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Sample records for structures selected topics

  1. Chaotic features of nuclear structure and dynamics: selected topics

    NASA Astrophysics Data System (ADS)

    Zelevinsky, Vladimir; Volya, Alexander

    2016-03-01

    Quantum chaos has become an important element of our knowledge about physics of complex systems. In typical mesoscopic systems of interacting particles the dynamics invariably become chaotic when the level density, growing by combinatorial reasons, leads to the increasing probability of mixing simple mean-field (particle-hole) configurations. The resulting stationary states have exceedingly complicated structures that are comparable to those in random matrix theory. We discuss the main properties of mesoscopic quantum chaos and show that it can serve as a justification for application of statistical mechanics to mesoscopic systems. We show that quantum chaos becomes a powerful instrument for experimental, theoretical and computational work. The generalization to open systems and effects in the continuum are discussed with the help of the effective non-Hermitian Hamiltonian; it is shown how to formulate this approach for numerous problems of quantum signal transmission. The artificially introduced randomness can also be helpful for a deeper understanding of physics. We indicate the problems that require more investigation so as to be understood further.

  2. 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.

  3. Classical Integrable Systems: Selected Topics

    NASA Astrophysics Data System (ADS)

    Perelomov, A. M.

    In this paper two topics are considered: • Poisson structures and Hamiltonian systems. • Explicit integration of equations of motion for the Calogero-Sutherland and Toda systems. It must be said that a part of the material is well known to specialists in this field for a long time (see for example the book57). Even so, it may not always be easily accessible to nonspecialists. Within the limited space it was not possible to give a completely systematic exposition of these topics. Rather I tried to illustrate the main ideas on simple examples and in an as elementary and explicit way as possible. The examples considered here are therefore restricted to the systems related to the algebras An sun+1. For the case of arbitrary simple Lie algebra, we have only mentioned the results at best. Due to insufficient space many important results are omitted here. Nevertheless I hope that this paper may be useful and may serve as a guide, so that the interested reader may proceed to read original articles.

  4. Neutron transport simulation (selected topics)

    NASA Astrophysics Data System (ADS)

    Vaz, P.

    2009-10-01

    Neutron transport simulation is usually performed for criticality, power distribution, activation, scattering, dosimetry and shielding problems, among others. During the last fifteen years, innovative technological applications have been proposed (Accelerator Driven Systems, Energy Amplifiers, Spallation Neutron Sources, etc.), involving the utilization of intermediate energies (hundreds of MeV) and high-intensity (tens of mA) proton accelerators impinging in targets of high Z elements. Additionally, the use of protons, neutrons and light ions for medical applications (hadrontherapy) impose requirements on neutron dosimetry-related quantities (such as kerma factors) for biologically relevant materials, in the energy range starting at several tens of MeV. Shielding and activation related problems associated to the operation of high-energy proton accelerators, emerging space-related applications and aircrew dosimetry-related topics are also fields of intense activity requiring as accurate as possible medium- and high-energy neutron (and other hadrons) transport simulation. These applications impose specific requirements on cross-section data for structural materials, targets, actinides and biologically relevant materials. Emerging nuclear energy systems and next generation nuclear reactors also impose requirements on accurate neutron transport calculations and on cross-section data needs for structural materials, coolants and nuclear fuel materials, aiming at improved safety and detailed thermal-hydraulics and radiation damage studies. In this review paper, the state-of-the-art in the computational tools and methodologies available to perform neutron transport simulation is presented. Proton- and neutron-induced cross-section data needs and requirements are discussed. Hot topics are pinpointed, prospective views are provided and future trends identified.

  5. 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.

  6. 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.

  7. Selected topics from classical bacterial genetics.

    PubMed

    Raleigh, Elisabeth A; Elbing, Karen; Brent, Roger

    2002-08-01

    Current cloning technology exploits many facts learned from classical bacterial genetics. This unit covers those that are critical to understanding the techniques described in this book. Topics include antibiotics, the LAC operon, the F factor, nonsense suppressors, genetic markers, genotype and phenotype, DNA restriction, modification and methylation and recombination.

  8. RUC at TREC 2014: Select Resources Using Topic Models

    DTIC Science & Technology

    2014-11-01

    them being observed (i.e. sampled). To infer the topic Report Documentation Page Form ApprovedOMB No. 0704-0188 Public reporting burden for the...Selection. In CIKM 2009, pages 1277-1286. [10] M. Baillie, M. Carmen, and F. Crestani. A Multiple- Collection Latent Topic Model for Federated...RUC at TREC 2014: Select Resources Using Topic Models Qiuyue Wang, Shaochen Shi, Wei Cao School of Information Renmin University of China Beijing

  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. 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

  11. Selected Topics on the Dark Side

    NASA Astrophysics Data System (ADS)

    Ilie, Cosmin

    Although significant progress has been made in understanding the nature and history of our universe there are still many open questions in cosmology. The nature of the dark energy (DE) and dark matter (DM) are still elusive. Phantom Cosmology provides an unique opportunity to "connect" the phantom driven DE phase to the inflationary era. We present a concrete model where the energy density cycles through several phases. The model predicts transitions from a standard radiation/matter dominated regime to a dark energy/inflationary phases, in a repetitive pattern. An interesting feature of this formalism is that once we include interactions between the "phantom fluid" and ordinary matter, the phantom phase naturally gives way to a near exponential inflationary expansion, avoiding the Big Rip singularity. The first phase of stellar evolution in the history of the Universe may be Dark Stars (DS), powered by DM heating. We investigated the properties of DS assuming DM annihilations explain recently found cosmic ray anomalies. Our results show that the final stellar properties, once the star enters the main sequence, are always roughly the same. However the lifetime, final mass, and final luminosity of the DS show moderate dependence on boost factor and concentration parameter. We propose two mechanisms that could explain the growth of Dark Stars to become supermassive (SMDS). The launch of the James Webb Space Telescope (JWST) opens up the possibility of detecting SMDS. Using various dropout redshift selection functions we show that JWST could detect SMDS in a typical deep field survey. Specifically, at z ˜ 10 there could be several 106 M⊙ SMDS detected as J115 dropouts. The detection of 107 M⊙ SMDS is relatively slim at the same z ˜ 10. The 107 M⊙ SMDS have a significant chance of being observed as a H 150 dropout at z ˜ 12, whereas the 106 M⊙ SMDS could show up in extremely large numbers (˜ 200) in a typical deep field survey as an F150W dropout. The most

  12. A topic evolution model with sentiment and selective attention

    NASA Astrophysics Data System (ADS)

    Si, Xia-Meng; Wang, Wen-Dong; Zhai, Chun-Qing; Ma, Yan

    2017-04-01

    Topic evolution is a hybrid dynamics of information propagation and opinion interaction. The dynamics of opinion interaction is inherently interwoven with the dynamics of information propagation in the network, owing to the bidirectional influences between interaction and diffusion. The degree of sentiment determines if the topic can continue to spread from this node, and the selective attention determines the information flow direction and communicatee selection. For this end, we put forward a sentiment-based mixed dynamics model with selective attention, and applied the Bayesian updating rules on it. Our model can indirectly describe the isolated users who seem isolated from a topic due to some reasons even everybody around them has heard about it. Numerical simulations show that, more insiders initially and fewer simultaneous spreaders can lessen the extremism. To promote the topic diffusion or restrain the prevailing of extremism, fewer agents with constructive motivation and more agents with no involving motivation are encouraged.

  13. Selected topics on the topology of ideal fluid flows

    NASA Astrophysics Data System (ADS)

    Peralta-Salas, Daniel

    2016-08-01

    This is a survey of certain geometric aspects of inviscid and incompressible fluid flows, which are described by the solutions to the Euler equations. We will review Arnold’s theorem on the topological structure of stationary fluids in compact manifolds, and Moffatt’s theorem on the topological interpretation of helicity in terms of knot invariants. The recent realization theorem by Enciso and Peralta-Salas of vortex lines of arbitrarily complicated topology for stationary solutions to the Euler equations will also be introduced. The aim of this paper is not to provide detailed proofs of all the stated results but to introduce the main ideas and methods behind certain selected topics of the subject known as Topological Fluid Mechanics. This is the set of lecture notes, the author gave at the XXIV International Fall Workshop on Geometry and Physics held in Zaragoza (Spain) during September 2015.

  14. 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.

  15. Topics in the structure of hadronic systems

    SciTech Connect

    Lebed, Richard Felix

    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 (md-mu) 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.

  16. 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.

  17. Issues in Selecting Topics for Projects. ERIC Digest.

    ERIC Educational Resources Information Center

    Katz, Lilian G.; Chard, Sylvia C.

    Unlike units and themes in the early childhood and primary curriculum, projects are defined as children's in-depth investigations of various topics--ideally, topics worthy of the children's time and energy. As increasing numbers of teachers and school districts incorporate project work into their curriculum, questions have been raised about what…

  18. 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.…

  19. Student-Based Topic Selection for ESL Courses.

    ERIC Educational Resources Information Center

    Boyle, Joseph P.

    Ninety students in a Hong Kong course in English as a second language were asked to list 20 topics they considered to be of interest for classroom study. The most popular topic areas, in descending order of popularity, were education, the students' home country (Hong Kong), family life, money, human relationships, marriage, nationalism and…

  20. Combining formal and functional approaches to topic structure.

    PubMed

    Zellers, Margaret; Post, Brechtje

    2012-03-01

    Fragmentation between formal and functional approaches to prosodic variation is an ongoing problem in linguistic research. In particular, the frameworks of the Phonetics of Talk-in-Interaction (PTI) and Empirical Phonology (EP) take very different theoretical and methodological approaches to this kind of variation. We argue that it is fruitful to adopt the insights of both PTI's qualitative analysis and EP's quantitative analysis and combine them into a multiple-methods approach. One realm in which it is possible to combine these frameworks is in the analysis of discourse topic structure and the prosodic cues relevant to it. By combining a quantitative and a qualitative approach to discourse topic structure, it is possible to give a better account of the observed variation in prosody, for example in the case of fundamental frequency (F0) peak timing, which can be explained in terms of pitch accent distribution over different topic structure categories. Similarly, local and global patterns in speech rate variation can be better explained and motivated by adopting insights from both PTI and EP in the study of topic structure. Combining PTI and EP can provide better accounts of speech data as well as opening up new avenues of investigation which would not have been possible in either approach alone.

  1. 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…

  2. Methods of Teaching Selected Topics in Business Communication.

    ERIC Educational Resources Information Center

    Golen, Steven P., Ed.; And Others

    In order to help teachers of business communication look for new and innovative ways to improve their teaching, this book offers a "how to" approach to various topics in business communication. The ideas expressed in this book are a collaboration of 32 members of The Association for Business Communication who served on the Teaching…

  3. 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)

  4. Consumer involvement in topic and outcome selection in the development of clinical practice guidelines

    PubMed Central

    Tong, Allison; Lopez‐Vargas, Pamela; Howell, Martin; Phoon, Richard; Johnson, David; Campbell, Denise; Walker, Rowan G; Craig, Jonathan C

    2011-01-01

    Abstract Background  Consumer involvement in guideline development is advocated, but minimal participation, such as a nominated consumer representative on a guideline working group, can inhibit their decision‐making power and contribution. Little is known about how to involve consumers more effectively in guideline development. Objective  To describe a targeted approach for involving consumers actively in guideline development, by focusing on topic and outcome selection, and to discuss the impact on content and structure of the final guideline. Design  Descriptive study. Setting and participants  Patients and carers (n = 24) from a tertiary hospital in Sydney attended three structured peer‐facilitated workshops to complete group‐based exercises on topic and outcome selection for guidelines for early stage chronic kidney disease. These workshops were run in parallel with the guideline‐writing group. For each exercise, participants formed small groups and facilitated their own discussion, recorded their responses and presented them to the wider group. The topics and outcomes identified were fed back to the guideline writers. Results  The participants actively engaged in the workshop discussions and articulated topics and outcomes they perceived should be included in clinical guidelines. Four main changes to guideline‐related outputs were observed. A new guideline subtopic was introduced, guidelines were consumer‐endorsed, guideline recommendations and suggestions for clinical care were augmented with consumer‐focused issues, and plain English guidelines were developed. Conclusions  Consumer workshops in parallel and feeding into guideline development can be a feasible and effective approach for active consumer contribution. This process can inform the development of both consumer‐focused guidelines for clinicians and specific versions for consumers. PMID:23134217

  5. 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.

  6. 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.

  7. 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…

  8. 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,…

  9. Exploring the structure-permeation relationship of topical tricyclic antidepressants used for skin analgesia.

    PubMed

    Liu, Kuo-Sheng; Huang, Tse-Hung; Aljuffali, Ibrahim A; Chen, En-Li; Wang, Jhi-Joung; Fang, Jia-You

    2017-03-23

    The purpose of this study was to evaluate the skin permeation of tricyclic antidepressants (TCAs) with propamine moiety to select candidates for the development of topical analgesics to treat cutaneous pain. We sought to establish the structure-permeation relationship (SPR) of topical TCAs. The lipophilicity, melting point, and aqueous solubility were determined to develop the physicochemical characterization. The TCA permeation into pig and nude mouse skins was estimated using Franz diffusion cell. TCAs and lidocaine were comparatively examined for cutaneous analgesia by pinprick assay. Cutaneous tolerance to TCAs was assessed using nude mouse skin. The skin deposition increased following the increase of lipophilicity after excluding the effect of solubility, with clomipramine exhibiting the highest skin retention. A contrary result was observed for TCA penetration into the receptor. Of the permeants tested, clomipramine demonstrated the best skin-targeting ability. Nortriptyline and clomipramine demonstrated selective uptake into the hair follicles, exhibiting a 2.5-fold higher follicular accumulation than desipramine. Replacement of nitrogen with carbon in the seven-member ring increased skin absorption. The tertiary amine TCAs demonstrated higher absorption than the secondary amine TCAs. The position of the double bond also affected skin transport. Topical clomipramine had a longer duration of analgesic action than lidocaine (240min versus 60min). Exploring the SPR revealed that clomipramine could be an analgesic candidate drug for future development.

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

    SciTech Connect

    Naus, Dan J

    2008-01-01

    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.

  11. 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.

  12. Topical liposome targeting of dyes, melanins, genes, and proteins selectively to hair follicles.

    PubMed

    Hoffman, R M

    1998-01-01

    For therapeutic and cosmetic modification of hair, we have developed a hair-follicle-selective macromolecule and small molecule targeting system with topical application of phosphatidylcholine-based liposomes. Liposome-entrapped melanins, proteins, genes, and small-molecules have been selectively targeted to the hair follicle and hair shafts of mice. Liposomal delivery of these molecules is time dependent. Negligible amounts of delivered molecules enter the dermis, epidermis, or bloodstream thereby demonstrating selective follicle delivery. Naked molecules are trapped in the stratum corneum and are unable to enter the follicle. The potential of the hair-follicle liposome delivery system for therapeutic use for hair disease as well as for cosmesis has been demonstrated in 3-dimensional histoculture of hair-growing skin and mouse in vivo models. Topical liposome selective delivery to hair follicles has demonstrated the ability to color hair with melanin, the delivery of the active lac-Z gene to hair matrix cells and delivery of proteins as well. Liposome-targeting of molecules to hair follicles has also been achieved in human scalp in histoculture. Liposomes thus have high potential in selective hair follicle targeting of large and small molecules, including genes, opening the field of gene therapy and other molecular therapy of the hair process to restore hair growth, physiologically restore or alter hair pigment, and to prevent or accelerate hair loss.

  13. 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…

  14. 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

  15. 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…

  16. 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.

  17. Receptor specificity of retinoid-induced epidermal hyperplasia: effect of RXR-selective agonists and correlation with topical irritation.

    PubMed

    Thacher, S M; Standeven, A M; Athanikar, J; Kopper, S; Castilleja, O; Escobar, M; Beard, R L; Chandraratna, R A

    1997-08-01

    Retinoid induction of epidermal hyperplasia was investigated in hairless mice with synthetic ligands for the retinoic acid (RAR) and retinoid X (RXR) nuclear receptors. Induction of hyperplasia by all-trans retinoic acid and the RAR-specific retinoids TTNPB, tazarotene and AGN 190121 varied over a wide range (ED50 = 0.2-100 nmol/animal in three daily applications). Potency of induction was not directly correlated to receptor-binding affinity, but specificity of action could be demonstrated by inhibition with the high-affinity antagonist of the RARs, AGN 193109. Although RAR is functionally complexed with RXR in vivo, RXR-selective compounds have only weak potency in induction of hyperplasia. The ED50 value of the RXR-selective AGN 191701 was 600 nmol/animal compared with an ED50 value of 0.2 nmol for the structurally similar RAR-selective TTNPB. SR11237 and SR11217, also RXR-selective, each have an ED50 value of >1000 nmol. Unlike RAR-specific retinoids, RXR-selective retinoids cause only very mild skin flaking at high doses. Relative potencies for cumulative topical irritation (flaking and abrasion) of both RAR and RXR ligands were well correlated with epidermal hyperplasia. These data are consistent with RXR as a silent partner in the RAR-RXR heterodimer in skin.

  18. 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.

  19. Structural Complexity in Linguistic Systems Research Topic 3: Mathematical Sciences

    DTIC Science & Technology

    2015-04-01

    Kevin Taylor, “Extending Reinforcement Learning Methods with a Simple Robot”, Undergraduate Senior Thesis (June 2013), awarded Highest Honors by Physics...expressed in vocabulary and syntax) and entropy (the need to convey novelty and express meaning 1. REPORT DATE (DD-MM-YYYY) 4. TITLE AND SUBTITLE...evolves over time and to explore the tendency of language systems to develop in ways that balance structure (expressed in vocabulary and syntax) and

  20. 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.

  1. 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.

  2. 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.)

  3. 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.

  4. 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

  5. Topical Corticosteroid Application and the Structural and Functional Integrity of the Epidermal Barrier

    PubMed Central

    Cash, Kimberly

    2013-01-01

    Topical corticosteroids are a very important part of the treatment of many skin disorders, especially eczematous dermatoses. When utilized properly and judiciously these agents often achieve excellent results in clearing or markedly improving many dermatological disorders. As some studies have shown, topical corticosteroids, despite their ability to decrease inflammation through several mechanisms, induce abnormalities in lipid synthesis and intercellular bilayer structure in the stratum corneum, which appear to prolong epidermal barrier recovery. These adverse effects may contribute to eariier eczematous flaring if measures to provide barrier repair are not undertaken. In addition, although topical corticosteroids are applied only to sites affected by the skin eruption, the incorporation of “barrier friendly” excipients into the vehicle that improve stratum corneum permeability barrier function and integrity is very rational. PMID:24307921

  6. 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.

  7. 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.

  8. Colloquium on Selected Topics in Behavioral Science Basic Research. (Alexandria, Virginia, April 23-25, 1980).

    ERIC Educational Resources Information Center

    Nogami, Glenda Y., Ed.; And Others

    The 21 summaries of research programs, funded by the United States Army Research Institute (ARI) for the Behavioral and Social Sciences which are presented are grouped in five broad topic areas: computer-based systems; information processing; learning, memory and transfer; human relations; and related issues and trends. Papers presented include:…

  9. History of Research on Physical Activity and Health: Selected Topics, 1867 to the 1950s.

    ERIC Educational Resources Information Center

    Park, Roberta J.

    1995-01-01

    Developments in the biomedical sciences affect how people think about health and fitness, as do social and cultural factors. This paper examines two topics of interest to educators, physicians, and researchers in the physiological sciences from 1867-1950 (the phenomenon referred to as the athlete's heart and anthropometrical/growth and development…

  10. 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.

  11. 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…

  12. Selection of topically applied non-steroidal anti-inflammatory drugs for oral cancer chemoprevention.

    PubMed

    Sood, Sandeep; Shiff, Steven J; Yang, Chung S; Chen, Xiaoxin

    2005-07-01

    Topical delivery of non-steroidal anti-inflammatory drugs through the oral mucosa has been used for oral cancer chemoprevention. Local permeation of these agents has been one of the major concerns. Here we propose an approach to predict the permeability of topically applied agents for oral cancer chemoprevention. In theory, the total flux through the oral mucosa (Jmax) can be estimated by adding the transcellular flux (JTC) and the paracellular flux (JPC). To target the Cox-2 enzyme in oral epithelial cells, it is desirable to maximize the theoretical activity index, the ratio of JTC and IC50 of a Cox-2 inhibitor (JTC/IC50-Cox-2). Among the 12 commonly used NSAIDs, celecoxib, nimesulide and ibuprofen had the highest values and may be the agents of choice to target Cox-2 in oral epithelial cells through topical application. Based on these calculations, a long-term chemopreventive experiment using celecoxib (3% or 6%) through topical application was performed in a DMBA induced hamster oral cancer model. Both 3% and 6% reduced the incidence of squamous cell carcinoma at the post-initiation stage.

  13. 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.

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

    PubMed Central

    Lerche, Catharina M.; Wulf, Hans Christian

    2010-01-01

    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

  15. Topic selection in undergraduate medical education and relevance to general practice.

    PubMed

    Haagedoorn, E M; de Vries, J

    1998-01-01

    Most patients who have possibly malignant diseases are first seen by physicians not specifically trained in oncology. The cancer education that undergraduate medical students receive is frequently dominated by basic science topics, detailed staging data, pharmacology of cancer drugs, and treatment protocols. This is not in accordance with the needs in general practice. In pre-course information and correspondence with reference to the International Summer School "Oncology for Medical Students," held in Groningen, The Netherlands, it is emphasized that the Summer School focuses on cancer care in general practice. As part of the education program participants are required to prepare abstracts and posters on oncologic topics in general health care in their own countries. Despite the emphasis on cancer care in general practice and despite suggestions for topics, some students have first sent in abstracts describing basic sciences research projects. Evidently during their medical training the relevancy of cancer education to the reality of daily practice had not been taught or had already been lost. In teaching undergraduate medical students, it should be realized that the vast majority will choose non-oncology disciplines. Thus, cancer education of these students should focus mainly on clinical cancer issues that are relevant in general practice.

  16. The 4th Bologna Winter School: Hot Topics in Structural Genomics

    PubMed Central

    2003-01-01

    The 4th Bologna Winter School on Biotechnologies was held on 9–15 February 2003 at the University of Bologna, Italy, with the specific aim of discussing recent developments in bioinformatics. The school provided an opportunity for students and scientists to debate current problems in computational biology and possible solutions. The course, co-supported (as last year) by the European Science Foundation program on Functional Genomics, focused mainly on hot topics in structural genomics, including recent CASP and CAPRI results, recent and promising genomewide predictions, protein–protein and protein–DNA interaction predictions and genome functional annotation. The topics were organized into four main sections (http://www.biocomp.unibo.it). PMID:18629078

  17. 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

  18. In vitro selection and efficacy of topical skin protectants against the nerve agent VX.

    PubMed

    Millerioux, J; Cruz, C; Bazire, A; Lallement, G; Lefeuvre, L; Josse, D

    2009-04-01

    Against highly toxic chemicals that are quickly absorbed in the skin, topical formulations could adequately complement specific protective suits and equipments. In this work, we evaluated in vitro and compared the skin protection efficacy against the nerve agent VX of four different topical formulations: oil-in-water and water-in-oil emulsions, a perfluorinated-based cream and a hydrogel. Semi-permeable silicone membrane, pig-ear and human abdominal split-thickness skin samples mounted in diffusion cells were compared as in vitro permeation tests. The results showed that silicone membrane could be used instead of skin samples to screen for potentially effective formulations. However, the results indicated that due to potentially significant interactions between formulations and skin, relevant ranking of formulations according to their protective efficacy could require tests with skin samples. The main phase of emulsions, water or oil, was not found to be critical for skin protective efficacy against VX. Instead, specific film-forming ingredients such as perfluorinated-based polymers and silicones could significantly affect the skin protective efficacy of formulations. We showed that a hydrogel containing specific hydrophilic polymers was by far the most effective of the formulations evaluated against VX skin permeation in vitro.

  19. Determination of the Mutant Prevention Concentration and the Mutant Selection Window of Topical Antimicrobial Agents against Propionibacterium acnes.

    PubMed

    Nakase, Keisuke; Nakaminami, Hidemasa; Toda, Yuta; Noguchi, Norihisa

    2017-01-01

    Determination of the mutant prevention concentration (MPC) and the mutant selection window (MSW) of antimicrobial agents used to treat pathogenic bacteria is important in order to apply effective antimicrobial therapies. Here, we determined the MPCs of the major topical antimicrobial agents against Propionibacterium acnes and Staphylococcus aureus which cause skin infections and compared their MSWs. Among the MPCs of nadifloxacin and clindamycin, the clindamycin MPC was determined to be the lowest against P. acnes. In contrast, the nadifloxacin MPC was the lowest against S. aureus. Calculations based on the minimum inhibitory concentrations and MPCs showed that clindamycin has the lowest MSW against both P. acnes and S. aureus. Nadifloxacin MSWs were 4-fold higher against P. acnes than against S. aureus. It is more likely for P. acnes to acquire resistance to fluoroquinolones than S. aureus. Therefore, topical application of clindamycin contributes very little to the emergence of resistant P. acnes and S. aureus strains.

  20. Optimization of topical gels with betamethasone dipropionate: selection of gel forming and optimal cosolvent system.

    PubMed

    Băiţan, Mariana; Lionte, Mihaela; Moisuc, Lăcrămioara; Gafiţanu, Eliza

    2011-01-01

    The purpose of these studies was to develop a 0.05% betamethasone gel characterized by physical-chemical stability and good release properties. The preliminary studies were designed to select the gel-forming agents and the excipients compatible with betamethasone dipropionate. In order to formulate a clear gel without particles of drug substances in suspension, a solvent system for the drug substance was selected. The content of drug substance released, the rheological and in vitro release tests were the tools used for the optimal formulation selection. A stable carbomer gel was obtained by solubilization of betamethasone dipropionate in a vehicle composed by 40% PEG 400, 10% ethanol and 5% Transcutol.

  1. 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.

  2. 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.

  3. Selected topics in personnel selection: primarily in the early to mid-years of the 20th century.

    PubMed

    Merenda, Peter F

    2005-06-01

    A brief historical review is presented of the events in the USA relating to personnel selection in business and industry from 1903 to 2003. Emphasis is placed on the early periods of the century through the midyears. Involved in these events have been applied psychologists, the American Psychological Association, Government Agencies, Federal, Circuit Courts of Appeals, and the Supreme Court.

  4. 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.

  5. Selected Topics in Light Front Field Theory and Applications to the High Energy Phenomena

    NASA Astrophysics Data System (ADS)

    Kundu, Rajen

    1999-10-01

    In this thesis, we have presented some of the aspects of light-front (LF) field theory through their successful application in the Deep Inelastic Scattering (DIS). We have developed a LFQCD Hamiltonian description of the DIS structure functions starting from Bjorken-Johnson-Low limit of virtual forward Compton scattering amplitude and using LF current commutators. We worked in the LF gauge A^+=0 and used the old-fashioned LFQCD perturbation theory in our calculations. The importance of our work are summarized below. Our approach shares the intution of parton model and addresses directly the structure functions, which are experimental objects, instead of its moments as in OPE method. Moreover, it can potentially incorporate the non-perturbative contents of the structure functions as we have demonstrated by introducing a new factorization scheme. In the context of nucleonic helicity structure, the well known gauge fixed LF helicity operator is shown to provide consistent physical information and helps us defining new relevant structure functions. The anomalous dimensions relevant for the Q^2-evolution of such structure functions are calculated. Our study is important in establishing the equivalance of LF field theory and the usual equal-time one through perturbative calculations of the dressed parton structure functions reproducing the well known results. Also the importance of Gallilean boost symmetry in understanding the correctness of any higher order calculation using (x^+)-ordered LFQCD perturbation theory are emphasized.

  6. 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

  7. 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.

  8. Topical Structure in Argumentative Essays of EFL Learners and Implications for Writing Classes

    ERIC Educational Resources Information Center

    Kiliç, Mehmet; Genç, Bilal; Bada, Erdogan

    2016-01-01

    The literature on the topical organization of essays suggests that there are four possible types of progression from the topic of one clause to the topics of the following clauses. These are parallel, sequential, extended parallel, and extended sequential progressions. Essay writers' ability to create cohesion and coherence can be evaluated on the…

  9. Selected Occupational Topics

    ERIC Educational Resources Information Center

    Business Education Forum, 1973

    1973-01-01

    Research studies are classified in this regular section as marketing and distribution, typewriting, basic business and economics, shorthand and transcription, data processing, and the beginning teacher. (MU)

  10. 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.

  11. Structure and selectivity in bestrophin ion channels

    DOE PAGES

    Yang, Tingting; Liu, Qun; Kloss, Brian; ...

    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

  12. Hierarchical Theme and Topic Modeling.

    PubMed

    Chien, Jen-Tzung

    2016-03-01

    Considering the hierarchical data groupings in text corpus, e.g., words, sentences, and documents, we conduct the structural learning and infer the latent themes and topics for sentences and words from a collection of documents, respectively. The relation between themes and topics under different data groupings is explored through an unsupervised procedure without limiting the number of clusters. A tree stick-breaking process is presented to draw theme proportions for different sentences. We build a hierarchical theme and topic model, which flexibly represents the heterogeneous documents using Bayesian nonparametrics. Thematic sentences and topical words are extracted. In the experiments, the proposed method is evaluated to be effective to build semantic tree structure for sentences and the corresponding words. The superiority of using tree model for selection of expressive sentences for document summarization is illustrated.

  13. 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…

  14. 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.…

  15. Natural selection and age-structured populations.

    PubMed

    Demetrius, L

    1975-03-01

    This paper studies the properties of a new class of demographic parameters for age-structured populations and analyzes the effect of natural selection on these parameters. Two new demographic variables are introduced: the entropy of a population and the reproductive potential. The entropy of a population measures the variability of the contribution of the different age classes to the stationary population. The reproductive potential measures the mean of the contribution of the different age classes to the Malthusian parameter. The Malthusian parameter is precisely the difference between the entropy and the reproductive potential. The effect of these demographic variables on changes in gene frequency is discussed. The concept of entropy of a genotype is introduced and it is shown that in a random mating population in Hardy-Weinberg equilibrium and under slow selection, the rate of change of entropy is equal to the genetic variance in entropy minus the covariance in entropy and reproductive potential. This result is an information theoretic analog of Fisher's fundamental theorem of natural selection.

  16. 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…

  17. 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...

  18. 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.

  19. 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…

  20. 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…

  1. 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.

  2. REVIEWS OF TOPICAL PROBLEMS: Minimal chaos, stochastic webs, and structures of quasicrystal symmetry

    NASA Astrophysics Data System (ADS)

    Zaslavskiĭ, G. M.; Sagdeev, Roal'd. Z.; Usikov, D. A.; Chernikov, A. A.

    1988-10-01

    The relationship between the problem of the symmetry of a plane tiling and the properties of nonintegrable dynamic systems is reviewed. The formation of stochastic layers and a stochastic web in the motion of linear and nonlinear oscillators subjected to a perturbation is discussed in detail. Emphasis is placed on research on the symmetry properties of a stochastic web with a fractal structure of a quasicrystal type. Structures with a quasicrystal symmetry form as a result of an interaction of two types of symmetries: translational and rotational. Various characteristics of structures with a quasicrystal symmetry are discussed: the distributions of stable and unstable points, the state density, and the Fourier spectrum. Quasicrystal structures in solid state physics, hydrodynamics, botany, and ornamental art are discussed.

  3. Discriminating the molecular identity and function of discrete supramolecular structures in topical pharmaceutical formulations.

    PubMed

    Benaouda, F; Brown, M B; Ganguly, S; Jones, S A; Martin, G P

    2012-09-04

    There is a need to understand how solvent structuring influences drug presentation in pharmaceutical preparations, and the aim of this study was to characterize the properties of propylene glycol (PG)/water supramolecular structures such that their functional consequences on drug delivery could be assessed. Shifts to higher wavenumbers in the C-H and C-O infrared stretching vibrations of PG (up to 8.6 and 11 cm(-1), respectively) implied that water supramolecular structures were being formed as a consequence of hydrophobic hydration. However, unlike analogous binary solvent systems, water structuring was not enhanced by the presence of the cosolvent. Two discrete populations of supramolecular structures were evident from the infrared spectroscopy: water-rich structures, predominant below a PG volume fraction (f(PG)) of 0.4 (unmoving water bending vibration at 1211 cm(-1)) and PG-rich structures, predominant above 0.4 f(PG) (both C-H and water peaks moved to lower wavenumbers). The un-ionized diclofenac log-linear solubility and transmembrane transport altered dramatically when f(PG) > 0.55 (a 10-fold increase in transport from 0.28 ± 0.06 μg·cm(-2)·h(-1) at 0.2 f(PG) to 2.81 ± 0.16 μg·cm(-2)·h(-1) at 0.9 f(PG)), and this demonstrated the ability of the PG rich supramolecular structures, formed in the PG/water solvent, to specifically modify the behavior of un-ionized diclofenac.

  4. 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

  5. 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.

  6. 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…

  7. REVIEWS OF TOPICAL PROBLEMS: Prediction and discovery of new structures in spiral galaxies

    NASA Astrophysics Data System (ADS)

    Fridman, Aleksei M.

    2007-02-01

    A review is given of the last 20 years of published research into the nature, origin mechanisms, and observed features of spiral-vortex structures found in galaxies. The so-called rotating shallow water experiments are briefly discussed, carried out with a facility designed by the present author and built at the Russian Scientific Center 'Kurchatov Institute' to model the origin of galactic spiral structures. The discovery of new vortex-anticyclone structures in these experiments stimulated searching for them astronomically using the RAS Special Astrophysical Observatory's 6-meter BTA optical telescope, formerly the world's and now Europe's largest. Seven years after the pioneering experiments, Afanasyev and the present author discovered the predicted giant anticyclones in the galaxy Mrk 1040 by using BTA. Somewhat later, the theoretical prediction of giant cyclones in spiral galaxies was made, also to be verified by BTA afterwards. To use the observed line-of-sight velocity field for reconstructing the 3D velocity vector distribution in a galactic disk, a method for solving a problem from the class of ill-posed astrophysical problems was developed by the present author and colleagues. In addition to the vortex structure, other new features were discovered — in particular, slow bars (another theoretical prediction), for whose discovery an observational test capable of distinguishing them from their earlier-studied normal (fast) counterparts was designed.

  8. Efinaconazole Topical

    MedlinePlus

    ... may catch fire. Stay away from heat and flames while you are applying this medication.Do not get a pedicure or apply nail polish or other cosmetic nail products to your toenails during your treatment with efinaconazole topical solution.To apply the topical ...

  9. TOPICAL REVIEW: Asymptotic directional structure of radiative fields in spacetimes with a cosmological constant

    NASA Astrophysics Data System (ADS)

    Krtous, Pavel; Podolský, Jirí

    2004-12-01

    We analyse the directional properties of general gravitational, electromagnetic and spin-s fields near conformal infinity \\scri . The fields are evaluated in normalized tetrads which are parallelly propagated along null geodesics which approach a point P of \\scri . The standard peeling-off property is recovered and its meaning is discussed and refined. When the (local) character of the conformal infinity is null, such as in asymptotically flat spacetimes, the dominant term which is identified with radiation is unique. However, for spacetimes with a non-vanishing cosmological constant the conformal infinity is spacelike (for Λ > 0) or timelike (for Λ < 0), and the radiative component of each field depends substantially on the null direction along which P is approached. The directional dependence of asymptotic fields near such de Sitter-like or anti-de Sitter-like \\scri is explicitly found and described. We demonstrate that the corresponding directional structure of radiation has a universal character that is determined by the algebraic (Petrov) type of the field. In particular, when Λ > 0 the radiation vanishes only along directions which are opposite to principal null directions. For Λ < 0 the directional dependence is more complicated because it is necessary to distinguish outgoing and ingoing radiation. Near such anti-de Sitter-like conformal infinity the corresponding directional structures differ, depending not only on the number and degeneracy of the principal null directions at P but also on their specific orientation with respect to \\scri . The directional structure of radiation near (anti-)de Sitter-like infinities supplements the standard peeling-off property of spin-s fields. This characterization offers a better understanding of the asymptotic behaviour of the fields near conformal infinity under the presence of a cosmological constant.

  10. 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...

  11. 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

  12. Selecting the Optimum Army Stock Fund Structure

    DTIC Science & Technology

    1991-08-01

    to manage more effectively the DoD and its defense resources.ŕ As a part of the DMR , finance and accounting functions of the Services have been...budget reductions, consolidation of accounting and supply functions across the Services , Army strategic logistics programs, and other initiatives of the...either vertical or horizontal in their structure. In a vertical structure, all Service -managed materiel for both wholesale and retail requirements is

  13. The use of plants in prospecting for gold: A brief overview with a selected bibliography and topic index

    USGS Publications Warehouse

    Erdman, J.A.; Olson, J.C.

    1985-01-01

    The focal point of this report is a bibliography of 133 references and an associated topic index - both of which could be useful to geochemists attempting to locate new Au deposits. Fifty of these references originated in the Soviet Union, where most of the initial work on biogeochemical exploration for Au had been done. The 15 topics in the index range from agriculture (Au in crop plants) to silver. As an introduction to the bibliography, we have briefly described some examples of applications and difficulties in using plants. These examples are drawn from the literature and from field experience. Because of the generally low Au concentrations found in plants, the analysis of plant tissue is critical to the successful application of the biogeochemical method of prospecting. Neuron activation analysis is the most widely used method to detect Au in plants, due largely to its sensitivity; levels in the parts per billion range are easily attained. Two general types of sampling media are used in prospecting for Au: humus and living plants. Humus has been widely used in Canada, but the sampling of plants has increased there and elsewhere in recent years. Our use of douglas-fir (Pseudotsuga menziesii) at a Au-bearing stockwork in Idaho is a prime example. A maximum Au concentration of 14 ??g/g (ppm) was detected in the wood ash of this coniferous tree, well above the normal concentration of ??? 0.15 ??g/g. Among shrubs that might be useful in Au prospecting, we recommend sagebrush or wormwood (genus Artemisia), because it is extremely responsive to concealed mineralization. It has been used extensively in the Soviet Union and could be used in areas of the western United States where disseminated Au occurrences might be located. Among the problems one may encounter in using plants for Au prospecting are: (1) physiological barriers, by which many plant species simply do not absorb Au at detectable levels; (2) misconceptions of soil-plant correlations; (3) localization of

  14. 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.

  15. 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…

  16. 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.

  17. 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 ...

  18. Estradiol Topical

    MedlinePlus

    Estradiol topical gel and emulsion (lotion type mixture) are used to treat and prevent hot flushes (hot flashes; sudden strong feelings of heat and sweating) in women who are experiencing menopause ( ...

  19. Testosterone Topical

    MedlinePlus

    ... eyes, wash them right away with warm, clean water. Call a doctor if your eyes become irritated.Testosterone topical comes in single use tubes and packets and a multiple use pump. The pump releases a specific amount of testosterone ...

  20. Target selection and determination of function in structural genomics.

    PubMed

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

    2003-01-01

    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.

  1. 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.

  2. 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.…

  3. 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

  4. Structure of artificial enamel lesions after topical applications of high-concentration sodium fluoride solution in vitro.

    PubMed

    Wen, H B; Cui, F Z; Chen, X Q; Wang, Q; Li, H D

    1995-01-01

    A three-layer structure, including a columnar layer (CL), a buffer layer, and unaffected intact enamel, was successively formed from the outer to the inner part of artificial enamel lesions (AEL) by topical applications of a high-concentration acidic sodium fluoride solution (10,000 ppm, pH 5.6) in vitro. The AEL was produced in bovine enamel that was decalcified for 5 days in a lactic acid gel system. The morphological observations by using scanning electron microscopy showed that the CL was made of columnar deposits of small globules about 0.5 microns in diameter. It was observed for the first time that small globules filled the demineralized interprismatic regions in the buffer layer. The unaffected intact enamel was protected from further demineralization under the acidic condition. Structure and composition of the CL were investigated by using X-ray diffraction and X-ray photoelectron spectroscopy. In the CL the atomic ratio was Ca:P = 12.6 and Ca:F = 0.75, and the small globules were mainly a mixture of polycrystalline calcium fluoride and hydroxyapatite. For comparison, the sound enamel and the AEL attained by applications of 0 and 100 ppm acidic sodium fluoride solutions (pH 5.6) were also investigated. The formation mechanism of the three-layer structure and the related cariostatic effects are discussed.

  5. Selective traditions in group discussions: teachers' views about good science and the possible obstacles when encountering a new topic

    NASA Astrophysics Data System (ADS)

    Lundqvist, Eva; Sund, Per

    2016-11-01

    There is an ongoing discussion about what content that should be taught in science education and there are different views among teachers about what represent good science content. However, teachers are not isolated individuals making their own interpretations, but are part of institutionalised systems building on patterns in the selection of teaching goals and content. Earlier research shows that teachers teach in alignment with different selective traditions, which can be understood as well-developed teaching habits. Individual teachers seem to develop their personal habits on the basis of the contextual situations created by earlier generations of teachers. In order to find out which content teachers find representative for science education, we asked nine teachers to take part in group interviews to talk about what they value as "good" science content. The participants were grouped according to their selective traditions expressed in earlier studies. The method was used to dynamically explore, challenge and highlight teachers' views. The starting point for the group discussions is national tests in science. In Sweden, national tests in biology, physics and chemistry were introduced in secondary school science (year 9) in 2009. One overarching aim of these tests is to support the implementation of the science curricula and to include for example knowledge about socio-scientific issues (SSI). The content of the tests can consequently be seen as important for teachers to consider. The findings show that `resistance' to including SSI is not just an issue for individual teachers. As individuals teachers can create many kinds of obstacles, but still be interested in integrating SSI in their science teaching. However, in group discussions the teachers tend to collectively adopt the scientific rational discourse. This discourse is what joins them and creates their common identity as science teachers. In turn, they seek to free scientific knowledge from social knowledge

  6. 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.

  7. 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)

  8. 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.

  9. 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.

  10. 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.

  11. Image Modeling and Enhancement via Structured Sparse Model Selection

    DTIC Science & Technology

    2010-01-01

    signal estimation is then calculated with the selected model. The model selection leads to a guaranteed near optimal denoising estimator. The degree...are adapted to the image of interest and are computed with a simple and fast procedure. State-of-the-art results are shown in image denoising ...deblurring, and inpainting. Index Terms— Model selection, structured sparsity, best basis, denoising , deblurring, inpainting 1. INTRODUCTION Image enhancement

  12. Lack of selectivity of protoporphyrin IX fluorescence for basal cell carcinoma after topical application of 5-aminolevulinic acid: implications for photodynamic treatment.

    PubMed

    Martin, A; Tope, W D; Grevelink, J M; Starr, J C; Fewkes, J L; Flotte, T J; Deutsch, T F; Anderson, R R

    1995-01-01

    Clinical trials of topical ALA in photodynamic therapy (PDT) of basal cell carcinoma (BCC) show significant recurrence rates. Exogenous 5-aminolevulinic acid (ALA) is converted by intracellular enzymes to photoactive protoporphyrin IX (PpIX) in human tissues. PpIX generates cytotoxic singlet oxygen when irradiated with visible light in the 400-640 nm range. To evaluate variability and heterogeneity in PpIX production by tumors in such trials, and to assess the usefulness of PpIX for marking skin tumors, we measured PpIX fluorescence distribution in BCC after topical application of 20% ALA cream. ALA cream was applied under occlusion for periods ranging from 3 to 18 h (average 6.9 h, SD 4 h) to 16 BCCs. ALA conversion to PpIX in the BCCs was assessed by in vivo photography, ex vivo video fluorescence imaging, and fluorescence microscopy. External macroscopic PpIX fluorescence, as assessed by in vivo and ex vivo imaging, correlated with the clinical presence of BCC. Examination by a digital imaging fluorescence microscope revealed inter- and intratumor fluorescence variability and heterogeneity. PpIX fluorescence corresponding to full tomor thickness was found in six superficial and four nodular tumors, and partial-thickness fluorescence was observed in five nodular tumors, but no PpIX fluorescence was observed in some areas of superficial, nodular and infiltrating tumors. In a significant number of nodular and infiltrating BCCs, topical ALA appeared to provide little or no PpIX in deep tumor lobules. In addition, no selectivity for tumor tissue versus normal epidermis was seen. The grossly brighter external PpIX fluorescence over tumors may be due, therefore, to enhanced penetration through tumor-reactive stratum corneum and to the tumor thickness.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Spinosad Topical

    MedlinePlus

    Spinosad suspension is used to treat head lice (small insects that attach themselves to the skin) in adults and ... Topical spinosad comes as a suspension (liquid) to apply to the scalp and hair. It is usually applied to the scalp and hair in one or sometimes ...

  14. Ciclopirox Topical

    MedlinePlus

    ... use this medication near heat or an open flame, such as a cigarette.To use ciclopirox topical solution, follow these steps: Be sure that you have trimmed your nails properly before your first treatment. Use the applicator brush attached to the bottle ...

  15. Acyclovir Topical

    MedlinePlus

    Zovirax® Cream ... Acyclovir cream is used to treat cold sores (fever blisters; blisters that are caused by a virus called herpes ... Topical acyclovir comes as a cream and an ointment to apply to the skin. Acyclovir cream is usually applied five times a day for 4 days. Acyclovir ...

  16. Clindamycin Topical

    MedlinePlus

    ... doctor if you have or have ever had asthma, eczema (sensitive skin that often becomes itchy or irritated) or allergies.tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while using topical clindamycin, ...

  17. Task 2.6 - Catalyst for Utilization of Methane in Selective Catalytic Reduction of NOx: Topical report, July 1, 1995

    SciTech Connect

    1997-12-31

    Selective catalytic reduction (SCR) of nitrogen oxides (NO{sub x}) in flue gas or engine exhaust gas with hydrocarbons as the reductant has great potential for less expense, less pollution, and easier operation than SCR with ammonia. Methane is the preferred reducing gas because of its low cost and low toxicity. Stable, low-cost catalysts for SCR with methane are required to demonstrate this technology for controlling NO{sub x} emissions. Several cobalt and nickel catalysts on synthetic clay and uranium oxide supports were investigated for their activities in reducing NO{sub x} with methane in the presence of air. The efficiency of the synthetic clay-supported nickel and cobalt catalysts for nitric oxide (NO) reduction with methane as the reducing gas was poor. The nickel oxide-uranium oxide catalyst, which was chosen for its high stability, was also ineffective. Results from the two-step experiments conducted at two temperatures produced some interesting information on the reactions of methane with the catalysts and the reactivity of the carbonaceous intermediate. The carbonaceous material formed from methane dissociation at 450{degrees}C not only reduces NO to N{sub 2}O at lower temperatures, but also prevents oxidation of NO to NO{sub 2}. Unfortunately, the carbonaceous forms that reduce the NO are not available for reactions at 400{degrees}C in the presence of oxygen. A two-step process employing this chemistry would be difficult because the catalyst would have to be cycled between the two temperatures. Also the desired reduction to nitrogen is not very efficient.

  18. Bibliographic analysis of scientific research on selected topics in public health nutrition in West Africa: Review of articles published from 1998 to 2008.

    PubMed

    Aaron, Grant J; Wilson, Shelby E; Brown, Kenneth H

    2010-01-01

    Few countries in West Africa have the capacity for carrying out advanced training in nutrition and public health. To provide additional information on current regional applied nutrition research capacity and productivity, we analysed peer-reviewed articles on key public health nutrition topics that were published from 1998 to 2008. Using MEDLINE/PubMed, the following terms were searched: 'breast feeding', 'infant nutrition physiology' (comprising complementary feeding and weaning), 'protein energy malnutrition', 'nutrition and infection', 'vitamin A', 'iodine', 'zinc' and 'overweight', each linked with the term 'Western Africa'. In total, 412 unique articles (37±6 articles per year) were identified. Most research focused on infant and young child feeding practices, selected micronutrient deficiencies, and the emerging problem of overweight and obesity. The primary author of nearly half (46%) the publications was located in an institution outside of West Africa. Most articles were published in English (90%), and nearly half of all articles (41%) were cross-sectional studies. Our findings indicate that few peer-reviewed research studies are being published on key public health topics in the West African region, considering the magnitude of nutrition problems in this region. New approaches are needed to encourage and support research capacity and output in West Africa.

  19. Selective Refinement and Molecular Dynamics Ranking Selection of Near-native Protein Structures

    NASA Astrophysics Data System (ADS)

    Zhang, Jiong; Zhang, Jingfen; Xu, Dong; Shang, Yi; Kosztin, Ioan

    2014-03-01

    In recent years in silico protein structure prediction reached a level where a variety of servers can generate large pools of near-native structures. However, the identification and further refinement of the best structures from the pool of decoys remain problematic. To address these issues, we have developed a selective refinement protocol (SRP), and a molecular dynamics (MD) simulation based ranking method (MDR). In SRP the refinement of structures is accomplished by using the relax mode of the Rosetta software package, subject to specific constraints determined by the type and complexity of the target. The final best models are selected with MDR by testing their relative stability against gradual heating during all atom MD simulations. We have implemented the selective refinement protocol and the MDR method in Mufold-MD, our fully automated protein structure prediction server. Mufold-MD was one of the top servers in the CASP10 competition.

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. 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…

  5. 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…

  6. Topicality and the Structure of Interactive Talk in Face-to-Face Seminar Discussions: Implications for Research in Distributed Learning Media

    ERIC Educational Resources Information Center

    Gibson, Will; Hall, Andy; Callery, Peter

    2006-01-01

    This article examines the structure of topic movement within face-to-face postgraduate university seminar discussion forums through a conversation analytic approach. The analysis of 12 audio recordings of seminars showed that in spite of clear differences in the management style of sessions by seminar leaders there were important consistencies in…

  7. 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.

  8. TSTMP: target selection for structural genomics of human transmembrane proteins

    PubMed Central

    Varga, Julia; Dobson, László; Reményi, István; Tusnády, Gábor E.

    2017-01-01

    The TSTMP database is designed to help the target selection of human transmembrane proteins for structural genomics projects and structure modeling studies. Currently, there are only 60 known 3D structures among the polytopic human transmembrane proteins and about a further 600 could be modeled using existing structures. Although there are a great number of human transmembrane protein structures left to be determined, surprisingly only a small fraction of these proteins have ‘selected’ (or above) status according to the current version the TargetDB/TargetTrack database. This figure is even worse regarding those transmembrane proteins that would contribute the most to the structural coverage of the human transmembrane proteome. The database was built by sorting out proteins from the human transmembrane proteome with known structure and searching for suitable model structures for the remaining proteins by combining the results of a state-of-the-art transmembrane specific fold recognition algorithm and a sequence similarity search algorithm. Proteins were searched for homologues among the human transmembrane proteins in order to select targets whose successful structure determination would lead to the best structural coverage of the human transmembrane proteome. The pipeline constructed for creating the TSTMP database guarantees to keep the database up-to-date. The database is available at http://tstmp.enzim.ttk.mta.hu. PMID:27924015

  9. Advanced Topics in Control Systems Theory

    NASA Astrophysics Data System (ADS)

    Lorsa, Antonio; Lamnabhi-Lagarrigue, Françoise; Panteley, Elena

    Advanced Topics in Control Systems Theory contains selected contributions written by lecturers at the third (annual) Formation d'Automatique de Paris (FAP) (Graduate Control School in Paris). Following on from the lecture notes from the second FAP (Volume 311 in the same series) it is addressed to graduate students and researchers in control theory with topics touching on a variety of areas of interest to the control community such as nonlinear optimal control, observer design, stability analysis and structural properties of linear systems.

  10. Computer program simplifies selection of structural steel columns

    NASA Technical Reports Server (NTRS)

    Vissing, G. S.

    1966-01-01

    Computer program rapidly selects appropriate size steel columns and base plates for construction of multistory structures. The program produces a printed record containing the size of a section required at a particular elevation, the stress produced by the loads, and the allowable stresses for that section.

  11. Refinement and Selection of Near-native Protein Structures

    NASA Astrophysics Data System (ADS)

    Zhang, Jiong; Zhang, Jingfen; Shang, Yi; Xu, Dong; Kosztin, Ioan

    2013-03-01

    In recent years in silico protein structure prediction reached a level where a variety of servers can generate large pools of near-native structures. However, the identification and further refinement of the best structures from the pool of decoys continue to be problematic. To address these issues, we have developed a selective refinement protocol (based on the Rosetta software package), and a molecular dynamics (MD) simulation based ranking method (MDR). The refinement of the selected structures is done by employing Rosetta's relax mode, subject to certain constraints. The selection of the final best models is done with MDR by testing their relative stability against gradual heating during all atom MD simulations. We have implemented the selective refinement protocol and the MDR method in our fully automated server Mufold-MD. Assessments of the performance of the Mufold-MD server in the CASP10 competition and other tests will be presented. This work was supported by grants from NIH. Computer time was provided by the University of Missouri Bioinformatics Consortium.

  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. Topics, methods and challenges in health promotion for people with intellectual disabilities: a structured review of literature.

    PubMed

    Naaldenberg, Jenneken; Kuijken, Noortje; van Dooren, Kate; van Schrojenstein Lantman de Valk, Henny

    2013-12-01

    People with intellectual disabilities (ID) experience substantial health inequities compared, with the general population. Many secondary conditions and lifestyle related health problems could be, prevented with adequate health promotion. The aim of this structured review is to provide insight into, the main characteristics of published health promotion intervention studies for people with ID and, in, doing so, to identify best practice and knowledge gaps. Relevant studies were identified through a, structured literature search of multiple electronic databases (PubMed, CINHAS, Scopus, PsychINFO), the search strategy covered health promotion and intellectual disabilities for available papers, published between February 2002 and 2012. In total, 25 studies were included and analyzed. Overall, studies were diverse and explored a variety of health issues. Papers included a variety of participants (in relation to level of disability) and intervention approaches. With regard to quality, many studies, failed to report how they recruited their participants, and there were substantial challenges identified, by authors in relation to recruitment, implementation of interventions, and the selection of outcome, measures used as well as the usability of measures themselves. Our findings suggest that this field, experiences methodological weaknesses and inconsistencies that make it difficult to compare and, contrast results. Theoretically driven studies that take into account the views and expectations of, participants themselves are needed, as is research that investigates the reliability and validity of, outcome measures for the ID population. Collaboration with mainstream health promotion research is, critical.

  14. Solution structures and molecular interactions of selective melanocortin receptor antagonists.

    PubMed

    Lee, Chul-Jin; Yun, Ji-Hye; Lim, Sung-Kil; Lee, Weontae

    2010-12-01

    The solution structures and inter-molecular interaction of the cyclic melanocortin antagonists SHU9119, JKC363, HS014, and HS024 with receptor molecules have been determined by NMR spectroscopy and molecular modeling. While SHU9119 is known as a nonselective antagonist, JKC363, HS014, and HS024 are selective for the melanocortin subtype-4 receptor (MC4R) involved in modulation of food intake. Data from NMR and molecular dynamics suggest that the conformation of the Trp9 sidechain in the three MC4R-selective antagonists is quite different from that of SHU9119. This result strongly supports the concept that the spatial orientation of the hydrophobic aromatic residue is more important for determining selectivity than the presence of a basic, "arginine-like" moiety responsible for biological activity. We propose that the conformation of hydrophobic residues of MCR antagonists is critical for receptor-specific selectivity.

  15. Comparative study between synthetic and phospholipids of natural origin: effect of phospholipid selection on the behavior of a topical liposomal dosage form incorporating terbinafine.

    PubMed

    Koutsoulas, Charalampos; Suleiman, Ehsan; Wagner, Andreas; Žabka, Marian

    2014-12-01

    Selection of excipients used is a critical step in the design of a pharmaceutical dosage form as it affects its behavior upon application, as during storage. The purpose of the present study is to evaluate and compare the behavior of six liposomal formulations intended for topical application composed of two widely used phospholipids 1,2-diacyl-sn-glycero-3-phosphocholine and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine with and without incorporation of cholesterol. Liposomal hydrogels made of hydroxyethylcellulose 3% and incorporating the anti-fungal agent terbinafine hydrochloride (E)-N-(6,6-dimethyl-2-hepten-4-inyl)-N-methyl-1-naphthalene-methanamine (-hydrochloride) were prepared, their viscosity was measured and in vitro drug release was studied. Moreover, physical stability and drug retention during storage at two different temperatures (2-8 °C and RT) were examined over time. The results showed differences in the behavior between the two phospholipids while incorporation of cholesterol at the studied concentrations was found to be of minor importance. Drug release was found to be favorable from 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) liposomal hydrogels and drug retention was found to be higher at lower storage temperature for all batches. Original physicochemical properties of all batches were found to be retained at least for a week.

  16. Sexual selection predicts brain structure in dragon lizards.

    PubMed

    Hoops, D; Ullmann, J F P; Janke, A L; Vidal-Garcia, M; Stait-Gardner, T; Dwihapsari, Y; Merkling, T; Price, W S; Endler, J A; Whiting, M J; Keogh, J S

    2017-02-01

    Phenotypic traits such as ornaments and armaments are generally shaped by sexual selection, which often favours larger and more elaborate males compared to females. But can sexual selection also influence the brain? Previous studies in vertebrates report contradictory results with no consistent pattern between variation in brain structure and the strength of sexual selection. We hypothesize that sexual selection will act in a consistent way on two vertebrate brain regions that directly regulate sexual behaviour: the medial preoptic nucleus (MPON) and the ventromedial hypothalamic nucleus (VMN). The MPON regulates male reproductive behaviour whereas the VMN regulates female reproductive behaviour and is also involved in male aggression. To test our hypothesis, we used high-resolution magnetic resonance imaging combined with traditional histology of brains in 14 dragon lizard species of the genus Ctenophorus that vary in the strength of precopulatory sexual selection. Males belonging to species that experience greater sexual selection had a larger MPON and a smaller VMN. Conversely, females did not show any patterns of variation in these brain regions. As the volumes of both these regions also correlated with brain volume (BV) in our models, we tested whether they show the same pattern of evolution in response to changes in BV and found that the do. Therefore, we show that the primary brain nuclei underlying reproductive behaviour in vertebrates can evolve in a mosaic fashion, differently between males and females, likely in response to sexual selection, and that these same regions are simultaneously evolving in concert in relation to overall brain size.

  17. Target selection and deselection at the Berkeley Structural Genomics Center.

    PubMed

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

    2006-02-01

    At the Berkeley Structural Genomics Center (BSGC), our goal is to obtain a near-complete structural complement of proteins in the minimal organisms Mycoplasma genitalium and M. pneumoniae, two closely related pathogens. Current targets for structure determination have been selected in six major stages, starting with those predicted to be most tractable to high throughput study and likely to yield new structural information. We report on the process used to select these proteins, as well as our target deselection procedure. Target deselection reduces experimental effort by eliminating targets similar to those recently solved by the structural biology community or other centers. We measure the impact of the 69 structures solved at the BSGC as of July 2004 on structure prediction coverage of the M. pneumoniae and M. genitalium proteomes. The number of Mycoplasma proteins for which the fold could first be reliably assigned based on structures solved at the BSGC (24 M. pneumoniae and 21 M. genitalium) is approximately 25% of the total resulting from work at all structural genomics centers and the worldwide structural biology community (94 M. pneumoniae and 86 M. genitalium) during the same period. As the number of structures contributed by the BSGC during that period is less than 1% of the total worldwide output, the benefits of a focused target selection strategy are apparent. If the structures of all current targets were solved, the percentage of M. pneumoniae proteins for which folds could be reliably assigned would increase from approximately 57% (391 of 687) at present to around 80% (550 of 687), and the percentage of the proteome that could be accurately modeled would increase from around 37% (254 of 687) to about 64% (438 of 687). In M. genitalium, the percentage of the proteome that could be structurally annotated based on structures of our remaining targets would rise from 72% (348 of 486) to around 76% (371 of 486), with the percentage of accurately modeled

  18. Social dilemma structure hidden behind traffic flow with route selection

    NASA Astrophysics Data System (ADS)

    Tanimoto, Jun; Nakamura, Kousuke

    2016-10-01

    Several traffic flows contain social dilemma structures. Herein, we explored a route-selection problem using a cellular automaton simulation dovetailed with evolutionary game theory. In our model, two classes of driver-agents coexist: D agents (defective strategy), which refer to traffic information for route selection to move fast, and C agents (cooperative strategy), which are insensitive to information and less inclined to move fast. Although no evidence suggests that the social dilemma structure in low density causes vehicles to move freely and that in high density causes traffic jams, we found a structure that corresponds to an n-person (multiplayer) Chicken (n-Chicken) game if the provided traffic information is inappropriate. If appropriate traffic information is given to the agents, the n-Chicken game can be solved. The information delivered to vehicles is crucial for easing the social dilemma due to urban traffic congestion when developing technologies to support the intelligent transportation system (ITS).

  19. Prediction of Protein Structural Class Based on Gapped-Dipeptides and a Recursive Feature Selection Approach.

    PubMed

    Liu, Taigang; Qin, Yufang; Wang, Yongjie; Wang, Chunhua

    2015-12-24

    The prior knowledge of protein structural class may offer useful clues on understanding its functionality as well as its tertiary structure. Though various significant efforts have been made to find a fast and effective computational approach to address this problem, it is still a challenging topic in the field of bioinformatics. The position-specific score matrix (PSSM) profile has been shown to provide a useful source of information for improving the prediction performance of protein structural class. However, this information has not been adequately explored. To this end, in this study, we present a feature extraction technique which is based on gapped-dipeptides composition computed directly from PSSM. Then, a careful feature selection technique is performed based on support vector machine-recursive feature elimination (SVM-RFE). These optimal features are selected to construct a final predictor. The results of jackknife tests on four working datasets show that our method obtains satisfactory prediction accuracies by extracting features solely based on PSSM and could serve as a very promising tool to predict protein structural class.

  20. The structure and regulation of magnesium selective ion channels.

    PubMed

    Payandeh, Jian; Pfoh, Roland; Pai, Emil F

    2013-11-01

    The magnesium ion (Mg(2+)) is the most abundant divalent cation within cells. In man, Mg(2+)-deficiency is associated with diseases affecting the heart, muscle, bone, immune, and nervous systems. Despite its impact on human health, little is known about the molecular mechanisms that regulate magnesium transport and storage. Complete structural information on eukaryotic Mg(2+)-transport proteins is currently lacking due to associated technical challenges. The prokaryotic MgtE and CorA magnesium transport systems have recently succumbed to structure determination by X-ray crystallography, providing first views of these ubiquitous and essential Mg(2+)-channels. MgtE and CorA are unique among known membrane protein structures, each revealing a novel protein fold containing distinct arrangements of ten transmembrane-spanning α-helices. Structural and functional analyses have established that Mg(2+)-selectivity in MgtE and CorA occurs through distinct mechanisms. Conserved acidic side-chains appear to form the selectivity filter in MgtE, whereas conserved asparagines coordinate hydrated Mg(2+)-ions within the selectivity filter of CorA. Common structural themes have also emerged whereby MgtE and CorA sense and respond to physiologically relevant, intracellular Mg(2+)-levels through dedicated regulatory domains. Within these domains, multiple primary and secondary Mg(2+)-binding sites serve to staple these ion channels into their respective closed conformations, implying that Mg(2+)-transport is well guarded and very tightly regulated. The MgtE and CorA proteins represent valuable structural templates to better understand the related eukaryotic SLC41 and Mrs2-Alr1 magnesium channels. Herein, we review the structure, function and regulation of MgtE and CorA and consider these unique proteins within the expanding universe of ion channel and transporter structural biology.

  1. Topical Search: AIDS and Youth.

    ERIC Educational Resources Information Center

    Department of Justice, Washington, DC. National Inst. of Justice.

    This topical search includes 30 of the most representative citations on the subject of Acquired Immune Deficiency Syndrome (AIDS) and youth selected from the National Institute of Justice/NCJRS (National Criminal Justice Reference Service) database. Topics covered in this package include education programs for in-school youth, policies and…

  2. Topics in composite materials and structures; Proceedings of the Sessions, ASME Summer Mechanics and Materials Conference, Tempe, AZ, Apr. 28-May 1, 1992

    NASA Astrophysics Data System (ADS)

    Birman, Victor; Nagar, Arvind

    Various papers on composite materials and structures are presented. The individual topics addressed include: dynamic stress concentrations in particle- and fiber-reinforced composite materials, structural analysis of textile composites, effect of fiber microstructure on evolution of residual stresses in silicon carbide/titanium aluminide composites, fracture strength modeling and analysis of notched composites, structural similitude and scaling laws for laminated beam plates, dynamic and static pseudo-axisymemtric thermal problems of generally laminated cylindrical shells, analytical method for developing the contact law of laminated plates.

  3. 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…

  4. 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

  5. [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

  6. 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.

  7. 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.

  8. 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

  9. Structural basis of PROTAC cooperative recognition for selective protein degradation.

    PubMed

    Gadd, Morgan S; Testa, Andrea; Lucas, Xavier; Chan, Kwok-Ho; Chen, Wenzhang; Lamont, Douglas J; Zengerle, Michael; Ciulli, Alessio

    2017-03-13

    Inducing macromolecular interactions with small molecules to activate cellular signaling is a challenging goal. PROTACs (proteolysis-targeting chimeras) are bifunctional molecules that recruit a target protein in proximity to an E3 ubiquitin ligase to trigger protein degradation. Structural elucidation of the key ternary ligase-PROTAC-target species and its impact on target degradation selectivity remain elusive. We solved the crystal structure of Brd4 degrader MZ1 in complex with human VHL and the Brd4 bromodomain (Brd4(BD2)). The ligand folds into itself to allow formation of specific intermolecular interactions in the ternary complex. Isothermal titration calorimetry studies, supported by surface mutagenesis and proximity assays, are consistent with pronounced cooperative formation of ternary complexes with Brd4(BD2). Structure-based-designed compound AT1 exhibits highly selective depletion of Brd4 in cells. Our results elucidate how PROTAC-induced de novo contacts dictate preferential recruitment of a target protein into a stable and cooperative complex with an E3 ligase for selective degradation.

  10. Quantification of Structural Isomers via Mode-Selective Irmpd

    NASA Astrophysics Data System (ADS)

    Polfer, Nicolas C.

    2016-06-01

    Mixtures of structural isomers can pose a challenge for vibrational ion spectroscopy. In cases where particular structures display diagnostic vibrations, these structures can be selectively "burned away". In ion traps, the ion population can be subjected to multiple laser shots, in order to fully deplete a particular structure, in effect allowing a quantification of this structure. Protonated para-amino benzoic acid (PABA) serves as an illustrative example. PABA is known to preferentially exist in the N-protonated (N-prot) form in solution, but in the gas phase it is energetically favorable in the O-protonated (O-prot) form. As shown in Figure 1, the N-prot structure can be kinetically trapped in the gas phase when sprayed from non-protic solvent, whereas the O-prot structure is obtained when sprayed from protic solvents, analogous to results by others [1,2]. y parking the light source on the diagnostic 3440 wn mode, the percentage of the O-prot structure can be determined, and by default the remainder is assumed to adopt the N-prot structure. It will be shown that the relative percentages of O-prot vs N-prot are highly dependent on the solvent mixture, going from close to 0% O-prot in non-protic solvents, to 99% in protic solvents. Surprisingly, water behaves much more like a non-protic solvent than methanol. It is observed that the capillary temperature, which aids droplet desolvation by black-body radiation in the ESI source, is critical to promote the appearance of O-prot structures. These results are consistent with the picture that a protic bridge mechanism is at play to facilitate proton transfer, and thus allow conversion from N-prot to O-prot, but that this mechanism is subject to appreciable kinetic barriers on the timescale of solvent evaporation. 1. J. Phys. Chem. A 2011, 115, 7625. 2. Anal. Chem. 2012, 84, 7857.

  11. Selected scientific topics of the 11th International Isotope Symposium on the Synthesis and Applications of Isotopes and Isotopically Labeled Compounds.

    PubMed

    Atzrodt, Jens; Derdau, Volker

    2013-01-01

    This micro-review describes hot topics and new trends in isotope science discussed at the 11th International Isotope Symposium on the Synthesis and Applications of Isotopes and Isotopically Labeled Compounds from a personal perspective.

  12. Helicopter aeroelastic stability and response - Current topics and future trends

    NASA Technical Reports Server (NTRS)

    Friedmann, Peretz P.

    1990-01-01

    This paper presents several current topics in rotary wing aeroelasticity and concludes by attempting to anticipate future trends and developments. These topics are: (1) the role of geometric nonlinearities; (2) structural modeling, and aeroelastic analysis of composite rotor blades; (3) aeroelastic stability and response in forward flight; (4) modeling of coupled rotor/fuselage aeromechanical problems and their active control; and (5) the coupled rotor-fuselage vibration problem and its alleviation by higher harmonic control. Selected results illustrating the fundamental aspects of these topics are presented. Future developments are briefly discussed.

  13. 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.

  14. The Selective Mutism Questionnaire: Measurement Structure and Validity

    PubMed Central

    Letamendi, Andrea M.; Chavira, Denise A.; Hitchcock, Carla A.; Roesch, Scott C.; Shipon-Blum, Elisa; Stein, Murray B.; Roesch, Scott C.

    2010-01-01

    Objective To evaluate the factor structure, reliability, and validity of the 17-item Selective Mutism Questionnaire. Method Diagnostic interviews were administered via telephone to 102 parents of children identified with selective mutism (SM) and 43 parents of children without SM from varying U.S. geographic regions. Children were between the ages of 3 and 11 inclusive and comprised 58% girls and 42% boys. SM diagnoses were determined using the Anxiety Disorders Interview Schedule for Children - Parent Version (ADIS-C/P); SM severity was assessed using the 17-item Selective Mutism Questionnaire (SMQ); and behavioral and affective symptoms were assessed using the Child Behavior Checklist (CBCL). An exploratory factor analysis (EFA) was conducted to investigate the dimensionality of the SMQ and a modified parallel analysis procedure was used to confirm EFA results. Internal consistency, construct validity, and incremental validity were also examined. Results The EFA yielded a 13-item solution consisting of three factors: a) Social Situations Outside of School, b) School Situations, and c) Home and Family Situations. Internal consistency of SMQ factors and total scale ranged from moderate to high. Convergent and incremental validity were also well supported. Conclusions Measure structure findings are consistent with the 3-factor solution found in a previous psychometric evaluation of the SMQ. Results also suggest that the SMQ provides useful and unique information in the prediction of SM phenomenon beyond other child anxiety measures. PMID:18698268

  15. Structure coefficients and strategy selection in multiplayer games.

    PubMed

    McAvoy, Alex; Hauert, Christoph

    2016-01-01

    Evolutionary processes based on two-player games such as the Prisoner's Dilemma or Snowdrift Game are abundant in evolutionary game theory. These processes, including those based on games with more than two strategies, have been studied extensively under the assumption that selection is weak. However, games involving more than two players have not received the same level of attention. To address this issue, and to relate two-player games to multiplayer games, we introduce a notion of reducibility for multiplayer games that captures what it means to break down a multiplayer game into a sequence of interactions with fewer players. We discuss the role of reducibility in structured populations, and we give examples of games that are irreducible in any population structure. Since the known conditions for strategy selection, otherwise known as [Formula: see text]-rules, have been established only for two-player games with multiple strategies and for multiplayer games with two strategies, we extend these rules to multiplayer games with many strategies to account for irreducible games that cannot be reduced to those simpler types of games. In particular, we show that the number of structure coefficients required for a symmetric game with [Formula: see text]-player interactions and [Formula: see text] strategies grows in [Formula: see text] like [Formula: see text]. Our results also cover a type of ecologically asymmetric game based on payoff values that are derived not only from the strategies of the players, but also from their spatial positions within the population.

  16. Widespread purifying selection on RNA structure in mammals.

    PubMed

    Smith, Martin A; Gesell, Tanja; Stadler, Peter F; Mattick, John S

    2013-09-01

    Evolutionarily conserved RNA secondary structures are a robust indicator of purifying selection and, consequently, molecular function. Evaluating their genome-wide occurrence through comparative genomics has consistently been plagued by high false-positive rates and divergent predictions. We present a novel benchmarking pipeline aimed at calibrating the precision of genome-wide scans for consensus RNA structure prediction. The benchmarking data obtained from two refined structure prediction algorithms, RNAz and SISSIz, were then analyzed to fine-tune the parameters of an optimized workflow for genomic sliding window screens. When applied to consistency-based multiple genome alignments of 35 mammals, our approach confidently identifies >4 million evolutionarily constrained RNA structures using a conservative sensitivity threshold that entails historically low false discovery rates for such analyses (5-22%). These predictions comprise 13.6% of the human genome, 88% of which fall outside any known sequence-constrained element, suggesting that a large proportion of the mammalian genome is functional. As an example, our findings identify both known and novel conserved RNA structure motifs in the long noncoding RNA MALAT1. This study provides an extensive set of functional transcriptomic annotations that will assist researchers in uncovering the precise mechanisms underlying the developmental ontologies of higher eukaryotes.

  17. Widespread purifying selection on RNA structure in mammals

    PubMed Central

    Smith, Martin A.; Gesell, Tanja; Stadler, Peter F.; Mattick, John S.

    2013-01-01

    Evolutionarily conserved RNA secondary structures are a robust indicator of purifying selection and, consequently, molecular function. Evaluating their genome-wide occurrence through comparative genomics has consistently been plagued by high false-positive rates and divergent predictions. We present a novel benchmarking pipeline aimed at calibrating the precision of genome-wide scans for consensus RNA structure prediction. The benchmarking data obtained from two refined structure prediction algorithms, RNAz and SISSIz, were then analyzed to fine-tune the parameters of an optimized workflow for genomic sliding window screens. When applied to consistency-based multiple genome alignments of 35 mammals, our approach confidently identifies >4 million evolutionarily constrained RNA structures using a conservative sensitivity threshold that entails historically low false discovery rates for such analyses (5–22%). These predictions comprise 13.6% of the human genome, 88% of which fall outside any known sequence-constrained element, suggesting that a large proportion of the mammalian genome is functional. As an example, our findings identify both known and novel conserved RNA structure motifs in the long noncoding RNA MALAT1. This study provides an extensive set of functional transcriptomic annotations that will assist researchers in uncovering the precise mechanisms underlying the developmental ontologies of higher eukaryotes. PMID:23847102

  18. 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

  19. Structural insight for chain selection and stagger control in collagen

    PubMed Central

    Boudko, Sergei P.; Bächinger, Hans Peter

    2016-01-01

    Collagen plays a fundamental role in all known metazoans. In collagens three polypeptides form a unique triple-helical structure with a one-residue stagger to fit every third glycine residue in the inner core without disturbing the poly-proline type II helical conformation of each chain. There are homo- and hetero-trimeric types of collagen consisting of one, two or three distinct chains. Thus there must be mechanisms that control composition and stagger during collagen folding. Here, we uncover the structural basis for both chain selection and stagger formation of a collagen molecule. Three distinct chains (α1, α2 and α3) of the non-collagenous domain 2 (NC2) of type IX collagen are assembled to guide triple-helical sequences in the leading, middle and trailing positions. This unique domain opens the door for generating any fragment of collagen in its native composition and stagger. PMID:27897211

  20. Modulation of chemical dermal absorption by 14 natural products: a quantitative structure permeation analysis of components often found in topical preparations.

    PubMed

    Muhammad, Faqir; Jaberi-Douraki, Majid; de Sousa, Damião Pergentino; Riviere, Jim E

    2016-12-14

    A large number of cosmetics and topical pharmaceuticals contain compounds of natural origin. There is a rising concern if these compounds can interact with the activity of other topically applied components in these formulations. The current study demonstrates modulation of dermal absorption of model components often found in topical preparations ((14)C caffeine and (14)C salicylic acid) by a set of 14 compounds of natural origin using a flow through in vitro porcine skin diffusion system. The parameters of flux and permeability were calculated and quantitative structure permeation relationship (QSPR) analysis conducted on different molecular descriptors of modulator compounds. Terpinyl acetate was the greatest permeability/flux enhancer for caffeine followed by s-perillyl acetate and limonene 1,2-epoxide. The permeability/flux of salicylic acid was highest with hydroxycitronellal followed by limonene 1,2-epoxide and s-perillyl acetate. The optimum descriptors using stepwise regression analysis for predicting additive modulation on penetrant permeability/flux were polar surface area, log P for caffeine and Henry's Law constant, number of freely rotatable bonds, and water solubility for salicylic acid. In parallel with the experimental techniques, a novel mathematical model was developed to estimate the permeability coefficients and improve the stepwise regression analysis for assessing modulator effects. The r(2) values significantly increased for multicomponent QSPR models. Notably, limonene 1,2-epoxide and s-perillyl acetate were excellent enhancers for both caffeine and salicylic acid. These results confirm that some natural products incorporated into topical formulations will enhance absorption of other components which could affect their safety and efficacy profiles.

  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. Coevolution of cooperation and network structure under natural selection

    NASA Astrophysics Data System (ADS)

    Yang, D.-P.; Lin, H.; Shuai, J. W.

    2011-02-01

    A coevolution model by coupling mortality and fertility selection is introduced to investigate the evolution of cooperation and network structure in the prisoner's dilemma game. The cooperation level goes through a continuous phase transition vs. defection temptation b for low mortality selection intensity β and through a discontinuous one for infinite β. The cooperation level is enhanced most at β≈1 for any b. The local and global properties of the network structure, such as cluster and cooperating k-core, are investigated for the understanding of cooperation evolution. Cooperation is promoted by forming a tight cooperating k-core at moderate β, but too large β will destroy the cooperating k-core rapidly resulting in a rapid drop of the cooperation level. Importantly, the infinite β changes the normalized sucker's payoff S from 0 to 1-b and its dynamics of the cooperation level undergoes a very slow power-law decay, which leads the evolution into the regime of neutral evolution.

  3. 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.

  4. 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.

  5. The age structure of selected countries in the ESCAP region.

    PubMed

    Hong, S

    1982-01-01

    The study objective was to examine the age structure of selected countries in the Economic and Social Commission for Asia and the Pacific (ESCAP) region, using available data and frequently applied indices such as the population pyramid, aged-child ratio, and median age. Based on the overall picture of the age structure thus obtained, age trends and their implication for the near future were arrived at. Countries are grouped into 4 types based on the fertility and mortality levels. Except for Japan, Hong Kong, and Singapore, the age structure in the 18 ESCAP region countries changed comparatively little over the 1950-80 period. The largest structural change occurred in Singapore, where the proportion of children under age 15 in the population declined significantly from 41-27%, while that of persons 65 years and older more than doubled. This was due primarily to the marked decline in fertility from a total fertility rate (TFR) of 6.7-1.8 during the period. Hong Kong also had a similar major transformation during the same period: the proportion of the old age population increased 2 1/2 times, from 2.5-6.3%. The age structures of the 18 ESCAP countries varied greatly by country. 10 countries of the 2 high fertility and mortality types showed a similar young age structural pattern, i.e., they have higher dependency ratios, a higher proportion of children under 15 years, a lower proportion of population 65 years and older, lower aged-child ratios, and younger median ages than the average countries in the less developed regions of the world. With minimal changes over the 1950-80 period, the gap between these countries and the average of the less developed regions widened. Unlike these 10 (mostly South Asian) countries, moderately low fertility and mortality countries (China, Korea, and Sri Lanka) are located between the world average and the less developed region in most of the indices, particularly during the last decade. Although their rate of population aging is not

  6. The objective structured interview for medical student selection

    PubMed Central

    Powis, D A; Neame, R L B; Bristow, T; Murphy, L B

    1988-01-01

    An objective structured interview is an integral part of the process of selecting and admitting applicants to study medicine at this university. During the nine years (to the end of 1986) that the interview has been used 1600 candidates were interviewed out of roughly 13 000 applicants, and from these, 584 students were admitted to the course. Analysis of the interview data was carried out based on two aspects of student progress: graduation with honours and failure to complete the course of study. The interview as a whole, and especially some of the subscales, appears to identify students who may fail to complete the course: it may also help to predict which students are likely to graduate with honours. PMID:3126966

  7. 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.

  8. 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

  9. Geographical structure and differential natural selection among North European populations.

    PubMed

    McEvoy, Brian P; Montgomery, Grant W; McRae, Allan F; Ripatti, Samuli; Perola, Markus; Spector, Tim D; Cherkas, Lynn; Ahmadi, Kourosh R; Boomsma, Dorret; Willemsen, Gonneke; Hottenga, Jouke J; Pedersen, Nancy L; Magnusson, Patrik K E; Kyvik, Kirsten Ohm; Christensen, Kaare; Kaprio, Jaakko; Heikkilä, Kauko; Palotie, Aarno; Widen, Elisabeth; Muilu, Juha; Syvänen, Ann-Christine; Liljedahl, Ulrika; Hardiman, Orla; Cronin, Simon; Peltonen, Leena; Martin, Nicholas G; Visscher, Peter M

    2009-05-01

    Population structure can provide novel insight into the human past, and recognizing and correcting for such stratification is a practical concern in gene mapping by many association methodologies. We investigate these patterns, primarily through principal component (PC) analysis of whole genome SNP polymorphism, in 2099 individuals from populations of Northern European origin (Ireland, United Kingdom, Netherlands, Denmark, Sweden, Finland, Australia, and HapMap European-American). The major trends (PC1 and PC2) demonstrate an ability to detect geographic substructure, even over a small area like the British Isles, and this information can then be applied to finely dissect the ancestry of the European-Australian and European-American samples. They simultaneously point to the importance of considering population stratification in what might be considered a small homogeneous region. There is evidence from F(ST)-based analysis of genic and nongenic SNPs that differential positive selection has operated across these populations despite their short divergence time and relatively similar geographic and environmental range. The pressure appears to have been focused on genes involved in immunity, perhaps reflecting response to infectious disease epidemic. Such an event may explain a striking selective sweep centered on the rs2508049-G allele, close to the HLA-G gene on chromosome 6. Evidence of the sweep extends over a 8-Mb/3.5-cM region. Overall, the results illustrate the power of dense genotype and sample data to explore regional population variation, the events that have crafted it, and their implications in both explaining disease prevalence and mapping these genes by association.

  10. Geographical structure and differential natural selection among North European populations

    PubMed Central

    McEvoy, Brian P.; Montgomery, Grant W.; McRae, Allan F.; Ripatti, Samuli; Perola, Markus; Spector, Tim D.; Cherkas, Lynn; Ahmadi, Kourosh R.; Boomsma, Dorret; Willemsen, Gonneke; Hottenga, Jouke J.; Pedersen, Nancy L.; Magnusson, Patrik K.E.; Kyvik, Kirsten Ohm; Christensen, Kaare; Kaprio, Jaakko; Heikkilä, Kauko; Palotie, Aarno; Widen, Elisabeth; Muilu, Juha; Syvänen, Ann-Christine; Liljedahl, Ulrika; Hardiman, Orla; Cronin, Simon; Peltonen, Leena; Martin, Nicholas G.; Visscher, Peter M.

    2009-01-01

    Population structure can provide novel insight into the human past, and recognizing and correcting for such stratification is a practical concern in gene mapping by many association methodologies. We investigate these patterns, primarily through principal component (PC) analysis of whole genome SNP polymorphism, in 2099 individuals from populations of Northern European origin (Ireland, United Kingdom, Netherlands, Denmark, Sweden, Finland, Australia, and HapMap European-American). The major trends (PC1 and PC2) demonstrate an ability to detect geographic substructure, even over a small area like the British Isles, and this information can then be applied to finely dissect the ancestry of the European-Australian and European-American samples. They simultaneously point to the importance of considering population stratification in what might be considered a small homogeneous region. There is evidence from FST-based analysis of genic and nongenic SNPs that differential positive selection has operated across these populations despite their short divergence time and relatively similar geographic and environmental range. The pressure appears to have been focused on genes involved in immunity, perhaps reflecting response to infectious disease epidemic. Such an event may explain a striking selective sweep centered on the rs2508049-G allele, close to the HLA-G gene on chromosome 6. Evidence of the sweep extends over a 8-Mb/3.5-cM region. Overall, the results illustrate the power of dense genotype and sample data to explore regional population variation, the events that have crafted it, and their implications in both explaining disease prevalence and mapping these genes by association. PMID:19265028

  11. 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.

  12. [Structural Life Science towards the Regulation of Selective GPCR Signaling].

    PubMed

    Kobayashi, Takuya

    2016-01-01

    G protein-coupled receptors (GPCRs) are the largest family of receptors in the human genome. They are involved in many diseases and also the target of approximately 30% of all modern medicinal drugs. GPCRs respond to a broad spectrum of chemical entities, ranging from photons, protons, and calcium ions to small organic molecules (including odorants and neurotransmitters), peptides, and glycoproteins. Many GPCRs are members of closely related subfamilies that respond to the same hormone or neurotransmitter. However, they have different physiologic functions based on the cells in which they are expressed and the different signaling pathways that they exploit (e.g., coupling through heterotrimeric G-proteins such as Gs, Gi, and Gq, as well as β-arrestins). Antibody fragments including Fab and Fv can effectively stabilize and crystallize membrane proteins. However, using the mouse hybridoma technology it has been difficult to develop monoclonal antibodies that can recognize conformational epitopes of native GPCRs. We have recently succeeded in developing antibodies against native GPCRs using this technology in combination with our improved immunization and screening methods. In this symposium review, I present a successful example of prostaglandin E2 receptor (one of the GPCRs) crystallization using antibody fragments. To avoid several adverse effects of current therapeutics, it is essential to understand the molecular mechanism of GPCR signaling in a monomeric, dimeric, or oligomeric state. Also, we are interested in selectively regulating GPCR signaling via functional antibodies developed using our methods and/or the designed small organic molecules depending on the GPCR structure.

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

    PubMed

    Stompor, Monika; Żarowska, Barbara

    2016-05-11

    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.

  14. Cutaneous Injury-Related Structural Changes and Their Progression following Topical Nitrogen Mustard Exposure in Hairless and Haired Mice

    PubMed Central

    Orlicky, David J.; White, Carl W.; Agarwal, Rajesh

    2014-01-01

    To identify effective therapies against sulfur mustard (SM)-induced skin injuries, various animals have been used to assess the cutaneous pathology and related histopathological changes of SM injuries. However, these efforts to establish relevant skin injury endpoints for efficacy studies have been limited mainly due to the restricted assess of SM. Therefore, we employed the SM analog nitrogen mustard (NM), a primary vesicating and bifunctional alkylating agent, to establish relevant endpoints for efficient efficacy studies. Our published studies show that NM (3.2 mg) exposure for 12–120 h in both the hairless SKH-1 and haired C57BL/6 mice caused clinical sequelae of toxicity similar to SM exposure in humans. The NM-induced cutaneous pathology-related structural changes were further analyzed in this study and quantified morphometrically (as percent length or area of epidermis or dermis) of skin sections in mice showing these lesions. H&E stained skin sections of both hairless and haired mice showed that NM (12–120 h) exposure caused epidermal histopathological effects such as increased epidermal thickness, epidermal-dermal separation, necrotic/dead epidermis, epidermal denuding, scab formation, parakeratosis (24–120 h), hyperkeratosis (12–120 h), and acanthosis with hyperplasia (72–120 h). Similar NM exposure in both mice caused dermal changes including necrosis, edema, increase in inflammatory cells, and red blood cell extravasation. These NM-induced cutaneous histopathological features are comparable to the reported lesions from SM exposure in humans and animal models. This study advocates the usefulness of these histopathological parameters observed due to NM exposure in screening and optimization of rescue therapies against NM and SM skin injuries. PMID:24416404

  15. Cutaneous injury-related structural changes and their progression following topical nitrogen mustard exposure in hairless and haired mice.

    PubMed

    Tewari-Singh, Neera; Jain, Anil K; Orlicky, David J; White, Carl W; Agarwal, Rajesh

    2014-01-01

    To identify effective therapies against sulfur mustard (SM)-induced skin injuries, various animals have been used to assess the cutaneous pathology and related histopathological changes of SM injuries. However, these efforts to establish relevant skin injury endpoints for efficacy studies have been limited mainly due to the restricted assess of SM. Therefore, we employed the SM analog nitrogen mustard (NM), a primary vesicating and bifunctional alkylating agent, to establish relevant endpoints for efficient efficacy studies. Our published studies show that NM (3.2 mg) exposure for 12-120 h in both the hairless SKH-1 and haired C57BL/6 mice caused clinical sequelae of toxicity similar to SM exposure in humans. The NM-induced cutaneous pathology-related structural changes were further analyzed in this study and quantified morphometrically (as percent length or area of epidermis or dermis) of skin sections in mice showing these lesions. H&E stained skin sections of both hairless and haired mice showed that NM (12-120 h) exposure caused epidermal histopathological effects such as increased epidermal thickness, epidermal-dermal separation, necrotic/dead epidermis, epidermal denuding, scab formation, parakeratosis (24-120 h), hyperkeratosis (12-120 h), and acanthosis with hyperplasia (72-120 h). Similar NM exposure in both mice caused dermal changes including necrosis, edema, increase in inflammatory cells, and red blood cell extravasation. These NM-induced cutaneous histopathological features are comparable to the reported lesions from SM exposure in humans and animal models. This study advocates the usefulness of these histopathological parameters observed due to NM exposure in screening and optimization of rescue therapies against NM and SM skin injuries.

  16. 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

  17. 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.…

  18. INSTITUTIONAL POLICIES ON CONTROVERSIAL TOPICS.

    ERIC Educational Resources Information Center

    DUTTON, THOMAS B.; AND OTHERS

    THIS STUDY WAS DESIGNED TO DETERMINE INSTITUTIONAL POLICIES WITH REGARD TO SELECTED CONTROVERSIAL TOPICS WHICH ARE FREQUENTLY THE FOCUS OF ADMINISTRATIVE CONCERN AND ACTION. THE STUDY WAS DESIGNED TO GAIN INFORMATION ABOUT THE NATURE AND PURPOSES OF THE POLICIES, THE FORMULATION AND IMPLEMENTATION PROCESSES, AND THE SIGNIFICANCE OF THE ISSUES ON…

  19. 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.

  20. Women's Health Topics

    MedlinePlus

    ... Information by Audience For Women Women's Health Topics Women's Health Topics Share Tweet Linkedin Pin it More ... Print Take Time to Care about Your Health . Women often spend so much time helping others that ...

  1. Regulatory Information By Topic

    EPA Pesticide Factsheets

    EPA develops and enforces regulations that span many environmental topics, from acid rain reduction to wetlands restoration. Each topic listed below may include related laws and regulations, compliance enforcement information, policies guidance

  2. Structural correlates of selectivity and inactivation in potassium channels

    PubMed Central

    McCoy, Jason G.; Nimigean, Crina M.

    2011-01-01

    Potassium channels are involved in a tremendously diverse range of physiological applications requiring distinctly different functional properties. Not surprisingly, the amino acid sequences for these proteins are diverse as well, except for the region that has been ordained the “selectivity filter”. The goal of this review is to examine our current understanding of the role of the selectivity filter and regions adjacent to it in specifying selectivity as well as its role in gating/inactivation and possible mechanisms by which these processes are coupled. Our working hypothesis is that an amino acid network behind the filter modulates selectivity in channels with the same signature sequence while at the same time affecting channel inactivation properties. PMID:21958666

  3. TopicPanorama: A Full Picture of Relevant Topics.

    PubMed

    Wang, Xiting; Liu, Shixia; Liu, Junlin; Chen, Jianfei; Zhu, Jun; Guo, Baining

    2016-12-01

    This paper presents a visual analytics approach to analyzing a full picture of relevant topics discussed in multiple sources, such as news, blogs, or micro-blogs. The full picture consists of a number of common topics covered by multiple sources, as well as distinctive topics from each source. Our approach models each textual corpus as a topic graph. These graphs are then matched using a consistent graph matching method. Next, we develop a level-of-detail (LOD) visualization that balances both readability and stability. Accordingly, the resulting visualization enhances the ability of users to understand and analyze the matched graph from multiple perspectives. By incorporating metric learning and feature selection into the graph matching algorithm, we allow users to interactively modify the graph matching result based on their information needs. We have applied our approach to various types of data, including news articles, tweets, and blog data. Quantitative evaluation and real-world case studies demonstrate the promise of our approach, especially in support of examining a topic-graph-based full picture at different levels of detail.

  4. 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.…

  5. Structural characterization of the GSK-3beta active site using selective and non-selective ATP-mimetic inhibitors.

    PubMed

    Bertrand, J A; Thieffine, S; Vulpetti, A; Cristiani, C; Valsasina, B; Knapp, S; Kalisz, H M; Flocco, M

    2003-10-17

    GSK-3beta is a regulatory serine/threonine kinase with a plethora of cellular targets. Consequently, selective small molecule inhibitors of GSK-3beta may have a variety of therapeutic uses including the treatment of neurodegenerative diseases, type II diabetes and cancer. In order to characterize the active site of GSK-3beta, we determined crystal structures of unphosphorylated GSK-3beta in complex with selective and non-selective ATP-mimetic inhibitors. Analysis of the inhibitors' interactions with GSK-3beta in the structures reveals how the enzyme can accommodate a number of diverse molecular scaffolds. In addition, a conserved water molecule near Thr138 is identified that can serve a functional role in inhibitor binding. Finally, a comparison of the interactions made by selective and non-selective inhibitors highlights residues on the edge of the ATP binding-site that can be used to obtain inhibitor selectivity. Information gained from these structures provides a promising route for the design of second-generation GSK-3beta inhibitors.

  6. Protein structure and ionic selectivity in calcium channels: Selectivity filter size, not shape, matters

    PubMed Central

    Malasics, Attila; Gillespie, Dirk; Nonner, Wolfgang; Henderson, Douglas; Eisenberg, Bob; Boda, Dezső

    2009-01-01

    Calcium channels have highly charged selectivity filters (4 COO− groups) that attract cations in to balance this charge and minimize free energy, forcing the cations (Na+ and Ca2+) to compete for space in the filter. A reduced model was developed to better understand the mechanism of ion selectivity in calcium channels. The charge/space competition (CSC) mechanism implies that Ca2+ is more efficient in balancing the charge of the filter because it provides twice the charge as Na+ while occupying the same space. The CSC mechanism further implies that the main determinant of Ca2+ vs. Na+ selectivity is the density of charged particles in the selectivity filter, i.e., the volume of the filter (after fixing the number of charged groups in the filter). In this paper we test this hypothesis by changing filter length and/or radius (shape) of the cylindrical selectivity filter of our reduced model. We show that varying volume and shape together has substantially stronger effects than varying shape alone with volume fixed. Our simulations show the importance of depletion zones of ions in determining channel conductance calculated with the integrated Nernst-Planck equation. We show that confining the protein side chains with soft or hard walls does not influence selectivity. PMID:19818330

  7. HierarchicalTopics: visually exploring large text collections using topic hierarchies.

    PubMed

    Dou, Wenwen; Yu, Li; Wang, Xiaoyu; Ma, Zhiqiang; Ribarsky, William

    2013-12-01

    Analyzing large textual collections has become increasingly challenging given the size of the data available and the rate that more data is being generated. Topic-based text summarization methods coupled with interactive visualizations have presented promising approaches to address the challenge of analyzing large text corpora. As the text corpora and vocabulary grow larger, more topics need to be generated in order to capture the meaningful latent themes and nuances in the corpora. However, it is difficult for most of current topic-based visualizations to represent large number of topics without being cluttered or illegible. To facilitate the representation and navigation of a large number of topics, we propose a visual analytics system--HierarchicalTopic (HT). HT integrates a computational algorithm, Topic Rose Tree, with an interactive visual interface. The Topic Rose Tree constructs a topic hierarchy based on a list of topics. The interactive visual interface is designed to present the topic content as well as temporal evolution of topics in a hierarchical fashion. User interactions are provided for users to make changes to the topic hierarchy based on their mental model of the topic space. To qualitatively evaluate HT, we present a case study that showcases how HierarchicalTopics aid expert users in making sense of a large number of topics and discovering interesting patterns of topic groups. We have also conducted a user study to quantitatively evaluate the effect of hierarchical topic structure. The study results reveal that the HT leads to faster identification of large number of relevant topics. We have also solicited user feedback during the experiments and incorporated some suggestions into the current version of HierarchicalTopics.

  8. Structure dependent spin selectivity in electron transport through oligopeptides

    NASA Astrophysics Data System (ADS)

    Kiran, Vankayala; Cohen, Sidney R.; Naaman, Ron

    2017-03-01

    The chiral-induced spin selectivity (CISS) effect entails spin-selective electron transmission through chiral molecules. In the present study, the spin filtering ability of chiral, helical oligopeptide monolayers of two different lengths is demonstrated using magnetic conductive probe atomic force microscopy. Spin-specific nanoscale electron transport studies elucidate that the spin polarization is higher for 14-mer oligopeptides than that of the 10-mer. We also show that the spin filtering ability can be tuned by changing the tip-loading force applied on the molecules. The spin selectivity decreases with increasing applied force, an effect attributed to the increased ratio of radius to pitch of the helix upon compression and increased tilt angles between the molecular axis and the surface normal. The method applied here provides new insights into the parameters controlling the CISS effect.

  9. Value of Topics in Consumer Education

    ERIC Educational Resources Information Center

    Garman, E. Thomas; Gummerson, Ronald R.

    1977-01-01

    Reports preliminary findings from students who have completed a course in consumer education which address this question: What value do you now place on selected topics in consumer education? Topics with the greatest value were budgeting, dishonest and deceptive sales schemes, automobile insurance, principles of wise buying, and value comparison.…

  10. Topical vehicles based on natural surfactant/fatty alcohols mixed emulsifier: The influence of two polyols on the colloidal structure and in vitro/in vivo skin performance.

    PubMed

    Savic, Snezana; Weber, Christian; Tamburic, Slobodanka; Savic, Miroslav; Müller-Goymann, Christel

    2009-06-01

    There is a growing need for in-depth research into new skin- and environment-friendly surfactants, such as alkylpolyglucosides. The aim of this study was to assess whether, to which extent and by what mechanism the two commonly used hydrophilic excipients, propylene glycol (PG) and glycerol (GL), affect the colloidal structure of emulsions formed by a natural mixed emulsifier, cetearyl glucoside and cetearyl alcohol. Furthermore, the study was concerned with the effect of these changes on in vitro permeation profiles of two model drugs (diclofenac sodium and caffeine) and in vivo skin performance of the test samples. The results have shown that the emulsion vehicles consisted of a complex colloidal structure of lamellar liquid crystalline and lamellar gel crystalline type. PG addition produced a stronger hydrophilic lamellar gel phase than GL, which was independent on the model drug used. PG-containing vehicles have revealed a considerable amount of interlamellar PG/water mixture, with incorporated drug. In vitro permeation data obtained using artificial skin constructs (ASC) confirmed the relationship between rheological profiles of vehicles and the extent of skin delivery. Higher permeation profiles of both drugs from PG-containing formulations coincided with a higher increase in transepidermal water loss observed in in vivo study on human volunteers, which confirms the penetration/permeation enhancer effect of PG. It also indicates the existence of the vehicle/ASC interactions analogous to those between the vehicle and the skin, thus affirming the use of ASC as a reliable tool for permeation studies. Contrary to the effect of PG, the results obtained with GL suggest that it may have a permeation-retarding rather than a permeation-enhancing effect in topical vehicles of this type.

  11. 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

  12. 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...

  13. 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.

  14. 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.

  15. Structure-based design of estrogen receptor-beta selective ligands.

    PubMed

    Manas, Eric S; Unwalla, Rayomand J; Xu, Zhang B; Malamas, Michael S; Miller, Chris P; Harris, Heather A; Hsiao, Chulai; Akopian, Tatos; Hum, Wah-Tung; Malakian, Karl; Wolfrom, Scott; Bapat, Ashok; Bhat, Ramesh A; Stahl, Mark L; Somers, William S; Alvarez, Juan C

    2004-11-24

    We present the structure-based optimization of a series of estrogen receptor-beta (ERbeta) selective ligands. X-ray cocrystal structures of these ligands complexed to both ERalpha and ERbeta are described. We also discuss how molecular modeling was used to take advantage of subtle differences between the two binding cavities in order to optimize selectivity for ERbeta over ERalpha. Quantum chemical calculations are utilized to gain insight into the mechanism of selectivity enhancement. Despite only two relatively conservative residue substitutions in the ligand binding pocket, the most selective compounds have greater than 100-fold selectivity for ERbeta relative to ERalpha when measured using a competitive radioligand binding assay.

  16. 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.

  17. Topical azithromycin and clarithromycin inhibit acute and chronic skin inflammation in sensitized mice, with apparent selectivity for Th2-mediated processes in delayed-type hypersensitivity.

    PubMed

    Ivetić Tkalčević, Vanesa; Cužić, Snježana; Kramarić, Miroslava Dominis; Parnham, Michael J; Eraković Haber, Vesna

    2012-02-01

    Macrolide antibiotics inhibit the secretion of Th1 cytokines while their effects on the release of Th2 cytokines are variable. We investigated molecular and cellular markers of Th1- and Th2-mediated inflammatory mechanisms and the anti-inflammatory activity of azithromycin and clarithromycin in phorbol 12-myristate 13-acetate (PMA) and oxazolone (OXA)-induced skin inflammation. Dexamethasone (50 μg/ear), azithromycin, and clarithromycin (500 μg/ear) reduced TNF-α and interleukin (IL)-1β concentration in ear tissue by inhibiting inflammatory cell accumulation in PMA-induced inflammation. In OXA-induced early delayed-type hypersensitivity (DTH), the macrolides (2 mg/ear) and dexamethasone (25 μg/ear) reduced ear tissue inflammatory cell infiltration and secretion of IL-4 while clarithromycin also decreased IFN-γ concentration. Macrolides showed better activity when administered after the challenge. In OXA-induced chronic DTH, azithromycin (1 mg/ear) reduced the number of ear tissue mast cells and decreased the concentration of IL-4 in ear tissue and of immunoglobulin (Ig)E in serum. Clarithromycin (1 mg/ear) reduced serum IgE concentration, possibly by a mechanism independent of IL-4, while both macrolides attenuated mast cell degranulation. In conclusion, azithromycin and clarithromycin attenuate pro-inflammatory cytokine production and leukocyte infiltration during innate immune reactions, while selectively affecting Th2 rather than Th1 immunity in DTH reactions.

  18. 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.

  19. Prey community structure affects how predators select for Mullerian mimicry.

    PubMed

    Ihalainen, Eira; Rowland, Hannah M; Speed, Michael P; Ruxton, Graeme D; Mappes, Johanna

    2012-06-07

    Müllerian mimicry describes the close resemblance between aposematic prey species; it is thought to be beneficial because sharing a warning signal decreases the mortality caused by sampling by inexperienced predators learning to avoid the signal. It has been hypothesized that selection for mimicry is strongest in multi-species prey communities where predators are more prone to misidentify the prey than in simple communities. In this study, wild great tits (Parus major) foraged from either simple (few prey appearances) or complex (several prey appearances) artificial prey communities where a specific model prey was always present. Owing to slower learning, the model did suffer higher mortality in complex communities when the birds were inexperienced. However, in a subsequent generalization test to potential mimics of the model prey (a continuum of signal accuracy), only birds that had foraged from simple communities selected against inaccurate mimics. Therefore, accurate mimicry is more likely to evolve in simple communities even though predator avoidance learning is slower in complex communities. For mimicry to evolve, prey species must have a common predator; the effective community consists of the predator's diet. In diverse environments, the limited diets of specialist predators could create 'simple community pockets' where accurate mimicry is selected for.

  20. Special topics in infrared interferometry

    NASA Astrophysics Data System (ADS)

    Hanel, R. A.

    1985-01-01

    Topics in IR interferometry related to the development of a Michelson interferometer are treated. The selection and reading of the signal from the detector to the analog to digital converter is explained. The requirements for the Michelson interferometer advance speed are deduced. The effects of intensity modulation on the interferogram are discussed. Wavelength and intensity calibration of the interferometer are explained. Noise sources (Nyquist or Johnson noise, phonon noise), definitions of measuring methods of noise, and noise measurements are presented.

  1. 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.

  2. 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

  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. 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.

  5. Exploration of the Structure of Selected Reading Readiness Tests.

    ERIC Educational Resources Information Center

    Olson, Arthur V.; Rosen Carl L.

    A variety of factor analysis techniques were employed to explore the structure of five reading readiness instruments (Gates Reading Readiness Test, Developmental Tests of Visual Perception, Metropolitan Readiness Tests, Specially Constructed Readiness Test by Olson, Wechsler Intelligence Scale for Children) as predictor variables of performance on…

  6. 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…

  7. 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 ...

  8. Investigation of the Thermal Conductance of Selected Opal Structures

    NASA Astrophysics Data System (ADS)

    Lamberton, , Jr.; Tritt, Terry M.; Zakhidov, A.; Baughmann, R.; Khayrullin, I.

    1999-11-01

    In relation to thermoelectrics, recently some attention has come to opal structures.^1 The structure of the SiO2 opals is hoped to be useful in lowering thermal conductivity when this structure is infiltrated with traditional thermoelectric materials, such as Bi or Bi_2Te_3. Preliminary measurements show that, by infiltration, it may be possible to increase the thermoelectric figure of merit by improving the ratio of electrical conductivity to thermal conductivity.^2 We have built a new steady state thermal conductivity apparatus for measuring thermal conductivity of samples between 10K and 350K. With this new system the thermal properties of the opal systems and the effects of infiltration will be investigated. Data from the thermal conductivity and heat capacity measurements will be presented and discussed, along with a comparison of thermal conductivity obtained with the laser flash method. 1.) A. Zakhidov et al., Science , 282, 897 (1998) 2.) R. Baughman, A. Zakhidov, et.al, Proc. of ICT '98, IEEE Press, p 288 (1998)

  9. Selection of Structures with Grid Optimization, in Multiagent Data Warehouse

    NASA Astrophysics Data System (ADS)

    Gorawski, Marcin; Bańkowski, Sławomir; Gorawski, Michał

    The query optimization problem in data base and data warehouse management systems is quite similar. Changes to Joins sequences, projections and selections, usage of indexes, and aggregations are all decided during the analysis of an execution schedule. The main goal of these changes is to decrease the query response time. The optimization operation is often dedicated to a single node. This paper proposes optimization to grid or cluster data warehouses / databases. Tests were conducted in a multi-agent environment, and the optimization focused not only on a single node but on the whole system as well. A new idea is proposed here with multi-criteria optimization that is based on user-given parameters. Depending on query time, result admissible errors, and the level of system usage, task results were obtained along with grid optimization.

  10. 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.

  11. Structure-based prediction of subtype-selectivity of Histamine H3 receptor selective antagonists in clinical trials

    PubMed Central

    Kim, Soo-Kyung; Fristrup, Peter; Abrol, Ravinder; Goddard, William A.

    2011-01-01

    Histamine receptors (HRs) are excellent drug targets for the treatment of diseases such as schizophrenia, psychosis, depression, migraine, allergies, asthma ulcers, and hypertension. Among them, the human H3 Histamine receptor (hH3HR) antagonists have been proposed for specific therapeutic applications, including treatment of Alzheimer's disease, attention deficit hyperactivity disorder (ADHD), epilepsy, and obesity.1 However, many of these drug candidates cause undesired side effects through the cross-reactivity with other histamine receptor subtypes. In order to develop improved selectivity and activity for such treatments it would be useful to have the three dimensional structures for all four HRs. We report here the predicted structures of four HR subtypes (H1, H2, H3, and H4) using the GEnSeMBLE (GPCR Ensemble of Structures in Membrane BiLayer Environment) Monte Carlo protocol.2 sampling ~ 35 million combinations of helix packings to predict the 10 most stable packings for each of the four subtypes. Then we used these best 10 protein structures with the DarwinDock Monte Carlo protocol to sample ~ 50,000*20 poses to predict the optimum ligand-protein structures for various agonists and antagonists. We find that E2065.46 contributes most in binding H3 selective agonists (5, 6, 7) in agreement with experimental mutation studies. We also find that conserved E5.46/ S5.43 in both of hH3HR and hH4HR are involved in H3/ H4 subtype selectivity. In addition, we find that M3786.55 in hH3HR provides additional hydrophobic interactions different from hH4HR (the corresponding amino acid of T3236.55 in hH4HR) to provide additional subtype bias. From these studies we developed a pharmacophore model based on our predictions for known hH3HR selective antagonists in clinical study [ABT-239 1, GSK-189,254 2, PF-3654746 3, and BF2.649 (Tiprolisant) 4] that suggests critical selectivity directing elements are: the basic proton interacting with D1143.32, the spacer, the aromatic

  12. Application of composites to the selective reinforcement of metallic aerospace structures

    NASA Technical Reports Server (NTRS)

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

    1973-01-01

    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.

  13. 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

  14. 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

  15. Structure, function, and wavelength selection in blue-absorbing proteorhodopsin.

    PubMed

    Hillebrecht, Jason R; Galan, Jhenny; Rangarajan, Rekha; Ramos, Lavoisier; McCleary, Kristina; Ward, Donald E; Stuart, Jeffrey A; Birge, Robert R

    2006-02-14

    The absorption maximum of blue proteorhodopsin (BPR) is the most blue-shifted of all retinal proteins found in archaea or bacteria, with the exception of sensory rhodopsin II (SRII). The absorption spectrum also exhibits a pH dependence larger than any other retinal protein. We examine the structural origins of these two properties of BPR by using optical spectroscopy, homology modeling, and molecular orbital theory. Bacteriorhodopsin (BR) and SRII are used as homology parents for comparative purposes. We find that the tertiary structure of BPR based on SRII is more realistic with respect to free energy, dynamic stability, and spectroscopic properties. Molecular orbital calculations including full single- and double-configuration interaction within the chromophore pi-electron system provide perspectives on the wavelength regulation in this protein and indicate that Arg-95, Gln-106, Glu-143, and Asp-229 play important, and in some cases pH-dependent roles. A possible model for the 0.22 eV red shift of BPR at low pH is examined, in which Glu-143 becomes protonated and releases Arg-95 to rotate up into the binding site, altering the electrostatic environment of the chromophore. At high pH, BPR has spectroscopic properties similar to SRII, but at low pH, BPR has spectroscopic properties more similar to BR. Nevertheless, SRII is a significantly better homology model for BPR and opens up the question of whether this protein serves as a proton pump, as commonly believed, or is a light sensor with structure-function properties more comparable to those of SRII. The function of BPR in the native organism is discussed with reference to the results of the homology model.

  16. Factor selection and structural identification in the interaction ANOVA model.

    PubMed

    Post, Justin B; Bondell, Howard D

    2013-03-01

    When faced with categorical predictors and a continuous response, the objective of an analysis often consists of two tasks: finding which factors are important and determining which levels of the factors differ significantly from one another. Often times, these tasks are done separately using Analysis of Variance (ANOVA) followed by a post hoc hypothesis testing procedure such as Tukey's Honestly Significant Difference test. When interactions between factors are included in the model the collapsing of levels of a factor becomes a more difficult problem. When testing for differences between two levels of a factor, claiming no difference would refer not only to equality of main effects, but also to equality of each interaction involving those levels. This structure between the main effects and interactions in a model is similar to the idea of heredity used in regression models. This article introduces a new method for accomplishing both of the common analysis tasks simultaneously in an interaction model while also adhering to the heredity-type constraint on the model. An appropriate penalization is constructed that encourages levels of factors to collapse and entire factors to be set to zero. It is shown that the procedure has the oracle property implying that asymptotically it performs as well as if the exact structure were known beforehand. We also discuss the application to estimating interactions in the unreplicated case. Simulation studies show the procedure outperforms post hoc hypothesis testing procedures as well as similar methods that do not include a structural constraint. The method is also illustrated using a real data example.

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

    NASA Astrophysics Data System (ADS)

    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

  18. 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

    2017-01-05

    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

  19. 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…

  20. RNA structures, genomic organization and selection of recombinant HIV.

    PubMed

    Simon-Loriere, Etienne; Rossolillo, Paola; Negroni, Matteo

    2011-01-01

    Recombination is an evolutionary mechanism intrinsic to the evolution of many RNA viruses. In retroviruses and notably in the case of HIV, recombination is so frequent that it can be considered as part of its mode of replication. This process not only plays a central role in shaping HIV genetic diversity worldwide, but has also been involved in immune escape and development of resistance to antiviral treatments. Recombination does not create new mutations in the existing genetic repertoire of the virus, but creates new combinations of pre-existing polymorphisms. The simultaneous insertion of multiple substitutions in a single replication cycle leaves little room for the progressive coevolution of regions of proteins, RNA or, more in general, genomes, to accommodate these drastic sequence changes. Therefore, recombination, while allowing the virus to rapidly explore larger sequence space than the slow accumulation of point mutations, also runs the risk of generating non functional viruses. Recombination is the consequence of a switch in the template used during reverse transcription and is promoted by the presence of structured regions in the genomic RNA template. In this review, we discuss new observations suggesting that the distribution of RNA structures along the HIV genome may enhance recombination rates in regions where the resultant progeny is less likely to be impaired, and could therefore maximize the evolutionary value of this source of genetic diversity.

  1. 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.

  2. Synthesis, structure and physical properties of selected transition metal oxides

    NASA Astrophysics Data System (ADS)

    Waldron, Joanna Elizabeth Leah

    Monoclinic Nb12O29 has been synthesised by topotactic reduction of H-Nb2O5. It has a complex crystallographic shear structure made up of 3x4 blocks of corner shared NbO6 octahedra. Nb12O29 is mixed d0/d1 compound which, can be written as Nb4+2NB5+10O29. It has been found, using Rietveld refinement of powder neutron diffraction data, to undergo a charge ordering transition at around 12K resulting in a lowering of symmetry from A2/m to Am. Below this transition, one Nb4+ ion is localised on a crystallographically distinct site in the centre of the 3x4 blocks. This charge ordering transition has an associated transition to an incommensurate one dimensional antiferromagnetic state. The nature of the magnetic order has been investigated using susceptibility and SR measurements. Susceptibility measurements reveal that only 48% of the Nb4+ in the system is localised, and its temperature dependence is well fitted to a Bonner-Fisher model for S=1/2 one dimensional antiferromagnets. It is found that the remaining valence electrons in NB12O29 itinerant and contribute to its metallic conductivity. Further evidence for the unique properties of monoclinic Nb12O29 has been obtained by doping the structure with small amounts of diamagnetic Ti4+, which rapidly causes a destruction of the long range magnetic order at only 3% doping, but leaves the metallic conductivity unaffected, as is expected for a one dimensional chain.

  3. 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.

  4. 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

  5. 'Hot Topics' in Astrophysics

    NASA Technical Reports Server (NTRS)

    Maran, Stephen P.

    2000-01-01

    Three current topics in astrophysics are described here on the occasion of the joint meeting of the American Association of Physics Teachers and the American Astronomical Society (Jan. 7-11, 2001, San Diego, Calif.). Many equally exciting topics--ranging from the dozens of newly discovered planets of sunlike stars to evidence suggesting that the expansion of the universe is accelerating--could have been chosen. The topics discussed are: (1) the habitability of Mars, (2) black holes, galaxy bulges, and the X-ray background, and (3) the greatest explosions since the Big Bang.

  6. Selected topics in the rheology of fluids

    NASA Astrophysics Data System (ADS)

    Joseph, Daniel D.

    1991-08-01

    Problems of flow of viscoelastic liquids were considered emphasizing the issues generated by the fluid's elasticity, which gives rise to hyperbolicity and waves. These studies are summarized with many studies of drag reductions using water lubrication, riblets, and polymers. These studies will be summarized in my new book (with Yuriko Renardy): Two-Fluid Dynamics. We started a computational numerical effort aimed at studying the motion of particles in fluids using the Navier Stokes equations and the particle equations of motion.

  7. Selected Topics of Interest: 1980. Part I.

    ERIC Educational Resources Information Center

    American Annals of the Deaf, 1980

    1980-01-01

    The special section contains three papers focusing on the effects of federal legislation on deaf education: "Public Residential Schools for Deaf Students in the United States, 1970-1978" (A. Schildroth); "Due Process--A Status Report on Schools for Deaf Children" (G. Holman); "The Impact of 504 on Schools for the…

  8. 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…

  9. 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.

  10. 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.

  11. Topicalization: A Psycholinguistic Perspective.

    ERIC Educational Resources Information Center

    Li, Ruilin

    2001-01-01

    Explores topicalization in the Chinese-English translation classroom. Examines translation in language teaching, Advocates translation as a useful skill and discusses it as a means of mastering a foreign language--in this case, English. (Author/VWL)

  12. The pharmacology of topical analgesics.

    PubMed

    Barkin, Robert L

    2013-07-01

    Pain management of patients continues to pose challenges to clinicians. Given the multiple dimensions of pain--whether acute or chronic, mild, moderate, or severe, nociceptive or neuropathic--a multimodal approach may be needed. Fortunately, clinicians have an array of nonpharmacologic and pharmacologic treatment choices; however, each modality must be chosen carefully, because some often used oral agents are associated with safety and tolerability issues that restrict their use in certain patients. In particular, orally administered nonsteroidal antiinflammatory drugs, opioids, antidepressants, and anticonvulsants are known to cause systemic adverse effects in some patients. To address this problem, a number of topical therapies in various therapeutic classes have been developed to reduce systemic exposure and minimize the risks of patients developing adverse events. For example, topical nonsteroidal anti-inflammatory drug formulations produce a site-specific effect (ie, cyclo-oxygenase inhibition) while decreasing the systemic exposure that may lead to undesired effects in patients. Similarly, derivatives of acetylsalicylic acid (ie, salicylates) are used in topical analgesic formulations that do not significantly enter the patient's systemic circulation. Salicylates, along with capsaicin, menthol, and camphor, compose the counterirritant class of topical analgesics, which produce analgesia by activating and then desensitizing epidermal nociceptors. Additionally, patches and creams that contain the local anesthetic lidocaine, alone or co-formulated with other local anesthetics, are also used to manage patients with select acute and chronic pain states. Perhaps the most common topical analgesic modality is the cautious application of cutaneous cold and heat. Such treatments may decrease pain not by reaching the target tissue through systemic distribution, but by acting more directly on the affected tissue. Despite the tolerability benefits associated with avoiding

  13. Structural elements of metal selectivity in metal sensor proteins.

    PubMed

    Pennella, Mario A; Shokes, Jacob E; Cosper, Nathaniel J; Scott, Robert A; Giedroc, David P

    2003-04-01

    Staphylococcus aureus CzrA and Mycobacterium tuberculosis NmtR are homologous zinccobalt-responsive and nickelcobalt-responsive transcriptional repressors in vivo, respectively, and members of the ArsRSmtB superfamily of prokaryotic metal sensor proteins. We show here that Zn(II) is the most potent negative allosteric regulator of czr operatorpromoter binding in vitro with the trend Zn(II)>Co(II)Ni(II), whereas the opposite holds for the binding of NmtR to the nmt operatorpromoter, Ni(II)>Co(II)>Zn(II). Characterization of the metal coordination complexes of CzrA and NmtR by UVvisible and x-ray absorption spectroscopies reveals that metals that form four-coordinate tetrahedral complexes with CzrA [Zn(II) and Co(II)] are potent regulators of DNA binding, whereas metals that form five- or six-coordinate complexes with NmtR [Ni(II) and Co(II)] are the strongest allosteric regulators in this system. Strikingly, the Zn(II) coordination complexes of CzrA and NmtR cannot be distinguished from one another by x-ray absorption spectroscopy, with the best fit a His-3-carboxylate complex in both cases. Inspection of the primary structures of CzrA and NmtR, coupled with previous functional data, suggests that three conserved His and one Asp from the C-terminal alpha5 helix donate ligands to create a four-coordinate complex in both CzrA and NmtR, with NmtR uniquely capable of expanding its coordination number in the Ni(II) and Co(II) complexes by recruiting additional His ligands from a C-terminal extension of the alpha5 helix.

  14. Topical therapies for osteoarthritis.

    PubMed

    Altman, Roy D; Barthel, H Richard

    2011-07-09

    This review discusses the pharmacology, analgesic efficacy, safety and tolerability of topical NSAIDs, salicylates and capsaicin for the management of osteoarthritis (OA) pain. Topical therapies present a valuable therapeutic option for OA pain management, with substantial evidence supporting the efficacy and safety of topical NSAIDs, but less robust support for capsaicin and salicylates. We define topical therapies as those intended to act locally, in contrast to transdermal therapies intended to act systemically. Oral therapies for patients with mild to moderate OA pain include paracetamol (acetaminophen) and NSAIDs. Paracetamol has only weak efficacy at therapeutic doses and is hepatotoxic at doses >3.25 g/day. NSAIDs have demonstrated efficacy in patients with OA, but are associated with dose-, duration- and age-dependent risks of gastrointestinal, cardiovascular, renal, haematological and hepatic adverse events (AEs), as well as clinically meaningful drug interactions. To minimize AE risks, treatment guidelines for OA suggest minimizing NSAID exposure by prescribing the lowest effective dose for the shortest duration of time. Systemic NSAID exposure may also be limited by prescribing topical NSAIDs, particularly in patients with OA pain limited to a few superficial joints. Topical NSAIDs have been available in Europe for decades and were introduced to provide localized analgesia with minimal systemic NSAID exposure. Guidelines of the American Academy of Orthopaedic Surgeons, European League Against Rheumatism (EULAR), Osteoarthritis Research Society International, and National Institute for Health and Clinical Excellence (NICE) state that topical NSAIDs may be considered for patients with mild to moderate OA of the knee or hand, particularly in patients with few affected joints and/or a history of sensitivity to oral NSAIDs. In fact, the EULAR and NICE guidelines state that topical NSAIDs should be considered before oral therapies. Clinical trials of topical

  15. Selective Structural Transformation of Supramolecules to Multinuclear Heterosubstituted Pt Complexes via Ligand Exchange.

    PubMed

    Molev, Gregory; Arif, Atta; Stang, Peter J

    2011-11-16

    Selective triflate to chlorine ligand exchange reaction between ditriflate and dichloride Pt complexes producing pure heterosubstituted complexes is demonstrated. We show that this reaction can be applied for selective chlorination of supramolecules leading to their structural transformation into multinuclear mono-chlorinated Pt(II) complexes. The X-ray structure of complex of 4,4'-bipyridine with two molecules of (Et(3)P)(2)Pt(Cl)OTf is reported.

  16. Structural Analysis of Triacylglycerols by Using a MALDI-TOF/TOF System with Monoisotopic Precursor Selection

    NASA Astrophysics Data System (ADS)

    Kubo, Ayumi; Satoh, Takaya; Itoh, Yoshiyuki; Hashimoto, Masahiro; Tamura, Jun; Cody, Robert B.

    2013-05-01

    A new MALDI-TOF/TOF system with monoisotopic precursor selection was applied to the analysis of triacylglycerols in an olive oil sample. Monoisotopic precursor selection made it possible to obtain product-ion mass spectra without interference from species that differed by a single double bond. Complete structure determination of all triacylglycerols, including structural isomers, was made possible by interpreting the charge-remote fragmentation resulting from high-energy collision-induced dissociation (CID) of the sodiated triacylglycerols.

  17. 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

  18. 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…

  19. Investigation of orexin-2 selective receptor antagonists: Structural modifications resulting in dual orexin receptor antagonists.

    PubMed

    Skudlarek, Jason W; DiMarco, Christina N; Babaoglu, Kerim; Roecker, Anthony J; Bruno, Joseph G; Pausch, Mark A; O'Brien, Julie A; Cabalu, Tamara D; Stevens, Joanne; Brunner, Joseph; Tannenbaum, Pamela L; Wuelfing, W Peter; Garson, Susan L; Fox, Steven V; Savitz, Alan T; Harrell, Charles M; Gotter, Anthony L; Winrow, Christopher J; Renger, John J; Kuduk, Scott D; Coleman, Paul J

    2017-03-15

    In an ongoing effort to explore the use of orexin receptor antagonists for the treatment of insomnia, dual orexin receptor antagonists (DORAs) were structurally modified, resulting in compounds selective for the OX2R subtype and culminating in the discovery of 23, a highly potent, OX2R-selective molecule that exhibited a promising in vivo profile. Further structural modification led to an unexpected restoration of OX1R antagonism. Herein, these changes are discussed and a rationale for selectivity based on computational modeling is proposed.

  20. Estimating Selection Coefficients in Spatially Structured Populations from Time Series Data of Allele Frequencies

    PubMed Central

    Mathieson, Iain; McVean, Gil

    2013-01-01

    Inferring the nature and magnitude of selection is an important problem in many biological contexts. Typically when estimating a selection coefficient for an allele, it is assumed that samples are drawn from a panmictic population and that selection acts uniformly across the population. However, these assumptions are rarely satisfied. Natural populations are almost always structured, and selective pressures are likely to act differentially. Inference about selection ought therefore to take account of structure. We do this by considering evolution in a simple lattice model of spatial population structure. We develop a hidden Markov model based maximum-likelihood approach for estimating the selection coefficient in a single population from time series data of allele frequencies. We then develop an approximate extension of this to the structured case to provide a joint estimate of migration rate and spatially varying selection coefficients. We illustrate our method using classical data sets of moth pigmentation morph frequencies, but it has wide applications in settings ranging from ecology to human evolution. PMID:23307902

  1. 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.

  2. Fabrication and characterisation of a fully auxetic 3D lattice structure via selective electron beam melting

    NASA Astrophysics Data System (ADS)

    Warmuth, Franziska; Osmanlic, Fuad; Adler, Lucas; Lodes, Matthias A.; Körner, Carolin

    2017-02-01

    A three-dimensional fully auxetic cellular structure with negative Poisson’s ratio is presented. Samples are fabricated from Ti6Al4V powder via selective electron beam melting. The influence of the strut thickness and the amplitude of the strut on the mechanical properties and the deformation behaviour of cellular structures is studied.

  3. Topic Prominence in Japanese EFL Students' Existential Constructions.

    ERIC Educational Resources Information Center

    Sasaki, Miyuki

    1990-01-01

    Investigations of Japanese speakers' interlanguage constructions of English existential sentences with a locative sentential topic found a general shift from topic-comment to subject-predicate structures as proficiency increased. (24 references) (Author/CB)

  4. Topical hemostatic agents in gynecologic surgery.

    PubMed

    Duenas-Garcia, Omar Felipe; Goldberg, Jeffrey M

    2008-06-01

    Biosurgical compounds and pharmacologic agents can serve as surgical adjuncts to prevent or curtail intraoperative bleeding. Medline, PubMed, and Cochrane electronic data bases were used to search the English literature from 1966 to March 2007 using the terms topical, hemostatic agents, and gynecologic surgery. Several effective topical hemostatic agents are available to reduce intraoperative blood loss. Data on their application in gynecologic surgery are limited, and guidelines for selecting one over another for specific indications are lacking.

  5. 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.

  6. 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.

  7. Frequency-selective multilayer electromagnetic bandgap structure combining carbon nanotubes with polymeric or ceramic substrates

    NASA Astrophysics Data System (ADS)

    Danlée, Y.; Huynen, I.; Bailly, C.

    2014-09-01

    We present an electromagnetic bandgap (EBG) multilayer structure, acting as a frequency-selective surface able to absorb in specified narrow frequency bands within the GHz-range. The structure is a lossy EBG using ultra-thin conductive layers to generate a controlled resonance in homogenous high permittivity slabs. The basic structure is composed of carbon nanotubes depositions sandwiched between polycarbonate films, which are stacked in alternation between dielectric slabs. The physical properties (i.e., relative permittivity and thickness) of the dielectric spacers allow creating narrow high-absorption bands at defined frequencies. This multilayer approach offers a smart and versatile solution for tuning the selectivity of EBG performance.

  8. 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.

  9. 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.

  10. 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

  11. Novel Topic Authorship Attribution

    DTIC Science & Technology

    2011-03-01

    include area code ) NSN 7540-01-280-5500 Standard Form 298 (Rev. 8–98) Prescribed by ANSI Std. Z39.18 25-03-2011 Master’s Thesis 2010-01-01—2011-03-25...your writer’s voice. St. Martin’s Press, 1994. 43 [35] S. Roman, Introduction to Coding and Information Theory. Springer-Verlag New York, New York...0 0 0 0 T50077 0 0 0 0 0 0 0 0 TOTALS 1582 3293 1493 1858 1182 1129 1160 1107 Table B.2: Topic/Author Data Tabulation 48 AUTHORS TOPICS A100512

  12. Structure-based discovery of selective serotonin 5-HT(1B) receptor ligands.

    PubMed

    Rodríguez, David; Brea, José; Loza, María Isabel; Carlsson, Jens

    2014-08-05

    The development of safe and effective drugs relies on the discovery of selective ligands. Serotonin (5-hydroxytryptamine [5-HT]) G protein-coupled receptors are therapeutic targets for CNS disorders but are also associated with adverse drug effects. The determination of crystal structures for the 5-HT1B and 5-HT2B receptors provided an opportunity to identify subtype selective ligands using structure-based methods. From docking screens of 1.3 million compounds, 22 molecules were predicted to be selective for the 5-HT1B receptor over the 5-HT2B subtype, a requirement for safe serotonergic drugs. Nine compounds were experimentally verified as 5-HT1B-selective ligands, with up to 300-fold higher affinities for this subtype. Three of the ligands were agonists of the G protein pathway. Analysis of state-of-the-art homology models of the two 5-HT receptors revealed that the crystal structures were critical for predicting selective ligands. Our results demonstrate that structure-based screening can guide the discovery of ligands with specific selectivity profiles.

  13. Improving the correlation structure selection approach for generalized estimating equations and balanced longitudinal data.

    PubMed

    Westgate, Philip M

    2014-06-15

    Generalized estimating equations are commonly used to analyze correlated data. Choosing an appropriate working correlation structure for the data is important, as the efficiency of generalized estimating equations depends on how closely this structure approximates the true structure. Therefore, most studies have proposed multiple criteria to select the working correlation structure, although some of these criteria have neither been compared nor extensively studied. To ease the correlation selection process, we propose a criterion that utilizes the trace of the empirical covariance matrix. Furthermore, use of the unstructured working correlation can potentially improve estimation precision and therefore should be considered when data arise from a balanced longitudinal study. However, most previous studies have not allowed the unstructured working correlation to be selected as it estimates more nuisance correlation parameters than other structures such as AR-1 or exchangeable. Therefore, we propose appropriate penalties for the selection criteria that can be imposed upon the unstructured working correlation. Via simulation in multiple scenarios and in application to a longitudinal study, we show that the trace of the empirical covariance matrix works very well relative to existing criteria. We further show that allowing criteria to select the unstructured working correlation when utilizing the penalties can substantially improve parameter estimation.

  14. 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…

  15. Transportation: Topic Paper E.

    ERIC Educational Resources Information Center

    National Council on the Handicapped, Washington, DC.

    As one of a series of topic papers assessing federal laws and programs affecting persons with disabilities, this paper reviews the issue of transportation services. In the area of urban mass transit, four relevant pieces of legislation and public transportation accessibility regulations are cited, and cost issues are explored. Paratransit systems,…

  16. An experimental model for the spatial structuring and selection of bacterial communities.

    PubMed

    Thomas, Torsten; Kindinger, Ilona; Yu, Dan; Esvaran, Meera; Blackall, Linda; Forehead, Hugh; Johnson, Craig R; Manefield, Mike

    2011-11-01

    Community-level selection is an important concept in evolutionary biology and has been predicted to arise in systems that are spatially structured. Here we develop an experimental model for spatially-structured bacterial communities based on coaggregating strains and test their relative fitness under a defined selection pressure. As selection we apply protozoan grazing in a defined, continuous culturing system. We demonstrate that a slow-growing bacterial strain Blastomonas natatoria 2.1, which forms coaggregates with Micrococcus luteus, can outcompete a fast-growing, closely related strain Blastomonas natatoria 2.8 under conditions of protozoan grazing. The competitive benefit provided by spatial structuring has implications for the evolution of natural bacterial communities in the environment.

  17. Multi-atlas pancreas segmentation: Atlas selection based on vessel structure.

    PubMed

    Karasawa, Ken'ichi; Oda, Masahiro; Kitasaka, Takayuki; Misawa, Kazunari; Fujiwara, Michitaka; Chu, Chengwen; Zheng, Guoyan; Rueckert, Daniel; Mori, Kensaku

    2017-03-31

    Automated organ segmentation from medical images is an indispensable component for clinical applications such as computer-aided diagnosis (CAD) and computer-assisted surgery (CAS). We utilize a multi-atlas segmentation scheme, which has recently been used in different approaches in the literature to achieve more accurate and robust segmentation of anatomical structures in computed tomography (CT) volume data. Among abdominal organs, the pancreas has large inter-patient variability in its position, size and shape. Moreover, the CT intensity of the pancreas closely resembles adjacent tissues, rendering its segmentation a challenging task. Due to this, conventional intensity-based atlas selection for pancreas segmentation often fails to select atlases that are similar in pancreas position and shape to those of the unlabeled target volume. In this paper, we propose a new atlas selection strategy based on vessel structure around the pancreatic tissue and demonstrate its application to a multi-atlas pancreas segmentation. Our method utilizes vessel structure around the pancreas to select atlases with high pancreatic resemblance to the unlabeled volume. Also, we investigate two types of applications of the vessel structure information to the atlas selection. Our segmentations were evaluated on 150 abdominal contrast-enhanced CT volumes. The experimental results showed that our approach can segment the pancreas with an average Jaccard index of 66.3% and an average Dice overlap coefficient of 78.5%.

  18. 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.

  19. Bayesian hierarchical structured variable selection methods with application to MIP studies in breast cancer.

    PubMed

    Zhang, Lin; Baladandayuthapani, Veerabhadran; Mallick, Bani K; Manyam, Ganiraju C; Thompson, Patricia A; Bondy, Melissa L; Do, Kim-Anh

    2014-08-01

    The analysis of alterations that may occur in nature when segments of chromosomes are copied (known as copy number alterations) has been a focus of research to identify genetic markers of cancer. One high-throughput technique recently adopted is the use of molecular inversion probes (MIPs) to measure probe copy number changes. The resulting data consist of high-dimensional copy number profiles that can be used to ascertain probe-specific copy number alterations in correlative studies with patient outcomes to guide risk stratification and future treatment. We propose a novel Bayesian variable selection method, the hierarchical structured variable selection (HSVS) method, which accounts for the natural gene and probe-within-gene architecture to identify important genes and probes associated with clinically relevant outcomes. We propose the HSVS model for grouped variable selection, where simultaneous selection of both groups and within-group variables is of interest. The HSVS model utilizes a discrete mixture prior distribution for group selection and group-specific Bayesian lasso hierarchies for variable selection within groups. We provide methods for accounting for serial correlations within groups that incorporate Bayesian fused lasso methods for within-group selection. Through simulations we establish that our method results in lower model errors than other methods when a natural grouping structure exists. We apply our method to an MIP study of breast cancer and show that it identifies genes and probes that are significantly associated with clinically relevant subtypes of breast cancer.

  20. Bayesian hierarchical structured variable selection methods with application to molecular inversion probe studies in breast cancer

    PubMed Central

    Zhang, Lin; Baladandayuthapani, Veerabhadran; Mallick, Bani K.; Manyam, Ganiraju C.; Thompson, Patricia A.; Bondy, Melissa L.; Do, Kim-Anh

    2015-01-01

    Summary The analysis of alterations that may occur in nature when segments of chromosomes are copied (known as copy number alterations) has been a focus of research to identify genetic markers of cancer. One high-throughput technique recently adopted is the use of molecular inversion probes (MIPs) to measure probe copy number changes. The resulting data consist of high-dimensional copy number profiles that can be used to ascertain probe-specific copy number alterations in correlative studies with patient outcomes to guide risk stratification and future treatment. We propose a novel Bayesian variable selection method, the hierarchical structured variable selection (HSVS) method, which accounts for the natural gene and probe-within-gene architecture to identify important genes and probes associated with clinically relevant outcomes. We propose the HSVS model for grouped variable selection, where simultaneous selection of both groups and within-group variables is of interest. The HSVS model utilizes a discrete mixture prior distribution for group selection and group-specific Bayesian lasso hierarchies for variable selection within groups. We provide methods for accounting for serial correlations within groups that incorporate Bayesian fused lasso methods for within-group selection. Through simulations we establish that our method results in lower model errors than other methods when a natural grouping structure exists. We apply our method to an MIP study of breast cancer and show that it identifies genes and probes that are significantly associated with clinically relevant subtypes of breast cancer. PMID:25705056

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

    PubMed

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

    2014-11-04

    Magnesium is the most abundant divalent cation in living cells and is crucial to several biological processes. MgtE is a Mg(2+) channel distributed in all domains of life that contributes to the maintenance of cellular Mg(2+) homeostasis. Here we report the high-resolution crystal structures of the transmembrane domain of MgtE, bound to Mg(2+), Mn(2+) and Ca(2+). The high-resolution Mg(2+)-bound crystal structure clearly visualized the hydrated Mg(2+) 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 Mg(2+) 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.

  2. 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

  3. Structures of the four subfamilies of phosphodiesterase-4 provide insight into the selectivity of their inhibitors.

    PubMed

    Wang, Huanchen; Peng, Ming-Sheng; Chen, Yi; Geng, Jie; Robinson, Howard; Houslay, Miles D; Cai, Jiwen; Ke, Hengming

    2007-12-01

    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.

  4. 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.

  5. 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

  6. Structure-selection techniques applied to continuous-time nonlinear models

    NASA Astrophysics Data System (ADS)

    Aguirre, Luis A.; Freitas, Ubiratan S.; Letellier, Christophe; Maquet, Jean

    2001-10-01

    This paper addresses the problem of choosing the multinomials that should compose a polynomial mathematical model starting from data. The mathematical representation used is a nonlinear differential equation of the polynomial type. Some approaches that have been used in the context of discrete-time models are adapted and applied to continuous-time models. Two examples are included to illustrate the main ideas. Models obtained with and without structure selection are compared using topological analysis. The main differences between structure-selected models and complete structure models are: (i) the former are more parsimonious than the latter, (ii) a predefined fixed-point configuration can be guaranteed for the former, and (iii) the former set of models produce attractors that are topologically closer to the original attractor than those produced by the complete structure models.

  7. In situ definition of semiconductor structures by selective area growth and etching

    NASA Astrophysics Data System (ADS)

    Colas, E.; Caneau, C.; Frei, M.; Clausen, E. M., Jr.; Quinn, W. E.; Kim, M. S.

    1991-10-01

    Selective area growth (etching) by low-pressure organometallic chemical vapor deposition (LP-OMCVD) is utilized to intentionally modulate the local growth (etch) rate by choosing the pattern of dielectric-masked areas, thereby defining III-V semiconductor structures in situ. This technique is applied to tune the emission wavelength of a GaAs/AlGaAs quantum well structure, and to obtain InP/InGaAs superlattice structures tapered in thickness with growth rate increases as high as 800%, suitable for integrated optics applications. In contrast, selective deposition by organometallic molecular beam epitaxy (OMMBE) does not produce growth rate enhancements, thereby preventing similar in situ definition schemes but allowing to integrate structures with optimized nominal thicknesses.

  8. Selective Epitaxy of InP on Si and Rectification in Graphene/InP/Si Hybrid Structure.

    PubMed

    Niu, Gang; Capellini, Giovanni; Hatami, Fariba; Di Bartolomeo, Antonio; Niermann, Tore; Hussein, Emad Hameed; Schubert, Markus Andreas; Krause, Hans-Michael; Zaumseil, Peter; Skibitzki, Oliver; Lupina, Grzegorz; Masselink, William Ted; Lehmann, Michael; Xie, Ya-Hong; Schroeder, Thomas

    2016-10-12

    The epitaxial integration of highly heterogeneous material systems with silicon (Si) is a central topic in (opto-)electronics owing to device applications. InP could open new avenues for the realization of novel devices such as high-mobility transistors in next-generation CMOS or efficient lasers in Si photonics circuitry. However, the InP/Si heteroepitaxy is highly challenging due to the lattice (∼8%), thermal expansion mismatch (∼84%), and the different lattice symmetries. Here, we demonstrate the growth of InP nanocrystals showing high structural quality and excellent optoelectronic properties on Si. Our CMOS-compatible innovative approach exploits the selective epitaxy of InP nanocrystals on Si nanometric seeds obtained by the opening of lattice-arranged Si nanotips embedded in a SiO2 matrix. A graphene/InP/Si-tip heterostructure was realized on obtained materials, revealing rectifying behavior and promising photodetection. This work presents a significant advance toward the monolithic integration of graphene/III-V based hybrid devices onto the mainstream Si technology platform.

  9. 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

  10. Three-dimensional window analysis for detecting positive selection at structural regions of proteins.

    PubMed

    Suzuki, Yoshiyuki

    2004-12-01

    Detection of natural selection operating at the amino acid sequence level is important in the study of molecular evolution. Single-site analysis and one-dimensional window analysis can be used to detect selection when the biological functions of amino acid sites are unknown. Single-site analysis is useful when selection operates more or less constantly over evolutionary time, but less so when selection operates temporarily. One-dimensional window analysis is more sensitive than single-site analysis when the functions of amino acid sites in close proximity in the linear sequence are similar, although this is not always the case. Here I present a three-dimensional window analysis method for detecting selection given the three-dimensional structure of the protein of interest. In the three-dimensional structure, the window is defined as the sphere centered on the alpha-carbon of an amino acid site. The window size is the radius of the sphere. The sites whose alpha-carbons are included in the window are grouped for the neutrality test. The window is moved within the three-dimensional structure by sequentially moving the central site along the primary amino acid sequence. To detect positive selection, it may also be useful to group the surface-exposed sites in the window separately. Three-dimensional window analysis appears not only to be more sensitive than single-site analysis and one-dimensional window analysis but also to provide similar specificity for inferring positive selection in the analyses of the hemagglutinin and neuraminidase genes of human influenza A viruses. This method, however, may fail to detect selection when it operates only on a particular site, in which case single-site analysis may be preferred, although a large number of sequences is required.

  11. Acquisition Research Topics Catalog.

    DTIC Science & Technology

    1979-01-01

    expected to increase; if the weapon is models depend upon various types of being phased out, demand for the computational techniques to reach related EOQ...being able to identify these assets, we could Topic: Inventory Model Simulation establish inventory levels based upon Requirements specific product ...eseloresorce reuird fo th prducion management approaches and techniques to resources required for the production minimize loss and damage to Government and

  12. Concluding remarks: Emerging topics

    NASA Astrophysics Data System (ADS)

    Perret-Gallix, D.

    2006-04-01

    In summing up this workshop, we would like to open a broad discussion on additional emerging topics that may contribute to shape the future of physics research computing activities. To initiate this global discussion let me address in this short contribution some of these issues: distributed public computing, social or collaborative software, web computing, high precision numerical computation, common development platforms and languages issues. We welcome contributions to this discussion on the ACAT Twiki web site.

  13. PA Discussion Topics

    DTIC Science & Technology

    2011-02-04

    Vehicle Power & Mobility PA Discussion Topics UNCLASSIFIED: Dist A. Approved for public releas Report Documentation Page Form ApprovedOMB No. 0704...0188 Public reporting burden for the collection of information is estimated to average 1 hour per response, including the time for reviewing instructions...Headquarters Services, Directorate for Information Operations and Reports , 1215 Jefferson Davis Highway, Suite 1204, Arlington VA 22202-4302

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

    PubMed

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

    2014-08-19

    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.

  15. On selection and scaling of ground motions for analysis of seismically isolated structures

    NASA Astrophysics Data System (ADS)

    Pant, Deepak R.; Maharjan, Manika

    2016-12-01

    A broader consensus on the number of ground motions to be used and the method of scaling to be adopted for nonlinear response history analysis (RHA) of structures is yet to be reached. Therefore, in this study, the effects of selection and scaling of ground motions on the response of seismically isolated structures, which are routinely designed using nonlinear RHA, are investigated. For this purpose, isolation systems with a range of properties subjected to bidirectional excitation are considered. Benchmark response of the isolation systems is established using large sets of unscaled ground motions systematically categorized into pulse-like, non-pulse-like, and mixed set of motions. Different subsets of seven to 14 ground motions are selected from these large sets using (a) random selection and (b) selection based on the best match of the shape of the response spectrum of ground motions to the target spectrum. Consequences of weighted scaling (also commonly referred to as amplitude scaling or linear scaling) as well as spectral matching are investigated. The ground motion selection and scaling procedures are evaluated from the viewpoint of their accuracy, efficiency, and consistency in predicting the benchmark response. It is confirmed that seven time histories are sufficient for a reliable prediction of isolation system displacement demands, for all ground motion subsets, selection and scaling procedures, and isolation systems considered. If ground motions are selected based on their best match to the shape of the target response spectrum (which should be preferred over randomly selected motions), weighted scaling should be used if pulse-like motions are considered, either of weighted scaling or spectral matching can be used if non-pulse-like motions are considered, and an average of responses from weighted-scaled and spectrum-matched ground motions should be used for a mixed set of motions. On the other hand, the importance of randomly selected motions in

  16. Structural Basis for the Design of Selective Phosphodiesterase 4B Inhibitors

    PubMed Central

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

    2014-01-01

    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

  17. 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.

  18. SHAPE Selection (SHAPES) enrich for RNA structure signal in SHAPE sequencing-based probing data.

    PubMed

    Poulsen, Line Dahl; Kielpinski, Lukasz Jan; Salama, Sofie R; Krogh, Anders; Vinther, Jeppe

    2015-05-01

    Selective 2' Hydroxyl Acylation analyzed by Primer Extension (SHAPE) is an accurate method for probing of RNA secondary structure. In existing SHAPE methods, the SHAPE probing signal is normalized to a no-reagent control to correct for the background caused by premature termination of the reverse transcriptase. Here, we introduce a SHAPE Selection (SHAPES) reagent, N-propanone isatoic anhydride (NPIA), which retains the ability of SHAPE reagents to accurately probe RNA structure, but also allows covalent coupling between the SHAPES reagent and a biotin molecule. We demonstrate that SHAPES-based selection of cDNA-RNA hybrids on streptavidin beads effectively removes the large majority of background signal present in SHAPE probing data and that sequencing-based SHAPES data contain the same amount of RNA structure data as regular sequencing-based SHAPE data obtained through normalization to a no-reagent control. Moreover, the selection efficiently enriches for probed RNAs, suggesting that the SHAPES strategy will be useful for applications with high-background and low-probing signal such as in vivo RNA structure probing.

  19. 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…

  20. Selective Auditory Attention in Adults: Effects of Rhythmic Structure of the Competing Language

    ERIC Educational Resources Information Center

    Reel, Leigh Ann; Hicks, Candace Bourland

    2012-01-01

    Purpose: The authors assessed adult selective auditory attention to determine effects of (a) differences between the vocal/speaking characteristics of different mixed-gender pairs of masking talkers and (b) the rhythmic structure of the language of the competing speech. Method: Reception thresholds for English sentences were measured for 50…

  1. SHAPE Selection (SHAPES) enrich for RNA structure signal in SHAPE sequencing-based probing data

    PubMed Central

    Poulsen, Line Dahl; Kielpinski, Lukasz Jan; Salama, Sofie R.; Krogh, Anders; Vinther, Jeppe

    2015-01-01

    Selective 2′ Hydroxyl Acylation analyzed by Primer Extension (SHAPE) is an accurate method for probing of RNA secondary structure. In existing SHAPE methods, the SHAPE probing signal is normalized to a no-reagent control to correct for the background caused by premature termination of the reverse transcriptase. Here, we introduce a SHAPE Selection (SHAPES) reagent, N-propanone isatoic anhydride (NPIA), which retains the ability of SHAPE reagents to accurately probe RNA structure, but also allows covalent coupling between the SHAPES reagent and a biotin molecule. We demonstrate that SHAPES-based selection of cDNA–RNA hybrids on streptavidin beads effectively removes the large majority of background signal present in SHAPE probing data and that sequencing-based SHAPES data contain the same amount of RNA structure data as regular sequencing-based SHAPE data obtained through normalization to a no-reagent control. Moreover, the selection efficiently enriches for probed RNAs, suggesting that the SHAPES strategy will be useful for applications with high-background and low-probing signal such as in vivo RNA structure probing. PMID:25805860

  2. Comparison of the Factor Structure of Selected Cognitive Abilities in Bilinguals.

    ERIC Educational Resources Information Center

    Wanous, Donna S.

    The organization of nine selected cognitive abilities from Guilford's structure-of-intellect model (SI) was explored in a sample of Spanish-English bilingual students. One hundred and ninety-four seventh and eighth graders were assigned to take a battery of nine cognitive ability tests in Spanish or English. The nine tests measured convergent…

  3. 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.

  4. 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.

  5. 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.

  6. 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.

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

    SciTech Connect

    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.

  8. 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

  9. A method for selecting structure-switching aptamers applied to a colorimetric gold nanoparticle assay.

    PubMed

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

    2015-02-28

    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

  10. 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.

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

    PubMed Central

    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

  12. 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.

  13. Thermal stability of the cellular structure of an austenitic alloy after selective laser melting

    NASA Astrophysics Data System (ADS)

    Bazaleeva, K. O.; Tsvetkova, E. V.; Balakirev, E. V.; Yadroitsev, I. A.; Smurov, I. Yu.

    2016-05-01

    The thermal stability of the cellular structure of an austenitic Fe-17% Cr-12% Ni-2% Mo-1% Mn-0.7% Si-0.02% C alloy produced by selective laser melting in the temperature range 20-1200°C is investigated. Metallographic analysis, transmission electron microscopy, and scanning electron microscopy show that structural changes in the alloy begin at 600-700°C and are fully completed at ~1150°C. Differential scanning calorimetry of the alloy with a cellular structure reveals three exothermic processes occurring upon annealing within the temperature ranges 450-650, 800-1000, and 1050-1200°C.

  14. 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)

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

    PubMed

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

    2010-01-01

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

  16. 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.

  17. 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.

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

    DOE PAGES

    Hart-Cooper, William M.; Zhao, Chen; Triano, Rebecca M.; ...

    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

  19. 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.

  20. 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.

  1. 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.

  2. Drugs and related topics.

    PubMed

    Cereijo, Ines

    2006-01-01

    Drugs is a topic that was certainly an issue of discussion at this year's annual meeting. This Committee had the responsibility of organizing a half day symposium on "Pharmaceutical Authenticity and Safety" that took place September 12, 2005. This symposium aims at improving the critical points in the analytical pharmaceutical field related to traceability assessment, use of certified reference materials (CRMs), and proficiency testing implementation to get the highest quality of the obtained results. Recognized experts presented these topics. Also, other complementary subjects, such as the application of advanced analytical technologies to reach the authenticity and safety of the pharmaceutical drugs and drug products, their microbiological quality assessment, without disregarding an important topic such as sampling, was presented and discussed. The talks that were presented are the following: "Proficiency Testing as a Need in the Pharmaceutical Field," Arlene Fox (AOAC INTERNATIONAL, Gaithersburg, MD); "Implementation of Traceability in the Pharmaceutical Laboratory," Thomas Layloff, (Management Sciences for Health, Arlington, VA); "Harmonized Characteristics of Certified Reference Materials According to ISO Guides-Attractive also for Pharmaceutical Analysis," Hendrik Emons (Reference Materials, Unit Institute for Reference Materials and Measurements (IRMM), Joint Research Centre European Commission, (Geel, Belgium); "Importance of LC/MS/MS for the Fingerprinting of Pharmaceutical Drugs," Paul A. Steinberg, (Thermo Electron Corp., Woodstock, GA); "Process Analytical Technology (PAT) as a Way for Better Manufacturing and Quality Assurance," John F. Kauffman (Division of Pharmaceutical Analysis, U.S. Food and Drug Administration (St. Louis, MO); "Stability Testing for the Safety Assessment of Pharmaceuticals," Marta Vidal (Boeringher Ingelheim Argentina, Buenos Aires, Argentina); "Validation of Microbiological Methods for Sterile and Nonsterile Pharmaceutical

  3. Observation selection bias in contact prediction and its implications for structural bioinformatics

    PubMed Central

    Orlando, G.; Raimondi, D.; Vranken, W. F.

    2016-01-01

    Next Generation Sequencing is dramatically increasing the number of known protein sequences, with related experimentally determined protein structures lagging behind. Structural bioinformatics is attempting to close this gap by developing approaches that predict structure-level characteristics for uncharacterized protein sequences, with most of the developed methods relying heavily on evolutionary information collected from homologous sequences. Here we show that there is a substantial observational selection bias in this approach: the predictions are validated on proteins with known structures from the PDB, but exactly for those proteins significantly more homologs are available compared to less studied sequences randomly extracted from Uniprot. Structural bioinformatics methods that were developed this way are thus likely to have over-estimated performances; we demonstrate this for two contact prediction methods, where performances drop up to 60% when taking into account a more realistic amount of evolutionary information. We provide a bias-free dataset for the validation for contact prediction methods called NOUMENON. PMID:27857150

  4. 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.

  5. Threats to Aircraft Structural Safety Including a Compendium of Selected Structural Accidents/Incidents

    DTIC Science & Technology

    2010-03-01

    Air Materiel Command tested the structural strength of the F-84s and concluded that wing failure was caused by high speed pull- up in excess of...Locations of the B-47 Aircraft A10 The same day a TB-47B broke up at 23,000 feet over Tulsa, Oklahoma, after the left wing lower surface failed...from the aircraft and flew up and over the port wing and fell back on the runway behind the aircraft (See Figure C8). As a result of this engine

  6. Structural analysis of uniformly (13)C-labelled solids from selective angle measurements at rotational resonance.

    PubMed

    Patching, Simon G; Edwards, Rachel; Middleton, David A

    2009-08-01

    We demonstrate that individual H-C-C-H torsional angles in uniformly labelled organic solids can be estimated by selective excitation of (13)C double-quantum coherences under magic-angle spinning at rotational resonance. By adapting a straightforward one-dimensional experiment described earlier [T. Karlsson, M. Eden, H. Luhman, M.H. Levitt, J. Magn. Reson. 145 (2000) 95-107], a double-quantum filtered spectrum selective for Calpha and Cbeta of uniformly labelled L-[(13)C,(15)N]valine is obtained with 25% efficiency. The evolution of Calpha-Cbeta double-quantum coherence under the influence of the dipolar fields of bonded protons is monitored to provide a value of the Halpha-Calpha-Cbeta-Hbeta torsional angle that is consistent with the crystal structure. In addition, double-quantum filtration selective for C6 and C1' of uniformly labelled [(13)C,(15)N]uridine is achieved with 12% efficiency for a (13)C-(13)C distance of 2.5A, yielding a reliable estimate of the C6-H and C1'-H projection angle defining the relative orientations of the nucleoside pyrimidine and ribose rings. This procedure will be useful, in favourable cases, for structural analysis of fully labelled small molecules such as receptor ligands that are not readily synthesised with labels placed selectively at structurally diagnostic sites.

  7. Structural analysis of uniformly 13C-labelled solids from selective angle measurements at rotational resonance

    NASA Astrophysics Data System (ADS)

    Patching, Simon G.; Edwards, Rachel; Middleton, David A.

    2009-08-01

    We demonstrate that individual H-C-C-H torsional angles in uniformly labelled organic solids can be estimated by selective excitation of 13C double-quantum coherences under magic-angle spinning at rotational resonance. By adapting a straightforward one-dimensional experiment described earlier [T. Karlsson, M. Eden, H. Luhman, M.H. Levitt, J. Magn. Reson. 145 (2000) 95-107], a double-quantum filtered spectrum selective for Cα and Cβ of uniformly labelled L-[ 13C, 15N]valine is obtained with 25% efficiency. The evolution of Cα-Cβ double-quantum coherence under the influence of the dipolar fields of bonded protons is monitored to provide a value of the Hα-Cα-Cβ-Hβ torsional angle that is consistent with the crystal structure. In addition, double-quantum filtration selective for C6 and C1' of uniformly labelled [ 13C, 15N]uridine is achieved with 12% efficiency for a 13C- 13C distance of 2.5 Å, yielding a reliable estimate of the C6-H and C1'-H projection angle defining the relative orientations of the nucleoside pyrimidine and ribose rings. This procedure will be useful, in favourable cases, for structural analysis of fully labelled small molecules such as receptor ligands that are not readily synthesised with labels placed selectively at structurally diagnostic sites.

  8. 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

  9. 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.

  10. Positive selection sites in tertiary structure of Leguminosae chalcone isomerase 1.

    PubMed

    Wang, R K; Zhan, S F; Zhao, T J; Zhou, X L; Wang, C E

    2015-03-20

    Isoflavonoids and the related synthesis enzyme, chalcone isomerase 1 (CHI1), are unique in the Leguminosae, with diverse biological functions. Among the Leguminosae, the soybean is an important oil, protein crop, and model plant. In this study, we aimed to detect the generation pattern of Leguminosae CHI1. Genome-wide sequence analysis of CHI in 3 Leguminosae and 3 other closely related model plants was performed; the expression levels of soybean chalcone isomerases were also analyzed. By comparing positively selected sites and their protein structures, we retrieved the evolution patterns for Leguminosae CHI1. A total of 28 CHI and 7 FAP3 (CHI4) genes were identified and separated into 4 clades: CHI1, CHI2, CHI3, and FAP3. Soybean genes belonging to the same chalcone isomerase subfamily had similar expression patterns. CHI1, the unique chalcone isomerase subfamily in Leguminosae, showed signs of significant positive selection as well as special expression characteristics, indicating an accelerated evolution throughout its divergence. Eight sites were identified as undergoing positive selection with high confidence. When mapped onto the tertiary structure of CHI1, these 8 sites were observed surrounding the enzyme substrate only; some of them connected to the catalytic core of CHI. Thus, we inferred that the generation of Leguminosae CHI1 is dependent on the positively selected amino acids surrounding its catalytic substrate. In other words, the evolution of CHI1 was driven by specific selection or processing conditions within the substrate.

  11. Structural Biology Insight for the Design of Sub-type Selective Aurora Kinase Inhibitors.

    PubMed

    Sarvagalla, Sailu; Coumar, Mohane Selvaraj

    2015-01-01

    Aurora kinase A, B and C, are key regulators of mitosis and are over expressed in many of the human cancers, making them an ideal drug target for cancer chemotherapy. Currently, over a dozen of Aurora kinase inhibitors are in various phases of clinical development. The majority of the inhibitors (VX-680/MK-0457, PHA-739358, CYC116, SNS-314, AMG 900, AT-9283, SCH- 1473759, ABT-348, PF-03814735, R-763/AS-703569, KW-2449 and TAK-901) are pan-selective (isoform non-selective) and few are Aurora A (MLN8054, MLN8237, VX-689/MK5108 and ENMD 2076) and Aurora B (AZD1152 and GSK1070916) sub-type selective. Despite the intensive research efforts in the past decade, no Aurora kinase inhibitor has reached the market. Recent evidence suggests that the sub-type selective Aurora kinase A inhibitor could possess advantages over pan-selective Aurora inhibitors, by avoiding Aurora B mediated neutropenia. However, sub-type selective Aurora kinase A inhibitor design is very challenging due to the similarity in the active site among the isoforms. Structural biology and computational aspects pertaining to the design of Aurora kinase inhibitors were analyzed and found that a possible means to develop sub-type selective inhibitor is by targeting Aurora A specific residues (Leu215, Thr217 and Arg220) or Aurora B specific residues (Arg159, Glu161 and Lys164), near the solvent exposed region of the protein. Particularly, a useful strategy for the design of sub-type selective Aurora A inhibitor could be by targeting Thr217 residue as in the case of MLN8054. Further preclinical and clinical studies with the sub-type selective Aurora inhibitors could help bring them to the market for the treatment of cancer.

  12. 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

  13. 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.

  14. CONDENSED MATTER: ELECTRONIC STRUCTURE, ELECTRICAL, MAGNETIC, AND OPTICAL PROPERTIES: Frequency selective surface structure optimized by genetic algorithm

    NASA Astrophysics Data System (ADS)

    Lu, Jun; Wang, Jian-Bo; Sun, Guan-Cheng

    2009-04-01

    Frequency selective surface (FSS) is a two-dimensional periodic structure which has prominent characteristics of bandpass or bandblock when interacting with electromagnetic waves. In this paper, the thickness, the dielectric constant, the element graph and the arrangement periodicity of an FSS medium are investigated by Genetic Algorithm (GA) when an electromagnetic wave is incident on the FSS at a wide angle, and an optimized FSS structure and transmission characteristics are obtained. The results show that the optimized structure has better stability in relation to incident angle of electromagnetic wave and preserves the stability of centre frequency even at an incident angle as large as 80°, thereby laying the foundation for the application of FSS to curved surfaces at wide angles.

  15. Structure-Based Design of Potent and Selective CK1γ Inhibitors

    PubMed Central

    2012-01-01

    Aberrant activation of the Wnt pathway is believed to drive the development and growth of some cancers. The central role of CK1γ in Wnt signal transduction makes it an attractive target for the treatment of Wnt-pathway dependent cancers. We describe a structure-based approach that led to the discovery of a series of pyridyl pyrrolopyridinones as potent and selective CK1γ inhibitors. These compounds exhibited good enzyme and cell potency, as well as selectivity against other CK1 isoforms. A single oral dose of compound 13 resulted in significant inhibition of LRP6 phosphorylation in a mouse tumor PD model. PMID:24900428

  16. Structure-activity relationship study of selective benzimidazole-based inhibitors of Cryptosporidium parvum IMPDH

    PubMed Central

    Kirubakaran, Sivapriya; Gorla, Suresh Kumar; Sharling, Lisa; Zhang, Minjia; Liu, Xiaoping; Ray, Soumya S.; MacPherson, Iain S.; Striepen, Boris; Hedstrom, Lizbeth; Cuny, Gregory D.

    2012-01-01

    Cryptosporidium parasites are important waterborne pathogens of both humans and animals. The C. parvum and C. hominis genomes indicate that the only route to guanine nucleotides is via inosine 5'-monophosphate dehydrogenase (IMPDH). Thus the inhibition of the parasite IMPDH presents a potential strategy for treating Cryptosporidium infections. A selective benzimidazole-based inhibitor of C. parvum IMPDH (CpIMPDH) was previously identified in a high throughput screen. Here we report a structure-activity relationship study of benzimidazole-based compounds that resulted in potent and selective inhibitors of CpIMPDH. Several compounds display potent antiparasitic activity in vitro. PMID:22310229

  17. Structural characterization of nonactive site, TrkA-selective kinase inhibitors

    SciTech Connect

    Su, Hua-Poo; Rickert, Keith; Burlein, Christine; Narayan, Kartik; Bukhtiyarova, Marina; Hurzy, Danielle M.; Stump, Craig A.; Zhang, Xufang; Reid, John; Krasowska-Zoladek, Alicja; Tummala, Srivanya; Shipman, Jennifer M.; Kornienko, Maria; Lemaire, Peter A.; Krosky, Daniel; Heller, Amanda; Achab, Abdelghani; Chamberlin, Chad; Saradjian, Peter; Sauvagnat, Berengere; Yang, Xianshu; Ziebell, Michael R.; Nickbarg, Elliott; Sanders, John M.; Bilodeau, Mark T.; Carroll, Steven S.; Lumb, Kevin J.; Soisson, Stephen M.; Henze, Darrell A.; Cooke, Andrew J.

    2016-12-30

    Current therapies for chronic pain can have insufficient efficacy and lead to side effects, necessitating research of novel targets against pain. Although originally identified as an oncogene, Tropomyosin-related kinase A (TrkA) is linked to pain and elevated levels of NGF (the ligand for TrkA) are associated with chronic pain. Antibodies that block TrkA interaction with its ligand, NGF, are in clinical trials for pain relief. Here, we describe the identification of TrkA-specific inhibitors and the structural basis for their selectivity over other Trk family kinases. The X-ray structures reveal a binding site outside the kinase active site that uses residues from the kinase domain and the juxtamembrane region. Three modes of binding with the juxtamembrane region are characterized through a series of ligand-bound complexes. The structures indicate a critical pharmacophore on the compounds that leads to the distinct binding modes. The mode of interaction can allow TrkA selectivity over TrkB and TrkC or promiscuous, pan-Trk inhibition. This finding highlights the difficulty in characterizing the structure-activity relationship of a chemical series in the absence of structural information because of substantial differences in the interacting residues. These structures illustrate the flexibility of binding to sequences outside of—but adjacent to—the kinase domain of TrkA. This knowledge allows development of compounds with specificity for TrkA or the family of Trk proteins.

  18. Topical Knowledge and Topical Interest Predictors of Listening Comprehension.

    ERIC Educational Resources Information Center

    Hare, Victoria Chou; Devine, Denise A.

    1983-01-01

    A study investigated whether preassessments of general and specific knowledge can predict children's listening comprehension. Topical knowledge, assessed by multiple-choice questions, did predict story comprehension; topical interest, however, did not correlate either with topical knowledge or comprehension. (Authors/PP)

  19. Identification of selectivity determinants in CYP monooxygenases by modelling and systematic analysis of sequence and structure.

    PubMed

    Seifert, Alexander; Pleiss, Jurgen

    2012-02-01

    Cytochrome P450 monooxygenases (CYPs) form a large, ubiquitous enzyme family and are of great interest in red and white biotechnology. To investigate the effect of protein structure on selectivity, the binding of substrate molecules near to the active site was modelled by molecular dynamics simulations. From a comprehensive and systematic comparison of more than 6300 CYP sequences and 31 structures using the Cytochrome P450 Engineering Database (CYPED), residues were identified which are predicted to point close to the heme centre and thus restrict accessibility for substrates. As a result, sequence-structure-function relationships are described that can be used to predict selectivity-determining positions from CYP sequences and structures. Based on this analysis, a minimal library consisting of bacterial CYP102A1 (P450(BM3)) and 24 variants was constructed. All variants were functionally expressed in E. coli, and the library was screened with four terpene substrates. Only 3 variants showed no activity towards all 4 terpenes, while 11 variants demonstrated either a strong shift or improved regio- or stereoselectivity during oxidation of at least one substrate as compared to CYP102A1 wild type. The minimal library also contains variants that show interesting side products which are not generated by the wild type enzyme. By two additional rounds of molecular modelling, diversification, and screening, the selectivity of one of these variants for a new product was optimised with a minimal screening effort. We propose this as a generic approach for other CYP substrates.

  20. Selective self-assembly of hexameric homo- and heteropolymetallic lanthanide wheels: synthesis, structure, and photophysical studies.

    PubMed

    Chen, Xiao-Yan; Bretonnière, Yann; Pécaut, Jacques; Imbert, Daniel; Bünzli, Jean-Claude; Mazzanti, Marinella

    2007-02-05

    A rational approach to the formation of pure heteropolymetallic lanthanide complexes that uses a two-step assembly strategy and exploits the different size requirements of the two metals included in the final structure is described. The investigation of the assembly of [LnL2](Otf) (L = 2,2':6',2' '-terpyridine-6-carboxylate) complexes into hexametallic rings hosting an additional hexacoordinated lanthanide cation was crucial for the development of this strategy. The formation and size of the cyclic assembly are controlled by the ionic radius and by the coordination number of the lanthanides. The rather high luminescence quantum yield of the heptaeuropium complex (25%) indicates that the ring structure is well adapted to include highly luminescent lanthanide complexes in nanosized architecture. The use of a stepwise synthetic strategy leads to the selective assembly of large heteropolymetallic rings. The addition of a smaller lanthanide ion to the [EuL2](Otf) complex in anhydrous acetonitrile leads selectively to heterometallic species with the Eu ions located on the peripheral sites and the smaller ion occupying only the central site. The high selectivity is the result of the different size requirements of the two metal sites present in the cyclic structure. The heterometallic structure of the isolated [Lu subset (EuL2)6](Otf)9 complex was confirmed by X-ray diffraction and by high resolution solid-state photophysical studies. The described synthetic approach allowed us to obtain the first example of selective assembly of two different lanthanide ions in a large polymetallic structure characterized in solution and in the solid state and will make the isolation of planned dimetallic combinations presenting different lanthanide emitters in the peripheral sites possible.

  1. 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

  2. Hot topics for leadership development.

    PubMed

    Bleich, Michael R

    2015-02-01

    Three areas stand out from a health systems perspective that should be on the development agenda for all leaders. These topics include population health, predictive analytics, and supply chain management. Together, these topics address access, quality, and cost management.

  3. 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

  4. 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

    2013-12-07

    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.

  5. 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)).

  6. Genomic hypomethylation in the human germline associates with selective structural mutability in the human genome.

    PubMed

    Li, Jian; Harris, R Alan; Cheung, Sau Wai; Coarfa, Cristian; Jeong, Mira; Goodell, Margaret A; White, Lisa D; Patel, Ankita; Kang, Sung-Hae; Shaw, Chad; Chinault, A Craig; Gambin, Tomasz; Gambin, Anna; Lupski, James R; Milosavljevic, Aleksandar

    2012-01-01

    The hotspots of structural polymorphisms and structural mutability in the human genome remain to be explained mechanistically. We examine associations of structural mutability with germline DNA methylation and with non-allelic homologous recombination (NAHR) mediated by low-copy repeats (LCRs). Combined evidence from four human sperm methylome maps, human genome evolution, structural polymorphisms in the human population, and previous genomic and disease studies consistently points to a strong association of germline hypomethylation and genomic instability. Specifically, methylation deserts, the ~1% fraction of the human genome with the lowest methylation in the germline, show a tenfold enrichment for structural rearrangements that occurred in the human genome since the branching of chimpanzee and are highly enriched for fast-evolving loci that regulate tissue-specific gene expression. Analysis of copy number variants (CNVs) from 400 human samples identified using a custom-designed array comparative genomic hybridization (aCGH) chip, combined with publicly available structural variation data, indicates that association of structural mutability with germline hypomethylation is comparable in magnitude to the association of structural mutability with LCR-mediated NAHR. Moreover, rare CNVs occurring in the genomes of individuals diagnosed with schizophrenia, bipolar disorder, and developmental delay and de novo CNVs occurring in those diagnosed with autism are significantly more concentrated within hypomethylated regions. These findings suggest a new connection between the epigenome, selective mutability, evolution, and human disease.

  7. Tribological behavior of Ti6Al4V cellular structures produced by Selective Laser Melting.

    PubMed

    Bartolomeu, F; Sampaio, M; Carvalho, O; Pinto, E; Alves, N; Gomes, J R; Silva, F S; Miranda, G

    2017-05-01

    Additive manufacturing (AM) technologies enable the fabrication of innovative structures with complex geometries not easily manufactured by traditional processes. Regarding metallic cellular structures with tailored/customized mechanical and wear performance aiming to biomedical applications, Selective Laser Melting (SLM) is a remarkable solution for their production. Focusing on prosthesis and implants, in addition to a suitable Young's modulus it is important to assess the friction response and wear resistance of these cellular structures in a natural environment. In this sense, five cellular Ti6Al4V structures with different open-cell sizes (100-500µm) were designed and produced by SLM. These structures were tribologicaly tested against alumina using a reciprocating sliding ball-on-plate tribometer. Samples were submerged in Phosphate Buffered Saline (PBS) fluid at 37°C, in order to mimic in some extent the human body environment. The results showed that friction and wear performance of Ti6Al4V cellular structures is influenced by the structure open-cell size. The higher wear resistance was obtained for structures with 100µm designed open-cell size due to the higher apparent area of contact to support tribological loading.

  8. 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

  9. Discovery of Potent and Selective Leads against Toxoplasma gondii Dihydrofolate Reductase via Structure-Based Design.

    PubMed

    Welsch, Matthew E; Zhou, Jian; Gao, Yueqiang; Yan, Yunqing; Porter, Gene; Agnihotri, Gautam; Li, Yingjie; Lu, Henry; Chen, Zhongguo; Thomas, Stephen B

    2016-12-08

    Current treatment of toxoplasmosis targets the parasite's folate metabolism through inhibition of dihydrofolate reductase (DHFR). The most widely used DHFR antagonist, pyrimethamine, was introduced over 60 years ago and is associated with toxicity that can be largely attributed to a similar affinity for parasite and human DHFR. Computational analysis of biochemical differences between Toxoplasma gondii and human DHFR enabled the design of inhibitors with both improved potency and selectivity. The approach described herein yielded TRC-19, a promising lead with an IC50 of 9 nM and 89-fold selectivity in favor of Toxoplasma gondii DHFR, as well as crystallographic data to substantiate in silico methodology. Overall, 50% of synthesized in silico designs met hit threshold criteria of IC50 < 10 μM and >2-fold selectivity favoring Toxoplasma gondii, further demonstrating the efficiency of our structure-based drug design approach.

  10. 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

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

    SciTech Connect

    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.

  12. 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.

  13. 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.

  14. 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.

  15. Heterogeneous selection in a spatially structured environment affects fitness tradeoffs of plasmid carriage in pseudomonads.

    PubMed

    Slater, Frances R; Bruce, Kenneth D; Ellis, Richard J; Lilley, Andrew K; Turner, Sarah L

    2008-05-01

    Environmental conditions under which fitness tradeoffs of plasmid carriage are balanced to facilitate plasmid persistence remain elusive. Periodic selection for plasmid-encoded traits due to the spatial and temporal variation typical in most natural environments (such as soil particles, plant leaf and root surfaces, gut linings, and the skin) may play a role. However, quantification of selection pressures and their effects is difficult at a scale relevant to the bacterium in situ. The present work describes a novel experimental system for such fine-scale quantification, with conditions designed to mimic the mosaic of spatially variable selection pressures present in natural surface environments. The effects of uniform and spatially heterogeneous mercuric chloride (HgCl(2)) on the dynamics of a model community of plasmid-carrying, mercury-resistant (Hg(r)) and plasmid-free, mercury-sensitive (Hg(s)) pseudomonads were compared. Hg resulted in an increase in the surface area occupied by, and therefore an increase in the fitness of, Hg(r) bacteria relative to Hg(s) bacteria. Uniform and heterogeneous Hg distributions were demonstrated to result in different community structures by epifluorescence microscopy, with heterogeneous Hg producing spatially variable selection landscapes. The effects of heterogeneous Hg were only apparent at scales of a few hundred micrometers, emphasizing the importance of using appropriate analysis methods to detect effects of environmental heterogeneity on community dynamics. Heterogeneous Hg resulted in negative frequency-dependent selection for Hg(r) cells, suggesting that sporadic selection may facilitate the discontinuous distribution of plasmids through host populations in complex, structured environments.

  16. 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

  17. Characterization of Two Distinct Structural Classes of Selective Aldehyde Dehydrogenase 1A1 Inhibitors

    PubMed Central

    Morgan, Cynthia A.; Hurley, Thomas D.

    2015-01-01

    Aldehyde dehydrogenases (ALDH) catalyze the irreversible oxidation of aldehydes to their corresponding carboxylic acid. Alterations in ALDH1A1 activity are associated with such diverse diseases as cancer, Parkinson’s disease, obesity, and cataracts. Inhibitors of ALDH1A1 could aid in illuminating the role of this enzyme in disease processes. However, there are no commercially available selective inhibitors for ALDH1A1. Here we characterize two distinct chemical classes of inhibitors that are selective for human ALDH1A1 compared to eight other ALDH isoenzymes. The prototypical members of each structural class, CM026 and CM037, exhibit sub-micromolar inhibition constants, but have different mechanisms of inhibition. The crystal structures of these compounds bound to ALDH1A1 demonstrate that they bind within the aldehyde binding pocket of ALDH1A1 and exploit the presence of a unique Glycine residue to achieve their selectivity. These two novel and selective ALDH1A1 inhibitors may serve as chemical tools to better understand the contributions of ALDH1A1 to normal biology and to disease states. PMID:25634381

  18. Structure-Activity Relationships in Salinomycin: Cytotoxicity and Phenotype Selectivity of Semi-synthetic Derivatives.

    PubMed

    Borgström, Björn; Huang, Xiaoli; Hegardt, Cecilia; Oredsson, Stina; Strand, Daniel

    2017-02-10

    The ionophore salinomycin has attracted attention for its exceptional ability to selectively reduce the proportion of cells with stem-like properties in cancer cell populations of varying origin. Targeting the tumorigenicity of such cells is of interest as they are implicated in recurrence, metastasis, and drug resistance. Structural derivatives of salinomycin are thus sought after, both as tools for probing the molecular mechanism(s) underlying the observed phenotype effects, and for improving selectivity and activity against cancer stem cells. Synthetic strategies for modification of each of the directly accessible functional groups of salinomycin are presented and the resulting library of analogues was investigated to establish structure-activity relationships, both with respect to cytotoxicity and phenotype selectivity in breast cancer cells. 20-O-Acylated derivatives stand out by exhibiting both improved selectivity and activity. Mechanistically, the importance of the ionophore properties of salinomycin is highlighted by a significant loss of activity by modifications directly interfering with either of the two primary ion coordinating motifs in salinomycin, the C11 ketone and the C1 carboxylate.

  19. Feature Selection Using Information Gain for Improved Structural-Based Alert Correlation.

    PubMed

    Alhaj, Taqwa Ahmed; Siraj, Maheyzah Md; Zainal, Anazida; Elshoush, Huwaida Tagelsir; Elhaj, Fatin

    2016-01-01

    Grouping and clustering alerts for intrusion detection based on the similarity of features is referred to as structurally base alert correlation and can discover a list of attack steps. Previous researchers selected different features and data sources manually based on their knowledge and experience, which lead to the less accurate identification of attack steps and inconsistent performance of clustering accuracy. Furthermore, the existing alert correlation systems deal with a huge amount of data that contains null values, incomplete information, and irrelevant features causing the analysis of the alerts to be tedious, time-consuming and error-prone. Therefore, this paper focuses on selecting accurate and significant features of alerts that are appropriate to represent the attack steps, thus, enhancing the structural-based alert correlation model. A two-tier feature selection method is proposed to obtain the significant features. The first tier aims at ranking the subset of features based on high information gain entropy in decreasing order. The‏ second tier extends additional features with a better discriminative ability than the initially ranked features. Performance analysis results show the significance of the selected features in terms of the clustering accuracy using 2000 DARPA intrusion detection scenario-specific dataset.

  20. Feature Selection Using Information Gain for Improved Structural-Based Alert Correlation

    PubMed Central

    Siraj, Maheyzah Md; Zainal, Anazida; Elshoush, Huwaida Tagelsir; Elhaj, Fatin

    2016-01-01

    Grouping and clustering alerts for intrusion detection based on the similarity of features is referred to as structurally base alert correlation and can discover a list of attack steps. Previous researchers selected different features and data sources manually based on their knowledge and experience, which lead to the less accurate identification of attack steps and inconsistent performance of clustering accuracy. Furthermore, the existing alert correlation systems deal with a huge amount of data that contains null values, incomplete information, and irrelevant features causing the analysis of the alerts to be tedious, time-consuming and error-prone. Therefore, this paper focuses on selecting accurate and significant features of alerts that are appropriate to represent the attack steps, thus, enhancing the structural-based alert correlation model. A two-tier feature selection method is proposed to obtain the significant features. The first tier aims at ranking the subset of features based on high information gain entropy in decreasing order. The‏ second tier extends additional features with a better discriminative ability than the initially ranked features. Performance analysis results show the significance of the selected features in terms of the clustering accuracy using 2000 DARPA intrusion detection scenario-specific dataset. PMID:27893821

  1. 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.

  2. 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.

  3. Local selection and population structure in a deep-sea fish, the roundnose grenadier (Coryphaenoides rupestris).

    PubMed

    White, Thomas A; Stamford, Joanne; Rus Hoelzel, A

    2010-01-01

    Local populations within a species can become isolated by stochastic or adaptive processes, though it is most commonly the former that we quantify. Using presumably neutral markers we can assess the time-dependent process of genetic drift, and thereby quantify patterns of differentiation in support of the effective management of diversity. However, adaptive differences can be overlooked in these studies, and these are the very characteristics that we hope to conserve by managing neutral diversity. In this study, we used 16 hypothetically neutral microsatellite markers to investigate the genetic structure of the roundnose grenadier in the North Atlantic. We found that one locus was a clear outlier under directional selection, with F(ST) values much greater than at the remaining loci. Differentiation between populations at this locus was related to depth, suggesting directional selection, presumably acting on a linked locus. Considering only the loci identified as neutral, there remained significant population structure over the region of the North Atlantic studied. In addition to a weak pattern of isolation by distance, we identified a putative barrier to gene flow between sample sites either side of the Charlie-Gibbs Fracture Zone, which marks the location where the sub-polar front crosses the Mid-Atlantic Ridge. This may reflect a boundary across which larvae are differentially distributed in separate current systems to some extent, promoting differentiation by drift. Structure due to both drift and apparent selection should be considered in management policy.

  4. A computational proposal for designing structured RNA pools for in vitro selection of RNAs

    PubMed Central

    Kim, Namhee; Gan, Hin Hark; Schlick, Tamar

    2007-01-01

    Although in vitro selection technology is a versatile experimental tool for discovering novel synthetic RNA molecules, finding complex RNA molecules is difficult because most RNAs identified from random sequence pools are simple motifs, consistent with recent computational analysis of such sequence pools. Thus, enriching in vitro selection pools with complex structures could increase the probability of discovering novel RNAs. Here we develop an approach for engineering sequence pools that links RNA sequence space regions with corresponding structural distributions via a “mixing matrix” approach combined with a graph theory analysis. We define five classes of mixing matrices motivated by covariance mutations in RNA; these constructs define nucleotide transition rates and are applied to chosen starting sequences to yield specific nonrandom pools. We examine the coverage of sequence space as a function of the mixing matrix and starting sequence via clustering analysis. We show that, in contrast to random sequences, which are associated only with a local region of sequence space, our designed pools, including a structured pool for GTP aptamers, can target specific motifs. It follows that experimental synthesis of designed pools can benefit from using optimized starting sequences, mixing matrices, and pool fractions associated with each of our constructed pools as a guide. Automation of our approach could provide practical tools for pool design applications for in vitro selection of RNAs and related problems. PMID:17322501

  5. 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.

  6. LASER APPLICATIONS AND OTHER TOPICS IN LASER TECHNOLOGY: Formation of the structure of a laser-arc molten zone in VT22 titanium alloy

    NASA Astrophysics Data System (ADS)

    Gureev, D. M.; Laletin, A. P.; Chulkin, V. N.

    1988-08-01

    An investigation was made of structural and phase changes in the molten zone of a concentrated titanium alloy VT22 as a result of exposure to a laser-arc source and subsequent conventional annealing. Irreversibility of the changes was attributed to a redistribution of the alloying elements, particularly of molybdenum acting as the stabilizer of the β phase. An analysis of the results indicated the need to reduce the duration of action of the thermal source and to improve heat removal, and also to ensure multiple alloying of the molten zone (in a welding seam) with elements characterized by different distribution coefficients in order to reduce the degree of irreversibility of structural and phase changes and to improve the mechanical properties of welding seams.

  7. Target selection and annotation for the structural genomics of the amidohydrolase and enolase superfamilies.

    PubMed

    Pieper, Ursula; Chiang, Ranyee; Seffernick, Jennifer J; Brown, Shoshana D; Glasner, Margaret E; Kelly, Libusha; Eswar, Narayanan; Sauder, J Michael; Bonanno, Jeffrey B; Swaminathan, Subramanyam; Burley, Stephen K; Zheng, Xiaojing; Chance, Mark R; Almo, Steven C; Gerlt, John A; Raushel, Frank M; Jacobson, Matthew P; Babbitt, Patricia C; Sali, Andrej

    2009-04-01

    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.

  8. Selecting a separable parametric spatiotemporal covariance structure for longitudinal imaging data.

    PubMed

    George, Brandon; Aban, Inmaculada

    2015-01-15

    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 patient's 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 types 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 performed in practice, as well as how covariance structure choice can change inferences about fixed effects.

  9. 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

  10. 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

  11. 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.

  12. Site selectivity for protein tyrosine nitration: insights from features of structure and topological network.

    PubMed

    Cheng, Shangli; Lian, Baofeng; Liang, Juan; Shi, Ting; Xie, Lu; Zhao, Yi-Lei

    2013-11-01

    Tyrosine nitration is a covalent post-translational modification, which regulates protein functions such as hindering tyrosine phosphorylation and affecting essential signal transductions in cells. Based on up-to-date proteomics data, tyrosine nitration appears to be a highly selective process since not all tyrosine residues in proteins or all proteins are nitrated in vivo. Quite a few investigations included the protein structural information from the RCSB PDB database, where near 100,000 high-quality three-dimensional structures are available. In this work, we analyzed the local protein structures and amino acid topological networks of the nitrated and non-nitrated tyrosine sites in nitrated proteins, including neighboring atomic distribution, amino acid pair (AAP) and amino acid triangle (AAT). It has been found that aromatic and aliphatic residues, particularly with large volume, aromatic, aliphatic, or acidic side chains, are disfavored for the nitration. After integrating these structural features and topological network features with traditional sequence features, the predictive model achieves a sensitivity of 63.30% and a specificity of 92.24%, resulting in a much better accuracy compared to the previous models with only protein sequence information. Our investigation implies that the site selectivity may stem from a more open, hydrophilic and high-pH chemical environment around the tyrosine residue.

  13. Mutant p53 proteins bind DNA in a DNA structure-selective mode

    PubMed Central

    Göhler, Thomas; Jäger, Stefan; Warnecke, Gabriele; Yasuda, Hideyo; Kim, Ella; Deppert, Wolfgang

    2005-01-01

    Despite the loss of sequence-specific DNA binding, mutant p53 (mutp53) proteins can induce or repress transcription of mutp53-specific target genes. To date, the molecular basis for transcriptional modulation by mutp53 is not understood, but increasing evidence points to the possibility that specific interactions of mutp53 with DNA play an important role. So far, the lack of a common denominator for mutp53 DNA binding, i.e. the existence of common sequence elements, has hampered further characterization of mutp53 DNA binding. Emanating from our previous discovery that DNA structure is an important determinant of wild-type p53 (wtp53) DNA binding, we analyzed the binding of various mutp53 proteins to oligonucleotides mimicking non-B DNA structures. Using various DNA-binding assays we show that mutp53 proteins bind selectively and with high affinity to non-B DNA. In contrast to sequence-specific and DNA structure-dependent binding of wtp53, mutp53 DNA binding to non-B DNA is solely dependent on the stereo-specific configuration of the DNA, and not on DNA sequence. We propose that DNA structure-selective binding of mutp53 proteins is the basis for the well-documented interaction of mutp53 with MAR elements and for transcriptional activities mediates by mutp53. PMID:15722483

  14. 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.

  15. 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

  16. 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)

  17. Layer selective magnetometry in ultrathin magnetic structures by polarised neutron reflection

    NASA Astrophysics Data System (ADS)

    Bland, J. A. C.; Lee, J.; Hope, S.; Lauhoff, G.; Penfold, J.; Bucknall, D.

    1997-06-01

    We discuss the application of polarised neutron reflection to layer selective vector magnetometry measurements in thin magnetic films. To illustrate the application of PNR, we review recent measurements of the absolute moment in X/Fe/Ag(001) structures with X = Pd, Ag, Au and Cu and compare the results with the predictions based on theoretical calculations which take into account the measured interface roughness. For the case of strained fct Ni/Cu(001) structures we illustrate the use of PNR as a self-calibrating magnetometric technique in determining both the magnetic layer thickness and total sample moment for which a reduced moment per Ni atom is observed. Finally we present measurements of the layer dependent moments in FeNi/Cu/Co spin valve structures. We show that by comparing the PNR measurements with SQUID magnetometry measurements of the total sample moment we are able to determine the interface moments on an atomic scale.

  18. Layer selective magnetometry in ultrathin magnetic structures by polarised neutron reflection

    NASA Astrophysics Data System (ADS)

    Bland, J. A. C.; Lee, J.; Hope, S.; Lauhoff, G.; Penfold, J.; Bucknall, D.

    1997-01-01

    We discuss the application of polarised neutron reflection to layer selective vector magnetometry measurements in thin magnetic films. To illustrate the application of PNR, we review recent measurements of the absolute moment in X/Fe/Ag(001) structures with X = Pd, Ag, Au and Cu and compare the results with the predictions based on theoretical calculations which take into account the measured interface roughness. For the case of strained fct Ni/Cu(001) structures we illustrate the use of PNR as a self-calibrating magnetometric technique in determining both the magnetic layer thickness and total sample moment for which a reduced moment per Ni atom is observed. Finally we present measurements of the layer dependent moments in FeNi/Cu/Co spin valve structures. We show that by comparing the PNR measurements with SQUID magnetometry measurements of the total sample moment we are able to determine the interface moments on an atomic scale.

  19. The type of carbohydrates specifically selects microbial community structures and fermentation patterns.

    PubMed

    Chatellard, Lucile; Trably, Eric; Carrère, Hélène

    2016-12-01

    The impact on dark fermentation of seven carbohydrates as model substrates of lignocellulosic fractions (glucose, cellobiose, microcrystalline cellulose, arabinose, xylose, xylan and wheat straw) was investigated. Metabolic patterns and bacterial communities were characterized at the end of batch tests inoculated with manure digestate. It was found that hydrogen production was linked to the sugar type (pentose or hexose) and the degree of polymerisation. Hexoses produced less hydrogen, with a specific selection of lactate-producing bacterial community structures. Maximal hydrogen production was five times higher on pentose-based substrates, with specific bacterial community structures producing acetate and butyrate as main metabolites. Low hydrogen amounts accumulated from complex sugars (cellulose, xylan and wheat straw). A relatively high proportion of the reads was affiliated to Ruminococcaceae suggesting an efficient hydrolytic activity. Knowing that the bacterial community structure is very specific to a particular substrate offers new possibilities to design more efficient H2-producing biological systems.

  20. 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.

  1. Hot topics in noise

    NASA Astrophysics Data System (ADS)

    Stinson, Michael R.

    2003-10-01

    Our world continues to be a noisy place and the challenge to ``increase and diffuse knowledge of noise propagation, passive and active noise control, and the effects of noise'' remains. In the last several years, noise in the classroom has emerged as one of the hotter topics: Considerable progress has been made in the underpinning research, the formulation of recommendations, and the process of educating society on the social and personal impact of inadequate acoustical conditions in classrooms. The establishment of the ANSI S12.60-2002 standard for classroom acoustics was a milestone event. Noise in cities and the understanding of our soundscapes are subjects of ongoing significance. The development of standards and regulations is a continuing process, with urban community noise regulations, aviation noise, and the preservation of natural quiet in national parks being of current concern. New methods to reduce noise are under development and include passive and active methods of noise control, techniques for modeling the performance of noise barriers, and approaches for designing product sound quality.

  2. 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.

  3. 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.

  4. Elucidating features that drive the design of selective antifolates using crystal structures of human dihydrofolate reductase.

    PubMed

    Lamb, Kristen M; G-Dayanandan, Narendran; Wright, Dennis L; Anderson, Amy C

    2013-10-15

    The pursuit of antimicrobial drugs that target dihydrofolate reductase (DHFR) exploits differences in sequence and dynamics between the pathogenic and human enzymes. Here, we present five crystal structures of human DHFR bound to a new class of antimicrobial agents, the propargyl-linked antifolates (PLAs), with a range of potency (IC50 values of 0.045-1.07 μM) for human DHFR. These structures reveal that interactions between the ligands and Asn 64, Phe 31, and Phe 34 are important for increased affinity for human DHFR and that loop residues 58-64 undergo ligand-induced conformational changes. The utility of these structural studies was demonstrated through the design of three new ligands that reduce the number of contacts with Asn 64, Phe 31, and Phe 34. Synthesis and evaluation show that one of the designed inhibitors exhibits the lowest affinity for human DHFR of any of the PLAs (2.64 μM). Comparisons of structures of human and Staphylococcus aureus DHFR bound to the same PLA reveal a conformational change in the ligand that enhances interactions with residues Phe 92 (Val 115 in huDHFR) and Ile 50 (Ile 60 in huDHFR) in S. aureus DHFR, yielding selectivity. Likewise, comparisons of human and Candida glabrata DHFR bound to the same ligand show that hydrophobic interactions with residues Ile 121 and Phe 66 (Val 115 and Asn 64 in human DHFR) yield selective inhibitors. The identification of residue substitutions that are important for selectivity and the observation of active site flexibility will help guide antimicrobial antifolate development for the inhibition of pathogenic species.

  5. ESL/EFL Methodology: Topical, Annotated Bibliographies. Volume 1.

    ERIC Educational Resources Information Center

    Tannacito, Dan J., Comp.; Gebhard, Jerry G., Comp.

    Six annotated bibliographies prepared by graduate students address topics related to methodology for teaching English as a Second Language (ESL) or English as a Foreign Language (EFL). Each bibliography defines a topic area, gives pedagogical criteria for selecting entries, and provides brief annotations for relevant recent citations. The six…

  6. Hot Topics on the Web: Strategies for Research.

    ERIC Educational Resources Information Center

    Diaz, Karen R.; O'Hanlon, Nancy

    2001-01-01

    Presents strategies for researching topics on the Web that are controversial or current in nature. Discusses topic selection and overviews, including the use of online encyclopedias; search engines; finding laws and pending legislation; advocacy groups; proprietary databases; Web site evaluation; and the continuing usefulness of print materials.…

  7. CLIENT (Communication Law Information: Edited Notes by Topic), Autumn 1975.

    ERIC Educational Resources Information Center

    LeDuc, Don R., Ed.; Krasnow, Erwin G., Ed.

    This issue of CLIENT (Communication Law Information: Edited Notes by Topic) contains the following features: a recent listing of topics related to telecommunications studies in legal journals; an article by Stuart Brotman on financial self-sufficiency for the public interest communication law movement; a selected annotated bibliography of 1974-75…

  8. 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.

  9. 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.

  10. 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

  11. Discovering health topics in social media using topic models.

    PubMed

    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.

  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. 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.

  14. Impact of migration on the multi-strategy selection in finite group-structured populations

    PubMed Central

    Zhang, Yanling; Liu, Aizhi; Sun, Changyin

    2016-01-01

    For large quantities of spatial models, the multi-strategy selection under weak selection is the sum of two competition terms: the pairwise competition and the competition of multiple strategies with equal frequency. Two parameters σ1 and σ2 quantify the dependence of the multi-strategy selection on these two terms, respectively. Unlike previous studies, we here do not require large populations for calculating σ1 and σ2, and perform the first quantitative analysis of the effect of migration on them in group-structured populations of any finite sizes. The Moran and the Wright-Fisher process have the following common findings. Compared with well-mixed populations, migration causes σ1 to change with the mutation probability from a decreasing curve to an inverted U-shaped curve and maintains the increase of σ2. Migration (probability and range) leads to a significant change of σ1 but a negligible one of σ2. The way that migration changes σ1 is qualitatively similar to its influence on the single parameter characterizing the two-strategy selection. The Moran process is more effective in increasing σ1 for most migration probabilities and the Wright-Fisher process is always more effective in increasing σ2. Finally, our findings are used to study the evolution of cooperation under direct reciprocity. PMID:27767074

  15. Structural plasticity and dynamic selectivity of acid-sensing ion channel-spider toxin complexes.

    PubMed

    Baconguis, Isabelle; Gouaux, Eric

    2012-09-20

    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 pH 7.25 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 pH 7.25 the pore is approximately 10 Å in diameter, whereas at pH 5.5 the pore is largely hydrophobic and elliptical in cross-section with dimensions of approximately 5 by 7 Å, 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.

  16. Predicting Significant Factors of Selective Marine Corps Reserve Marines’ Career Decisions in Response to the Force Structure Review

    DTIC Science & Technology

    2014-03-01

    SIGNIFICANT FACTORS OF SELECTIVE MARINE CORPS RESERVE MARINES’ CAREER DECISIONS IN RESPONSE TO THE FORCE STRUCTURE REVIEW by Ryan F. Capdepon...PREDICTING SIGNIFICANT FACTORS OF SELECTIVE MARINE CORPS RESERVE MARINES’ CAREER DECISIONS IN RESPONSE TO THE FORCE STRUCTURE REVIEW 5. FUNDING...Corps Reserve Marine’s career decision when faced with changes initiated by the Force Structure Review Group (FSRG). This thesis identifies those

  17. 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.

  18. Structural basis for selective targeting of leishmanial ribosomes: Aminoglycoside derivatives as promising therapeutics

    DOE PAGES

    Shalev, Moran; Rozenberg, Haim; Smolkin, Boris; ...

    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

  19. 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.

  20. 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.

  1. 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.

  2. Using a two-phase evolutionary framework to select multiple network spreaders based on community structure

    NASA Astrophysics Data System (ADS)

    Fu, Yu-Hsiang; Huang, Chung-Yuan; Sun, Chuen-Tsai

    2016-11-01

    Using network community structures to identify multiple influential spreaders is an appropriate method for analyzing the dissemination of information, ideas and infectious diseases. For example, data on spreaders selected from groups of customers who make similar purchases may be used to advertise products and to optimize limited resource allocation. Other examples include community detection approaches aimed at identifying structures and groups in social or complex networks. However, determining the number of communities in a network remains a challenge. In this paper we describe our proposal for a two-phase evolutionary framework (TPEF) for determining community numbers and maximizing community modularity. Lancichinetti-Fortunato-Radicchi benchmark networks were used to test our proposed method and to analyze execution time, community structure quality, convergence, and the network spreading effect. Results indicate that our proposed TPEF generates satisfactory levels of community quality and convergence. They also suggest a need for an index, mechanism or sampling technique to determine whether a community detection approach should be used for selecting multiple network spreaders.

  3. 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.

  4. 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

  5. The radio structure source of X-ray-selected BL Lacertae objects

    NASA Technical Reports Server (NTRS)

    Perlman, Eric S.; Stocke, John T.

    1993-01-01

    Arcsecond-size radio structure for a complete sample of 14 X-ray-selected BL Lac objects (XBLs) from the Einstein Extended Medium-Sensitivity Survey is presented. Most objects possess radio morphologies which are similar to those of nearby Fanaroff-Riley type 1 (FR 1) radio galaxies once the effects of surface brightness dimming and beam dilution as a function of redshift are taken into account. In order to test the beamed FR 1 hypothesis for BL Lac objects, the core and extended power levels are determined for these sources and compared with samples of radio-selected BL Lac objects (RBLs) and FR 1 from galaxies from the literature. RBLs and XBLs are found to possess extended (and thus unbeamed) power levels and the largest angular sizes similar to those of the FR 1 galaxies both supporting the beaming hypothesis and a common parent population for XBLs and RBLs.

  6. 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.

  7. Evaluating structure selection in the hydrothermal growth of FeS2 pyrite and marcasite

    PubMed Central

    Kitchaev, Daniil A.; Ceder, Gerbrand

    2016-01-01

    While the ab initio prediction of the properties of solids and their optimization towards new proposed materials is becoming established, little predictive theory exists as to which metastable materials can be made and how, impeding their experimental realization. Here we propose a quasi-thermodynamic framework for predicting the hydrothermal synthetic accessibility of metastable materials and apply this model to understanding the phase selection between the pyrite and marcasite polymorphs of FeS2. We demonstrate that phase selection in this system can be explained by the surface stability of the two phases as a function of ambient pH within nano-size regimes relevant to nucleation. This result suggests that a first-principles understanding of nano-size phase stability in realistic synthesis environments can serve to explain or predict the synthetic accessibility of structural polymorphs, providing a guideline to experimental synthesis via efficient computational materials design. PMID:27966547

  8. Joint Bayesian variable and graph selection for regression models with network-structured predictors.

    PubMed

    Peterson, Christine B; Stingo, Francesco C; Vannucci, Marina

    2016-03-30

    In this work, we develop a Bayesian approach to perform selection of predictors that are linked within a network. We achieve this by combining a sparse regression model relating the predictors to a response variable with a graphical model describing conditional dependencies among the predictors. The proposed method is well-suited for genomic applications because it allows the identification of pathways of functionally related genes or proteins that impact an outcome of interest. In contrast to previous approaches for network-guided variable selection, we infer the network among predictors using a Gaussian graphical model and do not assume that network information is available a priori. We demonstrate that our method outperforms existing methods in identifying network-structured predictors in simulation settings and illustrate our proposed model with an application to inference of proteins relevant to glioblastoma survival.

  9. Evaluating structure selection in the hydrothermal growth of FeS2 pyrite and marcasite

    NASA Astrophysics Data System (ADS)

    Kitchaev, Daniil A.; Ceder, Gerbrand

    2016-12-01

    While the ab initio prediction of the properties of solids and their optimization towards new proposed materials is becoming established, little predictive theory exists as to which metastable materials can be made and how, impeding their experimental realization. Here we propose a quasi-thermodynamic framework for predicting the hydrothermal synthetic accessibility of metastable materials and apply this model to understanding the phase selection between the pyrite and marcasite polymorphs of FeS2. We demonstrate that phase selection in this system can be explained by the surface stability of the two phases as a function of ambient pH within nano-size regimes relevant to nucleation. This result suggests that a first-principles understanding of nano-size phase stability in realistic synthesis environments can serve to explain or predict the synthetic accessibility of structural polymorphs, providing a guideline to experimental synthesis via efficient computational materials design.

  10. Structural properties of size-selected FeCo nanoparticles deposited on W(110)

    NASA Astrophysics Data System (ADS)

    Bulut, Furkan; Rosellen, Wolfgang; Getzlaff, Mathias

    2009-10-01

    Size-selected iron and iron-cobalt alloy clusters have been studied with high resolution transmission electron microscopy (HRTEM) and scanning tunneling microscopy (STM). The clusters were produced by a continuously working arc cluster ion source and subsequently size-selected by an electrostatic quadrupole deflector. The crystalline structure of pure clusters has been investigated with HRTEM to ensure a reliable determination of the lattice parameter for the alloy clusters. The composition of the alloy clusters was checked with energy dispersive X-ray spectroscopy (EDX). The height of the deposited FeCo clusters on the (110) surface of tungsten was determined via STM. These results were compared with the lateral size distribution being investigated by TEM and allow a conclusion on the shape of the deposited alloy clusters. Furthermore, the behavior of the alloy clusters on the W(110) surface at elevated temperatures has been examined, at which the clusters show anisotropic spreading.

  11. 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

  12. Heterogeneous Configuration of a Ag Nanowire/Polymer Composite Structure for Selectively Stretchable Transparent Electrodes.

    PubMed

    Kim, Youngmin; Jun, Sungwoo; Ju, Byeong-Kwon; Kim, Jong-Woong

    2017-03-01

    One of the most important aspects that we need to consider in the design of intrinsically stretchable electrodes is that most electronic devices that can be formed on them are not stretchable themselves. This discrepancy can induce severe stress singularities at the interfaces between stiff devices and stretchable electrodes, leading to catastrophic device delamination when the substrate is stretched. Here, we suggest a novel solution to this challenge which involves introducing a photolithography-based rigid-island approach to fabricate the heterogeneous configuration of a silver nanowire (AgNW)/polymer composite structure. For this, we designed two new transparent polymers: a photopatternable polymer that is rigid yet flexible, and a stretchable polymer, both of which have identical acrylate functional groups. Patterning of the rigid polymer and subsequent overcoating of the soft polymer formed rigid island disks embedded in the soft polymer, resulting in a selectively stretchable transparent film. Strong covalent bonds instead of weak physical interactions between the polymers strengthened the cohesive force at the interface of the rigid/soft polymers. Inverted-layer processing with a percolated AgNW network was used to form a heterogeneous AgNW/polymer composite structure that can be used as a selectively stretchable transparent electrode. An optimized structural configuration prevented the resistance of the rigid electrode from varying up to a lateral strain of 70%. A repeated stretch/release test with 60% strain for 5000 cycles did not cause any severe damage to the structure, revealing that the fabricated structure was mechanically stable and reliable.

  13. 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

  14. 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.

  15. 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.

  16. Diverse Actions and Target-Site Selectivity of Neonicotinoids: Structural Insights

    PubMed Central

    Matsuda, Kazuhiko; Kanaoka, Satoshi; Akamatsu, Miki; Sattelle, David B.

    2009-01-01

    The nicotinic acetylcholine receptors (nAChRs) are targets for human and veterinary medicines as well as insecticides. Subtype-selectivity among the diverse nAChR family members is important for medicines targeting particular disorders, and pest-insect selectivity is essential for the development of safer, environmentally acceptable insecticides. Neonicotinoid insecticides selectively targeting insect nAChRs have important applications in crop protection and animal health. Members of this class exhibit strikingly diverse actions on their nAChR targets. Here we review the chemistry and diverse actions of neonicotinoids on insect and mammalian nAChRs. Electrophysiological studies on native nAChRs and on wild-type and mutagenized recombinant nAChRs have shown that basic residues particular to loop D of insect nAChRs are likely to interact electrostatically with the nitro group of neonicotinoids. In 2008, the crystal structures were published showing neonicotinoids docking into the acetylcholine binding site of molluscan acetylcholine binding proteins with homology to the ligand binding domain (LBD) of nAChRs. The crystal structures showed that 1) glutamine in loop D, corresponding to the basic residues of insect nAChRs, hydrogen bonds with the NO2 group of imidacloprid and 2) neonicotinoid-unique stacking and CH-π bonds at the LBD. A neonicotinoid-resistant strain obtained by laboratory-screening has been found to result from target site mutations, and possible reasons for this are also suggested by the crystal structures. The prospects of designing neonicotinoids that are safe not only for mammals but also for beneficial insects such as honey bees (Apis mellifera) are discussed in terms of interactions with non-α nAChR subunits. PMID:19321668

  17. 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

  18. 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

    2016-06-16

    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.

  19. Diverse actions and target-site selectivity of neonicotinoids: structural insights.

    PubMed

    Matsuda, Kazuhiko; Kanaoka, Satoshi; Akamatsu, Miki; Sattelle, David B

    2009-07-01

    The nicotinic acetylcholine receptors (nAChRs) are targets for human and veterinary medicines as well as insecticides. Subtype-selectivity among the diverse nAChR family members is important for medicines targeting particular disorders, and pest-insect selectivity is essential for the development of safer, environmentally acceptable insecticides. Neonicotinoid insecticides selectively targeting insect nAChRs have important applications in crop protection and animal health. Members of this class exhibit strikingly diverse actions on their nAChR targets. Here we review the chemistry and diverse actions of neonicotinoids on insect and mammalian nAChRs. Electrophysiological studies on native nAChRs and on wild-type and mutagenized recombinant nAChRs have shown that basic residues particular to loop D of insect nAChRs are likely to interact electrostatically with the nitro group of neonicotinoids. In 2008, the crystal structures were published showing neonicotinoids docking into the acetylcholine binding site of molluscan acetylcholine binding proteins with homology to the ligand binding domain (LBD) of nAChRs. The crystal structures showed that 1) glutamine in loop D, corresponding to the basic residues of insect nAChRs, hydrogen bonds with the NO(2) group of imidacloprid and 2) neonicotinoid-unique stacking and CH-pi bonds at the LBD. A neonicotinoid-resistant strain obtained by laboratory-screening has been found to result from target site mutations, and possible reasons for this are also suggested by the crystal structures. The prospects of designing neonicotinoids that are safe not only for mammals but also for beneficial insects such as honey bees (Apis mellifera) are discussed in terms of interactions with non-alpha nAChR subunits.

  20. Ocular Safety of Topical Naltrexone

    DTIC Science & Technology

    2010-05-01

    AD_________________ AWARD NUMBER: W81XWH-09-1-0312 TITLE: Ocular Safety of Topical Naltrexone ...Topical Naltrexone 5b. GRANT NUMBER W81XWH-09-1-0312 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER Joseph W. Sassani, M.D.; Ian...associates have been funded to perform a Phase I Clinical Trial of Naltrexone dissolved in Vigamox® and applied topically as eye drops preliminary to a

  1. Special Operations Research Topics 2016

    DTIC Science & Technology

    2015-01-01

    religious and cultural conflict? A6. Preventing, countering, and disrupting foreign fighter flow The steady state of foreign fighter flow ( FFF ) across...militants from the Middle East, North Africa, and Europe can access this region. The same is true of FFF across Southeast Asia and 5 A. Priority...Topics Previous years’ topics lists are available online at https://jsou.socom.mil. the relationship of VEOs with the FFF phenomenon. This research topic

  2. [Selective excitation spectra and energy level structure of Dy3+:ThO2 crystal].

    PubMed

    Yin, M; Krupa, J C

    2001-08-01

    Dy3+:ThO2 crystal was grown by the flux technique for the first time. The emission spectra, excitation spectra and fluorescence decay curves were measured and discussed. By using emission spectra obtained under selective dye laser excitation at 12 K, together with the crystal-field theory, the site symmetry of Dy3+ ions in ThO2 was determined as C3 nu and its energy level structure was tabulated. The lifetime of radiative level 4F9/2 was also determined as 0.40 ms.

  3. (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)

  4. A Study of Topic and Topic Change in Conversational Threads

    DTIC Science & Technology

    2009-09-01

    4 and = 6 (LDA Topics = 50). Vertical lines show identified topic transitions. Personally identifying terms are grayed out for privacy purposes...50). Personally identifying terms are grayed out for privacy purposes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56 5.4...Matt, thank you for being a generous mentor and wonderful friend. To Marco Draeger, Jenny Tam , Jon Durham, and the rest of the NLP lab, thanks for

  5. Topicality 1 and Topicality 2: A Quest for True Meaning.

    ERIC Educational Resources Information Center

    Olson, Clark D.; Vasilius, Janet M.

    The actual nature of topicality as it is presented in intercollegiate debate rounds has become so split that there are two different types of topicality. The first type (T1) is a "real" argument that is subjective, intentional, absolute, jurisdictional, pragmatic, and focuses on content and product. The second type (T2) is strategic,…

  6. Orbital-Parity Selective Superconducting Pairing Structures of Fe-based Superconductors under Glide Symmetry

    NASA Astrophysics Data System (ADS)

    Lin, Chiahui; Chou, Chung-Pin; Yin, Wei-Guo; Ku, Wei

    2014-03-01

    We show that the superconductivity in Fe-based superconductors consists of zero and finite momentum (π , π , 0) Cooper pairs with the same and different parities of the Fe 3 d orbitals respectively. The former develops the distinct gap structures for each orbital parity, and the latter is characteristic of spin singlet, spacial oddness and time reversal symmetry breaking. This originates from the unit cell containing two Fe atoms and two anions of staggered positioning with respect to the Fe square lattice. The in-plane translation is turned into glide translation, which dictates orbital-parity selective quasiparticles. Such novel pairing structures explain the unusual gap angular modulation on the hole pockets in recent ARPES and STS experiments. Work supported by DOE DE-AC02-98CH10886 and Chinese Academy of Engineering Physics and Ministry of Science and Technology.

  7. 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.

  8. 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

  9. 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.

  10. Structural and biochemical characterization of AidC, a quorum-quenching lactonase with atypical selectivity

    DOE PAGES

    Mascarenhas, Romila; Thomas, Pei W.; Wu, Chun -Xiang; ...

    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

  11. Asymmetry in structural defenses: insights into selective predation in the wild.

    PubMed

    Bergstrom, C A; Reimchen, T E

    2003-09-01

    Assessment of geographical patterns in fluctuating asymmetry (small, random differences between sides of bilateral characters) among populations shows promise as a tool to resolve the relative biomechanical importance of traits, in addition to being a possible indicator of habitat quality. We used 115 endemic freshwater populations of threespine stickleback (Gasterosteus aculeatus) from Haida Gwaii (Queen Charlotte Islands), British Columbia, Canada, to explore the degree of concordance between geographical variation of asymmetry in a predator defense structure (bony lateral plates) and geographical variation in several indirect measures of predation regime as well as several abiotic habitat variables. We found a geographical cline in the population frequency of lateral plate asymmetries, with reduced asymmetry in the southern clear-water regions of the archipelago characterized by long reaction distances and greater chance of capture by predators, and elevated asymmetry in the northern stained-water regions with poor visibility and low chances of capture. Lateral plate asymmetry was strongly correlated with expression of several defensive armor traits, including total plate numbers among populations, mean cross-sectional diameter of stickleback with the dorsal and pelvic spines erect, and mean degree of overlap between the plates and spine supports. There were no significant correlations between frequency of asymmetric fish and any of our abiotic habitat variables. Stickleback with structural plate asymmetries had fewer trout-induced scars than symmetric fish in the significant majority of populations, and there was a decrease in structural plate asymmetry with age in stained-water habitats, suggesting that trout predators may be selectively removing asymmetric fish in some lakes. This study provides evidence that geographical variation in developmental stability of threespine stickleback, as seen in the frequencies of asymmetry, reflects differences among

  12. Structural Basis for Isoform-Selective Inhibition in Nitric Oxide Synthase

    PubMed Central

    LI, HUIYING

    2013-01-01

    CONSPECTUS Nitric oxide synthase (NOS) converts L-arginine into L-citrulline and releases the important signaling molecule nitric oxide (NO). In the cardiovascular system NO produced by endothelial NOS (eNOS) relaxes smooth muscle which controls vascular tone and blood pressure.Neuronal NOS (nNOS) produces NO in the brain, where it influences a variety of neural functions such as neural transmitter release. NO can also support immune system, serving as a cytotoxic agent during infections. Even with all of these important functions, NO is a free radical, and, when overproduced, it can cause tissue damage. This mechanism can operate in many neurodegenerative diseases, and as a result, the development of drugs targeting nNOS is a desirable therapeutic goal. However, the active sites of all 3 human isoforms are very similar, and designing inhibitors specific for nNOS is a challenging problem. It is critically important, for example, not to inhibit eNOS owing to its central role in controlling blood pressure. In this Account we summarize our efforts in collaboration with Rick Silverman at Northwestern University to develop drug candidates that specifically target NOS using crystallography, computational chemistry, and organic synthesis. As a result we have developed aminopyridine compounds that are 3,800 fold more selective for nNOS than eNOS, some of which show excellent neuro-protective effects in animal models. Our group has solved approximately 130 NOS-inhibitor crystal structures which have provided the structural basis for our design efforts. Initial crystal structures of nNOS and eNOS bound to selective dipeptide inhibitors showed that a single amino acid difference (Asp in nNOS and Asn in eNOS) results in much tighter binding to nNOS. The NOS active site is open and rigid, which produces few large structural changes when inhibitors bind. However, we have found that relatively small changes in the active site and inhibitor chirality can account for large

  13. Selective Targeting of G-Quadruplex Structures by a Benzothiazole-Based Binding Motif.

    PubMed

    Buchholz, Ina; Karg, Beatrice; Dickerhoff, Jonathan; Sievers-Engler, Adrian; Lämmerhofer, Michael; Weisz, Klaus

    2017-03-09

    A benzothiazole derivative was identified as potent ligand for DNA G-quadruplex structures. Fluorescence titrations revealed selective binding to quadruplexes of different topologies including parallel, antiparallel and (3+1) hybrid structures. The parallel c-MYC sequence was found to constitute the preferred target with dissociation constants in the micromolar range. Binding of the benzothiazole-based ligand to c-MYC was structurally and thermodynamically characterized in detail by employing a comprehensive set of spectroscopic and calorimetric techniques. Job plot analyses and mass spectral data indicate non-cooperative ligand binding to form 1:1 and 2:1 complex stoichiometries. Whereas stacking interactions are suggested by optical methods, NMR chemical shift perturbations also indicate significant rearrangements of both 5'- and 3'-flanking sequences upon ligand binding. Additional isothermal calorimetry studies yield a thermodynamic profile of the ligand-quadruplex association and reveal enthalpic contributions to be the major driving force for binding. The structural and thermodynamic information obtained in the present work provides the basis for the rational development of benzothiazole derivatives as promising quadruplex binding agents.

  14. Selection of flowing liquid lead target structural materials for accelerator driven transmutation applications

    NASA Astrophysics Data System (ADS)

    Park, John J.; Buksa, John J.

    1995-09-01

    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.

  15. TOPICAL REVIEW Gravitational lensing

    NASA Astrophysics Data System (ADS)

    Bartelmann, Matthias

    2010-12-01

    Gravitational lensing has developed into one of the most powerful tools for the analysis of the dark universe. This review summarizes the theory of gravitational lensing, its main current applications and representative results achieved so far. It has two parts. In the first, starting from the equation of geodesic deviation, the equations of thin and extended gravitational lensing are derived. In the second, gravitational lensing by stars and planets, galaxies, galaxy clusters and large-scale structures is discussed and summarized.

  16. Time-Dependent Tree-Structured Survival Analysis with Unbiased Variable Selection through Permutation Tests

    PubMed Central

    Wallace, M. L.

    2014-01-01

    Incorporating time-dependent covariates into tree-structured survival analysis (TSSA) may result in more accurate prognostic models than if only baseline values are used. Available time-dependent TSSA methods exhaustively test every binary split on every covariate; however, this approach may result in selection bias towards covariates with more observed values. We present a method that uses unbiased significance levels from newly proposed permutation tests to select the time-dependent or baseline covariate with the strongest relationship with the survival outcome. The specific splitting value is identified using only the selected covariate. Simulation results show that the proposed time-dependent TSSA method produces tree models of equal or greater accuracy as compared to baseline TSSA models, even with high censoring rates and large within-subject variability in the time-dependent covariate. To illustrate, the proposed method is applied to data from a cohort of bipolar youth to identify subgroups at risk for self-injurious behavior. PMID:25043382

  17. Haplotype structure and selection of the MDM2 oncogene in humans.

    PubMed

    Atwal, Gurinder Singh; Bond, Gareth L; Metsuyanim, Sally; Papa, Moshe; Friedman, Eitan; Distelman-Menachem, Tal; Ben Asher, Edna; Lancet, Doron; Ross, David A; Sninsky, John; White, Tomas J; Levine, Arnold J; Yarden, Ronit

    2007-03-13

    The MDM2 protein is an ubiquitin ligase that plays a critical role in regulating the levels and activity of the p53 protein, which is a central tumor suppressor. A SNP in the human MDM2 gene (SNP309 T/G) occurs at frequencies dependent on demographic history and has been shown to have important differential effects on the activity of the MDM2 and p53 proteins and to associate with altered risk for the development of several cancers. In this report, the haplotype structure of the MDM2 gene is determined by using 14 different SNPs across the gene from three different population samples: Caucasians, African Americans, and the Ashkenazi Jewish ethnic group. The results presented in this report indicate that there is a substantially reduced variability of the deleterious SNP309 G allele haplotype in all three populations studied, whereas multiple common T allele haplotypes were found in all three populations. This observation, coupled with the relatively high frequency of the G allele haplotype in both and Caucasian and Ashkenazi Jewish population data sets, suggests that this haplotype could have undergone a recent positive selection sweep. An entropy-based selection test is presented that explicitly takes into account the correlations between different SNPs, and the analysis of MDM2 reveals a significant departure from the standard assumptions of selective neutrality.

  18. 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.

  19. Observation and understanding of anisotropic strain relaxation in selectively grown SiGe fin structures.

    PubMed

    Schulze, A; Loo, R; Ryan, P; Wormington, M; Favia, P; Witters, L; Collaert, N; Bender, H; Vandervorst, W; Caymax, M

    2017-04-07

    The performance of heterogeneous 3D transistor structures critically depends on the composition and strain state of the buffer, channel and source/drain regions. In this paper we used an in-line high resolution x-ray diffraction (HRXRD) tool to study in detail the composition and strain in selectively grown SiGe/Ge fin structures with widths down to 20 nm. For this purpose we arranged fins of identical dimensions into larger arrays which were then analyzed using an x-ray beam several tens of micrometers in size. Asymmetric reciprocal space maps measured both parallel and perpendicular to the fins allowed us to extract the lattice parameters in all three spatial directions. Our results demonstrate an anisotropic in-plane strain state of the selectively grown SiGe buffer in case of narrower fins with significantly reduced relaxation in the direction along the fin. This observation was verified using nano-beam electron diffraction, and is explained based on the reduced probability for dislocation half-loops to evolve in trenches narrower than a few times the critical radius. Moreover, we introduce and discuss in detail a methodology for the determination of the composition in case of an anisotropic in-plane strain state which differs from the procedure commonly used for blanket layers. Our findings verify the importance of in-line HRXRD measurements for process development and monitoring as well as the fundamental study of relaxation and defect formation in confined volumes.

  20. Ruthenium Complex “Light Switches” that are Selective for Different G-Quadruplex Structures

    PubMed Central

    Wachter, Erin; Moyá, Diego; Parkin, Sean

    2015-01-01

    Recognition and regulation of G-quadruplex nucleic acid structures is an important goal for the development of chemical tools and medicinal agents. The addition of a bromo substituent to the dipyridylphenazine (dppz) ligands in the photophysical “light switch”, [Ru(bpy)2dppz]2+, and the photochemical “light switch”, [Ru(bpy)2dmdppz]2+, creates compounds with increased selectivity for an intermolecular parallel G-quadruplex and the mixed-hybrid G-quadruplex, respectively. When [Ru(bpy)2dppz-Br]2+ and [Ru(bpy)2dmdppz-Br]2+ are incubated with the G-quadruplexes, they have a stabilizing effect on the DNA structures. Activation of [Ru(bpy)2dmdppz-Br]2+ with light results in covalent adduct formation with the DNA. These complexes demonstrate that subtle chemical modifications of RuII complexes can alter G-quadruplex selectivity, and could be useful for the rational design of in vivo G-quadruplex probes. PMID:26560887

  1. Observation and understanding of anisotropic strain relaxation in selectively grown SiGe fin structures

    NASA Astrophysics Data System (ADS)

    Schulze, A.; Loo, R.; Ryan, P.; Wormington, M.; Favia, P.; Witters, L.; Collaert, N.; Bender, H.; Vandervorst, W.; Caymax, M.

    2017-04-01

    The performance of heterogeneous 3D transistor structures critically depends on the composition and strain state of the buffer, channel and source/drain regions. In this paper we used an in-line high resolution x-ray diffraction (HRXRD) tool to study in detail the composition and strain in selectively grown SiGe/Ge fin structures with widths down to 20 nm. For this purpose we arranged fins of identical dimensions into larger arrays which were then analyzed using an x-ray beam several tens of micrometers in size. Asymmetric reciprocal space maps measured both parallel and perpendicular to the fins allowed us to extract the lattice parameters in all three spatial directions. Our results demonstrate an anisotropic in-plane strain state of the selectively grown SiGe buffer in case of narrower fins with significantly reduced relaxation in the direction along the fin. This observation was verified using nano-beam electron diffraction, and is explained based on the reduced probability for dislocation half-loops to evolve in trenches narrower than a few times the critical radius. Moreover, we introduce and discuss in detail a methodology for the determination of the composition in case of an anisotropic in-plane strain state which differs from the procedure commonly used for blanket layers. Our findings verify the importance of in-line HRXRD measurements for process development and monitoring as well as the fundamental study of relaxation and defect formation in confined volumes.

  2. Linguistic Extensions of Topic Models

    ERIC Educational Resources Information Center

    Boyd-Graber, Jordan

    2010-01-01

    Topic models like latent Dirichlet allocation (LDA) provide a framework for analyzing large datasets where observations are collected into groups. Although topic modeling has been fruitfully applied to problems social science, biology, and computer vision, it has been most widely used to model datasets where documents are modeled as exchangeable…

  3. [Violence Prevention: A Topical Newsletter.

    ERIC Educational Resources Information Center

    Bourland, Eric

    1995-01-01

    This newsletter theme issue addresses the issue of violence prevention in American schools and is based on presentations and discussions at the Workgroup To Improve the Quality of Technical Assistance around the Topic of Violence Prevention held in Washington, D.C. on June 12-14, 1995. The newsletter reports on the following presentation topics:…

  4. Resources for Topics in Architecture.

    ERIC Educational Resources Information Center

    Van Noate, Judith, Comp.

    This guide for conducting library research on topics in architecture or on the work of a particular architect presents suggestions for utilizing four categories of resources: books, dictionaries and encyclopedias, indexes, and a periodicals and series list (PASL). Two topics are researched as examples: the contemporary architect Richard Meier, and…

  5. Resources for Topics in Art.

    ERIC Educational Resources Information Center

    Van Noate, Judith, Comp.

    This guide for conducting library research on topics in art or the work of a particular artist presents suggestions for utilizing four categories of resources: books, dictionaries and encyclopedias, indexes, and a periodicals and serials list (PASL). Three topics are researched as examples: the contemporary artist and author Frank Stella, the…

  6. Working Topics for Students' Papers.

    ERIC Educational Resources Information Center

    Marting, Janet

    Students enrolled in composition classes may provide the answer to the dilemma of coming up with a writing topic: work--the "four letter word." Most, if not all, students have already become part of the labor force. The theme of "work" is naturally successful because it centers around a topic students know well, something that…

  7. 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

  8. 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

  9. 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

  10. 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

  11. Active Labour Market Policy and Gender Mainstreaming in Germany: Gender-Specific Aspects of Participation and Destination in Selected Instruments of the Federal Employment Service. IAB Labour Market Research Topics.

    ERIC Educational Resources Information Center

    Muller, Petra; Kurtz, Beate

    The equality of the opportunities available to males and females in Germany's labor market was examined. The study compared employment patterns among women and men and the extent to which selected discretionary benefits of Germany's Federal Employment Service benefit women and men. Selected results were as follows: (1) women are under-represented…

  12. 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…

  13. Selectivity switch in the catalytic functionalization of nonprotected carbohydrates: selective synthesis in the presence of anomeric and structurally similar carbohydrates under mild conditions.

    PubMed

    Muramatsu, Wataru; Takemoto, Yuki

    2013-03-15

    A catalytic process for the chemo- and regioselective functionalization of nonprotected carbohydrates has been developed. This novel process allows selective thiocarbonylation, acylation, and sulfonylation of a particular hydroxy group in a particular carbohydrate in the simultaneous presence of structurally similar carbohydrates such as anomers. In addition, the chemoselectivity can be switched by regulating only the length of the alkyl chain in the organotin catalyst.

  14. Topical Treatment of Allergic Rhinitis

    PubMed Central

    Greenbaum, Joseph

    1982-01-01

    Topical medications have dramatically changed the treatment of rhinitis. While systemic treatment is often more potent, topical treatment has fewer side effects. However, topical preparations also have side effects which should be considered when treating rhinitis. Topical steroids are potent anti-inflammatories but may cause nasal bleeding; sodium cromoglycate improves allergic and general inflammation but is less potent than steroids. Topical decongestants are beneficial for short-term use when there is nasal obstruction or copious discharge, but can cause damage to nasal epithelium or atrophy and dryness of the nasal mucous membrane after years of use. Anticholinergic spray is effective when watery discharge predominates, and saline is helpful when there is nasal dryness. Treatment of associated conjunctivitis is also discussed. PMID:21286563

  15. 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.

  16. Investigations into the chemical structure based selectivity of the microfabricated nitrogen-phosphorus detector

    DOE PAGES

    Brocato, Terisse A.; Hess, Ryan F.; Moorman, Matthew; ...

    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

  17. 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

  18. Using multilocus sequence data to assess population structure, natural selection, and linkage disequilibrium in wild tomatoes.

    PubMed

    Arunyawat, Uraiwan; Stephan, Wolfgang; Städler, Thomas

    2007-10-01

    We employed a multilocus approach to examine the effects of population subdivision and natural selection on DNA polymorphism in 2 closely related wild tomato species (Solanum peruvianum and Solanum chilense), using sequence data for 8 nuclear loci from populations across much of the species' range. Both species exhibit substantial levels of nucleotide variation. The species-wide level of silent nucleotide diversity is 18% higher in S. peruvianum (pi(sil) approximately 2.50%) than in S. chilense (pi(sil) approximately 2.12%). One of the loci deviates from neutral expectations, showing a clinal pattern of nucleotide diversity and haplotype structure in S. chilense. This geographic pattern of variation is suggestive of an incomplete (ongoing) selective sweep, but neutral explanations cannot be entirely dismissed. Both wild tomato species exhibit moderate levels of population differentiation (average F(ST) approximately 0.20). Interestingly, the pooled samples (across different demes) exhibit more negative Tajima's D and Fu and Li's D values; this marked excess of low-frequency polymorphism can only be explained by population (or range) expansion and is unlikely to be due to population structure per se. We thus propose that population structure and population/range expansion are among the most important evolutionary forces shaping patterns of nucleotide diversity within and among demes in these wild tomatoes. Patterns of population differentiation may also be impacted by soil seed banks and historical associations mediated by climatic cycles. Intragenic linkage disequilibrium (LD) decays very rapidly with physical distance, suggesting high recombination rates and effective population sizes in both species. The rapid decline of LD seems very promising for future association studies with the purpose of mapping functional variation in wild tomatoes.

  19. Modification and activation of Ras proteins by electrophilic prostanoids with different structure are site-selective.

    PubMed

    Renedo, Marta; Gayarre, Javier; García-Domínguez, Carlota A; Pérez-Rodríguez, Andrea; Prieto, Alicia; Cañada, F Javier; Rojas, José M; Pérez-Sala, Dolores

    2007-06-05

    Cyclopentenone prostanoids (cyP) arise as important modulators of inflammation and cell proliferation. Although their physiological significance has not been fully elucidated, their potent biological effects have spurred their study as leads for the development of therapeutic agents. A key determinant of cyP action is their ability to bind to thiol groups in proteins or in glutathione through Michael addition. Even though several protein targets for cyP addition have been identified, little is known about the structural determinants from the protein or the cyP that drive this modification. The results herein presented provide the first evidence that cyP with different structures target distinct thiol sites in a protein molecule, namely, H-Ras. Whereas 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2) and Delta12-PGJ2 preferentially target the C-terminal region containing cysteines 181 and 184, PGA1 and 8-iso-PGA1 bind mainly to cysteine 118, located in the GTP-binding motif. The biological counterparts of this specificity are the site-selective modification and activation of H-Ras in cells and the differential interaction of cyP with H, N, and K-Ras proteins. Cysteine 184 is unique to H-Ras, whereas cysteine 118 is present in the three Ras homologues. Consistent with this, PGA1 binds to and activates H-, N-, and K-Ras, thus differing from the preferential interaction of 15d-PGJ2 with H-Ras. These results put forward the possibility of influencing the selectivity of cyP-protein addition by modifying cyP structure. Furthermore, they may open new avenues for the development of cyP-based drugs.

  20. 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 ...

  1. 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

  2. Plate-impact loading of cellular structures formed by selective laser melting

    NASA Astrophysics Data System (ADS)

    Winter, R. E.; Cotton, M.; Harris, E. J.; Maw, J. R.; Chapman, D. J.; Eakins, D. E.; McShane, G.

    2014-03-01

    Porous materials are of great interest because of improved energy absorption over their solid counterparts. Their properties, however, have been difficult to optimize. Additive manufacturing has emerged as a potential technique to closely define the structure and properties of porous components, i.e. density, strut width and pore size; however, the behaviour of these materials at very high impact energies remains largely unexplored. We describe an initial study of the dynamic compression response of lattice materials fabricated through additive manufacturing. Lattices consisting of an array of intersecting stainless steel rods were fabricated into discs using selective laser melting. The resulting discs were impacted against solid stainless steel targets at velocities ranging from 300 to 700 m s-1 using a gas gun. Continuum CTH simulations were performed to identify key features in the measured wave profiles, while 3D simulations, in which the individual cells were modelled, revealed details of microscale deformation during collapse of the lattice structure. The validated computer models have been used to provide an understanding of the deformation processes in the cellular samples. The study supports the optimization of cellular structures for application as energy absorbers.

  3. Structural plasticity in the human cytosolic sulfotransferase dimer and its role in substrate selectivity and catalysis.

    PubMed

    Tibbs, Zachary E; Rohn-Glowacki, Katie Jo; Crittenden, Frank; Guidry, Amber L; Falany, Charles N

    2015-02-01

    The cytosolic sulfotransferases (SULTs) are dimeric enzymes that help maintain homeostasis through the modulation of hormone and drug activity by catalyzing their transformation into hydrophilic sulfate esters and increasing their excretion. Each of the thirteen active human SULT isoforms displays a unique substrate specificity pattern that underlies its individual role in our bodies. These specificities have proven to be complex, in some cases masking the biological role of specific isoforms. The first part of this review offers a short summary of historical underpinnings of human SULTs, primarily centered on the characterization of each isoform's kinetic and structural properties. Recent structural investigations have revealed each SULT has an active site "lid" that undergoes restructuring once the cofactor/sulfonate donor, 3'-phosphoadenosine-5'-phosphosulfate (PAPS), binds to the enzyme. This structural rearrangement can alter substrate-binding profiles, therefore complicating enzyme/substrate interactions and making substrate/cosubstrate concentrations and binding order important considerations in enzyme functionality. Molecular dynamic simulations have recently been employed to describe this restructuring in an attempt to offer insight to its effects on substrate selectivity. In addition to reviewing new data on SULT molecular dynamics, we will discuss the contribution of PAPS concentrations and SULT dimerization in the regulation of SULT activity within the human body.

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. Structural and functional insight into an unexpectedly selective N-methyltransferase involved in plantazolicin biosynthesis

    PubMed Central

    Lee, Jaeheon; Hao, Yue; Blair, Patricia M.; Melby, Joel O.; Agarwal, Vinayak; Burkhart, Brandon J.; Nair, Satish K.; Mitchell, Douglas A.

    2013-01-01

    Plantazolicin (PZN), a polyheterocyclic, Nα,Nα-dimethylarginine–containing antibiotic, harbors remarkably specific bactericidal activity toward strains of Bacillus anthracis, the causative agent of anthrax. Previous studies demonstrated that genetic deletion of the S-adenosyl-l-methionine–dependent methyltransferase from the PZN biosynthetic gene cluster results in the formation of desmethylPZN, which is devoid of antibiotic activity. Here we describe the in vitro reconstitution, mutational analysis, and X-ray crystallographic structure of the PZN methyltransferase. Unlike all other known small molecule methyltransferases, which act upon diverse substrates in vitro, the PZN methyltransferase is uncharacteristically limited in substrate scope and functions only on desmethylPZN and close derivatives. The crystal structures of two related PZN methyltransferases, solved to 1.75 Å (Bacillus amyloliquefaciens) and 2.0 Å (Bacillus pumilus), reveal a deep, narrow cavity, putatively functioning as the binding site for desmethylPZN. The narrowness of this cavity provides a framework for understanding the molecular basis of the extreme substrate selectivity. Analysis of a panel of point mutations to the methyltransferase from B. amyloliquefaciens allowed the identification of residues of structural and catalytic importance. These findings further our understanding of one set of orthologous enzymes involved in thiazole/oxazole-modified microcin biosynthesis, a rapidly growing sector of natural products research. PMID:23878226

  11. Topics in Extrasolar Planet Characterization

    NASA Astrophysics Data System (ADS)

    Howe, Alex Ryan

    I present four papers exploring different topics in the area of characterizing the atmospheric and bulk properties of extrasolar planets. In these papers, I present two new codes, in various forms, for modeling these objects. A code to generate theoretical models of transit spectra of exoplanets is featured in the first paper and is refined and expanded into the APOLLO code for spectral modeling and parameter retrieval in the fourth paper. Another code to model the internal structure and evolution of planets is featured in the second and third papers. The first paper presents transit spectra models of GJ 1214b and other super-Earth and mini-Neptune type planets--planets with a "solid", terrestrial composition and relatively small planets with a thick hydrogen-helium atmosphere, respectively--and fit them to observational data to estimate the atmospheric compositions and cloud properties of these planets. The second paper presents structural models of super-Earth and mini-Neptune type planets and estimates their bulk compositions from mass and radius estimates. The third paper refines these models with evolutionary calculations of thermal contraction and ultraviolet-driven mass loss. Here, we estimate the boundaries of the parameter space in which planets lose their initial hydrogen-helium atmospheres completely, and we also present formation and evolution scenarios for the planets in the Kepler-11 system. The fourth paper uses more refined transit spectra models, this time for hot jupiter type planets, to explore the methods to design optimal observing programs for the James Webb Space Telescope to quantitatively measure the atmospheric compositions and other properties of these planets.

  12. 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

  13. 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

  14. Development of a topically active imiquimod formulation.

    PubMed

    Chollet, J L; Jozwiakowski, M J; Phares, K R; Reiter, M J; Roddy, P J; Schultz, H J; Ta, Q V; Tomai, M A

    1999-01-01

    The purpose of this work was to develop a topical formulation of imiquimod, a novel immune response modifier, to induce local cytokine production for the treatment of external genital and perianal warts. A pH-solubility profile and titration data were used to calculate a pKa of 7.3, indicative of a weak base. Solubility experiments were conducted to identify a solvent that dissolves imiquimod to achieve a 5% formulation concentration. Studies to select surfactants, preservatives, and viscosity-enhancing excipients to formulate an oil-in-water cream indicated that fatty acids were the preferred solvent for topical imiquimod formulations, and isostearic acid (ISA) was selected. A relationship existed between the fatty acid composition of four commercially available ISA sources and the solubility of imiquimod. A combination of polysorbate 60, sorbitan monostearate, and xanthan gum was used to produce a physically stable cream. The preservative system included parabens and benzyl alcohol to meet the USP criteria for preservative activity. An in vitro method was developed to demonstrate that imiquimod was released from the formulation. Topical application of the formulation induced local cytokine activity in mice.

  15. Mental mechanisms for topics identification.

    PubMed

    Massey, Louis

    2014-01-01

    Topics identification (TI) is the process that consists in determining the main themes present in natural language documents. The current TI modeling paradigm aims at acquiring semantic information from statistic properties of large text datasets. We investigate the mental mechanisms responsible for the identification of topics in a single document given existing knowledge. Our main hypothesis is that topics are the result of accumulated neural activation of loosely organized information stored in long-term memory (LTM). We experimentally tested our hypothesis with a computational model that simulates LTM activation. The model assumes activation decay as an unavoidable phenomenon originating from the bioelectric nature of neural systems. Since decay should negatively affect the quality of topics, the model predicts the presence of short-term memory (STM) to keep the focus of attention on a few words, with the expected outcome of restoring quality to a baseline level. Our experiments measured topics quality of over 300 documents with various decay rates and STM capacity. Our results showed that accumulated activation of loosely organized information was an effective mental computational commodity to identify topics. It was furthermore confirmed that rapid decay is detrimental to topics quality but that limited capacity STM restores quality to a baseline level, even exceeding it slightly.

  16. The future of topical analgesics.

    PubMed

    Arnstein, Paul M

    2013-07-01

    Topically applied analgesic therapies have been used throughout history to treat a variety of patient conditions that present with pain. Before modem pharmaceuticals became readily available, mud-based emollients, salves, cold therapies, and other natural remedies were often used. Now we have effective therapies and are developing advanced topical analgesics as we learn more about the physiology and pathophysiology of pain. The use of topical analgesics may be associated with fewer patient systemic side effects than are seen with oral, parenteral, or transdermally administered agents, making the topical route of administration attractive to prescribers and patients. With further refinement of existing drugs and the development of novel agents, topical analgesics may offer relief for treating patient pain conditions that are currently challenging to treat, such as pain resulting from burns, wound debridement, and pressure ulcers. Recognizing the value of a multimodal approach, topical analgesics may offer a therapeutic option that can become part of a comprehensive treatment plan for the patient. With continued advancements in targeted drug-delivery systems, topical analgesics may be able to provide a method to prevent or reverse the phenomena of peripheral and central sensitization, or the neuroplastic changes believed to be responsible for the transition from acute to chronic pain states in patients. For those patients at risk for developing chronic pain states, such as complex regional pain syndrome, the combination of cutaneous stimulation (achieved through rubbing during application) and analgesic effects produced by the drug itself may prevent the disabling pain that often emerges during the subacute phase of disease. In summary, better utilization of currently available topical analgesics and continued research promise to ensure that topical analgesics are, and will continue to be, important tools in the treatment of patients with resistant pain.

  17. Engineering A-kinase anchoring protein (AKAP)-selective regulatory subunits of protein kinase A (PKA) through structure-based phage selection.

    PubMed

    Gold, Matthew G; Fowler, Douglas M; Means, Christopher K; Pawson, Catherine T; Stephany, Jason J; Langeberg, Lorene K; Fields, Stanley; Scott, John D

    2013-06-14

    PKA is retained within distinct subcellular environments by the association of its regulatory type II (RII) subunits with A-kinase anchoring proteins (AKAPs). Conventional reagents that universally disrupt PKA anchoring are patterned after a conserved AKAP motif. We introduce a phage selection procedure that exploits high-resolution structural information to engineer RII mutants that are selective for a particular AKAP. Selective RII (RSelect) sequences were obtained for eight AKAPs following competitive selection screening. Biochemical and cell-based experiments validated the efficacy of RSelect proteins for AKAP2 and AKAP18. These engineered proteins represent a new class of reagents that can be used to dissect the contributions of different AKAP-targeted pools of PKA. Molecular modeling and high-throughput sequencing analyses revealed the molecular basis of AKAP-selective interactions and shed new light on native RII-AKAP interactions. We propose that this structure-directed evolution strategy might be generally applicable for the investigation of other protein interaction surfaces.

  18. [Topics in clinical dentistry. Trends in the Dutch dental literature].

    PubMed

    van der Sanden, W J; Mettes, T G; Grol, R; Plasschaert, A J; Verdonschot, E H

    1999-10-01

    Aim of the study was to evaluate a method for selecting topics suitable for developing dental clinical practice guidelines in the Netherlands, based on an analysis of Dutch dental journals. A search for dental clinical topics was conducted by analysing Dutch dental journals, magazines and series over the period 1992-1997. The numbers of publications per topic were plotted against the publication years. The number of publications as well as the value of the slope of the linear regression were considered to be indicators of the importance of a topic. 'Dental implants (indication)' had the highest number of publications, followed by 'orthodontic treatment planning' and 'periodontology (indication)'. The topic 'practice hygiene' showed the highest value of the slope of the linear regression, followed by 'TMJ dysfunction' and 'dental implants (indication)'. With this method, it is feasible to detect changes and tendencies in the Dutch dental literature. It permits a selection of clinically relevant topics over a time span. It was concluded that this method may be very useful in the selection of a topic, but should probably be combined with other methods.

  19. Synthesis and structural characterisation of selective non-carbohydrate-based inhibitors of bacterial sialidases.

    PubMed

    Brear, Paul; Telford, Judith; Taylor, Garry L; Westwood, Nicholas J

    2012-11-05

    The major human pathogen Streptococcus pneumoniae plays a key role in several disease states including septicaemia, meningitis and community-acquired pneumonia. Although vaccines against S. pneumoniae are available as prophylactics, there remains a need to identify and characterise novel chemical entities that can treat the diseases caused by this pathogen. S. pneumoniae expresses three sialidases, enzymes that cleave sialic acid from carbohydrate-based surface molecules. Two of these enzymes, NanA and NanB, have been implicated in the pathogenesis of S. pneumoniae and are considered to be validated drug targets. Here we report our studies on the synthesis and structural characterisation of novel NanB-selective inhibitors that are inspired by the β-amino-sulfonic acid family of buffers.

  20. 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.

  1. Tailoring the local structure and electronic property of AuPd nanoparticles by selecting capping molecules

    NASA Astrophysics Data System (ADS)

    Liu, Feng; Zhang, Peng

    2010-01-01

    Nine AuPd nanoparticle samples selectively capped with tetraoctylphosphonium bromide, primary amine and tertiary amine molecules were studied with the Au L3-edge x-ray absorption spectroscopy (XAS). The AuPd mixing patterns were analyzed by comparing the XAS results with the theoretical coordination numbers of 24 AuPd model clusters of varied size, Au concentration, and bimetal mixing pattern. It was found that the use of amines, particularly tertiary amine, produced a more homogeneous AuPd mixing pattern and the Au d-electron density was fine-tunable by tailoring the density of Au-Pd bonds. Mechanisms for the tailored structural and electronic properties of these nanoparticles were proposed.

  2. Index structures for selective dissemination of information under the Boolean model

    SciTech Connect

    Yan, T.W.; Garcia-Molina, H.

    1994-06-01

    The number, size, and user population of bibliographic and full-text document databases are rapidly growing. With a high document arrival rate, it becomes essential for users of such databases to have access to the very latest documents; yet the high document arrival rate also makes it difficult for users to keep themselves updated. It is desirable to allow users to submit profiles, i.e., queries that are constantly evaluated, so that they will be automatically informed of new additions that may be of interest. Such service is traditionally called Selective Dissemination of Information (SDI). The high document arrival rate, the huge number of users, and the timeliness requirement of the service pose a challenge in achieving efficient SDI. In this article, we propose several index structures for indexing profiles and algorithms that efficiently match documents against large number of profiles. We also present analysis and simulation results to compare their performance under different scenarios. 18 refs., 14 figs., 2 tabs.

  3. 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.

  4. Biochemical characterization and structure determination of a potent, selective antibody inhibitor of human MMP9.

    PubMed

    Appleby, Todd C; Greenstein, Andrew E; Hung, Magdeleine; Liclican, Albert; Velasquez, Maile; Villaseñor, Armando G; Wang, Ruth; Wong, Melanie H; Liu, Xiaohong; Papalia, Giuseppe A; Schultz, Brian E; Sakowicz, Roman; Smith, Victoria; Kwon, Hyock Joo

    2017-02-24

    Matrix metalloproteinase 9 (MMP9) is a key regulator of the extracellular matrix (ECM), involved in the degradation of various ECM proteins. MMP9 is a member of a large family of proteases that are secreted as inactive zymogens. MMP9 plays a pathological role in a variety of inflammatory and oncology disorders and has long been considered an attractive therapeutic target. GS-5745 is a potent, highly selective humanized monoclonal antibody inhibitor of MMP9 that has shown promise in treating ulcerative colitis and gastric cancer. Here we describe the crystal structure of GS-5745:MMP9 complex and biochemical studies to elucidate the mechanism of GS-5745 inhibition of MMP9. GS-5745 binds MMP9 distal to the active site, near the junction between the prodomain and catalytic domain. GS-5745 inhibits MMP9 by two mechanisms: binding to active MMP9 allosterically inhibits MMP9 activity and binding to pro-MMP9 prevents MMP9 activation.

  5. Discovery of Potent, Selective, and Structurally Novel Dot1L Inhibitors by a Fragment Linking Approach.

    PubMed

    Möbitz, Henrik; Machauer, Rainer; Holzer, Philipp; Vaupel, Andrea; Stauffer, Frédéric; Ragot, Christian; Caravatti, Giorgio; Scheufler, Clemens; Fernandez, Cesar; Hommel, Ulrich; Tiedt, Ralph; Beyer, Kim S; Chen, Chao; Zhu, Hugh; Gaul, Christoph

    2017-03-09

    Misdirected catalytic activity of histone methyltransferase Dot1L is believed to be causative for a subset of highly aggressive acute leukemias. Targeting the catalytic domain of Dot1L represents a potential therapeutic approach for these leukemias. In the context of a comprehensive Dot1L hit finding strategy, a knowledge-based virtual screen of the Dot1L SAM binding pocket led to the discovery of 2, a non-nucleoside fragment mimicking key interactions of SAM bound to Dot1L. Fragment linking of 2 and 3, an induced back pocket binder identified in earlier studies, followed by careful ligand optimization led to the identification of 7, a highly potent, selective and structurally novel Dot1L inhibitor.

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. Structure based lead optimization approach in discovery of selective DPP4 inhibitors.

    PubMed

    Ghate, Manjunath; Jain, Shailesh V

    2013-05-01

    Diabetes mellitus is a chronic progressive metabolic disorder that has profound consequences for individuals, families, and society. To date, main available oral antidiabetic medications target either insulin resistance (metformin, glitazones), or insulin deficiency (sulfonylureas, glinides), but leading to shortfalls in medication. Advancement in modern oral hypoglycemic agents may be encouraged with or in place of traditional therapies. The lower risk for hypoglycemic events as compared with other insulinotropic or insulin-sensitizing agents make DPP-4 inhibitors very promising candidates for a more physiological treatment of type-2 diabetes. Only some DPP-4 inhibitors are currently used for the treatment of type 2 diabetes (T2DM) and various inhibitors currently undergoing animal and human testing. A number of catalytically active DPPs distinct from DPP-4 (DPP II, FAP, DPP-8, and DPP-9) have been described that is associated with side-effect and toxicity. To discover potent and selective and safer drugs in a shorter time frame and with reduced cost it requires using an innovative approach for designing novel inhibitors. This review article focuses on the status of advanced lead candidates of DPP group and their binding affinity with the active site residue of target structure which help in discovery of potent and selective DPP-4 inhibitors by lead optimization approach.

  11. 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

  12. Population differentiation in G matrix structure due to natural selection in Rana temporaria.

    PubMed

    Cano, José Manuel; Laurila, Anssi; Pało, Jukka; Merilä, Juha

    2004-09-01

    The additive genetic variance-covariance matrix (G) is a concept central to discussions about evolutionary change over time in a suite of traits. However, at the moment we do not know how fast G itself changes as a consequence of selection or how sensitive it is to environmental influences. We investigated possible evolutionary divergence and environmental influences on G using data from a factorial common-garden experiment where common frog (Rana temporaria) tadpoles from two divergent populations were exposed to three different environmental treatments. G-matrices were estimated using an animal model approach applied to data from a NCII breeding design. Matrix comparisons using both Flury and multivariate analysis of variance methods revealed significant differences in G matrices both between populations and between treatments within populations, the former being generally larger than the latter. Comparison of levels of population differentiation in trait means using Q(ST) indices with that observed in microsatellite markers (F(ST)) revealed that the former values generally exceeded the neutral expectation set by F(ST). Hence, the results suggest that intraspecific divergence in G matrix structure has occurred mainly due to natural selection.

  13. 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.

  14. Diverse modes of binding in structures of Leishmania major N-myristoyltransferase with selective inhibitors

    PubMed Central

    Brannigan, James A.; Roberts, Shirley M.; Bell, Andrew S.; Hutton, Jennie A.; Hodgkinson, Michael R.; Tate, Edward W.; Leatherbarrow, Robin J.; Smith, Deborah F.; Wilkinson, Anthony J.

    2014-01-01

    The leishmaniases are a spectrum of global diseases of poverty associated with immune dysfunction and are the cause of high morbidity. Despite the long history of these diseases, no effective vaccine is available and the currently used drugs are variously compromised by moderate efficacy, complex side effects and the emergence of resistance. It is therefore widely accepted that new therapies are needed. N-Myristoyltransferase (NMT) has been validated pre-clinically as a target for the treatment of fungal and parasitic infections. In a previously reported high-throughput screening program, a number of hit compounds with activity against NMT from Leishmania donovani have been identified. Here, high-resolution crystal structures of representative compounds from four hit series in ternary complexes with myristoyl-CoA and NMT from the closely related L. major are reported. The structures reveal that the inhibitors associate with the peptide-binding groove at a site adjacent to the bound myristoyl-CoA and the catalytic α-carboxylate of Leu421. Each inhibitor makes extensive apolar contacts as well as a small number of polar contacts with the protein. Remarkably, the compounds exploit different features of the peptide-binding groove and collectively occupy a substantial volume of this pocket, suggesting that there is potential for the design of chimaeric inhibitors with significantly enhanced binding. Despite the high conservation of the active sites of the parasite and human NMTs, the inhibitors act selectively over the host enzyme. The role of conformational flexibility in the side chain of Tyr217 in conferring selectivity is discussed. PMID:25075346

  15. Genetic Structure and Selection of a Core Collection for Long Term Conservation of Avocado in Mexico

    PubMed Central

    Guzmán, Luis F.; Machida-Hirano, Ryoko; Borrayo, Ernesto; Cortés-Cruz, Moisés; Espíndola-Barquera, María del Carmen; Heredia García, Elena

    2017-01-01

    Mexico, as the center of origin of avocado (Persea americama Mill.), harbors a wide genetic diversity of this species, whose identification may provide the grounds to not only understand its unique population structure and domestication history, but also inform the efforts aimed at its conservation. Although molecular characterization of cultivated avocado germplasm has been studied by several research groups, this had not been the case in Mexico. In order to elucidate the genetic structure of avocado in Mexico and the sustainable use of its genetic resources, 318 avocado accessions conserved in the germplasm collection in the National Avocado Genebank were analyzed using 28 markers [9 expressed sequence tag-Simple Sequence Repeats (SSRs) and 19 genomic SSRs]. Deviation from Hardy Weinberg Equilibrium and high inter-locus linkage disequilibrium were observed especially in drymifolia, and guatemalensis. Total averages of the observed and expected heterozygosity were 0.59 and 0.75, respectively. Although clear genetic differentiation was not observed among 3 botanical races: americana, drymifolia, and guatemalensis, the analyzed Mexican population can be classified into two groups that correspond to two different ecological regions. We developed a core-collection by K-means clustering method. The selected 36 individuals as core-collection successfully represented more than 80% of total alleles and showed heterozygosity values equal to or higher than those of the original collection, despite its constituting slightly more than 10% of the latter. Accessions selected as members of the core collection have now become candidates to be introduced in cryopreservation implying a minimum loss of genetic diversity and a back-up for existing field collections of such important genetic resources. PMID:28286510

  16. Structure, genesis and scale selection of the tropical quasi-biweekly mode

    NASA Astrophysics Data System (ADS)

    Chatterjee, Piyali; Goswami, B. N.

    2004-04-01

    The quasi-biweekly mode (QBM) and the 30-60 day mode are two major intraseasonal oscillations (ISOs) in the tropics. The QBM is known to have a major influence in determining the active and break conditions of the Indian monsoon during the northern summer. A westward-propagating equatorial Rossby wave with quasi- biweekly period influences the Australian monsoon during the northern winter. Universality between the summer and winter QBM is established through analysis of daily circulation and convection data for 10 years. It is shown that the mean spatial structure of the QBM in circulation and convection resembles that of a gravest meridional mode equatorial Rossby wave with wavelength of about 6000 km and westward phase speed of approximately 4.5 m s-1. However, the maximum zonal wind occurs at around 5°N (5°S) during the northern summer (winter). The wave structure appears to be translated northward (southward) by about 5° during the northern summer (winter). The relationship between outgoing long-wave radiation and circulation data indicates that the mode is driven unstable by coupling with moist convection. Similarity in temporal and spatial characteristics of the mode during the two seasons leads us to propose that the same mechanism governs the genesis and scale selection of the mode in both the seasons. An acceptable mechanism for genesis and scale selection of the QBM has been lacking. In the present study, a mechanism for genesis and scale selection of the observed QBM is proposed. A simple 2½ -layer model that includes a steady Ekman boundary layer (BL) formulation incorporating effect of entrainment mixing is constructed for the convectively coupled equatorial waves. Without influence of the background mean flow, moist feedback in the presence of frictional BL convergence drives the gravest meridional mode equatorial Rossby wave unstable with observed wavelength and period but with zonal winds symmetric about the equator. Potential temperature

  17. Topics in string theory

    NASA Astrophysics Data System (ADS)

    Jejjala, Vishnumohan

    2002-01-01

    makes falsifiable predictions about TeV scale physics. Susskind has proposed that the fractional quantum Hall system can be realized through an Abelian Chern-Simons theory with a Moyal product. Susskind's Chern-Simons field is a hydrodynamical quantity. Lopez and Fradkin have an alternate Chern-Simons description couched in terms of a statistical gauge field. We show that this statistical Chern-Simons theory also possesses a non-commutative structure and develop the dictionary between the two Chern-Simons pictures.

  18. Safety and Health Topics: Asbestos

    MedlinePlus

    ... Videos E-Tools Safety and Health Topics / Asbestos Asbestos This page requires that javascript be enabled for ... Hazards and Toxic Substances Hazardous Waste What is asbestos? Asbestos is the name given to a group ...

  19. Conversational topics in transsexual persons.

    PubMed

    Van Borsel, John; Cayzeele, Miet; Heirman, Eva; T'sjoen, Guy

    2014-06-01

    Abstract In general, speech language therapy for transsexual persons focuses on pitch and pitch variation and more recently also on resonance. Other communicative aspects are dealt with far less often, especially language. This study investigated to what extent conversational topics might need attention in therapy for transsexual persons. A total of 111 males, 116 females, 28 male-to-female and 18 female-to-male transsexuals were asked to indicate on a list with 34 topics how often they speak about each topic (never, sometimes, often) in conversations with males, with females and in a gender mixed group. Results showed that transsexual persons behave in accordance with the desired gender. However, they also tend to adopt a position depending on the gender of their conversational partner. It can be concluded that in general it is not necessary to pay attention to conversational topics in therapy for transsexual persons.

  20. New approaches to topical therapy.

    PubMed

    Smith, C H

    2000-10-01

    Despite the rapid and proven efficacy of topical corticosteroids, side-effects can limit their clinical usefulness. Topically active macrolide immunosuppressants such as ascomycin and tacrolimus appear to provide comparable therapeutic potency without significant local or adverse effects. Data from ongoing studies will be crucial in determining the safety of these agents in the long term, and also their place within the current therapeutic armamentarium available for patients with atopic dermatitis. Enzyme inhibitors of PLA(2) and PDE 4 currently in the very early stages of clinical development also show potential promise as additional alternative strategies to topical treatment and may perhaps act as steroid sparing agents. Having been in the therapeutic doldrums for years, topical management of atopic dermatitis is likely to show great changes in the very near future.

  1. Bed Bug Clearinghouse by Topic

    EPA Pesticide Factsheets

    This information is intended to help states, communities, and consumers prevent and control bed bug infestations. Topics include bed bug biology and behavior, detection and monitoring, non-chemical techniques such as heat treatment, and pesticides.

  2. 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.

  3. Topical NSAIDs for acute pain in adults

    PubMed Central

    Massey, Thomas; Derry, Sheena; Moore, R Andrew; McQuay, Henry J

    2014-01-01

    Background Use of topical NSAIDs to treat acute musculoskeletal conditions is widely accepted in some parts of the world, but not in others. Their main attraction is their potential to provide pain relief without associated systemic adverse events. Objectives To review the evidence from randomised, double-blind, controlled trials on the efficacy and safety of topically applied NSAIDs in acute pain. Search methods We searched MEDLINE, EMBASE, The Cochrane Library, and our own in-house database to December 2009. We sought unpublished studies by asking personal contacts and searching on-line clinical trial registers and manufacturers web sites. Selection criteria We included randomised, double-blind, active or placebo (inert carrier)-controlled trials in which treatments were administered to adult patients with acute pain resulting from strains, sprains or sports or overuse-type injuries (twisted ankle, for instance). There had to be at least 10 participants in each treatment arm, with application of treatment at least once daily. Data collection and analysis Two review authors independently assessed trial quality and validity, and extracted data. Numbers of participants achieving each outcome were used to calculate relative risk and numbers needed to treat (NNT) or harm (NNH) compared to placebo or other active treatment. Main results Forty-seven studies were included; most compared topical NSAIDs in the form of a gel, spray, or cream with a similar placebo, with 3455 participants in the overall analysis of efficacy. For all topical NSAIDs combined, compared with placebo, the number needed to treat to benefit (NNT) for clinical success, equivalent to 50% pain relief, was 4.5 (3.9 to 5.3) for treatment periods of 6 to 14 days. Topical diclofenac, ibuprofen, ketoprofen, and piroxicam were of similar efficacy, but indomethacin and benzydamine were not significantly better than placebo. Local skin reactions were generally mild and transient, and did not differ from

  4. Special Operations Research Topics 2014

    DTIC Science & Technology

    2014-01-01

    overcome the crisis culture? Is the USSOCOM crisis management style driven by the direct action door kickers at the expense of thinkers? Could Sun...themselves lecturing in JSOU classrooms . This gives our students the unique opportunity to experience first-hand the author’s perspectives on their...Priority Topics Topic Titles A1. No time to think: Crisis management culture in SOF is inhibiting strategic thought A2. SOF in under-governed spaces

  5. Continuous Time Dynamic Topic Models

    DTIC Science & Technology

    2008-06-20

    called topics, can be used to explain the observed collection. LDA is a probabilistic extension of latent semantic indexing (LSI) [5] and probabilistic... latent semantic indexing (pLSI) [11]. Owing to its formal generative semantics, LDA has been extended and applied to authorship [19], email [15...Steyvers. Probabilistic topic models. In Latent Semantic Analysis: A Road to Meaning. 2006. [9] T. L. Griffiths and M. Steyvers. Finding scientific

  6. Linguistic Extensions of Topic Models

    DTIC Science & Technology

    2010-09-01

    analyzing large datasets where observations are collected into groups. Although topic modeling has been fruitfully applied to problems social science...topic modeling has been fruitfully applied to problems social science, biology, and computer vision, it has been most widely used to model datasets... socialization , and I’m glad that it was a conduit for me to meet and get to know such great people as Leonard Kostovetsky, Guy David, Kunle Demuren

  7. The topical treatment of psoriasis.

    PubMed

    van de Kerkhof, P C M; Vissers, W H P M

    2003-01-01

    According to the patients, improvement of efficacy, long-term safety and improvement of compliance are needed. The topical treatment has been innovated during the last decade. Most important are the introduction of two new classes of treatments: topical vitamin D(3) analogues and the retinoid tazarotene. To what extent, however, have we achieved developments which are in line with the needs as expressed by the patients? Improved efficacy has been realized by successful combinations of topical treatments. In particular, the combinations of dithranol, vitamin D(3) and tazarotene with a topical corticosteroid proved to be very effective with a reduced profile of side-effects. The efficacy of vitamin D(3) analogues and tazarotene is such that the efficacy of a potent corticosteroid (betamethasone-17-valerate) is approached; calcipotriol even showed an efficacy which is at least as good as this corticosteroid. The long-term safety of new compounds has been evaluated for at least 12 months in large studies. Remarkably for corticosteroids such information is available for only 12 weeks. However, intermittent applications of a topical corticosteroid in combination with another topical treatment provide an effective and safe long-term control of psoriasis. Compliance is a conditio sine qua non for an effective topical treatment. Important progress has been made to increase compliance. Short-contact dithranol has been popularized as an ambulatory treatment which is a highly effective approach as a care instruction programme. Formulations which are better from a cosmetical point of view have been developed for various topical treatments. Reduction of the frequency of applications proved to be possible for most treatments. Once daily applications for corticosteroids, vitamin D(3) analogues and retinoids have been developed, and intermittent applications, a few times per week, are possible for corticosteroids, which proved to be very effective with a reduced profile of side

  8. Refinements to the structure of graphite oxide: absolute quantification of functional groups via selective labelling.

    PubMed

    Eng, Alex Yong Sheng; Chua, Chun Kiang; Pumera, Martin

    2015-12-21

    Chemical modification and functionalization of inherent functional groups within graphite oxide (GO) are essential aspects of graphene-based nano-materials used in wide-ranging applications. Despite extensive research, there remains some discrepancy in its structure, with current knowledge limited primarily to spectroscopic data from XPS, NMR and vibrational spectroscopies. We report herein an innovative electrochemistry-based approach. Four electroactive labels are chosen to selectively functionalize groups in GO, and quantification of each group is achieved by voltammetric analysis. This allows for the first time quantification of absolute amounts of each group, with a further advantage of distinguishing various carbonyl species: namely ortho- and para-quinones from aliphatic ketones. Intrinsic variations in the compositions of permanganate versus chlorate-oxidized GOs were thus observed. Principal differences include permanganate-GO exhibiting substantial quinonyl content, in comparison to chlorate-GO with the vast majority of its carbonyls as isolated ketones. The results confirm that carboxylic groups are rare in actuality, and are in fact entirely absent from chlorate-GO. These observations refine and advance our understanding of GO structure by addressing certain disparities in past models resulting from employment of different oxidation routes, with the vital implication that GO production methods cannot be used interchangeably in the manufacture of graphene-based devices.

  9. Quantitative 2D HSQC NMR determination of polymer structures by selecting suitable internal standard references.

    PubMed

    Zhang, Liming; Gellerstedt, Göran

    2007-01-01

    A new analytical method based on the 2D HSQC NMR sequence is presented, which can be applied for quantitative structural determination of complicated polymers. The influence of T1 and T2 relaxations, off-resonance effects, coupling constants and homonuclear couplings are discussed. It was found that the T2 values measured on polymeric samples with the conventional HSQC-CPMG sequence could not be used to correct the errors caused by T2 relaxations during the polarization transfer delay. A unique way of selecting the proper internal standard reference signal(s) is therefore proposed to eliminate the major errors caused by T2 relaxations, resonance offsets, coupling constant deviations and homonuclear couplings. Two polymer samples, a cellulose triacetate and an acetylated lignin, have been used to illustrate the principles. The methodology developed in this work is robust to instrument miss-setting and it can find wide-spread applications in areas where a quantitative analysis of structurally complicated polymers is necessary.

  10. Behavior problems among children from different family structures: the influence of genetic self-selection.

    PubMed

    Cleveland, H H; Wiebe, R P; van den Oord, E J; Rowe, D C

    2000-01-01

    To examine both genetic and environmental influences on children's behavior problems in households defined by marital status and sibling relatedness, this study applied behavioral genetic methodology to four groups totalling 1524 sibling pairs drawn from 796 households: (1) two-parent full siblings, (2) two-parent half siblings, (3) mother-only full siblings, and (4) mother-only half siblings. Model-fitting procedures found that within-group variation on four subscales from the Behavior Problems Index was best explained by a model including both genetic and shared environmental factors. This model was then fit to the behavior problems means of the four groups. Its successful fit to these mean structures suggested that mean-level differences between groups were explained with the same influences that accounted for within-group variation. Genetic influences accounted for 81% to 94% of the mean-level difference in behavior problems between the two-parent, full sibling and the mother-only, half sibling groups. In contrast, shared environmental influences accounted for 67% to 88% of the mean-level difference in behavior problems between the two-parent, full sibling and mother-only, full sibling groups. The genetic influences are interpreted in terms of genetic self-selection into family structures.

  11. 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.

  12. 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.

  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. Combining structure-based pharmacophore and in silico approaches to discover novel selective serotonin reuptake inhibitors.

    PubMed

    Zhou, Zheng-Li; Liu, Hsuan-Liang; Wu, Josephine W; Tsao, Cheng-Wen; Chen, Wei-Hsi; Liu, Kung-Tien; Ho, Yih

    2013-12-01

    Inhibition of human serotonin transporter (hSERT) has been reported to be a potent strategy for the treatment for depression. To discover novel selective serotonin reuptake inhibitors (SSRIs), a structure-based pharmacophore model (SBPM) was developed using the docked conformations of six highly active SSRIs. The best SBPM, consisting of four chemical features: two ring aromatics (RAs), one hydrophobic (HY), and one positive ionizable (PI), was further validated using Gunner-Henry (GH) scoring and receiver operating characteristic (ROC) curve methods. This well-validated SBPM was then used as a 3D-query in virtual screening to identify potential hits from National Cancer Institute (NCI) database. These hits were subsequently filtered by absorption, distribution, metabolism, excretion, and toxicity (ADMET) prediction and molecular docking, and their binding stabilities were validated by 20-ns MD simulations. Finally, only two compounds (NSC175176 and NSC705841) were identified as potential leads, which exhibited higher binding affinities in comparison with the paroxetine. Our results also suggest that cation-π interaction plays a crucial role in stabilizing the hSERT-inhibitor complex. To our knowledge, the present work is the first structure-based virtual screening study for new SSRI discovery, which should be a useful guide for the rapid identification of novel therapeutic agents from chemical database.

  15. Structure, function and binding selectivity and stereoselectivity of siderophore-iron outer membrane transporters.

    PubMed

    Schalk, Isabelle J; Mislin, Gaëtan L A; Brillet, Karl

    2012-01-01

    To get access to iron, microorganisms produce and release into their environment small organic metal chelators called siderophores. In parallel, they produce siderophore-iron outer membrane transporters (also called TonB-Dependent Transporters or TBDT) embedded in the outer membrane; these proteins actively reabsorb the siderophore loaded with iron from the extracellular medium. This active uptake requires energy in the form of the proton motive force transferred from the inner membrane to the outer membrane transporter via the inner membrane TonB complex. Siderophores produced by microorganisms are structurally very diverse with molecular weights of 150 up to 2000Da. Siderophore-iron uptake from the extracellular medium by TBDTs is a highly selective and sometimes even stereoselective process, with each siderophore having a specific TBDT. Unlike the siderophores, all TBDTs have similar structures and belong to the outer membrane β-barrel protein superfamily. The way in which the siderophore-iron complex passes through the TBDT is still unclear. In some bacteria, TBDTs are also partners of signaling cascades regulating the expression of proteins involved in siderophore biosynthesis and siderophore-iron acquisition.

  16. 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.

  17. Saccharomyces cerevisiae Mus81-Mms4 is a catalytic, DNA structure-selective endonuclease

    PubMed Central

    Ehmsen, Kirk Tevebaugh; Heyer, Wolf-Dietrich

    2008-01-01

    The DNA structure-selective endonuclease Mus81-Mms4/Eme1 is a context-specific recombination factor that supports DNA replication, but is not essential for DSB repair in Saccharomyces cerevisiae. We overexpressed Mus81-Mms4 in S. cerevisiae, purified the heterodimer to apparent homogeneity, and performed a classical enzymological characterization. Kinetic analysis (kcat, KM) demonstrated that Mus81-Mms4 is catalytically active and identified three substrate classes in vitro. Class I substrates reflect low KM (3–7 nM) and high kcat (∼1 min−1) and include the nicked Holliday junction, 3′-flapped and replication fork-like structures. Class II substrates share low KM (1–6 nM) but low kcat (≤0.3 min−1) relative to Class I substrates and include the D-loop and partial Holliday junction. The splayed Y junction defines a class III substrate having high KM (∼30 nM) and low kcat (0.26 min−1). Holliday junctions assembled from oligonucleotides with or without a branch migratable core were negligibly cut in vitro. We found that Mus81 and Mms4 are phosphorylated constitutively and in the presence of the genotoxin MMS. The endogenous complex purified in either modification state is negligibly active on Holliday junctions. Hence, Holliday junction incision activity in vitro cannot be attributed to the Mus81-Mms4 heterodimer in isolation. PMID:18281703

  18. Topics in Theoretical Physics

    SciTech Connect

    Cohen, Andrew; Schmaltz, Martin; Katz, Emmanuel; Rebbi, Claudio; Glashow, Sheldon; Brower, Richard; Pi, So-Young

    2016-09-30

    computers Brower, Rebbi and colleagues have been using calculational techniques, similar to those successfully employed for many years to investigate the interactions among quarks in nucleons, to study theories that can describe the expected "beyond the standard model" (BSM) interactions. Their results, which include also a model for dark matter, have been published in several refereed papers in prestigious journals. Various ideas in topologically interesting field theories predict hypothetical objects such as fractional charges and Majorana excitations. However, such fascinating objects have not been seen in particle physics. Nevertheless, these objects demonstrate possible phenomena that quantum field theory can support. Pi used condensed matter physics as a laboratory to study possible realizations and observable effects of these objects predicted by quantum field theory. In recent times there has developed considerable interest among condensed matter field theorists in precisely the same geometrical and topological structures, which were first discovered in particle physics field theories. From particle physicists' point of view, this is an interesting development, since condensed matter provides an arena in which one can concretely realize particle physics ideas. Moreover, particle physicists can learn new ideas from condensed matter physics. Higgs phenomenon is precisely an important particle physics realization of condensed matter ideas. In contrast to the small distance characterizing condensed matter systems, field theory also describes large distance physics characterizing cosmology. Pi worked on various geometrical effects in the standard theory of cosmology, viz general relativity.

  19. Structure-selectivity investigations of D2-like receptor ligands by CoMFA and CoMSIA guiding the discovery of D3 selective PET radioligands.

    PubMed

    Salama, Ismail; Hocke, Carsten; Utz, Wolfgang; Prante, Olaf; Boeckler, Frank; Hübner, Harald; Kuwert, Torsten; Gmeiner, Peter

    2007-02-08

    Elucidation of the physiological role of the D3 receptor and its distribution in the brain using positron emission tomography (PET) is hampered by the lack of bioavailable subtype selective tracer ligands. To develop appropriate D3 radioligands, we designed an integrative procedure involving the elucidation of structural features determining D3 selectivity over both congeners D2 and D4 by comparative molecular analysis. Thus, we have successfully generated CoMFA and CoMSIA models based on the affinitiy differences of a series of 79 ligands representing a broad range of selectivities. These models yielded highly significant cross-validations (q2cv(D3/D2) = 0.86; q2cv(D3/D4) = 0.92) and excellent predictions of a 16-ligand test set (r2pred = 0.79-0.93). Exploiting this information, synthesis and receptor binding studies directed us to the fluorinated lead compounds 78 and 79, featuring subnanomolar D3 affinities and considerable selectivities over D2 and D4 and, subsequently, to the subtype selective PET tracers [18F]78 and [18F]79.

  20. Selectivity in ligand binding to uranyl compounds: A synthetic, structural, thermodynamic and computational study

    SciTech Connect

    Arnold, John

    2015-01-21

    The uranyl cation (UO₂²⁺) is the most abundant form of uranium on the planet. It is estimated that 4.5 billion tons of uranium in this form exist in sea water. The ability to bind and extract the uranyl cation from aqueous solution while separating it from other elements would provide a limitless source of nuclear fuel. A large body of research concerns the selective recognition and extraction of uranyl. A stable molecule, the cation has a linear O=U=O geometry. The short U-O bonds (1.78 Å) arise from the combination of uranium 5f/6d and oxygen 2p orbitals. Due to the oxygen moieties being multiply bonded, these sites were not thought to be basic enough for Lewis acidic coordination to be a viable approach to sequestration. The goal of this research is thus to broaden the coordination chemistry of the uranyl ion by studying new ligand systems via synthetic, structural, thermodynamic and computational methods. It is anticipated that this fundamental science will find use beyond actinide separation technologies in areas such as nuclear waste remediation and nuclear materials. The focus of this study is to synthesize uranyl complexes incorporating amidinate and guanidinate ligands. Both synthetic and computational methods are used to investigate novel equatorial ligand coordination and how this affects the basicity of the oxo ligands. Such an understanding will later apply to designing ligands incorporating functionalities that can bind uranyl both equatorially and axially for highly selective sequestration. Efficient and durable chromatography supports for lanthanide separation will be generated by (1) identifying robust peptoid-based ligands capable of binding different lanthanides with variable affinities, and (2) developing practical synthetic methods for the attachment of these ligands to Dowex ion exchange resins.