Science.gov

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. Prioritizing dermatoses: rationally selecting guideline topics.

    PubMed

    Borgonjen, R J; van Everdingen, J J E; van de Kerkhof, P C M; Spuls, Ph I

    2015-08-01

    Clinical practice guideline (CPG) development starts with selecting appropriate topics, as resources to develop a guideline are limited. However, a standardized method for topic selection is commonly missing and the way different criteria are used to prioritize is not clear. To select and prioritize dermatological topics for CPG development and elucidate criteria dermatologists find important in selecting guideline topics. All 410 dermatologists in the Netherlands were asked to create a top 20 of dermatological topics for which a guideline would be desirable, regardless of existing guidelines. They also rated, on a 5-point Likert scale, 10 determinative criteria derived from a combined search in literature and across (inter)national guideline developers. Top 20 topics received scores ranging from 0.01 to 0.2 and combined scores yielded a total score. The 118 surveys (response 29%) identified 157 different topics. Melanoma, squamous cell carcinoma, basal cell carcinoma, psoriasis and atopic dermatitis are top priority guideline topics. Venous leg ulcer, vasculitis, varicose veins, urticaria, acne, Lyme borreliosis, cutaneous lupus erythematosus, pruritus, syphilis, lymphoedema, decubitus ulcer, hidradenitis suppurativa, androgenic alopecia and bullous pemphigoïd complete the top 20. A further 15 topics have overlapping confidence intervals. Mortality and healthcare costs are regarded as less important criteria in topic selection (P < 0.04), than other criteria like the potential to reduce unwanted variation in practice. Dermatological professional organizations worldwide succeeded in developing guidelines for all top 20 topics. Respondents mostly agree with (inter)national guideline programmes and literature concerning the criteria important to selecting guideline topics. © 2014 European Academy of Dermatology and Venereology.

  8. 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.

  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 site contamination history. Final topical report

    SciTech Connect

    1995-09-29

    This is the Final Report that contains the ``Selected Site Contamination History`` for the project titled ``Development of an On-line, Real-time Alpha Radiation Monitor for Liquid Streams.`` It consists of a summary of sampling data for nine locations at the Oak Ridge Reservation. These nine locations were chosen to be representative of those expected across the DOE Complex, and were selected from three distinct Oak Ridge facilities: the Oak Ridge National Laboratory (ORNL); the Y-12 Plant; the K-25 Plant (the old Gaseous Diffusion Plant). The location selected from ORNL is the influent to the Process Waste Treatment Plant (PWTP). This location is representative of those Wastewater Treatment Plants that process water that is known to be radionuclide-containing. The location selected from the Y-12 Plant is the City Flow Monitoring Station. This location represents those sanitary sewer discharges from the DOE Complex that are routed off-site to a civilian waste water treatment plant. The seven locations selected from the K-25 Plant consist of various storm drains and surface waters that are tested during the normal course of K-25`s environmental monitoring program. These locations represent the varied surface waters that are tested for radioactivity levels across the DOE Complex. Final ranking and prioritization of these sites will result in a final selection of at least four sites for testing of the Thermo Alpha Monitor during Phase 2 (the Optional Phase) of the current program. It is anticipated that testing will include the ORNL, PWTP, the Y-12 City Flow Monitoring Station, and two of the K-25 surface water sites.

  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 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

  14. 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.

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

    SciTech Connect

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

    2003-09-15

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

  16. Time variation of some selected topics in bioethical publications.

    PubMed

    Cohen, C; Vianna, J A R; Battistella, L R; Massad, E

    2008-02-01

    To analyse the time variation of topics in bioethical publications as a proxy of the relative importance. We searched the Medline database for bioethics publications using the words "ethics or bioethics", and for 360 specific topics publications, associating Medical Subject Heading topic descriptors to those words. We calculated the ratio of bioethics publications to the total publications of Medline, and the ratio of each topic publications to the total bioethics publications, for five-year intervals, from 1970 to 2004. We calculated the time variation of ratios, dividing the difference between the highest and lowest ratio of each topic by its highest ratio. Four topics were described, selected to illustrate different patterns of variation: "Induced Abortion", "Conflict of Interest", "Acquired Immunodeficiency Syndrome", "Medical Education." The ratio of bioethics publications to total Medline publications increased from 0.003 to 0.012. The variation of the topic's ratios was higher than 0.7 for 68% of the topics. The Induced Abortion ratios decreased from 0.12 to 0.02. Conflict of Interest ratios increased from zero to 0.07. The Acquired Immunodeficiency Syndrome ratios were nearly zero in the first three intervals, had a peak of 0.06 during 1985-9, followed by a decrease to 0.01. Medical Education ratios varied few, from 0.04 to 0.03. There was an increase of bioethical publications in the Medline database. The topics in bioethics literature have an important time variation. Some factors were suggested to explain this variation: current legal cases, resolution of the issue, saturation of a discussion and epidemiologic importance.

  17. Selection of retapamulin, a novel pleuromutilin for topical use.

    PubMed

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

    2006-11-01

    The in vitro activity of retapamulin was determined and compared to that of topical and community antibiotics. The MIC(90)s of retapamulin against Staphylococcus aureus and Streptococcus pyogenes were 0.12 microg/ml and 0.016 microg/ml, respectively. Retapamulin has a low propensity to select resistance and produces an in vitro postantibiotic effect.

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

    PubMed Central

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

    2006-01-01

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

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

    DTIC Science & Technology

    2014-11-01

    federated search techniques in a realistic Web setting with a large number of online Web search services. This year the track contains three tasks...Selection. In CIKM 2009, pages 1277-1286. [10] M. Baillie, M. Carmen, and F. Crestani. A Multiple- Collection Latent Topic Model for Federated ... Search . Information Retrieval (2011) 14:390-412. [11] A. Bellogin, G. G. Gebremeskel, J. He, A. Said, T. Samar, A. P. de Vries. CWI and TU Delft at TREC

  20. Selected Topics on Hadronic B Decays From BaBar

    SciTech Connect

    Suzuki, K.; /SLAC

    2011-11-23

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

  1. 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.

  2. Effects of Signaling Topic Structure on Text Recall.

    ERIC Educational Resources Information Center

    Lorch, Robert F., Jr.; And Others

    1993-01-01

    Two experiments involving 285 college students investigated effects of signaling devices (headings, overviews, and summaries) on text memory. Signals produced recalls better organized by text topics. Results support a model in which signals influence readers' representations of a text's topic structure, which in turn guides recall of text content.…

  3. 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.

  4. 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.

  5. 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.…

  6. 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…

  7. 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.…

  8. 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…

  9. 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…

  10. 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.

  11. 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)

  12. 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)

  13. 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…

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

    PubMed

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

    2012-12-01

    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. 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. Descriptive study. 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. 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. 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. © 2011 Blackwell Publishing Ltd.

  15. 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

  16. 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.

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

    ERIC Educational Resources Information Center

    Lei, Simon A.

    2009-01-01

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

  18. Selected Topics in Experimental Statistics with Army Applications

    DTIC Science & Technology

    1983-12-01

    Failure of Thermal Batteries 9-9 10-1 Plot of Typical Residual and Striking Velocities for a Penetrator Against Armor 10-4 10-2 Linear... fatigue test specimens to examine closely on a metallurgical basis, as an example, the 10% or perhaps even the 25% probability level might be selected...1 ,N» C180 WRnEtft.20’.0)MP3, H13 ,N23,N33,Hl,N12,N32,M3,Nll,N2l,N3l,HPl,MDP ClRl WRIIE(6.10301

  19. Selected National Cancer Institute Breast Cancer Research Topics | NIH MedlinePlus the Magazine

    MedlinePlus

    ... Breast Cancer Selected National Cancer Institute Breast Cancer Research Topics Past Issues / Summer 2014 Table of Contents ... cancer.gov/clinicaltrials/Taking-Part-in-Cancer-Treatment-Research-Studies NIH Senior Health http://nihseniorhealth.gov/breastcancer/ ...

  20. 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.

  1. Selected topics in solution-phase biomolecular NMR spectroscopy

    NASA Astrophysics Data System (ADS)

    Kay, Lewis E.; Frydman, Lucio

    2017-05-01

    Solution bio-NMR spectroscopy continues to enjoy a preeminent role as an important tool in elucidating the structure and dynamics of a range of important biomolecules and in relating these to function. Equally impressive is how NMR continues to 'reinvent' itself through the efforts of many brilliant practitioners who ask increasingly demanding and increasingly biologically relevant questions. The ability to manipulate spin Hamiltonians - almost at will - to dissect the information of interest contributes to the success of the endeavor and ensures that the NMR technology will be well poised to contribute to as yet unknown frontiers in the future. As a tribute to the versatility of solution NMR in biomolecular studies and to the continued rapid advances in the field we present a Virtual Special Issue (VSI) that includes over 40 articles on various aspects of solution-state biomolecular NMR that have been published in the Journal of Magnetic Resonance in the past 7 years. These, in total, help celebrate the achievements of this vibrant field.

  2. A SELECTED BIBLIOGRAPHY ON SOCIO-CULTURALLY DISADVANTAGED CHILDREN AND YOUTH AND RELATED TOPICS.

    ERIC Educational Resources Information Center

    AURBACH, HERBERT A.

    THIS BIBLIOGRAPHY WAS COMPILED AND EDITED FOR USE IN A WORKSHOP ON MEETING SPECIAL EDUCATIONAL NEEDS OF SOCIALLY AND CULTURALLY DISADVANTAGED STUDENTS. SELECTED READINGS FROM THE BIBLIOGRAPHY WERE USED TO ACCOMPANY WORKSHOP ACTIVITIES. BESIDES LISTING SELECTED WORKS ON DISADVANTAGED YOUTH, THE BIBLIOGRAPHY PRESENTED REFERENCES ON SUCH TOPICS AS…

  3. 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…

  4. 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…

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

    PubMed

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

    2014-09-01

    The ultradeformable archaeosomes (UDA, made of total polar archaeolipids (TPA) extracted from the extreme halophile archaea Halorubrum tebenquichense:soybean phosphatidylcholine (SPC):sodium cholate (NaChol), 3:3:1 w:w), are promising topical adjuvants showing high deformability, an essential property for intact skin penetration up to the viable epidermis/dermis. To gain insights on UDA structure, the interactions between TPA, SPC and the edge activator NaChol, were assessed by electrospray ionization mass spectroscopy (ESI-MS) and confocal fluorescence microscopy of giant unilamellar vesicles (GUV). The non covalent heterodimers NaChol-SPC, NaChol-phosphatidylglycerophosphate methyl ether (PGPMe), NaChol-sulfated diglycosyl diphytanyl-glycerol diether (SDGD5) and SPC-PGPMe detected in the gas phase by ESI-MS after direct infusion of UDA, together with the homogeneous partition of FASTDiO and DiIC18 in GUV suggested that in these proportions, lipids and NaChol were miscible. We propose therefore, a model where in UDA the SPC diluted sufficient enough in the rich PGPMe TPA, so as to the low lateral mobility of molecules (typical of rich in PGPMe bilayers) was no longer experienced. We also found that 50μm deep within in vitro human skin canyons, the fluorescence of Alexa fluor 647-ovalbumin in UDL was ∼1.5 folds higher than in UDA, indicating a potential steric hindrance of the voluminous structure of PGPMe UDA bilayer, to the penetration of a particulate cargo such as the 7nm diameter ovalbumin. According to these observations, a further reduction in PGPMe - a lipid playing no immune role - content could help to improve the performance of UDA as topical adjuvants. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. [Structural and immunohistochemical changes of conjunctiva induced by topical glaucoma medication].

    PubMed

    Nenciu, A; Stefan, C; Ardelean, Carmen

    2004-01-01

    The topical medication represents the first line therapy for the primary open angle glaucoma. The study is aimed at assessing the structural and immunohistochemical changes of conjunctiva induced by topical glaucoma medication. For this purpose, we carried out a 40 weeks, prospective, experimental, epidemiological-operational and randomized study enrolling 18 patients (36 eyes) with recently primary open angle glaucoma. The eyes were divided into treatment (non-selective beta blockers or selective, prostaglandin analogues, topical carbonic anhydrase inhibitors) in four groups. The assessment was performed by comparison with control group (4 patients) who was instilled with natural tears (with different preservative). Both the cytology and the conjunctival biopsy specimens were investigated by histological exams and immunohistochemistry using different monoclonal antibodies. The study was performed by collaboration with The National Institute of Research and Development in Pathology and Biomedical Sciences-"V. Babes"-Bucharest. The morphometric analysis of histological sections of conjunctiva showed the following changes: squamous metaplasia (significant increases in the thickness and number of epithelial cell layers), inflammation (increase the number of lymphocytes, macrophages and fibroblasts) and subconjunctival fibrosis. According to the type of medication, we observed the significant increase of subepithelial collagen density and degenerative changes of fibrocytes, the reduction of extracellular matrix and also the up-regulation of antibodies against matrix metalloproteinase and allergic changes. According to structural changes, the immunohistochemistry confirmed the tendency of chronic inflammation. This study revealed important structural and immunohistochemical changes of conjunctiva after topical glaucoma medication. The category and the intensity of these changes are dependent on the sort of therapy and the topical treatment period. The findings showed

  7. Selected topics related to the transport and superconductivity in boron-doped diamond

    PubMed Central

    Mareš, JiříJ; Hubík, Pavel; Krištofik, Jozef; Nesládek, Miloš

    2008-01-01

    This contribution deals with a few topics closely related to the superconductivity in the heavily boron-doped diamond which are, in our opinion, not properly treated in the current literature. Attention is paid especially to the classification of metallic and insulating state, selection of pairing mechanism, limits of weak coupling approximation and to the influence of granularity on the superconducting transition. PMID:27878014

  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 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,…

  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. 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.

  12. 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.

  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. 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.

  15. Structured interviewing: avoiding selection problems.

    PubMed

    Pursell, E D; Campion, M A; Gaylord, S R

    1980-11-01

    In place of the old-fashioned, casual interview, which is unreliable and occasionally invalid in the context of EEO and affirmative action developments, the authors propose the adoption of structured interviewing for job selection. They contend that objective testing--oral, written and physical--would be more reliable, avoid the labyrinth of EEO, and ultimately yield better candidates for the jobs offered.

  16. 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

  17. Topic Structure Affects Semantic Integration: Evidence from Event-Related Potentials

    PubMed Central

    Yang, Xiaohong; Chen, Xuhai; Chen, Shuang; Xu, Xiaoying; Yang, Yufang

    2013-01-01

    This study investigated whether semantic integration in discourse context could be influenced by topic structure using event-related brain potentials. Participants read discourses in which the last sentence contained a critical word that was either congruent or incongruent with the topic established in the first sentence. The intervening sentences between the first and the last sentence of the discourse either maintained or shifted the original topic. Results showed that incongruent words in topic-maintained discourses elicited an N400 effect that was broadly distributed over the scalp while those in topic-shifted discourses elicited an N400 effect that was lateralized to the right hemisphere and localized over central and posterior areas. Moreover, a late positivity effect was only elicited by incongruent words in topic-shifted discourses, but not in topic-maintained discourses. This suggests an important role for discourse structure in semantic integration, such that compared with topic-maintained discourses, the complexity of discourse structure in topic-shifted condition reduces the initial stage of semantic integration and enhances the later stage in which a mental representation is updated. PMID:24348994

  18. 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…

  19. 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…

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. ORNL R and D on advanced small and medium power reactors: Selected topics

    SciTech Connect

    White, J.D.; Trauger, D.B.

    1988-01-01

    From 1984-1985, ORNL studied several innovative small and medium power nuclear concepts with respect to viability. Criteria for assessment of market attractiveness were developed and are described here. Using these criteria and descriptions of selected advanced reactor concepts, and assessment of their projected market viability in the time period 2000-2010 was made. All of these selected concepts could be considered as having the potential for meeting the criteria but, in most cases, considerable RandD would be required to reduce uncertainties. This work and later studies of safety and licensing of advanced, passively safe reactor concepts by ORNL are described. The results of these studies are taken into account in most of the current (FY 1989) work at ORNL on advanced reactors. A brief outline of this current work is given. One of the current RandD efforts at ORNL which addresses the operability and safety of advanced reactors is the Advanced Controls Program. Selected topics from this Program are described. 13 refs., 1 fig.

  6. 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.)

  7. 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.)

  8. Influence of professional preparation and class structure on sexuality topics taught in middle and high schools.

    PubMed

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

    2013-05-01

    This study examined the impact of professional preparation and class structure on sexuality topics taught and use of practice-based instructional strategies in US middle and high school health classes. Data from the classroom-level file of the 2006 School Health Policies and Programs were used. A series of multivariable logistic regression models were employed to determine if sexuality content taught was dependent on professional preparation and /or class structure (HE only versus HE/another subject combined). Additional multivariable logistic regression models were employed to determine if use of practice-based instructional strategies was dependent upon professional preparation and/or class structure. Years of teaching health topics and size of the school district were included as covariates in the multivariable logistic regression models. Findings indicated professionally prepared health educators were significantly more likely to teach 7 of the 13 sexuality topics as compared to nonprofessionally prepared health educators. There was no statistically significant difference in the instructional strategies used by professionally prepared and nonprofessionally prepared health educators. Exclusively health education classes versus combined classes were significantly more likely to have included 6 of the 13 topics and to have incorporated practice-based instructional strategies in the curricula. This study indicated professional preparation and class structure impacted sexuality content taught. Class structure also impacted whether opportunities for students to practice skills were made available. Results support the need for continued advocacy for professionally prepared health educators and health only courses. © 2013, American School Health Association.

  9. Topics and structure in preoperative nursing consultations with patients undergoing colorectal cancer surgery.

    PubMed

    Pettersson, Monica E; Öhlén, Joakim; Friberg, Febe; Hydén, Lars-Christer; Carlsson, Eva

    2016-11-08

    The preoperative education, which occurs in preoperative patient consultations, is an important part of the surgical nurse's profession. These consultations may be the building blocks of a partnership that facilitates communication between patient and nurse. The aim of the study was to describe topics and structure and documentation in preoperative nursing consultations with patients undergoing surgery for colorectal cancer. The study was based on analysis of consultations between seven patients and nurses at a Swedish university hospital. The preplanned preoperative consultations were audio-recorded and transcribed verbatim. The structure of the consultations was described in terms of phases and the text was analysed according to a manifest content analysis RESULTS: The consultations were structured on an agenda that was used variously and communicating different topics in an equally varied manner. Seven main topics were found: Health status, Preparation before surgery, Discovery, Tumour, Operation, Symptoms and Recovery after surgery. The topic structure disclosed a high number of subtopics. The main topics 'Discovery', 'Tumour' and 'Symptoms' were only raised by patients and occupied only 11% of the discursive space. Documentation was sparse and included mainly task-oriented procedures rather than patients' worries and concerns. There was no clear structure regarding preoperative consultation purpose and content. Using closed questions instead of open is a hindrance of developing a dialogue and thus patient participation. Preoperative consultation practice needs to be strengthened to include explicit communication of the consultations' purpose and agenda, with nurses actively discussing and responding to patients' concerns and sensitive issues. The results of the study facilitate the development of methods and structure to support person-centred communication where the patient is given space to get help with the difficult issues he/she may have when undergoing

  10. 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.

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

    ERIC Educational Resources Information Center

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

    2013-01-01

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

  12. 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

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

    ERIC Educational Resources Information Center

    Blackmon, C. Robert; Jones, Sue C.

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

  14. 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

  15. 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.

  16. 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.

  17. Resin selection criteria for tough composite structures

    NASA Technical Reports Server (NTRS)

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

    1983-01-01

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

  18. Researcher or nurse? Difficulties of undertaking semi-structured interviews on sensitive topics.

    PubMed

    Ashton, Susan

    2014-09-01

    To reflect on the author's personal and professional journey when undertaking semi-structured interviews on sensitive topics with potentially vulnerable people. When discussing care at the end of life, researchers must accept that some participants may become distressed or emotional, depending on their previous experiences. Interviews that involve sensitive topics require careful planning. The semi-structured interviews were conducted as part of the author's PhD study examining the experiences of advance care planning among family caregivers of people with advanced dementia. A reflection on my personal and professional journey when undertaking semi-structured interviews on sensitive topics with potentially vulnerable people. The frustration and tragedy of dementia, as experienced by the family caregivers, were powerful and required the author to exert self-control to avoid being overly sympathetic and offering words of reassurance, agreement and comfort. This blurring of roles between researcher and nurse has implications for all nurse researchers who undertake qualitative interviews, particularly when an intense emotional response is likely. Nurse researchers should plan and prepare for potential blurring of roles during emotional interviews and should never automatically assume that they are sufficiently prepared as a result of their previous experience and nurse training.

  19. 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.

  20. 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.

  1. 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:…

  2. 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…

  3. 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…

  4. 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…

  5. 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

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

    PubMed

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

    2014-04-01

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

  7. Topical minoxidil for androgenetic alopecia: optimizing the chance for success by appropriate patient selection.

    PubMed

    DeVillez, R L

    1987-01-01

    Cosmetically acceptable hair growth was achieved in 18 (32%) of 56 balding male subjects during a 12-month study using 2 or 3% topical minoxidil. The criteria for successful hair regrowth devised from those subjects were: (1) no baldness greater than a Hamilton pattern IV; (2) a balding vertex area smaller than 10 cm in diameter, and (3) a balding process of less than 5 years' duration. Frontotemporal hair loss did not respond to treatment and in fact progressed in severity, despite the twice-daily applications of minoxidil. In a subsequent study of 91 subjects who met these three criteria, 51 (56%) subjects achieved cosmetically acceptable hair growth after 1 year using 2% topical minoxidil (Regaine; registered trade mark of The Upjohn Company) twice daily.

  8. 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.

  9. 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

  10. 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.

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

    PubMed

    Sachs, Hari Cheryl

    2013-09-01

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

  12. In vivo characterization of structural changes after topical application of glucocorticoids in healthy human skin

    NASA Astrophysics Data System (ADS)

    Jung, Sora; Lademann, Jürgen; Darvin, Maxim E.; Richter, Claudia; Pedersen, Claus Bang; Richter, Heike; Schanzer, Sabine; Kottner, Jan; Blume-Peytavi, Ulrike; Røpke, Mads Almose

    2017-07-01

    Topical glucocorticoids (GC) are known to induce changes in human skin with the potential to develop skin atrophy. Here, atrophogenic effects and subsequent structural changes in the skin after topical application of GC were investigated in vivo. Sixteen healthy volunteers were topically treated daily on the forearms with clobetasol propionate, betamethasone dipropionate, and the petrolatum vehicle for 4 weeks. All treated skin areas and a nontreated control area were examined by ultrasound, optical coherence tomography, confocal laser scanning microscopy, multiphoton tomography (MPT), and resonance Raman spectroscopy at baseline 1 day after last application and 1 week after last application. Investigated parameters included stratum corneum thickness, epidermal, and full skin thickness, keratinocyte size and density, keratinocyte nucleus-to-cytoplasm ratio, skin surface classification, relative collagen and elastin signal intensity, second-harmonic generation-to-autofluorescence aging index of dermis (SAAID), and the antioxidant status of the skin. A reduction in epidermal and dermal skin thickness was observed in GC treated as well as in vehicle-treated and untreated skin areas on the volar forearm. MPT analysis showed an increased epidermal cell density and reduced cell size and nucleus-to-cytoplasm ratio and a significant increase of SAAID after GC treatment indicating a restructuring or compression of collagen fibers clinically being observed as atrophic changes.

  13. TPDSci.com: A Continually Updated Monograph of Selected Topics in the Optics of Turbid Media

    DTIC Science & Technology

    2010-04-01

    of SPIE Vol. 7678 76780W-1 Downloaded from SPIE Digital Library on 23 Apr 2010 to 128.160.24.76. Terms of Use: http:/lspiedl.org/terms The VBA is...links to a VBA and/or a topical note (if available). Proc. of SPIE Vol. 7678 76780W-5 Downloaded from SPIE Digital Library on 23 Apr 2010 to...review publication continually builds a comprehensive review from conclusion-oriented "very brief abstracts" ( VBAs ) as the building blocks. The review

  14. 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

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

    PubMed Central

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

    2012-01-01

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

  16. 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.

  17. 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.

  18. Emergence of social structures via preferential selection

    NASA Astrophysics Data System (ADS)

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

    2014-09-01

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

  19. 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.

  20. 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.

  1. Selection of natural Gas Fired Advanced Turbine Systems (GFATS) program - Task 3. Topical report

    SciTech Connect

    1994-06-01

    Research continued on natural gas-fired turbines.The objective of Task 3 was to perform initial trade studies and select one engine system (Gas-Fired Advanced Turbine System [GFATS]) that the contractor could demonstrate, at full scale, in the 1998 to 2000 time frame. This report describes the results of the selection process. This task, including Allison internal management reviews of the selected system, has been completed. Allison`s approach to ATS is to offer an engine family that is based on the newest T406 high technology engine. This selection was based on a number of parameters including return on investment (ROI), internal rate of return (IRR) market size and potential sales into that market. This base engine family continues a history at Allison of converting flight engine products to industrial use.

  2. The Internet and patient education--resources and their reliability: focus on a select urologic topic.

    PubMed

    Sacchetti, P; Zvara, P; Plante, M K

    1999-06-01

    The information revolution triggered by the rapid growth of the Internet has allowed healthcare providers and patients to access a rapidly expanding volume of information. To address the quality of this information, a survey of the data on a single urology-related topic available on the Internet was performed. The search on the World Wide Web (Web) was performed using the search engine HotBot and search directory Yahoo. The Web pages were assessed according to their relevancy to the topic chosen. Relevance rates were derived from the number of relevant sites divided by the total number of sites found. Relevant sites were subsequently ranked for quality on the basis of their accuracy, comprehensiveness, and objectivity. HotBot was then subsequently divided by domain, with each assessed separately. Yahoo was analyzed in its entirety. The resources were then compared for relevance and quality of information. When using the keyword "Viagra," HotBot responded with 15,109 hits. Yahoo presented 51 hits under the category, "Health: Pharmacy: Drugs and Medications: Specific Drugs and Medications: Viagra (Sildenafil)." The relevance rate for the first 50 hits in the search engine HotBot was 0.08. The relevance rates for the edu and org domains found by HotBot were 0.22 and 0.24, respectively; those for com and net were both 0.10. The relevance rate for the search directory Yahoo was 0.20. For relevant sites, the quality of the information presented was significantly higher in the Yahoo and in the HotBot domains hosted by nonprofit organizations when compared with HotBot in general and with its commercially oriented domains. HotBot overall was found to contain seven excellent sites, of which only three were found within Yahoo. Although the medical information available on the Web has proliferated at a remarkable rate, the number of Web sites providing complete, nonbiased information continues to represent only a small portion of the total. We have shown that the 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. 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.

  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. The Supervision of Teachers: A Selected Annotated Bibliography. Bibliographies on Educational Topics No. 10.

    ERIC Educational Resources Information Center

    Nerenz, Anne G., Comp.; Knop, Constance K., Comp.

    Focusing on various facets of the supervision of teachers in all capacities, this selected annotated bibliography was prepared for those cooperating teachers, student teachers, university supervisors, school supervisors, administrators, and other school personnel who wish to investigate in greater detail any number of aspects of the theory and…

  7. 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.

  8. 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

  9. 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.

  10. Development of Potent, Selective SRPK1 Inhibitors as Potential Topical Therapeutics for Neovascular Eye Disease.

    PubMed

    Batson, Jennifer; Toop, Hamish D; Redondo, Clara; Babaei-Jadidi, Roya; Chaikuad, Apirat; Wearmouth, Stephen F; Gibbons, Brian; Allen, Claire; Tallant, Cynthia; Zhang, Jingxue; Du, Chunyun; Hancox, Jules C; Hawtrey, Tom; Da Rocha, Joana; Griffith, Renate; Knapp, Stefan; Bates, David O; Morris, Jonathan C

    2017-03-17

    Serine/arginine-protein kinase 1 (SRPK1) regulates alternative splicing of VEGF-A to pro-angiogenic isoforms and SRPK1 inhibition can restore the balance of pro/antiangiogenic isoforms to normal physiological levels. The lack of potency and selectivity of available compounds has limited development of SRPK1 inhibitors, with the control of alternative splicing by splicing factor-specific kinases yet to be translated. We present here compounds that occupy a binding pocket created by the unique helical insert of SRPK1, and trigger a backbone flip in the hinge region, that results in potent (<10 nM) and selective inhibition of SRPK1 kinase activity. Treatment with these inhibitors inhibited SRPK1 activity and phosphorylation of serine/arginine splicing factor 1 (SRSF1), resulting in alternative splicing of VEGF-A from pro-angiogenic to antiangiogenic isoforms. This property resulted in potent inhibition of blood vessel growth in models of choroidal angiogenesis in vivo. This work identifies tool compounds for splice isoform selective targeting of pro-angiogenic VEGF, which may lead to new therapeutic strategies for a diversity of diseases where dysfunctional splicing drives disease development.

  11. 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…

  12. Penetration enhancing effects of selected natural oils utilized in topical dosage forms.

    PubMed

    Viljoen, Joe M; Cowley, Amé; du Preez, Jan; Gerber, Minja; du Plessis, Jeanetta

    2015-01-01

    Various natural products, including oils, have been utilized as penetration enhancers due to their "safety profiles". These oils contain fatty acids promoting skin permeability through lipid fluidization within the stratum corneum; and might therefore be able to effectively enhance transdermal drug delivery. We investigated possible penetration enhancing properties of selected oils, utilizing flurbiprofen as marker compound in emulgel formulations. The formulations were compared to a liquid paraffin emulgel and a hydrogel to establish any significant penetration enhancing effects. Gas chromatographic analysis of the natural oils was performed at ambient temperature to determine the fatty acid composition in each selected natural oils. Franz cell diffusion studies and tape stripping methods were employed to study delivery of the marker into, and through the skin. The following rank order for the emulgel flux-values was obtained: Hydrogel > olive oil > liquid paraffin > coconut oil > grape seed oil > Avocado oil ≥ Crocodile oil > Emu oil. Results suggested that oils containing predominantly mono-unsaturated oleic acid, on average increased the flux of the marker to a larger extent than oils containing an almost even mixture of both mono- and poly-unsaturated fatty acids. Oils comprising saturated fatty acids (SFAs) with alkyl chains between C12 and C14, increased the marker flux to a higher extent than oils containing C16-C18 SFAs. Effects observed for branched fatty acids, however, did not vary significantly from effects for unbranched fatty acids with the same carbon chain length. Natural oils possess penetration enhancing effects.

  13. Novel topical cream delivers safe and effective sunlight therapy for vitiligo by selectively filtering damaging ultraviolet radiation.

    PubMed

    Goren, Andy; Salafia, Antonio; McCoy, John; Keene, Sharon; Lotti, Torello

    2014-01-01

    Numerous studies have demonstrated that natural sunlight therapy at the Dead Sea provides therapeutic efficacy for vitiligo patients on par with artificial broadband and narrowband ultraviolet B (UVB) phototherapy; however, similar treatments at locals at or above sea level fail due to the development of erythema prior to sufficient therapeutic dosage. We conducted a pilot study at sea level to assess the efficacy of a novel topical cream that selectively filters nontherapeutic wavelengths of UVB from natural sunlight and delivers treatment for acrofacial vitiligo. In our pilot study, after an average of 11 weeks of treatment, all patients in the treatment arm responded to therapy. In particular, 28% of the treatment group had 70% surface area repigmentation, 28% had 50% repigmentation, and 44% had 30-40% repigmentation. In contrast, only 10% of the patients in the placebo arm had 20% repigmentation. Our results demonstrate that the novel topical cream can provide a safe and effective alternative to artificial light phototherapy. © 2014 Wiley Periodicals, Inc.

  14. A review of selected topics in physics based modeling for tunnel field-effect transistors

    NASA Astrophysics Data System (ADS)

    Esseni, David; Pala, Marco; Palestri, Pierpaolo; Alper, Cem; Rollo, Tommaso

    2017-08-01

    The research field on tunnel-FETs (TFETs) has been rapidly developing in the last ten years, driven by the quest for a new electronic switch operating at a supply voltage well below 1 V and thus delivering substantial improvements in the energy efficiency of integrated circuits. This paper reviews several aspects related to physics based modeling in TFETs, and shows how the description of these transistors implies a remarkable innovation and poses new challenges compared to conventional MOSFETs. A hierarchy of numerical models exist for TFETs covering a wide range of predictive capabilities and computational complexities. We start by reviewing seminal contributions on direct and indirect band-to-band tunneling (BTBT) modeling in semiconductors, from which most TCAD models have been actually derived. Then we move to the features and limitations of TCAD models themselves and to the discussion of what we define non-self-consistent quantum models, where BTBT is computed with rigorous quantum-mechanical models starting from frozen potential profiles and closed-boundary Schrödinger equation problems. We will then address models that solve the open-boundary Schrödinger equation problem, based either on the non-equilibrium Green’s function NEGF or on the quantum-transmitting-boundary formalism, and show how the computational burden of these models may vary in a wide range depending on the Hamiltonian employed in the calculations. A specific section is devoted to TFETs based on 2D crystals and van der Waals hetero-structures. The main goal of this paper is to provide the reader with an introduction to the most important physics based models for TFETs, and with a possible guidance to the wide and rapidly developing literature in this exciting research field.

  15. Structure and selectivity in bestrophin ion channels

    SciTech Connect

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

    2014-09-25

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

  16. 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

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

    NASA Astrophysics Data System (ADS)

    Rendina, Ivo; Fazio, Eugenio; Ferraro, Pietro

    2008-06-01

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

  18. Topical delivery of acetyl hexapeptide-8 from different emulsions: influence of emulsion composition and internal structure.

    PubMed

    Hoppel, Magdalena; Reznicek, Gottfried; Kählig, Hanspeter; Kotisch, Harald; Resch, Günter P; Valenta, Claudia

    2015-02-20

    Acetyl hexapeptide-8 (AH-8) is a well-known component of anti-aging products and was recently explored as a promising topical treatment of blepharospasm. Although AH-8 appears in a variety of cosmetic products, its skin penetration is sparsely studied and controversially discussed. Therefore, the aim of the present study was to investigate the influence of the vehicle type on the AH-8 delivery to the skin. Besides skin permeation experiments with Franz type diffusion cells, the spatial distribution of AH-8 in the stratum corneum after a real in-use application was investigated by in vitro tape stripping on porcine ear skin. By applying LC-MS/MS for quantification of AH-8, we demonstrated that a multiple water-in-oil-in-water (W/O/W) emulsion can significantly increase penetration of AH-8 into porcine skin compared to simple O/W and W/O emulsions. The internal structure of the developed multiple emulsion was confirmed by electron microscopic investigations and NMR self diffusion studies. In general, a clear superiority of water-rich W/O/W and O/W emulsions over an oil-rich W/O emulsion in terms of dermal delivery of AH-8 was found. This enhanced delivery of AH-8 could be explained by an increased absorption of the water-rich emulsions into the skin, confirmed by combined ATR-FTIR and tape stripping experiments. Copyright © 2014 Elsevier B.V. All rights reserved.

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

    PubMed Central

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

    2015-01-01

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

  20. 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)

  1. 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…

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

    ERIC Educational Resources Information Center

    Huang, Heng-Tsung Danny

    2010-01-01

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

  3. 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.

  4. Topically delivered dissolved oxygen reduces inflammation and positively influences structural proteins in healthy intact human skin.

    PubMed

    Kellar, Robert S; Audet, Robert G; Roe, David F; Rheins, Lawrence A; Draelos, Zoe Diana

    2013-06-01

    As oxygen is essential for wound healing and there is limited diffusion across the stratum corneum into the epidermis, we wanted to evaluate whether the topical delivery of a total dissolved oxygen in dressing form on intact human subject skin would improve clinical and histologic skin functioning. Fifty normal, healthy subjects completed a pilot clinical evaluation to assess the efficacy and tolerability of a dissolved oxygen dressing (OxygeneSys™-Continuous) to improve the health and appearance of intact skin. Clinical analysis was performed on 50 subjects; histological and gene expression analysis was performed on 12 of the 50 subjects to assess the effect of the dissolved oxygen dressing. Clinical data demonstrate that the dressing is well tolerated, and several measures of skin health and integrity showed improvements compared with a control dressing site. Skin hydration measurements showed a statistically significant increase in skin hydration at 0-4, 4-8, and 0-8 weeks (P < 0.05 at each time point). The blinded clinical investigator's grading of desquamation, roughness, and skin texture show significant decreases from baseline to the 8-week time point (P < 0.05). The dressings were removed prior to the blinded clinical investigator's grading. These data were supported by the histological and gene expression studies, which showed a general reduction in inflammatory response markers and transcription products (IL-6, IL-8, TNF-alpha, MMP-1, and MMP-12), while facilitating a general increase in structural skin proteins (collagen I, elastin, and filaggrin). Additionally, p53 signals from biopsy samples support the clinical investigator's observations of no safety concerns. The data from this study demonstrate that the dressing has no deleterious effects and stimulates beneficial effects on intact, nonwounded skin. © 2013 Wiley Periodicals, Inc.

  5. 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.

  6. Structural analysis of the phimotic prepuce in patients with failed topical treatment compared with untreated phimosis.

    PubMed

    Favorito, Luciano Alves; Balassiano, Carlos M; Rosado, João Pedro; Cardoso, Luiz Eduardo M; Costa, Waldemar Silva; Sampaio, Francisco José Barcellos

    2012-01-01

    To evaluate histological alterations in prepuce of patients with phimosis submitted to topic treatment with betamethasone in association with hyaluronidase. We studied sixty patients (mean age 4.5), presenting true phimosis and treated with a topical treatment with betamethasone cream (0.2%) + hyaluronidase. The parents of seven of these patients opted for circumcision (control group). The other fifty-three patients were submitted to clinical treatment. The samples were stained with Weigert's resorcin-fuchsin (analysis of the elastic fibers) and Picro-Sirius Red, for analysis of the collagen. The volumetric density of the elastic fibers was determined by stereological methods. Only eight (15 %) of the fifty-three patients submitted to topical treatment presented failure, being indicated for circumcision (histological analysis). We observed an increase of the collagen type III of the patients submitted to topical treatment. The quantification showed a reduction of the volumetric density of the prepuce's elastic fibers of the patients submitted to the cream treatment, when compared to the control group (p = 0.056). The volumetric density of the elastic fibers of the prepuce at the group not submitted to topical treatment showed an average of 14.60% (11.06 to 21.64%); in the group submitted to the cream treatment, the volumetric density of the elastic fibers of the prepuce showed an average of 10.34% (3.45 to 17.9%). The topical treatment of phimosis with betamethasone 0.2 % + hyaluronidase had a success rate of 85 %. Patients with failure of the topical treatment with steroid had histological alterations in the prepuce.

  7. An in vitro approach to investigate ocular metabolism of a topical, selective β1-adrenergic blocking agent, betaxolol.

    PubMed

    Bushee, Jennifer L; Dunne, Christine E; Argikar, Upendra A

    2015-05-01

    1. Topical glaucoma treatments have often been limited by poor absorption and bioavailability. Betaxolol, a selective β1-blocker, has been well studied for its pharmacokinetics and disposition. Limited ocular, betaxolol metabolism data is available despite a growing number of novel ocular treatments. 2. In vitro ocular fractions indicated the formation of an active metabolite, across rat, rabbit and human, which was only observed historically in the liver. 3. Ocular metabolic profiles of preclinical toxicology species, rat and rabbit, were not predictive of human in vitro ocular data. M1 was specific to human and only captured by the liver data. 4. Liver S9 over predicted the extent of ocular metabolism compared to ocular fractions. Rabbit liver S9 fractions demonstrated extensive glucuronidation and higher parent turn-over in 1 h as compared to other matrices. 5. This research assesses in vitro species and organ differences across preclinical species and human. The complex data set highlights the need for an in vitro ocular system to explore poorly documented ocular metabolism.

  8. 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.…

  9. 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.…

  10. 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…

  11. 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…

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

    USDA-ARS?s Scientific Manuscript database

    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...

  13. Influence of internal structure and composition of liquid crystalline phases on topical delivery of paclitaxel.

    PubMed

    Hosmer, Jaclyn M; Shin, Soo H; Nornoo, Adwoa; Zheng, Haian; Lopes, Luciana B

    2011-04-01

    This study aimed to evaluate whether and how the internal structure and composition of liquid crystalline systems can be tailored to maximize paclitaxel cutaneous delivery. Liquid crystalline phases of water, Brij-97, and medium-chain mono/diglycerides (MCG) were characterized by polarized light microscopy. Lamellar phases containing 20% (w/w) water and MCG at 10% (LP-10) or 20% (LP-20), and a hexagonal phase (HP) with 45% water and 10% MCG were selected; paclitaxel was incorporated at 0.5% (w/w). Compared with drug solution in myvacet oil, LP-20 provided the highest paclitaxel cutaneous delivery (threefold), and LP-10 the highest transdermal delivery (fourfold). Using a fluorescent drug derivative [at 0.5%, (w/w)], we observed that penetration occurred through intact stratum corneum. To evaluate whether penetration results relate to drug release differences, paclitaxel self-diffusion coefficient (D) and in vitro release were studied. D was the highest in LP-20, but release from LP-20 and LP-10 was similar. The low D in HP was associated with the lowest drug release. As an index of efficacy, we assessed the cytotoxicity of paclitaxel-loaded LP-20 against fibroblasts. Cell viability was 1.3-2 times smaller with LP-20 than with drug solution. Our results demonstrate that LP-20 provides optimization of paclitaxel cutaneous delivery and efficient cytotoxicity. Copyright © 2010 Wiley-Liss, Inc.

  14. Topicalization: A Stylistic Process.

    ERIC Educational Resources Information Center

    Penelope, Julia

    Although the nature of topicalization is complex and cannot be easily separated from considerations of syntactic structure and sentence focus, analysis of language usage has indicated that topicalization is more a stylistic than a syntactic process. Topicalization refers to moving a noun phrase (NP) into the initial position of a sentence.…

  15. 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…

  16. 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…

  17. Effect of topical betaxolol on the acute rise of aqueous flare induced by highly selective agonists for prostaglandin E2 receptor subtypes in pigmented rabbits.

    PubMed

    Yanagisawa, Shuichiro; Hayasaka, Seiji; Zhang, Xue-Yun; Hayasaka, Yoriko; Nagaki, Yasunori; Kitagawa, Kiyotaka

    2002-01-01

    To evaluate the role of topical betaxolol on experimental ocular inflammation in rabbits. Transcorneal diffusion of highly selective agonists for prostaglandin E2 receptor subtypes (EP), 25 microg/ml, with the use of a glass cylinder, was performed to produce aqueous flare elevation in pigmented rabbits. Betaxolol was topically administered before EP agonist application. Aqueous flare was measured with a laser flare cell meter. Performing topical instillation of 0.5% betaxolol 4 times inhibited 52 +/- 9% of EP2-agonist (ONO-AE1-259-01)-induced aqueous flare elevation. The inhibition of flare elevation was dependent on the number of betaxolol instillations. Betaxolol did not suppress the elevation induced by an EP4 agonist (ONO-AE1-392). Betaxolol inhibited EP2-agonist-induced aqueous flare elevation in pigmented rabbits. Copyright 2002 S. Karger AG, Basel

  18. The Interest of Bavarian Primary School Pupils in Geographical Topics and Methods--Selected Results of an Empirical Survey

    ERIC Educational Resources Information Center

    Lorenz, Aline; Roth, Anna; Priese, Carolin; Peukert, Eva; Mertel, Stefanie; Bloß, Susanne; Mehren, Rainer

    2017-01-01

    Interest is a central learning prerequisite for teaching. The article deals with a survey among 1600 primary school pupils in forms 2, 3 and 4 (ages 7-10) in the German federal state of Bavaria who were interviewed on their interest in geographical topics and working methods. They were given a questionnaire including 40 items to indicate their…

  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. 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.

  1. 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…

  2. Selective Mutism Questionnaire: Measurement Structure and Validity

    ERIC Educational Resources Information Center

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

    2008-01-01

    The psychometric properties of the Selective Mutism Questionnaire (SMQ) are evaluated using a clinical sample of children with selective mutism (SM). The study shows that SMQ is useful in determining the severity of a child's nonspeaking behaviors, the scope of these behaviors and necessary follow up assessment.

  3. Current topics in bioenergetics: Structure, biogenesis, and assembly of energy transducing enzyme systems. Volume 15

    SciTech Connect

    Lee, C.P.

    1987-01-01

    This book contains 11 chapters. The chapter titles are: Structure of NADH-Ubiquinone Reductase (Complex I); Structure of the Succinate-Ubiquinone Oxidoreductase (Complex II); Structure of Mitochondrial Ubiquinol-Cytochrome-c Redutase (Complex III); Structure of Cytochrome-c Oxidase; Evolution of a Regulatory Enzyme: Cytochrome-c Oxidase (Complex IV); The Assembly of F/sub 1/F/sub 0/-ATPase in Escherichia coli; Biogenesis of Mitochondrial Energy Transducing Complexes; Biogenesis of Mammalian Mitochondria; Structure and Biogenesis of Chloroplast Coupling Factor (CF/sub 0/CF/sub 1/)-ATPase; Mitochondrial Gene Products; and Overview: Bioenergetics between Chemistry, Genetics, and Physics.

  4. 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.

  5. Reversibly changing a painkiller structure: a hot topic for a cold case--ibuprofen lysine salt.

    PubMed

    Vladiskovic, Chiara; Masciocchi, Norberto

    2015-03-25

    Ibuprofen lysine salt can undergo a fully reversible, thermally induced phase transition into a different enantiotropically related polymorphic form. The structures of both the high and low temperature phases were solved using state-of-the-art X-ray powder diffraction methods, showing many similarities both in the molecular conformation and in the crystal packing. The full structural analysis and comparison of the two crystal structures allowed to understand the mechanism of the phase transition and explain its reversible nature in what appears to be a rare case of isosymmetric temperature-driven phase transformation of an organic solid. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. 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.

  7. 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.

  8. Structured variable selection with q-values

    USDA-ARS?s Scientific Manuscript database

    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...

  9. 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

  10. 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

  11. 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.

  12. 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.

  13. 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…

  14. 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…

  15. 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.

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

    NASA Astrophysics Data System (ADS)

    Roman, B.; Bico, J.

    2010-12-01

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

  17. 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.

  18. 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.…

  19. 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.

  20. TOPICAL REVIEW: Structural health monitoring for a wind turbine system: a review of damage detection methods

    NASA Astrophysics Data System (ADS)

    Ciang, Chia Chen; Lee, Jung-Ryul; Bang, Hyung-Joon

    2008-12-01

    Renewable energy sources have gained much attention due to the recent energy crisis and the urge to get clean energy. Among the main options being studied, wind energy is a strong contender because of its reliability due to the maturity of the technology, good infrastructure and relative cost competitiveness. In order to harvest wind energy more efficiently, the size of wind turbines has become physically larger, making maintenance and repair works difficult. In order to improve safety considerations, to minimize down time, to lower the frequency of sudden breakdowns and associated huge maintenance and logistic costs and to provide reliable power generation, the wind turbines must be monitored from time to time to ensure that they are in good condition. Among all the monitoring systems, the structural health monitoring (SHM) system is of primary importance because it is the structure that provides the integrity of the system. SHM systems and the related non-destructive test and evaluation methods are discussed in this review. As many of the methods function on local damage, the types of damage that occur commonly in relation to wind turbines, as well as the damage hot spots, are also included in this review.

  1. 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 ...

  2. 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

  3. Structure activity relationships of selected naphthalene derivatives

    SciTech Connect

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

    1983-01-01

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

  4. 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…

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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 ...

  11. Oxybutynin Topical

    MedlinePlus

    Oxybutynin topical gel is used to treat overactive bladder (a condition in which the bladder muscles contract uncontrollably and cause frequent ... bladder even when it is not full). Oxybutynin gel is in a class of medications called antimuscarinics. ...

  12. 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)

  13. 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

  14. 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.

  15. 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.

  16. 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.

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

    PubMed

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

    2017-01-04

    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. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  18. 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.

  19. 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.

  20. 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)

  1. 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.

  2. Selection against tandem splice sites affecting structured protein regions.

    PubMed

    Hiller, Michael; Szafranski, Karol; Huse, Klaus; Backofen, Rolf; Platzer, Matthias

    2008-03-21

    Alternative selection of splice sites in tandem donors and acceptors is a major mode of alternative splicing. Here, we analyzed whether in-frame tandem sites leading to subtle mRNA insertions/deletions of 3, 6, or 9 nucleotides are under natural selection. We found multiple lines of evidence that the human protein coding sequences are under selection against such in-frame tandem splice events, indicating that these events are often deleterious. The strength of selection is not homogeneous within the coding sequence as protein regions that fold into a fixed 3D structure (intrinsically ordered) are under stronger selection, especially against sites with a strong minor splice site. Investigating structures of functional protein domains, we found that tandem acceptors are preferentially located at the domain surface and outside structural elements such as helices and sheets. Using three-species comparisons, we estimate that more than half of all mutations that create NAGNAG acceptors in the coding region have been eliminated by selection. We estimate that ~2,400 introns are under selection against possessing a tandem site.

  3. 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.

  4. In vitro evaluation of a novel topical cream for vitiligo and psoriasis that selectively delivers NB-UVB therapy when exposed to sunlight.

    PubMed

    McCoy, John; Goren, Andy; Lotti, Torello

    2014-01-01

    Ultraviolet-B (UVB) phototherapy is a well-established mode of treatment for several types of dermatological disease. For psoriasis and vitiligo, narrow band UVB (NB-UVB) phototherapy is an effective therapy, demonstrating greater efficacy and safety compared to broadband UVB or psoralen plus UVA treatments. While the treatment efficacy of NB-UVB artificial light sources is well documented, the long term time and cost commitment of the therapy remains a barrier to treatment adherence. Natural sunlight is an ideal source of accessible UVB radiation; however, exposure to natural sunlight generally results in erythema prior to the accumulation of sufficient dosage of therapeutic wavelengths of UVB. This communication describes a novel topical cream designed to selectively deliver NB-UVB therapy when exposed to sunlight. The topical cream when combined with natural sunlight could offer patients a more convenient phototherapy option for psoriasis and vitiligo, potentially increasing patient compliance. © 2013 Applied Biology Inc. Dermatologic Therapy © 2013 Wiley Periodicals, Inc.

  5. 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.

  6. Plasmonic nanochannel structure for narrow-band selective thermal emitter

    NASA Astrophysics Data System (ADS)

    Wang, Zhiyu; Clark, J. Kenji; Huang, Li-Chung; Ho, Ya-Lun; Delaunay, Jean-Jacques

    2017-06-01

    A plasmonic structure consisting of a periodic arrangement of vertical silicon nanochannels connected by U-shaped gold layers is demonstrated as a spectrally selective thermal emitter. The plasmonic nanochannel structure sustains a coupled mode between a surface plasmon polariton and a stationary surface plasmon resonance, which induces a strong and sharp resonance observed in the form of a reflectance dip in the far field. Upon heating the structure, a strong and narrow-bandwidth thermal emittance peak is observed with a maximum emittance value of 0.72 and a full-width-at-half-maximum of 248 nm at a wavelength of 5.66 μm, which corresponds to the reflectance dip wavelength. Moreover, we demonstrate the control of the emission peak wavelength by varying the period of the structure. The plasmonic nanochannel structure realizes a small-size and selective infrared thermal emitter, which is expected to be applicable as an infrared light source.

  7. 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, ...

  8. 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 ...

  9. 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 ...

  10. Structural dissimilarity sampling with dynamically self-guiding selection.

    PubMed

    Harada, Ryuhei; Shigeta, Yasuteru

    2017-08-15

    Structural dissimilarity sampling (SDS) has been proposed as an enhanced conformational sampling method for reproducing the structural transitions of a given protein. SDS consists of cycles of two steps: (1) Selections of initial structures with structural dissimilarities by referring to a measure. (2) Conformational resampling by restarting short-time molecular dynamics (MD) simulations from the initial structures. In the present study, an efficient measure is proposed as a dynamically self-guiding selection to accelerate the structural transitions from a reactant state to a product state as an extension to the original SDS. In the extended SDS, the inner product (IP) between the reactant and the snapshots generated by short-time MD simulations are evaluated and ranked according to the IPs at every cycle. Then, the snapshots with low IPs are selected as initial structures for the short-time MD simulations. This scheme enables one to choose dissimilar and distant initial structures from the reactant, and thus the initial structures dynamically head towards the product, promoting structural transitions from the reactant. To confirm the conformational sampling efficiency, the extended SDS was applied to maltodextrin binding protein (MBP), and we successfully reproduced the structural transition from the open to closed states with submicrosecond-order simulation times. However, a conventional long-time MD simulation failed to reproduce the same structural transition. We also compared the performance with that obtained by the ordinary SDS and other sampling techniques that have been developed by us to characterize the possible utility of the extended SDS for actual applications. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  11. 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

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

    PubMed Central

    Overton, Ian M.; Barton, Geoffrey J.

    2011-01-01

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

  13. Selective refinement and selection of near-native models in protein structure prediction.

    PubMed

    Zhang, Jiong; Barz, Bogdan; Zhang, Jingfen; Xu, Dong; Kosztin, Ioan

    2015-10-01

    In recent years in silico protein structure prediction reached a level where fully automated servers can generate large pools of near-native structures. However, the identification and further refinement of the best structures from the pool of models remain problematic. To address these issues, we have developed (i) a target-specific selective refinement (SR) protocol; and (ii) molecular dynamics (MD) simulation based ranking (SMDR) method. In SR the all-atom refinement of structures is accomplished via the Rosetta Relax protocol, subject to specific constraints determined by the size and complexity of the target. The best-refined models are selected with SMDR by testing their relative stability against gradual heating through all-atom MD simulations. Through extensive testing we have found that Mufold-MD, our fully automated protein structure prediction server updated with the SR and SMDR modules consistently outperformed its previous versions. © 2015 Wiley Periodicals, Inc.

  14. Selective refinement and selection of near-native models in protein structure prediction

    PubMed Central

    Zhang, Jiong; Barz, Bagdan; Zhang, Jingfen; Xu, Dong; Kosztin, Ioan

    2015-01-01

    In recent years in silico protein structure prediction reached a level where fully automated servers can generate large pools of near-native structures. However, the identification and further refinement of the best structures from the pool of models remain problematic. To address these issues, we have developed (i) a target-specific selective refinement (SR) protocol; and (ii) molecular dynamics (MD) simulation based ranking (SMDR) method. In SR the all-atom refinement of structures is accomplished via the Rosetta Relax protocol, subject to specific constraints determined by the size and complexity of the target. The best-refined models are selected with SMDR by testing their relative stability against gradual heating through all-atom MD simulations. Through extensive testing we have found that Mufold-MD, our fully automated protein structure prediction server updated with the SR and SMDR modules consistently outperformed its previous versions. PMID:26214389

  15. Selective small-molecule inhibition of an RNA structural element

    SciTech Connect

    Howe, John A.; Wang, Hao; Fischmann, Thierry O.; Balibar, Carl J.; Xiao, Li; Galgoci, Andrew M.; Malinverni, Juliana C.; Mayhood, Todd; Villafania, Artjohn; Nahvi, Ali; Murgolo, Nicholas; Barbieri, Christopher M.; Mann, Paul A.; Carr, Donna; Xia, Ellen; Zuck, Paul; Riley, Dan; Painter, Ronald E.; Walker, Scott S.; Sherborne, Brad; de Jesus, Reynalda; Pan, Weidong; Plotkin, Michael A.; Wu, Jin; Rindgen, Diane; Cummings, John; Garlisi, Charles G.; Zhang, Rumin; Sheth, Payal R.; Gill, Charles J.; Tang, Haifeng; Roemer, Terry

    2015-09-30

    Riboswitches are non-coding RNA structures located in messenger RNAs that bind endogenous ligands, such as a specific metabolite or ion, to regulate gene expression. As such, riboswitches serve as a novel, yet largely unexploited, class of emerging drug targets. Demonstrating this potential, however, has proven difficult and is restricted to structurally similar antimetabolites and semi-synthetic analogues of their cognate ligand, thus greatly restricting the chemical space and selectivity sought for such inhibitors. Here we report the discovery and characterization of ribocil, a highly selective chemical modulator of bacterial riboflavin riboswitches, which was identified in a phenotypic screen and acts as a structurally distinct synthetic mimic of the natural ligand, flavin mononucleotide, to repress riboswitch-mediated ribB gene expression and inhibit bacterial cell growth. Our findings indicate that non-coding RNA structural elements may be more broadly targeted by synthetic small molecules than previously expected.

  16. Structural Features for Functional Selectivity at Serotonin Receptors

    PubMed Central

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

    2013-01-01

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

  17. 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.

  18. 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

  19. 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…

  20. 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…

  1. 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…

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. Topical Research: Africa.

    ERIC Educational Resources Information Center

    Lynn, Karen

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

  9. Sexual networks: measuring sexual selection in structured, polyandrous populations

    PubMed Central

    McDonald, Grant C.; James, Richard; Krause, Jens; Pizzari, Tommaso

    2013-01-01

    Sexual selection is traditionally measured at the population level, assuming that populations lack structure. However, increasing evidence undermines this approach, indicating that intrasexual competition in natural populations often displays complex patterns of spatial and temporal structure. This complexity is due in part to the degree and mechanisms of polyandry within a population, which can influence the intensity and scale of both pre- and post-copulatory sexual competition. Attempts to measure selection at the local and global scale have been made through multi-level selection approaches. However, definitions of local scale are often based on physical proximity, providing a rather coarse measure of local competition, particularly in polyandrous populations where the local scale of pre- and post-copulatory competition may differ drastically from each other. These limitations can be solved by social network analysis, which allows us to define a unique sexual environment for each member of a population: ‘local scale’ competition, therefore, becomes an emergent property of a sexual network. Here, we first propose a novel quantitative approach to measure pre- and post-copulatory sexual selection, which integrates multi-level selection with information on local scale competition derived as an emergent property of networks of sexual interactions. We then use simple simulations to illustrate the ways in which polyandry can impact estimates of sexual selection. We show that for intermediate levels of polyandry, the proposed network-based approach provides substantially more accurate measures of sexual selection than the more traditional population-level approach. We argue that the increasing availability of fine-grained behavioural datasets provides exciting new opportunities to develop network approaches to study sexual selection in complex societies. PMID:23339246

  10. 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).

  11. 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.

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

    PubMed Central

    Pettersson, Erik; Turkheimer, Eric

    2010-01-01

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

  13. 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.

  14. 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.

  15. Structural Basis for Selectivity and Diversity in Angiotensin II Receptors

    PubMed Central

    Zhang, Haitao; Han, Gye Won; Batyuk, Alexander; Ishchenko, Andrii; White, Kate L.; Patel, Nilkanth; Sadybekov, Anastasiia; Zamlynny, Beata; Rudd, Michael T.; Hollenstein, Kaspar; Tolstikova, Alexandra; White, Thomas A.; Hunter, Mark S.; Weierstall, Uwe; Liu, Wei; Babaoglu, Kerim; Moore, Eric L.; Katz, Ryan D.; Shipman, Jennifer M.; Garcia-Calvo, Margarita; Sharma, Sujata; Sheth, Payal; Soisson, Stephen M.; Stevens, Raymond C.; Katritch, Vsevolod; Cherezov, Vadim

    2017-01-01

    Angiotensin II receptors, AT1R and AT2R, serve as key components of the renin-angiotensin-aldosterone system. While AT1R plays a central role in the regulation of blood pressure, the function of AT2R is enigmatic with a variety of reported effects. To elucidate the mechanisms for the functional diversity and ligand selectivity between these receptors, we report crystal structures of the human AT2R bound to an AT2R-selective and an AT1R/AT2R-dual ligand, respectively, capturing the receptor in an active-like conformation. Unexpectedly, helix VIII was found in a non-canonical position, stabilizing the active-like state, but at the same time preventing the recruitment of G proteins/β-arrestins, in agreement with the lack of signaling responses in standard cellular assays. Structure-activity relationship, docking and mutagenesis studies revealed the interactions critical for ligand binding and selectivity. Our results thus provide insights into the structural basis for distinct functions of the angiotensin receptors, and may guide the design of novel selective ligands. PMID:28379944

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. Why are structured interviews so rarely used in personnel selection?

    PubMed

    van der Zee, Karen I; Bakker, Arnold B; Bakker, Paulien

    2002-02-01

    By adopting the theory of planned behavior, this study tried to predict human resources managers' (N = 79) intentions toward unstructured and structured interview techniques. Managers evaluated case descriptions of both techniques and were interviewed about their own practices. The data revealed stronger intentions toward unstructured interviewing than toward structured interviewing, which was consistent with their own practices in selecting staff, which appeared to be rather unstructured. l. Ajzen's (1991) theory appeared to be a useful framework for predicting managers' intentions. In particular, attitudes and subjective norms were predictive of intentions to engage in either method. Only intentions toward the unstructured case were related to managers' actual behavior.

  2. Structural basis for selectivity and toxicity of ribosomal antibiotics

    PubMed Central

    Böttger, Erik C.; Springer, Burkhard; Prammananan, Therdsak; Kidan, Yishak; Sander, Peter

    2001-01-01

    Ribosomal antibiotics must discriminate between bacterial and eukaryotic ribosomes to various extents. Despite major differences in bacterial and eukaryotic ribosome structure, a single nucleotide or amino acid determines the selectivity of drugs affecting protein synthesis. Analysis of resistance mutations in bacteria allows the prediction of whether cytoplasmic or mitochondrial ribosomes in eukaryotic cells will be sensitive to the drug. This has important implications for drug specificity and toxicity. Together with recent data on the structure of ribosomal subunits these data provide the basis for development of new ribosomal antibiotics by rationale drug design. PMID:11306553

  3. Neuronal selectivity and local map structure in visual cortex

    PubMed Central

    Nauhaus, I.; Benucci, A.; Carandini, M.; Ringach, D. L.

    2008-01-01

    Summary The organization of primary visual cortex into functional maps makes individual cells operate in a variety of contexts. For instance, some neurons lie in regions of fairly homogeneous orientation preference (iso-orientation domains), while others lie in regions with a variety of preferences (e.g., pinwheel centers). We asked whether this diversity in local map structure correlates with the degree of selectivity of spike responses. We used a novel combination of imaging and electrophysiology to reveal that neurons in regions of homogeneous orientation preference have much sharper tuning. Moreover, in both monkeys and cats, a common principle links the structure of the orientation map, on the spatial scale of dendritic integration, to the degree of selectivity of individual cells. We conclude that neural computation is not invariant across the cortical surface: its relationship to local context must be considered by theories of receptive field wiring and map development. PMID:18341988

  4. Model Order Selection Rules for Covariance Structure Classification in Radar

    NASA Astrophysics Data System (ADS)

    Carotenuto, Vincenzo; De Maio, Antonio; Orlando, Danilo; Stoica, Petre

    2017-10-01

    The adaptive classification of the interference covariance matrix structure for radar signal processing applications is addressed in this paper. This represents a key issue because many detection architectures are synthesized assuming a specific covariance structure which may not necessarily coincide with the actual one due to the joint action of the system and environment uncertainties. The considered classification problem is cast in terms of a multiple hypotheses test with some nested alternatives and the theory of Model Order Selection (MOS) is exploited to devise suitable decision rules. Several MOS techniques, such as the Akaike, Takeuchi, and Bayesian information criteria are adopted and the corresponding merits and drawbacks are discussed. At the analysis stage, illustrating examples for the probability of correct model selection are presented showing the effectiveness of the proposed rules.

  5. 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.

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

    PubMed

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

    2016-01-26

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

  7. Structural basis for selectivity and diversity in angiotensin II receptors

    DOE PAGES

    Zhang, Haitao; Han, Gye Won; Batyuk, Alexander; ...

    2017-04-20

    The angiotensin II receptors AT1R and AT2R serve as key components of the renin–angiotensin–aldosterone system. AT1R has a central role in the regulation of blood pressure, but the function of AT2R is unclear and it has a variety of reported effects. To identify the mechanisms that underlie the differences in function and ligand selectivity between these receptors, here we report crystal structures of human AT2R bound to an AT2R-selective ligand and to an AT1R/AT2R dual ligand, capturing the receptor in an active-like conformation. Unexpectedly, helix VIII was found in a non-canonical position, stabilizing the active-like state, but at the samemore » time preventing the recruitment of G proteins or β-arrestins, in agreement with the lack of signalling responses in standard cellular assays. Structure–activity relationship, docking and mutagenesis studies revealed the crucial interactions for ligand binding and selectivity. Finally, our results thus provide insights into the structural basis of the distinct functions of the angiotensin receptors, and may guide the design of new selective ligands.« less

  8. Ovarian structure in mice lines selected for weight.

    PubMed

    Bernardi, S F; Brogliatti, G; Oyarzabal, M I

    2009-06-01

    Selection for body weight at 49 day of age (s and h, downward selected lines; s' and h', upward selected lines) affected reproductive traits in CF1 mice lines. The objective of this study was to compare ovarian structures in females of these lines, as well as in unselected controls (Line t). The number of ovarian follicles (N), follicle diameter (FD), number of corpora lutea (CL), litter size (LS), and body weight (W), were recorded. There were significant differences among lines for N, FD, CL, LS and W; means values for the lines with the greatest difference for post-pubertal females were: N(s) = 19.3 and N(s') = 32.7; FD(h') = 161.7 and FD(s') = 178.2; CL(h) = 10.3 and CL(s') = 21.9; LS(s) = 6.0 and LS(h') = 11.1; W(h) = 18.9 and W(s') = 32.4. There were also differences between positive lines; Line s' had a higher proportion of large follicles in pre-pubertal females, a greater capacity to convert these follicles into CL, but a lower capacity to maintain embryos until term than Line h'. For negative lines, Line h apparently had a reduced incidence of embryonic loss when compared with Line s. In conclusion, selection for body weight modified ovarian structure, as well as reproductive efficiency.

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

    PubMed Central

    Chan, Kwok-Ho; Chen, Wenzhang; Lamont, Douglas J.; Zengerle, Michael; Ciulli, Alessio

    2017-01-01

    Inducing macromolecular interactions with small molecules to activate cellular signaling is a challenging goal. PROTACs (proteolysis-targeting chimaeras) 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 how this impacts target degradation selectivity remains elusive. We solved the crystal structure of Brd4-degrader MZ1 in complex with human VHL and the Brd4 bromodomain (Brd4BD2). 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 Brd4BD2. 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. PMID:28288108

  10. 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.

  11. 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.

  12. 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. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

  13. 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.

  14. 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…

  15. 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…

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

    PubMed Central

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

    2016-01-01

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

  17. 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…

  18. Molecular structural characteristics as determinants of estrogen receptor selectivity.

    PubMed

    Agatonovic-Kustrin, S; Turner, J V; Glass, B D

    2008-09-29

    Recent reports that a wide variety of natural and man-made compounds are capable of competing with natural hormones for estrogen receptors serve as timely examples of the need to advance screening techniques to support human health and ascertain ecological risk. Quantitative structure-activity relationships (QSARs) can potentially serve as screening tools to identify and prioritize untested compounds for further empirical evaluations. Computer-based QSAR molecular models have been used to describe ligand-receptor interactions and to predict chemical structures that possess desired pharmacological characteristics. These have recently included combined and differential relative binding affinities of potential estrogenic compounds at estrogen receptors (ER) alpha and beta. In the present study, artificial neural network (ANN) QSAR models were developed that were able to predict differential relative binding affinities of a series of structurally diverse compounds with estrogenic activity. The models were constructed with a dataset of 93 compounds and tested with an additional dataset of 30 independent compounds. High training correlations (r2=0.83-0.91) were observed while validation results for the external compounds were encouraging (r2=0.62-0.86). The models were used to identify structural features of phytoestrogens that are responsible for selective ligand binding to ERalpha and ERbeta. Numerous structural characteristics are required for complexation with receptors. In particular, size, shape and polarity of ligands, heterocyclic rings, lipophilicity, hydrogen bonding, presence of quaternary carbon atom, presence, position, length and configuration of a bulky side chain, were identified as the most significant structural features responsible for selective binding to ERalpha and ERbeta.

  19. 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.

  20. 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

  1. 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.

  2. [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

  3. 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

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. 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.

  9. Quantitative Structure-Activity Relationship Modeling of Kinase Selectivity Profiles.

    PubMed

    Kothiwale, Sandeepkumar; Borza, Corina; Pozzi, Ambra; Meiler, Jens

    2017-09-19

    The discovery of selective inhibitors of biological target proteins is the primary goal of many drug discovery campaigns. However, this goal has proven elusive, especially for inhibitors targeting the well-conserved orthosteric adenosine triphosphate (ATP) binding pocket of kinase enzymes. The human kinome is large and it is rather difficult to profile early lead compounds against around 500 targets to gain an upfront knowledge on selectivity. Further, selectivity can change drastically during derivatization of an initial lead compound. Here, we have introduced a computational model to support the profiling of compounds early in the drug discovery pipeline. On the basis of the extensive profiled activity of 70 kinase inhibitors against 379 kinases, including 81 tyrosine kinases, we developed a quantitative structure-activity relation (QSAR) model using artificial neural networks, to predict the activity of these kinase inhibitors against the panel of 379 kinases. The model's performance in predicting activity ranges from 0.6 to 0.8 depending on the kinase, from the area under the curve (AUC) of the receiver operating characteristics (ROC). The profiler is available online at http://www.meilerlab.org/index.php/servers/show?s_id=23.

  10. 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.

  11. 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.

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

    PubMed

    Millis, Michael B; Zaltz, Ira

    2014-01-01

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

  13. Flexibility of inorganic tennis ball structures inducing anion selectivity.

    PubMed

    Kim, Ki-Hyun; Park, Jung Su; Kang, Tae Yi; Oh, Kyungeun; Seo, Mi-Sook; Sohn, Youn Soo; Jun, Moo-Jin; Nam, Wonwoo; Kim, Kwan Mook

    2006-09-18

    Inorganic tennis balls (ITBs), [[{Pt(betmp)(dach)}(2)Cu](2)(X)][X](3) (in which X=ClO(4) (-) (3), NO(3) (-) (4), Cl(-) (5) and Br(-) (6); dach=trans-1,2-diaminocyclohexane and betmp=bisethylthiomethylidenepropanedioate) and [[{Pt(dteym)(dach)}(2)Cu](2)(PF(6))][PF(6)](3) (7; dteym=1,3-dithiepane-2-ylidenemalonate), were prepared as crystals. Investigation of their X-ray crystal structures revealed that shapes of the cavities in ITBs show significant distortions that depend on the properties of the encapsulated anions. The CuCu* distance was observed to be longest in 7 and shortest in 5, the difference between them being 2.05 A. The flexibility of cavity structures of ITBs makes it possible to encapsulate various anions inside the cavity, while their distortions may be a reason for the difference in the encapsulating ability for anions, that is, anion selectivity. Especially, the distortions observed in 7 are so severe that the encapsulating ability of the cavity for PF(6) (-) is very low compared to other anions. The shapes of ITBs with ClO(4) (-) and BF(4) (-) ions inside their cavities are very similar; however, ClO(4) (-) is encapsulated by the cavity better than BF(4) (-), which is explicable by the difference of metal-anion interactions. This structural study on ITBs gives a clue to the origin of the anion selectivity of the cavity in ITBs previously investigated by (19)F NMR spectroscopy of the ITBs in methanol.

  14. Structural Basis for α-Conotoxin Potency and Selectivity

    PubMed Central

    Turner, Matt; Eidemiller, Seth; Martin, Bryan; Narver, Andrew; Marshall, Joshua; Zemp, Logan; Cornell, Kenneth A.; McIntosh, J. Michael; McDougal, Owen M.

    2009-01-01

    Parkinson’s disease is a debilitating movement disorder characterized by altered levels of α6β2* nicotinic acetylcholine receptors (nAChRs) localized on presynaptic striatal catecholaminergic neurons. α-Conotoxin MII (α-CTx MII) is a highly useful ligand to probe α6β2 nAChRs structure and function, but it does not discriminate among closely related α6* nAChR subtypes. Modification of the α-CTx MII primary sequence led to the identification of α-CTx MII[E11A], an analog with 500–5300 fold discrimination between α6* subtypes found in both human and non-human primates. α-CTx MII[E11A] binds most strongly (femtomolar dissociation constant) to the high affinity α6 nAChR, a subtype that is selectively lost in Parkinson’s disease. Here we present the three-dimensional solution structure for α-CTx MII[E11A] as determined by two-dimensional 1H NMR spectroscopy to 0.13 +/− 0.09 Ǻ backbone and 0.45 +/− 0.08 Ǻ heavy atom root mean square deviation from mean structure. Structural comparisons suggest that the increased hydrophobic area of α-CTx MII[E11A] relative to other members of the α-CTx family may be responsible for its exceptionally high affinity for α6α4β2* nAChR as well as discrimination between α6β2 and α3β2 containing nAChRs. This finding may enable the rational design of novel peptide analogs that demonstrate enhanced specificity for α6* nAChR subunit interfaces and provide a means to better understand nAChR structural determinants that modulate brain dopamine levels and the pathophysiology of Parkinson’s disease. PMID:19628399

  15. 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

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

    PubMed

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

    2015-03-01

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

  17. 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.

  18. 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

  19. Composite Load Spectra for Select Space Propulsion Structural Components

    NASA Technical Reports Server (NTRS)

    Ho, Hing W.; Newell, James F.

    1994-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  1. 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.

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

    PubMed Central

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

    2016-01-01

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

  3. 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.

  4. 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.

  5. [Standardized selection and its consequences for genetic population structure (examplified by Sus scrofa L.)].

    PubMed

    Kniazev, S P; Nikitin, S V

    2011-01-01

    Type of selection for total fitness, specific for domestic animals and termed by us standardizing selection, is discussed. Consequences of such selection for the population structure genetic are considered taking a population of domestic pigs as an example. Examples of effective and ineffective standardizing selection are presented. Specific features of genetic determination often quantitative traits detected in analysis of standardizing selection are discussed.

  6. 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.

  7. 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.

  8. [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.

  9. 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.

  10. Degeneracy-driven self-structuring dynamics in selective repertoires.

    PubMed

    Atamas, Sergei P; Bell, Jonathan

    2009-08-01

    Numerous biological interactions, such as interactions between T cell receptors or antibodies with antigens, interactions between enzymes and substrates, or interactions between predators and prey are often not strictly specific. In such less specific, or "sloppy," systems, referred to here as degenerate systems, a given unit of a diverse resource (antigens, enzymatic substrates, prey) is at risk of being recognized and consumed by multiple consumers (lymphocytes, enzymes, predators). In this study, we model generalized degenerate consumer-resource systems of Lotka-Volterra and Verhulst types. In the degenerate systems of Lotka-Volterra, there is a continuum of types of consumer and resource based on variation of a single trait (characteristic, or preference). The consumers experience competition for a continuum of resource types. This non-local interaction system is modeled with partial differential-integral equations and shows spontaneous self-structuring of the consumer population that depends on the degree of interaction degeneracy between resource and consumer, but does not mirror the distribution of resource. We also show that the classical Verhulst (i.e. logistic) single population model can be generalized to a degenerate model, which shows qualitative behavior similar to that in the degenerate Lotka-Volterra model. These results provide better insight into the dynamics of selective systems in biology, suggesting that adaptation of degenerate repertoires is not a simple "mirroring" of the environment by the "fittest" elements of population.

  11. 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

  12. 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.

  13. Liposomes in topical photodynamic therapy.

    PubMed

    Dragicevic-Curic, Nina; Fahr, Alfred

    2012-08-01

    Topical photodynamic therapy (PDT) refers to topical application of a photosensitizer onto the site of skin disease which is followed by illumination and results in death of selected cells. The main problem in topical PDT is insufficient penetration of the photosensitizer into the skin, which limits its use to superficial skin lesions. In order to overcome this problem, recent studies tested liposomes as delivery systems for photosensitizers. This paper reviews the use of different types of liposomes for encapsulating photosensitizers for topical PDT. Liposomes should enhance the photosensitizers' penetration into the skin, while decreasing its absorption into systemic circulation. Only few photosensitizers have currently been encapsulated in liposomes for topical PDT: 5-aminolevulinic acid (5-ALA), temoporfin (mTHPC) and methylene blue. Investigated liposomes enhanced the skin penetration of 5-ALA and mTHPC, reduced their systemic absorption and reduced their cytotoxicity compared with free drugs. Their high tissue penetration should enable the treatment of deep and hyperkeratotic skin lesions, which is the main goal of using liposomes. However, liposomes still do not attract enough attention as drug carriers in topical PDT. In vivo studies of their therapeutic effectiveness are needed in order to obtain enough evidence for their potential clinical use as carriers for photosensitizers in topical PDT.

  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. Crystal structure, site selectivity, and electronic structure of layered chalcogenide LaOBiPbS3

    NASA Astrophysics Data System (ADS)

    Mizuguchi, Y.; Hijikata, Y.; Abe, T.; Moriyoshi, C.; Kuroiwa, Y.; Goto, Y.; Miura, A.; Lee, S.; Torii, S.; Kamiyama, T.; Lee, C. H.; Ochi, M.; Kuroki, K.

    2017-07-01

    We have investigated the crystal structure of LaOBiPbS3 using neutron diffraction and synchrotron X-ray diffraction. From structural refinements, we found that the two metal sites, occupied by Bi and Pb, were differently surrounded by the sulfur atoms. Calculated bond valence sum suggested that one metal site was nearly trivalent and the other was nearly divalent. Neutron diffraction also revealed site selectivity of Bi and Pb in the LaOBiPbS3 structure. These results suggested that the crystal structure of LaOBiPbS3 can be regarded as alternate stacks of the rock-salt–type Pb-rich sulfide layers and the LaOBiS2-type Bi-rich layers. From band calculations for an ideal (LaOBiS2)(PbS) system, we found that the S bands of the PbS layer were hybridized with the Bi bands of the BiS plane at around the Fermi energy, which resulted in the electronic characteristics different from that of LaOBiS2. Stacking the rock-salt type sulfide (chalcogenide) layers and the BiS2-based layered structure could be a new strategy to exploration of new BiS2-based layered compounds, exotic two-dimensional electronic states, or novel functionality.

  17. 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

  18. 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

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

    NASA Technical Reports Server (NTRS)

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

    1999-01-01

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

  20. 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…

  1. 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.…

  2. 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.

  3. 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.

  4. Origin of Unusually High Rigidity in Selected Helical Coil Structures

    NASA Astrophysics Data System (ADS)

    Tománek, David; Every, Arthur G.

    2017-07-01

    Using continuum elasticity theory, we describe the elastic behavior of helical coils with an asymmetric double-helix structure and identify conditions under which they become very rigid. Theoretical insight gained for macrostructures including a stretched telephone cord and an unsupported helical staircase is universal and of interest for the elastic behavior of helical structures on the micrometer and nanometer scale.

  5. Structural Basis for Receptor Selectivity by the Whitewater Arroyo Mammarenavirus.

    PubMed

    Shimon, Amir; Shani, Orly; Diskin, Ron

    2017-09-01

    Whitewater Arroyo virus belongs to the "New World" group of mammarenaviruses that reside in rodent reservoirs and are prevalent in North and South Americas. Clades B and A/B of New World mammarenaviruses use transferrin receptor 1 (TfR1) for entry. While all of these viruses use rodent-derived TfR1 orthologs, some can also use the human-TfR1 and thereby infect humans. Although we have structural information for TfR1 recognition by pathogenic virus, we do not know what the structural differences are between the receptor-binding domains of pathogenic and non-pathogenic viruses that allow some but not all viruses to utilize the human receptor for entry. The poor understanding of the molecular determinants of mammarenavirus host range, and thus pathogenicity, is partly due to the low sequence similarity between the receptor-binding domains from these viruses and the limited available structural information that preclude the use of modeling approaches. Here we present the first crystal structure of a receptor-binding domain of a non-pathogenic clade A/B mammarenavirus. This structure reveals the magnitude of structural differences within the receptor-binding domains of TfR1-tropic viruses. Our structural and sequence analyses indicate that the same structural incompatibilities with the human receptor equally affect both pathogenic and non-pathogenic mammarenaviruses. Non-pathogenic viruses do not have specific structural elements that prevent them from using the human receptor. Instead, the ability to utilize the human receptor directly depends on the extent of weak interactions throughout the receptor-binding site that in some viruses are sufficiently strong to overcome the structural incompatibilities. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Training set optimization under population structure in genomic selection

    USDA-ARS?s Scientific Manuscript database

    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...

  7. 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

  8. 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.

  9. Optical microscopy of targeted drug delivery and local distribution in skin of a topical minocycline: implications in translational research and guidance for therapeutic dose selection (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Hermsmeier, Maiko; Sawant, Tanvee; Lac, Diana; Yamamoto, Akira; Chen, Xin; Huang, Susan Y.; Nagavarapu, Usha; Evans, Conor L.; Chan, Kin Foong; Daniels, AnnaMarie

    2017-02-01

    Acne vulgaris is a chronic inflammatory skin condition commonly resulting in negative aesthetic and social impacts on those affected. Minocycline, currently available as an oral antibiotic for moderate to severe acne, has a known minimum inhibitory concentration (MIC) for the acne-causing bacterium Propionibacterium acnes (P. acnes) in vitro, with its anti-inflammatory properties also eliciting inhibitory effects on pro-inflammatory molecules. A novel topical gel composition containing solubilized minocycline (BPX-01) has been developed to directly deliver the drug to the skin. Because minocycline is a known fluorophore, fluorescence microscopy and concurrent quantitative measurements were performed on excised human facial skin dosed with different concentrations, in order to determine the spatial distribution of the drug and quantification of its local concentration in the epidermis and the pilosebaceous unit where P. acnes generally reside. Local minocycline delivery confirmed achievement of an adequate therapeutic dose to support clinical studies. Subsequently, a 4-week double-blind, randomized, vehicle controlled clinical study was performed to assess the safety and efficacy of 1% minocycline BPX-01 applied daily. No instances of cutaneous toxicity were reported, and a greater than 1 log reduction of P. acnes count was observed at week 4 with statistical significance from baseline and vehicle control. In addition, no detectable amounts of minocycline in the plasma were reported, suggesting the potential of this new formulation to diminish the known systemic adverse effects associated with oral minocycline. Follow-on clinical plans are underway to further establish the safety of BPX-01 and to evaluate its efficacy against inflammatory acne lesions in a 225 patient multi-center dose-finding study.

  10. Child Development & Behavior Topics

    MedlinePlus

    ... Your Child Topics Commentaries Featured Links Contact Us Child Development & Behavior Topics A B C D E F ... Seat Safety Carbon Monoxide Chewing Tobacco Child Care Child Development Milestones Child Development, What Do Grown-Ups Know ...

  11. 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

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

    EIA Publications

    1998-01-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1989-01-01

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

  14. Structure-selective modification of aromatic side chains with dirhodium metallopeptide catalysts.

    PubMed

    Popp, Brian V; Ball, Zachary T

    2010-05-19

    The combination of peptide molecular recognition and residue-selective dirhodium catalysis allows modification of aromatic side chains that is selective for coil structures. A rate enhancement of >10(3) relative to nonselective dirhodium modification was observed. The increased reactivity of this approach creates the first selective chemical modification of the phenylalanine residue.

  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. Haplotype structure and positive selection at TLR1

    PubMed Central

    Heffelfinger, Christopher; Pakstis, Andrew J; Speed, William C; Clark, Allison P; Haigh, Eva; Fang, Rixun; Furtado, Mahohar R; Kidd, Kenneth K; Snyder, Michael P

    2014-01-01

    Toll-like receptor 1, when dimerized with Toll-like receptor 2, is a cell surface receptor that, upon recognition of bacterial lipoproteins, activates the innate immune system. Variants in TLR1 associate with the risk of a variety of medical conditions and diseases, including sepsis, leprosy, tuberculosis, and others. The foremost of these is rs5743618 c.2079T>G(p.(Ile602Ser)), the derived allele of which is associated with reduced risk of sepsis, leprosy, and other diseases. Interestingly, 602Ser, which shows signatures of selection, inhibits TLR1 surface trafficking and subsequent activation of NFκB upon recognition of a ligand. This suggests that reduced TLR1 activity may be beneficial for human health. To better understand TLR1 variation and its link to human health, we have typed all 7 high-frequency missense variants (>5% in at least one population) along with 17 other variants in and around TLR1 in 2548 individuals from 56 populations from around the globe. We have also found additional signatures of selection on missense variants not associated with rs5743618, suggesting that there may be multiple functional alleles under positive selection in this gene. PMID:24002163

  17. 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.

  18. 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.

  19. Issues in the Development of Long Term Care Gerontology Centers: The Centers Concept. Selected Topics in Long Term Care. Volume 6.

    ERIC Educational Resources Information Center

    Mortenson, Lee E.; Berdes, Celia M.

    This document, one in a series developed to provide technical assistance to 22 Long-Term Care Gerontology Centers, describes the current administrative and structural phenomenon of these centers. Precedents useful in assessing both the current climate and actual prospects for development of long term care centers are cited. The first section…

  20. 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.…

  1. Topic Prominence in Chinese EFL Learners' Interlanguage

    ERIC Educational Resources Information Center

    Li, Shaopeng; Yang, Lianrui

    2014-01-01

    The present study aims to investigate the general characteristics of topicprominent typological interlanguage development of Chinese learners of English in terms of acquiring subject-prominent English structures from a discourse perspective. Topic structures mainly appear in Chinese discourse in the form of topic chains (Wang, 2002; 2004). The…

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

    ERIC Educational Resources Information Center

    Sasmor, James C.

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

  3. 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…

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

    ERIC Educational Resources Information Center

    Dole, Arthur A.; And Others

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

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

    ERIC Educational Resources Information Center

    Olson, Arthur V.; Rosen, Carl L.

    The technique of factor analysis was used to explore the structure of five batteries of readiness tests (Gates Reading Readiness Test, Developmental Tests of Visual Perception, Metropolitan Readiness Tests, Specially Constructed Readiness Test by Olson, and Wechsler Intelligence for Children) as predictor variables for the Stanford Achievement…

  6. Image Modeling and Enhancement via Structured Sparse Model Selection

    DTIC Science & Technology

    2010-01-01

    f − f kM‖2 +T 2M ) + 32σ2 KN , (9) where f kM = ∑ M m=1〈 f ,φ km〉φ km. Theorem 1 is derived from the general model selection result of Barron ... Michel Morel for the inspiring discussions. 5. REFERENCES [1] M. Aharon, M. Elad, and A. Bruckstein. K-SVD: An algorithm for designing overcomplete...Model-based compressive sensing. Submitted to IEEE Trans on Information The- ory, 2008. [3] A. Barron , L. Birgé, and P. Massart. Risk bounds for model

  7. 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.

  8. 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.

  9. 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.

  10. Target selection of soluble protein complexes for structural proteomics studies

    PubMed Central

    Shen, Weiping; Yun, Steven; Tam, Bonny; Dalal, Kush; Pio, Frederic F

    2005-01-01

    Background Protein expression in E. coli is the most commonly used system to produce protein for structural studies, because it is fast and inexpensive and can produce large quantity of proteins. However, when proteins from other species such as mammalian are produced in this system, problems of protein expression and solubility arise [1]. Structural genomics project are currently investigating proteomics pipelines that would produce sufficient quantities of recombinant proteins for structural studies of protein complexes. To investigate how the E. coli protein expression system could be used for this purpose, we purified apoptotic binary protein complexes formed between members of the Caspase Associated Recruitment Domain (CARD) family. Results A combinatorial approach to the generation of protein complexes was performed between members of the CARD domain protein family that have the ability to form hetero-dimers between each other. In our method, each gene coding for a specific protein partner is cloned in pET-28b (Novagen) and PGEX2T (Amersham) expression vectors. All combinations of protein complexes are then obtained by reconstituting complexes from purified components in native conditions, after denaturation-renaturation or co-expression. Our study applied to 14 soluble CARD domain proteins revealed that co-expression studies perform better than native and denaturation-renaturation methods. In this study, we confirm existing interactions obtained in vivoin mammalian cells and also predict new interactions. Conclusion The simplicity of this screening method could be easily scaled up to identify soluble protein complexes for structural genomic projects. This study reports informative statistics on the solubility of human protein complexes expressed in E.coli belonging to the human CARD protein family. PMID:15904526

  11. 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.…

  12. 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)

  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. [Incentive for Regional Risk Selection in the German Risk Structure Compensation Scheme].

    PubMed

    Wende, Danny

    2017-03-22

    The introduction of the new law GKV-FQWG strengthens the competition between statutory health insurance. If incentives for risk selection exist, they may force a battle for cheap customers. This study aims to document and discuss incentives for regional risk selection in the German risk structure compensation scheme. Identify regional autocorrelation with Moran's l on financial parameters of the risk structure compensation schema. Incentives for regional risk selection do indeed exist. The risk structure compensation schema reduces 91% of the effect and helps to reduce risk selection. Nevertheless, a connection between regional situation and competition could be shown (correlation: 69.5%). Only the integration of regional control variables into the risk compensation eliminates regional autocorrelation. The actual risk structure compensation is leading to regional inequalities and as a consequence to risk selection and distortion in competition. © Georg Thieme Verlag KG Stuttgart · New York.

  15. 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.

  16. 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.

  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. 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.

  19. 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

  20. 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.

  1. Factor Selection and Structural Identification in the Interaction ANOVA Model

    PubMed Central

    Post, Justin B.; Bondell, Howard D.

    2013-01-01

    Summary When faced with categorical predictors and a continuous response, the objective of 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 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 paper 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. PMID:23323643

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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.

  7. 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.

  8. Welding process selection for fabrication of a superconducting magnet structure

    SciTech Connect

    Goodwin, G.M.

    1985-08-01

    The magnets that will provide containment of the intensely hot plasma in fusion reactors must be wound with superconductors to enable these reactors to produce more energy than they consume (Ref. 1). With current superconductor technology, this requires the use of liquid helium at its boiling point (about 4 K, or -269/sup 0/C) as a coolant. At this temperature, all other known materials are solid. Austenitic stainless steels are the most widely used alloys for structural applications below 77 K (-196/sup 0/C) (Ref. 2). Their physical properties offer advantages over those of competing materials; the elastic modulus is high, and the thermal expansion, magnetic permeability, and electrical and thermal conductivities are low. Their mechanical properties, including strength, ductility and fracture toughness, are generally adequate to withstand the large forces imposed on magnet structures reliably. A possible exception to this statement arises in the case of weldments; the limited 4 K (-269/sup 0/C) fracture toughness data for austenitic stainless steel weld metal show a wide range of values, with no obvious explanation for the large differences. This report summarizes the data available in the literature, contributes new data for three different welding processes - gas tungsten arc (GTAW), shielded metal arc (SMAW) and flux cored arc (FCAW) - and offers some observations of the fracture morphology.

  9. From an understanding of structural restoration mechanisms towards a selective processing of extreme nanolamellar structures

    NASA Astrophysics Data System (ADS)

    Renk, O.; Ghosh, P.; Pippan, R.

    2017-07-01

    It has been successfully proven that severe cold deformation can be used to generate bulk nanostructured materials. However, there is a limit to grain refinement, as recovery processes, together with grain boundary and triple junction motion, occur to continuously fragment and remove grains. Although believed to be mechanically driven at low temperatures, it is clear that such movement can be thermally assisted, as reflected in decreased grain aspect ratios at elevated deformation temperatures. Interestingly, for tantalum, a different behaviour can be found. Grain aspect ratios after high pressure torsion increase steadily up to deformation temperatures of 673 K before dropping again. Moreover, extremely large aspect ratios of 10 can be generated. The reasons for this behaviour are discussed and it is suggested from results based on nickel that this phenomenon can be adapted to any metal. This offers the possibility to selectively process materials with extreme grain aspect ratios, to achieve structures which are thought to be the key to the design of materials that combine both, exceptional strength and good damage tolerance.

  10. 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.

  11. 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.

  12. Structure and ligand selection of hemoglobin II from Lucina pectinata.

    PubMed

    Gavira, José A; Camara-Artigas, Ana; De Jesús-Bonilla, Walleska; López-Garriga, Juan; Lewis, Ariel; Pietri, Ruth; Yeh, Syun-Ru; Cadilla, Carmen L; García-Ruiz, Juan Manuel

    2008-04-04

    Lucina pectinata ctenidia harbor three heme proteins: sulfide-reactive hemoglobin I (HbI(Lp)) and the oxygen transporting hemoglobins II and III (HbII(Lp) and HbIII(Lp)) that remain unaffected by the presence of H(2)S. The mechanisms used by these three proteins for their function, including ligand control, remain unknown. The crystal structure of oxygen-bound HbII(Lp) shows a dimeric oxyHbII(Lp) where oxygen is tightly anchored to the heme through hydrogen bonds with Tyr(30)(B10) and Gln(65)(E7). The heme group is buried farther within HbII(Lp) than in HbI(Lp). The proximal His(97)(F8) is hydrogen bonded to a water molecule, which interacts electrostatically with a propionate group, resulting in a Fe-His vibration at 211 cm(-1). The combined effects of the HbII(Lp) small heme pocket, the hydrogen bonding network, the His(97) trans-effect, and the orientation of the oxygen molecule confer stability to the oxy-HbII(Lp) complex. Oxidation of HbI(Lp) Phe(B10) --> Tyr and HbII(Lp) only occurs when the pH is decreased from pH 7.5 to 5.0. Structural and resonance Raman spectroscopy studies suggest that HbII(Lp) oxygen binding and transport to the host bacteria may be regulated by the dynamic displacements of the Gln(65)(E7) and Tyr(30)(B10) pair toward the heme to protect it from changes in the heme oxidation state from Fe(II) to Fe(III).

  13. 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.

  14. 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

  15. 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

  16. 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

  17. 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.

  18. Association between selected structural defects and chromosomal abnormalities.

    PubMed

    Acevedo-Gallegos, Sandra; García, Mónica; Benavides-Serralde, Andrés; Camargo-Marín, Lisbeth; Aguinaga-Ríos, Mónica; Ramírez-Calvo, José; Velázquez-Torres, Berenice; Gallardo-Gaona, Juan; Guzmán-Huerta, Mario

    2013-01-01

    To determine the association between some major structural abnormalities detected prenatally by ultrasound and chromosomal abnormalities. The present study was a retrolective, transversal study. We analyzed case records of patients during the fetal follow-up at the Department of Maternal Fetal Medicine from January 1994 to May 2010 to identify fetal patients with a diagnosis of holoprosencephaly, diaphragmatic hernia, omphalocele, cystic hygroma, hydrops and cardiac defects. We analyzed patients who had a prenatal invasive diagnosis procedure to obtain the odds ratio (OR) for some major isolated anomalies and their different combinations with respect to chromosomal abnormalities. We examined 280 patients with ultrasonographic markers for chromosomal alteration, 197 met inclusion criteria, from which 88 had chromosomal abnormalities. The most frequent diagnosis was trisomy 18 (31.8%), which was followed by trisomy 21 (21.6%), trisomy 13 (21.6%), Turner syndrome (monosomy X) (14.8%) and other chromosomal abnormalities (10.2%). Among the fetuses with nonisolated holoprosencephaly, we obtained an OR of 4.9 95% CI (0.99-24.2) for aneuploidy. Associated omphalocele had an OR of 7.63 95% CI (2.07-46.75), p < 0.01. Interestingly, 62% of aneuploidy cases had associated cardiac defects [OR = 7.7 95% CI (1.4-41.7)]. In addition, associated cystic hygroma had an OR of 2.5 95% CI (0.59-10.91). Heart defects were the most common defects in fetuses with trisomy 18 (57.1%), when they were associated with facial cleft, we had an OR of 11.08 95% CI (2.99-41.11), p < 0.0001. Statistical potency was calculated for each analyzed defect and it was over 80% for all of them but diaphragmatic hernia. The association of 2 or more structural defects increased the probability of a fetus to be a carrier of a chromosomal disorder; however this was not statistically significative except for associated omphalocele. Heart defects showed the greatest association with all chromosomal abnormalities

  19. The optimization of diffraction structures based on the principle selection of the main criterion

    NASA Astrophysics Data System (ADS)

    Kravets, O.; Beletskaja, S.; Lvovich, Ya; Lvovich, I.; Choporov, O.; Preobrazhenskiy, A.

    2017-02-01

    The possibilities of optimizing the characteristics of diffractive structures are analysed. A functional block diagram of a subsystem of diffractive structure optimization is shown. Next, a description of the method for the multicriterion optimization of diffractive structures is given. We then consider an algorithm for selecting the main criterion in the process of optimization. The algorithm efficiency is confirmed by an example of optimization of the diffractive structure.

  20. Structural aspects of rubidium ion selectivity by tribenzo-21-crown-7

    SciTech Connect

    Bryan, J.C.; Sachleben, R.A.; Lavis, J.M.; Davis, M.C.; Burns, J.H.; Hay, B.P.

    1998-06-01

    The structural origins of the selectivity of rubidium ion over other alkali metal ions (Cs, Rb, Na, Re) by tribenzo-21-crown-7 is investigated from single-crystal X-ray diffraction. The structures reported here are the first reported for a tribenzo-21-crown-7, and the alkali metal ion complexes are the first reported structures of these ions with any 21-crown-7 ether. Different crown conformations are observed for each structure. Molecular mechanics calculations were performed on all conformers, and the results are related to the observed extraction selectivity for rubidium.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

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

    PubMed Central

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

    2012-01-01

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

  6. 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 ...

  7. Long Live Topic Work!

    ERIC Educational Resources Information Center

    Bennett, Paul

    1995-01-01

    Reviews the value of topic work with regard to the British National Curriculum guidelines on curriculum planning. After years of concentrating on issues of content in planning, consideration of basic aims and values in education is again urged. Topic work allows teachers to teach in depth areas of personal expertise and interest in a local…

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

    PubMed

    Wang, Qingguo; Shang, Yi; Xu, Dong

    2011-01-01

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

  9. Quantile hydrologic model selection and model structure deficiency assessment: 2. Applications

    NASA Astrophysics Data System (ADS)

    Pande, Saket

    2013-09-01

    Quantile hydrologic model selection and structure deficiency assessment is applied in three case studies. The performance of quantile model selection problem is rigorously evaluated using a model structure on the French Broad river basin data set. The case study shows that quantile model selection encompasses model selection strategies based on summary statistics and that it is equivalent to maximum likelihood estimation under certain likelihood functions. It also shows that quantile model predictions are fairly robust. The second case study is of a parsimonious hydrological model for dry land areas in Western India. The case study shows that an intuitive improvement in the model structure leads to reductions in asymmetric loss function values for all considered quantiles. The asymmetric loss function is a quantile specific metric that is minimized to obtain a quantile specific prediction model. The case study provides evidence that a quantile-wise reduction in the asymmetric loss function is a robust indicator of model structure improvement. Finally a case study of modeling daily streamflow for the Guadalupe River basin is presented. A model structure that is least deficient for the study area is identified from nine different model structures based on quantile structural deficiency assessment. The nine model structures differ in interception, routing, overland flow and base flow conceptualizations. The three case studies suggest that quantile model selection and deficiency assessment provides a robust mechanism to compare deficiencies of different model structures and helps to identify better model structures. In addition to its novelty, quantile hydrologic model selection is a frequentist approach that seeks to complement existing Bayesian approaches to hydrological model uncertainty.

  10. 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…

  11. 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.

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

    PubMed

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

    2016-08-25

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

  13. Structural Basis of Cyclic Nucleotide Selectivity in cGMP-dependent Protein Kinase II

    DOE PAGES

    Campbell, James C.; Kim, Jeong Joo; Li, Kevin Y.; ...

    2016-01-14

    Membrane-bound cGMP-dependent protein kinase (PKG) II is an important regulator of bone growth, renin secretion, and memory formation. Despite its crucial physiological roles, little is known about its cyclic nucleotide selectivity mechanism due to a lack of structural information. Here, we find that the C-terminal cyclic nucleotide binding (CNB-B) domain of PKGII binds cGMP with higher affinity and selectivity when compared with its N-terminal CNB (CNB-A) domain. To understand the structural basis of cGMP selectivity, we solved co-crystal structures of the CNB domains with cyclic nucleotides. Our structures combined with mutagenesis demonstrate that the guanine-specific contacts at Asp-412 and Arg-415more » of the αC-helix of CNB-B are crucial for cGMP selectivity and activation of PKG II. Structural comparison with the cGMP selective CNB domains of human PKG I and Plasmodium falciparum PKG (PfPKG) shows different contacts with the guanine moiety, revealing a unique cGMP selectivity mechanism for PKG II.« less

  14. Structural Basis of Cyclic Nucleotide Selectivity in cGMP-dependent Protein Kinase II

    SciTech Connect

    Campbell, James C.; Kim, Jeong Joo; Li, Kevin Y.; Huang, Gilbert Y.; Reger, Albert S.; Matsuda, Shinya; Sankaran, Banumathi; Link, Todd M.; Yuasa, Keizo; Ladbury, John E.; Casteel, Darren E.; Kim, Choel

    2016-01-14

    Membrane-bound cGMP-dependent protein kinase (PKG) II is an important regulator of bone growth, renin secretion, and memory formation. Despite its crucial physiological roles, little is known about its cyclic nucleotide selectivity mechanism due to a lack of structural information. Here, we find that the C-terminal cyclic nucleotide binding (CNB-B) domain of PKGII binds cGMP with higher affinity and selectivity when compared with its N-terminal CNB (CNB-A) domain. To understand the structural basis of cGMP selectivity, we solved co-crystal structures of the CNB domains with cyclic nucleotides. Our structures combined with mutagenesis demonstrate that the guanine-specific contacts at Asp-412 and Arg-415 of the αC-helix of CNB-B are crucial for cGMP selectivity and activation of PKG II. Structural comparison with the cGMP selective CNB domains of human PKG I and Plasmodium falciparum PKG (PfPKG) shows different contacts with the guanine moiety, revealing a unique cGMP selectivity mechanism for PKG II.

  15. Structural Basis of Cyclic Nucleotide Selectivity in cGMP-dependent Protein Kinase II*

    PubMed Central

    Campbell, James C.; Kim, Jeong Joo; Li, Kevin Y.; Huang, Gilbert Y.; Reger, Albert S.; Matsuda, Shinya; Sankaran, Banumathi; Link, Todd M.; Yuasa, Keizo; Ladbury, John E.; Casteel, Darren E.; Kim, Choel

    2016-01-01

    Membrane-bound cGMP-dependent protein kinase (PKG) II is a key regulator of bone growth, renin secretion, and memory formation. Despite its crucial physiological roles, little is known about its cyclic nucleotide selectivity mechanism due to a lack of structural information. Here, we find that the C-terminal cyclic nucleotide binding (CNB-B) domain of PKG II binds cGMP with higher affinity and selectivity when compared with its N-terminal CNB (CNB-A) domain. To understand the structural basis of cGMP selectivity, we solved co-crystal structures of the CNB domains with cyclic nucleotides. Our structures combined with mutagenesis demonstrate that the guanine-specific contacts at Asp-412 and Arg-415 of the αC-helix of CNB-B are crucial for cGMP selectivity and activation of PKG II. Structural comparison with the cGMP selective CNB domains of human PKG I and Plasmodium falciparum PKG (PfPKG) shows different contacts with the guanine moiety, revealing a unique cGMP selectivity mechanism for PKG II. PMID:26769964

  16. 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.

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

    ERIC Educational Resources Information Center

    Martin, Robert A.

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

  18. 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.

  19. Structural basis for the design and synthesis of selective HDAC inhibitors.

    PubMed

    Di Micco, Simone; Chini, Maria Giovanna; Terracciano, Stefania; Bruno, Ines; Riccio, Raffaele; Bifulco, Giuseppe

    2013-07-01

    Histone Deacetylases are considered promising targets for cancer epigenetic therapy, and small molecules able to modulate their biological function have recently gained an increasing interest as potential anticancer agents. In spite of their potential application in cancer therapy, most HDAC inhibitors unselectively bind the several HDAC isoforms, giving rise to different side-effects. In this context, we have traced out the structural elements responsible of selective binding for the therapeutically relevant different HDAC isoforms. The structural analysis has been carried out by molecular modeling, docking in the binding pockets of HDAC1-4 and HDAC6-8, 36 inhibitors presenting a well defined selectivity for the different isoforms. As quick proof of evidence, we have designed, synthesized and experimentally tested three selective ligands. The experimental data suggest that the obtained structural guidelines can be useful tools for the rational design of new potent inhibitors against selected HDAC isoforms. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. 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.

  1. 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…

  2. 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…

  3. 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…

  4. 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.

  5. Selected Topics in Peace Corps Training.

    ERIC Educational Resources Information Center

    Hubchen, Jonathan

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

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. '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.

  11. '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.

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

    NASA Astrophysics Data System (ADS)

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

    2012-11-01

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

  13. 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

  14. 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)

  15. Women's Health Topics

    MedlinePlus

    ... HPV Breast Implants Caregiving College Health Diabetes Healthy Aging Heart Health Mammograms Menopause Pregnancy Safe Medication Use Other Topics like cosmetics and nutrition Other Tips Hispanic Women's Health 4 Tips for ...

  16. 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.

  17. Intrinsic selectivity and structure sensitivity of Rhodium catalysts for C2+ oxygenate production [On the intrinsic selectivity and structure sensitivity of Rhodium catalysts for C2+ oxygenate production

    DOE PAGES

    Yang, Nuoya; Medford, Andrew J.; Liu, Xinyan; ...

    2016-01-31

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

  18. 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

  19. 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.

  20. 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

  1. Topical Therapies in Psoriasis

    PubMed Central

    Torsekar, R.; Gautam, Manjyot M.

    2017-01-01

    Topical therapy as monotherapy is useful in psoriasis patients with mild disease. Topical agents are also used as adjuvant for moderate-to-severe disease who are being concurrently treated with either ultraviolet light or systemic medications. Emollients are useful adjuncts to the treatment of psoriasis. Use of older topical agents such as anthralin and coal tar has declined over the years. However, they are cheaper and can still be used for the treatment of difficult psoriasis refractory to conventional treatment. Salicylic acid can be used in combination with other topical therapies such as topical corticosteroids (TCS) and calcineurin inhibitors for the treatment of thick limited plaques to increase the absorption of the latter into the psoriatic plaques. Low- to mid-potent TCS are used in facial/flexural psoriasis and high potent over palmoplantar/thick psoriasis lesions. The addition of noncorticosteroid treatment can also facilitate the avoidance of long-term daily TCS. Tacrolimus and pimecrolimus can be used for the treatment of facial and intertriginous psoriasis. Tazarotene is indicated for stable plaque psoriasis usually in combination with other therapies such as TCS. Vitamin D analogs alone in combination with TCS are useful in stable plaques over limbs and palmoplantar psoriasis. Topical therapies for scalp psoriasis include TCS, Vitamin D analogs, salicylic acid, coal tar, and anthralin in various formulations such as solutions, foams, and shampoos. TCS, vitamin D analogs, and tazarotene can be used in the treatment of nail psoriasis. PMID:28761838

  2. [Material selection and structural design of simulated space module for field].

    PubMed

    Huang, Y; Jin, X G; Wang, L G; Hu, Y Y; Shi, X Y

    2000-02-01

    To select the suitable material for the structure of simulated space cabin to meet the special requirements which the unitary metallic material cannot do. The structural material was selected through comparison between the mechanical properties of fiber reinforced plastics (FRP) and a few conventional metallic materials. The content and arrangement of the fibers in the composite material were suitably designed according to load condition and structural shape of the cabin. High strength and high stiffness, light weight, anti-fatigue and shock proof were achieved for the whole module structure. It meets the medical and hygienic standard for hazardous gases. The structural design of fiber glass reinforced plastics composite module was proved to be successful. It reduced the weight of the module body, and increased the strength and toughness of the whole module.

  3. Environmental Topics for Introductory Physics Courses

    ERIC Educational Resources Information Center

    Hodges, Laurent

    1974-01-01

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

  4. 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…

  5. 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)

  6. 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.

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

    NASA Astrophysics Data System (ADS)

    Mao, Lei; Lu, Yong

    2016-07-01

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

  8. A Love/Hate Relationship: Dissertation Topic to Doctoral Committee.

    ERIC Educational Resources Information Center

    Woodbury, Jacqueline

    This paper outlines the steps involved in developing a dissertation topic and selecting a Dissertation Committee. It suggests that students assess their personal interest in the topic and their technical competence to complete the research required. A checklist of topic feasibility and appropriateness, developed by J. Mauch and J. Birch, is…

  9. 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.

  10. 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%.

  11. 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.

  12. IP Internal Movement and Topicalization

    ERIC Educational Resources Information Center

    Kuo, Pei-Jung

    2009-01-01

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

  13. 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.

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

    PubMed Central

    Finnerty, Justin John

    2015-01-01

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

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. Selection of the intrinsic polarization properties of animal optical materials creates enhanced structural reflectivity and camouflage

    PubMed Central

    Feller, Kathryn D.; Jordan, Thomas M.

    2017-01-01

    Many animals use structural coloration to create bright and conspicuous visual signals. Selection of the size and shape of the optical structures animals use defines both the colour and intensity of the light reflected. The material used to create these reflectors is also important; however, animals are restricted to a limited number of materials: commonly chitin, guanine and the protein, reflectin. In this work we highlight that a particular set of material properties can also be under selection in order to increase the optical functionality of structural reflectors. Specifically, polarization properties, such as birefringence (the difference between the refractive indices of a material) and chirality (which relates to molecular asymmetry) are both under selection to create enhanced structural reflectivity. We demonstrate that the structural coloration of the gold beetle Chrysina resplendens and silvery reflective sides of the Atlantic herring, Clupea harengus are two examples of this phenomenon. Importantly, these polarization properties are not selected to control the polarization of the reflected light as a source of visual information per se. Instead, by creating higher levels of reflectivity than are otherwise possible, such internal polarization properties improve intensity-matching camouflage. This article is part of the themed issue ‘Animal coloration: production, perception, function and application’. PMID:28533453

  20. 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

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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

  6. Whole mitochondrial genome scan for population structure and selection in the Atlantic herring.

    PubMed

    Teacher, Amber Gf; André, Carl; Merilä, Juha; Wheat, Christopher W

    2012-12-22

    Marine fish, such as the Atlantic herring (Clupea harengus), often show a low degree of differentiation over large geographical regions. Despite strong environmental gradients (salinity and temperature) in the Baltic Sea, population genetic studies have shown little genetic differentiation among herring in this area, but some evidence for environmentally-induced selection has been uncovered. The mitochondrial genome is a likely target for selection in this system due to its functional role in metabolism. We sequenced whole mitochondrial genomes for herring from throughout the Baltic region (n=98) in order to investigate evidence for geographical structuring, selection, and associations between genetic and environmental variation. Three well-supported clades that predate the formation of the Baltic Sea were identified, but geographic structuring of this variation was weak (ΦST = 0.036). There was evidence for significant positive selection, particularly in the ND2, ND4 and ND5 genes, and amino acids under significant selection in these genes explained some of the clade formation. Despite uncovering evidence for selection, correlations between genetic diversity or differentiation with environmental factors (temperature, salinity, latitude) were weak. The results indicate that most of the current mtDNA diversity in herring predates the formation of the Baltic Sea, and that little structuring has evolved since. Thus, fisheries management units in this region cannot be determined on the basis of mtDNA variability. Preliminary evidence for selection underlying clade formation indicates that the NADH complex may be useful for examining adaptation and population structuring at a broader geographical scale.

  7. Whole mitochondrial genome scan for population structure and selection in the Atlantic herring

    PubMed Central

    2012-01-01

    Background Marine fish, such as the Atlantic herring (Clupea harengus), often show a low degree of differentiation over large geographical regions. Despite strong environmental gradients (salinity and temperature) in the Baltic Sea, population genetic studies have shown little genetic differentiation among herring in this area, but some evidence for environmentally-induced selection has been uncovered. The mitochondrial genome is a likely target for selection in this system due to its functional role in metabolism. Results We sequenced whole mitochondrial genomes for herring from throughout the Baltic region (n=98) in order to investigate evidence for geographical structuring, selection, and associations between genetic and environmental variation. Three well-supported clades that predate the formation of the Baltic Sea were identified, but geographic structuring of this variation was weak (ΦST = 0.036). There was evidence for significant positive selection, particularly in the ND2, ND4 and ND5 genes, and amino acids under significant selection in these genes explained some of the clade formation. Despite uncovering evidence for selection, correlations between genetic diversity or differentiation with environmental factors (temperature, salinity, latitude) were weak. Conclusions The results indicate that most of the current mtDNA diversity in herring predates the formation of the Baltic Sea, and that little structuring has evolved since. Thus, fisheries management units in this region cannot be determined on the basis of mtDNA variability. Preliminary evidence for selection underlying clade formation indicates that the NADH complex may be useful for examining adaptation and population structuring at a broader geographical scale. PMID:23259908

  8. 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.

  9. 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.

  10. 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

  11. 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

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

    PubMed Central

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

    2014-01-01

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

  13. 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.

  14. 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

  15. 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.

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

    DOE PAGES

    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.

  17. Topics in Bethe Ansatz

    NASA Astrophysics Data System (ADS)

    Wang, Chunguang

    Integrable quantum spin chains have close connections to integrable quantum field. theories, modern condensed matter physics, string and Yang-Mills theories. Bethe. ansatz is one of the most important approaches for solving quantum integrable spin. chains. At the heart of the algebraic structure of integrable quantum spin chains is. the quantum Yang-Baxter equation and the boundary Yang-Baxter equation. This. thesis focuses on four topics in Bethe ansatz. The Bethe equations for the isotropic periodic spin-1/2 Heisenberg chain with N. sites have solutions containing ±i/2 that are singular: both the corresponding energy and the algebraic Bethe ansatz vector are divergent. Such solutions must be carefully regularized. We consider a regularization involving a parameter that can be. determined using a generalization of the Bethe equations. These generalized Bethe. equations provide a practical way of determining which singular solutions correspond. to eigenvectors of the model. The Bethe equations for the periodic XXX and XXZ spin chains admit singular. solutions, for which the corresponding eigenvalues and eigenvectors are ill-defined. We use a twist regularization to derive conditions for such singular solutions to bephysical, in which case they correspond to genuine eigenvalues and eigenvectors of. the Hamiltonian. We analyze the ground state of the open spin-1/2 isotropic quantum spin chain. with a non-diagonal boundary term using a recently proposed Bethe ansatz solution. As the coefficient of the non-diagonal boundary term tends to zero, the Bethe roots. split evenly into two sets: those that remain finite, and those that become infinite. We. argue that the former satisfy conventional Bethe equations, while the latter satisfy a. generalization of the Richardson-Gaudin equations. We derive an expression for the. leading correction to the boundary energy in terms of the boundary parameters. We argue that the Hamiltonians for A(2) 2n open quantum spin chains

  18. 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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2014-03-01

    Phosphodiesterase-4B (PDE4B) regulates the pro-inflammatory Toll Receptor -Tumor Necrosis Factor α (TNFα) pathway in monocytes, macrophages and microglial cells. As such, it is an important, although under-exploited molecular target for anti-inflammatory drugs. This is due in part to the difficulty of developing selective PDE4B inhibitors as the amino acid sequence of the PDE4 active site is identical in all PDE4 subtypes (PDE4A-D). We show that highly selective PDE4B inhibitors can be designed by exploiting sequence differences outside the active site. Specifically, PDE4B selectivity can be achieved by capture of a C-terminal regulatory helix, now termed CR3 (Control Region 3), across the active site in a conformation that closes access by cAMP. PDE4B selectivity is driven by a single amino acid polymorphism in CR3 (Leu674 in PDE4B1 versus Gln594 in PDE4D). The reciprocal mutations in PDE4B and PDE4D cause a 70-80 fold shift in selectivity. Our structural studies show that CR3 is flexible and can adopt multiple orientations and multiple registries in the closed conformation. The new co-crystal structure with bound ligand provides a guide map for the design of PDE4B selective anti-inflammatory drugs. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  1. 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. © 2015 Poulsen et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  2. 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…

  3. 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

  4. 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…

  5. 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…

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

    PubMed Central

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

    2007-01-01

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

  7. 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…

  8. 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.

  9. 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.

  10. Polyfunctional Lewis acids: intriguing solid-state structure and selective detection and discrimination of nitroaromatic explosives.

    PubMed

    Swamy P, Chinna Ayya; Thilagar, Pakkirisamy

    2015-06-08

    Synthesis and crystal structures of three porphyrin-based polyfunctional Lewis acids 1-3 are reported. Intermolecular HgCl⋅⋅⋅HgCl (linear and μ-type) interactions in the solid state of the peripherally ArHgCl-decorated compound 3 lead to a fascinating 3D supramolecular architecture. Compound 3 shows a selective fluorescence quenching response to picric acid and discriminates other nitroaromatic-based explosives. For the first time, an electron-deficient polyfunctional Lewis acid is shown to be useful for the selective detection and discrimination of nitroaromatic explosives. The Stern-Volmer quenching constant and detection limits of compound 3 for picric acid are the best among the reported small-molecular receptors for nitroaromatic explosives. The electronic structure, Lewis acidity, and selective sensing characteristics of 3 are well corroborated by DFT calculations. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. 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.

  12. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2014-11-01

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

  14. Topical management of facial burns.

    PubMed

    Leon-Villapalos, Jorge; Jeschke, Marc G; Herndon, David N

    2008-11-01

    The face is the central point of the physical features of the human being. It transmits expressions and emotions, communicates feelings and allows for individual identity. It contains complex musculature and a pliable and unique skin envelope that reacts to the environment through a vast network of nerve endings. The face hosts vital areas that make phonation, feeding, and vision possible. Facial burns disrupt these anatomical and functional structures creating pain, deformity, swelling, and contractures that may lead to lasting physical and psychological sequelae. The management of facial burns may include operative and non-operative treatment or both, depending on the depth and extent of the burn. This paper intends to provide a review of the available options for topical management of facial burns. Topical agents will be defined as any agent applied to the surface of the skin that alters the outcome of the facial burn. Therefore, the classic concept of topical therapy will be expanded and developed within two major stages: acute and rehabilitation. Comparison of the effectiveness of the different treatments and relevant literature will be discussed.

  15. Housing: Topic Paper F.

    ERIC Educational Resources Information Center

    National Council on the Handicapped, Washington, DC.

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

  16. Integrating Local Governmental Topics.

    ERIC Educational Resources Information Center

    Centner, Terence J.

    1994-01-01

    Students who pursue business and professional careers in natural resources and life science (NRLS) will have a decided need for a basic understanding of local government topics that shape public policy. Suggests that a responsible curriculum in NRLS should provide students with opportunities to explore these issues, and discusses methods for…

  17. Diclofenac Topical (actinic keratosis)

    MedlinePlus

    Solaraze® Gel ... Diclofenac topical gel (Solaraze) is used to treat actinic keratosis (flat, scaly growths on the skin caused by too much sun ... nonsteroidal anti-inflammatory drugs (NSAIDs). The way diclofenac gel works to treat actinic keratosis is not known. ...

  18. 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,…

  19. 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,…

  20. 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…

  1. Network Structure and Selection Asymmetry Drive Coevolution in Species-Rich Antagonistic Interactions.

    PubMed

    Andreazzi, Cecilia S; Thompson, John N; Guimarães, Paulo R

    2017-07-01

    Ecological interactions shape and are shaped by the evolution of interacting species. Mathematical models and empirical work have explored the multiple ways coevolution could occur in small sets of species, revealing that the addition of even one species can change the coevolutionary dynamics of a pairwise interaction. As a consequence, one of the current challenges in evolutionary biology is to understand how species-rich assemblages evolve and coevolve as networks of interacting species. We combined an adaptive network framework, a trait evolutionary model, and data on network structure to study how network organization affects and is affected by selection in antagonistic interactions such as parasitism, predation, and herbivory. We explored how selection imposed by interactions shapes the evolution of attack and defense traits, parameterizing our models with structural information from 31 empirical assemblages of antagonistic species. In the simulations, the form of coevolution in antagonistic interactions is affected by the intensity and asymmetry of the selection imposed by the interacting partners. Transient escalation in attack and defensive traits was the most prevalent form of coevolutionary dynamics, especially in networks formed by modules of highly interacting species. Fluctuating evolution of traits was observed when the intensity of selection was higher in exploiters than in victims and was especially favored in nested networks. At the species level, highly connected species experienced higher temporal variation in selection regardless of the network structure, resulting in high trait mismatching with their partners. The mismatched patterns of highly connected species, in turn, may explain the emergence of modularity in antagonistic interactions in which selection is stronger on exploiters than on their victims. Our results highlight the roles of different aspects of network structure on antagonistic coevolution: nestedness shapes coevolutionary

  2. 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.

  3. Approaches to optimum selection of space-planning and structural solutions of low-rise buildings

    NASA Astrophysics Data System (ADS)

    Gusakova, Natalya; Minaev, Nikolay; Filushina, Kristina; Gusakov, Alexander

    2017-01-01

    The paper is devoted to the development of approaches to optimum selection of space-planning and structural solutions of low-rise buildings for different kinds of territories. The aim of the study is to develop a system of criteria that influence the choice of optimum space-planning and structural solutions of buildings and structures aimed at enhancement of capital investment efficiency, energy and resource efficiency and creating comfortable living conditions for people. Developed solutions can be applied during implementation of investment construction projects of low-rise housing at different kinds of territories based on the local building materials.

  4. 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.

  5. 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)

  6. 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.

  7. 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

  8. 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

  9. 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.

  10. 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

  11. Quaternary ammonium surfactant structure determines selective toxicity towards bacteria: mechanisms of action and clinical implications in antibacterial prophylaxis.

    PubMed

    Inácio, Ângela S; Domingues, Neuza S; Nunes, Alexandra; Martins, Patrícia T; Moreno, Maria J; Estronca, Luís M; Fernandes, Rui; Moreno, António J M; Borrego, Maria J; Gomes, João P; Vaz, Winchil L C; Vieira, Otília V

    2016-03-01

    Broad-spectrum antimicrobial activity of quaternary ammonium surfactants (QAS) makes them attractive and cheap topical prophylactic options for sexually transmitted infections and perinatal vertically transmitted urogenital infections. Although attributed to their high affinity for biological membranes, the mechanisms behind QAS microbicidal activity are not fully understood. We evaluated how QAS structure affects antimicrobial activity and whether this can be exploited for use in prophylaxis of bacterial infections. Acute toxicity of QAS to in vitro models of human epithelial cells and bacteria were compared to identify selective and potent bactericidal agents. Bacterial cell viability, membrane integrity, cell cycle and metabolism were evaluated to establish the mechanisms involved in selective toxicity of QAS. QAS toxicity normalized relative to surfactant critical micelle concentration showed n-dodecylpyridinium bromide (C12PB) to be the most effective, with a therapeutic index of ∼10 for an MDR strain of Escherichia coli and >20 for Neisseria gonorrhoeae after 1 h of exposure. Three modes of QAS antibacterial action were identified: impairment of bacterial energetics and cell division at low concentrations; membrane permeabilization and electron transport inhibition at intermediate doses; and disruption of bacterial membranes and cell lysis at concentrations close to the critical micelle concentration. In contrast, toxicity to mammalian cells occurs at higher concentrations and, as we previously reported, results primarily from mitochondrial dysfunction and apoptotic cell death. Our data show that short chain (C12) n-alkyl pyridinium bromides have a sufficiently large therapeutic window to be good microbicide candidates. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  12. Orbital selective pairing and gap structures of iron-based superconductors

    NASA Astrophysics Data System (ADS)

    Kreisel, Andreas; Andersen, Brian M.; Sprau, P. O.; Kostin, A.; Davis, J. C. Séamus; Hirschfeld, P. J.

    2017-05-01

    We discuss the influence on spin-fluctuation pairing theory of orbital selective strong correlation effects in Fe-based superconductors, particularly Fe chalcogenide systems. We propose that a key ingredient for an improved itinerant pairing theory is orbital selectivity, i.e., incorporating the reduced coherence of quasiparticles occupying specific orbital states. This modifies the usual spin-fluctuation theory via suppression of pair scattering processes involving those less coherent states and results in orbital selective Cooper pairing of electrons in the remaining states. We show that this paradigm yields remarkably good agreement with the experimentally observed anisotropic gap structures in both bulk and monolayer FeSe, as well as LiFeAs, indicating that orbital selective Cooper pairing plays a key role in the more strongly correlated iron-based superconductors.

  13. Tactile friction of topical formulations.

    PubMed

    Skedung, L; Buraczewska-Norin, I; Dawood, N; Rutland, M W; Ringstad, L

    2016-02-01

    The tactile perception is essential for all types of topical formulations (cosmetic, pharmaceutical, medical device) and the possibility to predict the sensorial response by using instrumental methods instead of sensory testing would save time and cost at an early stage product development. Here, we report on an instrumental evaluation method using tactile friction measurements to estimate perceptual attributes of topical formulations. Friction was measured between an index finger and an artificial skin substrate after application of formulations using a force sensor. Both model formulations of liquid crystalline phase structures with significantly different tactile properties, as well as commercial pharmaceutical moisturizing creams being more tactile-similar, were investigated. Friction coefficients were calculated as the ratio of the friction force to the applied load. The structures of the model formulations and phase transitions as a result of water evaporation were identified using optical microscopy. The friction device could distinguish friction coefficients between the phase structures, as well as the commercial creams after spreading and absorption into the substrate. In addition, phase transitions resulting in alterations in the feel of the formulations could be detected. A correlation was established between skin hydration and friction coefficient, where hydrated skin gave rise to higher friction. Also a link between skin smoothening and finger friction was established for the commercial moisturizing creams, although further investigations are needed to analyse this and correlations with other sensorial attributes in more detail. The present investigation shows that tactile friction measurements have potential as an alternative or complement in the evaluation of perception of topical formulations. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Coursework selection: a frame of reference approach using structural equation modelling.

    PubMed

    Dickhäuser, Oliver; Reuter, Martin; Hilling, Christine

    2005-12-01

    Choice behaviour has far-reaching consequences on students' educational careers. Previous models on course selection for example, the model of achievement-related choices (Wigfield & Eccles, 2000) and of self-efficacy theory (Bandura, 1997), stress the importance of ability perceptions (self-concept of ability) as major determinants of choice. This article suggests a model of course selection, which assumes that comparisons within an internal frame of reference (as proposed by Marsh, 1986, for the association between achievement and self-concepts) can also be applied to the association between self-concepts and course selection. It is therefore hypothesized that course selection is not only positively influenced by the self-concept with respect to the corresponding subject, but also negatively with respect to alternative subjects. Moreover, it should be tested whether the effects of previous achievement on course selection are completely mediated by the self-concepts. These assumptions were empirically tested using a sample of 296 students from secondary school classes, who were specializing in, for example, chemistry or biology in the following school term. Self-concepts and course selection were assessed via questionnaire. The postulated models were tested using a structural equation modelling approach for ordinal variables. The core assumption, that course selection is determined by dimensional comparisons, was supported by significant negative paths from self-concepts on the selection of non-corresponding subjects. Furthermore, the effects of previous achievement on selection were completely mediated by self-concepts. Previous models of choice behaviour should be extended, by considering not only the selected alternatives, but also the unselected ones. The finding that the influence of achievement on choice is completely mediated by self-concepts, demonstrates that subjective interpretations of previous achievement determine subsequent behaviour.

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

    PubMed

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

    2016-05-20

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

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. A cross-validation deletion–substitution–addition model selection algorithm: Application to marginal structural models

    PubMed Central

    Haight, Thaddeus J.; Wang, Yue; van der Laan, Mark J.; Tager, Ira B.

    2014-01-01

    The cross-validation deletion–substitution–addition (cvDSA) algorithm is based on data-adaptive estimation methodology to select and estimate marginal structural models (MSMs) for point treatment studies as well as models for conditional means where the outcome is continuous or binary. The algorithm builds and selects models based on user-defined criteria for model selection, and utilizes a loss function-based estimation procedure to distinguish between different model fits. In addition, the algorithm selects models based on cross-validation methodology to avoid “over-fitting” data. The cvDSA routine is an R software package available for download. An alternative R-package (DSA) based on the same principles as the cvDSA routine (i.e., cross-validation, loss function), but one that is faster and with additional refinements for selection and estimation of conditional means, is also available for download. Analyses of real and simulated data were conducted to demonstrate the use of these algorithms, and to compare MSMs where the causal effects were assumed (i.e., investigator-defined), with MSMs selected by the cvDSA. The package was used also to select models for the nuisance parameter (treatment) model to estimate the MSM parameters with inverse-probability of treatment weight (IPTW) estimation. Other estimation procedures (i.e., G-computation and double robust IPTW) are available also with the package. PMID:25505354

  1. The Role of Evolutionary Selection in the Dynamics of Protein Structure Evolution.

    PubMed

    Gilson, Amy I; Marshall-Christensen, Ahmee; Choi, Jeong-Mo; Shakhnovich, Eugene I

    2017-04-11

    Homology modeling is a powerful tool for predicting a protein's structure. This approach is successful because proteins whose sequences are only 30% identical still adopt the same structure, while structure similarity rapidly deteriorates beyond the 30% threshold. By studying the divergence of protein structure as sequence evolves in real proteins and in evolutionary simulations, we show that this nonlinear sequence-structure relationship emerges as a result of selection for protein folding stability in divergent evolution. Fitness constraints prevent the emergence of unstable protein evolutionary intermediates, thereby enforcing evolutionary paths that preserve protein structure despite broad sequence divergence. However, on longer timescales, evolution is punctuated by rare events where the fitness barriers obstructing structure evolution are overcome and discovery of new structures occurs. We outline biophysical and evolutionary rationale for broad variation in protein family sizes, prevalence of compact structures among ancient proteins, and more rapid structure evolution of proteins with lower packing density. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  2. 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.

  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. 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.

  5. 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.

  6. 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.

  7. R-gene variation across Arabidopsis lyrata subspecies: effects of population structure, selection and mating system.

    PubMed

    Buckley, James; Kilbride, Elizabeth; Cevik, Volkan; Vicente, Joana G; Holub, Eric B; Mable, Barbara K

    2016-05-05

    Examining allelic variation of R-genes in closely related perennial species of Arabidopsis thaliana is critical to understanding how population structure and ecology interact with selection to shape the evolution of innate immunity in plants. We finely sampled natural populations of Arabidopsis lyrata from the Great Lakes region of North America (A. l. lyrata) and broadly sampled six European countries (A. l. petraea) to investigate allelic variation of two R-genes (RPM1 and WRR4) and neutral genetic markers (Restriction Associated DNA sequences and microsatellites) in relation to mating system, phylogeographic structure and subspecies divergence. Fine-scale sampling of populations revealed strong effects of mating system and population structure on patterns of polymorphism for both neutral loci and R-genes, with no strong evidence for selection. Broad geographic sampling revealed evidence of balancing selection maintaining polymorphism in R-genes, with elevated heterozygosity and diversity compared to neutral expectations and sharing of alleles among diverged subspecies. Codon-based tests detected both positive and purifying selection for both R-genes, as commonly found for animal immune genes. Our results highlight that combining fine and broad-scale sampling strategies can reveal the multiple factors influencing polymorphism and divergence at potentially adaptive genes such as R-genes.

  8. Structural insight into selectivity and resistance profiles of ROS1 tyrosine kinase inhibitors.

    PubMed

    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

    2015-09-29

    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-ROS1(G2032R) 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.

  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. 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

  12. ProSelection: A novel algorithm to select proper protein structure subsets for in silico target identification and drug discovery research.

    PubMed

    Wang, Nanyi; Wang, Lirong; Xie, Xiang-Qun Sean

    2017-10-10

    Molecular docking is widely applied to computer-aided drug design and has become relatively mature in the recent decades. Application of docking in modeling varies from single lead compound optimization to large-scale virtual screening. The performance of molecular docking is highly dependent on the protein structures selected. It is especially challenging for large-scale target prediction research when multiple structures are available for a single target. Therefore, we have established ProSelection, a docking preferred-protein selection algorithm, in order to generate the proper structure subset(s). By ProSelection algorithm, protein structures of "weak selector" are filtered out whereas structures of "strong selector" are kept. Specifically, the structure which has a good statistical performance of distinguishing active ligands from inactive ligands is defined as a "strong selector". In this study, 249 protein structures of 14 autophagy-related targets are investigated. Surflex-dock was used as the docking engine to distinguish active and inactive compounds against these protein structures. Both t-test and Mann-Whitney U test were used to distinguish the "strong selector" from "weak selector" based on the normality of the docking score distribution. The suggested docking score threshold for active ligands (SDA) was generated for each "strong selector" structure according to the receiver operating characteristic (ROC) curve. The performance of ProSelection was further validated by predicting the potential off-targets of 43 FDA-approved small molecule antineoplastic drugs. Overall, ProSelection will accelerate the computational work in protein structure selection and could be a useful tool for molecular docking, target prediction, and protein-chemical database establishment research.

  13. 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

  14. 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.

  15. 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.

  16. 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.

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

    PubMed Central

    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.

    2017-01-01

    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. PMID:28039433

  18. Competition dialysis: a method for the study of structural selective nucleic acid binding.

    PubMed

    Ragazzon, Patricia A; Garbett, Nichola C; Chaires, Jonathan B

    2007-06-01

    Competition dialysis is a powerful new tool for the discovery of ligands that bind to nucleic acids with structural- or sequence-selectivity. The method is based on firm thermodynamic principles and is simple to implement. In the competition dialysis experiment, an array of nucleic acid structures and sequences is dialyzed against a common test ligand solution. After equilibration, the amount of ligand bound to each structure or sequence is determined by absorbance or fluorescence measurements. Since all structures and sequences are in equilibrium with the same free ligand concentration, the amount bound is directly proportional to the ligand binding affinity. Competition dialysis thus provides a direct and quantitative measure of selectivity, and unambiguously identifies which of the samples within the array are preferred by a particular ligand. We describe here the third generation implementation of the method, in which competition dialysis was adapted for use in a 96-well plate format. In this format, we have been able to greatly expand the array of nucleic acid structures studied, and now can routinely study the interactions of a ligand of interest with 46 different structures and sequences.

  19. 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

  20. 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

  1. Selectivity of small molecule ligands for parallel and anti-parallel DNA G-quadruplex structures.

    PubMed

    Garner, Thomas P; Williams, Huw E L; Gluszyk, Katarzyna I; Roe, Stephen; Oldham, Neil J; Stevens, Malcolm F G; Moses, John E; Searle, Mark S

    2009-10-21

    We report CD, ESI-MS and molecular modelling studies of ligand binding interactions with DNA quadruplex structures derived from the human telomeric repeat sequence (h-Tel) and the proto-oncogenic c-kit promoter sequence. These sequences form anti-parallel (both 2 + 2 and 3 + 1) and parallel conformations, respectively, and demonstrate distinctively different degrees of structural plasticity in binding ligands. With h-Tel, we show that an extended heteroaromatic 1,4-triazole (TRZ), designed to exploit pi-stacking interactions and groove-specific contacts, shows some selectivity for parallel folds, however, the polycyclic fluorinated acridinium cation (RHPS4), which is a similarly potent telomerase inhibitor, shows selectivity for anti-parallel conformations implicating favourable interactions with lateral and diagonal loops. In contrast, the unique c-kit parallel-stranded quadruplex shows none of the structural plasticity of h-Tel with either ligand. We show by quantitative ESI-MS analysis that both sequences are able to bind a ligand on either end of the quadruplex. In the case of h-Tel the two sites have similar affinities, however, in the case of the c-kit quadruplex the affinities of the two sites are different and ligand-dependent. We demonstrate that two different small molecule architectures result in significant differences in selectivity for parallel and anti-parallel quadruplex structures that may guide quadruplex targeted drug-design.

  2. Optimizing Stem Length To Improve Ligand Selectivity in a Structure-Switching Cocaine-Binding Aptamer.

    PubMed

    Neves, Miguel A D; Shoara, Aron A; Reinstein, Oren; Abbasi Borhani, Okty; Martin, Taylor R; Johnson, Philip E

    2017-10-02

    Understanding how aptamer structure and function are related is crucial in the design and development of aptamer-based biosensors. We have analyzed a series of cocaine-binding aptamers with different lengths of their stem 1 in order to understand the role that this stem plays in the ligand-induced structure-switching binding mechanism utilized in many of the sensor applications of this aptamer. In the cocaine-binding aptamer, the length of stem 1 controls whether the structure-switching binding mechanism for this aptamer occurs or not. We varied the length of stem 1 from being one to seven base pairs long and found that the structural transition from unfolded to folded in the unbound aptamer is when the aptamer elongates from 3 to 4 base pairs in stem 1. We then used this knowledge to achieve new binding selectivity of this aptamer for quinine over cocaine by using an aptamer with a stem 1 two base pairs long. This selectivity is achieved by means of the greater affinity quinine has for the aptamer compared with cocaine. Quinine provides enough free energy to both fold and bind the 2-base pair-long aptamer while cocaine does not. This tuning of binding selectivity of an aptamer by reducing its stability is likely a general mechanism that could be used to tune aptamer specificity for tighter binding ligands.

  3. 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.

  4. 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.

  5. 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.

  6. Topical peptides as cosmeceuticals.

    PubMed

    Pai, Varadraj Vasant; Bhandari, Prasana; Shukla, Pankaj

    2017-01-01

    Peptides are known to have diverse biological roles, most prominently as signaling/regulatory molecules in a broad variety of physiological processes including defense, immunity, stress, growth, homeostasis and reproduction. These aspects have been used in the field of dermatology and cosmetology to produce short, stable and synthetic peptides for extracellular matrix synthesis, pigmentation, innate immunity and inflammation. The evolution of peptides over the century, which started with the discovery of penicillin, has now extended to their usage as cosmeceuticals in recent years. Cosmeceutical peptides may act as signal modulators of the extracellular matrix component, as structural peptides, carrier peptides and neurotransmitter function modulators. Transdermal delivery of peptides can be made more effective by penetration enhancers, chemical modification or encapsulation of peptides. The advantages of using peptides as cosmeceuticals include their involvement in many physiological functions of the skin, their selectivity, their lack of immunogenicity and absence of premarket regulatory requirements for their use. However, there are disadvantages: clinical evidence for efficacy is often weak, absorption may be poor due to low lipophilicity, high molecular weight and binding to other ingredients, and prices can be quite high.

  7. 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.

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-01-01

    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. 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. 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 is based on the nationality or residence, which the insured by

  10. Competition between Coiled-Coil Structures and the Impact on Myosin-10 Bundle Selection.

    PubMed

    Vavra, Kevin C; Xia, Youlin; Rock, Ronald S

    2016-06-07

    Coiled-coil fusions are a useful approach to enforce dimerization in protein engineering. However, the final structures of coiled-coil fusion proteins have received relatively little attention. Here, we determine the structural outcome of adjacent parallel and antiparallel coiled coils. The targets are coiled coils that stabilize myosin-10 in single-molecule biophysical studies. We reveal the solution structure of a short, antiparallel, myosin-10 coiled-coil fused to the parallel GCN4-p1 coiled coil. Surprisingly, this structure is a continuous, antiparallel coiled coil where GCN4-p1 pairs with myosin-10 rather than itself. We also show that longer myosin-10 segments in these parallel/antiparallel fusions are dynamic and do not fold cooperatively. Our data resolve conflicting results on myosin-10 selection of actin filament bundles, demonstrating the importance of understanding coiled-coil orientation and stability. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  11. 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.

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

    PubMed

    Zhao, Kuiwen; Wu, Huiying

    2015-04-28

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

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

    NASA Astrophysics Data System (ADS)

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

    1987-07-01

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

  14. 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.

  15. 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.

  16. Genomic Hypomethylation in the Human Germline Associates with Selective Structural Mutability in the Human Genome

    PubMed Central

    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. PMID:22615578

  17. Three-Dimensional Virtual Bone Bank System Workflow for Structural Bone Allograft Selection: A Technical Report

    PubMed Central

    Ritacco, Lucas Eduardo; Farfalli, German Luis; Milano, Federico Edgardo; Ayerza, Miguel Angel; Muscolo, Domingo Luis

    2013-01-01

    Structural bone allograft has been used in bone defect reconstruction during the last fifty years with acceptable results. However, allograft selection methods were based on 2-dimensional templates using X-rays. Thanks to preoperative planning platforms, three-dimensional (3D) CT-derived bone models were used to define size and shape comparison between host and donor. The purpose of this study was to describe the workflow of this virtual technique in order to explain how to choose the best allograft using a virtual bone bank system. We measured all bones in a 3D virtual environment determining the best match. The use of a virtual bone bank system has allowed optimizing the allograft selection in a bone bank, providing more information to the surgeons before surgery. In conclusion, 3D preoperative planning in a virtual environment for allograft selection is an important and helpful tool in order to achieve a good match between host and donor. PMID:23690733

  18. Structure-functional selectivity relationship studies of β-arrestin-biased dopamine D₂ receptor agonists.

    PubMed

    Chen, Xin; Sassano, Maria F; Zheng, Lianyou; Setola, Vincent; Chen, Meng; Bai, Xu; Frye, Stephen V; Wetsel, William C; Roth, Bryan L; Jin, Jian

    2012-08-23

    Functionally selective G protein-coupled receptor (GPCR) ligands, which differentially modulate canonical and noncanonical signaling, are extremely useful for elucidating key signal transduction pathways essential for both the therapeutic actions and side effects of drugs. However, few such ligands have been created, and very little purposeful attention has been devoted to studying what we term: "structure-functional selectivity relationships" (SFSR). We recently disclosed the first β-arrestin-biased dopamine D(2) receptor (D(2)R) agonists UNC9975 (44) and UNC9994 (36), which have robust in vivo antipsychotic drug-like activities. Here we report the first comprehensive SFSR studies focused on exploring four regions of the aripiprazole scaffold, which resulted in the discovery of these β-arrestin-biased D(2)R agonists. These studies provide a successful proof-of-concept for how functionally selective ligands can be discovered.

  19. 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

  20. 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.