identified a particular conformation which was able to generate ring-shaped pentamers and hexamers, when docked onto itself. The structures of these aggregates were stable during microsecond all-atom MD simulations in explicit solvent. In addition to high resolution models of these oligomers, this study provides support for the conformational selection mechanism of Aβ peptide self-assembly. PMID:26868929

  20. Topical Review: Molecular reaction and solvation visualized by time-resolved X-ray solution scattering: Structure, dynamics, and their solvent dependence

    PubMed Central

    Hwan Kim, Kyung; Kim, Jeongho; Hyuk Lee, Jae; Ihee, Hyotcherl

    2014-01-01

    Time-resolved X-ray solution scattering is sensitive to global molecular structure and can track the dynamics of chemical reactions. In this article, we review our recent studies on triiodide ion (I3–) and molecular iodine (I2) in solution. For I3–, we elucidated the excitation wavelength-dependent photochemistry and the solvent-dependent ground-state structure. For I2, by combining time-slicing scheme and deconvolution data analysis, we mapped out the progression of geminate recombination and the associated structural change in the solvent cage. With the aid of X-ray free electron lasers, even clearer observation of ultrafast chemical events will be made possible in the near future. PMID:26798770

  1. Structural and Biochemical Characterization of AidC, a Quorum-Quenching Lactonase With Atypical Selectivity

    PubMed Central

    Mascarenhas, Romila; Thomas, Pei W.; Wu, Chun-Xiang; Nocek, Boguslaw P.; Hoang, Quyen Q.; Liu, Dali; Fast, Walter

    2015-01-01

    Quorum-quenching catalysts are of interest for potential application as biochemical tools to interrogate interbacterial communication pathways, as anti-biofouling agents, and as anti-infective agents in plants and animals. Herein, the structure and function of AidC, an N-acyl-L-homoserine (AHL) lactonase from Chryseobacterium, is characterized. Steady-state kinetics show that zinc-supplemented AidC is one of the most efficient wild-type quorum-quenching enzymes characterized to date, with a kcat/KM value of approximately 2 × 106 M−1s−1 for N-heptanoyl-L-homoserine lactone. The enzyme has stricter substrate selectivity and significantly lower KM values (ca. 50 μM for preferred substrates) than typical AHL lactonases (ca. > 1 mM). X-ray crystal structures of AidC alone, and with the product N-hexanoyl-L-homoserine were determined at resolutions of 1.09 and 1.67 Å, respectively. Each structure displays as a dimer, and dimeric oligiomerization was also observed in solution by size-exclusion chromatography coupled with multi-angle light scattering. The structures reveal two atypical features as compared to previously characterized AHL lactonases: a ‘kinked’ α-helix that forms part of a closed binding pocket which provides affinity and enforces selectivity for AHL substrates, and an active-site His substitution that is usually found in a homologous family of phosphodiesterases. Implications for the catalytic mechanism of AHL lactonases are discussed. PMID:26115006

  2. Structural and biochemical characterization of AidC, a quorum-quenching lactonase with atypical selectivity

    SciTech Connect

    Mascarenhas, Romila; Thomas, Pei W.; Wu, Chun -Xiang; Nocek, Boguslaw P.; Hoang, Quyen Q.; Liu, Dali; Fast, Walter

    2015-06-26

    Quorum-quenching catalysts are of interest for potential application as biochemical tools for interrogating interbacterial communication pathways, as antibiofouling agents, and as anti-infective agents in plants and animals. Herein, the structure and function of AidC, an N-acyl-l-homoserine lactone (AHL) lactonase from Chryseobacterium, is characterized. Steady-state kinetics show that zinc-supplemented AidC is the most efficient wild-type quorum-quenching enzymes characterized to date, with a kcat/KM value of approximately 2 × 106 M-1 s-1 for N-heptanoyl-l-homoserine lactone. The enzyme has stricter substrate selectivity and significantly lower KM values (ca. 50 μM for preferred substrates) compared to those of typical AHL lactonases (ca. >1 mM). X-ray crystal structures of AidC alone and with the product N-hexanoyl-l-homoserine were determined at resolutions of 1.09 and 1.67 Å, respectively. Each structure displays as a dimer, and dimeric oligiomerization was also observed in solution by size-exclusion chromatography coupled with multiangle light scattering. Lastly, the structures reveal two atypical features as compared to previously characterized AHL lactonases: a "kinked" α-helix that forms part of a closed binding pocket that provides affinity and enforces selectivity for AHL substrates and an active-site His substitution that is usually found in a homologous family of phosphodiesterases. We discuss implications for the catalytic mechanism of AHL lactonases.

  3. Structural and biochemical characterization of AidC, a quorum-quenching lactonase with atypical selectivity

    DOE PAGESBeta

    Mascarenhas, Romila; Thomas, Pei W.; Wu, Chun -Xiang; Nocek, Boguslaw P.; Hoang, Quyen Q.; Liu, Dali; Fast, Walter

    2015-06-26

    Quorum-quenching catalysts are of interest for potential application as biochemical tools for interrogating interbacterial communication pathways, as antibiofouling agents, and as anti-infective agents in plants and animals. Herein, the structure and function of AidC, an N-acyl-l-homoserine lactone (AHL) lactonase from Chryseobacterium, is characterized. Steady-state kinetics show that zinc-supplemented AidC is the most efficient wild-type quorum-quenching enzymes characterized to date, with a kcat/KM value of approximately 2 × 106 M-1 s-1 for N-heptanoyl-l-homoserine lactone. The enzyme has stricter substrate selectivity and significantly lower KM values (ca. 50 μM for preferred substrates) compared to those of typical AHL lactonases (ca. >1 mM).more » X-ray crystal structures of AidC alone and with the product N-hexanoyl-l-homoserine were determined at resolutions of 1.09 and 1.67 Å, respectively. Each structure displays as a dimer, and dimeric oligiomerization was also observed in solution by size-exclusion chromatography coupled with multiangle light scattering. Lastly, the structures reveal two atypical features as compared to previously characterized AHL lactonases: a "kinked" α-helix that forms part of a closed binding pocket that provides affinity and enforces selectivity for AHL substrates and an active-site His substitution that is usually found in a homologous family of phosphodiesterases. We discuss implications for the catalytic mechanism of AHL lactonases.« less

  4. Structural Basis of the Substrate Range and Enantioselectivity of Two (S)-Selective ω-Transaminases.

    PubMed

    van Oosterwijk, Niels; Willies, Simon; Hekelaar, Johan; Terwisscha van Scheltinga, Anke C; Turner, Nicholas J; Dijkstra, Bauke W

    2016-08-01

    ω-Transaminases are enzymes that can introduce an amino group in industrially interesting compounds. We determined crystal structures of two (S)-selective ω-transaminases, one from Arthrobacter sp. (Ars-ωTA) and one from Bacillus megaterium (BM-ωTA), which have 95% identical sequences but somewhat different activity profiles. Substrate profiling measurements using a range of (R)- and (S)-substrates showed that both enzymes have a preference for substrates with large, flat cyclic side groups, for which the activity of BM-ωTA is generally somewhat higher. BM-ωTA has a preference for (S)-3,3-dimethyl-2-butylamine significantly stronger than that of Ars-ωTA, as well as a weaker enantiopreference for 1-cyclopropylethylamine. The crystal structures showed that, as expected for (S)-selective transaminases, both enzymes have the typical transaminase type I fold and have spacious active sites to accommodate largish substrates. A structure of BM-ωTA with bound (R)-α-methylbenzylamine explains the enzymes' preference for (S)-substrates. Site-directed mutagenesis experiments revealed that the presence of a tyrosine, instead of a cysteine, at position 60 increases the relative activities on several small substrates. A structure of Ars-ωTA with bound l-Ala revealed that the Arg442 side chain has been repositioned to bind the l-Ala carboxylate. Compared to the arginine switch residue in other transaminases, Arg442 is shifted by six residues in the amino acid sequence, which appears to be a consequence of extra loops near the active site that narrow the entrance to the active site. PMID:27428867

  5. Effects of Topic Familiarity and Training in Generative Learning Activities on Poor Readers' Comprehension of Comparison/Contrast Expository Text Structure: Transfer to Real-World Materials.

    ERIC Educational Resources Information Center

    Weisberg, Renee; Balajthy, Ernest

    A study investigated transfer effects of training below average high school readers in the use of graphic organizers and summary writing on their recognition of compare/contrast text structure. Subjects, 32 high school students with below-expectancy standardized test scores, were placed in two groups: an experimental group (five males and 11…

  6. Structural basis of nucleoside and nucleoside drug selectivity by concentrative nucleoside transporters

    PubMed Central

    Johnson, Zachary Lee; Lee, Jun-Ho; Lee, Kiyoun; Lee, Minhee; Kwon, Do-Yeon; Hong, Jiyong; Lee, Seok-Yong

    2014-01-01

    Concentrative nucleoside transporters (CNTs) are responsible for cellular entry of nucleosides, which serve as precursors to nucleic acids and act as signaling molecules. CNTs also play a crucial role in the uptake of nucleoside-derived drugs, including anticancer and antiviral agents. Understanding how CNTs recognize and import their substrates could not only lead to a better understanding of nucleoside-related biological processes but also the design of nucleoside-derived drugs that can better reach their targets. Here, we present a combination of X-ray crystallographic and equilibrium-binding studies probing the molecular origins of nucleoside and nucleoside drug selectivity of a CNT from Vibrio cholerae. We then used this information in chemically modifying an anticancer drug so that it is better transported by and selective for a single human CNT subtype. This work provides proof of principle for utilizing transporter structural and functional information for the design of compounds that enter cells more efficiently and selectively. DOI: http://dx.doi.org/10.7554/eLife.03604.001 PMID:25082345

  7. Structure-guided design of a selective BCL-X(L) inhibitor.

    PubMed

    Lessene, Guillaume; Czabotar, Peter E; Sleebs, Brad E; Zobel, Kerry; Lowes, Kym N; Adams, Jerry M; Baell, Jonathan B; Colman, Peter M; Deshayes, Kurt; Fairbrother, Wayne J; Flygare, John A; Gibbons, Paul; Kersten, Wilhelmus J A; Kulasegaram, Sanji; Moss, Rebecca M; Parisot, John P; Smith, Brian J; Street, Ian P; Yang, Hong; Huang, David C S; Watson, Keith G

    2013-06-01

    The prosurvival BCL-2 family protein BCL-X(L) is often overexpressed in solid tumors and renders malignant tumor cells resistant to anticancer therapeutics. Enhancing apoptotic responses by inhibiting BCL-X(L) will most likely have widespread utility in cancer treatment and, instead of inhibiting multiple prosurvival BCL-2 family members, a BCL-X(L)-selective inhibitor would be expected to minimize the toxicity to normal tissues. We describe the use of a high-throughput screen to discover a new series of small molecules targeting BCL-X(L) and their structure-guided development by medicinal chemistry. The optimized compound, WEHI-539 (7), has high affinity (subnanomolar) and selectivity for BCL-X(L) and potently kills cells by selectively antagonizing its prosurvival activity. WEHI-539 will be an invaluable tool for distinguishing the roles of BCL-X(L) from those of its prosurvival relatives, both in normal cells and notably in malignant tumor cells, many of which may prove to rely upon BCL-X(L) for their sustained growth. PMID:23603658

  8. Quantitative structure-retention relationship of selected imidazoline derivatives on α1-acid glycoprotein column.

    PubMed

    Filipic, Slavica; Ruzic, Dusan; Vucicevic, Jelica; Nikolic, Katarina; Agbaba, Danica

    2016-08-01

    The retention behaviour of 22 selected imidazoline drugs and derivatives was investigated on α1-acid glycoprotein (AGP) column using Sørensen phosphate buffer (pH 7.0) and 2-propanol as organic modifier. Quantitative Structure-Retention Relationships (QSRR) models were built using extrapolated logkw values as well as isocratic retention factors (logk5, logk8, logk10, logk12, logk15 obtained for 5%, 8%, 10%, 12%, and 15%, of 2-propanol in mobile phase, respectively) as dependant variables and calculated physicochemical parameters as independant variables. The established QSRR models were built by stepwise multiple linear regression (MLR) and partial least squares regression (PLS). The performance of the stepwise and PLS models was tested by cross-validation and the external test set prediction. The validated QSRR models were compared and the optimal PLS-QSRR model for logkw and each isocratic retention factors (PLS-QSRR(logk5), PLS-QSRR(logk8), PLS-QSRR(logk10), MLR-QSRR(logk12), MLR-QSRR(logk15)) were selected. The QSRR results were further confirmed by Linear Solvation Energy Relationships (LSER). LSER analysis indicated on hydrogen bond basicity, McGowan volume and excess molar refraction as the most significant parameters for all AGP chromatographic retention factors and logkw values of 22 selected imidazoline drugs and derivatives. PMID:26968888

  9. Preparation of magnetic graphene composites with hierarchical structure for selective capture of phosphopeptides

    PubMed Central

    Cheng, Gong; Yu, Xu; Zhou, Mingda

    2014-01-01

    A novel graphene composite affinity material consisting of graphene scaffold, Fe3O4 nanoparticles for actuation and fully covered porous titania nanostructures as affinity coating has been designed and constructed. The obtained magnetic graphene composites have a saturation magnetization (Ms) value of 7.3 emu g-1, a BET specific surface area of 111.8 m2 g-1 and an average pore size of 15.1 nm for the porous affinity coating. The multifunctional graphene composites can realize the selective capture and convenient magnetic separation of target phosphopeptides by taking advantage of the decorated magnetic nanoparticles, highly pure and well crystallized affinity coating, and unique porous structure. Sensitivity and selectivity of the affinity graphene composites were evaluated using digests of standard proteins and complex biosamples as well as by comparison with the widely used TiO2 affinity microspheres. The results show that the affinity graphene composites can realize selective capture and rapid separation of low-abundance phosphopeptides from complex biological samples. Thus, this work will contribute to future applications in the purification and separation of specific biomolecules, in particular, low-abundance phosphopeptide biomarkers. PMID:25264490

  10. Correlation structure and variable selection in generalized estimating equations via composite likelihood information criteria.

    PubMed

    Nikoloulopoulos, Aristidis K

    2016-06-30

    The method of generalized estimating equations (GEE) is popular in the biostatistics literature for analyzing longitudinal binary and count data. It assumes a generalized linear model for the outcome variable, and a working correlation among repeated measurements. In this paper, we introduce a viable competitor: the weighted scores method for generalized linear model margins. We weight the univariate score equations using a working discretized multivariate normal model that is a proper multivariate model. Because the weighted scores method is a parametric method based on likelihood, we propose composite likelihood information criteria as an intermediate step for model selection. The same criteria can be used for both correlation structure and variable selection. Simulations studies and the application example show that our method outperforms other existing model selection methods in GEE. From the example, it can be seen that our methods not only improve on GEE in terms of interpretability and efficiency but also can change the inferential conclusions with respect to GEE. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26822854

  11. 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

  12. Selection of flowing liquid lead target structural materials for accelerator driven transmutation applications

    SciTech Connect

    Park, J.J.; Buksa, J.J.

    1994-08-01

    The beam entry window and container for a liquid lead spallation target will be exposed to high fluxes of protons and neutrons that are both higher in magnitude and energy than have been experienced in proton accelerators and fission reactors, as well as in a corrosive environment. The structural material of the target should have a good compatibility with liquid lead, a sufficient mechanical strength at elevated temperatures, a good performance under an intense irradiation environment, and a low neutron absorption cross section; these factors have been used to rank the applicability of a wide range of materials for structural containment Nb-1Zr has been selected for use as the structural container for the LANL ABC/ATW molten lead target. Corrosion and mass transfer behavior for various candidate structural materials in liquid lead are reviewed, together with the beneficial effects of inhibitors and various coatings to protect substrate against liquid lead corrosion. Mechanical properties of some candidate materials at elevated temperatures and the property changes resulting from 800 MeV proton irradiation are also reviewed.

  13. Study of Sodium Ion Selective Electrodes and Differential Structures with Anodized Indium Tin Oxide

    PubMed Central

    Lin, Jyh-Ling; Hsu, Hsiang-Yi

    2010-01-01

    The objective of this work is the study and characterization of anodized indium tin oxide (anodized-ITO) as a sodium ion selective electrode and differential structures including a sodium-selective-membrane/anodized-ITO as sensor 1, an anodized-ITO membrane as the contrast sensor 2, and an ITO as the reference electrode. Anodized-ITO was fabricated by anodic oxidation at room temperature, a low cost and simple manufacture process that makes it easy to control the variation in film resistance. The anodized-ITO based on EGFET structure has good linear pH sensitivity, approximately 54.44 mV/pH from pH 2 to pH 12. The proposed sodium electrodes prepared by PVC-COOH, DOS embedding colloid, and complex Na-TFBD and ionophore B12C4, show good sensitivity at 52.48 mV/decade for 10−4 M to 1 M, and 29.96 mV/decade for 10−7 M to 10−4 M. The sodium sensitivity of the differential sodium-sensing device is 58.65 mV/decade between 10−4 M and 1 M, with a corresponding linearity of 0.998; and 19.17 mV/decade between 10−5 M and 10−4 M. PMID:22294900

  14. Neisseria gonorrhoeae PilC expression provides a selective mechanism for structural diversity of pili.

    PubMed Central

    Jonsson, A B; Pfeifer, J; Normark, S

    1992-01-01

    Pili of Neisseria gonorrhoeae undergo both phase and structural variation. Phase variation of gonococcal pili can be caused by a RecA-independent on/off switch in PilC, a protein involved in pilus biogenesis. We show here that spontaneous nonpiliated PilC- derivatives as well as PilC- insertional mutants have also acquired sequence alterations in pilE relative to the pilE gene of the piliated MS11mk(P+)-u parent, so that the pilin produced is processed to soluble S-pilin and can be released into the medium. It is proposed that pilin alterations are selected for in PilC- bacteria if the parental nonassembled pilin is toxic to the cells--i.e., is not degradable to S-pilin at rates sufficient to allow viability of the cells. Toxicity is indicated by the extreme instability of certain unassembled pilin sequences and by the low frequency of nonpiliated, pilin+, PilC- variants that emerge from piliated recA- cells. The presence of a point mutation changing leucine-39 to phenylalanine at the cleavage site for S-pilin in one nonpiliated, PilC-, recA- variant relative to its piliated parent is a further argument for a selective mechanism of structural diversity of the gonococcal pilin. Images PMID:1348857

  15. Mode-selective coupling structures for monolithic integrated waveguide-detector systems

    NASA Astrophysics Data System (ADS)

    Koster, Tom M.; Houtsma, V. E.; Lambeck, Paul V.; Klunder, Dion J.; Popma, Th. J. A.; Holleman, J.

    1999-03-01

    Microsystems are presented in which a SiON based optical waveguiding system is monolithically integrated with photodiodes, which are implemented in the Si substrate. Coupling structures of various type enable to transfer whether (part of) the power of one selected mode or the power of all modi propagating through the waveguide, to the photodiode. Here we focus on coupling structures for use in integrated optical absorption sensor systems, where information can be obtained from both the TE0 and TM0 mode, propagating simultaneously through the waveguide system. The coupling into the photodiodes is achieved by thinning down the thickness of the core layer in the region above the photodiode, which results in a mode specific modewidth expansion of the propagating modi. It will be shown that in asymmetrical layer systems, within a certain interaction length all TM0 power can be absorbed by the Si detector, while the TE0 mode shows only a negligible attenuation. The selectivity of the coupling can be strongly enhanced by implementing an additional substrate layer, having a refractive index in between that of the TE0 and TM0 mode. Both theoretical and experimental results will be presented.

  16. Structural Plasticity of Malaria Dihydroorotate Dehydrogenase Allows Selective Binding of Diverse Chemical Scaffolds

    SciTech Connect

    Deng, Xiaoyi; Gujjar, Ramesh; El Mazouni, Farah; Kaminsky, Werner; Malmquist, Nicholas A.; Goldsmith, Elizabeth J.; Rathod, Pradipsinh K.; Phillips, Margaret A.

    2010-01-20

    Malaria remains a major global health burden and current drug therapies are compromised by resistance. Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) was validated as a new drug target through the identification of potent and selective triazolopyrimidine-based DHODH inhibitors with anti-malarial activity in vivo. Here we report x-ray structure determination of PfDHODH bound to three inhibitors from this series, representing the first of the enzyme bound to malaria specific inhibitors. We demonstrate that conformational flexibility results in an unexpected binding mode identifying a new hydrophobic pocket on the enzyme. Importantly this plasticity allows PfDHODH to bind inhibitors from different chemical classes and to accommodate inhibitor modifications during lead optimization, increasing the value of PfDHODH as a drug target. A second discovery, based on small molecule crystallography, is that the triazolopyrimidines populate a resonance form that promotes charge separation. These intrinsic dipoles allow formation of energetically favorable H-bond interactions with the enzyme. The importance of delocalization to binding affinity was supported by site-directed mutagenesis and the demonstration that triazolopyrimidine analogs that lack this intrinsic dipole are inactive. Finally, the PfDHODH-triazolopyrimidine bound structures provide considerable new insight into species-selective inhibitor binding in this enzyme family. Together, these studies will directly impact efforts to exploit PfDHODH for the development of anti-malarial chemotherapy.

  17. Structures of Pseudomonas aeruginosa LpxA Reveal the Basis for Its Substrate Selectivity.

    PubMed

    Smith, Emmanuel W; Zhang, XiuJun; Behzadi, Cyrus; Andrews, Logan D; Cohen, Frederick; Chen, Yu

    2015-09-29

    In Gram-negative bacteria, the first step of lipid A biosynthesis is catalyzed by UDP-N-acetylglucosamine acyltransferase (LpxA) through the transfer of a R-3-hydroxyacyl chain from the acyl carrier protein (ACP) to the 3-hydroxyl group of UDP-GlcNAc. Previous studies suggest that LpxA is a critical determinant of the acyl chain length found in lipid A, which varies among species of bacteria. In Escherichia coli and Leptospira interrogans, LpxA prefers to incorporate longer R-3-hydroxyacyl chains (C14 and C12, respectively), whereas in Pseudomonas aeruginosa, the enzyme is selective for R-3-hydroxydecanoyl, a 10-hydrocarbon long acyl chain. We now report three P. aeruginosa LpxA crystal structures: apo protein, substrate complex with UDP-GlcNAc, and product complex with UDP-3-O-(R-3-hydroxydecanoyl)-GlcNAc. A comparison between the apo form and complexes identifies key residues that position UDP-GlcNAc appropriately for catalysis and supports the role of catalytic His121 in activating the UDP-GlcNAc 3-hydroxyl group for nucleophilic attack during the reaction. The product-complex structure, for the first time, offers structural insights into how Met169 serves to constrain the length of the acyl chain and thus functions as the so-called hydrocarbon ruler. Furthermore, compared with ortholog LpxA structures, the purported oxyanion hole, formed by the backbone amide group of Gly139, displays a different conformation in P. aeruginosa LpxA, which suggests flexibility of this structural feature important for catalysis and the potential need for substrate-induced conformational change in catalysis. Taken together, the three structures provide valuable insights into P. aeruginosa LpxA catalysis and substrate specificity as well as templates for future inhibitor discovery. PMID:26352800

  18. Structure-Based Consensus Scoring Scheme for Selecting Class A Aminergic GPCR Fragments.

    PubMed

    Kelemen, Ádám A; Kiss, Róbert; Ferenczy, György G; Kovács, László; Flachner, Beáta; Lőrincz, Zsolt; Keserű, György M

    2016-02-22

    Aminergic G-protein coupled receptors (GPRCs) represent well-known targets of central nervous-system related diseases. In this study a structure-based consensus virtual screening scheme was developed for designing targeted fragment libraries against class A aminergic GPCRs. Nine representative aminergic GPCR structures were selected by first clustering available X-ray structures and then choosing the one in each cluster that performs best in self-docking calculations. A consensus scoring protocol was developed using known promiscuous aminergic ligands and decoys as a training set. The consensus score (FrACS-fragment aminergic consensus score) calculated for the optimized protein ensemble showed improved enrichments in most cases as compared to stand-alone structures. Retrospective validation was carried out on public screening data for aminergic targets (5-HT1 serotonin receptor, TA1 trace-amine receptor) showing 8-17-fold enrichments using an ensemble of aminergic receptor structures. The performance of the structure based FrACS in combination with our ligand-based prefilter (FrAGS) was investigated both in a retrospective validation on the ChEMBL database and in a prospective validation on an in-house fragment library. In prospective validation virtual fragment hits were tested on 5-HT6 serotonin receptors not involved in the development of FrACS. Six out of the 36 experimentally tested fragments exhibited remarkable antagonist efficacies, and 4 showed IC50 values in the low micromolar or submicromolar range in a cell-based assay. Both retrospective and prospective validations revealed that the methodology is suitable for designing focused class A GPCR fragment libraries from large screening decks, commercial compound collections, or virtual databases. PMID:26760056

  19. Phenotypic variation and water selection potential in the stem structure of invasive alligator weed

    NASA Astrophysics Data System (ADS)

    Du, Leshan; Yang, Beifen; Guan, Wenbin; Li, Junmin

    2016-02-01

    The morphological and anatomical characteristics of stems have been found to be related to drought resistance in plants. Testing the phenotypic selection of water availability on stem anatomical traits would be useful for exploring the evolutionary potential of the stem in response to water availability. To test the phenotypic variation of the stem anatomical traits of an invasive plant in response to water availability, we collected a total of 320 individuals of Alternanthera philoxeroides from 16 populations from terrestrial and aquatic habitats in 8 plots in China and then analyzed the variation, differentiation, plasticity and selection potential of water availability on the stem anatomical traits. We found that except for the thickness of the cortex, all of the examined phenotypic parameters of the A. philoxeroides stem were significantly and positively correlated with soil water availability. The phenotypic differentiation coefficient for all of the anatomical structural parameters indicated that most of the variation existed between habitats within the same plot, whereas there was little variation among plots or among individuals within the same habitat except for variation in the thickness of the cortex. A significant phenotypic plasticity response to water availability was found for all of the anatomical traits of A. philoxeroides stem except for the thickness of the cortex. The associations between fitness and some of the anatomical traits, such as the stem diameter, the cortex area-to-stem area ratio, the pith cavity area-to-stem area ratio and the density of vascular bundles, differed with heterogeneous water availability. In both the aquatic and terrestrial habitats, no significant directional selection gradient was found for the stem diameter, the cortex area-to-stem area ratio or the density of vascular bundles. These results indicated that the anatomical structure of the A. philoxeroides stem may play an important role in the adaptation to changes

  20. Structure- and function-based design of Plasmodium-selective proteasome inhibitors.

    PubMed

    Li, Hao; O'Donoghue, Anthony J; van der Linden, Wouter A; Xie, Stanley C; Yoo, Euna; Foe, Ian T; Tilley, Leann; Craik, Charles S; da Fonseca, Paula C A; Bogyo, Matthew

    2016-02-11

    The proteasome is a multi-component protease complex responsible for regulating key processes such as the cell cycle and antigen presentation. Compounds that target the proteasome are potentially valuable tools for the treatment of pathogens that depend on proteasome function for survival and replication. In particular, proteasome inhibitors have been shown to be toxic for the malaria parasite Plasmodium falciparum at all stages of its life cycle. Most compounds that have been tested against the parasite also inhibit the mammalian proteasome, resulting in toxicity that precludes their use as therapeutic agents. Therefore, better definition of the substrate specificity and structural properties of the Plasmodium proteasome could enable the development of compounds with sufficient selectivity to allow their use as anti-malarial agents. To accomplish this goal, here we use a substrate profiling method to uncover differences in the specificities of the human and P. falciparum proteasome. We design inhibitors based on amino-acid preferences specific to the parasite proteasome, and find that they preferentially inhibit the β2-subunit. We determine the structure of the P. falciparum 20S proteasome bound to the inhibitor using cryo-electron microscopy and single-particle analysis, to a resolution of 3.6 Å. These data reveal the unusually open P. falciparum β2 active site and provide valuable information about active-site architecture that can be used to further refine inhibitor design. Furthermore, consistent with the recent finding that the proteasome is important for stress pathways associated with resistance of artemisinin family anti-malarials, we observe growth inhibition synergism with low doses of this β2-selective inhibitor in artemisinin-sensitive and -resistant parasites. Finally, we demonstrate that a parasite-selective inhibitor could be used to attenuate parasite growth in vivo without appreciable toxicity to the host. Thus, the Plasmodium proteasome is a

  1. Allocating structure to function: the strong links between neuroplasticity and natural selection

    PubMed Central

    Anderson, Michael L.; Finlay, Barbara L.

    2014-01-01

    A central question in brain evolution is how species-typical behaviors, and the neural function-structure mappings supporting them, can be acquired and inherited. Advocates of brain modularity, in its different incarnations across scientific subfields, argue that natural selection must target domain-dedicated, separately modifiable neural subsystems, resulting in genetically-specified functional modules. In such modular systems, specification of neuron number and functional connectivity are necessarily linked. Mounting evidence, however, from allometric, developmental, comparative, systems-physiological, neuroimaging and neurological studies suggests that brain elements are used and reused in multiple functional systems. This variable allocation can be seen in short-term neuromodulation, in neuroplasticity over the lifespan and in response to damage. We argue that the same processes are evident in brain evolution. Natural selection must preserve behavioral functions that may co-locate in variable amounts with other functions. In genetics, the uses and problems of pleiotropy, the re-use of genes in multiple networks have been much discussed, but this issue has been sidestepped in neural systems by the invocation of modules. Here we highlight the interaction between evolutionary and developmental mechanisms to produce distributed and overlapping functional architectures in the brain. These adaptive mechanisms must be robust to perturbations that might disrupt critical information processing and action selection, but must also recognize useful new sources of information arising from internal genetic or environmental variability, when those appear. These contrasting properties of “robustness” and “evolvability” have been discussed for the basic organization of body plan and fundamental cell physiology. Here we extend them to the evolution and development, “evo-devo,” of brain structure. PMID:24431995

  2. Structure and function based design of Plasmodium-selective proteasome inhibitors

    PubMed Central

    Li, Hao; O'Donoghue, Anthony J.; van der Linden, Wouter A.; Xie, Stanley C.; Yoo, Euna; Foe, Ian T.; Tilley, Leann; Craik, Charles S.; da Fonseca, Paula C. A.; Bogyo, Matthew

    2016-01-01

    The proteasome is a multi-component protease complex responsible for regulating key processes such as the cell cycle and antigen presentation1. Compounds that target the proteasome are potentially valuable tools for the treatment of pathogens that depend on proteasome function for survival and replication. In particular, proteasome inhibitors have been shown to be toxic for the malaria parasite Plasmodium falciparum at all stages of its life cycle2-5. Most compounds that have been tested against the parasite also inhibit the mammalian proteasome resulting in toxicity that precludes their use as therapeutic agents2,6. Therefore, better definition of the substrate specificity and structural properties of the Plasmodium proteasome could enable the development of compounds with sufficient selectivity to allow their use as anti-malarial agents. To accomplish this goal, we used a substrate profiling method to uncover differences in the specificities of the human and P. falciparum proteasome. We designed inhibitors based on amino acid preferences specific to the parasite proteasome, and found that they preferentially inhibit the β 2 subunit. We determined the structure of the P. falciparum 20S proteasome bound to the inhibitor using cryo-electron microscopy (cryo-EM) and single particle analysis, to a resolution of 3.6 Å. These data reveal the unusually open P. falciparum β2 active site and provide valuable information regarding active site architecture that can be used to further refine inhibitor design. Furthermore, consistent with the recent finding that the proteasome is important for stress pathways associated with resistance of artemisinin (ART) family anti-malarials7,8, we observed growth inhibition synergism with low doses of this β 2 selective inhibitor in ART sensitive and resistant parasites. Finally, we demonstrated that a parasite selective inhibitor could be used to attenuate parasite growth in vivo without significant toxicity to the host. Thus, the

  3. Organizational Structures and Operational Practices of Selected Educational R & D Centers and Educational Laboratories and of Selected Centers, Laboratories, and Institutes on One University Campus.

    ERIC Educational Resources Information Center

    Lins, L. Joseph

    This study investigates and analyzes the organizational structures, institutional ties, and operational practices of selected extramurally-supported centers, laboratories, and institutes. The primary goal is to provide one type of data, some experiences, and judgments on the basis of which an assessment might be made of the conditions of the…

  4. Nursing and Dental Hygiene Selection Procedures. Part I: The Structured Interview as a Tool for Selecting Students into an Associate of Arts Degree Program.

    ERIC Educational Resources Information Center

    Tatham, Elaine L.; And Others

    A structured interview procedure was used during the spring of 1975 as a tool in selecting nursing and dental hygiene students at Johnson County Community College. Potential students had two 20-minute interviews: one by a staff member of the program to which application was made, and one by another staff member. Interviewers rated the applicants…

  5. Investigations into the chemical structure based selectivity of the microfabricated nitrogen-phosphorus detector

    SciTech Connect

    Brocato, Terisse A.; Hess, Ryan F.; Moorman, Matthew; Simonson, Robert J.

    2015-10-28

    The nitrogen and phosphorus atoms are constituents of some of the most toxic chemical vapors. Nitrogen-phosphorus gas chromatograph detectors (NPDs) rely on selective ionization of such compounds using ionization temperatures typically greater than 600 °C. NPDs have previously been reported to be 7*104× and 105× more sensitive for nitrogen and phosphorus, respectively, than for carbon. Presented here is an investigation of the structure-based selectivity of a microfabricated nitrogen-phosphorus detector (μNPD). The μNPD presented here is smaller than a dime and can be placed in a system that is 1/100th the size of a commercial NPD. Comparison of responses of such devices to homologous anilines (p-methoxyaniline, p-fluoroaniline, and aniline) revealed that detection selectivity, determined by the ratio of μNPD to nonselective flame ionization detector (FID) peak areas, is correlated with acid disassociation pKa values for the respective analine. Selectivity was determined to be greatest for p-methoxyaniline, followed by p-fluoroaniline, with aniline having the smallest response. The limit of detection for a nitrogen containing chemical, p-methoxyaniline, using the μNPD was determined to be 0.29 ng compared to 59 ng for a carbon chemical containing no nitrogen or phosphorus, 1,3,5-trimethybenzene. The μNPD presented here has increased detection for nitrogen and phosphorus compared to the FID and with a slight increase in detection of carbon compounds compared to commercial NPD's sensitivity to nitrogen and carbon.

  6. Investigations into the chemical structure based selectivity of the microfabricated nitrogen-phosphorus detector

    DOE PAGESBeta

    Brocato, Terisse A.; Hess, Ryan F.; Moorman, Matthew; Simonson, Robert J.

    2015-10-28

    The nitrogen and phosphorus atoms are constituents of some of the most toxic chemical vapors. Nitrogen-phosphorus gas chromatograph detectors (NPDs) rely on selective ionization of such compounds using ionization temperatures typically greater than 600 °C. NPDs have previously been reported to be 7*104× and 105× more sensitive for nitrogen and phosphorus, respectively, than for carbon. Presented here is an investigation of the structure-based selectivity of a microfabricated nitrogen-phosphorus detector (μNPD). The μNPD presented here is smaller than a dime and can be placed in a system that is 1/100th the size of a commercial NPD. Comparison of responses of suchmore » devices to homologous anilines (p-methoxyaniline, p-fluoroaniline, and aniline) revealed that detection selectivity, determined by the ratio of μNPD to nonselective flame ionization detector (FID) peak areas, is correlated with acid disassociation pKa values for the respective analine. Selectivity was determined to be greatest for p-methoxyaniline, followed by p-fluoroaniline, with aniline having the smallest response. The limit of detection for a nitrogen containing chemical, p-methoxyaniline, using the μNPD was determined to be 0.29 ng compared to 59 ng for a carbon chemical containing no nitrogen or phosphorus, 1,3,5-trimethybenzene. The μNPD presented here has increased detection for nitrogen and phosphorus compared to the FID and with a slight increase in detection of carbon compounds compared to commercial NPD's sensitivity to nitrogen and carbon.« less

  7. Symbiosis: Rich, Exciting, Neglected Topic

    ERIC Educational Resources Information Center

    Rowland, Jane Thomas

    1974-01-01

    Argues that the topic of symbiosis has been greatly neglected and underemphasized in general-biology textbooks. Discusses many types and examples of symbiosis, and provides an extensive bibliography of the literature related to this topic. (JR)

  8. Serial data acquisition for the X-ray plasma diagnostics with selected GEM detector structures

    NASA Astrophysics Data System (ADS)

    Czarski, T.; Chernyshova, M.; Pozniak, K. T.; Kasprowicz, G.; Zabolotny, W.; Kolasinski, P.; Krawczyk, R.; Wojenski, A.; Zienkiewicz, P.

    2015-10-01

    The measurement system based on GEM—Gas Electron Multiplier detector is developed for X-ray diagnostics of magnetic confinement tokamak plasmas. The paper is focused on the measurement subject and describes the fundamental data processing to obtain reliable characteristics (histograms) useful for physicists. The required data processing have two steps: 1—processing in the time domain, i.e. events selections for bunches of coinciding clusters, 2—processing in the planar space domain, i.e. cluster identification for the given detector structure. So, it is the software part of the project between the electronic hardware and physics applications. The whole project is original and it was developed by the paper authors. The previous version based on 1-D GEM detector was applied for the high-resolution X-ray crystal spectrometer KX1 in the JET tokamak. The current version considers 2-D detector structures for the new data acquisition system. The fast and accurate mode of data acquisition implemented in the hardware in real time can be applied for the dynamic plasma diagnostics. Several detector structures with single-pixel sensors and multi-pixel (directional) sensors are considered for two-dimensional X-ray imaging. Final data processing is presented by histograms for selected range of position, time interval and cluster charge values. Exemplary radiation source properties are measured by the basic cumulative characteristics: the cluster position distribution and cluster charge value distribution corresponding to the energy spectra. A shorter version of this contribution is due to be published in PoS at: 1st EPS conference on Plasma Diagnostics

  9. Elucidation of the surface structure-selectivity relationship in ethanol electro-oxidation over platinum by density functional theory.

    PubMed

    Sheng, Tian; Lin, Wen-Feng; Sun, Shi-Gang

    2016-06-21

    We have successfully built a general framework to comprehend the structure-selectivity relationship in ethanol electrooxidation on platinum by density functional theory calculations. Based on the reaction mechanisms on three basal planes and five stepped surfaces, it was found that only (110) and n(111) × (110) sites can enhance CO2 selectivity but other non-selective step sites are more beneficial to activity. PMID:27181461

  10. Structure of corrective feedback for selection of ineffective vegetable parenting practices for use in a simulation videogame

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A serious videogame is being developed to train parents of preschool children in selecting and using parenting practices that are likely to encourage their child to eat more vegetables. The structure of feedback to the parents on their selection may influence what they learn from the game. Feedback ...

  11. Structure Design Approach and Technology Selection for Next Generation European Launchers

    NASA Astrophysics Data System (ADS)

    Baiocco, P.; Ramusat, G.; Kauffmann, J.; Jaredson, D.; Bouilly, Th.; Lavelle, F.; Louaas, E.

    2012-07-01

    In the framework of the next generation launchers activity at ESA, a top-down and a bottom-up approach has been performed for the alternative conception and promising technologies of NGL sub-assemblies and sub-systems. The top-down approach consisted in looking for system-driven design solutions and the bottom-up in the proposal of design solutions taking to substantial advantages for the system. The main investigations have been focused on structures and technologies tight to structures and interfaces. Specifications coming from a preliminary system design have been used in order to permit sub-system design with the goal to find the major advantage for the overall launch system. In this respect selection criteria have been identified and among these a specific evaluation of the payload mass over recurring cost advantage has been evaluated. The development cost, recurring cost and operational aspects have been considered as competitiveness factors for the identification of the most interesting solutions. The TRL/IRL has been assessed and a preliminary development plan has been identified. This approach is dedicated to reference NGL architectures, but alternative architectures have been investigated in order to assess their interest in terms of competitiveness factors and study of other technologies. This paper deals mainly with metallic and composite structures owing to sub-systems or sub-assemblies proposed for the NGL. The major sub-systems and structures analysed are the engine thrust frame (ETF), inter stage structures (ISS), cryogenic propellant tanks, feeding lines and attachments, pressurisation systems and fairing. The paper provides an overview of the main results of this investigation and the potential benefit it can provide.

  12. [INVITED] Ultrafast laser photoinscription of large-mode-area waveguiding structures in bulk dielectrics. Invited paper for the section : Hot topics in Ultrafast Lasers

    NASA Astrophysics Data System (ADS)

    Stoian, R.; D'Amico, C.; Bhuyan, M. K.; Cheng, G.

    2016-06-01

    Ultrafast laser photoinscription and laser-based refractive index engineering develop towards a unique way for three-dimensional optical design inside bulk materials for the conception of embedded photonic applications. The specific optical functions for the light guiding elements, notably their single mode characteristics and the accessible spectral domains, depend on the achieved refractive index contrast in the material transparency window and on the characteristic dimensions of the optical modification. We give here an overview of several laser processing options, developed to increase the effective index area and contrast using pulse engineering methods in space and time, and optical design involving focal shaping, tubular concepts, evanescently coupled waveguide arrays, or structured waveguides.

  13. Activation and micropore structure determination of carbon-fiber composite molecular sieves. Topical report, 30 March 1994--14 April 1995

    SciTech Connect

    Jagtoyen, M.; Derbyshire, F.; Kimber, G.; Fei, You Qing

    1995-05-19

    Progress in developing novel, rigid, monolithic adsorbent carbon fiber composites is described. Carbon fiber composites are activated using steam or CO{sub 2}, in order to produce uniform activation through the material and to control the pore structure and adsorptive properties. There is an overall shrinkage during activation, which is directly correlated with burnoff; burnoff above 40% results in fracture. Burnoffs higher than 10% does not produce any benefit for separation of CH{sub 4}-CO{sub 2} mixtures. Five samples of CFCMS have been prepared for testing as molecular sieves; all have relatively narrow pore size distributions with average pore diameters around 6A.

  14. Selective ligands of estrogen receptor β discovered using pharmacophore mapping and structure-based virtual screening

    PubMed Central

    Chen, Lei; Wu, Dang; Bian, Han-ping; Kuang, Guang-lin; Jiang, Jing; Li, Wei-hua; Liu, Gui-xia; Zou, Shi-en; Huang, Jin; Tang, Yun

    2014-01-01

    Aim: To discover novel ligands of estrogen receptor (ER) β using pharmacophore mapping and structure-based screening. Methods: A computer-aided strategy combining pharmacophore mapping and structure-based screening was used to screen the Maybridge and Enamine databases. Yeast two-hybrid (Y2H) assay was used to detect the activity and selectivity of the chosen compounds. The transcriptional activities of the chosen compounds were demonstrated with luciferase reporter assays. The anti-proliferative effects of ER antagonists against MCF-7 and MDA-MB-231 breast cancer cells were examined using MTT assay, and the mechanisms of action were analyzed with flow cytometry analysis and Western blotting. Results: Through in silico screen, 95 compounds were chosen for testing in Y2H assay, which led to 20 potent ligands, including 10 agonists, 8 antagonists and 2 partial agonists with EC50 or IC50 values at μmol/L. Furthermore, 6 agonists exhibited absolute selectivity for ERβ, and 3 agonists showed higher selectivity for ERβ. The agonists 1g and 1h (10, 25, and 50 μmol/L) dose-dependently increased ER transcriptional activities, whereas the antagonists 2a and 2d (10, 25, and 50 μmol/L) caused dose-dependent inhibition on the activities. The antagonists and partial agonists at 100 μmol/L suppressed the proliferation of ERα positive MCF-7 cells and ERβ positive MDA-MB-231 cells, but were more effective against MDA-MB-231 cells. Treatment of MDA-MB-231 cells with antagonists 2a and 2d (25 and 50 μmol/L) dose-dependently increased the population of cells in the S phase. Both 2a and 2d treatment dose-dependently decreased the expression levels of cyclin A and CDK2. Meanwhile, the downregulation of cyclin E was only caused by 2d, while 2a treatment did not cause significant changes in the protein levels of cyclin E. Conclusion: The selective ligands discovered in this study are promising drug candidates to be used as molecular probes to explore the differences between ER

  15. Defect structure and selective swelling of a lamellar diblock copolymer film

    NASA Astrophysics Data System (ADS)

    Fan, Yin; Alexander-Katz, Alfredo; Thomas, Edwin

    2012-02-01

    Previous work in our group introduced a responsive photonic gel made by swelling a lamellar poly(styrene-b-2-vinylpyridine) (PS-P2VP) film in selective solvents. The photonic gels can be used as colorimetric sensors for temperature, pH or solvent composition and the responses are highly tunable. The film's swollen structure can be measured in situ by real-time spectrometry. The study reported in this abstract focuses on the defect structures and swelling kinetics of the block copolymer (BCP) films. Using polymers of the same molecular weight, we made films of the same lamellar periodicity and observed variations in color change during swelling. Cross-sectional transmission electron microscopy (TEM) images showed edge or screw dislocation-type defects. We built a structural model for the defects in the lamellar BCP films and found the defect geometry and density responsible for the swelling behavior. The result suggested that the film's photonic property could be tuned by defect control.

  16. Osteoinduction of porous Ti implants with a channel structure fabricated by selective laser melting.

    PubMed

    Fukuda, A; Takemoto, M; Saito, T; Fujibayashi, S; Neo, M; Pattanayak, Deepak K; Matsushita, T; Sasaki, K; Nishida, N; Kokubo, T; Nakamura, T

    2011-05-01

    Many studies have shown that certain biomaterials with specific porous structures can induce bone formation in non-osseous sites without the need for osteoinductive biomolecules, however, the mechanisms responsible for this phenomenon (intrinsic osteoinduction of biomaterials) remain unclear. In particular, to our knowledge the type of pore structure suitable for osteoinduction has not been reported in detail. In the present study we investigated the effects of interconnective pore size on osteoinductivity and the bone formation processes during osteoinduction. Selective laser melting was employed to fabricate porous Ti implants (diameter 3.3mm, length 15 mm) with a channel structure comprising four longitudinal square channels, representing pores, of different diagonal widths, 500, 600, 900, and 1200 μm (termed p500, p600, p900, and p1200, respectively). These were then subjected to chemical and heat treatments to induce bioactivity. Significant osteoinduction was observed in p500 and p600, with the highest observed osteoinduction occurring at 5mm from the end of the implants. A distance of 5mm probably provides a favorable balance between blood circulation and fluid movement. Thus, the simple architecture of the implants allowed effective investigation of the influence of the interconnective pore size on osteoinduction, as well as the relationship between bone quantity and its location for different pore sizes. PMID:21295166

  17. Use of selected toxicology information resources in assessing relationships between chemical structure and biological activity

    SciTech Connect

    Wassom, J.S.

    1985-09-01

    This paper addresses the subject of the use of the selected toxicology information resources in assessing relationships between chemical structure and specific end points. To assist the researcher in how to access the primary literature of genetic toxicology, teratogenesis, and carcinogenesis, three specific specialized information centers are discussed - Environmental Mutagen Information Center, Environmental Teratology Information Center, and Environmental Carcinogenesis Information Center. Also included are descriptions of information resources that contain evaluated (peer-reviewed) biological research results. The US Environmental Protection Agency Genetic Toxicology Program, the International Agency for Research on Cancer Monographs, and the Toxicology Data Bank are the best sources currently available to obtain peer-reviewed results for compounds tested for genotoxicity, carcinogenicity, and other toxicological end points. The value of published information lies in its use. It has become evident that most information cannot be accepted at face value for interpretation and analysis when subjected to stringent quality evaluation criteria. This deficit can be corrected by rigid editorship and the cognizance of authors. Increased interest in alternative methods to in vivo animal testing will be exemplified by use of short-term bioassays and in structure-activity relationship studies. With respect to this latter area, it must be remembered that mechanically (computer generated) derived data cannot substitute, at least at this stage, for data obtained from actual animal testing. The future of structure-activity relationship studies will rest only in their use as a predictive tool.

  18. Selectively Structural Determination of Cellulose and Hemicellulose in Plant Cell Wall

    NASA Astrophysics Data System (ADS)

    Huang, Shih-Chun; Park, Yong; Cosgrove, Daniel; Maranas, Janna; Janna Maranas Team; Daniel Cosgrove Team

    2013-03-01

    Primary plant cell walls support the plant body, and regulate cell size, and plant growth. It contains several biopolymers that can be categorized into three groups: cellulose, hemicellulose and pectin. To determine the structure of plant cell wall, we use small angle neutron scattering in combination with selective deuteration and contrast matching method. We compare the structure between wild Arabidopsis thaliana and its xyloglucan-deficient mutant. Hemicellulose in both samples forms coil with similar radii of gyration, and weak scattering from the mutant suggests a limited amount of hemicellulose in the xyloglucan-deficient mutant. We observe good amount of hemicellulose coating on cellulose microfibrils only in wild Arabidopsis. The absence of coating in its xyloglucan-deficient mutation suggests the other polysaccharides do not have comparable interaction with cellulose. This highlights the importance of xyloglucan in plant cell wall. At larger scale, the average distance between cellulose fibril is found smaller than reported value, which directly reflects on their smaller matured plant size. U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences, Center for LignoCellulose Structure and Formation

  19. Optimization of chemical structure of Schottky-type selection diode for crossbar resistive memory.

    PubMed

    Kim, Gun Hwan; Lee, Jong Ho; Jeon, Woojin; Song, Seul Ji; Seok, Jun Yeong; Yoon, Jung Ho; Yoon, Kyung Jean; Park, Tae Joo; Hwang, Cheol Seong

    2012-10-24

    The electrical performances of Pt/TiO(2)/Ti/Pt stacked Schottky-type diode (SD) was systematically examined, and this performance is dependent on the chemical structures of the each layer and their interfaces. The Ti layers containing a tolerable amount of oxygen showed metallic electrical conduction characteristics, which was confirmed by sheet resistance measurement with elevating the temperature, transmission line measurement (TLM), and Auger electron spectroscopy (AES) analysis. However, the chemical structure of SD stack and resulting electrical properties were crucially affected by the dissolved oxygen concentration in the Ti layers. The lower oxidation potential of the Ti layer with initially higher oxygen concentration suppressed the oxygen deficiency of the overlying TiO(2) layer induced by consumption of the oxygen from TiO(2) layer. This structure results in the lower reverse current of SDs without significant degradation of forward-state current. Conductive atomic force microscopy (CAFM) analysis showed the current conduction through the local conduction paths in the presented SDs, which guarantees a sufficient forward-current density as a selection device for highly integrated crossbar array resistive memory. PMID:22999222

  20. Use of selected toxicology information resources in assessing relationships between chemical structure and biological activity.

    PubMed Central

    Wassom, J S

    1985-01-01

    This paper addresses the subject of the use of selected toxicology information resources in assessing relationships between chemical structure and specific biological end points. To assist the researcher in how to access the primary literature of genetic toxicology, teratogenesis, and carcinogenesis, three specific specialized information centers are discussed--Environmental Mutagen Information Center, Environmental Teratology Information Center, and Environmental Carcinogenesis Information Center. Also included are descriptions of information resources that contain evaluated (peer-reviewed) biological research results. The U.S. Environmental Protection Agency Genetic Toxicology Program, the International Agency for Research on Cancer Monographs, and the Toxicology Data Bank are the best sources currently available to obtain peer-reviewed results for compounds tested for genotoxicity, carcinogenicity, and other toxicological end points. The value of published information lies in its use. It has become evident that most information cannot be accepted at face value for interpretation and analysis when subjected to stringent quality evaluation criteria. This deficit can be corrected by rigid editorship and the cognizance of authors. Increased interest in alternative methods to in vivo animal testing will be exemplified by use of short-term bioassays and in structure-activity relationship studies. With respect to this latter area, it must be remembered that mechanically (computer generated) derived data cannot substitute, at least at this stage, for data obtained from actual animal testing. The future of structure-activity relationship studies will rest only in their use as a predictive tool. PMID:4065070

  1. Habitat selection by breeding waterbirds at ponds with size-structured fish populations

    NASA Astrophysics Data System (ADS)

    Kloskowski, Janusz; Nieoczym, Marek; Polak, Marcin; Pitucha, Piotr

    2010-07-01

    Fish may significantly affect habitat use by birds, either as their prey or as competitors. Fish communities are often distinctly size-structured, but the consequences for waterbird assemblages remain poorly understood. We examined the effects of size structure of common carp ( Cyprinus carpio) cohorts together with other biotic and abiotic pond characteristics on the distribution of breeding waterbirds in a seminatural system of monocultured ponds, where three fish age classes were separately stocked. Fish age corresponded to a distinct fish size gradient. Fish age and total biomass, macroinvertebrate and amphibian abundance, and emergent vegetation best explained the differences in bird density between ponds. Abundance of animal prey other than fish (aquatic macroinvertebrates and larval amphibians) decreased with increasing carp age in the ponds. Densities of ducks and smaller grebes were strongly negatively associated with fish age/size gradient. The largest of the grebes, the piscivorous great crested grebe ( Podiceps cristatus), was the only species that preferred ponds with medium-sized fish and was positively associated with total fish biomass. Habitat selection by bitterns and most rallids was instead strongly influenced by the relative amount of emergent vegetation cover in the ponds. Our results show that fish size structure may be an important cue for breeding habitat choice and a factor affording an opportunity for niche diversification in avian communities.

  2. Structural modulation of nanowire interfaces grown over selectively disrupted single crystal surfaces

    NASA Astrophysics Data System (ADS)

    Garratt, E.; Nikoobakht, B.

    2015-08-01

    Recent breakthroughs in deterministic approaches to the fabrication of nanowire arrays have demonstrated the possibility of fabricating such networks using low-cost scalable methods. In this regard, we have developed a scalable growth platform for lateral fabrication of nanocrystals with high precision utilizing lattice match and symmetry. Using this planar architecture, a number of homo- and heterostructures have been demonstrated including ZnO nanowires grown over GaN. The latter combination produces horizontal, epitaxially formed crystals aligned in the plane of the substrate containing a very low number of intrinsic defects. We use such ordered structures as model systems in the interests of gauging the interfacial structural dynamics in relation to external stimuli. Nanosecond pulses of focused ion beams are used to slightly modify the substrate surface and selectively form lattice disorders in the path of nanowire growth to examine the nanocrystal, namely: its directionality and lattice defects. High resolution electron microscopies are used to reveal some interesting structural effects; for instance, a minimum threshold of surface defects that can divert nanowires. We also discuss data indicating formation of surface strains and show their mitigation during the growth process.

  3. Relationships between middle school students' science concept structure interrelatedness competence and selected cognitive and affective tendencies

    NASA Astrophysics Data System (ADS)

    Harty, Harold; Hamrick, Linda; Samuel, K. V.

    An investigation was conducted to determine the relationships between Concept Structure Interrelatedness Competence (ConSIC) and 10 predictor variables of which 6 comprised a cognitive cluster and 4 made up an affective set. Data were collected from 105 middle school students and treated by way of stepwise multiple regression, linear multiple regression, and product-moment correlation techniques. The findings revealed that previous experience with concept structure interrelatedness and verbal scholastic aptitude accounted for the greatest amount of variance in predicting ConSIC. Significant positive correlations were also found between ConSIC and science achievement-course grades, scholastic aptitude-verbal, scholastic aptitude-quantitative, previous experience with concept structure interrelatedness, and self-concept of science ability. Positive significant correlations also surfaced among all of the affective variables (attitudes toward science, interest in science, science curiosity, and self-concept of science ability). Implications have been discussed in terms of classroom science teaching, science content analysis, curriculum design, and content selection.

  4. [Topical felbinac in therapy of athletic injuries].

    PubMed

    Leeb, B

    1994-02-28

    In the treatment of acute soft tissue injuries, topical nonsteroidal anti-inflammatory drugs are both highly effective and well tolerated. Target is a monopreparation that meets the demands made on a modern topical agent. The active substance, felbinac, readily, penetrates into the tissue affected and accumulates locally, selectively inhibiting inflammation and alleviating pain. This synoptic report on the clinical trials confirm the significant clinical superiority of felbinac over placebo. As compared with piroxicam, felbinac, is more successful in eliminating symptoms. The rapid alleviation of pain by the topical felbinac results in an improvement in the restriction of mobility and rapid restitution of function. The cooling, nongreasy gel base further favors the high level of acceptance of this well-tolerated preparation. PMID:8163257

  5. Population Structure of a Widespread Species under Balancing Selection: The Case of Arbutus unedo L.

    PubMed Central

    Santiso, Xabier; Lopez, Lua; Retuerto, Rubén; Barreiro, Rodolfo

    2016-01-01

    Arbutus unedo L. is an evergreen shrub with a circum-Mediterranean distribution that also reaches the Eurosiberian region in northern Iberia, Atlantic France, and a disjunct population in southern Ireland. Due to the variety of climatic conditions across its distribution range, the populations of A. unedo were expected to display local adaptation. Conversely, common garden experiments revealed that diverse genotypes from a range of provenances produce similar phenotypes through adaptive plasticity, suggesting the action of stabilizing selection across its climatically heterogeneous range. Nonetheless, since a uniform response might also result from extensive gene flow, we have inferred the population structure of A. unedo and assessed whether its extended and largely one-dimensional range influences gene flow with the help of AFLP genotypes for 491 individuals from 19 populations covering the whole range of the species. As we had anticipated, gene flow is restricted in A. unedo, providing further support to the hypothesis that stabilizing selection is the most likely explanation for the homogeneous phenotypes along the range. The Euro-Siberian populations were not particularly isolated from the Mediterranean. Instead, there was a distinct genetic divide between the populations around the Mediterranean Sea and those sampled along Atlantic coasts from northern Africa up to Ireland. This genetic structure suggests the action of historic rather than biogeographic factors as it seems consistent with a scenario of independent glacial refugia in the Atlantic and Mediterranean portions of the range of A. unedo. Genetic exchange was likewise restricted within each set of populations. Nevertheless, isolation-by-distance (IBD) was stronger, and FST increased faster with distance, along the Atlantic, suggesting that gene flow might be larger among Mediterranean populations. Genetic diversity was significantly lower in NW Iberia and Ireland than in other populations whereas

  6. Selection bias in species distribution models: An econometric approach on forest trees based on structural modeling

    NASA Astrophysics Data System (ADS)

    Martin-StPaul, N. K.; Ay, J. S.; Guillemot, J.; Doyen, L.; Leadley, P.

    2014-12-01

    Species distribution models (SDMs) are widely used to study and predict the outcome of global changes on species. In human dominated ecosystems the presence of a given species is the result of both its ecological suitability and human footprint on nature such as land use choices. Land use choices may thus be responsible for a selection bias in the presence/absence data used in SDM calibration. We present a structural modelling approach (i.e. based on structural equation modelling) that accounts for this selection bias. The new structural species distribution model (SSDM) estimates simultaneously land use choices and species responses to bioclimatic variables. A land use equation based on an econometric model of landowner choices was joined to an equation of species response to bioclimatic variables. SSDM allows the residuals of both equations to be dependent, taking into account the possibility of shared omitted variables and measurement errors. We provide a general description of the statistical theory and a set of applications on forest trees over France using databases of climate and forest inventory at different spatial resolution (from 2km to 8km). We also compared the outputs of the SSDM with outputs of a classical SDM (i.e. Biomod ensemble modelling) in terms of bioclimatic response curves and potential distributions under current climate and climate change scenarios. The shapes of the bioclimatic response curves and the modelled species distribution maps differed markedly between SSDM and classical SDMs, with contrasted patterns according to species and spatial resolutions. The magnitude and directions of these differences were dependent on the correlations between the errors from both equations and were highest for higher spatial resolutions. A first conclusion is that the use of classical SDMs can potentially lead to strong miss-estimation of the actual and future probability of presence modelled. Beyond this selection bias, the SSDM we propose represents

  7. Current Topics in Epilepsy Surgery.

    PubMed

    Usui, Naotaka

    2016-05-15

    This article reviews the current topics in the field of epilepsy surgery. Each type of epilepsy is associated with a different set of questions and goals. In mesial temporal lobe epilepsy (MTLE) with hippocampal sclerosis (HS), postoperative seizure outcome is satisfactory. A recent meta-analysis revealed superior seizure outcome after anterior temporal lobectomy compared with selective amygdalohippocampectomy; in terms of cognitive outcome; however, amygdalohippocampectomy may be beneficial. In temporal lobe epilepsy with normal magnetic resonance imaging (MRI), postoperative seizure outcome is not as favorable as it is in MTLE with HS; further improvement of seizure outcome in these cases is necessary. Focal cortical dysplasia is the most common substrate in intractable neocortical epilepsy, especially in children, as well as in MRI-invisible neocortical epilepsy. Postoperative seizure-free outcome is approximately 60-70%; further diagnostic and therapeutic improvement is required. Regarding diagnostic methodology, an important topic currently under discussion is wideband electroencephalogram (EEG) analysis. Although high-frequency oscillations and ictal direct current shifts are considered important markers of epileptogenic zones, the clinical significance of these findings should be clarified further. Regarding alternatives to surgery, neuromodulation therapy can be an option for patients who are not amenable to resective surgery. In addition to vagus nerve stimulation, intracranial stimulation such as responsive neurostimulation or anterior thalamic stimulation is reported to have a modest seizure suppression effect. Postoperative management such as rehabilitation and antiepileptic drug (AED) management is important. It has been reported that postoperative rehabilitation improves postoperative employment status. Pre- and post-operative comprehensive care is mandatory for postoperative improvement of quality of life. PMID:26984452

  8. Current Topics in Epilepsy Surgery

    PubMed Central

    USUI, Naotaka

    2016-01-01

    This article reviews the current topics in the field of epilepsy surgery. Each type of epilepsy is associated with a different set of questions and goals. In mesial temporal lobe epilepsy (MTLE) with hippocampal sclerosis (HS), postoperative seizure outcome is satisfactory. A recent meta-analysis revealed superior seizure outcome after anterior temporal lobectomy compared with selective amygdalohippocampectomy; in terms of cognitive outcome; however, amygdalohippocampectomy may be beneficial. In temporal lobe epilepsy with normal magnetic resonance imaging (MRI), postoperative seizure outcome is not as favorable as it is in MTLE with HS; further improvement of seizure outcome in these cases is necessary. Focal cortical dysplasia is the most common substrate in intractable neocortical epilepsy, especially in children, as well as in MRI-invisible neocortical epilepsy. Postoperative seizure-free outcome is approximately 60–70%; further diagnostic and therapeutic improvement is required. Regarding diagnostic methodology, an important topic currently under discussion is wideband electroencephalogram (EEG) analysis. Although high-frequency oscillations and ictal direct current shifts are considered important markers of epileptogenic zones, the clinical significance of these findings should be clarified further. Regarding alternatives to surgery, neuromodulation therapy can be an option for patients who are not amenable to resective surgery. In addition to vagus nerve stimulation, intracranial stimulation such as responsive neurostimulation or anterior thalamic stimulation is reported to have a modest seizure suppression effect. Postoperative management such as rehabilitation and antiepileptic drug (AED) management is important. It has been reported that postoperative rehabilitation improves postoperative employment status. Pre- and post-operative comprehensive care is mandatory for postoperative improvement of quality of life. PMID:26984452

  9. Genetic structure in cultivated grapevines is linked to geography and human selection

    PubMed Central

    2013-01-01

    Background Grapevine (Vitis vinifera subsp. vinifera) is one of the most important and ancient horticultural plants in the world. Domesticated about 8–10,000 years ago in the Eurasian region, grapevine evolved from its wild relative (V. vinifera subsp. sylvestris) into very diverse and heterozygous cultivated forms. In this work we study grapevine genetic structure in a large sample of cultivated varieties, to interpret the wide diversity at morphological and molecular levels and link it to cultivars utilization, putative geographic origin and historical events. Results We analyzed the genetic structure of cultivated grapevine using a dataset of 2,096 multi-locus genotypes defined by 20 microsatellite markers. We used the Bayesian approach implemented in the STRUCTURE program and a hierarchical clustering procedure based on Ward’s method to assign individuals to sub-groups. The analysis revealed three main genetic groups defined by human use and geographic origin: a) wine cultivars from western regions, b) wine cultivars from the Balkans and East Europe, and c) a group mainly composed of table grape cultivars from Eastern Mediterranean, Caucasus, Middle and Far East countries. A second structure level revealed two additional groups, a geographic group from the Iberian Peninsula and Maghreb, and a group comprising table grapes of recent origins from Italy and Central Europe. A large number of admixed genotypes were also identified. Structure clusters regrouped together a large proportion of family-related genotypes. In addition, Ward’s method revealed a third level of structure, corresponding either to limited geographic areas, to particular grape use or to family groups created through artificial selection and breeding. Conclusions This study provides evidence that the cultivated compartment of Vitis vinifera L. is genetically structured. Genetic relatedness of cultivars has been shaped mostly by human uses, in combination with a geographical effect. The

  10. [Classical topical therapy of psoriasis].

    PubMed

    Gerdes, S; Mrowietz, U

    2006-08-01

    In most cases mild to moderate forms of psoriasis can be treated with topical therapy. In addition, topical agents are also routinely combined with UV or systemic therapy to treat severe forms of psoriasis. A variety of standard products are available. The oldest topical treatment is anthralin. Since 1952 the development of topical corticosteroids has revolutionized not only dermatological treatment in general but the treatment of psoriasis in particular. Through the continuous development of these compounds, a better risk-benefit profile has been achieved. Corticosteroids are the most frequently employed topical agent for psoriasis treatment worldwide. PMID:16841204

  11. An evolutionary theory of large-scale human warfare: Group-structured cultural selection.

    PubMed

    Zefferman, Matthew R; Mathew, Sarah

    2015-01-01

    When humans wage war, it is not unusual for battlefields to be strewn with dead warriors. These warriors typically were men in their reproductive prime who, had they not died in battle, might have gone on to father more children. Typically, they are also genetically unrelated to one another. We know of no other animal species in which reproductively capable, genetically unrelated individuals risk their lives in this manner. Because the immense private costs borne by individual warriors create benefits that are shared widely by others in their group, warfare is a stark evolutionary puzzle that is difficult to explain. Although several scholars have posited models of the evolution of human warfare, these models do not adequately explain how humans solve the problem of collective action in warfare at the evolutionarily novel scale of hundreds of genetically unrelated individuals. We propose that group-structured cultural selection explains this phenomenon. PMID:25914359

  12. Independent seismic evaluation of the Diablo Canyon Unit 1 containment annulus structure and selected piping systems

    SciTech Connect

    Philippacopoulos, A.J.; Reich, M.; Bezler, P.; Miller, C.; Wang, Y.K.; Subudhi, M.; Shteyngart, S.; Brown, P.

    1982-08-01

    An independent review and development of the vertical floor spectra for the Unit 1 containment annulus structure of the Diablo Canyon Power Plant was carried out using a detailed three-dimensional model. The developed floor spectra were then utilized for confirmatory evaluations of two selected piping systems. The latter were evaluated by the envelope response spectrum method, and by the independent support motion response spectrum method. ASME class 2 evaluations of the two systems were also performed. Finally, a confirmatory evaluation was carried out for the model utilized by URS/Blume for the development of the vertical floor response spectra. Sections 1.1 and 1.2 of the report summarize the work scope and the results of the study. Details pertaining to the specific areas of the work are given in sections 2 to 8.

  13. Structural Insights into Selective Histone H3 Recognition by the Human Polybromo bromodomain 2

    SciTech Connect

    Charlop-Powers, Z.; Zeng, L; Zhang, Q; Zhou, M

    2010-01-01

    The Polybromo (PB) protein functions as a key component of the human PBAF chromatin remodeling complex in regulation of gene transcription. PB is made up of modular domains including six bromodomains that are known as acetyl-lysine binding domains. However, histone-binding specificity of the bromodomains of PB has remained elusive. In this study, we report biochemical characterization of all six PB bromodomains' binding to a suite of lysine-acetylated peptides derived from known acetylation sites on human core histones. We demonstrate that bromodomain 2 of PB preferentially recognizes acetylated lysine 14 of histone H3 (H3K14ac), a post-translational mark known for gene transcriptional activation. We further describe the molecular basis of the selective H3K14ac recognition of bromodomain 2 by solving the protein structures in both the free and bound forms using X-ray crystallography and NMR, respectively.

  14. Structural isomers of C2N(+) - A selected-ion flow tube study

    NASA Technical Reports Server (NTRS)

    Knight, J. S.; Petrie, S. A. H.; Freeman, C. G.; Mcewan, M. J.; Mclean, A. D.

    1988-01-01

    Reactivities of the structural isomers CCN(+) and CNC(+) were examined in a selected-ion flow tube at 300 + or - 5 K. The less reactive CNC(+) isomer was identified as the product of the reactions of C(+) + HCN and C(+) + C2N2; in these reactions only CNC(+) can be produced because of energy constraints. Rate coefficients and branching ratios are reported for the reactions of each isomer with H2, CH4, NH3, H2O, C2H2, HCN, N2, O2, N2O, and CO2. Ab initio calculations are presented for CCN(+) and CNC(+); a saddle point for the reaction CCN(+) yielding CNC(+) is calculated to be 195 kJ/mol above CNC(+). The results provide evidence that the more reactive CCN(+) isomer is unlikely to be present in measurable densities in interstellar clouds.

  15. Selective fluorescence functionalization of dye-doped polymerized structures fabricated by direct laser writing (DLW) lithography

    NASA Astrophysics Data System (ADS)

    de Miguel, Gustavo; Vicidomini, Giuseppe; Duocastella, Martí; Diaspro, Alberto

    2015-11-01

    The continuous development of the vast arsenal of fabrication techniques is a pivotal factor in the breakthrough of nanotechnology. Although the broad interest is generally focused on the reduction of the dimensions of the fabricated structures, localized functionalization of the nanomaterials emerges as a key factor closely linked to their potential applications. In particular, fabrication of spatially selective fluorescence nanostructures is highly demanded in nanophotonics, as for example in three-dimensional (3D) optical data storage (ODS), where massive storage capacity and fast writing-reading processes are promised. We have developed an innovative method to control the location and intensity of the fluorescence signal in dye-doped photopolymerized structures fabricated with Direct Laser Writing (DLW) lithography. Well-defined fluorescent pixels (area = 0.24 μm2) were written inside a polymer matrix with the help of a femtosecond pulsed laser (multiphoton absorption) via a thermally-induced di-aggregation of a fluorescent dye. Moreover, we have accomplished a fine control of the fluorescence intensity which can increase the storage capacity of ODS systems fabricated with this approach.The continuous development of the vast arsenal of fabrication techniques is a pivotal factor in the breakthrough of nanotechnology. Although the broad interest is generally focused on the reduction of the dimensions of the fabricated structures, localized functionalization of the nanomaterials emerges as a key factor closely linked to their potential applications. In particular, fabrication of spatially selective fluorescence nanostructures is highly demanded in nanophotonics, as for example in three-dimensional (3D) optical data storage (ODS), where massive storage capacity and fast writing-reading processes are promised. We have developed an innovative method to control the location and intensity of the fluorescence signal in dye-doped photopolymerized structures fabricated

  16. Selection of hydrologic modeling approaches for climate change assessment: A comparison of model scale and structures

    NASA Astrophysics Data System (ADS)

    Surfleet, Christopher G.; Tullos, Desirèe; Chang, Heejun; Jung, Il-Won

    2012-09-01

    SummaryA wide variety of approaches to hydrologic (rainfall-runoff) modeling of river basins confounds our ability to select, develop, and interpret models, particularly in the evaluation of prediction uncertainty associated with climate change assessment. To inform the model selection process, we characterized and compared three structurally-distinct approaches and spatial scales of parameterization to modeling catchment hydrology: a large-scale approach (using the VIC model; 671,000 km2 area), a basin-scale approach (using the PRMS model; 29,700 km2 area), and a site-specific approach (the GSFLOW model; 4700 km2 area) forced by the same future climate estimates. For each approach, we present measures of fit to historic observations and predictions of future response, as well as estimates of model parameter uncertainty, when available. While the site-specific approach generally had the best fit to historic measurements, the performance of the model approaches varied. The site-specific approach generated the best fit at unregulated sites, the large scale approach performed best just downstream of flood control projects, and model performance varied at the farthest downstream sites where streamflow regulation is mitigated to some extent by unregulated tributaries and water diversions. These results illustrate how selection of a modeling approach and interpretation of climate change projections require (a) appropriate parameterization of the models for climate and hydrologic processes governing runoff generation in the area under study, (b) understanding and justifying the assumptions and limitations of the model, and (c) estimates of uncertainty associated with the modeling approach.

  17. Structural basis of femtomolar inhibitors for acetylcholinesterase subtype selectivity: insights from computational simulations.

    PubMed

    Zhu, Xiao-Lei; Yu, Ning-Xi; Hao, Ge-Fei; Yang, Wen-Chao; Yang, Guang-Fu

    2013-04-01

    Acetylcholinesterase (AChE) is a key enzyme of the cholinergic nervous system. More than one gene encodes the synaptic AChE target. As the most potent known AChE inhibitor, the syn1-TZ2PA6 isomer was recently shown to have higher affinity as a reversible organic inhibitor of acetylcholinesterase1 (AChE1) than the anti1-TZ2PA6 isomer. Opposite selectivity has been shown for acetylcholinesterase2 (AChE2). In an attempt to understand the selectivity of the syn1-TZ2PA6 and anti1-TZ2PA6 isomers for AChE1 and AChE2, six molecular dynamics (MD) simulations were carried out with mouse AChE (mAChE, type of AChE1), Torpedo californica AChE (TcAChE, type of AChE1), and Drosophila melanogaster AChE (DmAChE, type of AChE2) bound with syn1-TZ2PA6 and anti1-TZ2PA6 isomers. Within the structure of the inhibitor, the 3,8-diamino-6-phenylphenanthridinium subunit and 9-amino-1,2,3,4-tetrahydroacridine subunit, via π-π interactions, made more favorable contributions to syn1-TZ2PA6 or anti1-TZ2PA6 isomer binding in the mAChE/TcAChE enzyme than the 1,2,3-triazole subunit. Compared to AChE1, the triazole subunit had increased binding energy with AChE2 due to a greater negative charge in the active site. The binding free energy calculated using the MM/PBSA method suggests that selectivity between AChE1 and AChE2 is mainly attributed to decreased binding affinity for the inhibitor. PMID:23500627

  18. Mechanistic Insights into the Structure-Dependent Selectivity of Catalytic Furfural Conversion on Platinum Catalysts

    SciTech Connect

    Cai, Qiuxia; Wang, Jianguo; Wang, Yang-Gang; Mei, Donghai

    2015-11-01

    The effects of structure and size on the selectivity of catalytic furfural conversion over supported Pt catalysts in the presence of hydrogen have been studied using first principles density functional theory (DFT) calculations and microkinetic modeling. Four Pt model systems, i.e., periodic Pt(111), Pt(211) surfaces, as well as small nanoclusters (Pt13 and Pt55) are chosen to represent the terrace, step, and corner sites of Pt nanoparticles. Our DFT results show that the reaction routes for furfural hydrogenation and decarbonylation are strongly dependent on the type of reactive sites, which lead to the different selectivity. On the basis of the size-dependent site distribution rule, we correlate the site distributions as a function of the Pt particle size. Our microkinetic results indicate the critical particle size that controls the furfural selectivity is about 1.0 nm, which is in good agreement with the reported experimental value under reaction conditions. This work was supported by National Basic Research Program of China (973 Program) (2013CB733501) and the National Natural Science Foundation of China (NSFC-21306169, 21176221, 21136001, 21101137 and 91334103). This work was also partially supported by the US Department of Energy (DOE), the Office of Basic Energy Sciences, Division of Chemical Sciences, Geosciences & Biosciences. Pacific Northwest National Laboratory (PNNL) is a multiprogram national laboratory operated for DOE by Battelle. Computing time was granted by the grand challenge of computational catalysis of the William R. Wiley Environmental Molecular Sciences Laboratory (EMSL). EMSL is a national scientific user facility located at Pacific Northwest National Laboratory (PNNL) and sponsored by DOE’s Office of Biological and Environmental Research.

  19. Structural insight into mechanism and diverse substrate selection strategy of L-ribulokinase

    SciTech Connect

    Agarwal R.; Swaminathan S.; Burley, S. K.

    2012-01-01

    The araBAD operon encodes three different enzymes required for catabolism of L-arabinose, which is one of the most abundant monosaccharides in nature. L-ribulokinase, encoded by the araB gene, catalyzes conversion of L-ribulose to L-ribulose-5-phosphate, the second step in the catabolic pathway. Unlike other kinases, ribulokinase exhibits diversity in substrate selectivity and catalyzes phosphorylation of all four 2-ketopentose sugars with comparable k{sub cat} values. To understand ribulokinase recognition and phosphorylation of a diverse set of substrates, we have determined the X-ray structure of ribulokinase from Bacillus halodurans bound to L-ribulose and investigated its substrate and ATP co-factor binding properties. The polypeptide chain is folded into two domains, one small and the other large, with a deep cleft in between. By analogy with related sugar kinases, we identified {sup 447}{und GG}LPQ{und K}{sup 452} as the ATP-binding motif within the smaller domain. L-ribulose binds in the cleft between the two domains via hydrogen bonds with the side chains of highly conserved Trp126, Lys208, Asp274, and Glu329 and the main chain nitrogen of Ala96. The interaction of L-ribulokinase with L-ribulose reveals versatile structural features that help explain recognition of various 2-ketopentose substrates and competitive inhibition by L-erythrulose. Comparison of our structure to that of the structures of other sugar kinases revealed conformational variations that suggest domain-domain closure movements are responsible for establishing the observed active site environment.

  20. Structural and Functional Evidence Indicates Selective Oxygen Signaling in Caldanaerobacter subterraneus H-NOX.

    PubMed

    Hespen, Charles W; Bruegger, Joel J; Phillips-Piro, Christine M; Marletta, Michael A

    2016-08-19

    Acute and specific sensing of diatomic gas molecules is an essential facet of biological signaling. Heme nitric oxide/oxygen binding (H-NOX) proteins are a family of gas sensors found in diverse classes of bacteria and eukaryotes. The most commonly characterized bacterial H-NOX domains are from facultative anaerobes and are activated through a conformational change caused by formation of a 5-coordinate Fe(II)-NO complex. Members of this H-NOX subfamily do not bind O2 and therefore can selectively ligate NO even under aerobic conditions. In contrast, H-NOX domains encoded by obligate anaerobes do form stable 6-coordinate Fe(II)-O2 complexes by utilizing a conserved H-bonding network in the ligand-binding pocket. The biological function of O2-binding H-NOX domains has not been characterized. In this work, the crystal structures of an O2-binding H-NOX domain from the thermophilic obligate anaerobe Caldanaerobacter subterraneus (Cs H-NOX) in the Fe(II)-NO, Fe(II)-CO, and Fe(II)-unliganded states are reported. The Fe(II)-unliganded structure displays a conformational shift distinct from the NO-, CO-, and previously reported O2-coordinated structures. In orthogonal signaling assays using Cs H-NOX and the H-NOX signaling effector histidine kinase from Vibrio cholerae (Vc HnoK), Cs H-NOX regulates Vc HnoK in an O2-dependent manner and requires the H-bonding network to distinguish O2 from other ligands. The crystal structures of Fe(II) unliganded and NO- and CO-bound Cs H-NOX combined with functional assays herein provide the first evidence that H-NOX proteins from obligate anaerobes can serve as O2 sensors. PMID:27328180

  1. Topics in physico-chemical hydrodynamics

    SciTech Connect

    Sivashinsky, G.

    1989-01-01

    This paper discusses the following topics: theory of turbulent flame speed; flame extinction by periodic flow-field; influence of swirl on the structure and extinction of premixed flames; propagation and extinction of nonsteady spherical flame fronts; geometrically invariant formulation of intrinsic dynamics of premixed flames; nonlinear dynamics of oscillatory regime of premixed combustion; and pattern formation in premixed flames. (LSP)

  2. Exploiting orientation-selective DEER: determining molecular structure in systems containing Cu(ii) centres.

    PubMed

    Bowen, Alice M; Jones, Michael W; Lovett, Janet E; Gaule, Thembanikosi G; McPherson, Michael J; Dilworth, Jonathan R; Timmel, Christiane R; Harmer, Jeffrey R

    2016-02-17

    Orientation-selective DEER (Double Electron-Electron Resonance) measurements were conducted on a series of rigid and flexible molecules containing Cu(ii) ions. A system with two rigidly held Cu(ii) ions was afforded by the protein homo-dimer of copper amine oxidase from Arthrobacter globiformis. This system provided experimental DEER data between two Cu(ii) ions with a well-defined distance and relative orientation to assess the accuracy of the methodology. Evaluation of orientation-selective DEER (os DEER) on systems with limited flexibility was probed using a series of porphyrin-based Cu(ii)-nitroxide and Cu(ii)-Cu(ii) model systems of well-defined lengths synthesized for this project. Density functional theory was employed to generate molecular models of the conformers for each porphyrin-based Cu(ii) dimer studied. Excellent agreement was found between DEER traces simulated using these computed conformers and the experimental data. The performance of different parameterised structural models in simulating the experimental DEER data was also investigated. The results of this analysis demonstrate the degree to which the DEER data define the relative orientation of the two Cu(ii) ions and highlight the need to choose a parameterised model that captures the essential features of the flexibility (rotational freedom) of the system being studied. PMID:26837391

  3. Applicants regard structured interviews as a fair method of selection: an audit of candidates

    PubMed Central

    Westwood, Mark A; Nunn, Laurence M; Redpath, Calum; Mills, Peter; Crake, Tom

    2008-01-01

    Summary Objective To discover whether applicants regard structures interviews as a fair method of selection for jobs. Design Audit study of short-listed candidates for postgraduate specialty training programmes in the London Deanery. Setting Postgraduate applications for the London Deanery. Main outcome measures Satisfaction or otherwise with the application and selection process for postgraduate specialty training programmes amongst short-listed candidates in the London Deanery. Questions were asked under five categories: the applicant, the advertisement, the application form, the short-listing process, and the interview. Results 89 of 118 forms were completed and analysed. Candidates thought the advertisement was clear on who to contact (97%), when short-listed candidates would be notified of their interview (66%) and when interviews would occur (93%). The design of the application form and the short-listing process both scored a median of 1 or 2 (strongly agree or agree) on all points. The interview process itself also scored well, with most candidates scoring broadly positively. Conclusions As in the previous study, the overall response was broadly a positive one from the candidates' perspective, with the majority of candidates finding the system fair and objective. PMID:18463281

  4. Structural and taxonomic components of habitat selection in the neotropical folivore Lamponius portoricensis (Phasmetodea: Phasmatidae)

    SciTech Connect

    Willig, M.R.; Sandlin, E.A. Univ. of Arizona, Tucson ); Gannon, M.R. )

    1993-06-01

    Lamponius portoricensis Rhen is a folivorous neotropical walkingstick that is a common light-gap inhabitant of the tabonuco forest in Puerto Rico. Little is known concerning the spatial distribution of this phasmatid or the manner in which it selects habitats. Based on multiple regression analysis of a suite of taxonomic and structural characteristics of understory flora, we determined that the density of walkingsticks was associated with patches that exhibit high apparency values for Piper treleaseanum Britton Wilson and Symplocos martinicensis Jacq., and low apparency values for Dryopteris deltoidea (Sw.) Kuntze. The total development of the understory regardless of taxonomic composition at 76 cm (2.5 ft) and 107 cm (3.5 ft) also contributes to high walkingstick density, based on correlative analyses. Moreover, nonparametric analysis suggests that L. portoricensis disproportionately occurs on P. treleaseanum (approximately twice as often as expected based on plant apparency). Despite these associations, only a third of the variation in walkingstick density is accounted for by this suite of floral characteristics. The low vagility of L. portoricensis may result in its having incomplete information about the abundance and distribution of forage plants, whereas patch-dynamic processes involving changes in quality of forage can confound the significance of apparency alone in predicting density. The production of aromatic attractants by Piper may act as the proximate cue affecting patch selection.

  5. Selective Autooxidation of Ethanol over Titania-Supported Molybdenum Oxide Catalysts: Structure and Reactivity

    PubMed Central

    Caro, Carlos; Thirunavukkarasu, K; Anilkumar, M; Shiju, N R; Rothenberg, Gadi

    2012-01-01

    We study the selective catalytic oxidation of ethanol with air as a sustainable alternative route to acetaldehyde. The reaction is catalysed by molybdenum oxide supported on titania, in a flow reactor under ambient pressure. High selectivity to acetaldehyde (70%–89%, depending on the Mo loading) is obtained at 150 °C. Subsequently, we investigate the structure/performance relationship for various molybdenum oxide species using a combination of techniques including diffuse reflectance UV-visible, infrared, X-ray photoelectron spectroscopies, X-ray diffraction and temperature programmed reduction. As their surface density increases, the monomeric molybdenum oxide species undergo two-dimensional and three-dimensional oligomerisation. This results in polymolybdates and molybdenum oxide crystallites. Importantly, the ethanol oxidation rate depends not only on the overall molybdenum loading and dispersion, but also on the type of molybdenum oxide species prevalent at each surface density and on the domain size. As the molybdenum oxide oligomerisation increases, electron delocalisation becomes easier. This lowers the absorption edge energy and increases the reaction rate. PMID:23396482

  6. Structural insights into HDAC6 tubulin deacetylation and its selective inhibition.

    PubMed

    Miyake, Yasuyuki; Keusch, Jeremy J; Wang, Longlong; Saito, Makoto; Hess, Daniel; Wang, Xiaoning; Melancon, Bruce J; Helquist, Paul; Gut, Heinz; Matthias, Patrick

    2016-09-01

    We report crystal structures of zebrafish histone deacetylase 6 (HDAC6) catalytic domains in tandem or as single domains in complex with the (R) and (S) enantiomers of trichostatin A (TSA) or with the HDAC6-specific inhibitor nexturastat A. The tandem domains formed, together with the inter-domain linker, an ellipsoid-shaped complex with pseudo-twofold symmetry. We identified important active site differences between both catalytic domains and revealed the binding mode of HDAC6 selective inhibitors. HDAC inhibition assays with (R)- and (S)-TSA showed that (R)-TSA was a broad-range inhibitor, whereas (S)-TSA had moderate selectivity for HDAC6. We identified a uniquely positioned α-helix and a flexible tryptophan residue in the loop joining α-helices H20 to H21 as critical for deacetylation of the physiologic substrate tubulin. Using single-molecule measurements and biochemical assays we demonstrated that HDAC6 catalytic domain 2 deacetylated α-tubulin lysine 40 in the lumen of microtubules, but that its preferred substrate was unpolymerized tubulin. PMID:27454931

  7. Locus assignment of alpha-globin structural mutations by hybrid-selected translation.

    PubMed Central

    Liebhaber, S A; Cash, F E

    1985-01-01

    The two human alpha-globin genes, alpha 1 and alpha 2 located 3.4 kilobases apart on chromosome 16, encode identical alpha-globin proteins. A mutation in either gene could result in a structural hemoglobinopathy. It has only recently become possible to assign an alpha-chain mutant to one of these two loci by using recombinant DNA technology. While definitive, this approach has necessitated the cloning and sequencing of the specific gene in question. We present an alternative approach which results in rapid and definitive assignment of an alpha-globin mutation to its encoding genetic locus. This approach uses the technique of hybrid-selected translation. Reticulocyte RNA from individuals with alpha-globin mutations can be fractionated into beta-, alpha 9 (total)-, alpha 1-, and alpha 2-globin mRNA by selective hybridization of each mRNA species to its respective complementary DNA (cDNA) immobilized on nitrocellulose paper. Each mRNA purified in this way can be translated in vitro, and the mRNA species (and hence gene locus) encoding the globin mutant can then be directly identified by gel analysis of the radiolabeled translation products. This procedure can be used to identify globin mutants as alpha or beta and to localize alpha-globin mutants to the alpha 1 or alpha 2 gene. We have used this technique to localize the two alpha-globin mutants, alpha 125Pro (Hb Quong Sze) and alpha 47HIS (Hb Hasharon), to the alpha 2 locus. This approach could potentially be expanded to serve as an alternative to peptide analysis for the initial characterization of all globin structural mutants. Images PMID:2981252

  8. Topic modeling for cluster analysis of large biological and medical datasets

    PubMed Central

    2014-01-01

    Background The big data moniker is nowhere better deserved than to describe the ever-increasing prodigiousness and complexity of biological and medical datasets. New methods are needed to generate and test hypotheses, foster biological interpretation, and build validated predictors. Although multivariate techniques such as cluster analysis may allow researchers to identify groups, or clusters, of related variables, the accuracies and effectiveness of traditional clustering methods diminish for large and hyper dimensional datasets. Topic modeling is an active research field in machine learning and has been mainly used as an analytical tool to structure large textual corpora for data mining. Its ability to reduce high dimensionality to a small number of latent variables makes it suitable as a means for clustering or overcoming clustering difficulties in large biological and medical datasets. Results In this study, three topic model-derived clustering methods, highest probable topic assignment, feature selection and feature extraction, are proposed and tested on the cluster analysis of three large datasets: Salmonella pulsed-field gel electrophoresis (PFGE) dataset, lung cancer dataset, and breast cancer dataset, which represent various types of large biological or medical datasets. All three various methods are shown to improve the efficacy/effectiveness of clustering results on the three datasets in comparison to traditional methods. A preferable cluster analysis method emerged for each of the three datasets on the basis of replicating known biological truths. Conclusion Topic modeling could be advantageously applied to the large datasets of biological or medical research. The three proposed topic model-derived clustering methods, highest probable topic assignment, feature selection and feature extraction, yield clustering improvements for the three different data types. Clusters more efficaciously represent truthful groupings and subgroupings in the data than

  9. SS316 structure fabricated by selective laser melting and integrated with strain isolated optical fiber high temperature sensor

    NASA Astrophysics Data System (ADS)

    Mathew, Jinesh; Havermann, Dirk; Polyzos, Dimitrios; MacPherson, William N.; Hand, Duncan P.; Maier, Robert R. J.

    2015-09-01

    Smart metal having integrated high temperature sensing capability is reported. The SS316 structure is made by additive layer manufacturing via selective laser melting (SLM). Sensor component is embedded in to the structure during the SLM build process. The strain isolated in-fiber Fabry-Perot cavity sensor measures temperature up to 1100 °C inside the metal.

  10. Structure sensitive selectivity of the NO-CO reaction over rhodium single crystal catalysts

    SciTech Connect

    Peden, C.H.F.; Belton, D.N.; Schmieg, S.J.

    1995-05-01

    The control of automotive emissions of nitrogen oxides (NO{sub x}) in passenger cars is accomplished by a heavy reliance on after-treatment of the engine exhaust using catalytic converters that contain a mixture of platinum (Pt), rhodium (Rh), and sometimes palladium (Pd). In this paper we examine the effect of surface structure on the NO-CO activity and selectivity by comparing the reactivity of Rh(110) and Rh(111) single crystal catalysts. Selectivity for the two possible nitrogen containing products from NO reduction, N{sub 2}O and N{sub 2}, is particularly interesting. Here we report that the selectivity of the NO-CO reaction is quite sensitive to the structure of the Rh catalyst metal surface. (A more complete description of these studies will be published elsewhere.) The more open Rh(110) surface tends to make significantly less N{sub 2}O than Rh(111) under virtually all conditions that we probed with these experiments. Furthermore, under the conditions used in this study, the NO-CO activity over Rh(110), as measured by the rate of NO loss, is somewhat faster than over Rh(111) with a lower apparent activation energy (Ea), 27.6 vs. 35.4 kcal/mol. We attribute these results to the greater tendency of the more open (110) surface to dissociate NO. Notably, more facile NO dissociation on Rh(110) would lead to greater steady-state concentrations of adsorbed N-atoms; thus, the (110) surface favors N-atom recombination over the surface reaction between adsorbed NO and N-atoms to make N{sub 2}O. In support of this, post-reaction surface analysis shows only NO on the Rh(111) surface while the Rh(110) surface contains predominantly N-atoms and much lower concentrations of adsorbed NO. NO dissociation on Rh(110) is more favorable than on Rh(111), in part, because it is less-severely poisoned by high surface concentrations of NO. In addition, the more-open (110) surface may be intrinsically more active for the elementary process of dissociating adsorbed NO.

  11. Seed selection strategy in global network alignment without destroying the entire structures of functional modules

    PubMed Central

    2012-01-01

    Background Network alignment is one of the most common biological network comparison methods. Aligning protein-protein interaction (PPI) networks of different species is of great important to detect evolutionary conserved pathways or protein complexes across species through the identification of conserved interactions, and to improve our insight into biological systems. Global network alignment (GNA) problem is NP-complete, for which only heuristic methods have been proposed so far. Generally, the current GNA methods fall into global heuristic seed-and-extend approaches. These methods can not get the best overall consistent alignment between networks for the opinionated local seed. Furthermore These methods are lost in maximizing the number of aligned edges between two networks without considering the original structures of functional modules. Methods We present a novel seed selection strategy for global network alignment by constructing the pairs of hub nodes of networks to be aligned into multiple seeds. Beginning from every hub seed and using the membership similarity of nodes to quantify to what extent the nodes can participate in functional modules associated with current seed topologically we align the networks by modules. By this way we can maintain the functional modules are not damaged during the heuristic alignment process. And our method is efficient in resolving the fatal problem of most conventional algorithms that the initialization selected seeds have a direct influence on the alignment result. The similarity measures between network nodes (e.g., proteins) include sequence similarity, centrality similarity, and dynamic membership similarity and our algorithm can be called Multiple Hubs-based Alignment (MHA). Results When applying our seed selection strategy to several pairs of real PPI networks, it is observed that our method is working to strike a balance, extending the conserved interactions while maintaining the functional modules unchanged. In

  12. GIS based site and structure selection model for groundwater recharge: a hydrogeomorphic approach.

    PubMed

    Vijay, Ritesh; Sohony, R A

    2009-10-01

    The groundwater in India is facing a critical situation due to over exploitation, reduction in recharge potential by change in land use and land cover and improper planning and management. A groundwater development plan needs a large volume of multidisciplinary data from various sources. A geographic information system (GIS) based hydrogeomorphic approach can provide the appropriate platform for spatial analysis of diverse data sets for decision making in groundwater recharge. The paper presents development of GIS based model to provide more accuracy in identification and suitability analysis for finding out zones and locating suitable sites with suggested structures for artificial recharge. Satellite images were used to prepare the geomorphological and land use maps. For site selection, the items such as slope, surface infiltration, and order of drainage were generated and integrated in GIS using Weighted Index Overlay Analysis and Boolean logics. Similarly for identification of suitable structures, complex matrix was programmed based on local climatic, topographic, hydrogeologic and landuse conditions as per artificial recharge manual of Central Ground Water Board, India. The GIS based algorithm is implemented in a user-friendly way using arc macro language on Arc/Info platform. PMID:21117424

  13. Evaluation of selected thermal control coatings for long-life space structures

    NASA Technical Reports Server (NTRS)

    Teichman, Louis A.; Slemp, Wayne S.; Witte, William G., Jr.

    1992-01-01

    Graphite-reinforced resin matrix composites are being considered for spacecraft structural applications because of their light weight, high stiffness, and lower thermal expansion. Thin protective coatings with stable optical properties and the proper ratio of solar absorption (alpha sub s) to thermal emittance (epsilon) minimize orbital thermal extremes and protect these materials against space environment degradation. Sputtered coatings applied directly to graphite/epoxy composite surfaces and anodized coatings applied to thin aluminum foil were studied for use both as an atomic oxygen barrier and as thermal control coatings. Additional effort was made to develop nickel-based coatings which could be applied directly to composites. These coating systems were selected because their inherent tenacity made them potentially more reliable than commercial white paints for long-life space missions. Results indicate that anodized aluminum foil coatings are suitable for tubular and flat composite structures on large platforms in low Earth orbit. Anodized foil provides protection against some elements of the natural space environment (atomic oxygen, ultraviolet, and particulate radiation) and offers a broad range of tailored alpha sub s/epsilon. The foil is readily available and can be produced in large quantities, while the anodizing process is a routine commercial technique.

  14. Design and Structural Characterization of Potent and Selective Inhibitors of Phosphatidylinositol 4 Kinase IIIβ.

    PubMed

    Rutaganira, Florentine U; Fowler, Melissa L; McPhail, Jacob A; Gelman, Michael A; Nguyen, Khanh; Xiong, Anming; Dornan, Gillian L; Tavshanjian, Brandon; Glenn, Jeffrey S; Shokat, Kevan M; Burke, John E

    2016-03-10

    Type III phosphatidylinositol 4-kinase (PI4KIIIβ) is an essential enzyme in mediating membrane trafficking and is implicated in a variety of pathogenic processes. It is a key host factor mediating replication of RNA viruses. The design of potent and specific inhibitors of this enzyme will be essential to define its cellular roles and may lead to novel antiviral therapeutics. We previously reported the PI4K inhibitor PIK93, and this compound has defined key functions of PI4KIIIβ. However, this compound showed high cross reactivity with class I and III PI3Ks. Using structure-based drug design, we have designed novel potent and selective (>1000-fold over class I and class III PI3Ks) PI4KIIIβ inhibitors. These compounds showed antiviral activity against hepatitis C virus. The co-crystal structure of PI4KIIIβ bound to one of the most potent compounds reveals the molecular basis of specificity. This work will be vital in the design of novel PI4KIIIβ inhibitors, which may play significant roles as antiviral therapeutics. PMID:26885694

  15. All-benzene carbon nanocages: size-selective synthesis, photophysical properties, and crystal structure.

    PubMed

    Matsui, Katsuma; Segawa, Yasutomo; Itami, Kenichiro

    2014-11-19

    The design and synthesis of a series of carbon nanocages consisting solely of benzene rings are described. Carbon nanocages are appealing molecules not only because they represent junction unit structures of branched carbon nanotubes, but also because of their potential utilities as unique optoelectronic π-conjugated materials and guest-encapsulating hosts. Three sizes of strained, conjugated [n.n.n]carbon nanocages (1, n = 4; 2, n = 5; 3, n = 6) were synthesized with perfect size-selectivity. Cyclohexane-containing units and 1,3,5-trisubstituted benzene-containing units were assembled to yield the minimally strained bicyclic precursors, which were successfully converted into the corresponding carbon nanocages via acid-mediated aromatization. X-ray crystallography of 1 confirmed the cage-shaped structure with an approximately spherical void inside the cage molecule. The present studies revealed the unique properties of carbon nanocages, including strain energies, size-dependent absorption and fluorescence, as well as unique size-dependency for the electronic features of 1-3. PMID:25361385

  16. Structurally selective imaging mass spectrometry by imaging ion mobility-mass spectrometry.

    PubMed

    McLean, John A; Fenn, Larissa S; Enders, Jeffrey R

    2010-01-01

    This chapter describes the utility of structurally based separations combined with imaging mass spectrometry (MS) by ion mobility-MS (IM-MS) approaches. The unique capabilities of combining rapid (mus-ms) IM separations with imaging MS are detailed for an audience ranging from new to potential practitioners in IM-MS technology. Importantly, imaging IM-MS provides the ability to rapidly separate and elucidate various types of endogenous and exogenous biomolecules (e.g., nucleotides, carbohydrates, peptides, and lipids), including isobaric species. Drift tube and traveling wave IM-MS instrumentation are described and specific protocols are presented for calculating ion-neutral collision cross sections (i.e., apparent ion surface area or structure) from experimentally obtained IM-MS data. Special emphasis is placed on the use of imaging IM-MS for the analysis of samples in life sciences research (e.g., thin tissue sections), including selective imaging for peptide/protein and lipid distributions. Future directions for rapid and multiplexed imaging IM-MS/MS are detailed. PMID:20680602

  17. Topics in statistical mechanics

    SciTech Connect

    Elser, V.

    1984-05-01

    This thesis deals with four independent topics in statistical mechanics: (1) the dimer problem is solved exactly for a hexagonal lattice with general boundary using a known generating function from the theory of partitions. It is shown that the leading term in the entropy depends on the shape of the boundary; (2) continuum models of percolation and self-avoiding walks are introduced with the property that their series expansions are sums over linear graphs with intrinsic combinatorial weights and explicit dimension dependence; (3) a constrained SOS model is used to describe the edge of a simple cubic crystal. Low and high temperature results are derived as well as the detailed behavior near the crystal facet; (4) the microscopic model of the lambda-transition involving atomic permutation cycles is reexamined. In particular, a new derivation of the two-component field theory model of the critical behavior is presented. Results for a lattice model originally proposed by Kikuchi are extended with a high temperature series expansion and Monte Carlo simulation. 30 references.

  18. An update on topical therapies for mild-moderate psoriasis.

    PubMed

    van de Kerkhof, Peter C M

    2015-01-01

    Topical therapies are the mainstream treatment of psoriasis because most patients have mild disease. First-line treatments are vitamin D derivatives and corticosteroids. These treatments are usually given in combination schedules. For topical treatments the selection of the most appropriate vehicle is of major importance, thus improving adherence to the treatment, which frequently is impaired by the complexities of topical therapeutic choices. Evidence for efficacy and safety of topical treatments is readily available for vitamin D treatments and short-term treatment with corticosteroids. However, the scientific evidence for longer-term treatments is limited. Multiple new small molecules are in various stages of development and are reviewed. PMID:25412784

  19. Discovering Health Topics in Social Media Using Topic Models

    PubMed Central

    Paul, Michael J.; Dredze, Mark

    2014-01-01

    By aggregating self-reported health statuses across millions of users, we seek to characterize the variety of health information discussed in Twitter. We describe a topic modeling framework for discovering health topics in Twitter, a social media website. This is an exploratory approach with the goal of understanding what health topics are commonly discussed in social media. This paper describes in detail a statistical topic model created for this purpose, the Ailment Topic Aspect Model (ATAM), as well as our system for filtering general Twitter data based on health keywords and supervised classification. We show how ATAM and other topic models can automatically infer health topics in 144 million Twitter messages from 2011 to 2013. ATAM discovered 13 coherent clusters of Twitter messages, some of which correlate with seasonal influenza (r = 0.689) and allergies (r = 0.810) temporal surveillance data, as well as exercise (r = .534) and obesity (r = −.631) related geographic survey data in the United States. These results demonstrate that it is possible to automatically discover topics that attain statistically significant correlations with ground truth data, despite using minimal human supervision and no historical data to train the model, in contrast to prior work. Additionally, these results demonstrate that a single general-purpose model can identify many different health topics in social media. PMID:25084530

  20. (Topics in theoretical physics). Progress report

    SciTech Connect

    Not Available

    1985-01-01

    Progress is reported in these areas: supersymmetry and conformal invariance and new structures in two dimensional critical phenomena; spinor fields and new applications and techniques for studying Ising model correlation factors; superstring compactification and high energy physics applications for novel two dimensional critical points; ordered and disordered spatial structure in dynamical systems; and fermion-boson mass relations in BCS type theories. Research is proposed in covariant formulation of the superstring, topics in superconformal field theory and new structures in two dimensional critical phenomena, ordered and disordered spatial structure in dynamical systems, and field theory over Galois fields. 48 refs. (LEW)