WorldWideScience

Sample records for allosteric hot spots

  1. Reactor hot spot analysis

    Energy Technology Data Exchange (ETDEWEB)

    Vilim, R.B.

    1985-08-01

    The principle methods for performing reactor hot spot analysis are reviewed and examined for potential use in the Applied Physics Division. The semistatistical horizontal method is recommended for future work and is now available as an option in the SE2-ANL core thermal hydraulic code. The semistatistical horizontal method is applied to a small LMR to illustrate the calculation of cladding midwall and fuel centerline hot spot temperatures. The example includes a listing of uncertainties, estimates for their magnitudes, computation of hot spot subfactor values and calculation of two sigma temperatures. A review of the uncertainties that affect liquid metal fast reactors is also presented. It was found that hot spot subfactor magnitudes are strongly dependent on the reactor design and therefore reactor specific details must be carefully studied. 13 refs., 1 fig., 5 tabs.

  2. Coulomb explosion of "hot spot"

    CERN Document Server

    Oreshkin, V I; Chaikovsky, S A; Artyomov, A P

    2016-01-01

    The study presented in this paper has shown that the generation of hard x rays and high-energy ions, which are detected in pinch implosion experiments, may be associated with the Coulomb explosion of the hot spot that is formed due to the outflow of the material from the pinch cross point. During the process of material outflow, the temperature of the hot spot plasma increases, and conditions arise for the plasma electrons to become continuously accelerated. The runaway of electrons from the hot spot region results in the buildup of positive space charge in this region followed by a Coulomb explosion. The conditions for the hot spot plasma electrons to become continuously accelerated have been revealed and estimates have been obtained for the kinetic energy of the ions generated by the Coulomb explosion.

  3. ESA uncovers Geminga's `hot spot'

    Science.gov (United States)

    2004-07-01

    16 July 2004 Astronomers using ESA’s X-ray observatory XMM-Newton have detected a small, bright ‘hot spot’ on the surface of the neutron star called Geminga, 500 light-years away. The hot spot is the size of a football field and is caused by the same mechanism producing Geminga’s X-ray tails. This discovery identifies the missing link between the X-ray and gamma-ray emission from Geminga. hi-res Size hi-res: 1284 kb Credits: ESA, P. Caraveo (IASF, Milan) Geminga's hot spot This figure shows the effects of charged particles accelerated in the magnetosphere of Geminga. Panel (a) shows an image taken with the EPIC instrument on board the XMM-Newton observatory. The bright tails, made of particles kicked out by Geminga’s strong magnetic field, trail the neutron star as it moves about in space. Panel (b) shows how electrically charged particles interact with Geminga’s magnetic field. For example, if electrons (blue) are kicked out by the star, positrons (in red) hit the star’s magnetic poles like in an ‘own goal’. Panel (c) illustrates the size of Geminga’s magnetic field (blue) compared to that of the star itself at the centre (purple). The magnetic field is tilted with respect to Geminga’s rotation axis (red). Panel (d) shows the magnetic poles of Geminga, where charged particles hit the surface of the star, creating a two-million degrees hot spot, a region much hotter than the surroundings. As the star spins on its rotation axis, the hot spot comes into view and then disappears, causing the periodic colour change seen by XMM-Newton. An animated version of the entire sequence can be found at: Click here for animated GIF [low resolution, animated GIF, 5536 KB] Click here for AVI [high resolution, AVI with DIVX compression, 19128 KB] hi-res Size hi-res: 371 kb Credits: ESA, P. Caraveo (IASF, Milan) Geminga's hot spot, panel (a) Panel (a) shows an image taken with the EPIC instrument on board the XMM-Newton observatory. The bright tails, made of

  4. Computational Prediction of Hot Spot Residues

    OpenAIRE

    Morrow, John Kenneth; Zhang, Shuxing

    2012-01-01

    Most biological processes involve multiple proteins interacting with each other. It has been recently discovered that certain residues in these protein-protein interactions, which are called hot spots, contribute more significantly to binding affinity than others. Hot spot residues have unique and diverse energetic properties that make them challenging yet important targets in the modulation of protein-protein complexes. Design of therapeutic agents that interact with hot spot residues has pr...

  5. Hot Spot Removal System: System description

    International Nuclear Information System (INIS)

    Hazardous wastes contaminated with radionuclides, chemicals, and explosives exist across the Department of Energy complex and need to be remediated due to environmental concerns. Currently, an opportunity is being developed to dramatically reduce remediation costs and to assist in the acceleration of schedules associated with these wastes by deploying a Hot Spot Removal System. Removing the hot spot from the waste site will remove risk driver(s) and enable another, more cost effective process/option/remedial alternative (i.e., capping) to be applied to the remainder of the site. The Hot Spot Removal System consists of a suite of technologies that will be utilized to locate and remove source terms. Components of the system can also be used in a variety of other cleanup activities. This Hot Spot Removal System Description document presents technologies that were considered for possible inclusion in the Hot Spot Removal System, technologies made available to the Hot Spot Removal System, industrial interest in the Hot Spot Removal System''s subsystems, the schedule required for the Hot Spot Removal System, the evaluation of the relevant technologies, and the recommendations for equipment and technologies as stated in the Plan section

  6. Hot Spot Removal System: System description

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-09-01

    Hazardous wastes contaminated with radionuclides, chemicals, and explosives exist across the Department of Energy complex and need to be remediated due to environmental concerns. Currently, an opportunity is being developed to dramatically reduce remediation costs and to assist in the acceleration of schedules associated with these wastes by deploying a Hot Spot Removal System. Removing the hot spot from the waste site will remove risk driver(s) and enable another, more cost effective process/option/remedial alternative (i.e., capping) to be applied to the remainder of the site. The Hot Spot Removal System consists of a suite of technologies that will be utilized to locate and remove source terms. Components of the system can also be used in a variety of other cleanup activities. This Hot Spot Removal System Description document presents technologies that were considered for possible inclusion in the Hot Spot Removal System, technologies made available to the Hot Spot Removal System, industrial interest in the Hot Spot Removal System`s subsystems, the schedule required for the Hot Spot Removal System, the evaluation of the relevant technologies, and the recommendations for equipment and technologies as stated in the Plan section.

  7. HotSpot Software Configuration Management Plan

    Energy Technology Data Exchange (ETDEWEB)

    Walker, H; Homann, S G

    2009-03-12

    This Software Configuration Management Plan (SCMP) describes the software configuration management procedures used to ensure that the HotSpot dispersion model meets the requirements of its user base, which includes: (1) Users of the PC version of HotSpot for consequence assessment, hazard assessment and safety analysis calculations; and (2) Users of the NARAC Web and iClient software tools, which allow users to run HotSpot for consequence assessment modeling These users and sponsors of the HotSpot software and the organizations they represent constitute the intended audience for this document. This plan is intended to meet Critical Recommendations 1 and 3 from the Software Evaluation of HotSpot and DOE Safety Software Toolbox Recommendation for inclusion of HotSpot in the Department of Energy (DOE) Safety Software Toolbox. HotSpot software is maintained for the Department of Energy Office of Emergency Operations by the National Atmospheric Release Advisory Center (NARAC) at Lawrence Livermore National Laboratory (LLNL). An overview of HotSpot and NARAC are provided.

  8. Hot spots in fiber pinches

    International Nuclear Information System (INIS)

    Results are presented on the behavior of ''bright spots'' in carbon and deuterium fiber Z-pinches using the MAGPIE generator at the I MA current level. The experimental diagnosis was carried out using optical and X-ray framing and streak images, along with Schlieren and shadowgraphy laser probing. After a short (∼4 ns) duration formation phase, these bright spots exhibit highly dynamic behavior. Bifurcation of the bright spots gives rise to rapid axial motion at 1-3x105 m/sec. The post-bifurcation bright spots persist for up to 40 ns. The important features of bright spot evolution can be reproduced using a 2-D MHD code incorporating LTE ionization dynamics and cold start conditions. Construction of ''artificial'' diagnostic images from the simulation data allows direct comparison to experiment. From the close agreement between experiment and 2-D simulation we infer that the observed bright spot behavior can be explained entirely in terms of the non-linear evolution of the m=0 instability

  9. Statistical Hot Spot Model for Explosive Detonation

    Energy Technology Data Exchange (ETDEWEB)

    Nichols, III, A L

    2005-07-14

    The Non-local Thermodynamic Equilibrium Statistical Hot Spot Model (NLTE SHS), a new model for explosive detonation, is described. In this model, the formation, ignition, propagation, and extinction of hot spots is explicitly modeled. The equation of state of the explosive mixture is treated with a non-local equilibrium thermodynamic assumption. A methodology for developing the parameters for the model is discussed, and applied to the detonation velocity diameter effect. Examination of these results indicates where future improvements to the model can be made.

  10. Statistical Hot Spot Model for Explosive Detonation

    Energy Technology Data Exchange (ETDEWEB)

    Nichols III, A L

    2004-05-10

    The Non-local Thermodynamic Equilibrium Statistical Hot Spot Model (NLTE SHS), a new model for explosive detonation, is described. In this model, the formation, ignition, propagation, and extinction of hot spots is explicitly modeled. The equation of state of the explosive mixture is treated with a nonlocal equilibrium thermodynamic assumption. A methodology for developing the parameters for the model is discussed, and applied to the detonation velocity diameter effect. Examination of these results indicates where future improvements to the model can be made.

  11. Analysis of Binding Site Hot Spots on the Surface of Ras GTPase

    Energy Technology Data Exchange (ETDEWEB)

    Buhrman, Greg; O; #8242; Connor, Casey; Zerbe, Brandon; Kearney, Bradley M.; Napoleon, Raeanne; Kovrigina, Elizaveta A.; Vajda, Sandor; Kozakov, Dima; Kovrigin, Evgenii L.; Mattos, Carla (NCSU); (MCW); (BU)

    2012-09-17

    We have recently discovered an allosteric switch in Ras, bringing an additional level of complexity to this GTPase whose mutants are involved in nearly 30% of cancers. Upon activation of the allosteric switch, there is a shift in helix 3/loop 7 associated with a disorder to order transition in the active site. Here, we use a combination of multiple solvent crystal structures and computational solvent mapping (FTMap) to determine binding site hot spots in the 'off' and 'on' allosteric states of the GTP-bound form of H-Ras. Thirteen sites are revealed, expanding possible target sites for ligand binding well beyond the active site. Comparison of FTMaps for the H and K isoforms reveals essentially identical hot spots. Furthermore, using NMR measurements of spin relaxation, we determined that K-Ras exhibits global conformational dynamics very similar to those we previously reported for H-Ras. We thus hypothesize that the global conformational rearrangement serves as a mechanism for allosteric coupling between the effector interface and remote hot spots in all Ras isoforms. At least with respect to the binding sites involving the G domain, H-Ras is an excellent model for K-Ras and probably N-Ras as well. Ras has so far been elusive as a target for drug design. The present work identifies various unexplored hot spots throughout the entire surface of Ras, extending the focus from the disordered active site to well-ordered locations that should be easier to target.

  12. Research Hot Spots of Black Peanut

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    Taking the research papers on black peanut in National Knowledge Infrastructure(CNKI)as data sources,we determine the research hot spots on black peanut using word frequency analysis,and analyze the main research directions that change over the years.The results show that the relevant researches on black peanut are mainly concentrated in six themes(study of varieties,physiological property,cultivation management,development prospects,relationship with agriculture,and molecular level);varieties,physiology,cultivation and other aspects are the focus of current research hot spots;the researches on selection and breeding of variety and various physiological and ecological mechanisms,still need a breakthrough.

  13. Amorphous-silicon module hot-spot testing

    Science.gov (United States)

    Gonzalez, C. C.

    1985-01-01

    Hot spot heating occurs when cell short-circuit current is lower than string operating current. Amorphous cell hot spot are tested to develop the techniques required for performing reverse bias testing of amorphous cells. Also, to quantify the response of amorphous cells to reverse biasing. Guidelines are developed from testing for reducing hot spot susceptibility of amorphous modules and to develop a qualification test for hot spot testing of amorphous modules. It is concluded that amorphous cells undergo hot spot heating similarly to crystalline cells. Comparison of results obtained with submodules versus actual modules indicate heating levels lower in actual modules. Module design must address hot spot testing and hot spot qualification test conducted on modules showed no instabilities and minor cell erosion.

  14. Dispersion of hot spots in steam generators

    International Nuclear Information System (INIS)

    The streamwise development of hot spots in a helical type heat exchanger has been treated experimentally and theoretically as well. Velocity profiles across the bundle have been measured varying the Reynolds number, Re, from 103 to 1.35 x 105. Pressurized air or helium have been applied as coolant. In an additional series of tests the length scale parameter of the turbulence structure has been determined. It is correlated with the turbulent Peclet number, Pet, which occurs in the basic equation as an unknown parameter. Its value was found to be independent of Re (Pet = 8.2). Introducing this value leads to a good agreement of theoretical and experimental results. (author)

  15. Hot spot exercise: 1975 (HSX-75)

    International Nuclear Information System (INIS)

    A special unannounced exercise, called HOT SPOT Exercise--1975 (HSX-75), was prepared to test the general capability of the LLL ALERT Program to activate and deploy the LLL and Sandia Laboratory, Livermore (SLL) component of the ERDA/ARG. The exercise activities were limited to the LLL facilities in Livermore and the Site 300 explosive test facility located approximately 15 miles southeast of Livermore. The exercise simulated an accident at a U.S. Army storage facility (Site 300). The simulated accident involved two LLL designed weapons (W-70). One weapon was dropped during unloading operations and ignited the gas tank of the weapon transporter. The subsequent fire caused a low-order detonation of the high explosive component. The fire caused dispersal of fissile material downwind from the site. A second weapon was damaged in the explosion by fragments from the first weapon. The extent of damage to the second weapon was initially unknown. The exercise was conducted on September 23, 1975. A complete description of the specific nature of the simulated accident is contained in the scenario. Umpires were assigned to evaluate and subsequently report on the effectiveness of the response. All test objectives were accomplished. The following appendices are included: operational safety procedures, photographs and site map, HOT SPOT equipment, atmospheric release advisory capability, personnel list, chronology of events, and critique comments

  16. Protein determinants of meiotic DNA break hot spots

    OpenAIRE

    Fowler, Kyle R.; Gutiérrez-Velasco, Susana; Martín-Castellanos, Cristina; Smith, Gerald R.

    2013-01-01

    Meiotic recombination, crucial for proper chromosome segregation and genome evolution, is initiated by programmed DNA double-strand breaks (DSBs) in yeasts and likely all sexually reproducing species. In fission yeast, DSBs occur up to hundreds of times more frequently at special sites, called hot spots, than in other regions of the genome. What distinguishes hot spots from cold regions is an unsolved problem, although transcription factors determine some hot spots. We report the discovery th...

  17. KFC Server: interactive forecasting of protein interaction hot spots.

    Science.gov (United States)

    Darnell, Steven J; LeGault, Laura; Mitchell, Julie C

    2008-07-01

    The KFC Server is a web-based implementation of the KFC (Knowledge-based FADE and Contacts) model-a machine learning approach for the prediction of binding hot spots, or the subset of residues that account for most of a protein interface's; binding free energy. The server facilitates the automated analysis of a user submitted protein-protein or protein-DNA interface and the visualization of its hot spot predictions. For each residue in the interface, the KFC Server characterizes its local structural environment, compares that environment to the environments of experimentally determined hot spots and predicts if the interface residue is a hot spot. After the computational analysis, the user can visualize the results using an interactive job viewer able to quickly highlight predicted hot spots and surrounding structural features within the protein structure. The KFC Server is accessible at http://kfc.mitchell-lab.org. PMID:18539611

  18. Nuclear Hot Spot Factor of JMTR-LEU core

    International Nuclear Information System (INIS)

    The core conversion from MEU fuel to LEU fuel of the JMTR, a 50 MW light water moderated and cooled tank type reactor using ETR-type fuel, is scheduled in 1993. As a part of the safety analyses for JMTR LEU Core, the investigation of the Hot Spot Factor was carried out. This report describes the analytical methods and results of the Nuclear Hot Spot Factor of the Hot Spot Factor to be used in the thermohydraulic design and safety analysis of JMTR LEU Core. Factors of each compose of Nuclear Hot Spot Factor, which are based on neutronic calculations, were investigated. The maximum Nuclear Hot Spot Factor was 3.14. (author)

  19. An approach for addressing hard-to-detect hot spots.

    Science.gov (United States)

    Abelquist, Eric W; King, David A; Miller, Laurence F; Viars, James A

    2013-05-01

    The Multi-Agency Radiation Survey and Site Investigation Manual (MARSSIM) survey approach is comprised of systematic random sampling coupled with radiation scanning to assess acceptability of potential hot spots. Hot spot identification for some radionuclides may not be possible due to the very weak gamma or x-ray radiation they emit-these hard-to-detect nuclides are unlikely to be identified by field scans. Similarly, scanning technology is not yet available for chemical contamination. For both hard-to-detect nuclides and chemical contamination, hot spots are only identified via volumetric sampling. The remedial investigation and cleanup of sites under the Comprehensive Environmental Response, Compensation, and Liability Act typically includes the collection of samples over relatively large exposure units, and concentration limits are applied assuming the contamination is more or less uniformly distributed. However, data collected from contaminated sites demonstrate contamination is often highly localized. These highly localized areas, or hot spots, will only be identified if sample densities are high or if the environmental characterization program happens to sample directly from the hot spot footprint. This paper describes a Bayesian approach for addressing hard-to-detect nuclides and chemical hot spots. The approach begins using available data (e.g., as collected using the standard approach) to predict the probability that an unacceptable hot spot is present somewhere in the exposure unit. This Bayesian approach may even be coupled with the graded sampling approach to optimize hot spot characterization. Once the investigator concludes that the presence of hot spots is likely, then the surveyor should use the data quality objectives process to generate an appropriate sample campaign that optimizes the identification of risk-relevant hot spots. PMID:23528274

  20. Meteorology of Jupiter's Equatorial Hot Spots and Plumes from Cassini

    Science.gov (United States)

    Choi, David Sanghun; Showman, Adam P.; Vasavada, Ashwin R.; Simon-Miller, Amy A.

    2013-01-01

    We present an updated analysis of Jupiter's equatorial meteorology from Cassini observations. For two months preceding the spacecraft's closest approach, the Imaging Science Subsystem (ISS) onboard regularly imaged the atmosphere. We created time-lapse movies from this period in order to analyze the dynamics of equatorial hot spots and their interactions with adjacent latitudes. Hot spots are relatively cloud-free regions that emit strongly at 5 lm; improved knowledge of these features is crucial for fully understanding Galileo probe measurements taken during its descent through one. Hot spots are quasistable, rectangular dark areas on visible-wavelength images, with defined eastern edges that sharply contrast with surrounding clouds, but diffuse western edges serving as nebulous boundaries with adjacent equatorial plumes. Hot spots exhibit significant variations in size and shape over timescales of days and weeks. Some of these changes correspond with passing vortex systems from adjacent latitudes interacting with hot spots. Strong anticyclonic gyres present to the south and southeast of the dark areas appear to circulate into hot spots. Impressive, bright white plumes occupy spaces in between hot spots. Compact cirrus-like 'scooter' clouds flow rapidly through the plumes before disappearing within the dark areas. These clouds travel at 150-200 m/s, much faster than the 100 m/s hot spot and plume drift speed. This raises the possibility that the scooter clouds may be more illustrative of the actual jet stream speed at these latitudes. Most previously published zonal wind profiles represent the drift speed of the hot spots at their latitude from pattern matching of the entire longitudinal image strip. If a downward branch of an equatorially-trapped Rossby wave controls the overall appearance of hot spots, however, the westward phase velocity of the wave leads to underestimates of the true jet stream speed.

  1. Hot spots on Tc-99m MAA perfusion lung scan

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Seok Tae; Sohn, Myung Hee [Chonbuk National Univericity Medical School, Chonju (Korea, Republic of)

    2001-08-01

    A 61 year-old woman underwent perfusion and inhalation lung scan for the evaluation of pulmonary thromboembolism. Tc-99m MAA perfusion lung scan showed multiple round hot spots in both lung fields. Tc-99m DTPA aerosol inhalation lung scan and chest radiography taken at the same time showed normal findings. A repeated perfusion lung scan taken 24 hours later demonstrated no abnormalities. Hot spots on perfusion lung scan can be caused by microsphere clumping due to faulty injection technique by radioactive embolization from upper extremity thrombophlebitis after injection. Focal hot spots can signify zones of atelectasis, where the hot spots probably represent a failure of hypoxic vasoconstriction. Artifactual hot spots due to microsphere clumping usually appear to be round and in peripheral location, and the lesions due to a loss of hypoxic vasoconstriction usually appear to be hot uptakes having linear borders. Although these artifactual hot spots have been well-known, we rarely encounter them. This report presents a case with artifactual hot spots due to microsphere clumping on Tc-99m MAA perfusion lung scan.

  2. ''Hot spots'': Subnanometer femtosecond energy localization

    International Nuclear Information System (INIS)

    In a condensed energetic material an understanding of the dynamics and microscopic mechanisms underlying energy transfer between a shock front and various defects is of prime importance for a realistic description of ''hot spot'' formation and explosives initiation. A wide variety of simulations using the well-established technique of computer molecular dynamics has enabled us to obtain a general and very useful microscopic description of the processes beneath the macroscopic behavior of shocked systems. The calculation of the influence of heterogeneities such as point and line defects, voids, and grain boundaries is made possible by computer codes that can handle totally heterogeneous dynamical systems and track the dynamics of energy concentration and partitioning among the molecular bonds in the defect and the nearby region. One and two-dimensional calculations will be discussed in which the spatial and temporal dependence of the energy flux in a general lattice-defect system is calculated quantitatively as a function of shock strength, initial temperature, and initial parameters defining the lattice and defect

  3. Hot spot formation on different tokamak wall materials

    International Nuclear Information System (INIS)

    The thermal contraction phenomenon and generation of 'hot spots' due to thermoemission were described. The paper consider non-linear stages of heat contraction on the graphite, beryllium, tungsten and vanadium wall. It is shown that on the beryllium surface hot spot can't appear due to strong cooling by sublimation. For other materials the conditions of hot spot appearance due to local superheating of the wall have been calculated and their parameters were found: critical surface temperature, size of spots and their temperature profiles, heat fluxes from plasma to the spots. It have been calculated fluxes of sublimating materials from spots to the plasma. It is noticed that nominal temperature of the grafite divertor plate, accepted in ITER's project to being equal 1500 C, is lower then critical temperature of the development heat contraction due to thermoemission. (orig.)

  4. Hot spot formation on different tokamak wall materials

    Energy Technology Data Exchange (ETDEWEB)

    Nedospasov, A.V.; Bezlyudny, I.V. [IVTAN, Moscow (Russian Federation)

    1998-05-01

    The thermal contraction phenomenon and generation of `hot spots` due to thermoemission were described. The paper consider non-linear stages of heat contraction on the graphite, beryllium, tungsten and vanadium wall. It is shown that on the beryllium surface hot spot can`t appear due to strong cooling by sublimation. For other materials the conditions of hot spot appearance due to local superheating of the wall have been calculated and their parameters were found: critical surface temperature, size of spots and their temperature profiles, heat fluxes from plasma to the spots. It have been calculated fluxes of sublimating materials from spots to the plasma. It is noticed that nominal temperature of the grafite divertor plate, accepted in ITER`s project to being equal 1500 C, is lower then critical temperature of the development heat contraction due to thermoemission. (orig.) 5 refs.

  5. On the burn topology of hot-spot-initiated reactions

    Energy Technology Data Exchange (ETDEWEB)

    Hill, Larry G [Los Alamos National Laboratory; Zimmermann, Bjorn [WOLFRAM RESEARCH INC.; Nichols, Albert L [LLNL

    2009-01-01

    We determine the reaction progress function for an ideal hot spot model problem. The considered problem has an exact analytic solution that can derived from a reduction of Nichols statistical hot spot model. We perform numerical calculations to verify the analytic solution and to illustrate the error realized in real, finite systems. We show how the baseline problem, which does not distinguish between the reactant and product densities, can be scaled to handle general cases for which the two densities differ.

  6. Modelling propagation of deflagration waves out of hot spots

    Science.gov (United States)

    Partom, Yehuda

    2015-06-01

    It is widely accepted that shock initiation and detonation of heterogeneous explosives come about by a two-step process known as ignition and growth. In the first step a shock sweeping an explosive cell (control volume) creates hot spots that become ignition sites. In the second step deflagration waves (or burn waves) propagate out of those hot spots and transform the reactant in the cell into reaction products. The macroscopic (or average) reaction rate of the reactant in a cell depends on the speed of those deflagration waves and on the average distance between neighbouring hot spots. Here we simulate the propagation of deflagration waves out of hot spots on the mesoscale in axial symmetry using a 2D hydrocode, to which we add heat conduction and bulk reaction. The propagation speed of the deflagration wave depends on both pressure and temperature, where pressure dependence is dominant at low shock level, and temperature dependence is dominant at a higher shock level. From the simulation we obtain deflagration (or burn) fronts emanating out of the hot spots. For intermediate shock levels the deflagration waves consume the explosive between hot spots. For higher shock levels the deflagration waves strengthen to become detonation waves on the mesoscale. From the simulation results we extract average deflagration wave speeds and show how they depend on reaction rate and on other material parameters.

  7. ``Hot spots'' growth on single nanowire controlled by electric charge

    Science.gov (United States)

    Xi, Shaobo; Liu, Xuehua; He, Ting; Tian, Lei; Wang, Wenhui; Sun, Rui; He, Weina; Zhang, Xuetong; Zhang, Jinping; Ni, Weihai; Zhou, Xiaochun

    2016-06-01

    ``Hot spots'' - a kind of highly active site, which are usually composed of some unique units, such as defects, interfaces, catalyst particles or special structures - can determine the performance of nanomaterials. In this paper, we study a model system, i.e. ``hot spots'' on a single Ag nanowire in the galvanic replacement reaction (GRR), by dark-field microscopy. The research reveals that electric charge can be released by the formation reaction of AgCl, and consequently the electrochemical potential on Ag nanowire drops. The electric charge could induce the reduction of Ag+ to form the ``hot spots'' on the nanowire during the GRR. The appearance probability of ``hot spots'' is almost even along the Ag nanowire, while it is slightly lower near the two ends. The spatial distance between adjacent ``hot spots'' is also controlled by the charge, and obeys a model based on Boltzmann distribution. In addition, the distance distribution here has an advantage in electron transfer and energy saving. Therefore, it's necessary to consider the functions of electric charge during the synthesis or application of nanomaterials.``Hot spots'' - a kind of highly active site, which are usually composed of some unique units, such as defects, interfaces, catalyst particles or special structures - can determine the performance of nanomaterials. In this paper, we study a model system, i.e. ``hot spots'' on a single Ag nanowire in the galvanic replacement reaction (GRR), by dark-field microscopy. The research reveals that electric charge can be released by the formation reaction of AgCl, and consequently the electrochemical potential on Ag nanowire drops. The electric charge could induce the reduction of Ag+ to form the ``hot spots'' on the nanowire during the GRR. The appearance probability of ``hot spots'' is almost even along the Ag nanowire, while it is slightly lower near the two ends. The spatial distance between adjacent ``hot spots'' is also controlled by the charge, and obeys a

  8. Integrating sustainable hunting in biodiversity protection in Central Africa: hot spots, weak spots, and strong spots.

    Science.gov (United States)

    Fa, John E; Olivero, Jesús; Farfán, Miguel Ángel; Márquez, Ana Luz; Vargas, Juan Mario; Real, Raimundo; Nasi, Robert

    2014-01-01

    Wild animals are a primary source of protein (bushmeat) for people living in or near tropical forests. Ideally, the effect of bushmeat harvests should be monitored closely by making regular estimates of offtake rate and size of stock available for exploitation. However, in practice, this is possible in very few situations because it requires both of these aspects to be readily measurable, and even in the best case, entails very considerable time and effort. As alternative, in this study, we use high-resolution, environmental favorability models for terrestrial mammals (N = 165) in Central Africa to map areas of high species richness (hot spots) and hunting susceptibility. Favorability models distinguish localities with environmental conditions that favor the species' existence from those with detrimental characteristics for its presence. We develop an index for assessing Potential Hunting Sustainability (PHS) of each species based on their ecological characteristics (population density, habitat breadth, rarity and vulnerability), weighted according to restrictive and permissive assumptions of how species' characteristics are combined. Species are classified into five main hunting sustainability classes using fuzzy logic. Using the accumulated favorability values of all species, and their PHS values, we finally identify weak spots, defined as high diversity regions of especial hunting vulnerability for wildlife, as well as strong spots, defined as high diversity areas of high hunting sustainability potential. Our study uses relatively simple models that employ easily obtainable data of a species' ecological characteristics to assess the impacts of hunting in tropical regions. It provides information for management by charting the geography of where species are more or less likely to be at risk of extinction from hunting. PMID:25372705

  9. Cygnus A: A Long Wavelength Resolution of the Hot Spots

    CERN Document Server

    Lazio, T J W; Kassim, N E; Perley, R A; Erickson, W C; Carilli, C L; Crane, P C

    2006-01-01

    This paper presents observations of Cygnus A at 74 and 327 MHz at angular resolutions of approximately 10" and 3", respectively. These observations are among the highest angular resolutions obtained below 1000 MHz for this object. While the angular resolution at 74 MHz is not sufficient to separate clearly the hot spots from the lobes, guided by 151 and 327 MHz images, we have estimated the 74 MHz emission from the hot spots. We confirm that the emission from both the western and eastern hot spots flattens at low frequencies and that there is a spectral asymmetry between the two. For the eastern hot spot, a low-energy cutoff in the electron energy spectrum appears to explain the flattening, which implies a cutoff Lorentz factor \\gamma_min ~ 300, though we cannot exclude the possibility that there might be a moderate level of free-free absorption. For the western hot spot, the current observations are not sufficient to distinguish between a free-free absorped power-law spectrum and a synchrotron self-absorbed ...

  10. "Hot spots" growth on single nanowire controlled by electric charge.

    Science.gov (United States)

    Xi, Shaobo; Liu, Xuehua; He, Ting; Tian, Lei; Wang, Wenhui; Sun, Rui; He, Weina; Zhang, Xuetong; Zhang, Jinping; Ni, Weihai; Zhou, Xiaochun

    2016-06-01

    "Hot spots" - a kind of highly active site, which are usually composed of some unique units, such as defects, interfaces, catalyst particles or special structures - can determine the performance of nanomaterials. In this paper, we study a model system, i.e. "hot spots" on a single Ag nanowire in the galvanic replacement reaction (GRR), by dark-field microscopy. The research reveals that electric charge can be released by the formation reaction of AgCl, and consequently the electrochemical potential on Ag nanowire drops. The electric charge could induce the reduction of Ag(+) to form the "hot spots" on the nanowire during the GRR. The appearance probability of "hot spots" is almost even along the Ag nanowire, while it is slightly lower near the two ends. The spatial distance between adjacent "hot spots" is also controlled by the charge, and obeys a model based on Boltzmann distribution. In addition, the distance distribution here has an advantage in electron transfer and energy saving. Therefore, it's necessary to consider the functions of electric charge during the synthesis or application of nanomaterials. PMID:27240743

  11. Models and methods for hot spot safety work

    DEFF Research Database (Denmark)

    Vistisen, Dorte

    2002-01-01

    is the task of improving road safety through alterations of the geometrical and environmental characteristics of the existing road network. The presently applied models and methods in hot spot safety work on the Danish road network were developed about two decades ago, when data was more limited and software...... and statistical methods less developed. The purpose of this thesis is to contribute to improving "State of the art" in Denmark. Basis for the systematic hot spot safety work are the models describing the variation in accident counts on the road network. In the thesis hierarchical models disaggregated on time......Despite the fact that millions DKK each year are spent on improving roadsafety in Denmark, funds for traffic safety are limited. It is therefore vital to spend the resources as effectively as possible. This thesis is concerned with the area of traffic safety denoted "hot spot safety work", which...

  12. KFC Server: interactive forecasting of protein interaction hot spots

    OpenAIRE

    Darnell, Steven J.; LeGault, Laura; Mitchell, Julie C.

    2008-01-01

    The KFC Server is a web-based implementation of the KFC (Knowledge-based FADE and Contacts) model—a machine learning approach for the prediction of binding hot spots, or the subset of residues that account for most of a protein interface's; binding free energy. The server facilitates the automated analysis of a user submitted protein–protein or protein–DNA interface and the visualization of its hot spot predictions. For each residue in the interface, the KFC Server characterizes its local str...

  13. Simulations of Electron Transport in Laser Hot Spots

    International Nuclear Information System (INIS)

    Simulations of electron transport are carried out by solving the Fokker-Planck equation in the diffusive approximation. The system of a single laser hot spot, with open boundary conditions, is systematically studied by performing a scan over a wide range of the two relevant parameters: (1) Ratio of the stopping length over the width of the hot spot. (2) Relative importance of the heating through inverse Bremsstrahlung compared to the thermalization through self-collisions. As for uniform illumination [J.P. Matte et al., Plasma Phys. Controlled Fusion 30 (1988) 1665], the bulk of the velocity distribution functions (VDFs) present a super-Gaussian dependence. However, as a result of spatial transport, the tails are observed to be well represented by a Maxwellian. A similar dependence of the distributions is also found for multiple hot spot systems. For its relevance with respect to stimulated Raman scattering, the linear Landau damping of the electron plasma wave is estimated for such VD Fs. Finally, the nonlinear Fokker-Planck simulations of the single laser hot spot system are also compared to the results obtained with the linear non-local hydrodynamic approach [A.V. Brantov et al., Phys. Plasmas 5 (1998) 2742], thus providing a quantitative limit to the latter method: The hydrodynamic approach presents more than 10% inaccuracy in the presence of temperature variations of the order delta T/T greater than or equal to 1%, and similar levels of deformation of the Gaussian shape of the Maxwellian background

  14. Variability of Jupiter's Five-Micron Hot Spot Inventory

    Science.gov (United States)

    Yanamandra-Fisher, Padma A.; Orton, G. S.; Wakefield, L.; Rogers, J. H.; Simon-Miller, A. A.; Boydstun, K.

    2012-01-01

    Global upheavals on Jupiter involve changes in the albedo of entire axisymmetric regions, lasting several years, with the last two occurring in 1989 and 2006. Against this backdrop of planetary-scale changes, discrete features such as the Great Red Spot (GRS), and other vortices exhibit changes on shorter spatial- and time-scales. We track the variability of the discrete equatorial 5-micron hot spots, semi-evenly spaced in longitude and confined to a narrow latitude band centered at 6.5degN (southern edge of the North Equatorial Belt, NEB), abundant in Voyager images. Tantalizingly similar patterns were observed in the visible (bright plumes and blue-gray regions), where reflectivity in the red is anti-correlated with 5-microns thermal radiance. Ortiz et al. (1998, GRL, 103) characterized the latitude and drift rates of the hot spots, including the descent of the Galileo probe at the southern edge of a 5-micron hot spot, as the superposition of equatorial Rossby waves, with phase speeds between 99 - 103m/s, relative to System III. We note that the high 5-micron radiances correlate well but not perfectly with high 8.57-micron radiances. Because the latter are modulated primarily by changes in the upper ammonia (NH3) ice cloud opacity, this correlation implies that changes in the ammonia ice cloud field may be responsible for the variability seen in the 5-m maps. During the NEB fade (2011 - early 2012), however, these otherwise ubiquitous features were absent, an atmospheric state not seen in decades. The ongoing NEB revival indicates nascent 5-m hot spots as early as April 2012, with corresponding visible dark spots. Their continuing growth through July 2012 indicates the possit.le re-establishment of Rossby waves. The South Equatorial Belt (SEB) and NEB revivals began similarly with an instability that developed into a major outbreak, and many similarities in the observed propagation of clear regions.

  15. Structural hot spots for the solubility of globular proteins.

    Science.gov (United States)

    Ganesan, Ashok; Siekierska, Aleksandra; Beerten, Jacinte; Brams, Marijke; Van Durme, Joost; De Baets, Greet; Van der Kant, Rob; Gallardo, Rodrigo; Ramakers, Meine; Langenberg, Tobias; Wilkinson, Hannah; De Smet, Frederik; Ulens, Chris; Rousseau, Frederic; Schymkowitz, Joost

    2016-01-01

    Natural selection shapes protein solubility to physiological requirements and recombinant applications that require higher protein concentrations are often problematic. This raises the question whether the solubility of natural protein sequences can be improved. We here show an anti-correlation between the number of aggregation prone regions (APRs) in a protein sequence and its solubility, suggesting that mutational suppression of APRs provides a simple strategy to increase protein solubility. We show that mutations at specific positions within a protein structure can act as APR suppressors without affecting protein stability. These hot spots for protein solubility are both structure and sequence dependent but can be computationally predicted. We demonstrate this by reducing the aggregation of human α-galactosidase and protective antigen of Bacillus anthracis through mutation. Our results indicate that many proteins possess hot spots allowing to adapt protein solubility independently of structure and function. PMID:26905391

  16. Structural hot spots for the solubility of globular proteins

    Science.gov (United States)

    Ganesan, Ashok; Siekierska, Aleksandra; Beerten, Jacinte; Brams, Marijke; Van Durme, Joost; De Baets, Greet; Van der Kant, Rob; Gallardo, Rodrigo; Ramakers, Meine; Langenberg, Tobias; Wilkinson, Hannah; De Smet, Frederik; Ulens, Chris; Rousseau, Frederic; Schymkowitz, Joost

    2016-01-01

    Natural selection shapes protein solubility to physiological requirements and recombinant applications that require higher protein concentrations are often problematic. This raises the question whether the solubility of natural protein sequences can be improved. We here show an anti-correlation between the number of aggregation prone regions (APRs) in a protein sequence and its solubility, suggesting that mutational suppression of APRs provides a simple strategy to increase protein solubility. We show that mutations at specific positions within a protein structure can act as APR suppressors without affecting protein stability. These hot spots for protein solubility are both structure and sequence dependent but can be computationally predicted. We demonstrate this by reducing the aggregation of human α-galactosidase and protective antigen of Bacillus anthracis through mutation. Our results indicate that many proteins possess hot spots allowing to adapt protein solubility independently of structure and function. PMID:26905391

  17. Real-time satellite monitoring of volcanic hot spots

    Science.gov (United States)

    Harris, Andrew J. L.; Flynn, Luke P.; Dean, Ken; Pilger, Eric; Wooster, Martin; Okubo, Chris; Mouginis-Mark, Peter; Garbeil, Harold; Thornber, Carl; De la Cruz-Reyna, Servando; Rothery, Dave; Wright, Robert

    Direct satellite data reception at high temporal frequencies and automated processing enable near-real-time, near-continuous thermal monitoring of volcanoes. We review what has been achieved in terms of turning this capability into real-time tools of use to volcano monitoring agencies. Current capabilities focus on 2 instruments: the advanced very high resolution radiometer (AVHRR) and the Geostationary Operational Environmental Satellite (GOES) imager. Collection of lO AVHRR images per day covering Alaska, the Aleutians, and Kamchatka allows routine, on-reception analysis of volcanic hot spots across this region. Data collected between 1996 and 1998 detected 302 hot spots due to lava flows, lava domes, pyroclastic flows, fumaroles, and geothermally heated lakes at 12 different volcanoes. Information was used for hazard mitigation by the Alaskan Volcano Observatory. GOES provides data for North and South American volcanoes every 15-30 minutes. Automated processing allows eruption information and alerts to be posted on the Internet within 15-60 minutes of reception. We use June 1998 to demonstrate the frequency of data acquisition. During this month 2879 GOES images were collected from which 14,832 sub-images of 6 active volcanoes were processed. Although 82% (12,200) of these sub-images were cloud covered, hot spots were still evident on 11% (1634) of the sub-images. Analysis of GOES data for 1998 identified hot spots due to (1) lava flows at Kilauea and Cerro Azul, (2) dome extrusion and explosive activity at Lascar, Popocatepetl, Colima and Pacaya, and (3) dome cooling and collapse at Soufriere Hills. We were also able to suggest that reports of lava flow activity at Cerro Negro were false. This information was supplied to, and used by, various agencies whose task it is to monitor these volcanoes. Global thermal monitoring will become a reality with the launch of the Earth Observing System's moderate resolution imaging spectrometer (MODIS). An automated thermal

  18. Inhibition of turbulence in inertial-confinement-fusion hot spots by viscous dissipation

    Science.gov (United States)

    Weber, C. R.; Clark, D. S.; Cook, A. W.; Busby, L. E.; Robey, H. F.

    2014-05-01

    Achieving ignition in inertial confinement fusion (ICF) requires the formation of a high-temperature (>10 keV) central hot spot. Turbulence has been suggested as a mechanism for degrading the hot-spot conditions by altering transport properties, introducing colder, mixed material, or reducing the conversion of radially directed kinetic energy to hot-spot heating. We show, however, that the hot spot is very viscous, and the assumption of turbulent conditions in the hot spot is incorrect. This work presents the first high-resolution, three-dimensional simulations of National Ignition Facility (NIF) implosion experiments using detailed knowledge of implosion dynamics and instability seeds and including an accurate model of physical viscosity. We find that when viscous effects are neglected, the hot spot can exhibit a turbulent kinetic energy cascade. Viscous effects, however, are significant and strongly damp small-scale velocity structures, with a hot-spot Reynolds number in the range of only 10--100.

  19. PEBBED ANALYSIS OF HOT SPOTS IN PEBBLE-BED REACTORS

    Energy Technology Data Exchange (ETDEWEB)

    Abderrafi M. Ougouag; Hans D. Gougar; William K. Terry; Frederik Reitsma; Wessel Joubert

    2005-09-01

    The Idaho National Laboratory’s PEBBED code and simple probability considerations are used to estimate the likelihood and consequences of the accumulation of highly reactive pebbles in the region of peak power in a pebble-bed reactor. The PEBBED code is briefly described, and the logic of the probability calculations is presented in detail. The results of the calculations appear to show that hot-spot formation produces only moderate increases in peak accident temperatures, and no increases at all in normal operating temperatures.

  20. Protein hot spots at bio-nano interfaces

    Directory of Open Access Journals (Sweden)

    Gerald F. Audette

    2011-07-01

    Full Text Available Nanotechnology has influenced the direction of research across the sciences, medicine, and engineering. Carbon nanotubes (CNTs and, more recently, protein nanotubes (PNTs and protein-inorganic nanocomposites have received considerable attention due to their unique nanostructures that can be utilized as a scaffold to house proteins or create nanowires. A shift towards protein-inorganic interactions has numerous applications from biosensors to biofuel cells and bio-based nanodevices. We examine several systems where protein hot spots, the active domains on proteins and the interactive dynamics in them, play a critical role in the interactions at the interface of these unique systems.

  1. AY Ceti - A flaring, spotted star with a hot companion

    Science.gov (United States)

    Simon, T.; Fekel, F. C., Jr.; Gibson, D. M.

    1985-01-01

    AY Ceti is a late-type single-line spectroscopic binary, a bright X-ray source (L/x/ equal to about 1.5 x 10 to the 31st ergs/s), and a spotted star, as evidenced by its prominent photometric wave. In this paper, observations made with the IUE satellite and the VLA radio interferometer are reported. The 1200-2000 A UV spectrum of AY Cet shows a hot stellar continuum and a very broad Ly-alpha absorption line from a previously unobserved white dwarf secondary. The UV spectrum can be matched to the energy distribution of a (T/eff/ = 18,000 K, log g = 8) model atmosphere. Superposed on this hot continuum are high-excitation emission lines typical of chromospheres and transition regions of active late-type stars, e.g., the spotted RS CVn binaries. It is concluded that the bright lines and soft X-ray emission of AY Cet arise from the cool primary star, rather than from mass transfer and accretion onto the secondary as has recently been proposed for the similar system 56 Peg. Two strong radio flares on AY Cet were observed. The second was rapidly variable and left-hand circularly polarized at levels up to pi(c) = 86 + or - 5 percent at 20 cm wavelength. The most likely emission mechanism is an electron-cyclotron maser.

  2. Magnetised Accretion Discs in Kerr Spacetimes II: Hot Spots

    CERN Document Server

    García, Federico; Johannsen, Tim

    2015-01-01

    Context. Quasi-periodic variability has been observed in a number of X-ray binaries harboring black hole candidates. In general relativity, black holes are uniquely described by the Kerr metric and, according to the cosmic censorship conjecture, curvature singularities always have to be clothed by an event horizon. Aims. In this paper, we study the effect of an external magnetic field on the observed light curves of orbiting hot spots in thin accretion discs around Kerr black holes and naked singularities. Methods. We employ a ray-tracing algorithm to calculate the light curves and power spectra of such hot spots as seen by a distant observer for uniform and dipolar magnetic field configurations assuming a weak coupling between the magnetic field and the disc matter. Results. We show that the presence of an external dipolar magnetic field leads to potentially observable modifications of these signals for both Kerr black holes and naked singularities, while an external uniform magnetic field has practically no...

  3. Modeling Hot-Spot Contributions in Shocked High Explosives at the Mesoscale

    Energy Technology Data Exchange (ETDEWEB)

    Harrier, Danielle [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-08-12

    When looking at performance of high explosives, the defects within the explosive become very important. Plastic bonded explosives, or PBXs, contain voids of air and bonder between the particles of explosive material that aid in the ignition of the explosive. These voids collapse in high pressure shock conditions, which leads to the formation of hot spots. Hot spots are localized high temperature and high pressure regions that cause significant changes in the way the explosive material detonates. Previously hot spots have been overlooked with modeling, but now scientists are realizing their importance and new modeling systems that can accurately model hot spots are underway.

  4. Application of hot spot conception to analysis of spectra from reactions with light bombarding nuclei

    International Nuclear Information System (INIS)

    Data collection on the ''hot spot'' formation in nucleus-nuclear collisions and light particle emission from it is obtained. Some indications of the ''hot spot'' existence are received in the course of experimental data analysis - yield cross section of pre-equilibrium neutron escaping forward and spectra of light particles at backward angles. Calculations through the ''hot spot'' mechanism are compared with spectra. The forecast in respect to correlation experiment which may be considered as a critical one for the ''hot spot'' conception is drawn

  5. Hot spin spots in the laser-induced demagnetization

    Directory of Open Access Journals (Sweden)

    M. S. Si

    2012-03-01

    Full Text Available Laser-induced femtosecond magnetism or femtomagnetism simultaneously relies on two distinctive contributions: (a the optical dipole interaction (ODI between a laser field and a magnetic system and (b the spin expectation value change (SEC between two transition states. Surprisingly, up to now, no study has taken both contributions into account simultaneously. Here we do so by introducing a new concept of the optical spin generator, a product of SEC and ODI between transition states. In ferromagnetic nickel, our first-principles calculation demonstrates that the larger the value of optical spin generator is, the larger the dynamic spin moment change is. This simple generator directly links the time-dependent spin moment change ΔMzk(t at every crystal-momentum k point to its intrinsic electronic structure and magnetic properties. Those hot spin spots are a direct manifestation of the optical spin generator, and should be the focus of future research.

  6. Imaging dissipation and hot spots in carbon nanotube network transistors

    Science.gov (United States)

    Estrada, David; Pop, Eric

    2011-02-01

    We use infrared thermometry of carbon nanotube network (CNN) transistors and find the formation of distinct hot spots during operation. However, the average CNN temperature at breakdown is significantly lower than expected from the breakdown of individual nanotubes, suggesting extremely high regions of power dissipation at the CNN junctions. Statistical analysis and comparison with a thermal model allow the estimate of an upper limit for the average tube-tube junction thermal resistance, ˜4.4×1011 K/W (thermal conductance of ˜2.27 pW/K). These results indicate that nanotube junctions have a much greater impact on CNN transport, dissipation, and reliability than extrinsic factors such as low substrate thermal conductivity.

  7. Estimation method for volumes of hot spots created by heavy ions

    International Nuclear Information System (INIS)

    Studies on the nature of hot spots created by heavy ions have been an intensive interest for decades. The concept of 'hot spot' is sometimes discussed with the one of damage track, i.e., latent track. The latent track can be taken as the permanent remnant of a hot spot, in which excitation was confined and was transferred to electrons and lattice phonons. Recently, the latent tracks have been considered as an useful tool for 3-dimensional fabrication in nano scale. Although the latent tracks will be exploited for nano structure fabrication, the mechanism of producing damages in solids is still nuclear. Recently, the interests of study on the hot spot are the mechanism of the initial energy transfer into lattice and the degree of strength in the coupling between the electron system and the phonon system of the material. For the estimation of the coupling constant, it is necessary to calculate volumes of hot spots and the density distribution of deposited energy. This paper shows a simple estimation method of hot spot volumes and the deposited energy distribution in hot spots. The ratio of volumes and the deposited energy distribution in hot spots. The ratio of volumes of a hot spot (Vh) to a cone (Vc) is exploited, which has the same length and the bottom radium as with the ones of hot spot. The logarithm of the volume ratio(Vh/Vc) is fitted by two second polynomials (top side open and bottom side open) of the logarithm of the energy per unit mass of heavy ions. A pair of second polynomials fitting holds for all the elements with the atomic number up to 92, and probably higher. The energy density deposited in a hot spot is shown non-uniform but has density distribution. With assuming a threshold valued to created and imaginary 'excitation', the distribution of primary deposited energy in material is calculated. This primary process is common to any type of materials. (author)

  8. Rigorous assessment and integration of the sequence and structure based features to predict hot spots

    Directory of Open Access Journals (Sweden)

    Wang Yong

    2011-07-01

    Full Text Available Abstract Background Systematic mutagenesis studies have shown that only a few interface residues termed hot spots contribute significantly to the binding free energy of protein-protein interactions. Therefore, hot spots prediction becomes increasingly important for well understanding the essence of proteins interactions and helping narrow down the search space for drug design. Currently many computational methods have been developed by proposing different features. However comparative assessment of these features and furthermore effective and accurate methods are still in pressing need. Results In this study, we first comprehensively collect the features to discriminate hot spots and non-hot spots and analyze their distributions. We find that hot spots have lower relASA and larger relative change in ASA, suggesting hot spots tend to be protected from bulk solvent. In addition, hot spots have more contacts including hydrogen bonds, salt bridges, and atomic contacts, which favor complexes formation. Interestingly, we find that conservation score and sequence entropy are not significantly different between hot spots and non-hot spots in Ab+ dataset (all complexes. While in Ab- dataset (antigen-antibody complexes are excluded, there are significant differences in two features between hot pots and non-hot spots. Secondly, we explore the predictive ability for each feature and the combinations of features by support vector machines (SVMs. The results indicate that sequence-based feature outperforms other combinations of features with reasonable accuracy, with a precision of 0.69, a recall of 0.68, an F1 score of 0.68, and an AUC of 0.68 on independent test set. Compared with other machine learning methods and two energy-based approaches, our approach achieves the best performance. Moreover, we demonstrate the applicability of our method to predict hot spots of two protein complexes. Conclusion Experimental results show that support vector machine

  9. A feature-based approach to modeling protein-protein interaction hot spots.

    Science.gov (United States)

    Cho, Kyu-il; Kim, Dongsup; Lee, Doheon

    2009-05-01

    Identifying features that effectively represent the energetic contribution of an individual interface residue to the interactions between proteins remains problematic. Here, we present several new features and show that they are more effective than conventional features. By combining the proposed features with conventional features, we develop a predictive model for interaction hot spots. Initially, 54 multifaceted features, composed of different levels of information including structure, sequence and molecular interaction information, are quantified. Then, to identify the best subset of features for predicting hot spots, feature selection is performed using a decision tree. Based on the selected features, a predictive model for hot spots is created using support vector machine (SVM) and tested on an independent test set. Our model shows better overall predictive accuracy than previous methods such as the alanine scanning methods Robetta and FOLDEF, and the knowledge-based method KFC. Subsequent analysis yields several findings about hot spots. As expected, hot spots have a larger relative surface area burial and are more hydrophobic than other residues. Unexpectedly, however, residue conservation displays a rather complicated tendency depending on the types of protein complexes, indicating that this feature is not good for identifying hot spots. Of the selected features, the weighted atomic packing density, relative surface area burial and weighted hydrophobicity are the top 3, with the weighted atomic packing density proving to be the most effective feature for predicting hot spots. Notably, we find that hot spots are closely related to pi-related interactions, especially pi . . . pi interactions. PMID:19273533

  10. Dynamic programming-based hot spot identification approach for pedestrian crashes.

    Science.gov (United States)

    Medury, Aditya; Grembek, Offer

    2016-08-01

    Network screening techniques are widely used by state agencies to identify locations with high collision concentration, also referred to as hot spots. However, most of the research in this regard has focused on identifying highway segments that are of concern to automobile collisions. In comparison, pedestrian hot spot detection has typically focused on analyzing pedestrian crashes in specific locations, such as at/near intersections, mid-blocks, and/or other crossings, as opposed to long stretches of roadway. In this context, the efficiency of the some of the widely used network screening methods has not been tested. Hence, in order to address this issue, a dynamic programming-based hot spot identification approach is proposed which provides efficient hot spot definitions for pedestrian crashes. The proposed approach is compared with the sliding window method and an intersection buffer-based approach. The results reveal that the dynamic programming method generates more hot spots with a higher number of crashes, while providing small hot spot segment lengths. In comparison, the sliding window method is shown to suffer from shortcomings due to a first-come-first-serve approach vis-à-vis hot spot identification and a fixed hot spot window length assumption. PMID:27209154

  11. Accurate prediction of hot spot residues through physicochemical characteristics of amino acid sequences

    KAUST Repository

    Chen, Peng

    2013-07-23

    Hot spot residues of proteins are fundamental interface residues that help proteins perform their functions. Detecting hot spots by experimental methods is costly and time-consuming. Sequential and structural information has been widely used in the computational prediction of hot spots. However, structural information is not always available. In this article, we investigated the problem of identifying hot spots using only physicochemical characteristics extracted from amino acid sequences. We first extracted 132 relatively independent physicochemical features from a set of the 544 properties in AAindex1, an amino acid index database. Each feature was utilized to train a classification model with a novel encoding schema for hot spot prediction by the IBk algorithm, an extension of the K-nearest neighbor algorithm. The combinations of the individual classifiers were explored and the classifiers that appeared frequently in the top performing combinations were selected. The hot spot predictor was built based on an ensemble of these classifiers and to work in a voting manner. Experimental results demonstrated that our method effectively exploited the feature space and allowed flexible weights of features for different queries. On the commonly used hot spot benchmark sets, our method significantly outperformed other machine learning algorithms and state-of-the-art hot spot predictors. The program is available at http://sfb.kaust.edu.sa/pages/software.aspx. © 2013 Wiley Periodicals, Inc.

  12. Evidence for the Daxiawan as a hot spot in the Earth

    Institute of Scientific and Technical Information of China (English)

    汤懋苍; 钟大赉; 李文华; 冯松

    1999-01-01

    From the point of view of application, the definition of hot spot was given first. The solid geophysical evidence suggested that the Daxiawan (great gorge) in Yarlung Zangbo River should be a hot spot, which is a special region with high ground temperature, low density, low magnetism, negative gravity abnormality, frequent earthquake and strong tectonics. According to the data available, the center of the hot spot was preliminarily decided. The difference between the ground surface and air temperature in January is negatively correlated with the distance from the hot spot center to the meteorological station. According to the ground surface energy balance equation, the geothermal flux in the center of hot spot is about 25 W/m~2. Further analysis suggested that Daxiawan is a pilot region of climate change as well as the region of the heaviest rainfall and highest latitude of tropical forest in the world.

  13. Experimental Study of Ignition by Hot Spot in Internal Combustion Engines

    Science.gov (United States)

    Serruys, Max

    1938-01-01

    In order to carry out the contemplated study, it was first necessary to provide hot spots in the combustion chamber, which could be measured and whose temperature could be changed. It seemed difficult to realize both conditions working solely on the temperature of the cooling water in a way so as to produce hot spots on the cylinder wall capable of provoking autoignition. Moreover, in the majority of practical cases, autoignition is produced by the spark plug, one of the least cooled parts in the engine. The first procedure therefore did not resemble that which most generally occurs in actual engine operation. All of these considerations caused us to reproduce similar hot spots at the spark plugs. The hot spots produced were of two kinds and designated with the name of thermo-electric spark plug and of metallic hot spot.

  14. Methodology and software to detect viral integration site hot-spots

    Directory of Open Access Journals (Sweden)

    Kim Namshin

    2011-09-01

    Full Text Available Abstract Background Modern gene therapy methods have limited control over where a therapeutic viral vector inserts into the host genome. Vector integration can activate local gene expression, which can cause cancer if the vector inserts near an oncogene. Viral integration hot-spots or 'common insertion sites' (CIS are scrutinized to evaluate and predict patient safety. CIS are typically defined by a minimum density of insertions (such as 2-4 within a 30-100 kb region, which unfortunately depends on the total number of observed VIS. This is problematic for comparing hot-spot distributions across data sets and patients, where the VIS numbers may vary. Results We develop two new methods for defining hot-spots that are relatively independent of data set size. Both methods operate on distributions of VIS across consecutive 1 Mb 'bins' of the genome. The first method 'z-threshold' tallies the number of VIS per bin, converts these counts to z-scores, and applies a threshold to define high density bins. The second method 'BCP' applies a Bayesian change-point model to the z-scores to define hot-spots. The novel hot-spot methods are compared with a conventional CIS method using simulated data sets and data sets from five published human studies, including the X-linked ALD (adrenoleukodystrophy, CGD (chronic granulomatous disease and SCID-X1 (X-linked severe combined immunodeficiency trials. The BCP analysis of the human X-linked ALD data for two patients separately (774 and 1627 VIS and combined (2401 VIS resulted in 5-6 hot-spots covering 0.17-0.251% of the genome and containing 5.56-7.74% of the total VIS. In comparison, the CIS analysis resulted in 12-110 hot-spots covering 0.018-0.246% of the genome and containing 5.81-22.7% of the VIS, corresponding to a greater number of hot-spots as the data set size increased. Our hot-spot methods enable one to evaluate the extent of VIS clustering, and formally compare data sets in terms of hot-spot overlap

  15. Methodology and software to detect viral integration site hot-spots

    Science.gov (United States)

    2011-01-01

    Background Modern gene therapy methods have limited control over where a therapeutic viral vector inserts into the host genome. Vector integration can activate local gene expression, which can cause cancer if the vector inserts near an oncogene. Viral integration hot-spots or 'common insertion sites' (CIS) are scrutinized to evaluate and predict patient safety. CIS are typically defined by a minimum density of insertions (such as 2-4 within a 30-100 kb region), which unfortunately depends on the total number of observed VIS. This is problematic for comparing hot-spot distributions across data sets and patients, where the VIS numbers may vary. Results We develop two new methods for defining hot-spots that are relatively independent of data set size. Both methods operate on distributions of VIS across consecutive 1 Mb 'bins' of the genome. The first method 'z-threshold' tallies the number of VIS per bin, converts these counts to z-scores, and applies a threshold to define high density bins. The second method 'BCP' applies a Bayesian change-point model to the z-scores to define hot-spots. The novel hot-spot methods are compared with a conventional CIS method using simulated data sets and data sets from five published human studies, including the X-linked ALD (adrenoleukodystrophy), CGD (chronic granulomatous disease) and SCID-X1 (X-linked severe combined immunodeficiency) trials. The BCP analysis of the human X-linked ALD data for two patients separately (774 and 1627 VIS) and combined (2401 VIS) resulted in 5-6 hot-spots covering 0.17-0.251% of the genome and containing 5.56-7.74% of the total VIS. In comparison, the CIS analysis resulted in 12-110 hot-spots covering 0.018-0.246% of the genome and containing 5.81-22.7% of the VIS, corresponding to a greater number of hot-spots as the data set size increased. Our hot-spot methods enable one to evaluate the extent of VIS clustering, and formally compare data sets in terms of hot-spot overlap. Finally, we show that the

  16. Hot-Cold Spots in Italian Macroseismic Data

    CERN Document Server

    Molchan, G; Panza, G F

    2010-01-01

    The site effect is usually associated with local geological conditions, which increase or decrease the level of shaking compared with standard attenuation relations. We made an attempt to see in the macroseismic data of Italy some other effects, namely, hot/cold spots in the terminology of Olsen (2000), which are related to local fault geometry rather than to soil conditions. We give a list of towns and villages liable to amplify (+) or to reduce (-) the level of shaking in comparison with the nearby settlements. Relief and soil conditions cannot always account for the anomalous sites. Further, there are sites where both (+) and (-) effects are observed depending on the earthquake. The opposite effects can be generated by events from the same seismotectonic zone and along the same direction to the site. Anomalous sites may group themselves into clusters of different scales. All isolated anomalous patterns presented in this paper can be used in hazard analysis, in particular, for the modeling and testing of se...

  17. Mutation hot spots in the canine herpesvirus thymidine kinase gene.

    Science.gov (United States)

    Yamada, Shinya; Matsumoto, Yasunobu; Takashima, Yasuhiro; Otsuka, Haruki

    2005-08-01

    The guanine and cytosine content (GC-content) of alpha-herpesvirus genes are highly variable despite similar genome structures. It is known that drug resistant HSV, which has the genome with a high GC-content (approximately 70%), commonly includes frameshift mutations in homopolymer stretches of guanine (G) and cytosine (C) within the thymidine kinase (TK) gene. However, whether such mutation hotspots exist in the TK gene of canine herpesvirus (CHV) which has a low GC-content was unknown. In this study, we investigated mutations in the TK gene of CHV. CHV was passaged in the presence of iodo-deoxyuridine (IDU), and IDU-resistant clones were isolated. In all IDU-resistant virus clones, mutations in the TK gene were observed. The majority of these mutations were frameshift mutations of an adenine (A) insertion or deletion within either of 2 stretches of eight A's in the TK gene. It was demonstrated that CHV TK mutations frequently occur at a limited number of hot spots within long homopolymer nucleotide stretches. PMID:15965615

  18. Hot spot generation in energetic materials created by long-wavelength infrared radiation

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Ming-Wei; You, Sizhu; Suslick, Kenneth S.; Dlott, Dana D., E-mail: dlott@illinois.edu [School of Chemical Sciences and Fredrick Seitz Materials Research Laboratory, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801 (United States)

    2014-02-10

    Hot spots produced by long-wavelength infrared (LWIR) radiation in an energetic material, crystalline RDX (1,3,5-trinitroperhydro-1,3,5-triazine), were studied by thermal-imaging microscopy. The LWIR source was a CO{sub 2} laser operating in the 28-30 THz range. Hot spot generation was studied using relatively low intensity (∼100 W cm{sup −2}), long-duration (450 ms) LWIR pulses. The hot spots could be produced repeatedly in individual RDX crystals, to investigate the fundamental mechanisms of hot spot generation by LWIR, since the peak hot-spot temperatures were kept to ∼30 K above ambient. Hot spots were generated preferentially beneath RDX crystal planes making oblique angles with the LWIR beam. Surprisingly, hot spots were more prominent when the LWIR wavelength was tuned to be weakly absorbed (absorption depth ∼30 μm) than when the LWIR wavelength was strongly absorbed (absorption depth ∼5 μm). This unexpected effect was explained using a model that accounts for LWIR refraction and RDX thermal conduction. The weakly absorbed LWIR is slightly focused underneath the oblique crystal planes, and it penetrates the RDX crystals more deeply, increasing the likelihood of irradiating RDX defect inclusions that are able to strongly absorb or internally focus the LWIR beam.

  19. Coral bleaching and ocean ''hot spots''

    Energy Technology Data Exchange (ETDEWEB)

    Goreau, T.J. (Global Coral Reef Alliance, Chappaqua, NY (United States)); Hayes, R.L. (Howard Univ., Washington, DC (United States). College of Medicine)

    1994-05-01

    Global sea-surface temperature maps show that mass coral-reef bleaching episodes between 1983 and 1991 followed positive anomalies more than 1 deg C above long-term monthly averages (''hot spots'') during the preceding warm season. Irregular formation, movement, and disappearance of hot spots make their detailed long-term prediction impossible, but they can be tracked in real time from satellite data. Monitoring of ocean hot spots and of coral bleaching is needed if the Framework Convention of Climate Change is to meet its goal of protecting the most temperature sensitive ecosystems. 47 refs, 3 figs

  20. Frequency response function method with constraint efficiency factors for Hot/Cold spot problems

    International Nuclear Information System (INIS)

    Temperature fluctuation from incomplete fluid mixing induces typically bending plus peak stress across wall thickness. For this stress mode, author has developed the frequency response function to establish design-by-analysis methodology for this phenomenon. On the other hand, it is pointed out that hot and cold spots appear near T-junctions in piping systems. Those induce other stress modes from three-dimensional temperature distributions. This report describes the extension of the frequency response method to hot and cold spot problems by introducing constraint efficiency factors. Its applicability was validated by application to a hot spot near the T-junction of PHENIX secondary piping system. (author)

  1. Ring of nine Gamma Ray Burst overlap with the hot spot of my hypothesis

    Science.gov (United States)

    Cao, Dayong

    2016-03-01

    During 2004 to 2014, a symmetry axis and a cold spot (a structure of one billion light years across) of CMB were observed, and I supposed there is a hot spot, and there is a symmetry between the cold spot and the hot spot of CMB. http://www.dailymail.co.uk/sciencetech/article-2430415 http://meetings.aps.org/link/BAPS.2014.MAR.Y33.9 In 2015, a Ring of Nine Gamma Ray Burst (a structure of FIVE BILLION light years across) which is a part of structure of double helix and overlap with the hot spot was observed. http://www.dailymail.co.uk/sciencetech/article-3185193 The Ring of Nine Gamma Ray Burst could be explained by the hot spot. There is a balance systemic model with structure of double helix of the flat universe between cold spot and hot spot-a balance between stellar matter and dark massenergy (include dark matter and dark energy). The model can explain of the Hubble's redshift. There is a larger dark hole instead of the huge black hole of the center of the Milky Way galaxy, and a dark hole builds up a balance system with sun. This model should explain of the seasonal Extinctions. http://meetings.aps.org/link/BAPS.2015.APR.H14.8

  2. Magnetised accretion discs in Kerr spacetimes. II. Hot spots

    Science.gov (United States)

    García, Federico; Ranea-Sandoval, Ignacio F.; Johannsen, Tim

    2016-03-01

    Context. Quasi-periodic variability has been observed in a number of X-ray binaries that harbor black hole candidates. In general relativity, black holes are uniquely described by the Kerr metric and, according to the cosmic censorship conjecture, curvature singularities always have to be clothed by an event horizon. Aims: In this paper, we study the observed light curves that arise from orbiting hotspots in thin accretion discs around Kerr black holes and naked singularities, and the effect introduced by the presence of an external magnetic field. Methods: We employ a ray-tracing algorithm to calculate the light curves and power spectra of these hot spots as seen by a distant observer for uniform and dipolar magnetic field configurations, assuming a weak coupling between the magnetic field and the disc matter. Results: We show that the presence of an external dipolar magnetic field leads to potentially observable modifications of these light curves for both Kerr black holes and naked singularities, while an external uniform magnetic field has practically no effect. In particular, we demonstrate that the emission from a hotspot, which is orbiting near the innermost stable circular orbit of a naked singularity in a dipolar magnetic field, can be significantly harder than the emission of the same hotspot in the absence of this type of magnetic field. Conclusions: The comparison of our model with observational data may allow us to study the geometry of magnetic fields around compact objects and to test the cosmic censorship conjecture in conjunction with other observables, such as thermal continuum spectra and iron line profiles.

  3. Hot spot formation and stagnation properties in simulations of direct-drive NIF implosions

    Science.gov (United States)

    Schmitt, Andrew J.; Obenschain, Stephen P.

    2016-05-01

    We investigate different proposed methods of increasing the hot spot energy and radius in inertial confinement fusion implosions. In particular, shock mistiming (preferentially heating the inner edge of the target's fuel) and increasing the initial vapor gas density are investigated as possible control mechanisms. We find that only the latter is effective in substantially increasing the hot spot energy and dimensions while achieving ignition. In all cases an increase in the hot spot energy is accompanied by a decrease in the hot spot energy density (pressure) and both the yield and the gain of the target drop substantially. 2D simulations of increased vapor density targets predict an increase in the robustness of the target with respect to surface perturbations but are accompanied by significant yield degradation.

  4. Hot spots and the hollowness of proton-proton interactions at high energies

    CERN Document Server

    Albacete, Javier L

    2016-01-01

    We present a dynamical explanation of the hollowness effect observed in proton-proton scattering at $\\sqrt s\\!=\\!7$ TeV. This phenomenon, not observed at lower energies, consists in a depletion of the inelasticity density at zero impact parameter of the collision. Our analysis is based on three main ingredients: we rely gluonic hot spots inside the proton as effective degrees of freedom for the description of the scattering process. Next we assume that some non-trivial correlation between the transverse positions of the hot spots inside the proton exists. Finally we build the scattering amplitude from a multiple scattering, Glauber-like series of collisions between hot spots. In our approach, the onset of the hollowness effect is naturally explained as due to the diffusion or growth of the hot spots in the transverse plane with increasing collision energy.

  5. Calculation of the fast ion tail distribution for a spherically symmetric hot spot

    Science.gov (United States)

    McDevitt, C. J.; Tang, X.-Z.; Guo, Z.; Berk, H. L.

    2014-10-01

    The fast ion tail for a spherically symmetric hot spot is computed via the solution of a simplified Fokker-Planck collision operator. Emphasis is placed on describing the energy scaling of the fast ion distribution function in the hot spot as well as the surrounding cold plasma throughout a broad range of collisionalities and temperatures. It is found that while the fast ion tail inside the hot spot is significantly depleted, leading to a reduction of the fusion yield in this region, a surplus of fast ions is observed in the neighboring cold plasma region. The presence of this surplus of fast ions in the neighboring cold region is shown to result in a partial recovery of the fusion yield lost in the hot spot.

  6. Ion distribution in the hot spot of an inertial confinement fusion plasma

    Science.gov (United States)

    Tang, Xianzhu; Guo, Zehua; Berk, Herb

    2012-10-01

    Maximizing the fusion gain of inertial confinement fusion (ICF) for inertial fusion energy (IFE) applications leads to the standard scenario of central hot spot ignition followed by propagating burn wave through the cold/dense assembled fuel. The fact that the hot spot is surrounded by cold but dense fuel layer introduces subtle plasma physics which requires a kinetic description. Here we perform Fokker-Planck calculations and kinetic PIC simulations for an ICF plasma initially in pressure balance but having large temperature gradient over a narrow transition layer. The loss of the fast ion tail from the hot spot, which is important for fusion reactivity, is quantified by Fokker-Planck models. The role of electron energy transport and the ambipolar electric field is investigated via kinetic simulations and the fluid moment models. The net effect on both hot spot ion temperature and the ion tail distribution, and hence the fusion reactivity, is elucidated.

  7. Calculation of the fast ion tail distribution for a spherically symmetric hot spot

    Energy Technology Data Exchange (ETDEWEB)

    McDevitt, C. J.; Tang, X.-Z.; Guo, Z. [Theoretical Division, Los Alamos National Laboratory, Los Alamos, New Mexico 87545 (United States); Berk, H. L. [Department of Physics, University of Texas, Austin, Texas 78712 (United States)

    2014-10-15

    The fast ion tail for a spherically symmetric hot spot is computed via the solution of a simplified Fokker-Planck collision operator. Emphasis is placed on describing the energy scaling of the fast ion distribution function in the hot spot as well as the surrounding cold plasma throughout a broad range of collisionalities and temperatures. It is found that while the fast ion tail inside the hot spot is significantly depleted, leading to a reduction of the fusion yield in this region, a surplus of fast ions is observed in the neighboring cold plasma region. The presence of this surplus of fast ions in the neighboring cold region is shown to result in a partial recovery of the fusion yield lost in the hot spot.

  8. Hot-spot mix in ignition-scale inertial confinement fusion targets.

    Science.gov (United States)

    Regan, S P; Epstein, R; Hammel, B A; Suter, L J; Scott, H A; Barrios, M A; Bradley, D K; Callahan, D A; Cerjan, C; Collins, G W; Dixit, S N; Döppner, T; Edwards, M J; Farley, D R; Fournier, K B; Glenn, S; Glenzer, S H; Golovkin, I E; Haan, S W; Hamza, A; Hicks, D G; Izumi, N; Jones, O S; Kilkenny, J D; Kline, J L; Kyrala, G A; Landen, O L; Ma, T; MacFarlane, J J; MacKinnon, A J; Mancini, R C; McCrory, R L; Meezan, N B; Meyerhofer, D D; Nikroo, A; Park, H-S; Ralph, J; Remington, B A; Sangster, T C; Smalyuk, V A; Springer, P T; Town, R P J

    2013-07-26

    Mixing of plastic ablator material, doped with Cu and Ge dopants, deep into the hot spot of ignition-scale inertial confinement fusion implosions by hydrodynamic instabilities is diagnosed with x-ray spectroscopy on the National Ignition Facility. The amount of hot-spot mix mass is determined from the absolute brightness of the emergent Cu and Ge K-shell emission. The Cu and Ge dopants placed at different radial locations in the plastic ablator show the ablation-front hydrodynamic instability is primarily responsible for hot-spot mix. Low neutron yields and hot-spot mix mass between 34(-13,+50)  ng and 4000(-2970,+17 160)  ng are observed. PMID:23931375

  9. Characterizing Hot-Spot Dynamics of Direct-Drive Cryogenic Implosions on OMEGA

    Science.gov (United States)

    Anderson, K. S.; McKenty, P. W.; Shvydky, A.; Knauer, J. P.; Collins, T. J. B.; Delettrez, J. A.; Keller, D.; Marinak, M. M.

    2015-11-01

    In direct-drive inertial confinement fusion, nonuniformities in laser drive, capsule manufacture, and target positioning lead to non-radial hydrodynamic flow in the hot spot at stagnation. Characterizing such flow in the hot spot requires simulating the entire capsule in three dimensions to remove symmetry boundary conditions, which artificially constrain hot-spot flow. This paper will present results from 3-D simulations of cryogenic implosions on OMEGA using HYDRA. Low-mode asymmetries and their contributions to residual hot-spot kinetic energy will be discussed. This material is based upon work supported by the Department of Energy National Nuclear Security Administration under Award Number DE-NA0001944 and performed under the auspices of LLNL under Contract No. DE-AC52-07NA27344.

  10. Calculation of the fast ion tail distribution for a spherically symmetric hot spot

    International Nuclear Information System (INIS)

    The fast ion tail for a spherically symmetric hot spot is computed via the solution of a simplified Fokker-Planck collision operator. Emphasis is placed on describing the energy scaling of the fast ion distribution function in the hot spot as well as the surrounding cold plasma throughout a broad range of collisionalities and temperatures. It is found that while the fast ion tail inside the hot spot is significantly depleted, leading to a reduction of the fusion yield in this region, a surplus of fast ions is observed in the neighboring cold plasma region. The presence of this surplus of fast ions in the neighboring cold region is shown to result in a partial recovery of the fusion yield lost in the hot spot

  11. Translation of nanoantenna hot spots by a metal-dielectric composite superlens

    OpenAIRE

    Liu, Zhengtong; Thoreson, Mark D.; Kildishev, Alexander V.; Shalaev, V. M.

    2009-01-01

    We employ numerical simulations to show that highly localized, enhanced electromagnetic fields, also known as "hot spots," produced by a periodic array of silver nanoantennas can be spatially translated to the other side of a metal-dielectric composite superlens. The proposed translation of the hot spots enables surface-enhanced optical spectroscopy without the undesirable contact of molecules with metal, and thus it broadens and reinforces the potential applications of sensing based on field...

  12. Analysis of microstructure-dependent shock dissipation and hot-spot formation in granular metalized explosive

    Science.gov (United States)

    Chakravarthy, Sunada; Gonthier, Keith A.

    2016-07-01

    Variations in the microstructure of granular explosives (i.e., particle packing density, size, shape, and composition) can affect their shock sensitivity by altering thermomechanical fields at the particle-scale during pore collapse within shocks. If the deformation rate is fast, hot-spots can form, ignite, and interact, resulting in burn at the macro-scale. In this study, a two-dimensional finite and discrete element technique is used to simulate and examine shock-induced dissipation and hot-spot formation within low density explosives (68%-84% theoretical maximum density (TMD)) consisting of large ensembles of HMX (C4H8N8O8) and aluminum (Al) particles (size ˜ 60 -360 μm). Emphasis is placed on identifying how the inclusion of Al influences effective shock dissipation and hot-spot fields relative to equivalent ensembles of neat/pure HMX for shocks that are sufficiently strong to eliminate porosity. Spatially distributed hot-spot fields are characterized by their number density and area fraction enabling their dynamics to be described in terms of nucleation, growth, and agglomeration-dominated phases with increasing shock strength. For fixed shock particle speed, predictions indicate that decreasing packing density enhances shock dissipation and hot-spot formation, and that the inclusion of Al increases dissipation relative to neat HMX by pressure enhanced compaction resulting in fewer but larger HMX hot-spots. Ensembles having bimodal particle sizes are shown to significantly affect hot-spot dynamics by altering the spatial distribution of hot-spots behind shocks.

  13. Hot Spots and Hot Times: Wildlife Road Mortality in a Regional Conservation Corridor

    Science.gov (United States)

    Garrah, Evelyn; Danby, Ryan K.; Eberhardt, Ewen; Cunnington, Glenn M.; Mitchell, Scott

    2015-10-01

    Strategies to reduce wildlife road mortality have become a significant component of many conservation efforts. However, their success depends on knowledge of the temporal and spatial patterns of mortality. We studied these patterns along the 1000 Islands Parkway in Ontario, Canada, a 37 km road that runs adjacent to the St. Lawrence River and bisects the Algonquin-to-Adirondacks international conservation corridor. Characteristics of all vertebrate road kill were recorded during 209 bicycle surveys conducted from 2008 to 2011. We estimate that over 16,700 vertebrates are killed on the road from April to October each year; most are amphibians, but high numbers of birds, mammals, and reptiles were also found, including six reptiles considered at-risk in Canada. Regression tree analysis was used to assess the importance of seasonality, weather, and traffic on road kill magnitude. All taxa except mammals exhibited distinct temporal peaks corresponding to phases in annual life cycles. Variations in weather and traffic were only important outside these peak times. Getis-Ord analysis was used to identify spatial clusters of mortality. Hot spots were found in all years for all taxa, but locations varied annually. A significant spatial association was found between multiyear hot spots and wetlands. The results underscore the notion that multi-species conservation efforts must account for differences in the seasonality of road mortality among species and that multiple years of data are necessary to identify locations where the greatest conservation good can be achieved. This information can be used to inform mitigation strategies with implications for conservation at regional scales.

  14. An automated decision-tree approach to predicting protein interaction hot spots.

    Science.gov (United States)

    Darnell, Steven J; Page, David; Mitchell, Julie C

    2007-09-01

    Protein-protein interactions can be altered by mutating one or more "hot spots," the subset of residues that account for most of the interface's binding free energy. The identification of hot spots requires a significant experimental effort, highlighting the practical value of hot spot predictions. We present two knowledge-based models that improve the ability to predict hot spots: K-FADE uses shape specificity features calculated by the Fast Atomic Density Evaluation (FADE) program, and K-CON uses biochemical contact features. The combined K-FADE/CON (KFC) model displays better overall predictive accuracy than computational alanine scanning (Robetta-Ala). In addition, because these methods predict different subsets of known hot spots, a large and significant increase in accuracy is achieved by combining KFC and Robetta-Ala. The KFC analysis is applied to the calmodulin (CaM)/smooth muscle myosin light chain kinase (smMLCK) interface, and to the bone morphogenetic protein-2 (BMP-2)/BMP receptor-type I (BMPR-IA) interface. The results indicate a strong correlation between KFC hot spot predictions and mutations that significantly reduce the binding affinity of the interface. PMID:17554779

  15. Microwave interrogation of an air plasma plume as a model system for hot spots in explosives

    Science.gov (United States)

    Kane, Ron; Tringe, Joseph; Klunder, Greg; Baluyot, Emer; Densmore, John; Converse, Mark

    2015-06-01

    The evolution of hot spots within explosives is critical to understand for predicting how detonation waves form and propagate. However, it is challenging to observe hot spots directly because they are small (~ micron diameter), form quickly (much less than a microsecond), and many explosives of interest are optically opaque. Microwaves are well-suited to characterize hot spots because they readily penetrate most explosives. They also have sufficient temporal and spatial resolution to measure the coalescence of an ensemble of hot spots inside explosives. Here we employ 94 GHz microwaves to characterize the evolution of individual plasma plumes formed by laser ionization of air. We use interferometry to obtain velocity records as a function of plume position and orientation. Although the plasma plumes are larger than individual hot spots in explosives, they expand rapidly and predictably, and their structure can be optically imaged. They are therefore useful model systems to establish the spatial and temporal limits of microwave interferometry (MI) for understanding more complex hot spot behavior in solid explosives. This work performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344.

  16. Identification of hot-spot residues in protein-protein interactions by computational docking

    Directory of Open Access Journals (Sweden)

    Fernández-Recio Juan

    2008-10-01

    Full Text Available Abstract Background The study of protein-protein interactions is becoming increasingly important for biotechnological and therapeutic reasons. We can define two major areas therein: the structural prediction of protein-protein binding mode, and the identification of the relevant residues for the interaction (so called 'hot-spots'. These hot-spot residues have high interest since they are considered one of the possible ways of disrupting a protein-protein interaction. Unfortunately, large-scale experimental measurement of residue contribution to the binding energy, based on alanine-scanning experiments, is costly and thus data is fairly limited. Recent computational approaches for hot-spot prediction have been reported, but they usually require the structure of the complex. Results We have applied here normalized interface propensity (NIP values derived from rigid-body docking with electrostatics and desolvation scoring for the prediction of interaction hot-spots. This parameter identifies hot-spot residues on interacting proteins with predictive rates that are comparable to other existing methods (up to 80% positive predictive value, and the advantage of not requiring any prior structural knowledge of the complex. Conclusion The NIP values derived from rigid-body docking can reliably identify a number of hot-spot residues whose contribution to the interaction arises from electrostatics and desolvation effects. Our method can propose residues to guide experiments in complexes of biological or therapeutic interest, even in cases with no available 3D structure of the complex.

  17. Identification and location of hot and cold spots of treated prevalence of depression in Catalonia (Spain

    Directory of Open Access Journals (Sweden)

    Salinas-Pérez José A

    2012-08-01

    Full Text Available Abstract Background Spatial analysis is a relevant set of tools for studying the geographical distribution of diseases, although its methods and techniques for analysis may yield very different results. A new hybrid approach has been applied to the spatial analysis of treated prevalence of depression in Catalonia (Spain according to the following descriptive hypotheses: 1 spatial clusters of treated prevalence of depression (hot and cold spots exist and, 2 these clusters are related to the administrative divisions of mental health care (catchment areas in this region. Methods In this ecological study, morbidity data per municipality have been extracted from the regional outpatient mental health database (CMBD-SMA for the year 2009. The second level of analysis mapped small mental health catchment areas or groups of municipalities covered by a single mental health community centre. Spatial analysis has been performed using a Multi-Objective Evolutionary Algorithm (MOEA which identified geographical clusters (hot spots and cold spots of depression through the optimization of its treated prevalence. Catchment areas, where hot and cold spots are located, have been described by four domains: urbanicity, availability, accessibility and adequacy of provision of mental health care. Results MOEA has identified 6 hot spots and 4 cold spots of depression in Catalonia. Our results show a clear spatial pattern where one cold spot contributed to define the exact location, shape and borders of three hot spots. Analysing the corresponding domain values for the identified hot and cold spots no common pattern has been detected. Conclusions MOEA has effectively identified hot/cold spots of depression in Catalonia. However these hot/cold spots comprised municipalities from different catchment areas and we could not relate them to the administrative distribution of mental care in the region. By combining the analysis of hot/cold spots, a better statistical and

  18. SU-E-T-393: Investigation of Hot Spots in Tomotherapy 3D Conformal Breast Plan

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Q; Siebers, J; Khandelwal, S [University of Virginia, Charlottesville, VA (United States)

    2014-06-01

    Purpose: The purpose of this study is to determine the root-cause of hotspots inherent to Tomotherapy static beam 3D conformal radiotherapy (3DCRT) for breast treatment. ASTRO (ref here) recommends that IMRT be avoided for breast treatments. Despite Tomotherapy's inherent IMRT-like optimization and delivery, our experience at a Tomotherapy-only site has been that Tomotherapy 3DCRT fail to produce a clinically acceptable plan for 79% of our breast patients. Hot-spots have been one of the major obstacles. Methods: Eight lumpectomy patients were planned according to RTOG-1005 specification. Two or four tangential beams were used for 3DCRT breast planning. To spare the contralateral breast and ipsilateral lung, part of the PTV was not covered by the primary beam, yielding adjacent hot-spots. We hypothesize that the planning system creates hotspots adjacent to the cold spots to yield scatter radiation dose compensation in the blocked region. Various phantom and patient setup were used to test the hypothesis. Results: Hot spots outside of PTV in the range of 135% - 174% were observed for patient plan. It is confirmed that the PTV partial block causes the adjacent hot spot. The root cause is the optimizer quadratic objective function over- weighs improving the cold spot. The IMRT flexibility offered by Tomotherapy is counter-productive in static-beam 3DCRT breast treatment. For phantom case, as the Modulation-Factor increases from 1.1 to 5, the hot spot increases from 110% to 300%. Limiting the 3DCRT intensity modulation is shown to produce clinically acceptable plan. Conclusion: Most of the hot spots in Tomotherapy 3DCRT breast plan originate from the planning-system optimizer attempting to cover PTV cold spots rather than from the beam energy. Altering the objective function could improve clinical acceptability of static beam Tomotherapy 3DCRT.

  19. Accounting for "hot spots" and "hot moments" in soil carbon models for water-limited ecosystems

    Science.gov (United States)

    O'Donnell, Frances; Caylor, Kelly

    2010-05-01

    Soil organic carbon (SOC) dynamics in water-limited ecosystems are complicated by the stochastic nature of rainfall and patchy structure of vegetation, which can lead to "hot spots" and "hot moments" of high biological activity. Non-linear models that use spatial and temporal averages of forcing variables are unable to account for these phenomena and are likely to produce biased results. In this study we present a model of SOC abundance that accounts for spatial heterogeneity at the plant scale and temporal variability in soil moisture content at the daily scale. We approximated an existing simulation-based model of SOC dynamics as a stochastic differential equation driven by multiplicative noise that can be solved numerically for steady-state sizes of three SOC pools. We coupled this to a model of water balance and SOC input rate at a point for a given cover type, defined by the number of shrub and perennial grass root systems and canopies overlapping the point. Using a probabilistic description of vegetation structure based on a two dimensional Poisson process, we derived analytical expressions for the distribution of cover types across a landscape and produced weighted averages of SOC stocks. An application of the model to a shortgrass steppe ecosystem in Colorado, USA, replicated empirical data on spatial patterns and average abundance of SOC, whereas a version of the model using spatially averaged forcing variables overestimated SOC stocks by 12%. The model also successfully replicated data from paired desert grassland sites in New Mexico, USA, that had and had not been affected by woody plant encroachment, indicating that the model could be a useful tool for understanding and predicting the effect of woody plant encroachment on regional carbon budgets. We performed a theoretical analysis of a simplified version of the model to estimate the bias introduced by using spatial averages of forcing variables to model SOC stocks across a range of climatic conditions

  20. Prediction of hot spots in protein interfaces using a random forest model with hybrid features.

    Science.gov (United States)

    Wang, Lin; Liu, Zhi-Ping; Zhang, Xiang-Sun; Chen, Luonan

    2012-03-01

    Prediction of hot spots in protein interfaces provides crucial information for the research on protein-protein interaction and drug design. Existing machine learning methods generally judge whether a given residue is likely to be a hot spot by extracting features only from the target residue. However, hot spots usually form a small cluster of residues which are tightly packed together at the center of protein interface. With this in mind, we present a novel method to extract hybrid features which incorporate a wide range of information of the target residue and its spatially neighboring residues, i.e. the nearest contact residue in the other face (mirror-contact residue) and the nearest contact residue in the same face (intra-contact residue). We provide a novel random forest (RF) model to effectively integrate these hybrid features for predicting hot spots in protein interfaces. Our method can achieve accuracy (ACC) of 82.4% and Matthew's correlation coefficient (MCC) of 0.482 in Alanine Scanning Energetics Database, and ACC of 77.6% and MCC of 0.429 in Binding Interface Database. In a comparison study, performance of our RF model exceeds other existing methods, such as Robetta, FOLDEF, KFC, KFC2, MINERVA and HotPoint. Of our hybrid features, three physicochemical features of target residues (mass, polarizability and isoelectric point), the relative side-chain accessible surface area and the average depth index of mirror-contact residues are found to be the main discriminative features in hot spots prediction. We also confirm that hot spots tend to form large contact surface areas between two interacting proteins. Source data and code are available at: http://www.aporc.org/doc/wiki/HotSpot. PMID:22258275

  1. Hydrologic indicators of hot spots and hot moments of mercury methylation along river corridors

    Science.gov (United States)

    Singer, Michael; Harrison, Lee; Donovan, Patrick; Blum, Joel; Marvin-DiPasquale, Mark

    2016-04-01

    The biogeochemical cycling of metals and other contaminants river-floodplain corridors is controlled by microbial activity is often affected by dynamic redox conditions. Riverine flooding thus has the potential to affect speciation of redox-sensitive metals such as mercury (Hg). Therefore, flow history over a period of decades potentially holds information on past production of bioavailable Hg. We investigate this process within a Northern California river system that has a legacy of industrial-scale 19th century hydraulic gold mining. In the first known application of this methodology, we combine hydraulic modeling, measurements of Hg species in sediment and biota, and first-order calculations to assess the role of river floodplains in producing monomethylmercury (MMHg), which accumulates in local and migratory biota. We identify areas that represent 'hot spots' (frequently inundated areas of floodplains) and 'hot moments' (floodplain areas inundated for consecutive long periods). We show that the probability of MMHg production in each sector of the river system is dependent on the spatial patterns of overbank flow and drainage, which affect its long-term redox history. MMHg bioaccumulation within the aquatic food web may pose a major risk to humans and waterfowl that eat migratory salmonids, which are being encouraged to come up these rivers to spawn, and there appears to be no end to MMHg production under a regime of increasingly common large floods with extended duration. These findings identify river floodplains as periodic, temporary, yet important, loci of biogeochemical transformation in which contaminants may undergo change during limited periods of the historical hydrologic record. We suggest that inundation is the primary driver of MMHg production in river corridors and that the entire flow history must be analyzed in terms of magnitude and frequency of inundation in order to accurately assess biogeochemical risks, rather than merely highlighting the

  2. MICROSTRUCTURE AND PROPERTIES OF DEEP CROGENIC TREATMENT ELECTRODES FOR SPOT WELDING HOT DIP GALVANIZED STEEL

    Institute of Scientific and Technical Information of China (English)

    Wu Zhisheng; Liu Cuirong; Wang Jiuhai; Shan Ping; Hu Shengsun; Lian Jinrui

    2005-01-01

    The microstructure and elements distribution of the deep cryogenic treatment electrodes and non-cryogenic treatment electrodes for spot welding hot dip galvanized steel are observed by a scanning electrical microscope. The grain sizes, the resistivity and the hardness of the electrodes before and after deep cryogenic treatment are measured by X-ray diffraction, the DC double arms bridge and the Brinell hardness testing unit respectively. The spot welding process performance of hot dip galvanized steel plate is tested and the relationship between microstructure and physical properties of deep cryogenic treatment electrodes is analyzed. The experimental results show that deep cryogenic treatment makes Cr, Zr in deep cryogenic treatment electrodes emanate dispersedly and makes the grain of deep cryogenic treatment electrodes smaller than non-cryogenic treatment ones so that the electrical conductivity and the thermal conductivity of deep cryogenic treatment electrodes are improved very much, which make spot welding process performance of the hot dip galvanized steel be improved.

  3. Nano rolling-circle amplification for enhanced SERS hot spots in protein microarray analysis.

    Science.gov (United States)

    Yan, Juan; Su, Shao; He, Shijiang; He, Yao; Zhao, Bin; Wang, Dongfang; Zhang, Honglu; Huang, Qing; Song, Shiping; Fan, Chunhai

    2012-11-01

    Although "hot spots" have been proved to contribute to surface enhanced Raman scattering (SERS), less attention was paid to increase the number of the "hot spot" to directly enhance the Raman signals in bioanalytical systems. Here we report a new strategy based on nano rolling-circle amplification (nanoRCA) and nano hyperbranched rolling-circle amplification (nanoHRCA) to increase "hot spot" groups for protein microarrays. First, protein and ssDNA are coassembled on gold nanoparticles, making the assembled probe have both binding ability and hybridization ability. Second, the ssDNAs act as primers to initiate in situ RCA reaction to produced long ssDNAs. Third, a large number of SERS probes are loaded on the long ssDNA templetes, allowing thousands of SERS probes involved in each biomolecular recognition event. The strategy offered high-efficiency Raman enhancement and could detect less than 10 zeptomolar protein molecules in protein microarray analysis. PMID:23046056

  4. Finding radiation hot-spots for a private residence/decontamination manual

    International Nuclear Information System (INIS)

    Since the Fukushima Daiichi Nuclear Power Station accident, the radio-iodine and cesium analysis group of ad hoc committee of safety measures has investigated initial screening monitor of the soils and examined contamination and experienced decontamination works. Existence of hot-spots where Cs 137 is concentrated is confirmed. The report makes a manual to find such a hot-spot in a private residence and how the decontamination should be carried out. Particularly, the report provides the definite examples of hot-spots, for instances, a roof, an eaves trough (a gutter), a side drain (a ditch), dead leaves (withered grass), surface land, a wood block, etc. and how the decontamination should be confirmed and the dusts be collected and kept. (S. Ohno)

  5. Il Canyon di Caprera: un hot spot di cetacei nel Mar Tirreno centrale? = Is the Caprera Canyon an hot spot of cetaceans within the central Tyrrhenian Sea?

    OpenAIRE

    Bittau, Luca; Manconi, Renata

    2011-01-01

    Presence of cetaceans was monitored using a platform of opportunity (whale watching) off north eastern Sardinia, jrom summer 2010 to winter 2011. The monitoring consisted in seventeen surveys covering a total of 1930 km. Six cetacean species have been observed, totalizing 49 sightings. Striped dolphin was the most abundant species in the continental slope area. The waters in the Caprera Canyon appear as a potential hot spot of cetaceans and will be surveyed by dedicated campaigns. Moreover...

  6. Hot and Cold Spots in the First plus Second Year COBE/DMR Maps

    OpenAIRE

    Cayon, Laura; Smoot, George

    1995-01-01

    Density perturbations at the decoupling epoch produce angular fluctuations in the temperature of the Cosmic Microwave Background (CMB) radiation that may appear as hot and cold spots. Observational data of the CMB includes instrumental noise in addition to the cosmological signal. One would like to determine which of the observed spots are produced by the noise and which correspond to signal. In this work we first present a statistical analysis of the first plus second year COBE/DMR map at 53...

  7. Testing a class of non-Kerr metrics with hot spots orbiting SgrA*

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Dan; Li, Zilong; Bambi, Cosimo, E-mail: danliu12@fudan.edu.cn, E-mail: zilongli@fudan.edu.cn, E-mail: bambi@fudan.edu.cn [Center for Field Theory and Particle Physics and Department of Physics, Fudan University, 220 Handan Road, 200433 Shanghai (China)

    2015-01-01

    SgrA*, the supermassive black hole candidate at the Galactic Center, exhibits flares in the X-ray, NIR, and sub-mm bands that may be interpreted within a hot spot model. Light curves and images of hot spots orbiting a black hole are affected by a number of special and general relativistic effects, and they can be potentially used to check whether the object is a Kerr black hole of general relativity. However, in a previous study we have shown that the relativistic features are usually subdominant with respect to the background noise and the model-dependent properties of the hot spot, and eventually it is at most possible to estimate the frequency of the innermost stable circular orbit. In this case, tests of the Kerr metric are only possible in combination with other measurements. In the present work, we consider a class of non-Kerr spacetimes in which the hot spot orbit may be outside the equatorial plane. These metrics are difficult to constrain from the study of accretion disks and indeed current X-ray observations of stellar-mass and supermassive black hole candidates cannot put interesting bounds. Here we show that near future observations of SgrA* may do it. If the hot spot is sufficiently close to the massive object, the image affected by Doppler blueshift is brighter than the other one and this provides a specific observational signature in the hot spot's centroid track. We conclude that accurate astrometric observations of SgrA* with an instrument like GRAVITY should be able to test this class of metrics, except in the more unlikely case of a small viewing angle.

  8. Elucidation of the dynamics for hot-spot initiation at nonuniform interfaces of highly shocked materials

    Science.gov (United States)

    An, Qi; Zybin, Sergey V.; Goddard, William A., III; Jaramillo-Botero, Andres; Blanco, Mario; Luo, Sheng-Nian

    2011-12-01

    The fundamental processes in shock-induced instabilities of materials remain obscure, particularly for detonation of energetic materials. We simulated these processes at the atomic scale on a realistic model of a polymer-bonded explosive (3,695,375 atoms/cell) and observed that a hot spot forms at the nonuniform interface, arising from shear relaxation that results in shear along the interface that leads to a large temperature increase that persists long after the shock front has passed the interface. For energetic materials this temperature increase is coupled to chemical reactions that lead to detonation. We show that decreasing the density of the binder eliminates the hot spot.

  9. Translation of Nanoantenna Hot-Spots by a Metal-Dielectric Composite Superlens

    CERN Document Server

    Liu, Zhengtong; Kildishev, Alexander V; Shalaev, Vladimir M

    2009-01-01

    We employ numerical simulations to show that highly localized, enhanced electromagnetic fields, also known as "hot spots," produced by a periodic array of silver nanoantennas can be spatially translated to the other side of a metal-dielectric composite superlens. The proposed translation of the hot spots enables surface-enhanced optical spectroscopy without the undesirable contact of molecules with metal, and thus it broadens and reinforces the potential applications of sensing based on field-enhanced fluorescence and surface-enhanced Raman scattering.

  10. An evolving hot spot orbiting around Sgr A*

    International Nuclear Information System (INIS)

    Here we report on recent near-infrared observations of the Sgr A* counterpart associated with the super-massive ∼ 4 x 106Mo-dot black hole at the Galactic Center. We find that the May 2007 flare shows the highest sub-flare contrast observed until now, as well as evidence for variations in the profile of consecutive sub-flares. We modeled the flare profile variations according to the elongation and change of the shape of a spot due to differential rotation within the accretion disk.

  11. An evolving hot spot orbiting around Sgr A*

    Energy Technology Data Exchange (ETDEWEB)

    Zamaninasab, M; Eckart, A; Kunneriath, D; Witzel, G; Giessuebel, R; Koenig, S; Straubmeier, C [University of Cologne, Zuelpicher Str. 77, D-50937 Cologne (Germany); Meyer, L [Department of Physics and Astronomy, University of California, Los Angeles, CA 90095-1547 (United States); Schoedel, R [Instituto de AstrofIsica de AndalucIa, Apartado 3004, 18080 Granada (Spain); Dovciak, M; Karas, V [Astronomical Institute, Academy of Sciences, BocnI II, CZ-14131 Prague (Czech Republic); Zensus, A [Max-Planck-Institut fuer Radioastronomie, Auf dem Huegel 69, 53121 Bonn (Germany)], E-mail: zamani@phl.uni-koeln.de

    2008-10-15

    Here we report on recent near-infrared observations of the Sgr A* counterpart associated with the super-massive {approx} 4 x 10{sup 6}M{sub o-dot} black hole at the Galactic Center. We find that the May 2007 flare shows the highest sub-flare contrast observed until now, as well as evidence for variations in the profile of consecutive sub-flares. We modeled the flare profile variations according to the elongation and change of the shape of a spot due to differential rotation within the accretion disk.

  12. Semi-Supervised Transductive Hot Spot Predictor Working on Multiple Assumptions

    KAUST Repository

    Wang, Jingyan

    2014-05-23

    Protein-protein interactions are critically dependent on just a few residues (“hot spots”) at the interfaces. Hot spots make a dominant contribution to the binding free energy and if mutated they can disrupt the interaction. As mutagenesis studies require significant experimental efforts, there exists a need for accurate and reliable computational hot spot prediction methods. Compared to the supervised hot spot prediction algorithms, the semi-supervised prediction methods can take into consideration both the labeled and unlabeled residues in the dataset during the prediction procedure. The transductive support vector machine has been utilized for this task and demonstrated a better prediction performance. To the best of our knowledge, however, none of the transductive semi-supervised algorithms takes all the three semisupervised assumptions, i.e., smoothness, cluster and manifold assumptions, together into account during learning. In this paper, we propose a novel semi-supervised method for hot spot residue prediction, by considering all the three semisupervised assumptions using nonlinear models. Our algorithm, IterPropMCS, works in an iterative manner. In each iteration, the algorithm first propagates the labels of the labeled residues to the unlabeled ones, along the shortest path between them on a graph, assuming that they lie on a nonlinear manifold. Then it selects the most confident residues as the labeled ones for the next iteration, according to the cluster and smoothness criteria, which is implemented by a nonlinear density estimator. Experiments on a benchmark dataset, using protein structure-based features, demonstrate that our approach is effective in predicting hot spots and compares favorably to other available methods. The results also show that our method outperforms the state-of-the-art transductive learning methods.

  13. Ultra-high-energy-cosmic-ray hot spots from tidal disruption events

    CERN Document Server

    Pfeffer, Daniel N; Kamionkowski, Marc

    2015-01-01

    We consider the possibility that tidal disruption events (TDEs) caused by supermassive black holes (SMBHs) in nearby galaxies can account for the ultra-high-energy cosmic-ray (UHECR) hot spot reported recently by the Telescope Array (TA) and the warm spot by Pierre Auger Observatory (PAO). We describe the expected cosmic-ray signal from a TDE and derive the constraints set by the timescale for dispersion due to intergalactic magnetic fields and the accretion time of the SMBH. We demonstrate that TDEs in M82 can explain the hot spot detected by the TA. Based on data-driven assumptions regarding the SMBH mass function, the luminosity scaling of the TDEs and the mass dependence of their rate, we then analyze the full parameter space of the model to search for consistency with the full-sky isotropic signal. Doing so, we show that TDEs can account for both the TA hot spot and full-sky UHECR observations. Using our model we show that the warm spot in the PAO data in the direction of Centaurus A (Cen A) can also be ...

  14. Energy Relaxtation and Hot Spot Formation in Superconducting Single Photon Detectors SSPDS

    Directory of Open Access Journals (Sweden)

    Florya I.N.

    2015-01-01

    Full Text Available We have studied the mechanism of energy relaxation and resistive state formation after absorption of a single photon for different wavelengths and materials of single photon detectors. Our results are in good agreement with the hot spot model.

  15. Clustering Logistics Facilities in a Metropolitan Area via a Hot - Spot Analysis

    Directory of Open Access Journals (Sweden)

    İsmail Önden

    2014-12-01

    Full Text Available Hot spots can be described as the high attraction points. Defining the hot spots and clustering approaches in a metropolitan area helps to provide solutions for balancing the freight flows between the sub-areas in the city center. It also helps to provide solutions for secondary problems, such as traffic congestion and air pollution. The technique assists decision-makers in making inferences about the city’s future and taking precautions for sustainability. In this paper, a geographic information systems (GIS analysis tool, spatial statistics based on the Getis Ord* statistics, is used to illustrate which part of Istanbul has hot spots. The hot spot identification is based on logistics activities at the locations of the logistics facilities. The outputs of the analysis are discussed within the context of logistics costs and environmental effects.Anahtar Kelimeler: Mağaza yeri seçimi, delphi tekniği, makro analiz, mağaza yeri seçim kriterleri .

  16. Contribution of Local and Transported Atmospheric Aerosol in a European Air Pollution Hot-Spot

    Czech Academy of Sciences Publication Activity Database

    Zíková, Naděžda; Leoni, C.; Hovorka, J.; Ondráček, Jakub; Schwarz, Jaroslav

    -: Italian Aerosol Society, 2015. ISBN N. [European Aerosol Conference EAC 2015. Milano (IT), 06.09.2015-11.09.2015] R&D Projects: GA ČR(CZ) GBP503/12/G147 Institutional support: RVO:67985858 Keywords : atmospheric aerosol * air trajectories * hot-spot Subject RIV: DN - Health Impact of the Environment Quality

  17. A novel approach to detect hot-spots in large-scale multivariate data

    Directory of Open Access Journals (Sweden)

    Kendrick Keith M

    2007-09-01

    Full Text Available Abstract Background Progressive advances in the measurement of complex multifactorial components of biological processes involving both spatial and temporal domains have made it difficult to identify the variables (genes, proteins, neurons etc. significantly changed activities in response to a stimulus within large data sets using conventional statistical approaches. The set of all changed variables is termed hot-spots. The detection of such hot spots is considered to be an NP hard problem, but by first establishing its theoretical foundation we have been able to develop an algorithm that provides a solution. Results Our results show that a first-order phase transition is observable whose critical point separates the hot-spot set from the remaining variables. Its application is also found to be more successful than existing approaches in identifying statistically significant hot-spots both with simulated data sets and in real large-scale multivariate data sets from gene arrays, electrophysiological recording and functional magnetic resonance imaging experiments. Conclusion In summary, this new statistical algorithm should provide a powerful new analytical tool to extract the maximum information from complex biological multivariate data.

  18. Narrow-bandwidth high-order harmonics driven by long-duration hot spots

    Science.gov (United States)

    Kozlov, Maxim; Kfir, Ofer; Fleischer, Avner; Kaplan, Alex; Carmon, Tal; Schwefel, Harald G. L.; Bartal, Guy; Cohen, Oren

    2012-06-01

    We predict and investigate the emission of high-order harmonics by atoms that cross intense laser hot spots that last for a nanosecond or longer. An atom that moves through a nanometer-scale hot spot at characteristic thermal velocity can emit high-order harmonics in a similar fashion to an atom that is irradiated by a short-duration (picosecond-scale) laser pulse. We analyze the collective emission from a thermal gas and from a jet of atoms. In both cases, the line shape of a high-order harmonic exhibits a narrow spike with spectral width that is determined by the bandwidth of the driving laser. Finally, we discuss a scheme for producing long-duration laser hot spots with intensity in the range of the intensity threshold for high-harmonic generation. In the proposed scheme, the hot spot is produced by a long laser pulse that is consecutively coupled to a high-quality micro-resonator and a metallic nano-antenna. This system may be used for generating ultra-narrow bandwidth extreme-ultraviolet radiation through frequency up-conversion of a low-cost compact pump laser.

  19. CFD analysis of hot spot formation through a fixed bed reactor of Fischer-Tropsch synthesis

    Directory of Open Access Journals (Sweden)

    Hamed Aligolzadeh

    2015-12-01

    Full Text Available One of the interesting methods for conversion of synthesis gas to heavy hydrocarbons is Fischer–Tropsch process. The process has some bottlenecks, such as hot spot formation and low degree of conversion. In this work, computational fluid dynamics technique was used to simulate conversion of synthetic gas and product distribution. Also, hot spot formation in the catalytic fixed-bed reactor was investigated in several runs. Simulation results indicated that hot spot formation occurred more likely in the early and middle part of reactor due to high reaction rates. Based on the simulation results, the temperature of hot spots increased with increase in the inlet temperature as well as pressure. Among the many CFD runs conducted, it is found that the optimal temperature and pressure for Fischer–Tropsch synthesis are 565 K and 20 bar, respectively. As it seems that the reactor shall work very well under optimal conditions, the reaction rates and catalyst duration would simultaneously be maximum .

  20. Whole-genome sequencing in autism identifies hot spots for de novo germline mutation

    DEFF Research Database (Denmark)

    Michaelson, Jacob J.; Shi, Yujian; Gujral, Madhusudan;

    2012-01-01

    De novo mutation plays an important role in autism spectrum disorders (ASDs). Notably, pathogenic copy number variants (CNVs) are characterized by high mutation rates. We hypothesize that hypermutability is a property of ASD genes and may also include nucleotide-substitution hot spots. We investi...

  1. Molecular Determinants Underlying Binding Specificities of the ABL Kinase Inhibitors: Combining Alanine Scanning of Binding Hot Spots with Network Analysis of Residue Interactions and Coevolution.

    Directory of Open Access Journals (Sweden)

    Amanda Tse

    Full Text Available Quantifying binding specificity and drug resistance of protein kinase inhibitors is of fundamental importance and remains highly challenging due to complex interplay of structural and thermodynamic factors. In this work, molecular simulations and computational alanine scanning are combined with the network-based approaches to characterize molecular determinants underlying binding specificities of the ABL kinase inhibitors. The proposed theoretical framework unveiled a relationship between ligand binding and inhibitor-mediated changes in the residue interaction networks. By using topological parameters, we have described the organization of the residue interaction networks and networks of coevolving residues in the ABL kinase structures. This analysis has shown that functionally critical regulatory residues can simultaneously embody strong coevolutionary signal and high network centrality with a propensity to be energetic hot spots for drug binding. We have found that selective (Nilotinib and promiscuous (Bosutinib, Dasatinib kinase inhibitors can use their energetic hot spots to differentially modulate stability of the residue interaction networks, thus inhibiting or promoting conformational equilibrium between inactive and active states. According to our results, Nilotinib binding may induce a significant network-bridging effect and enhance centrality of the hot spot residues that stabilize structural environment favored by the specific kinase form. In contrast, Bosutinib and Dasatinib can incur modest changes in the residue interaction network in which ligand binding is primarily coupled only with the identity of the gate-keeper residue. These factors may promote structural adaptability of the active kinase states in binding with these promiscuous inhibitors. Our results have related ligand-induced changes in the residue interaction networks with drug resistance effects, showing that network robustness may be compromised by targeted mutations

  2. Role of hydrodynamic instability growth in hot-spot mass gain and fusion performance of inertial confinement fusion implosions

    International Nuclear Information System (INIS)

    In an inertial confinement fusion target, energy loss due to thermal conduction from the hot-spot will inevitably ablate fuel ice into the hot-spot, resulting in a more massive but cooler hot-spot, which negatively impacts fusion yield. Hydrodynamic mix due to Rayleigh-Taylor instability at the gas-ice interface can aggravate the problem via an increased gas-ice interfacial area across which energy transfer from the hot-spot and ice can be enhanced. Here, this mix-enhanced transport effect on hot-spot fusion-performance degradation is quantified using contrasting 1D and 2D hydrodynamic simulations, and its dependence on effective acceleration, Atwood number, and ablation speed is identified

  3. High-temperature hot spots on Io as seen by the Galileo solid state imaging (SSI) experiment

    Science.gov (United States)

    McEwen, A.S.; Simonelli, D.P.; Senske, D.R.; Klaasen, K.P.; Keszthelyi, L.; Johnson, T.V.; Geissler, P.E.; Carr, M.H.; Belton, M.J.S.

    1997-01-01

    High-temperature hot spots on Io have been imaged at ???50 km spatial resolution by Galileo's CCD imaging system (SSI). Images were acquired during eclipses (Io in Jupiter's shadow) via the SSI clear filter (???0.4-1.0 ??m), detecting emissions from both small intense hot spots and diffuse extended glows associated with Io's atmosphere and plumes. A total of 13 hot spots have been detected over ???70% of Io's surface. Each hot spot falls precisely on a low-albedo feature corresponding to a caldera floor and/or lava flow. The hot-spot temperatures must exceed ???700 K for detection by SSI. Observations at wavelengths longer than those available to SSI require that most of these hot spots actually have significantly higher temperatures (???1000 K or higher) and cover small areas. The high-temperature hot spots probably mark the locations of active silicate volcanism, supporting suggestions that the eruption and near-surface movement of silicate magma drives the heat flow and volcanic activity of Io. Copyright 1997 by the American Geophysical Union.

  4. Studies of plasmonic hot-spot translation by a metal-dielectric layered superlens

    Science.gov (United States)

    Thoreson, Mark D.; Nielsen, Rasmus B.; West, Paul R.; Kriesch, Arian; Liu, Zhengtong; Fang, Jieran; Kildishev, Alexander V.; Peschel, Ulf; Shalaev, Vladimir M.; Boltasseva, Alexandra

    2011-10-01

    We have studied the ability of a lamellar near-field superlens to transfer an enhanced electromagnetic field to the far side of the lens. In this work, we have experimentally and numerically investigated superlensing in the visible range. By using the resonant hot-spot field enhancements from optical nanoantennas as sources, we investigated the translation of these sources to the far side of a layered silver-silica superlens operating in the canalization regime. Using near-field scanning optical microscopy (NSOM), we have observed evidence of superlens-enabled enhanced-field translation at a wavelength of about 680 nm. Specifically, we discuss our recent experimental and simulation results on the translation of hot spots using a silver-silica layered superlens design. We compare the experimental results with our numerical simulations and discuss the perspectives and limitations of our approach.

  5. ELIPGRID-PC: A PC program for calculating hot spot probabilities

    International Nuclear Information System (INIS)

    ELIPGRID-PC, a new personal computer program has been developed to provide easy access to Singer's 1972 ELIPGRID algorithm for hot-spot detection probabilities. Three features of the program are the ability to determine: (1) the grid size required for specified conditions, (2) the smallest hot spot that can be sampled with a given probability, and (3) the approximate grid size resulting from specified conditions and sampling cost. ELIPGRID-PC also provides probability of hit versus cost data for graphing with spread-sheets or graphics software. The program has been successfully tested using Singer's published ELIPGRID results. An apparent error in the original ELIPGRID code has been uncovered and an appropriate modification incorporated into the new program

  6. Studies of plasmonic hot-spot translation by a metal-dielectric layered superlens

    DEFF Research Database (Denmark)

    Thoreson, Mark D.; Nielsen, Rasmus Bundgaard; West, Paul R.;

    2011-01-01

    We have studied the ability of a lamellar near-field superlens to transfer an enhanced electromagnetic field to the far side of the lens. In this work, we have experimentally and numerically investigated superlensing in the visible range. By using the resonant hot-spot field enhancements from...... optical nanoantennas as sources, we investigated the translation of these sources to the far side of a layered silver-silica superlens operating in the canalization regime. Using near-field scanning optical microscopy (NSOM), we have observed evidence of superlens-enabled enhanced-field translation at a...... wavelength of about 680 nm. Specifically, we discuss our recent experimental and simulation results on the translation of hot spots using a silver-silica layered superlens design. We compare the experimental results with our numerical simulations and discuss the perspectives and limitations of our approach....

  7. Fusion yield rate recovery by escaping hot-spot fast ions in the neighboring fuel layer

    Science.gov (United States)

    Tang, Xian-Zhu; McDevitt, C. J.; Guo, Zehua; Berk, H. L.

    2014-02-01

    Free-streaming loss by fast ions can deplete the tail population in the hot spot of an inertial confinement fusion (ICF) target. Escaping fast ions in the neighboring fuel layer of a cryogenic target can produce a surplus of fast ions locally. In contrast to the Knudsen layer effect that reduces hot-spot fusion reactivity due to tail ion depletion, the inverse Knudsen layer effect increases fusion reactivity in the neighboring fuel layer. In the case of a burning ICF target in the presence of significant hydrodynamic mix which aggravates the Knudsen layer effect, the yield recovery largely compensates for the yield reduction. For mix-dominated sub-ignition targets, the yield reduction is the dominant process.

  8. Estimation of α-particle induced hot spot size in Nb film using Abrikosov vortices

    International Nuclear Information System (INIS)

    A new experimental method for estimation of alpha-particle induced hot spot size in Nb films is proposed. The method is based on the jump-like motion of Abrikosov vortices induced by the impact of a single alpha particle (241Am 5.5 MeV) on a superconducting film. Preliminary experiments were carried out on a high quality 'small' Nb-AlOx-Nb Josephson tunnel junction with circular geometry and area 2500 μm2 (length smaller than λj) at T = 4.2 K. A preliminary value of d* = 2.5 μm is obtained for the dimension of the hot spot region. (author)

  9. Heat transport and electron distribution function in laser produced plasmas with hot spots

    International Nuclear Information System (INIS)

    Using Fokker-Planck and particle-in-cell simulations, the evolution of a single hot spot and multiple hot spot systems have been studied in laser produced plasmas. A practical formula for nonlocal heat flux has been derived as a generalized expression of a nonlocal linear approach [Bychenkov et al., Phys. Rev. Lett. 75, 4405 (1995)] and is tested in simulations. The electron distribution function is studied at different spatial locations with respect to a localized heating source. The electron distribution function displays several non-Maxwellian features which depend on the interplay between the effects of inverse bremsstrahlung heating and nonlocal transport. In particular, significant high-energy tails are found. They may have impact on the behavior of parametric instabilities in nonuniformly heated laser plasma

  10. Evaluation of hot spot factors for thermal and hydraulic design of HTTR

    International Nuclear Information System (INIS)

    High Temperature Engineering Test Reactor (HTTR) is a graphite-moderated and helium gas-cooled reactor with 30 MW in thermal power and 950degC in reactor outlet coolant temperature. One of the major items in thermal and hydraulic design of the HTTR is to evaluate the maximum fuel temperature with a sufficient margin from a viewpoint of integrity of coated fuel particles. Hot spot factors are considered in the thermal and hydraulic design to evaluate the fuel temperature not only under the normal operation condition but also under any transient condition conservatively. This report summarizes the items of hot spot factors selected in the thermal and hydraulic design and their estimated values, and also presents evaluation results of the thermal and hydraulic characteristics of the HTTR briefly. (author)

  11. Application of hot-spot stress fatigue analysis to attachments on flexible plate

    Energy Technology Data Exchange (ETDEWEB)

    Dexter, R.J.; Fisher, J.W. [Lehigh Univ., Bethlehem, PA (United States). Center for Advanced Tech. for Large Structural Systems; Tarquinio, J.E. [Greiner, Inc., King of Prussia, PA (United States)

    1994-12-31

    Cyclic axial and bending loads were applied to angle sections which were fillet welded normal to the flange of large box sections at various eccentricities relative to the webs. Local bending of the thin flange plate between the web and the angle leg parallel to the web caused cracking at the angle fillet weld toe. The hot-spot stress range, measured with a strain gage placed adjacent to the weld toe, was plotted with the number of cycles to through-thickness cracking. In some experiments, a membrane stress range was also applied in the direction perpendicular to the dominant hot-spot stress range. The data from the various configurations plot in the same scatterband just above the Category C fatigue design curve. If the angle is aligned with 10 mm eccentricity or less, cracking originates at the weld root. A method to predict the fatigue strength for this case of weld root cracking in eccentric joints is presented.

  12. Identification of a new genomic hot spot of evolutionary diversification of protein function.

    Directory of Open Access Journals (Sweden)

    Aline Winkelmann

    Full Text Available Establishment of phylogenetic relationships remains a challenging task because it is based on computational analysis of genomic hot spots that display species-specific sequence variations. Here, we identify a species-specific thymine-to-guanine sequence variation in the Glrb gene which gives rise to species-specific splice donor sites in the Glrb genes of mouse and bushbaby. The resulting splice insert in the receptor for the inhibitory neurotransmitter glycine (GlyR conveys synaptic receptor clustering and specific association with a particular synaptic plasticity-related splice variant of the postsynaptic scaffold protein gephyrin. This study identifies a new genomic hot spot which contributes to phylogenetic diversification of protein function and advances our understanding of phylogenetic relationships.

  13. Non-LTE Modelling of the Structure and Spectra of the Hot Accretion Spots on the Surface of Young Stars

    CERN Document Server

    Dodin, A V

    2014-01-01

    The paper describes the modelling of the structure and spectra of the hot accretion spots on the surface of young stars with taking into account departures from LTE for hydrogen and helium. It has been found that the existence of the ram pressure of the in-falling gas at the outer boundary of the hot spot leads to the Stark broadening of the hydrogen line profiles up to FWHM of about 1000 km/s at the considered accretion parameters. It is shown that taking into account departures from LTE for atoms and ions of carbon and oxygen does not lead to noticeable changes in the structure of the hot spot.

  14. Characteristic focal hot spots of bone marrow scintigraphic finding in aplastic anemia

    International Nuclear Information System (INIS)

    The bone marrow scintigraphy with 99mTc sulfur colloid has been performed in 168 patients with Aplastic anemia(AA) and 100 patients with others hematological disorders. Bone marrow imaging is a useful method to demonstrate the existence of active hematopoietic foci in living body. The features and clinical significance of these focal hot spots have been discussed. The bone marrow scintigraphy is proved to be helpful in diagnosis, therapy and assessing prognosis of A.A

  15. A feature-based approach to modeling protein–protein interaction hot spots

    OpenAIRE

    Cho, Kyu-il; Kim, Dongsup; Lee, Doheon

    2009-01-01

    Identifying features that effectively represent the energetic contribution of an individual interface residue to the interactions between proteins remains problematic. Here, we present several new features and show that they are more effective than conventional features. By combining the proposed features with conventional features, we develop a predictive model for interaction hot spots. Initially, 54 multifaceted features, composed of different levels of information including structure, seq...

  16. Studies of plasmonic hot-spot translation by a metal-dielectric layered superlens

    OpenAIRE

    Thoreson, Mark D.; Nielsen, Rasmus Bundgaard; West, Paul R.; Kriesch, Arian; Liu, Zhengtong; Fang, Jieran; Kildishev, Alexander V.; Peschel, Ulf; Shalaev, Vladimir M.; Boltasseva, Alexandra

    2011-01-01

    We have studied the ability of a lamellar near-field superlens to transfer an enhanced electromagnetic field to the far side of the lens. In this work, we have experimentally and numerically investigated superlensing in the visible range. By using the resonant hot-spot field enhancements from optical nanoantennas as sources, we investigated the translation of these sources to the far side of a layered silver-silica superlens operating in the canalization regime. Using near-field scanning opti...

  17. Microscopic examination of hot spots giving rise to nonlinearity in superconducting resonators

    OpenAIRE

    Kurter, Cihan; Zhuravel, Alexander P.; Ustinov, Alexey V.; Anlage, Steven M.

    2011-01-01

    We investigate the microscopic origins of nonlinear rf response in superconducting electromagnetic resonators. Strong nonlinearity appearing in the transmission spectra at high input powers manifests itself through the emergence of jumplike features near the resonant frequency that evolve toward lower quality factor with higher insertion loss as the rf input power is increased. We directly relate these characteristics to the dynamics of localized normal regions (hot spots) caused by microscop...

  18. Identification and location of hot and cold spots of treated prevalence of depression in Catalonia (Spain)

    OpenAIRE

    Salinas-Pérez José A; García-Alonso Carlos R; Molina-Parrilla Cristina; Jordà-Sampietro Esther; Salvador-Carulla Luis

    2012-01-01

    Abstract Background Spatial analysis is a relevant set of tools for studying the geographical distribution of diseases, although its methods and techniques for analysis may yield very different results. A new hybrid approach has been applied to the spatial analysis of treated prevalence of depression in Catalonia (Spain) according to the following descriptive hypotheses: 1) spatial clusters of treated prevalence of depression (hot and cold spots) exist and, 2) these clusters are related to th...

  19. Current-induced forces and hot-spots in biased nano-junctions

    OpenAIRE

    Lu, Jing Tao; Christensen, Rasmus Bjerregaard; Wang, Jian-Sheng; Hedegård, Per; Brandbyge, Mads

    2014-01-01

    We investigate theoretically the interplay of current-induced forces (CIFs), Joule heating, and heat transport inside a current-carrying nanoconductor. We find that the CIFs, due to the electron-phonon coherence, can control the spatial heat dissipation in the conductor. This yields a significant asymmetric concentration of excess heating (hot spot) even for a symmetric conductor. When coupled to the electrode phonons, CIFs drive different phonon heat flux into the two electrodes. First-princ...

  20. Highly Shocked Polymer Bonded Explosives at a Nonplanar Interface: Hot-Spot Formation Leading to Detonation

    OpenAIRE

    An, Qi; Goddard, William A.; Zybin, Sergey V.; Jaramillo-Botero, Andres; Zhou, Tingting

    2013-01-01

    We report reactive molecular dynamics simulations using the ReaxFF reactive force field to examine shock-induced hot-spot formation followed by detonation initiation in realistic (2.7 million atoms) models of polymer bonded explosives (PBX) with nonplanar interfaces. We considered here two energetic materials (EMs) pentaerythritol tetranitrate (PETN), a common EM for PBX, and silicon pentaerythritol tetranitrate (Si-PETN), which is so extremely sensitive that it has not been possible to chara...

  1. WiFi Hot Spot Service Business for the Automotive and Oil Industries: A Competitive Analysis

    OpenAIRE

    Louis-Francois PAU; M.H.P. OREMUS

    2010-01-01

    While you refuel for gas, why not refuel for information or upload vehicle data, using a cheap wireless technology as WiFi? This paper analyzes in extensive detail the user segmentation by vehicle usage, service offering, and full business models from WiFi hot spot services delivered to and from vehicles (private, professional, public) around gas stations. Are also analyzed the parties which play a role in such services: authorization, provisioning and delivery, with all the dependencies mode...

  2. A note on 'hot spot' hunting in deep-inelastic scattering

    International Nuclear Information System (INIS)

    We consider the inclusive cross section for jet production with large transverse momentum in deep-inelastic scattering. This process has been proposed as a probe of small-x physics, particularly the measurement of 'hot spots' inside the proton. We present a numerical calculation of this process, taking into account a larger phase space. The theoretical reliability, as well as phenomenological uncertainties in the calculation, are discussed. (Author)

  3. An analytical model of pipelined circuit switching in hypercubes in the presence of hot spot traffic

    OpenAIRE

    Safaei, F.; Khonsari, A.; Fathy, M.; Ould-Khaoua, M.

    2005-01-01

    Several recent studies have revealed that PCS can provide superior performance characteristics over wormhole switching under uniform traffic. Analytical model of PCS for common networks (e.g., hypercube) under uniform traffic pattern have recently been reported in the literature. In this paper we propose an analytical model of PCS in the hypercube network augmented with virtual channel in the presence of hot spot traffic. The model has a good agreement with simulation experiments.

  4. Hot-Spot Avoidance With Multi-Pathing Over Infiniband: An MPI Perspective

    Energy Technology Data Exchange (ETDEWEB)

    Vishnu, A; Koop, M; Moody, A; Mamidala, A R; Narravula, S; Panda, D K

    2007-03-06

    Large scale InfiniBand clusters are becoming increasingly popular, as reflected by the TOP 500 Supercomputer rankings. At the same time, fat tree has become a popular interconnection topology for these clusters, since it allows multiple paths to be available in between a pair of nodes. However, even with fat tree, hot-spots may occur in the network depending upon the route configuration between end nodes and communication pattern(s) in the application. To make matters worse, the deterministic routing nature of InfiniBand limits the application from effective use of multiple paths transparently and avoid the hot-spots in the network. Simulation based studies for switches and adapters to implement congestion control have been proposed in the literature. However, these studies have focused on providing congestion control for the communication path, and not on utilizing multiple paths in the network for hot-spot avoidance. In this paper, we design an MPI functionality, which provides hot-spot avoidance for different communications, without a priori knowledge of the pattern. We leverage LMC (LID Mask Count) mechanism of InfiniBand to create multiple paths in the network and present the design issues (scheduling policies, selecting number of paths, scalability aspects) of our design. We implement our design and evaluate it with Pallas collective communication and MPI applications. On an InfiniBand cluster with 48 processes, collective operations like MPI All-to-all Personalized and MPI Reduce Scatter show an improvement of 27% and 19% respectively. Our evaluation with MPI applications like NAS Parallel Benchmarks and PSTSWM on 64 processes shows significant improvement in execution time with this functionality.

  5. Wood ant nests as hot spots of carbon dioxide production and cold spots of methane oxidation in temperate forests

    Science.gov (United States)

    Jilkova, Veronika; Picek, Tomas; Cajthaml, Tomas; Frouz, Jan

    2016-04-01

    Wood ant nests are known as hot spots of carbon dioxide (CO2) production and are also thought to affect methane (CH4) flux. Stable high temperatures are maintained in ant nests even in cold environments. Here we focused on quantification of CO2 and CH4 flux in wood ant nests, contribution of ants and microbes to CO2 production, properties of nest material that affect CO2 production and the role of ants and microbes in the maintenance of nest temperature. The research was conducted in temperate and boreal forests inhabited by wood ants (Formica s. str.). Gas fluxes were measured either by an infrared gas analyser or a static chamber technique. Ants and nest materials were also incubated in a laboratory. Material properties potentially influencing CO2 flux, such as moisture, nutrient content or temperature were determined. According to the results, CH4 oxidation was lower in wood ant nests than in the surrounding forest soil suggesting that some characteristics of ant nests hinder CH4 oxidation or promote CH4 production. These characteristics were mainly available carbon and nitrogen contents. Wood ant nests clearly are hot spots of CO2 production in temperate forests originating mainly from ant and also from microbial metabolism. Most important properties positively affecting CO2 production were found to be moisture, nutrient content and temperature. Nest temperature is maintained by ant and microbial metabolism; nests from colder environments produce more metabolic heat to maintain similar temperature as nests from warmer environments. In conclusion, as the abundance of wood ant nests in some forests can be very high, ant nests may largely increase heterogeneity in greenhouse gas fluxes in forest ecosystems.

  6. Solvent-accessible surface area: How well can be applied to hot-spot detection?

    Science.gov (United States)

    Martins, João M; Ramos, Rui M; Pimenta, António C; Moreira, Irina S

    2014-03-01

    A detailed comprehension of protein-based interfaces is essential for the rational drug development. One of the key features of these interfaces is their solvent accessible surface area profile. With that in mind, we tested a group of 12 SASA-based features for their ability to correlate and differentiate hot- and null-spots. These were tested in three different data sets, explicit water MD, implicit water MD, and static PDB structure. We found no discernible improvement with the use of more comprehensive data sets obtained from molecular dynamics. The features tested were shown to be capable of discerning between hot- and null-spots, while presenting low correlations. Residue standardization such as rel SASAi or rel/res SASAi , improved the features as a tool to predict ΔΔGbinding values. A new method using support machine learning algorithms was developed: SBHD (Sasa-Based Hot-spot Detection). This method presents a precision, recall, and F1 score of 0.72, 0.81, and 0.76 for the training set and 0.91, 0.73, and 0.81 for an independent test set. PMID:24105801

  7. Characterization of hot spots for natural chloroform formation: Relevance for groundwater quality

    Science.gov (United States)

    Jacobsen, Ole S.; Albers, Christian N.; Laier, Troels

    2015-04-01

    Chloroform soil hot spot may deteriorate groundwater quality and may even result in chloroform concentration exceeding the Danish maximum limit of 1 µg/L in groundwater for potable use. In order to characterize the soil properties important for the chloroform production, various ecosystems were examined with respect to soil air chloroform and soil organic matter type and content. Coniferous forest areas, responsible for highest chloroform concentrations, were examined on widely different scales from km to cm scale. Furthermore, regular soil gas measurements including chloroform were performed during 4 seasons at various depths, together with various meteorological measurements and soil temperature recordings. Laboratory incubation experiments were also performed on undisturbed soil samples in order to examine the role of various microbiota, fungi and bacteria. To identify hot spots responsible for the natural contamination we have measured the production of chloroform in the upper soil from different terrestrial systems. Field measurements of chloroform in top soil air were used as production indicators. The production was however not evenly distributed at any scale. The ecosystems seem to have quite different net-productions of chloroform from very low in grassland to very high in some coniferous forests. Within the forest ecosystem we found large variation in chloroform concentrations depending on vegetation. In beech forest we found the lowest values, somewhat higher in an open pine forest, but the highest concentrations were detected in spruce forest without any vegetation beneath. Within this ecotype, it appeared that the variation was also large; hot spots with 2-4 decades higher production than the surrounding area. These hot spots were not in any way visually different from the surroundings and were of variable size from 3 to 20 meters in diameter. Besides this, measurements within a seemingly homogenous hot spot showed that there was still high

  8. How Similar Are Protein Folding and Protein Binding Nuclei? Examination of Vibrational Motions of Energy Hot Spots and Conserved Residues

    OpenAIRE

    Haliloglu, Turkan; Keskin, Ozlem; Ma, Buyong; Nussinov, Ruth

    2004-01-01

    The underlying physico-chemical principles of the interactions between domains in protein folding are similar to those between protein molecules in binding. Here we show that conserved residues and experimental hot spots at intermolecular binding interfaces overlap residues that vibrate with high frequencies. Similarly, conserved residues and hot spots are found in protein cores and are also observed to vibrate with high frequencies. In both cases, these residues contribute significantly to t...

  9. Hot-spot application of biocontrol agents to replace pesticides in large scale commercial rose farms in Kenya

    DEFF Research Database (Denmark)

    Gacheri, Catherine; Kigen, Thomas; Sigsgaard, Lene

    2015-01-01

    Rose (Rosa hybrida L.) is the most important ornamental crop in Kenya, with huge investments in pest management. We provide the first full-scale, replicated experiment comparing cost and yield of conventional two-spotted spider mite (Tetranychus urticae Koch) control with hot-spot applications of...

  10. Predicting hot spots in protein interfaces based on protrusion index, pseudo hydrophobicity and electron-ion interaction pseudopotential features

    Science.gov (United States)

    Xia, Junfeng; Yue, Zhenyu; Di, Yunqiang; Zhu, Xiaolei; Zheng, Chun-Hou

    2016-01-01

    The identification of hot spots, a small subset of protein interfaces that accounts for the majority of binding free energy, is becoming more important for the research of drug design and cancer development. Based on our previous methods (APIS and KFC2), here we proposed a novel hot spot prediction method. For each hot spot residue, we firstly constructed a wide variety of 108 sequence, structural, and neighborhood features to characterize potential hot spot residues, including conventional ones and new one (pseudo hydrophobicity) exploited in this study. We then selected 3 top-ranking features that contribute the most in the classification by a two-step feature selection process consisting of minimal-redundancy-maximal-relevance algorithm and an exhaustive search method. We used support vector machines to build our final prediction model. When testing our model on an independent test set, our method showed the highest F1-score of 0.70 and MCC of 0.46 comparing with the existing state-of-the-art hot spot prediction methods. Our results indicate that these features are more effective than the conventional features considered previously, and that the combination of our and traditional features may support the creation of a discriminative feature set for efficient prediction of hot spots in protein interfaces. PMID:26934646

  11. Hot spot mitigation in microprocessors by application of single phase microchannel heat sink and microprocessor floor planning

    Science.gov (United States)

    Chauhan, Anjali

    Poor thermal management in high frequency microprocessors results in thermal and mechanical stresses in the chip due to leakage losses, occurrence of hot spots and large temperature gradients. A micro-fluidics based cooling scheme of single phase microchannel heat sinks is found to be most promising cooling solution. Microchannel heat sinks have high cooling capability because of its high surface area to volume ratio and high heat transfer coefficient. Besides the fluid flow, heat transfer mechanism in microchannel heat sinks is affected by its installation on the microprocessor chip. Since microchannel heat sinks are capable of reducing only the average temperature rise of the microprocessor chip, technique of microprocessor floor planning can be applied to reduce hot spot temperature, mitigate multiple hot spots and reduce large temperature gradients on the surface of microprocessor chip. In this study, adequate installation of the microchannel heat sink on the processor chip has been proposed to extract maximum heat from the device. Microprocessor floor planning has also been explored to obtain an optimum chip floor plan on grounds of low performance penalty, low hot spot temperature and minimum number hot spots. The dependence of maximum hot spot temperature of the chip on pressure gradient across the microchannels has also been discussed.

  12. TERT promoter hot spot mutations are frequent in Indian cervical and oral squamous cell carcinomas.

    Science.gov (United States)

    Vinothkumar, Vilvanathan; Arunkumar, Ganesan; Revathidevi, Sundaramoorthy; Arun, Kanagaraj; Manikandan, Mayakannan; Rao, Arunagiri Kuha Deva Magendhra; Rajkumar, Kottayasamy Seenivasagam; Ajay, Chandrasekar; Rajaraman, Ramamurthy; Ramani, Rajendren; Murugan, Avaniyapuram Kannan; Munirajan, Arasambattu Kannan

    2016-06-01

    Squamous cell carcinoma (SCC) of the uterine cervix and oral cavity are most common cancers in India. Telomerase reverse transcriptase (TERT) overexpression is one of the hallmarks for cancer, and activation through promoter mutation C228T and C250T has been reported in variety of tumors and often shown to be associated with aggressive tumors. In the present study, we analyzed these two hot spot mutations in 181 primary tumors of the uterine cervix and oral cavity by direct DNA sequencing and correlated with patient's clinicopathological characteristics. We found relatively high frequency of TERT hot spot mutations in both cervical [21.4 % (30/140)] and oral [31.7 % (13/41)] squamous cell carcinomas. In cervical cancer, TERT promoter mutations were more prevalent (25 %) in human papilloma virus (HPV)-negative cases compared to HPV-positive cases (20.6 %), and both TERT promoter mutation and HPV infection were more commonly observed in advanced stage tumors (77 %). Similarly, the poor and moderately differentiated tumors of the uterine cervix had both the TERT hot spot mutations and HPV (16 and 18) at higher frequency (95.7 %). Interestingly, we observed eight homozygous mutations (six 228TT and two 250TT) only in cervical tumors, and all of them were found to be positive for high-risk HPV. To the best of our knowledge, this is the first study from India reporting high prevalence of TERT promoter mutations in primary tumors of the uterine cervix and oral cavity. Our results suggest that TERT reactivation through promoter mutation either alone or in association with the HPV oncogenes (E6 and E7) could play an important role in the carcinogenesis of cervical and oral cancers. PMID:26700669

  13. Airborne Remote Sensing of a Biological Hot Spot in the Southeastern Bering Sea

    Directory of Open Access Journals (Sweden)

    Michael F. Sigler

    2011-03-01

    Full Text Available Intense, ephemeral foraging events within localized hot spots represent important trophic transfers to top predators in marine ecosystems, though the spatial extent and temporal overlap of predators and prey are difficult to observe using traditional methods. The southeastern Bering Sea has high marine productivity along the shelf break, especially near marine canyons. At a hot spot located near Bering Canyon, we observed three foraging events over a 12 day period in June 2005. These were located by aerial surveys, quantified by airborne lidar and visual counts, and characterized by ship-based acoustics and net catches. Because of the high density of seabirds, the events could be seen in images from space-based synthetic aperture radar. The events developed at the shelf slope, adjacent to passes between the Aleutian Islands, persisted for 1 to 8 days, then abruptly disappeared. Build-up and break down of the events occurred on 24 hr time scales, and diameters ranged from 10 to 20 km. These events comprised large concentrations of euphausiids, copepods, herring, other small pelagic fishes, humpback whales, Dall’s porpoise, short-tailed shearwaters, northern fulmars, and other pelagic seabirds. The lidar and acoustic remote sensing data demonstrated that prey densities inside the events were several times higher than those outside, indicating the importance of including events in forage fish surveys. This implies a need for either very intensive traditional surveys covering large expanses or for adaptive surveys guided by remote sensing. To our knowledge, this is the first time that an Alaskan hot spot was monitored with the combination of airborne and satellite remote sensing.

  14. Longitudinal hot-spots in the mesospheric OH variations due to energetic electron precipitation

    Directory of Open Access Journals (Sweden)

    M. E. Andersson

    2013-07-01

    Full Text Available Using Microwave Limb Sounder (MLS/Aura and Medium Energy Proton and Electron Detector (MEPED/POES observations between 2005–2009, we study the longitudinal response of nighttime mesospheric OH to radiation belt electron precipitation. Our analysis concentrates on geomagnetic latitudes from 55–72° N/S and altitudes between 70–78 km. The aim of this study is to better assess the spatial distribution of electron forcing, which is important for more accurate modeling of its atmospheric and climate effects. In the Southern Hemisphere, OH data show a hot-spot at longitudes between 150° W–30° E, i.e., poleward of the Southern Atlantic Magnetic Anomaly (SAMA region. In the Northern Hemisphere, energetic electron precipitation–induced OH variations are more equally distributed with longitude. This longitudinal behaviour of OH can also be identified using Empirical Orthogonal Function analysis, and is found to be similar to that of MEPED–measured electron fluxes. The main difference is in the SAMA region, where MEPED appears to measure very large electron fluxes while MLS observations show no enhancement of OH. This indicates that in the SAMA region the MEPED observations are not related to precipitating electrons, at least not at energies > 100 keV, but related to instrument contamination. Analysis of selected OH data sets for periods of different geomagnetic activity levels shows that the longitudinal OH hot-spot south of the SAMA (the Antarctic Peninsula region is partly caused by strong, regional electron forcing, although atmospheric conditions also seem to play a role. This OH hot-spot is even seen weakly during periods of lower geomagnetic activity, which suggest that there is a steady drizzle of electrons affecting the atmosphere, due to the Earth's magnetic field being weaker in this region.

  15. Hot spot analysis applied to identify ecosystem services potential in Lithuania

    Science.gov (United States)

    Pereira, Paulo; Depellegrin, Daniel; Misiune, Ieva

    2016-04-01

    Hot spot analysis are very useful to identify areas with similar characteristics. This is important for a sustainable use of the territory, since we can identify areas that need to be protected, or restored. This is a great advantage in terms of land use planning and management, since we can allocate resources, reduce the economical costs and do a better intervention in the landscape. Ecosystem services (ES) are different according land use. Since landscape is very heterogeneous, it is of major importance understand their spatial pattern and where are located the areas that provide better ES and the others that provide less services. The objective of this work is to use hot-spot analysis to identify areas with the most valuable ES in Lithuania. CORINE land-cover (CLC) of 2006 was used as the main spatial information. This classification uses a grid of 100 m resolution and extracted a total of 31 land use types. ES ranking was carried out based on expert knowledge. They were asked to evaluate the ES potential of each different CLC from 0 (no potential) to 5 (very high potential). Hot spot analysis were evaluated using the Getis-ord test, which identifies cluster analysis available in ArcGIS toolbox. This tool identifies areas with significantly high low values and significant high values at a p level of 0.05. In this work we used hot spot analysis to assess the distribution of providing, regulating cultural and total (sum of the previous 3) ES. The Z value calculated from Getis-ord was used to statistical analysis to access the clusters of providing, regulating cultural and total ES. ES with high Z value show that they have a high number of cluster areas with high potential of ES. The results showed that the Z-score was significantly different among services (Kruskal Wallis ANOVA =834. 607, pcultural (0.080±1.979) and regulating (0.076±1.961). These results suggested that providing services are more clustered than the remaining. Ecosystem Services Z score were

  16. WiFi hot spot superdistribution : a profit scheme for WiFi access distribution

    OpenAIRE

    Fritsch, Lothar

    2005-01-01

    The wide-area deployment of WiFi hot spots challenges IP access providers. While new profit models are sought after by them, profitability as well as logistics for large-scale deployment of 802.11 wireless technology are still to be proven. Expenditure for hardware, locations, maintenance, connectivity, marketing, billing and customer care must be considered. Even for large carriers with infrastructure, the deployment of a large-scale WiFi infrastructure may be risky. This paper proposes a mu...

  17. A high resolution view of the jet termination shock in a hot spot of the nearby radio galaxy Pictor A: implications for X-ray models of radio galaxy hot spots

    CERN Document Server

    Tingay, S J; Brunetti, G; Bondi, M

    2008-01-01

    Images made with the VLBA have resolved the region in a nearby radio galaxy, Pictor A, where the relativistic jet that originates at the nucleus terminates in an interaction with the intergalactic medium, a so-called radio galaxy hot spot. This image provides the highest spatial resolution view of such an object to date (16 pc), more than three times better than previous VLBI observations of similar objects. The north-west Pictor A hot spot is resolved into a complex set of compact components, seen to coincide with the bright part of the hot spot imaged at arcsecond-scale resolution with the VLA. In addition to a comparison with VLA data, we compare our VLBA results with data from the HST and Chandra telescopes, as well as new Spitzer data. The presence of pc-scale components in the hot spot, identifying regions containing strong shocks in the fluid flow, leads us to explore the suggestion that they represent sites of synchrotron X-ray production, contributing to the integrated X-ray flux of the hot spot, alo...

  18. Analysis and Visualization for Hot Spot Based Route Recommendation Using Short-Dated Taxi GPS Traces

    Directory of Open Access Journals (Sweden)

    Ying Shen

    2015-04-01

    Full Text Available Taxi GPS traces, which contain a great deal of valuable information as regards to human mobility and city traffic, can be extracted to improve the quality of our lives. Since the method of visualized analysis is believed to be an effective way to present information vividly, we develop our analysis and visualization method based on a city’s short-dated taxi GPS traces, which can provide recommendation to help cruising taxi drivers to find potential passengers with optimal routes. With our approach, hot spots for loading and unloading passenger(s are extracted using an improved DBSCAN algorithm after data preprocessing including cleaning and filtering. Then, this paper describes the start-end point-based similar trajectory method to get coarse-level trajectories clusters, together with the density-based ε distance trajectory clustering algorithm to identify recommended potential routes. A weighted tree is defined including such factors as driving time, velocity, distance and endpoint attractiveness for optimal route evaluation from vacant to occupied hot spots. An example is presented to show the effectiveness of our visualization method.

  19. Investigation of PSEN1, 2 Hot Spots in Iranian Early-Onset Alzheimer's Disease Patients

    Directory of Open Access Journals (Sweden)

    Leila Akbari

    2015-02-01

    Full Text Available Background: Alzheimer's disease is a progressive, neurodegenerative disease with both genetic and non genetic causes. Familial Alzheimer's disease can be caused by mutations in the amyloid precursor protein, presenilin 1 and presenilin 2. Early-onset familial Alzheimer's disease (autosomal dominantly inherited accounts for a small fraction (2-3% of Alzheimer's disease cases. The aim of this study was investigation of exons 5, 7 in PSEN1 and exons 5, 6 in PSEN2 genes in Iranian patients with early onset Alzheimer disease. These exons were hot spots in different country. Materials and Methods: In this experimental study 24 patients with early onset Alzheimer disease and 48 healthy subjects as control group were included in this study. After DNAs extraction from whole blood, PCR-sequencing was used to amplify and analyze 4 exons. Results: Two known mutations (Glu 120 Lys in exon 3 of two patients and Arg 62 His in exon 5 of one patient were found. Conclusion: According to the above findings, these exons were not hot spot in Iran.

  20. Identifying geographic hot spots of reassortment in a multipartite plant virus.

    Science.gov (United States)

    Savory, Fiona R; Varma, Varun; Ramakrishnan, Uma

    2014-05-01

    Reassortment between different species or strains plays a key role in the evolution of multipartite plant viruses and can have important epidemiological implications. Identifying geographic locations where reassortant lineages are most likely to emerge could be a valuable strategy for informing disease management and surveillance efforts. We developed a predictive framework to identify potential geographic hot spots of reassortment based upon spatially explicit analyses of genome constellation diversity. To demonstrate the utility of this approach, we examined spatial variation in the potential for reassortment among Cardamom bushy dwarf virus (CBDV; Nanoviridae, Babuvirus) isolates in Northeast India. Using sequence data corresponding to six discrete genome components for 163 CBDV isolates, a quantitative measure of genome constellation diversity was obtained for locations across the sampling region. Two key areas were identified where viruses with highly distinct genome constellations cocirculate, and these locations were designated as possible geographic hot spots of reassortment, where novel reassortant lineages could emerge. Our study demonstrates that the potential for reassortment can be spatially dependent in multipartite plant viruses and highlights the use of evolutionary analyses to identify locations which could be actively managed to facilitate the prevention of outbreaks involving novel reassortant strains. PMID:24944570

  1. Full protein flexibility is essential for proper hot-spot mapping.

    Science.gov (United States)

    Lexa, Katrina W; Carlson, Heather A

    2011-01-19

    A traditional technique for structure-based drug design (SBDD) is mapping of protein surfaces with probe molecules to identify "hot spots" where key functional groups can best complement the receptor. Common methods, such as minimization of probes or calculation of grids, use a fixed protein structure in the gas phase, ignoring both protein flexibility and proper competition between the probes and water. As a result, the potential surface is quite rugged, and many spurious local minima are identified. In this work, we compared rigid and fully flexible proteins in mixed-solvent molecular dynamics, which allows for flexibility and full solvent effects. We were surprised to find that the large number of local minima are still found when a protein's conformational sampling is restricted; the dynamic averaging of probes and competition with water do not smooth the potential surface as one might expect. Only when a protein is allowed to be fully flexible in the simulation are the proper minima located and the spurious ones eliminated. Our results indicate that inclusion of full protein flexibility is critical to accurate hot-spot mapping for SBDD. PMID:21158470

  2. Sensitivity of inertial confinement fusion hot spot properties to the deuterium-tritium fuel adiabat

    Science.gov (United States)

    Melvin, J.; Lim, H.; Rana, V.; Cheng, B.; Glimm, J.; Sharp, D. H.; Wilson, D. C.

    2015-02-01

    We determine the dependence of key Inertial Confinement Fusion (ICF) hot spot simulation properties on the deuterium-tritium fuel adiabat, here modified by addition of energy to the cold shell. Variation of this parameter reduces the simulation to experiment discrepancy in some, but not all, experimentally inferred quantities. Using simulations with radiation drives tuned to match experimental shots N120321 and N120405 from the National Ignition Campaign (NIC), we carry out sets of simulations with varying amounts of added entropy and examine the sensitivities of important experimental quantities. Neutron yields, burn widths, hot spot densities, and pressures follow a trend approaching their experimentally inferred quantities. Ion temperatures and areal densities are sensitive to the adiabat changes, but do not necessarily converge to their experimental quantities with the added entropy. This suggests that a modification to the simulation adiabat is one of, but not the only explanation of the observed simulation to experiment discrepancies. In addition, we use a theoretical model to predict 3D mix and observe a slight trend toward less mixing as the entropy is enhanced. Instantaneous quantities are assessed at the time of maximum neutron production, determined dynamically within each simulation. These trends contribute to ICF science, as an effort to understand the NIC simulation to experiment discrepancy, and in their relation to the high foot experiments, which features a higher adiabat in the experimental design and an improved neutron yield in the experimental results.

  3. Sensitivity of inertial confinement fusion hot spot properties to the deuterium-tritium fuel adiabat

    Energy Technology Data Exchange (ETDEWEB)

    Melvin, J.; Lim, H.; Rana, V.; Glimm, J. [Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, New York 11794-3600 (United States); Cheng, B.; Sharp, D. H.; Wilson, D. C. [Los Alamos National Laboratory, Los Alamos, New Mexico 87545 (United States)

    2015-02-15

    We determine the dependence of key Inertial Confinement Fusion (ICF) hot spot simulation properties on the deuterium-tritium fuel adiabat, here modified by addition of energy to the cold shell. Variation of this parameter reduces the simulation to experiment discrepancy in some, but not all, experimentally inferred quantities. Using simulations with radiation drives tuned to match experimental shots N120321 and N120405 from the National Ignition Campaign (NIC), we carry out sets of simulations with varying amounts of added entropy and examine the sensitivities of important experimental quantities. Neutron yields, burn widths, hot spot densities, and pressures follow a trend approaching their experimentally inferred quantities. Ion temperatures and areal densities are sensitive to the adiabat changes, but do not necessarily converge to their experimental quantities with the added entropy. This suggests that a modification to the simulation adiabat is one of, but not the only explanation of the observed simulation to experiment discrepancies. In addition, we use a theoretical model to predict 3D mix and observe a slight trend toward less mixing as the entropy is enhanced. Instantaneous quantities are assessed at the time of maximum neutron production, determined dynamically within each simulation. These trends contribute to ICF science, as an effort to understand the NIC simulation to experiment discrepancy, and in their relation to the high foot experiments, which features a higher adiabat in the experimental design and an improved neutron yield in the experimental results.

  4. Wood ant nests as hot spots of microbial activity in forest ecosystems

    Science.gov (United States)

    Jilkova, Veronika; Frouz, Jan

    2015-04-01

    Wood ants build large and long-lasting nests from organic materials and mineral soil which have a very special structure. Nests are well-aerated due to numerous chambers and galleries and stable temperature and moisture are maintained there thanks to ant activities. These conditions together with the constant input of easily available nutrients from food of ants support microbial activity. Due to respiration of ants and microbes, wood ant nests are known as hot spots of CO2 production in forest ecosystems. Although the main source of CO2 is represented by ant respiration, a significant amount of CO2 originates also from microbial decomposition of organic materials. Several conditions affect microbial respiration, such as moisture of nest material, changes in temperatures or food input. As mineral nutrients are released from organic materials, wood ant nests represent hot spots of mineral nutrients in forest ecosystems which can be exploited by other organisms, such as roots of trees, and can also cause heterogeneity in species abundance and composition.

  5. Space and time resolved observations of hot spots dynamics in a vacuum spark discharge

    International Nuclear Information System (INIS)

    Experimental observations of the plasma formations in a vacuum spark discharge are presented. A low power Nd:YAG laser pulse incident onto a titanium cathode initiates the discharge. The evolution of the titanium plasma electron density and temperature is followed both in the visible and the soft X-ray part of the spectrum. The former uses a novel micro holographic interferometric technique permitting a spatial resolution better than 20 μm. The probing beam is a 6 ns frequency doubled Nd:YAG laser. The latter emission is resolved using a number of different methods. The spatial information is derived from a 1 ns multi framing camera X-ray camera which projects the plasma image using four different slit wire pinhole images and six pinhole images, each aperture being filtered differently. The temporal evolution of the emission of each discharge is followed using several silicon PIN diodes. The x-ray spectrum is unfolded from the filter and detector response and interpreted using a collisional radiative package. The hot spots are seen to form in a submillimeter pinch stemming from the incident laser focus which has a life time about 20 ns. The hot spots are much shorter events, reaching substantially higher densities, but involve only part of the line density of the pinch column. (author). 4 figs., 8 refs

  6. Hot spots and labyrinths: Why cortical neuromodulation for episodic migraine with aura should be personalized

    Directory of Open Access Journals (Sweden)

    Markus A Dahlem

    2015-03-01

    Full Text Available Stimulation protocols for medical devices should be rationally designed. For episodic migraine with aura we outline model-based design strategies towards preventive and acute therapies using stereotactic cortical neuromodulation. To this end, we regard a localized spreading depression (SD wave segment as a central element in migraine pathophysiology. To describe nucleation and propagation features of the SD wave segment, we define the new concepts of cortical hot spots and labyrinths, respectively. In particular, we firstly focus exclusively on curvature-induced dynamical properties by studying a generic reaction-diffusion model of SD on the folded cortical surface. This surface is described with increasing level of details, including finally personalized simulations using patient's magnetic resonance imaging (MRI scanner readings. At this stage, the only relevant factor that can modulate nucleation and propagation paths is the Gaussian curvature, which has the advantage of being rather readily accessible by MRI. We conclude with discussing further anatomical factors, such as areal, laminar, and cellular heterogeneity, that in addition to and in relation to Gaussian curvature determine the generalized concept of cortical hot spots and labyrinths as target structures for neuromodulation. Our numerical simulations suggest that these target structures are like fingerprints, they are individual features of each migraine sufferer. The goal in the future will be to provide individualized neural tissue simulations. These simulations should predict the clinical data and therefore can also serve as a test bed for exploring stereotactic cortical neuromodulation.

  7. Complex shock structure in the western hot-spot of Pictor A

    CERN Document Server

    Saxton, C J; Bicknell, G V; Blanchet, G; Wagner, S J; Metchnik, M V; Saxton, Curtis J.; Sutherland, Ralph S.; Bicknell, Geoffrey V.; Blanchet, Gwendoline; Wagner, Stefan J.; Metchnik, Marc V.

    2002-01-01

    We have carried out simulations of supersonic light jets in order to model the features observed in optical and radio images of the western hot-spot in the radio galaxy Pictor A. We have considered jets with density ratios eta=1e-2 - 1e-4, and Mach numbers ranging between 5 and 50. From each simulation, we have generated ray-traced maps of radio surface brightness at a variety of jet inclinations, in order to study the appearance of time-dependent luminous structures in the vicinity of the western hot-spot. We compare these rendered images with observed features of Pictor A. A remarkable feature of Pictor A observations is a bar-shaped "filament" inclined almost at right angles to the inferred jet direction and extending 24" (10.8 /h kpc) along its longest axis. The constraints of reproducing the appearance of this structure in simulations indicate that the jet of Pictor A lies nearly in the plane of the sky. The results of the simulation are also consistent with other features found in the radio image of Pic...

  8. The Amsterdam-St. Paul Plateau: A complex hot spot/DUPAL-flavored MORB interaction

    Science.gov (United States)

    Janin, M.; HéMond, C.; Maia, M.; Nonnotte, P.; Ponzevera, E.; Johnson, K. T. M.

    2012-09-01

    The Amsterdam-St Paul (ASP) oceanic plateau results from the interaction between the ASP hot spot and the Southeast Indian ridge. A volcanic chain, named the Chain of the Dead Poets (CDP), lies to its northward tip and is related to the hot spot intraplate activity. The ASP plateau and CDP study reveals that ASP plume composition is inherited from oceanic crust and pelagic sediments recycled in the mantle through a 1.5 Ga subduction process. The ASP plateau lavas have a composition (major and trace elements and Sr-Nd-Pb-Hf isotopes) reflecting the interaction between ASP plume and the Indian MORB mantle, including some clear DUPAL input. The Indian upper mantle below ASP plateau is heterogeneous and made of a depleted mantle with lower continental crust (LCC) fragments probably delaminated during the Gondwana break-up. The lower continental crust is one of the possible reservoirs for the DUPAL anomaly origin that our data support. The range of magnitude of each end-member required in ASP plateau samples is (1) 45% to 75% of ASP plume and (2) 25% to 55% of Indian DM within 0% to a maximum of 6% of LCC layers included within. The three end-members involved (plume, upper mantle and lower continental crust) and their mixing in different proportions enhances the geochemical variability in the plateau lavas. Consequently, the apparent composition homogeneity of Amsterdam Island, an aerial summit of the plateau, may result from the presence of intermediate magmatic chambers into the plateau structure.

  9. Possible hot spots excited by the relativistic jets of Cygnus X-3

    CERN Document Server

    Martí, J; Garrido, J L; Luque-Escamilla, P; Paredes, J M

    2005-01-01

    We present the results of a deep search for associated radio features in the vicinity of the microquasar Cygnus X-3. The motivation behind is to find out evidence for interaction between its relativistic jets and the surrounding interstellar medium, which could eventually allow us to perform calorimetry of the total energy released by this microquasar during its flaring lifetime. Remarkably, two radio sources with mJy emission level at centimeter wavelengths have been detected in excellent alignment with the position angle of the inner radio jets. We propose that these objects could be the hot spots where the relativitic outflow collides with the ambient gas in analogy with Fanaroff-Riley II radio galaxies. These candidate hot spots are within a few arc-minutes of Cygnus X-3 and, if physically related, the full linear extent of the jet would reach tens of parsecs. We discuss here the evidence currently available to support this hypothesis based on both archival data and our own observations.

  10. Deep-sea hydrothermal vents: potential hot spots for natural products discovery?

    Science.gov (United States)

    Thornburg, Christopher C; Zabriskie, T Mark; McPhail, Kerry L

    2010-03-26

    Deep-sea hydrothermal vents are among the most extreme and dynamic environments on Earth. However, islands of highly dense and biologically diverse communities exist in the immediate vicinity of hydrothermal vent flows, in stark contrast to the surrounding bare seafloor. These communities comprise organisms with distinct metabolisms based on chemosynthesis and growth rates comparable to those from shallow water tropical environments, which have been rich sources of biologically active natural products. The geological setting and geochemical nature of deep-sea vents that impact the biogeography of vent organisms, chemosynthesis, and the known biological and metabolic diversity of Eukarya, Bacteria, and Archaea, including the handful of natural products isolated to date from deep-sea vent organisms, are considered here in an assessment of deep-sea hydrothermal vents as potential hot spots for natural products investigations. Of critical importance too are the logistics of collecting deep vent organisms, opportunities for re-collection considering the stability and longevity of vent sites, and the ability to culture natural product-producing deep vent organisms in the laboratory. New cost-effective technologies in deep-sea research and more advanced molecular techniques aimed at screening a more inclusive genetic assembly are poised to accelerate natural product discoveries from these microbial diversity hot spots. PMID:20099811

  11. Hot and cold spots in the first plus second year COBE/DMR maps

    CERN Document Server

    Cayon, L; Cayon, Laura; Smoot, George

    1995-01-01

    Density perturbations at the decoupling epoch produce angular fluctuations in the temperature of the Cosmic Microwave Background (CMB) radiation that may appear as hot and cold spots. Observational data of the CMB includes instrumental noise in addition to the cosmological signal. One would like to determine which of the observed spots are produced by the noise and which correspond to signal. In this work we first present a statistical analysis of the first plus second year COBE/DMR map at 53 GHz that reveals the presence of cosmological signal in the data. The analysis is based on Harrison-Zeldovich Monte Carlo realizations and utilizes a generalized \\chi^2 statistic. The method is applied to the number of spots and the fraction of the total area that appear above/below a certain value of the dispersion of the noise, including and excluding the quadrupole, giving Q_{rms-PS}=15^{+3}_{-6}, 18^{+5}_{-7} \\mu K and Q_{rms-PS}=18^{+3}_{-4}, 21\\pm6 \\mu K, at the 95\\% confidence level, respectively. The data taken b...

  12. Experimental estimation of the hot spot size in Nb-based Josephson tunnel junctions using Abrikosov vortices

    International Nuclear Information System (INIS)

    We report on a new experimental approach to the size estimation of the hot spot induced by ionizing particles in a Josephson tunnel junction. Here, in contrast to the case of a superconducting strip, it is possible to investigate the hot spot dynamics in absence of effects due to the heating induced by the bias current. The reported experiment is based on the motion of Abrikosov vortices, trapped in the thin films constituting the junction electrodes, under 5.6 MeV α-particle irradiation. The fast time evolution of a hot spot, combined with the presence of Abrikosov vortices, produces a change of the static magnetic field in the junction area and thus a change of the critical current value, Ic. Measurements of Ic during the α-particle irradiation and in presence of trapped Abrikosov vortices allow to determine the rate of appearance of those Ic changes. The behavior of the average appearance rate as function of the Abrikosov vortices density provides a direct determination of the maximum hot spot area. The experiment is performed on a high quality Nb/Al endash AlOx/Nb junction of circular geometry and with open-quotes smallclose quotes dimensions with respect to the Josephson penetration depth. A value of 4.7±1.2μm2 is found for the maximum hot spot area. copyright 1997 American Institute of Physics

  13. Effects of Long- and Intermediate-Wavelength Nonuniformities on Hot-Spot Energetics of Hydrodynamic Equivalent Targets

    Science.gov (United States)

    Bose, A.; Betti, R.; Woo, K. M.; Christopherson, A. R.; Shvarts, D.

    2015-11-01

    The impact of intermediate- and low-mode nonuniformities on the performance of inertial confinement fusion (ICF) implosions is investigated by a detailed study of hot-spot energetics. It is found that low- (1 ~ 2) and intermediate-mode (1 >= 10) asymmetries affect the hot-spot hydrodynamics in very different ways. It is observed that for low-mode asymmetries, the fusion yield decreases because of a significant reduction in hot-spot pressure while the neutron-averaged hot-spot volume remains comparable to that of unperturbed (clean) simulations. On the other hand, implosions with moderate-amplitude, intermediate-wavelength modes, which are amplified by the Rayleigh-Taylor instability (RTI), exhibit a fusion-yield degradation primarily caused by a reduction in the burn volume without significant degradation of the pressure. For very large amplitudes, the intermediate modes show a ``secondary piston effect,'' where the converging RTI spikes compress a much smaller volume, allowing for a secondary conversion of the shell's kinetic energy to internal energy at a central region. Understanding the effects of nonuniformities on the hot-spot energetics provides valuable insight in determining the causes of performance degradation in current ICF experiments. This material is based upon work supported by the Department of Energy National Nuclear Security Administration under Award Number DE-NA0001944 and DE-FC02-04ER54789 (Fusion Science Center).

  14. Laser interaction effects of electromagnetic absorption and microstructural defects on hot-spot formation in RDX-PCTFE energetic aggregates

    International Nuclear Information System (INIS)

    Hot-spot formation in energetic aggregates subjected to dynamic pressure loading and laser irradiation has been investigated. Specialized finite-element techniques with a dislocation-density-based crystalline plasticity constitutive formulation and thermo-mechanical coupling of heat conduction, adiabatic heating, laser heating and thermal decomposition were used to predict hot-spot formation in RDX–polymer aggregates subjected to dynamic pressures and laser energies. The effects of the electromagnetic absorption coefficient coupled with void distribution and spacing, grain morphology, crystal–binder interactions and dislocation densities were analyzed to determine their influence on the time, location and mechanisms of hot-spot formation. Four different mechanisms for hot-spot initiation under dynamic laser and pressure loads were identified, which depend on the localization of plastic shear strain and laser heat absorption within the aggregate. The predictions indicate that hot-spot formation is accelerated by higher absorption coefficients and by localized plastic deformations that occur in areas of significant laser heating. (paper)

  15. KFC2: a knowledge-based hot spot prediction method based on interface solvation, atomic density, and plasticity features.

    Science.gov (United States)

    Zhu, Xiaolei; Mitchell, Julie C

    2011-09-01

    Hot spots constitute a small fraction of protein-protein interface residues, yet they account for a large fraction of the binding affinity. Based on our previous method (KFC), we present two new methods (KFC2a and KFC2b) that outperform other methods at hot spot prediction. A number of improvements were made in developing these new methods. First, we created a training data set that contained a similar number of hot spot and non-hot spot residues. In addition, we generated 47 different features, and different numbers of features were used to train the models to avoid over-fitting. Finally, two feature combinations were selected: One (used in KFC2a) is composed of eight features that are mainly related to solvent accessible surface area and local plasticity; the other (KFC2b) is composed of seven features, only two of which are identical to those used in KFC2a. The two models were built using support vector machines (SVM). The two KFC2 models were then tested on a mixed independent test set, and compared with other methods such as Robetta, FOLDEF, HotPoint, MINERVA, and KFC. KFC2a showed the highest predictive accuracy for hot spot residues (True Positive Rate: TPR = 0.85); however, the false positive rate was somewhat higher than for other models. KFC2b showed the best predictive accuracy for hot spot residues (True Positive Rate: TPR = 0.62) among all methods other than KFC2a, and the False Positive Rate (FPR = 0.15) was comparable with other highly predictive methods. PMID:21735484

  16. Tree Coring as a Complement to Soil Gas Screening to Locate PCE and TCE Source Zones and Hot Spots

    DEFF Research Database (Denmark)

    Nielsen, Mette Algreen; Trapp, Stefan; Rehne Jensen, Pernille;

    2015-01-01

    trichloroethylene (TCE) to evaluate their ability to locate source zones and contaminant hot spots. One test site represented a relatively homogeneous sandy soil and aquifer, and the second a more heterogeneous geology with both sandy and less permeable clay till layers overlying a chalk aquifer. Tree cores from...... different tree species were sampled and analysed, and compared to soil gas measurements and existing soil gas data. Both methods were found useful as screening tools to locate hot spots of PCE and TCE in the shallow subsurface. Tree coring was found to be particularly beneficial as a complement to soil gas...

  17. Ferrocyanide Safety Program: Waste tank sludge rheology within a hot spot or during draining

    International Nuclear Information System (INIS)

    The conditions under which ferrocyanide waste sludge flows as a homogeneous non-Newtonian two-phase (solid precipitate-liquid) mixture rather than as a liquid through a porous medium (of stationary precipitate) are examined theoretically, based on the notion that the preferred rheological behavior of the sludge is the one which imposes the least resistance to the sludge flow. The homogeneous two-phase mixture is modeled as a power-law fluid and simple criteria are derived that show that the homogeneous power-law sludge-flow is a much more likely flow situation than the porous medium model of sludge flow. The implication of this finding is that the formation of a hot spot or the drainage of sludge from a waste tank are not likely to result in the uncovering (drying) and subsequent potential overheating of the reactive-solid component of the sludge

  18. Hot spots effect on infrared spectral luminance emitted by carbon under plasma particles impact

    Energy Technology Data Exchange (ETDEWEB)

    Delchambre, E.; Reichle, R.; Mitteau, R.; Missirlian, M. [Association Euratom-CEA, Centre d' Etudes de Cadarache, 13 - Saint-Paul-lez-Durance (France). Dept. de Recherches sur la Fusion Controlee; Roubin, P. [Universite de Provence, PIIM, Centre Saint-Jerome, 13 - Marseille (France); Gobin, R. [CEA Saclay, Dept. d' Astrophysique de Physique des Particules, de Physique Nucleaire et de l' Instrumentation Associee, 91- Gif sur Yvette (France)

    2004-07-01

    During the last Tore Supra campaigns, an anomalous deformation in the near infrared spectrum of radiation has been observed on neutralizer underneath the Toroidal Pumped Limiter (TPL) on which we observed the growth of carbon layer. The consequence is the difficulty to asses the surface temperature of the components and the power loaded. Laboratory experiment has been performed, using an Electron Cyclotron Resonance (ECR) ions source, to reproduce, characterize and explain this phenomenon. The luminance emitted by Carbon Fibre Composite (CFC) and pyrolytic graphite, have been observed under 95 keV of H+ bombardments. The amplitude of the deformation was found to depend on the type of material used and the power density of the incident power loaded. This paper presents the possible hot spots explanation. The experimental luminance deformation is reproduced and these results are validated using a thermal model of dust in radiate equilibrium. (authors)

  19. Iridium-bearing sublimates at a hot-spot volcano (Piton de la Fournaise, Indian Ocean)

    Energy Technology Data Exchange (ETDEWEB)

    Toutain, J.P. (Observatorio Vesuviano, Napoli (Italy)); Meyer, G.

    1989-12-01

    Sublimates and incrustations derived upon the cooling of volcanic gases have been collected on various sites (Piton de la Fournaise, Poas, Momotombo, Etna, Ardoukoba and Erta-Ale). They have been analyzed for Ir and other volatile elements (Se, As, Cu, Au, Ag, Pb, Tl) by means of instrumental neutron activation analysis (INAA) and proton induced X-Ray emission (PIXE). Among the investigated volcanoes, only Piton de la Fournaise is found to release detectable amounts of iridium. Ir in Piton de la Fournaise sublimates is associated with F-minerals. This confirms its gaseous transport as a volatile fluoride compound. Iridium seems to be preferentialy released by hot-spot type volcanoes, and its detection in Piton de la Fournaise sublimates provides a positive argument in favor of a volcanic hypothesis to explain the KTB events.

  20. Enhancement of electron hot spot relaxation in photoexcited plasmonic structures by thermal diffusion

    CERN Document Server

    Spitzer, F; Belotelov, V I; Vondran, J; Akimov, I A; Kasture, S; Achanta, V G; Yakovlev, D R; Bayer, M

    2016-01-01

    We demonstrate that in confined plasmonic metal structures subject to ultra-fast laser excitation electron thermal diffusion can provide relaxation faster than the energy transfer to the lattice. This relaxation occurs due to excitation of nanometer-sized hot spots in the confined structure and the sensitivity of its optical parameters to the perturbation in these regions. Both factors become essential when the plasmonic resonance condition is met for both excitation and detection. A pump-probe experiment on plasmonic gold lattices shows sub-picosecond relaxation with the characteristic times well-described by a two-temperature model. The results suggest that dynamical optical response in plasmonic structures can be tuned by selection of the structural geometry as well as the choice of wavelength and polarization of the excitation and detection light.

  1. Geostatistical risk estimation at waste disposal sites in the presence of hot spots

    International Nuclear Information System (INIS)

    The present paper aims to estimate risk by using geostatistics at the wider coal mining/waste disposal site of Belkovskaya, Tula region, in Russia. In this area the presence of hot spots causes a spatial trend in the mean value of the random field and a non-Gaussian data distribution. Prior to application of geostatistics, subtraction of trend and appropriate smoothing and transformation of the data into a Gaussian form were carried out; risk maps were then generated for the wider study area in order to assess the probability of exceeding risk thresholds. Finally, the present paper discusses the need for homogenization of soil risk thresholds regarding hazardous elements that will enhance reliability of risk estimation and enable application of appropriate rehabilitation actions in contaminated areas.

  2. Current hot spot in the spin-valley blockade in carbon nanotubes

    Science.gov (United States)

    Széchenyi, Gábor; Pályi, András

    2013-12-01

    We present a theoretical study of the spin-valley blockade transport effect in a double quantum dot defined in a straight carbon nanotube. We find that intervalley scattering due to short-range impurities completely lifts the spin-valley blockade and induces a large leakage current in a certain confined range of the external magnetic field vector. This current hot spot emerges due to different effective magnetic fields acting on the spin-valley qubit states of the two quantum dots. Our predictions are compared to a recent measurement [F. Pei , Nat. Nanotech.1748-338710.1038/nnano.2012.160 7, 630 (2012)]. We discuss the implications for blockade-based schemes for qubit initialization/readout and motion sensing of nanotube-based mechanical resonators.

  3. Hot spot analysis applied to identify ecosystem services potential in Lithuania

    Science.gov (United States)

    Pereira, Paulo; Depellegrin, Daniel; Misiune, Ieva

    2016-04-01

    Hot spot analysis are very useful to identify areas with similar characteristics. This is important for a sustainable use of the territory, since we can identify areas that need to be protected, or restored. This is a great advantage in terms of land use planning and management, since we can allocate resources, reduce the economical costs and do a better intervention in the landscape. Ecosystem services (ES) are different according land use. Since landscape is very heterogeneous, it is of major importance understand their spatial pattern and where are located the areas that provide better ES and the others that provide less services. The objective of this work is to use hot-spot analysis to identify areas with the most valuable ES in Lithuania. CORINE land-cover (CLC) of 2006 was used as the main spatial information. This classification uses a grid of 100 m resolution and extracted a total of 31 land use types. ES ranking was carried out based on expert knowledge. They were asked to evaluate the ES potential of each different CLC from 0 (no potential) to 5 (very high potential). Hot spot analysis were evaluated using the Getis-ord test, which identifies cluster analysis available in ArcGIS toolbox. This tool identifies areas with significantly high low values and significant high values at a p level of 0.05. In this work we used hot spot analysis to assess the distribution of providing, regulating cultural and total (sum of the previous 3) ES. The Z value calculated from Getis-ord was used to statistical analysis to access the clusters of providing, regulating cultural and total ES. ES with high Z value show that they have a high number of cluster areas with high potential of ES. The results showed that the Z-score was significantly different among services (Kruskal Wallis ANOVA =834. 607, p<0.001). The Z score of providing services (0.096±2.239) were significantly higher than the total (0.093±2.045), cultural (0.080±1.979) and regulating (0.076±1.961). These

  4. Magnetic quadrupoles lens for hot spot proton imaging in inertial confinement fusion

    Science.gov (United States)

    Teng, J.; Gu, Y. Q.; Chen, J.; Zhu, B.; Zhang, B.; Zhang, T. K.; Tan, F.; Hong, W.; Zhang, B. H.; Wang, X. Q.

    2016-08-01

    Imaging of DD-produced protons from an implosion hot spot region by miniature permanent magnetic quadrupole (PMQ) lens is proposed. Corresponding object-image relation is deduced and an adjust method for this imaging system is discussed. Ideal point-to-point imaging demands a monoenergetic proton source; nevertheless, we proved that the blur of image induced by proton energy spread is a second order effect therefore controllable. A proton imaging system based on miniature PMQ lens is designed for 2.8 MeV DD-protons and the adjust method in case of proton energy shift is proposed. The spatial resolution of this system is better than 10 μm when proton yield is above 109 and the spectra width is within 10%.

  5. Accretion onto Stars with Octupole Magnetic Fields: Matter Flow, Hot Spots and Phase Shifts

    CERN Document Server

    Long, Min; Lamb, Frederick K

    2009-01-01

    Recent measurements of the surface magnetic fields of classical T Tauri stars (CTTSs) and magnetic cataclysmic variables show that their magnetic fields have a complex structure. The magnetic field associated with the octupole moment may dominate the magnetic field associated with other moments in some stars, such as the CTTS V2129 Oph. Previously, we studied disc accretion onto stars with magnetic fields described by a superposition of aligned or misaligned dipole and quadrupole moments. In this paper, we present results of the first simulations of disc accretion onto stars with an \\textit {octupole} field. As examples, we consider stars with a superposition of octupole and dipole fields of different strengths and investigate matter flow around them, the shapes of hot spots on their surfaces, and the light curves produced by their rotation. We investigate two possible mechanisms for producing phase shifts in the light curves of stars with complex fields: (1) change of the star's intrinsic magnetic field and ...

  6. The use of hot spot stress for estimating the fatigue strength of welded components

    Energy Technology Data Exchange (ETDEWEB)

    Han, S.; Shin, B. [Korea Inst. for Machinery and Materials, Daejeon (Korea). Dept. of Structural System Engineering

    2000-11-01

    The relatively complex geometry of welded joints makes an assessment of fatigue strength rather difficult in many cases, especially if the common nominal stress approach is applied. An alternative to this method is the hot spot stress approach which considers structural stress concentration factors at a welded discontinuity, in which a unified S-N curve is used to estimate fatigue strength, rather than using numerous curves corresponding to welded joint categories of welded structures. In this paper, using numerical and experimental results for a variety of welded joint models, a unified S-N curve was derived, which is independent of structural stress concentration factors. Based on a fatigue test of a real welded joint in a train bogie frame, it could be confirmed that the unified S-N curve can be directly applied to the estimation of fatigue strength and fatigue design for general welded steel constructions. (orig.)

  7. Measurement of lower hybrid hot spots using a retarding field analyzer in Tore Supra

    Czech Academy of Sciences Publication Activity Database

    Gunn, J. P.; Petržílka, Václav; Ekedahl, A.; Fuchs, Vladimír; Gauthier, E.; Goniche, M.; Kočan, M.; Pascal, J.Y.; Saint Laurent, F.

    390-391, č. 1 (2009), s. 904-906. ISSN 0022-3115. [International Conference on Plasma-Surface Interactions in Controlled Fusion Devices/18th./. Toledo, 26.05.2008-30.5.2008] R&D Projects: GA ČR GA202/07/0044 Institutional research plan: CEZ:AV0Z20430508 Keywords : Lower Hybrid * hot spots * ELECTRONS * POWER Subject RIV: BL - Plasma and Gas Discharge Physics Impact factor: 1.933, year: 2009 http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TXN-4VG7MW6-7&_user=6542793&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_acct=C000070123&_version=1&_urlVersion=0&_userid=6542793&md5=944ed4d95df86a149fa36439db6215db

  8. Thermally smart characteristics of nanofluids in parallel microchannel systems to mitigate hot spots in MEMS

    CERN Document Server

    Maganti, Lakshmi Sirisha; Sundararajan, T; Das, Sarit K

    2016-01-01

    Mitigation of hot spots in MEMS employing in situ microchannel systems requires a comprehensive picture of the maldistribution of the working fluid and uniformity of cooling within the same. In this article, detailed simulations employing parallel micro channel systems with specialized manifold-channel configurations i.e. U, I and Z have been performed. Eulerian Lagrangian Discrete Phase Model and Effective Property Model with water and alumina water nanofluid as working fluids have been employed. The distributions of the dispersed particulate phase and continuous phase have been observed to be, in general, different from the flow distribution and this has been found to be strongly dependent on the flow configuration. Particle maldistribution has been conclusively shown to be influenced by various migration and diffusive phenomena like Stokesian drag, Brownian motion, thermophoretic drift, etc. To understand the uniformity of cooling within the device, which is of importance in real time scenario, an appropri...

  9. Mapping the energy distribution of SERRS hot spots from anti-Stokes to Stokes intensity ratios.

    Science.gov (United States)

    dos Santos, Diego P; Temperini, Marcia L A; Brolo, Alexandre G

    2012-08-15

    The anomalies in the anti-Stokes to Stokes intensity ratios in single-molecule surface-enhanced resonance Raman scattering were investigated. Brilliant green and crystal violet dyes were the molecular probes, and the experiments were carried out on an electrochemically activated Ag surface. The results allowed new insights into the origin of these anomalies and led to a new method to confirm the single-molecule regime in surface-enhanced Raman scattering. Moreover, a methodology to estimate the distribution of resonance energies that contributed to the imbalance in the anti-Stokes to Stokes intensity ratios at the electromagnetic hot spots was proposed. This method allowed the local plasmonic resonance energies on the metallic surface to be spatially mapped. PMID:22804227

  10. Monolithic nanoporous gold disks with large surface area and high-density plasmonic hot-spots

    Science.gov (United States)

    Zhao, Fusheng; Zeng, Jianbo; Arnob, Md Masud Parvez; Santos, Greggy M.; Shih, Wei-Chuan

    2015-03-01

    Plasmonic metal nanostructures have shown great potential in sensing, photovoltaics, imaging and biomedicine, principally due to enhancement of the local electric field by light-excited surface plasmons, the collective oscillation of conduction band electrons. Thin films of nanoporous gold have received a great deal of interest due to the unique 3- dimensional bicontinuous nanostructures with high specific surface area. However, in the form of semi-infinite thin films, nanoporous gold exhibits weak plasmonic extinction and little tunability in the plasmon resonance, because the pore size is much smaller than the wavelength of light. Here we show that by making nanoporous gold in the form of disks of sub-wavelength diameter and sub-100 nm thickness, these limitations can be overcome. Nanoporous gold disks (NPGDs) not only possess large specific surface area but also high-density, internal plasmonic "hot-spots" with impressive electric field enhancement, which greatly promotes plasmon-matter interaction as evidenced by spectral shifts in the surface plasmon resonance. In addition, the plasmonic resonance of NPGD can be easily tuned from 900 to 1850 nm by changing the disk diameter from 300 to 700 nm. The coupling between external and internal nanoarchitecture provides a potential design dimension for plasmonic engineering. The synergy of large specific surface area, high-density hot spots, and tunable plasmonics would profoundly impact applications where plasmonic nanoparticles and non-plasmonic mesoporous nanoparticles are currently employed, e.g., in in-vitro and in-vivo biosensing, molecular imaging, photothermal contrast agents, and molecular cargos.

  11. Causes of hot-spot wetland loss in the Mississippi delta plain

    Science.gov (United States)

    Morton, R.A.; Tiling, G.; Ferina, N.F.

    2003-01-01

    Field surveys and sediment cores were used to estimate marsh erosion and land subsidence at Madison Bay, a well-known wetland loss hot spot in coastal Louisiana. Former marshes of Madison Bay are under about 1 m of water. Nearly two-thirds of the permanent flooding was caused by rapid subsidence in the late 1960s, whereas the other third was caused by subsequent erosion. Subsidence rates near Madison Bay since the 1960s (???20 mm/yr) are an order of magnitude greater than deltaic subsidence rates averaged for the past 400-4000 yr (???2 mm/yr). The rapid acceleration and unexpected decline in wetland losses in the Mississippi delta plain are difficult to explain on the basis of most physical and biogeochemical processes. There are, however, close temporal and spatial correlations among regional wetland loss, high subsidence rates, and large-volume fluid production from nearby hydrocarbon fields. The decreased rates of wetland loss since the 1970s may be related to decreased rates of subsidence caused by significantly decreased rates of subsurface fluid withdrawal. Annual fluid production from the Lapeyrouse, Lirette, and Bay Baptiste fields that encompass Madison Bay accelerated in the 1960s, peaked about 1970, and then declined abruptly. Large decreases in pore pressure in the Lapeyrouse field have likely altered subsurface stresses and reactivated a major fault that coincides with the wetland loss hot spot. Therefore, wetland losses at Madison Bay can be closely linked to rapid subsidence and possible fault reactivation induced by long-term, large-volume hydrocarbon production. ?? 2003. The American Association of Petroleum Geologists/Division of Environmental Geosciences. All rights reserved.

  12. Recent Trident Single Hot Spot Experiments: Evidence for kinetic effects, and observation of LDI cascade

    Science.gov (United States)

    Montgomery, D. S.

    2001-10-01

    Single hot spot experiments offer several unique opportunities for developing a quantitative understanding of laser-plasma instabilities. These include the ability to perform direct numerical simulations of the experiment due to the finite interaction volume, isolation of instabilities due to the nearly ideal laser intensity distribution, and observation of fine structure due to the very homogeneous plasma conditions. Recent experiments have been performed in the single hot spot regime^1 using the Trident laser, and have focused on the following issues. First, the intensity scaling of stimulated Raman scattering (SRS) for classically large damping regimes (kλ_D=0.35) was examined, and compared to classical SRS theory. SRS onset was observed at intensities much lower than expected (2 x 10^15 W/cm^2), from which non-classical damping is inferred. Second, scattering from a plasma wave was observed whose frequency and phase velocity are between an ion acoustic wave and an electron plasma wave^2. The presence of this wave cannot be explained by linear Landau theory, and it is shown to be consistent with a BGK-like mode due to electron trapping^3. These waves have been observed in past laser-plasma experiments, but were previously misinterpreted^4,5. Finally, Thomson scattering was used to probe plasma waves driven by SRS, and structure was observed in the scattered spectra consistent with multiple steps of the Langmuir decay instability. 1. D.S. Montgomery et al., Phys. Rev. Lett. 84, 678 (2000). 2. D.S. Montgomery et al., to appear in Phys. Rev. Lett. (2001). 3. J.P. Holloway and J.J. Dorning, Phys. Lett. 138, 279 (1989). 4. D.S. Montgomery et al., Phys. Plasmas 3, 1728 (1996). 5. J.A. Cobble et al., Phys. Plasmas 7, 323 (2000). Work performed under the auspices of the U.S. D.O.E. by LANL under contract no. W-7405-ENG-36

  13. The Effect of Particle Properties on Hot Particle Spot Fire Ignition

    Science.gov (United States)

    Zak, Casey David

    The ignition of natural combustible material by hot metal particles is an important fire ignition pathway by which wildland and wildland-urban-interface spot fires are started. There are numerous cases reported of wild fires started by clashing power-lines or from sparks generated by machines or engines. Similarly there are many cases reported of fires caused by grinding, welding and cutting sparks. Up to this point, research on hot particle spot fire ignition has largely focused on particle generation and transport. A small number of studies have examined what occurs after a hot particle contacts a natural fuel bed, but until recently the process remained poorly understood. This work describes an investigation of the effect of particle size, temperature and thermal properties on the ability of hot particles to cause flaming ignition of cellulosic fuel beds. Both experimental and theoretical approaches are used, with a focus on understanding the physics underlying the ignition process. For the experimental study, spheres of stainless steel, aluminum, brass and copper are heated in a tube furnace and dropped onto a powdered cellulose fuel bed; the occurrence of flaming ignition or lack thereof is visually observed and recorded. This procedure is repeated a large number of times for each metal type, varying particle diameter from 2 to 11 mm and particle temperature between 575 and 1100°C. The results of these experiments are statistically analyzed to find approximate ignition boundaries and identify boundary trends with respect to the particle parameters of interest. Schlieren images recorded during the ignition experiments are also used to more accurately describe the ignition process. Based on these images, a simple theoretical model of hot particle spot fire ignition is developed and used to explore the experimental trends further. The model under-predicts the minimum ignition temperatures required for small spheres, but agrees qualitatively with the experimental

  14. Standard Test Method for Hot Spot Protection Testing of Photovoltaic Modules

    CERN Document Server

    American Society for Testing and Materials. Philadelphia

    2008-01-01

    1.1 This test method provides a procedure to determine the ability of a photovoltaic (PV) module to endure the long-term effects of periodic “hot spot” heating associated with common fault conditions such as severely cracked or mismatched cells, single-point open circuit failures (for example, interconnect failures), partial (or non-uniform) shadowing or soiling. Such effects typically include solder melting or deterioration of the encapsulation, but in severe cases could progress to combustion of the PV module and surrounding materials. 1.2 There are two ways that cells can cause a hot spot problem; either by having a high resistance so that there is a large resistance in the circuit, or by having a low resistance area (shunt) such that there is a high-current flow in a localized region. This test method selects cells of both types to be stressed. 1.3 This test method does not establish pass or fail levels. The determination of acceptable or unacceptable results is beyond the scope of this test method....

  15. Study on the resistance spot welding technology of 22MnMoB hot stamping quenched steel

    Institute of Scientific and Technical Information of China (English)

    Feng Yi; Ma Mingtu; Hua Fuan; Zhang Junping; Song Leifeng; Jin Qingsheng

    2014-01-01

    In this paper,the spot welding technology of a new kind of 22MnMoB hot stamping quenched steel sheet was systematically studied by power frequency spot welder. Through a series of technology and test exper-iments,we have obtained the optimal spot welding technological parameter condition. According to the results, the relations among spot welding technological parameter,welding nugget,mechanical property and fracture mode were discussed. The effects of all the welding parameters such as welding current,welding time and elec-trode force on the quality of joint can be boiled down to one thing-the diameter of welding nugget. The experi-mental results showed that welding nugget diameter determines the mechanical property of spot welding joint and the relation between welding nugget diameter and the mechanical property of joint presents a kind of linear mathematic representation. There are two typical fracture models of 22MnMoB hot stamping quenched steel sheet,i.e.,interfacial fracture and nugget pullout. Other than mild steel or normal high strength steel,in the shearing tensile test,hot stamping quenched steel has a great tendency to fail in interfacial mode due to the ef-fects of high strength matrix structure,welding soft zone and the porosity level of fusion zone.

  16. Hot spots of DNA double-strand breaks in human rDNA units are produced in vivo.

    Science.gov (United States)

    Tchurikov, Nickolai A; Yudkin, Dmitry V; Gorbacheva, Maria A; Kulemzina, Anastasia I; Grischenko, Irina V; Fedoseeva, Daria M; Sosin, Dmitri V; Kravatsky, Yuri V; Kretova, Olga V

    2016-01-01

    Endogenous hot spots of DNA double-strand breaks (DSBs) are tightly linked with transcription patterns and cancer genomics(1,2). There are nine hot spots of DSBs located in human rDNA units(3-6). Here we describe that the profiles of these hot spots coincide with the profiles of γ-H2AX or H2AX, strongly suggesting a high level of in vivo breakage inside rDNA genes. The data were confirmed by microscopic observation of the largest γ-H2AX foci inside nucleoli in interphase chromosomes. In metaphase chromosomes, we observed that only some portion of rDNA clusters possess γ-H2AX foci and that all γ-H2AX foci co-localize with UBF-1 binding sites, which strongly suggests that only active rDNA units possess the hot spots of DSBs. Both γ-H2AX and UBF-1 are epigenetically inherited and thus indicate the rDNA units that were active in the previous cell cycle. These results have implications for diverse fields, including epigenetics and cancer genomics. PMID:27160357

  17. INVESTIGATION OF 'HOT-SPOTS' AS A FUNCTION OF MATERIAL REMOVAL IN A LARGE-GRAIN NIOBIUM CAVITY

    International Nuclear Information System (INIS)

    Poster - The performance of a single-cell cavity made of RRR > 200 large-grain niobium has been investigated as a function of material removal by buffered chemical polishing. Temperature maps of the cavity surface at 1.7 and 2.0 K were taken for each step of chemical etching and revealed several 'hot-spots', which contribute to the degradation of the cavity quality factor as a function of the RF surface field, mostly at high field levels. It was found that the number of 'hot-spots' decreased for larger material removal. Interestingly, the losses of the 'hot-spots' at different locations evolved differently for successive material removal. The cavity achieved peak surface magnetic fields of about of 130 mT and was limited mostly by thermal quench. By measuring the temperature dependence of the surface resistance at low field between 4.2 K and 1.7 K, the variation of niobium material parameters as a function of material removal could also be investigated. This contribution shows the results of the RF tests along with the temperature maps and the analysis of the losses caused by the 'hot-spots'.

  18. Investigation of ''Hot-Spots'' as a Function of Material Removal in a Large-Grain Niobium Cavity

    International Nuclear Information System (INIS)

    The performance of a single-cell cavity made of RRR > 200 large-grain niobium has been investigated as a function of material removal by buffered chemical polishing. Temperature maps of the cavity surface at 1.7 and 2.0 K were taken for each step of chemical etching and revealed several ''hot-spots'', which contribute to the degradation of the cavity quality factor as a function of the RF surface field, mostly at high field levels. It was found that the number of ''hot-spots'' decreased for larger material removal. Interestingly, the losses of the ''hot-spots'' at different locations evolved differently for successive material removal. The cavity achieved peak surface magnetic fields of about of 130 mT and was limited mostly by thermal quench. By measuring the temperature dependence of the surface resistance at low field between 4.2 K and 1.7 K, the variation of niobium material parameters as a function of material removal could also be investigated. This contribution shows the results of the RF tests along with the temperature maps and the analysis of the losses caused by the ''hot-spots''

  19. Localization of Temperature Using Plasmonic Hot Spots in Metal Nanostructures: The Nano-Optical Antenna Approach and Fano Effect

    CERN Document Server

    Khorashad, Larousse Khosravi; Valentine, Jason; Govorov, Alexander O

    2016-01-01

    It is challenging to strongly localize temperature in small volumes because heat transfer is a diffusive process. Here we show how to overcome this limitation using electrodynamic hot spots and interference effects in the regime of continuous-wave (CW) excitation. We introduce a set of figures of merit for the localization of temperature and for the efficiency of the plasmonic photo-thermal effect. Our calculations show that the temperature localization in a trimer nanoparticle assembly is a complex function of the geometry and sizes. Large nanoparticles in the trimer play the role of the nano-optical antenna whereas the small nanoparticle in the plasmonic hot spot acts as a nano-heater. Under the peculiar conditions, the temperature increase inside a nanoparticle trimer can be localized in a hot spot region at the small heater nanoparticle and, in this way, a thermal hot spot can be realized. However, the overall power efficiency of temperature generation in this trimer is much smaller than that of a single ...

  20. Hot spot formation of chloroform in forest soils caused pollution of groundwater

    Science.gov (United States)

    Jacobsen, Ole S.; Albers, Christian N.; Laier, Troels; Hunkeler, Daniel

    2015-04-01

    High concentration of chloroform in groundwater is usually attributed to anthropogenic input, but we have found that the groundwater beneath some pristine areas contained chloroform from 1 - 10 µg/L. Groundwater containing chloroform that exceeds 1 µg/L could not be used for drinking water according to Danish regulations. The strict demands on groundwater quality may have to be taken into account when decisions are made regarding the change of land use in order to protect major recharge areas from pollution with nitrate and pesticides resulting from high-yield agriculture production. The terrestrial environment and especially hot spots in forest soils seem to be important contributors to apparent pollution of groundwater with chloroform. We performed a field study to investigate concentration and fluxes of chloroform to the groundwater from in four coniferous forests in order to increase knowledge on the hot spot formation and fate of natural chloroform. We investigated four stations over a period of several years in order to measure the net-formation of chloroform. Field measurements soil air concentrations of chloroform were monitored in five soil profiles down to the groundwater table. Meteorological data were recorded at all stations In the hotspots up to 120 ppbv was found in soil air under the spruce forest, to be compared to an ambient atmospheric concentration of 0.02 ppbv. The concentration of chloroform in soil air showed seasonal variation with a maximum in August-September. The chloroform concentration decreased with depth in all profiles during the summer half-year to about 20 % of concentration in the production layer. However, the concentration is still high enough to give an equilibrium concentration in the upper groundwater of 1-10 µg/L. Stable carbon isotopic analyses of chloroform from the uppermost groundwater in different parts of the forests and from soil water showed values from δ13C = -13 ‰ to -27 ‰, corresponding to the ratio in

  1. Hot-spot application of biocontrol agents to replace pesticides in large scale commercial rose farms in Kenya

    DEFF Research Database (Denmark)

    Gacheri, Catherine; Kigen, Thomas; Sigsgaard, Lene

    2015-01-01

    of the predatory mite Phytoseiulus persimilis (Acari: Phytoseidae) in large commercial rose greenhouses. Hot-spot treatments replaced acaricides except at high infestations and the two treatments were applied in seven greenhouses each. With the conventional treatment, acaricides were applied when T. urticae......-spot treatment. The cost of pest management was significantly lower in the hotspot- treated greenhouses than in the conventional treatment. However, there was no significant difference in the number of harvested stems from the two treatments. It can therefore be concluded that acaricides can be replaced by P...

  2. Molecular Dynamics Simulations of Hot Spots and Detonation on the Roadrunner Supercomputer

    Science.gov (United States)

    Mniszewski, Susan; Cawkwell, Marc; Germann, Timothy

    2011-06-01

    The temporal and spatial scales intrinsic to a real detonating explosive are extremely difficult to capture using molecular dynamics (MD) simulations. Nevertheless, MD remains very attractive since it allows for the resolution of dynamic phenomena at the atomic scale. We have studied the effects of spherical voids on the build up to detonation in three dimensions (3D) in a model explosive using the reactive empirical bond order (REBO) potential for the A-B system. This force field is attractive because it has been shown to support a detonation while being simple, analytic, and short-ranged. The transition from 2D to 3D simulations was facilitated by our port of the REBO force field in the parallel MD code SPaSM to LANL's petaflop Roadrunner supercomputer based on previous work by Swaminarayan and Germann [T. C. Germann et al. Concurrency Computat.: Pract. Exper. 21, 2143 (2009)]. We will provide a detailed discussion of the challenges associated with computing interatomic forces on a hybrid Opteron/Cell BE computational architecture. We will compare and contrast our results in 3D from Roadrunner with earlier 2D simulations of hot-spot assisted detonations by Heim, Herring, and co-workers [S. D. Herring et al. Phys. Rev. B, 82, 214108 (2010)].

  3. Evaluation of the thermal safety margin for the KMRR using the hot-spot-factor approach

    International Nuclear Information System (INIS)

    In the thermal-hydraulic (T/H) design of a reactor, several design bases are usually established at the outset and they serve throughout the design process as a set of fundamental criteria on which the adequacy of the thermal-hydraulic design can be judged. Some examples of these are the maximum fuel temperature design bases (DB), departure from nucleate boiling (DNB) BD, and maximum linear heat generation rate DB for pressurized water reactors. The same line of design approach was adopted to design the Korean Multipurpose Research Reactor to be built in the Korean Advanced Energy Research Institute by the end of 1990. The most stringent design basis for T/H design is found to be the onset of nucleate boiling (ONB) margin which is defined as the difference between the ONB wall temperature and the actual wall temperature at the hottest spot in the core. The main objective of this study is to identify what kinds of uncertainties are to be included in the core thermal-margin calculation, to set up a core thermal-margin calculation procedure into which these uncertainty effects are implemented, and to model and quantify their effects on the safety margin. The hot channel factor method for three-dimensional core thermal analysis proposed by Chelemer was used with COBRA-IV-I as the mathematical tool to evaluate the core thermal margin and its sensitivity on these uncertainties

  4. A Machine Learning Approach for Hot-Spot Detection at Protein-Protein Interfaces.

    Science.gov (United States)

    Melo, Rita; Fieldhouse, Robert; Melo, André; Correia, João D G; Cordeiro, Maria Natália D S; Gümüş, Zeynep H; Costa, Joaquim; Bonvin, Alexandre M J J; Moreira, Irina S

    2016-01-01

    Understanding protein-protein interactions is a key challenge in biochemistry. In this work, we describe a more accurate methodology to predict Hot-Spots (HS) in protein-protein interfaces from their native complex structure compared to previous published Machine Learning (ML) techniques. Our model is trained on a large number of complexes and on a significantly larger number of different structural- and evolutionary sequence-based features. In particular, we added interface size, type of interaction between residues at the interface of the complex, number of different types of residues at the interface and the Position-Specific Scoring Matrix (PSSM), for a total of 79 features. We used twenty-seven algorithms from a simple linear-based function to support-vector machine models with different cost functions. The best model was achieved by the use of the conditional inference random forest (c-forest) algorithm with a dataset pre-processed by the normalization of features and with up-sampling of the minor class. The method has an overall accuracy of 0.80, an F1-score of 0.73, a sensitivity of 0.76 and a specificity of 0.82 for the independent test set. PMID:27472327

  5. Computer simulations of laser hot spots and implosion symmetry kiniform phase plate experiments on Nova

    International Nuclear Information System (INIS)

    LASNEX computer code simulations have been performed for radiation symmetry experiments on the Nova laser with vacuum and gas-filled hohlraum targets [R. L. Kauffman et al., Phys. Plasmas 5, 1927 (1998)]. In previous experiments with unsmoothed laser beams, the symmetry was substantially shifted by deflection of the laser beams. In these experiments, laser beams have been smoothed with Kiniform Phase Plates in an attempt to remove deflection of the beams. The experiments have shown that this smoothing significantly improves the agreement with LASNEX calculations of implosion symmetry. The images of laser produced hot spots on the inside of the hohlraum case have been found to differ from LASNEX calculations, suggesting that some beam deflection or self-focusing may still be present or that emission from interpenetrating plasmas is an important component of the images. The measured neutron yields are in good agreement with simulations for vacuum hohlraums but are far different for gas-filled hohlraums. (c) 2000 American Institute of Physics

  6. The Greenland Ice Sheet as a hot spot of phosphorus weathering and export in the Arctic

    Science.gov (United States)

    Hawkings, Jon; Wadham, Jemma; Tranter, Martyn; Telling, Jon; Bagshaw, Elizabeth; Beaton, Alexander; Simmons, Sarah-Louise; Chandler, David; Tedstone, Andrew; Nienow, Peter

    2016-02-01

    The contribution of ice sheets to the global biogeochemical cycle of phosphorus is largely unknown, due to the lack of field data. Here we present the first comprehensive study of phosphorus export from two Greenland Ice Sheet glaciers. Our results indicate that the ice sheet is a hot spot of phosphorus export in the Arctic. Soluble reactive phosphorus (SRP) concentrations, up to 0.35 µM, are similar to those observed in Arctic rivers. Yields of SRP are among the highest in the literature, with denudation rates of 17-27 kg P km-2 yr-1. Particulate phases, as with nonglaciated catchments, dominate phosphorus export (>97% of total phosphorus flux). The labile particulate fraction differs between the two glaciers studied, with significantly higher yields found at the larger glacier (57.3 versus 8.3 kg P km-2 yr-1). Total phosphorus yields are an order of magnitude higher than riverine values reported in the literature. We estimate that the ice sheet contributes ~15% of total bioavailable phosphorus input to the Arctic oceans (~11 Gg yr-1) and dominates total phosphorus input (408 Gg yr-1), which is more than 3 times that estimated from Arctic rivers (126 Gg yr-1). We predict that these fluxes will rise with increasing ice sheet freshwater discharge in the future.

  7. Thermal windows on the trunk of hauled-out seals: hot spots for thermoregulatory evaporation?

    Science.gov (United States)

    Mauck, Björn; Bilgmann, Kerstin; Jones, Daryl D; Eysel, Ulf; Dehnhardt, Guido

    2003-05-01

    Seals have adapted to the high heat transfer coefficient in the aquatic environment by effective thermal insulation of the body core. While swimming and diving, excess metabolic heat is supposed to be dissipated mainly over the sparsely insulated body appendages, whereas the location of main heat sinks in hauled-out seals remains unclear. Here, we demonstrate thermal windows on the trunk of harbour seals, harp seals and a grey seal examined under various ambient temperatures using infrared thermography. Thermograms were analysed for location, size and development of thermal windows. Thermal windows were observed in all experimental sessions, shared some common characteristics in all seals and tended to reappear in similar body sites of individual seals. Nevertheless, the observed variations in order and location of appearance, number, size and shape of thermal windows would imply no special anatomical site for this avenue of heat loss. Based on our findings, we suggest that, in hauled-out seals, heat may be transported by blood flow to a small area of the wet body surface where the elevation of temperature facilitates evaporation of water trapped within the seals' pelages due to increased saturation vapour pressure. The comparatively large latent heat necessary for evaporation creates a temporary hot spot for heat dissipation. PMID:12682104

  8. Hot spot detection and spatio-temporal dynamics of dengue in Queensland, Australia

    Science.gov (United States)

    Naish, S.; Tong, S.

    2014-11-01

    Dengue has been a major public health concern in Australia since it re-emerged in Queensland in 1992-1993. This study explored spatio-temporal distribution and clustering of locally-acquired dengue cases in Queensland State, Australia and identified target areas for effective interventions. A computerised locally-acquired dengue case dataset was collected from Queensland Health for Queensland from 1993 to 2012. Descriptive spatial and temporal analyses were conducted using geographic information system tools and geostatistical techniques. Dengue hot spots were detected using SatScan method. Descriptive spatial analysis showed that a total of 2,398 locally-acquired dengue cases were recorded in central and northern regions of tropical Queensland. A seasonal pattern was observed with most of the cases occurring in autumn. Spatial and temporal variation of dengue cases was observed in the geographic areas affected by dengue over time. Tropical areas are potential high-risk areas for mosquito-borne diseases such as dengue. This study demonstrated that the locally-acquired dengue cases have exhibited a spatial and temporal variation over the past twenty years in tropical Queensland, Australia. There is a clear evidence for the existence of statistically significant clusters of dengue and these clusters varied over time. These findings enabled us to detect and target dengue clusters suggesting that the use of geospatial information can assist the health authority in planning dengue control activities and it would allow for better design and implementation of dengue management programs.

  9. Distinguishing between hot-spots and melting-pots of genetic diversity using haplotype connectivity

    Directory of Open Access Journals (Sweden)

    Emerson Brent C

    2010-03-01

    Full Text Available Abstract We introduce a method to help identify how the genetic diversity of a species within a geographic region might have arisen. This problem appears, for example, in the context of identifying refugia in phylogeography, and in the conservation of biodiversity where it is a factor in nature reserve selection. Complementing current methods for measuring genetic diversity, we analyze pairwise distances between the haplotypes of a species found in a geographic region and derive a quantity, called haplotype connectivity, that aims to capture how divergent the haplotypes are relative to one another. We propose using haplotype connectivity to indicate whether, for geographic regions that harbor a highly diverse collection of haplotypes, diversity evolved inside a region over a long period of time (a "hot-spot" or is the result of a more recent mixture (a "melting-pot". We describe how the haplotype connectivity for a collection of haplotypes can be computed efficiently and briefly discuss some related optimization problems that arise in this context. We illustrate the applicability of our method using two previously published data sets of a species of beetle from the genus Brachyderes and a species of tree from the genus Pinus.

  10. A Machine Learning Approach for Hot-Spot Detection at Protein-Protein Interfaces

    Science.gov (United States)

    Melo, Rita; Fieldhouse, Robert; Melo, André; Correia, João D. G.; Cordeiro, Maria Natália D. S.; Gümüş, Zeynep H.; Costa, Joaquim; Bonvin, Alexandre M. J. J.; Moreira, Irina S.

    2016-01-01

    Understanding protein-protein interactions is a key challenge in biochemistry. In this work, we describe a more accurate methodology to predict Hot-Spots (HS) in protein-protein interfaces from their native complex structure compared to previous published Machine Learning (ML) techniques. Our model is trained on a large number of complexes and on a significantly larger number of different structural- and evolutionary sequence-based features. In particular, we added interface size, type of interaction between residues at the interface of the complex, number of different types of residues at the interface and the Position-Specific Scoring Matrix (PSSM), for a total of 79 features. We used twenty-seven algorithms from a simple linear-based function to support-vector machine models with different cost functions. The best model was achieved by the use of the conditional inference random forest (c-forest) algorithm with a dataset pre-processed by the normalization of features and with up-sampling of the minor class. The method has an overall accuracy of 0.80, an F1-score of 0.73, a sensitivity of 0.76 and a specificity of 0.82 for the independent test set. PMID:27472327

  11. Models of lithosphere and asthenosphere anisotropic structure of the Yellowstone hot spot from shear wave splitting

    Science.gov (United States)

    Waite, G.P.; Schutt, D.L.; Smith, R.B.

    2005-01-01

    Teleseismic shear wave splitting measured at 56 continuous and temporary seismographs deployed in a 500 km by 600 km area around the Yellowstone hot spot indicates that fast anisotropy in the mantle is parallel to the direction of plate motion under most of the array. The average split time from all stations of 0.9 s is typical of continental stations. There is little evidence for plume-induced radial strain, suggesting that any contribution of gravitationally spreading plume material is undetectably small with respect to the plate motion velocity. Two stations within Yellowstone have splitting measurements indicating the apparent fast anisotropy direction (??) is nearly perpendicular to plate motion. These stations are ???30 km from stations with ?? parallel to plate motion. The 70?? rotation over 30 km suggests a shallow source of anisotropy; however, split times for these stations are more than 2 s. We suggest melt-filled, stress-oriented cracks in the lithosphere are responsible for the anomalous ?? orientations within Yellowstone. Stations southeast of Yellowstone have measurements of ?? oriented NNW to WNW at high angles to the plate motion direction. The Archean lithosphere beneath these stations may have significant anisotropy capable of producing the observed splitting. Copyright 2005 by the American Geophysical Union.

  12. New Caledonia: A Hot Spot for Valuable Chemodiversity Part 3: Santalales, Caryophyllales, and Asterids.

    Science.gov (United States)

    Coulerie, Paul; Poullain, Cyril

    2016-04-01

    The flora of New Caledonia encompasses more than 3000 plant species and an endemism of almost 80%. New Caledonia is even considered as one of the 34 'hot spots' for biodiversity. Considering the current global loss of biodiversity and the fact that several drugs and pesticides become obsolete, there is an urgent need to increase sampling and research on new natural products. In this context, here, we reviewed the chemical knowledge available on New Caledonian native flora from economical perspectives. We expect that a better knowledge of the economic potential of plant chemistry will encourage the plantation of native plants for the development of a sustainable economy which will participate in the conservation of biodiversity. This review is divided into three parts, and the third part which is presented here summarizes the scientific literature related to the chemistry of endemic santalales, caryophyllales, and asterids. We show that the high rate of endemism is correlated with the originality of phytochemicals encountered in New Caledonian plants. A total of 176 original natural compounds have been identified from these plants, whereas many species have not been investigated so far. We also discuss the economic potential of plants and molecules with consideration of their medicinal and industrial perspectives. This review finally highlights several groups, such as Sapotaceae, that are unexplored in New Caledonia despite the high chemical interest in them. These plants are considered to have priority in future chemical investigations. PMID:26937845

  13. WLAN Hot Spot services for the automotive and oil industries. A business analysis

    International Nuclear Information System (INIS)

    While you refuel for gas, why not refuel for information or download vehicle data? This paper analyzes in extensive detail the user segmentation by vehicle usage, service offering, and full business models from WLAN (Wireless Local Area Network) hot spot services delivered to vehicles (private, professional, public) around gas stations. Also analyzed are the parties which play a role in such service authorization, provisioning and delivery, with all the dependencies modelled by attributed digraphs. Service planning is included as to WLAN base station capabilities. Five year financial models (CAPEX,OPEX), and data pertain to two possible service suppliers: multi-service oil companies, and mobile service operators (or MVNO). Model optimization on the return-on-investment (ROI) is carried out for different deployment scenarios, geographical coverage assumptions, as well as tariff structures. Comparison is also being made with public GPRS data services, as precursors for 3G services, and the effect of WLAN roaming is analyzed. Analysis shows that due to manpower costs and marketing costs, suitable ROI will not be achieved unless externalities are accounted for and innovative tariff structures are introduced. Open issues and further research are outlined. Further work is carried out, also with automotive electronics sector, wireless systems providers, wireless terminals platform suppliers, and vehicle manufacturers

  14. Optical and mechanical manipulation of plasmonic hot spots on gold nanoparticle tips; Optische und mechanische Manipulation plasmonischer Heisspunkte an Goldnanopartikelspitzen

    Energy Technology Data Exchange (ETDEWEB)

    Hrelescu, Calin-Alexander

    2011-06-15

    in the present thesis hybride systems based on alternative nanoparticle morphologies were studied in view of their optical properties in order to remove extensively the known limitations and insufficiencies of the established nanoparticle systems and shapes like rod-shaped or spherical nanoparticles. Star-shaped gold nanoparticles and their special plasmonic properties are presented. By methods of the dark-field spectroscopy, the photoelectron emission spectroscopy, and scanning electron microscopy the near- and far-field properties of single nanostars and their morphologies are correlated. So the first experimental proof of the localization of optically excited hot spots on the tips of the single nanostars could be given. By suited choice of the polarization and wavelength hot spots on several or exclusively single tips of a nanostar are selectively excited and the detected plasmon resonances assigned to single nanostar tips only due to experimental data. Furthermore field amplification factors in the range of 58-79 are for the first time quantitatively determined. The high and for molecules easily accessible hot spots on the tips of the nanostars are applied in order to demonstrate the excellent amplification of the Raman scattering on the level of single nanostars. The Raman amplification factors of 10{sup 7} for the studied nanostars without use of plasmonic coupling effects mark the nanostars as important candidates for the application in complex dynamical environments. A further possibility of the use of the hot spots localized on tips offer nanopyramides. By manipulation with a scanning force microscope a positioning of the hot spots until 1 nm above the surface and on arbitrary places on a sample substrate can be reached. Nanoresonators of two nanopyramides can be mechanically fabricated in three adsorption configurations concerning the tips of the two nanoparticles directed to each other. By the mechanical change of the configuration of the nanoresonator

  15. Prediction of hot spot residues at protein-protein interfaces by combining machine learning and energy-based methods

    Directory of Open Access Journals (Sweden)

    Pontil Massimiliano

    2009-10-01

    Full Text Available Abstract Background Alanine scanning mutagenesis is a powerful experimental methodology for investigating the structural and energetic characteristics of protein complexes. Individual amino-acids are systematically mutated to alanine and changes in free energy of binding (ΔΔG measured. Several experiments have shown that protein-protein interactions are critically dependent on just a few residues ("hot spots" at the interface. Hot spots make a dominant contribution to the free energy of binding and if mutated they can disrupt the interaction. As mutagenesis studies require significant experimental efforts, there is a need for accurate and reliable computational methods. Such methods would also add to our understanding of the determinants of affinity and specificity in protein-protein recognition. Results We present a novel computational strategy to identify hot spot residues, given the structure of a complex. We consider the basic energetic terms that contribute to hot spot interactions, i.e. van der Waals potentials, solvation energy, hydrogen bonds and Coulomb electrostatics. We treat them as input features and use machine learning algorithms such as Support Vector Machines and Gaussian Processes to optimally combine and integrate them, based on a set of training examples of alanine mutations. We show that our approach is effective in predicting hot spots and it compares favourably to other available methods. In particular we find the best performances using Transductive Support Vector Machines, a semi-supervised learning scheme. When hot spots are defined as those residues for which ΔΔG ≥ 2 kcal/mol, our method achieves a precision and a recall respectively of 56% and 65%. Conclusion We have developed an hybrid scheme in which energy terms are used as input features of machine learning models. This strategy combines the strengths of machine learning and energy-based methods. Although so far these two types of approaches have mainly been

  16. “Rings of saturn-like” nanoarrays with high number density of hot spots for surface-enhanced Raman scattering

    Energy Technology Data Exchange (ETDEWEB)

    Dai, Zhigao; Liao, Lei; Wu, Wei; Guo, Shishang; Zhao, Xinyue; Li, Wei; Ren, Feng; Jiang, Changzhong, E-mail: xxh@whu.edu.cn, E-mail: czjiang@whu.edu.cn [Department of Physics, Hubei Nuclear Solid Physics Key Laboratory and Center for Ion Beam Application, Wuhan University, Wuhan 430072 (China); Mei, Fei [Department of Physics, Hubei Nuclear Solid Physics Key Laboratory and Center for Ion Beam Application, Wuhan University, Wuhan 430072 (China); School of Electrical and Electronic Engineering, Hubei University of Technology, Wuhan 430068 (China); Xiao, Xiangheng, E-mail: xxh@whu.edu.cn, E-mail: czjiang@whu.edu.cn [Department of Physics, Hubei Nuclear Solid Physics Key Laboratory and Center for Ion Beam Application, Wuhan University, Wuhan 430072 (China); Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095 (United States); Fu, Lei; Wang, Jiao [College of Chemistry and Molecular Science, Wuhan University, Wuhan 430072 (China)

    2014-07-21

    The Ag nanoparticles (NPs) surrounding triangular nanoarrays (TNAs) with high number density of surface-enhanced Raman scattering (SERS) hot spots (SERS hot spots ring) are prepared by a combination of NPs deposition and subsequent colloid lithography processing. Owing to the SERS hot spots ring, the Ag NPs surrounding TNAs have been proved an excellent candidate for ultrasensitive molecular sensing for their high SERS signal enhancing capacity in experiments and theories. The Ag NPs surrounding TNAs can be readily used for the quick detection of low concentrations of molecules related to food safety; herein, detection of melamine is discussed.

  17. Five-way Smoking Status Classification Using Text Hot-Spot Identification and Error-correcting Output Codes

    OpenAIRE

    Cohen, Aaron M.

    2008-01-01

    We participated in the i2b2 smoking status classification challenge task. The purpose of this task was to evaluate the ability of systems to automatically identify patient smoking status from discharge summaries. Our submission included several techniques that we compared and studied, including hot-spot identification, zero-vector filtering, inverse class frequency weighting, error-correcting output codes, and post-processing rules. We evaluated our approaches using the same methods as the i2...

  18. Imaging challenges in 20nm and 14nm logic nodes: hot spots performance in Metal1 layer

    Science.gov (United States)

    Timoshkov, V.; Rio, D.; Liu, H.; Gillijns, W.; Wang, J.; Wong, P.; Van Den Heuvel, D.; Wiaux, V.; Nikolsky, P.; Finders, J.

    2013-10-01

    The 20nm Metal1 layer, based on ARM standard cells, has a 2D design with minimum pitch of 64nm. This 2D design requires a Litho-Etch-Litho-Etch (LELE) double patterning. The whole design is divided in 2 splits: Me1A and Me1B. But solution of splitting conflicts needs stitching at some locations, what requires good Critical Dimension (CD) and overlay control to provide reliable contact between 2 stitched line ends. ASML Immersion NXT tools are aimed at 20 and 14nm logic production nodes. Focus control requirements become tighter, as existing 20nm production logic layouts, based on ARM, have about 50-60nm focus latitude and tight CD Uniformity (CDU) specifications, especially for line ends. IMEC inspected 20nm production Metal1 ARM standard cells with a Negative Tone Development (NTD) process using the Process Window Qualification-like technique experimentally and by Brion Tachyon LMC by simulations. Stronger defects were found thru process variations. A calibrated Tachyon model proved a good overall predictability capability for this process. Selected defects are likely to be transferred to hard mask during etch. Further, CDU inspection was performed for these critical features. Hot spots showed worse CD uniformity than specifications. Intra-field CDU contribution is significant in overall CDU budget, where reticle has major impact due to high MEEF of hot spots. Tip-to-Tip and tip-to-line hot spots have high MEEF and its variation over the field. Best focus variation range was determined by best focus offsets between hot spots and its variation within the field.

  19. Five-way smoking status classification using text hot-spot identification and error-correcting output codes.

    Science.gov (United States)

    Cohen, Aaron M

    2008-01-01

    We participated in the i2b2 smoking status classification challenge task. The purpose of this task was to evaluate the ability of systems to automatically identify patient smoking status from discharge summaries. Our submission included several techniques that we compared and studied, including hot-spot identification, zero-vector filtering, inverse class frequency weighting, error-correcting output codes, and post-processing rules. We evaluated our approaches using the same methods as the i2b2 task organizers, using micro- and macro-averaged F1 as the primary performance metric. Our best performing system achieved a micro-F1 of 0.9000 on the test collection, equivalent to the best performing system submitted to the i2b2 challenge. Hot-spot identification, zero-vector filtering, classifier weighting, and error correcting output coding contributed additively to increased performance, with hot-spot identification having by far the largest positive effect. High performance on automatic identification of patient smoking status from discharge summaries is achievable with the efficient and straightforward machine learning techniques studied here. PMID:17947623

  20. Controlling dynamic SERS hot spots on a monolayer film of Fe3O4@Au nanoparticles by a magnetic field

    Science.gov (United States)

    Guo, Qing-Hua; Zhang, Chen-Jie; Wei, Chao; Xu, Min-Min; Yuan, Ya-Xian; Gu, Ren-Ao; Yao, Jian-Lin

    2016-01-01

    A large surface-enhanced Raman scattering (SERS) effect is critically dependent on the gap distance of adjacent nanostructures, i.e., "hot spots". However, the fabrication of dynamically controllable hot spots still remains a remarkable challenge. In the present study, we employed an external magnetic field to dynamically control the interparticle spacing of a two-dimensional monolayer film of Fe3O4@Au nanoparticles at a hexane/water interface. SERS measurements were performed to monitor the expansion and shrinkage of the nanoparticles gaps, which produced an obvious effect on SERS activities. The balance between the electrostatic repulsive force, surface tension, and magnetic attractive force allowed observation of the magnetic-field-responsive SERS effect. Upon introduction of an external magnetic field, a very weak SERS signal appeared initially, indicating weak enhancement due to a monolayer film with large interparticle spacing. The SERS intensity reached maximum after 5 s and thereafter remained almost unchanged. The results indicated that the observed variations in SERS intensities were fully reversible after removal of the external magnetic field. The reduction of interparticle spacing in response to a magnetic field resulted in about one order of magnitude of SERS enhancement. The combined use of the monolayer film and external magnetic field could be developed as a strategy to construct hot spots both for practical application of SERS and theoretical simulation of enhancement mechanisms.

  1. Prediction of hot spots in protein interfaces using extreme learning machines with the information of spatial neighbour residues.

    Science.gov (United States)

    Wang, Lin; Zhang, Wenjuan; Gao, Qiang; Xiong, Congcong

    2014-08-01

    The identification of hot spots, a small subset of protein interfaces that accounts for the majority of binding free energy, is becoming increasingly important for the research on protein-protein interaction and drug design. For each interface residue or target residue to be predicted, the authors extract hybrid features which incorporate a wide range of information of the target residue and its spatial neighbor residues, that is, the nearest contact residue in the other face (mirror-contact residue) and the nearest contact residue in the same face (intra-contact residue). Here, feature selection is performed using random forests to avoid over-fitting. Thereafter, the extreme learning machine is employed to effectively integrate these hybrid features for predicting hot spots in protein interfaces. By the 5-fold cross validation in the training set, their method can achieve accuracy (ACC) of 82.1% and Matthew's correlation coefficient (MCC) of 0.459, and outperforms some alternative machine learning methods in the comparison study. Furthermore, their method achieves ACC of 76.8% and MCC of 0.401 in the independent test set, and is more effective than the major existing hot spot predictors. Their prediction method offers a powerful tool for uncovering candidate residues in the studies of alanine scanning mutagenesis for functional protein interaction sites. PMID:25075532

  2. X-ray Radiation Mechanisms and the Beaming Effect of Hot Spots and Knots in AGN Jets

    Indian Academy of Sciences (India)

    Jin Zhang; Jin-Ming Bai; Liang Chen; Enwei Liang

    2011-03-01

    The observed broadband spectral energy distributions (SEDs) of 22 hot spots and 45 knots are modelled with single-zone lepton models. Considering the sources at rest, the X-rays of some hot spots can be explained by the SSC model with magnetic field being consistent with the equipartition magnetic field in magnitude of order 1, but at the same time an unreasonably low magnetic field is required to model the X-rays for all knots. When considering the relativistic bulk motion of the sources, the IC/CMB model well explains the X-ray emission for most of them under the equipartition condition. We show that the ratio of observational luminosity is tentatively correlated with the co-moving equipartition magnetic field 'eq and the beaming factor . These facts suggest that the observational differences of the X-rays from the knots and hot spots may be mainly due to the differences in the Doppler boosting effect and the co-moving magnetic field of the two kinds of source.

  3. Cooling water of power plant creates "hot spots" for tropical fishes and parasites.

    Science.gov (United States)

    Emde, Sebastian; Kochmann, Judith; Kuhn, Thomas; Dörge, Dorian D; Plath, Martin; Miesen, Friedrich W; Klimpel, Sven

    2016-01-01

    Thermally altered water bodies can function as "hot spots" where non-native species are establishing self-sustaining populations beyond their tropical and subtropical native regions. Whereas many tropical fish species have been found in these habitats, the introduction of non-native parasites often remains undetected. Here, n = 77 convict cichlids (Amatitlania nigrofasciata) were sampled by electro-fishing at two sites from a thermally altered stream in Germany and examined for parasite fauna and feeding ecology. Stomach content analysis suggests an opportunistic feeding strategy of A. nigrofasciata: while plant material dominated the diet at the warm water inlet (∼30 °C), relative contributions of insects, plants, and crustaceans were balanced 3 km downstream (∼27 °C). The most abundant non-native parasite species was the tropical nematode Camallanus cotti with P = 11.90 % and P = 80.00 % at the inlet and further downstream, respectively. Additionally, nematode larvae of Anguillicoloides crassus and one specimen of the subtropical species Bothriocephalus acheilognathi were isolated. A. nigrofasciata was also highly infected with the native parasite Acanthocephalus anguillae, which could be linked to high numbers of the parasite's intermediate host Asellus aquaticus. The aim of this study was to highlight the risk and consequences of the release and establishment of ornamental fish species for the introduction and spread of non-indigenous metazoan parasites using the convict cichlid as a model species. Furthermore, the spread of non-native parasites into adjacent fish communities needs to be addressed in the future as first evidence of Camallanus cotti in native fish species was also found. PMID:26374537

  4. Hierarchical Bayesian method for mapping biogeochemical hot spots using induced polarization imaging

    Science.gov (United States)

    Wainwright, Haruko M.; Flores Orozco, Adrian; Bücker, Matthias; Dafflon, Baptiste; Chen, Jinsong; Hubbard, Susan S.; Williams, Kenneth H.

    2016-01-01

    In floodplain environments, a naturally reduced zone (NRZ) is considered to be a common biogeochemical hot spot, having distinct microbial and geochemical characteristics. Although important for understanding their role in mediating floodplain biogeochemical processes, mapping the subsurface distribution of NRZs over the dimensions of a floodplain is challenging, as conventional wellbore data are typically spatially limited and the distribution of NRZs is heterogeneous. In this study, we present an innovative methodology for the probabilistic mapping of NRZs within a three-dimensional (3-D) subsurface domain using induced polarization imaging, which is a noninvasive geophysical technique. Measurements consist of surface geophysical surveys and drilling-recovered sediments at the U.S. Department of Energy field site near Rifle, CO (USA). Inversion of surface time domain-induced polarization (TDIP) data yielded 3-D images of the complex electrical resistivity, in terms of magnitude and phase, which are associated with mineral precipitation and other lithological properties. By extracting the TDIP data values colocated with wellbore lithological logs, we found that the NRZs have a different distribution of resistivity and polarization from the other aquifer sediments. To estimate the spatial distribution of NRZs, we developed a Bayesian hierarchical model to integrate the geophysical and wellbore data. In addition, the resistivity images were used to estimate hydrostratigraphic interfaces under the floodplain. Validation results showed that the integration of electrical imaging and wellbore data using a Bayesian hierarchical model was capable of mapping spatially heterogeneous interfaces and NRZ distributions thereby providing a minimally invasive means to parameterize a hydrobiogeochemical model of the floodplain.

  5. Thermal screening of facial skin arterial hot spots using non-contact infrared radiometry

    International Nuclear Information System (INIS)

    Non-contact infrared thermometry of facial skin offers advantages over less accessible internal body sites, especially when considering mass screening for febrile infectious disease. The forehead offers an obvious site, but does not present an isothermic surface, as various small arteries passing close to the surface create 'hot-spots'. The aim of this study is to use non-contact infrared (IR) thermometry to determine the link between the temperature at specific facial skin sites and clinical body temperature. A sample of 169 asymptomatic adults (age range 18–54 years) was screened with IR thermometers (Braun Thermoscan proLT for auditory meatus (AM) temperature representing clinical body temperature, and a Raytek, Raynger MX for skin surface temperature). Peak IR skin temperature was measured over the course of each posterior auricular artery (PAA) and each superficial temporal artery (STA). In a sub-group (n = 54) the peak skin temperature of the forehead's metopic region (MR) was also recorded. There were no differences (P > 0.05) between the PAA and STA at 34.2 ± 0.9 °C and 34.2 ± 0.7 °C, respectively, which were 2.5 °C cooler than the AM temperature (36.7 ± 0.5 °C, p 2 = 0.63, p < 0.001) between PAA and STA. There were no asymmetric temperature differences between the left and right sides and males had warmer skin over the MR (F, 33.6 ± 0.7 °C versus M, 34.4 ± 0.6 °C, p < 0.001). Although a lack of correlation between either PAA or STA and AM was apparent in asymptomatics, further research in symptomatics is required to determine the usefulness of these measurements in mass screening of conditions such as fever

  6. Shock Compression Induced Hot Spots in Energetic Material Detected by Thermal Imaging Microscopy

    Science.gov (United States)

    Chen, Ming-Wei; Dlott, Dana

    2014-06-01

    The chemical reaction of powder energetic material is of great interest in energy and pyrotechnic applications since the high reaction temperature. Under the shock compression, the chemical reaction appears in the sub-microsecond to microsecond time scale, and releases a large amount of energy. Experimental and theoretical research progresses have been made in the past decade, in order to characterize the process under the shock compression. However, the knowledge of energy release and temperature change of this procedure is still limited, due to the difficulties of detecting technologies. We have constructed a thermal imaging microscopy apparatus, and studied the temperature change in energetic materials under the long-wavelength infrared (LWIR) and ultrasound exposure. Additionally, the real-time detection of the localized heating and energy concentration in composite material is capable with our thermal imaging microscopy apparatus. Recently, this apparatus is combined with our laser driven flyer plate system to provide a lab-scale source of shock compression to energetic material. A fast temperature increase of thermite particulars induced by the shock compression is directly observed by thermal imaging with 15-20 μm spatial resolution. Temperature change during the shock loading is evaluated to be at the order of 10^9K/s, through the direct measurement of mid-wavelength infrared (MWIR) emission intensity change. We observe preliminary results to confirm the hot spots appear with shock compression on energetic crystals, and will discuss the data and analysis in further detail. M.-W. Chen, S. You, K. S. Suslick, and D. D. Dlott, {Rev. Sci. Instr., 85, 023705 (2014) M.-W. Chen, S. You, K. S. Suslick, and D. D. Dlott, {Appl. Phys. Lett., 104, 061907 (2014)} K. E. Brown, W. L. Shaw, X. Zheng, and D. D. Dlott, {Rev. Sci. Instr., 83, 103901 (2012)}

  7. WiFi Hot Spot Service Business for the Automotive and Oil Industries: A Competitive Analysis

    Directory of Open Access Journals (Sweden)

    Louis-Francois PAU

    2010-01-01

    Full Text Available While you refuel for gas, why not refuel for information or upload vehicle data, using a cheap wireless technology as WiFi? This paper analyzes in extensive detail the user segmentation by vehicle usage, service offering, and full business models from WiFi hot spot services delivered to and from vehicles (private, professional, public around gas stations. Are also analyzed the parties which play a role in such services: authorization, provisioning and delivery, with all the dependencies modelled by attributed digraphs. Account is made of WiFi base station technical capabilities and costs. Five year financial models (CAPEX, OPEX, and data pertain to two possible service suppliers: multi-service oil companies, and mobile service operators (or MVNOs. Model optimization on the return-on-investment (R.O.I. is carried out for different deployment scenarios, geographical coverage assumptions, as well as tariff structures. Comparison is also being made with public GPRS and 3G data services, as precursors to HSPA/LTE, and the effect of WiFi roaming is analyzed. Regulatory implications, including those dealing with public safety, are addressed. Analysis shows that due to manpower costs and marketing costs, suitable R.O.I. will not be achieved unless externalities are accounted for and innovative tariff structures are introduced. Open issues and further research are outlined. Further work is currently carried out with automotive electronics sector, wireless systems providers, wireless terminals platform suppliers, and vehicle manufacturers. Future relevance of this work is also discussed for the emerging electrical reloading grids for electrical vehicles.

  8. Hot Spots of Mercury Bioaccumulation in Amphibian Populations From the Conterminous United States

    Science.gov (United States)

    Bank, M. S.

    2008-12-01

    Mercury (Hg) contamination in the United States (U.S.) is well-documented and continues to be a public- health issue of great concern. Fish consumption advisories have been issued throughout much of the U.S. due to elevated levels of methylmercury (MeHg). Methylmercury contamination in the developing fetus and in young children is a major public health issue for certain sectors of the global human population. Moreover, identifying MeHg hot spots and the effects of MeHg pollution on environmental health and biodiversity are also considered a high priority for land managers, risk assessors, and conservation scientists. Despite their overall biomass and importance to aquatic and terrestrial ecosystems, Hg and MeHg bioaccumulation dynamics and toxicity in amphibians are not well studied, especially when compared to other vertebrate taxa such as birds, mammals, and fish species. Population declines in amphibians are well documented and likely caused by synergistic and interacting, multiple stressors such as climate change, exposure to toxic pollutants, fungal pathogens, and habitat loss and ecosystem degradation. Protecting quality of terrestrial ecosystems in the U.S. has enormous ramifications for economic and public health of the nation's residents and is fundamental to maintaining the biotic integrity of surface waters, riparian zones, and environmental health of forested landscapes nationwide. Determining Hg concentration levels for terrestrial and surface water ecosystems also has important implications for protecting the nation's fauna. Here I present an overview of the National Amphibian Mercury Program and evaluate variation in MeHg hotspots, Hg bioaccumulation and distribution in freshwater and terrestrial habitats across a broad gradient of physical, climatic, biotic, and ecosystem settings to identify the environmental conditions and ecosystem types that are most sensitive to Hg pollution. The role of geography, disturbance mechanisms, and abiotic and biotic

  9. Spin-fermion model with overlapping hot spots and charge modulation in cuprates

    Science.gov (United States)

    Volkov, Pavel A.; Efetov, Konstantin B.

    2016-02-01

    We study particle-hole instabilities in the framework of the spin-fermion (SF) model. In contrast to previous studies, we assume that adjacent hot spots can overlap due to a shallow dispersion of the electron spectrum in the antinodal region. In addition, we take into account effects of a remnant low energy and momentum Coulomb interaction. We demonstrate that at sufficiently small values |ɛ (π ,0 ) - EF|≲Γ , where EF is the Fermi energy, ɛ (π ,0 ) is the energy in the middle of the Brillouin zone edge, and Γ is a characteristic energy of the fermion-fermion interaction due to the antiferromagnetic fluctuations, the leading particle-hole instability is a d -form factor Fermi surface deformation (the Pomeranchuk instability) rather than the charge modulation along the Brillouin zone diagonals predicted within the standard SF model previously. At lower temperatures, we find that the deformed Fermi surface is further unstable to formation of a d -form factor charge density wave (CDW) with a wave vector along the Cu-O-Cu bonds (axes of the Brillouin zone). We show that the remnant Coulomb interaction enhances the d -form-factor symmetry of the CDW. These findings can explain the robustness of this order in the cuprates. The approximations made in the paper are justified by a small parameter that allows one to implement an Eliashberg-like treatment. Comparison with experiments suggests that in many cuprate compounds the prerequisites for the proposed scenario are indeed fulfilled and the results obtained may explain important features of the charge modulations observed recently.

  10. Effect of width, amplitude, and position of a core mantle boundary hot spot on core convection and dynamo action

    CERN Document Server

    Dietrich, Wieland; Hori, Kumiko

    2015-01-01

    Within the fluid iron cores of terrestrial planets, convection and the resulting generation of global magnetic fields are controlled by the overlying rocky mantle. The thermal structure of the lower mantle determines how much heat is allowed to escape the core. Hot lower mantle features, such as the thermal footprint of a giant impact or hot mantle plumes, will locally reduce the heat flux through the core mantle boundary (CMB), thereby weakening core convection and affecting the magnetic field generation process. In this study, we numerically investigate how parametrised hot spots at the CMB with arbitrary sizes, amplitudes, and positions affect core convection and hence the dynamo. The effect of the heat flux anomaly is quantified by changes in global flow symmetry properties, such as the emergence of equatorial antisymmetric, axisymmetric (EAA) zonal flows. For purely hydrodynamic models, the EAA symmetry scales almost linearly with the CMB amplitude and size, whereas self-consistent dynamo simulations typ...

  11. A study of the long-term properties of Jovian hot spots from HST and ground-based observations between 1994 and 1998

    Science.gov (United States)

    Arregui, E.; Rojas, J. F.; Sanchez-Lavega, A.; Lecacheux, J.; Colas, F.; Miyazaki, I.; Parker, D.

    2000-10-01

    We have used the HST-WFPC2 archived images of Jupiter in the period 1994-1998 together with a large set of CCD ground based images, to study the zonal distribution, long-term motions, lifetimes, interactions and other properties of the hot spot - plume regions at 7 degrees North. Red and near infrared filters covering the wavelength range 650 - 953 nm have been used since they show the hot spots with a high contrast. We have found that the hot spots have velocities ranging from 95 to 112 m/s and are grouped typically in families of three to six members. We do not found any correlation between their velocity and wavenumber. The long-term survey allowed us to identify mergers and splitting of the hot spots areas. The Spanish team was supported by Gobierno Vasco PI 034/97. The French team was supported by the "Programme National de Planetologie."

  12. The topographic wetness index as a predictor for hot spots of DOC export from catchments

    Science.gov (United States)

    Musolff, Andreas; Oosterwoud, Marieke; Tittel, Jörg; Selle, Benny; Fleckenstein, Jan H.

    2015-04-01

    Dissolved organic carbon (DOC) concentrations in the discharge of many catchments in Europe and North America are rising. This increase is of concern for the drinking water supply from reservoirs since high DOC concentrations cause additional costs in water treatment and potentially the formation of harmful disinfection by-products. A prerequisite for understanding this increase is the knowledge on the spatial distribution of dominant soil DOC sources within catchments and on mobilization as well as transfer processes to the surface water. A number of studies identified wetland soils as the dominant source with fast mobilization and short transit times to the receiving surface water. However, most studies have either focussed on smaller, hillslope and single catchment or on larger scale multi-catchment assessments. Moreover, information on the distribution of soil types in catchments is not always readily available. This study brings together both types of assessment in a data-driven top-down approach: (i) a detailed survey on DOC concentration and loads over the course of one year within two paired data-rich catchments discharging into a large drinking water reservoir in central Germany and (ii) a database of hydrochemistry and physio-geographic characteristics of 113 catchments draining into 58 reservoirs across Germany over the course of 16 years. The objective is to define hot spots of DOC export within the catchments for both types of assessments (i, ii) and to test the suitability of the topographic wetness index (TWI) as a proxy for well-connected wetland soils at various spatial scales. In the sub-catchments of assessment (i) the spatial variability of concentrations and loads was much smaller than expected. None of the studied sub-catchments was a predominant producer of the total DOC loads exported from the catchments. We found the mean concentrations and loads to be positively correlated with the share of groundwater-dominated soils in the sub

  13. Hot Spots and Mantle Plumes: A Window Into the Deep Earth and a Lesson on How Science Really Works

    Science.gov (United States)

    Caplan-Auerbach, J.

    2010-12-01

    Despite years of discussion, debate and controversy over the causes of ocean island volcanism, most students simply learn that such features form from fixed plumes of hot material rising from the core mantle boundary. Although we know that the Hawaiian plume exhibited substantial southward motion, most introductory geology textbooks still report that hot spots are fixed and that the Hawaiian-Emperor bend reflects a change in plate motion. That mantle plumes are the focus of significant controversy within the scientific community is rarely, if ever, discussed, and alternative models for the formation of intraplate volcanoes are ignored. Students may thus complete their studies without learning about the dynamic debate focused on the existence and formation of mantle plumes. This issue represents an opportunity for students to see how science really works, how new models are constructed, and what distinguishes a hypothesis from a theory. The culminating project in Western Washington University’s Introduction to Geophysics class, a course required for the BS degree in geology, focuses on the hot spot and mantle plume debate. For the first nine weeks of the quarter students learn about general topics in geophysics including plate tectonics, magnetism, seismology, gravity and heat flow. At the end of the course, students break into small research groups with the goal of investigating how geophysics may be used to address three questions: (1) Do ocean island volcanoes form from mantle plumes? (2) Are “hot spots” actually hot? (3) Are hot spots stationary? Each group examines how these questions may be addressed using a specific geophysical tool. In addition to the five topics described above, a sixth group investigates the question of “if not hot spots/mantle plumes, how do ocean island volcanoes form?” Students read the current literature on the topic and present their results to their classmates. Presentations focus on topics such as the use of seismic

  14. Bering-Okhotsk Seal Survey (BOSS) Identified Hot Spots (2012-13)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — US surveys were conducted of the Bering Sea pack ice for bearded, spotted, ribbon, and ringed seals using digital cameras and thermal imagers mounted in the belly...

  15. The southern stratospheric gravity-wave hot spot: individual waves and their momentum fluxes measured by COSMIC GPS-RO

    Directory of Open Access Journals (Sweden)

    N. P. Hindley

    2015-02-01

    Full Text Available During austral winter the mountains of the southern Andes and Antarctic Peninsula are a known hot spot of intense gravity wave momentum flux. There also exists a long leeward region of increased gravity wave energy that sweeps eastwards from the mountains out over the Southern Ocean, the source of which has historically proved difficult to determine. In this study we use Global Positioning System (GPS Radio Occultation (RO data from the Constellation Observing System for Meteorology, Ionosphere and Climate (COSMIC satellite constellation to investigate the distribution, variability and sources of waves in the hot spot region and over the Southern Ocean. We present evidence that suggests a southward focusing of waves into the stratospheric jet from sources to the north. We also describe a wavelet analysis technique for the quantitative identification of individual waves from COSMIC temperature profiles. This analysis reveals different geographical regimes of wave amplitude and short-timescale variability in the wave field over the Southern Ocean. Finally, we take advantage of the large numbers of closely spaced pairs of profiles from the deployment phase of the COSMIC constellation in 2006 to make estimates of gravity wave horizontal wavelengths. We show that, given sufficient numbers of these pairs, GPS-RO can then produce physically reasonable estimates of stratospheric gravity wave momentum flux in the hot spot region that are consistent with other studies. The results are discussed in the context of previous satellite and modelling studies to build up a better picture of the nature and origins of waves in the southern winter stratosphere.

  16. Finite volume analysis of temperature effects induced by active MRI implants: 2. Defects on active MRI implants causing hot spots

    Directory of Open Access Journals (Sweden)

    Grönemeyer Dietrich HW

    2006-05-01

    Full Text Available Abstract Background Active magnetic resonance imaging implants, for example stents, stent grafts or vena cava filters, are constructed as wireless inductively coupled transmit and receive coils. They are built as a resonator tuned to the Larmor frequency of a magnetic resonance system. The resonator can be added to or incorporated within the implant. This technology can counteract the shielding caused by eddy currents inside the metallic implant structure. This may allow getting diagnostic information of the implant lumen (in stent stenosis or thrombosis for example. The electro magnetic rf-pulses during magnetic resonance imaging induce a current in the circuit path of the resonator. A by material fatigue provoked partial rupture of the circuit path or a broken wire with touching surfaces can set up a relatively high resistance on a very short distance, which may behave as a point-like power source, a hot spot, inside the body part the resonator is implanted to. This local power loss inside a small volume can reach ¼ of the total power loss of the intact resonating circuit, which itself is proportional to the product of the resonator volume and the quality factor and depends as well from the orientation of the resonator with respect to the main magnetic field and the imaging sequence the resonator is exposed to. Methods First an analytical solution of a hot spot for thermal equilibrium is described. This analytical solution with a definite hot spot power loss represents the worst case scenario for thermal equilibrium inside a homogeneous medium without cooling effects. Starting with this worst case assumptions additional conditions are considered in a numerical simulation, which are more realistic and may make the results less critical. The analytical solution as well as the numerical simulations use the experimental experience of the maximum hot spot power loss of implanted resonators with a definite volume during magnetic resonance imaging

  17. Production of 'hot spot' image of a fast z-pinch by the linear Bragg-Fresnel lense

    International Nuclear Information System (INIS)

    The application of linear Bragg-Fresnel lense for focusing radiation of a powerful x-ray pulse source on the basis of a fast z-pinch is announced for the first time. It is shown that the size of plasma 'hot spot' images does not exceed 20-30 μm which pinpoints to the presence of rather dense plasma regions with high gradients which seems to be illuminated by an electron beam generated during current brench off in the pinch at the second stage of compression

  18. Hot spot formation and chemical reaction initiation in shocked HMX crystals with nanovoids: a large-scale reactive molecular dynamics study.

    Science.gov (United States)

    Zhou, Tingting; Lou, Jianfeng; Zhang, Yangeng; Song, Huajie; Huang, Fenglei

    2016-07-14

    We report million-atom reactive molecular dynamic simulations of shock initiation of β-cyclotetramethylene tetranitramine (β-HMX) single crystals containing nanometer-scale spherical voids. Shock induced void collapse and subsequent hot spot formation as well as chemical reaction initiation are observed which depend on the void size and impact strength. For an impact velocity of 1 km s(-1) and a void radius of 4 nm, the void collapse process includes three stages; the dominant mechanism is the convergence of upstream molecules toward the centerline and the downstream surface of the void forming flowing molecules. Hot spot formation also undergoes three stages, and the principal mechanism is kinetic energy transforming to thermal energy due to the collision of flowing molecules on the downstream surface. The high temperature of the hot spot initiates a local chemical reaction, and the breakage of the N-NO2 bond plays the key role in the initial reaction mechanism. The impact strength and void size have noticeable effects on the shock dynamical process, resulting in a variation of the predominant mechanisms leading to void collapse and hot spot formation. Larger voids or stronger shocks result in more intense hot spots and, thus, more violent chemical reactions, promoting more reaction channels and generating more reaction products in a shorter duration. The reaction products are mainly concentrated in the developed hot spot, indicating that the chemical reactivity of the hmx crystal is greatly enhanced by void collapse. The detailed information derived from this study can aid a thorough understanding of the role of void collapse in hot spot formation and the chemical reaction initiation of explosives. PMID:27307079

  19. Environmental hot spot analysis in agricultural life-cycle assessments – three case studies

    Directory of Open Access Journals (Sweden)

    Gerhard Piringer

    2016-06-01

    Full Text Available Present-day agricultural technology is facing the challenge of limiting the environmental impacts of agricultural production – such as greenhouse gas emissions and demand for additional land – while meeting growing demands for agricultural products. Using the well-established method of life-cycle assessment (LCA, potential environmental impacts of agricultural production chains can be quantified and analyzed. This study presents three case studies of how the method can pinpoint environmental hot spots at different levels of agricultural production systems. The first case study centers on the tractor as the key source of transportation and traction in modern agriculture. A common Austrian tractor model was investigated over its life-cycle, using primary data from a manufacturer and measured load profiles for field work. In all but one of the impact categories studied, potential impacts were dominated by the operation phase of the tractor’s life-cycle (mainly due to diesel fuel consumption, with 84.4-99.6% of total impacts. The production phase (raw materials and final assembly caused between 0.4% and 12.1% of impacts, while disposal of the tractor was below 1.9% in all impact categories. The second case study shifts the focus to an entire production chain for a common biogas feedstock, maize silage. System boundaries incorporate the effect of auxiliary materials such as fertilizer and pesticides manufacturing and application. The operation of machinery in the silage production chain was found to be critical to its environmental impact. For the climate change indicator GWP100 (global warming potential, 100-year reference period, emissions from tractor operation accounted for 15 g CO2-eq per kg silage (64% of total GWP100, followed by field emissions during fertilizer (biogas digestate application with 6 g CO2-eq per kg silage (24% of total GWP100. At a larger system scale that includes a silage-fed biogas plant with electricity generated by

  20. Resolving hot spots in the C-terminal dimerization domain that determine the stability of the molecular chaperone Hsp90.

    Directory of Open Access Journals (Sweden)

    Emanuele Ciglia

    Full Text Available Human heat shock protein of 90 kDa (hHsp90 is a homodimer that has an essential role in facilitating malignant transformation at the molecular level. Inhibiting hHsp90 function is a validated approach for treating different types of tumors. Inhibiting the dimerization of hHsp90 via its C-terminal domain (CTD should provide a novel way to therapeutically interfere with hHsp90 function. Here, we predicted hot spot residues that cluster in the CTD dimerization interface by a structural decomposition of the effective energy of binding computed by the MM-GBSA approach and confirmed these predictions using in silico alanine scanning with DrugScore(PPI. Mutation of these residues to alanine caused a significant decrease in the melting temperature according to differential scanning fluorimetry experiments, indicating a reduced stability of the mutant hHsp90 complexes. Size exclusion chromatography and multi-angle light scattering studies demonstrate that the reduced stability of the mutant hHsp90 correlates with a lower complex stoichiometry due to the disruption of the dimerization interface. These results suggest that the identified hot spot residues can be used as a pharmacophoric template for identifying and designing small-molecule inhibitors of hHsp90 dimerization.

  1. Hot spots and transient pockets: predicting the determinants of small-molecule binding to a protein-protein interface.

    Science.gov (United States)

    Metz, Alexander; Pfleger, Christopher; Kopitz, Hannes; Pfeiffer-Marek, Stefania; Baringhaus, Karl-Heinz; Gohlke, Holger

    2012-01-23

    Protein-protein interfaces are considered difficult targets for small-molecule protein-protein interaction modulators (PPIMs ). Here, we present for the first time a computational strategy that simultaneously considers aspects of energetics and plasticity in the context of PPIM binding to a protein interface. The strategy aims at identifying the determinants of small-molecule binding, hot spots, and transient pockets, in a protein-protein interface in order to make use of this knowledge for predicting binding modes of and ranking PPIMs with respect to their affinity. When applied to interleukin-2 (IL-2), the computationally inexpensive constrained geometric simulation method FRODA outperforms molecular dynamics simulations in sampling hydrophobic transient pockets. We introduce the PPIAnalyzer approach for identifying transient pockets on the basis of geometrical criteria only. A sequence of docking to identified transient pockets, starting structure selection based on hot spot information, RMSD clustering and intermolecular docking energies, and MM-PBSA calculations allows one to enrich IL-2 PPIMs from a set of decoys and to discriminate between subgroups of IL-2 PPIMs with low and high affinity. Our strategy will be applicable in a prospective manner where nothing else than a protein-protein complex structure is known; hence, it can well be the first step in a structure-based endeavor to identify PPIMs. PMID:22087639

  2. High frequency localised "hot spots" in temporal lobes of patients with intractable tinnitus: a quantitative electroencephalographic (QEEG) study.

    Science.gov (United States)

    Ashton, Heather; Reid, Keith; Marsh, Richard; Johnson, Ian; Alter, Kai; Griffiths, Tim

    2007-10-01

    Tinnitus, the perception of noise in the absence of an external auditory stimulus, is common, frequently distressing and often intractable. It is associated with a number of conditions including deafness but may arise spontaneously. Brain imaging studies indicate increased neuronal excitability and decreased density of benzodiazepine receptors in temporal (auditory) cortex but the source and mechanism of such changes are unknown. Various electroencephalographic (EEG) abnormalities involving temporal lobe and other brain areas have been described but recordings have been limited to standard EEG wave bands up to frequencies of 22Hz. This clinical study of otherwise healthy patients with intractable unilateral tinnitus, using quantitative EEG power spectral mapping (QEEG), identified discrete localised unilateral foci of high frequency activity in the gamma range (>40-80Hz) over the auditory cortex in eight patients experiencing tinnitus during recording. These high frequency "hot spots" were not present in 25 subjects without tinnitus. The results suggest that further EEG investigations should include recordings in the gamma frequency range since such high frequency oscillations are believed to be necessary for perception. Identification of "hot spots" in tinnitus patients would provide a means for monitoring the effects of new treatments. These findings may also provide a model for exploration of more complex phenomena such as verbal and musical hallucinations. PMID:17888572

  3. Disease Mutations in the Ryanodine Receptor Central Region: Crystal Structures of a Phosphorylation Hot Spot Domain

    Energy Technology Data Exchange (ETDEWEB)

    Yuchi, Zhiguang; Lau, Kelvin; Van Petegem, Filip (UBC)

    2015-02-09

    Ryanodine Receptors (RyRs) are huge Ca{sup 2+} release channels in the endoplasmic reticulum membrane and form targets for phosphorylation and disease mutations. We present crystal structures of a domain in three RyR isoforms, containing the Ser2843 (RyR1) and Ser2808/Ser2814 (RyR2) phosphorylation sites. The RyR1 domain is the target for 11 disease mutations. Several of these are clustered near the phosphorylation sites, suggesting that phosphorylation and disease mutations may affect the same interface. The L2867G mutation causes a drastic thermal destabilization and aggregation at room temperature. Crystal structures for other disease mutants show that they affect surface properties and intradomain salt bridges. In vitro phosphorylation experiments show that up to five residues in one long loop of RyR2 can be phosphorylated by PKA or CaMKII. Docking into cryo-electron microscopy maps suggests a putative location in the clamp region, implying that mutations and phosphorylation may affect the allosteric motions within this area.

  4. Effect of width, amplitude and position of a CMB hot spot on core convection and dynamo action

    Science.gov (United States)

    Dietrich, W.; Wicht, J.; Hori, K.

    2015-10-01

    Within the fluid iron cores of terrestrial planets, convection and hence the generation of global magnetic fields are controlled by the overlying rocky mantle. The thermal structure of the lower mantle determines how much heat is allowed to escape the core. Hot lower mantle features, like the thermal footprint of a giant impact or hot mantle plumes will reduce locally the heat flux through the core mantle boundary (CMB) and thereby weaken core convection and affect the magnetic field generation process. In this study, we numerically investigate how parametrised hot spots at the CMB with arbitrary size, amplitude and position affect core convection and hence the dynamo. The effect of the heat flux anomaly is quantified by changes in global flow symmetry properties, such as the emergence of equatorial antisymmetric and axisymmetric (EAA) zonal flows. For pure hydrodynamic models the EAA symmetry scales almost linearly with its respective amplitude and size, whereas self-consistent dynamo simulations typically either suppress or drastically enhance EAA depending mainly on the length scale of the heat flux anomaly. Our results suggest, that the horizontal extent of the anomaly should be on the order of the outer core radius to significantly affect flow and field symmetries. As an implication to Mars, the study concludes that an ancient core field modified by a CMB heat flux anomaly is not able to heteroge- neously magnetise the crust to the present-day level of north-south asymmetry.

  5. Structural and energetic hot-spots for the interaction between a ladder-like polycyclic ether and the anti-ciguatoxin antibody 10C9Fab.

    Science.gov (United States)

    Ui, Mihoko; Tanaka, Yoshikazu; Tsumuraya, Takeshi; Fujii, Ikuo; Inoue, Masayuki; Hirama, Masahiro; Tsumoto, Kouhei

    2011-03-01

    The mechanism by which anti-ciguatoxin antibody 10C9Fab recognizes a fragment of ciguatoxin CTX3C (CTX3C-ABCDE) was investigated by mutational analysis based on structural data. 10C9Fab has an extraordinarily large and deep antigen-binding pocket at the center of its variable region. We mutated several residues located at the antigen-binding pocket to Ala, and kinetic analysis of the interactions between the mutant proteins and the antigen fragment was performed. The results indicate that some residues associated with the rigid antigen-binding pocket are structural hot-spots and that L-N94 is an energetic hot-spot for association of the antibody with the antigen fragment CTX3C-ABCDE, suggesting the importance of structural complementarity and energetic hot-spot interactions for specific recognition of polycyclic ethers. PMID:21161086

  6. Demonstration of Fuel Hot-Spot Pressure in Excess of 50 Gbar for Direct-Drive, Layered Deuterium-Tritium Implosions on OMEGA

    Science.gov (United States)

    Regan, S. P.; Goncharov, V. N.; Igumenshchev, I. V.; Sangster, T. C.; Betti, R.; Bose, A.; Boehly, T. R.; Bonino, M. J.; Campbell, E. M.; Cao, D.; Collins, T. J. B.; Craxton, R. S.; Davis, A. K.; Delettrez, J. A.; Edgell, D. H.; Epstein, R.; Forrest, C. J.; Frenje, J. A.; Froula, D. H.; Gatu Johnson, M.; Glebov, V. Yu.; Harding, D. R.; Hohenberger, M.; Hu, S. X.; Jacobs-Perkins, D.; Janezic, R.; Karasik, M.; Keck, R. L.; Kelly, J. H.; Kessler, T. J.; Knauer, J. P.; Kosc, T. Z.; Loucks, S. J.; Marozas, J. A.; Marshall, F. J.; McCrory, R. L.; McKenty, P. W.; Meyerhofer, D. D.; Michel, D. T.; Myatt, J. F.; Obenschain, S. P.; Petrasso, R. D.; Radha, P. B.; Rice, B.; Rosenberg, M. J.; Schmitt, A. J.; Schmitt, M. J.; Seka, W.; Shmayda, W. T.; Shoup, M. J.; Shvydky, A.; Skupsky, S.; Solodov, A. A.; Stoeckl, C.; Theobald, W.; Ulreich, J.; Wittman, M. D.; Woo, K. M.; Yaakobi, B.; Zuegel, J. D.

    2016-07-01

    A record fuel hot-spot pressure Phs=56 ±7 Gbar was inferred from x-ray and nuclear diagnostics for direct-drive inertial confinement fusion cryogenic, layered deuterium-tritium implosions on the 60-beam, 30-kJ, 351-nm OMEGA Laser System. When hydrodynamically scaled to the energy of the National Ignition Facility, these implosions achieved a Lawson parameter ˜60 % of the value required for ignition [A. Bose et al., Phys. Rev. E 93, LM15119ER (2016)], similar to indirect-drive implosions [R. Betti et al., Phys. Rev. Lett. 114, 255003 (2015)], and nearly half of the direct-drive ignition-threshold pressure. Relative to symmetric, one-dimensional simulations, the inferred hot-spot pressure is approximately 40% lower. Three-dimensional simulations suggest that low-mode distortion of the hot spot seeded by laser-drive nonuniformity and target-positioning error reduces target performance.

  7. Hot topic: Black spot defect in Cheddar cheese linked to intramammary teat sealant.

    Science.gov (United States)

    Lay, A M; Kolpin, K M; Sommer, D A; Rankin, S A

    2007-11-01

    The objective of this work was to characterize a novel appearance defect found in Cheddar cheese, heretofore referred to as black spot defect (BSD), and to determine an etiology. Uniformly distributed throughout the cheese mass, BSD appears as small spherical black spots from 0.20 to 4.7 mm in diameter and at an average frequency of about 2 spots per kg of cheese. To date, BSD has only been found in aged Cheddar cheese. Selected elemental analysis found the BSD region in cheese to have average concentrations of the element bismuth of approximately 400 microg/g, representing an approximately 2,500-fold increase over native levels of bismuth in cheese. Transmission electron microscopy analysis of the BSD region revealed amorphous solid structures and one-dimensional hair-like structures, neither of which was present in non-BSD regions. Such amorphous "nanorod" structures can be formed by the crystallization of bismuth III sulfide and are proposed to be a source of black discoloration. We hypothesize that localized bismuth salts entrained within the cheese curd react with hydrogen sulfide generated during aging to generate bismuth III sulfide. We further propose that the presence of localized bismuth salt precursor results from residual levels of a commercial intra-mammary teat sealant containing bismuth subnitrate that becomes unintentionally entrained within the cheese milk. PMID:17954732

  8. TW Hydrae: evidence of stellar spots instead of a Hot Jupiter

    CERN Document Server

    Huélamo, N; Bonfils, X; Santos, N C; Pepe, F; Guillon, M; Azevedo, R; Barman, T; Fernández, M; di Folco, E; Guenther, E W; Lovis, C; Melo, C H F; Queloz, D; Udry, S

    2008-01-01

    TW Hydrae shows significant radial-velocity variations in the optical regime. They have been attributed to a 10 Jupiter Mass planet orbiting the star at 0.04 AU. In this work, we have tested whether the observed RV variations can be caused by stellar spots. We have also analyzed new optical and infrared data to confirm the signal of the planet companion. We fitted the RV variations of TW Hya using a cool spot model. Our model shows that a cold spot covering 7% of the stellar surface and located at a latitude of 54 deg can reproduce the reported RV variations. The model also predicts a bisector semi-amplitude variation <10 m/s, which is less than the errors of the RV measurements discussed in an earlier publication. The analysis of new optical RV data, with typical errors of 10 m/s, shows a larger RV amplitude that varies depending on the correlation mask used. A slight correlation between the RV variation and the bisector is also observed, although not at a very significant level. The infrared H-band RV cu...

  9. Collective excitation of plasmonic hot-spots for enhanced hot charge carrier transfer in metal/semiconductor contacts

    Science.gov (United States)

    Piot, Adrien; Earl, Stuart K.; Ng, Charlene; Dligatch, Svetlana; Roberts, Ann; Davis, Timothy J.; Gómez, Daniel E.

    2015-04-01

    We show how a combination of near- and far-field coupling of the localised surface plasmon resonances in aluminium nanoparticles deposited on TiO2 films greatly enhances the visible light photocatalytic activity of the semiconductor material. We demonstrate two orders of magnitude enhancement in the rate of decomposition of methylene blue under visible light illumination when the surface of TiO2 films is decorated with gratings of Al nanoparticle dimers.We show how a combination of near- and far-field coupling of the localised surface plasmon resonances in aluminium nanoparticles deposited on TiO2 films greatly enhances the visible light photocatalytic activity of the semiconductor material. We demonstrate two orders of magnitude enhancement in the rate of decomposition of methylene blue under visible light illumination when the surface of TiO2 films is decorated with gratings of Al nanoparticle dimers. Electronic supplementary information (ESI) available: Detailed information on estimates of hot-electron injection efficiencies, electrodynamic simulations, sample preparation, spectroscopic and structural characterization and photocatalytic experiments. See DOI: 10.1039/c5nr01592h

  10. Hot moments and hot spots in hyporheic nutrient transformation - To what degree does small-scale variability control stream-reach attenuation potential?

    Science.gov (United States)

    Krause, S.; Blume, T.; Binley, A.; Heathwaite, L.; Cassidy, N. J.; Munz, M.; Tecklenburg, C.; Kaeser, D.

    2011-12-01

    Concentrations of nutrients and contaminants in up-welling groundwater can significantly change along the passage through highly heterogeneous streambed sediments with substantial implications for the quality of connected surface water bodies. This study presents investigations into the physical drivers and chemical controls of nutrient transport and transformation at the aquifer-river interfaces of two upland and lowland UK rivers. It combines the application of in-stream geophysical exploration techniques, multi-level mini-piezometer networks, active and passive heat tracing methods (including fibre-optic distributed temperature sensing - FO-DTS) for identifying hyporheic exchange fluxes and residence time distributions with multi-scale approaches of hyporheic pore water sampling and reactive tracers for analysing the patterns of streambed redox conditions and chemical transformation rates. The analysis of hyporheic pore water from nested multi-level mini piezometers and passive gel probe samplers revealed significant spatial variability in streambed redox conditions and concentration changes of nitrogen species, dissolved oxygen and bioavailable organic carbon. Hot spots of increased nitrate attenuation were identified beneath semi-confining peat lenses in the streambed of the investigated lowland river. The intensity of concentration changes underneath the confining peat pockets correlated with the state of anoxia in the pore water as well as the supply of organic carbon and hyporheic residence times. In contrast, at locations where flow inhibiting peat layers were absent or disrupted - fast exchange between aquifer and river caused a break through of nitrate without significant concentration changes along the hyporheic flow path. Fibre-optic distributed temperature sensor networks and streambed electric resistivity tomography were applied for identifying exchange flow patterns between groundwater and surface water in dependency of streambed structural

  11. Professional- Amateur Astronomer Partnerships in Scientific Research: The Re-emergence of Jupiter's 5-Micron Hot Spots

    Science.gov (United States)

    Yanamandra-Fisher, P. A.

    2012-12-01

    The night sky, with all its delights and mysteries, enthrall professional and amateur astronomers alike. The discrete data sets acquired by professional astronomers via their approved observing programs at various national facilities are supplemented by the nearly daily observations of the same celestial object by amateur astronomers around the world. The emerging partnerships between professional and dedicated amateur astronomers rely on creating a niche for long timeline of multispectral remote sensing. "Citizen Astronomy" can be thought of as the paradigm shift transforming the nature of observational astronomy. In the past decade, it is the collective observations and their analyses by the ever-increasing global network of amateur astronomers that has discovered interesting phenomena and provided the reference backdrop for observations by ground-based professional astronomers and spacecraft missions. We shall present results from our collaborations to observe the recent global upheaval on Jupiter for the past five years and illustrate the strong synergy between the two groups. Global upheavals on Jupiter involve changes in the albedo of entire axisymmetric regions, lasting several years, with the last two occurring in 1989 and 2006. Against this backdrop of planetary-scale changes, discrete features such as the Great Red Spot (GRS), and other vortices exhibit changes on shorter spatial- and time-scales. One set of features we are currently tracking is the variability of the discrete equatorial 5-μm hot spots, semi-evenly spaced in longitude and confined to a narrow latitude band centered at 6.5°N (southern edge of the North Equatorial Belt, NEB), abundant in Voyager images (1980-1981). Tantalizingly similar patterns were observed in the visible (bright plumes and blue-gray regions), where reflectivity in the red is anti-correlated with 5-μm thermal radiance. During the recent NEB fade (2011 - early 2012), however, these otherwise ubiquitous features were

  12. Unusual seismic activity in 2011 and 2013 at the submarine volcano Rocard, Society hot spot (French Polynesia)

    Science.gov (United States)

    Talandier, Jacques; Hyvernaud, Olivier; Maury, René C.

    2016-05-01

    We analyze two seismic events that occurred on 27 May 2011 and 29 April 2013 at the Rocard submarine volcano which overlies the Society hot spot. The Polynesian Seismic Network recorded for the first time unusual associated short- and long-period signals, with perfectly monochromatic (0.0589 Hz) Rayleigh wave trains of long period and duration. None of the numerous observations of long-period (10-30 s) signals previously associated with volcanic activity in Japan, Italy, Mexico, Indonesia, Antarctica, and the Hawaiian Islands have the characteristics we observed at Rocard. We propose a tentative model for these unusual and rather enigmatic signals, in which the movement of lava excited the resonance of a shallow open conduit under a high hydrostatic pressure of ~400 bars.

  13. Spallation as a dominant source of pusher-fuel and hot-spot mix in inertial confinement fusion capsules

    Science.gov (United States)

    Orth, Charles D.

    2016-02-01

    We suggest that a potentially dominant but previously neglected source of pusher-fuel and hot-spot "mix" may have been the main degradation mechanism for fusion energy yields of modern inertial confinement fusion (ICF) capsules designed and fielded to achieve high yields—not hydrodynamic instabilities. This potentially dominant mix source is the spallation of small chunks or "grains" of pusher material into the fuel regions whenever (1) the solid material adjacent to the fuel changes its phase by nucleation and (2) this solid material spalls under shock loading and sudden decompression. We describe this mix mechanism, support it with simulations and experimental evidence, and explain how to eliminate it and thereby allow higher yields for ICF capsules and possibly ignition at the National Ignition Facility.

  14. The cross-correlation search for a hot spot of gravitational waves : Numerical study for point spread function

    International Nuclear Information System (INIS)

    The cross-correlation search for gravitational waves, also known as 'radiometry', has been previously applied to map the gravitational wave stochastic background in the sky and also to target gravitational waves from rotating neutron stars/pulsars. We consider the Virgo cluster which may appear as a 'hot spot' spanning few pixels in the sky in a radiometry analysis. Our results show that sufficient signal to noise ratio can be accumulated with integration times of the order of a year. We also present a numerical simulation of radiometric analysis, assuming ground-based detectors which are currently under construction or being upgraded. The point spread function of the injected sources is confirmed by numerical tests. The typical resolution of radiometry analysis is a few square degrees, as compared to the several thousand pixels for the full sky in an all-sky map.

  15. The cross-correlation search for a hot spot of gravitational waves : Numerical study for point spread function

    CERN Document Server

    Okada, Yuta; Dhurandhar, Sanjeev; Tagoshi, Hideyuki; Takahashi, Hirotaka

    2011-01-01

    The cross-correlation search for gravitational wave, which is known as 'radiometry', has been previously applied to map of the gravitational wave stochastic background in the sky and also to target on gravitational wave from rotating neutron stars/pulsars. We consider the Virgo cluster where may be appear as `hot spot' spanning few pixels in the sky in radiometry analysis. Our results show that sufficient signal to noise ratio can be accumulated with integration times of the order of a year. We also construct numerical simulation of radiometry analysis, assuming current constructing/upgrading ground-based detectors. Point spread function of the injected sources are confirmed by numerical test. Typical resolution of radiometry analysis is a few square degree which corresponds to several thousand pixels of sky mapping.

  16. Spallation as a dominant source of pusher-fuel and hot-spot mix in inertial confinement fusion capsules

    International Nuclear Information System (INIS)

    We suggest that a potentially dominant but previously neglected source of pusher-fuel and hot-spot ''mix'' may have been the main degradation mechanism for fusion energy yields of modern inertial confinement fusion (ICF) capsules designed and fielded to achieve high yields – not hydrodynamic instabilities. This potentially dominant mix source is the spallation of small chunks or ''grains'' of pusher material into the fuel regions whenever (1) the solid material adjacent to the fuel changes its phase by nucleation, and (2) this solid material spalls under shock loading and sudden decompression. Finally, we describe this mix mechanism, support it with simulations and experimental evidence, and explain how to eliminate it and thereby allow higher yields for ICF capsules and possibly ignition at the National Ignition Facility

  17. Target-Driven Positive Selection at Hot Spots of Scorpion Toxins Uncovers Their Potential in Design of Insecticides.

    Science.gov (United States)

    Zhu, Limei; Peigneur, Steve; Gao, Bin; Zhang, Shangfei; Tytgat, Jan; Zhu, Shunyi

    2016-08-01

    Positive selection sites (PSSs), a class of amino acid sites with an excess of nonsynonymous to synonymous substitutions, are indicators of adaptive molecular evolution and have been detected in many protein families involved in a diversity of biological processes by statistical approaches. However, few studies are conducted to evaluate their functional significance and the driving force behind the evolution (i.e., agent of selection). Scorpion α-toxins are a class of multigene family of peptide neurotoxins affecting voltage-gated Na(+ )(Nav) channels, whose members exhibit differential potency and preference for insect and mammalian Nav channels. In this study, we undertook a systematical molecular dissection of nearly all the PSSs newly characterized in the Mesobuthus α-toxin family and a two-residue insertion ((19)AlaPhe(20)) located within a positively selected loop via mutational analysis of α-like MeuNaTxα-5, one member affecting both insect and mammalian Nav channels. This allows to identify hot-spot residues on its functional face involved in interaction with the receptor site of Nav channels, which comprises two PSSs (Ile(40) and Leu(41)) and the small insertion, both located on two spatially separated functional loops. Mutations at these hot-spots resulted in a remarkably decreased anti-mammalian activity in MeuNaTxα-5 with partially impaired or enhanced insecticide activity, suggesting the potential of PSSs in designing promising candidate insecticides from scorpion α-like toxins. Based on an experiment-guided toxin-channel complex model and high evolutionary variability in the receptor site of predators and prey of scorpions, we provide new evidence for target-driven adaptive evolution of scorpion toxins to deal with their targets' diversity. PMID:27189560

  18. Full Protein Flexibility is Essential for Proper Hot-Spot Mapping

    OpenAIRE

    Lexa, Katrina W.; Carlson, Heather A.

    2010-01-01

    A traditional technique for structure-based drug design (SBDD) is mapping protein surfaces with probe molecules to identify “hot spots” where key functional groups can best complement the receptor. Common methods, such as minimizing probes or calculating grids, use a fixed protein structure in the gas phase, ignoring both protein flexibility and proper competition between the probes and water. As a result, the potential surface is quite rugged and many spurious, local minima are identified. H...

  19. Liquid Metal Embrittlement in Resistance Spot Welding and Hot Tensile Tests of Surface-refined TWIP Steels

    Science.gov (United States)

    Barthelmie, J.; Schram, A.; Wesling, V.

    2016-03-01

    Automotive industry strives to reduce vehicle weight and therefore fuel consumption and carbon dioxide emissions. Especially in the auto body, material light weight construction is practiced, but the occupant safety must be ensured. These requirements demand high-strength steels with good forming and crash characteristics. Such an approach is the use of high- manganese-content TWIP steels, which achieve strengths of around 1,000 MPa and fracture strains of more than 60%. Welding surface-refined TWIP steels reduces their elongation at break and produces cracks due to the contact with liquid metal and the subsequent liquid metal embrittlement (LME). The results of resistance spot welds of mixed joints of high-manganese- content steel in combination with micro-alloyed ferritic steel and hot tensile tests are presented. The influence of different welding parameters on the sensitivity to liquid metal embrittlement is investigated by means of spot welding. In a high temperature tensile testing machine, the influence of different parameters is determined regardless of the welding process. Defined strains just below or above the yield point, and at 25% of elongation at break, show the correlation between the applied strain and liquid metal crack initiation. Due to the possibility to carry out tensile tests on a wide range of temperatures, dependencies of different temperatures of the zinc coating to the steel can be identified. Furthermore, the attack time of the zinc on the base material is investigated by defined heating periods.

  20. Transport properties of a charged hot spot in an external electromagnetic field

    Science.gov (United States)

    Bondarenko, S.; Komoshvili, K.; Prygarin, A.

    2016-06-01

    We investigate adiabatic expansion of a charged and rotating fluid element consisting of weakly interacting particles, which is initially perturbed by an external electromagnetic field. A framework for the perturbative calculation of the non-equilibrium distribution function of this fluid volume is considered and the distribution function is calculated to the first order in the perturbative expansion. This distribution function, which describes the evolution of the element with constant entropy, allows to calculate momentum flux tensor and viscosity coefficients of the expanding system. We show, that these viscosity coefficients depend on the initial angular velocity of the spot and on the strength of its initial perturbation by the external field. Obtained results are applied to the phenomenology of the viscosity to the entropy ratio calculated in lattice models.

  1. Effect of width, amplitude, and position of a core mantle boundary hot spot on core convection and dynamo action

    Science.gov (United States)

    Dietrich, Wieland; Wicht, Johannes; Hori, Kumiko

    2015-12-01

    Within the fluid iron cores of terrestrial planets, convection and the resulting generation of global magnetic fields are controlled by the overlying rocky mantle. The thermal structure of the lower mantle determines how much heat is allowed to escape the core. Hot lower mantle features, such as the thermal footprint of a giant impact or hot mantle plumes, will locally reduce the heat flux through the core mantle boundary (CMB), thereby weakening core convection and affecting the magnetic field generation process. In this study, we numerically investigate how parametrised hot spots at the CMB with arbitrary sizes, amplitudes, and positions affect core convection and hence the dynamo. The effect of the heat flux anomaly is quantified by changes in global flow symmetry properties, such as the emergence of equatorial antisymmetric, axisymmetric (EAA) zonal flows. For purely hydrodynamic models, the EAA symmetry scales almost linearly with the CMB amplitude and size, whereas self-consistent dynamo simulations typically reveal either suppressed or drastically enhanced EAA symmetry depending mainly on the horizontal extent of the heat flux anomaly. Our results suggest that the length scale of the anomaly should be on the same order as the outer core radius to significantly affect flow and field symmetries. As an implication to Mars and in the range of our model, the study concludes that an ancient core field modified by a CMB heat flux anomaly is not able to heterogeneously magnetise the crust to the present-day level of north-south asymmetry on Mars. The resulting magnetic fields obtained using our model either are not asymmetric enough or, when they are asymmetric enough, show rapid polarity inversions, which are incompatible with thick unidirectional magnetisation.

  2. WLAN Hot Spot services for the automotive and oil industries :a business analysis Or : "Refuel the car with petrol and information, both ways at the gas station"

    NARCIS (Netherlands)

    L-F. Pau (Louis-François); M.H.P. Oremus

    2003-01-01

    textabstractWhile you refuel for gas ,why not refuel for information or download vehicle data ? This paper analyzes in extensive detail the user segmentation by vehicle usage , service offering , and full business models from WLAN hot spot services delivered to vehicles (private, professional , publ

  3. Quantitative Selective PCR of 16S Ribosomal DNA Correlates Well with Selective Agar Plating in Describing Population Dynamics of Indigenous Pseudomonas spp. in Soil Hot Spots

    OpenAIRE

    Johnsen, Kaare; Enger, Øivind; Jacobsen, Carsten S.; Thirup, Laila; Torsvik, Vigdis

    1999-01-01

    We used a quantitative PCR method targeting 16S ribosomal DNA using competitive PCR for specific detection of indigenous Pseudomonas DNA in soil hot spots. The amount of Pseudomonas DNA corresponded to the number of culturable Pseudomonas bacteria on Gould’s S1 agar. This represents the first use of PCR for quantification of indigenous bacteria in more than one sample of soil.

  4. Effect of BaAl2O4 Addition on Power Consumption and Oxygen Sensing Response of Er123 Ceramic Rods Utilizing Hot-Spot Phenomenon

    International Nuclear Information System (INIS)

    In this paper, we report the effect of BaAl2O4 addition (0-30 wt. %) on power consumption and oxygen sensing response of hot-spots developed on short Er123 ceramic rods of around 12 mm length synthesized using standard solid-state reaction. All the sensor rods showed increase in output current with increasing voltage followed by sudden reduction in output current and appearance of hot spot. After appearance of hot spot, for each rod, output current was observed to decrease gradually with increasing voltage with the slope of the I-V curve gradually approaching zero. Output current after the hot spot formation showed sensitivity to oxygen partial pressure, pO2 between 1 to 100 kPa. Addition of 30 wt. % BaAl2O4 reduced the fluctuation of current and increased the sensitivity for pO2 below 10 kPa. In addition, overshoot current was also reduced and resulted in improvement of response time from around 10 s to 5 s. Our result also showed that minimum power consumption was significantly reduced in the Er123 rods with 30 wt. % BaAl2O4. (author)

  5. Source apportionment of size resolved particulate matter at a European air pollution hot spot.

    Science.gov (United States)

    Pokorná, P; Hovorka, J; Klán, M; Hopke, P K

    2015-01-01

    Positive Matrix Factorization-PMF was applied to hourly resolved elemental composition of fine (PM0.15-1.15) and coarse (PM1.15-10) aerosol particles to apportion their sources in the airshed of residential district, Ostrava-Radvanice and Bartovice in winter 2012. Multiple-site measurement by PM2.5 monitors complements the source apportionment. As there were no statistical significant differences amongst the monitors, the source apportionment derived for the central site data is expected to apply to whole residential district. The apportioned sources of the fine aerosol particles were coal combustion (58.6%), sinter production-hot phase (22.9%), traffic (15%), raw iron production (3.5%), and desulfurization slag processing (air pollution sources helped to interpret the PMF solution. PMID:25260163

  6. Selecting optimal parallel microchannel configurations for active hot spot mitigation of multicore microprocessors in real time

    CERN Document Server

    Maganti, Lakshmi Sirisha; Sundararajan, T; Das, Sarit K

    2016-01-01

    Design of effective micro cooling systems to address the challenges of ever increasing heat flux from microdevices requires deep examination of real time problems and has been tackled in depth. The most common and apparently misleading assumption while designing micro cooling systems is that the heat flux generated by the device is uniform, but the reality is far from this. Detailed simulations have been performed by considering non uniform heat load employing the configurations U, I, Z for parallel microchannel systems with water and nanofluids as the coolants. An Intel Core i7 4770 3.40 GHz quad core processor has been mimicked using heat load data retrieved from a real microprocessor with non-uniform core activity. The study clearly demonstrates that there is a non-uniform thermal load induced temperature maldistribution along with the already existent flow maldistribution induced temperature maldistribution. The suitable configuration(s) for maximum possible overall heat removal for a hot zone while maxim...

  7. Testing the nature of the supermassive black hole candidate in SgrA* with light curves and images of hot spots

    International Nuclear Information System (INIS)

    General relativity makes clear predictions about the spacetime geometry around black holes. In the near future, new facilities will have the capability to explore the metric around SgrA*, the supermassive black hole candidate at the center of our Galaxy, and to open a new window to test the Kerr black hole hypothesis. In this paper, we compute light curves and images associated with compact emission regions (hot spots) orbiting around Kerr and non-Kerr black holes. We study how the analysis of the properties of the radiation emitted by a hot spot can be used to test the Kerr nature of SgrA*. We find that the sole observation of the hot spot light curve can at most constrain a combination of the black hole spin and of possible deviations from the Kerr solution. This happens because the same orbital frequency around a Kerr black hole can be found for a non-Kerr object with a different spin parameter. Second order corrections in the light curve due to the background geometry are typically too small to be identified. While the observation of the hot spot centroid track can potentially bound possible deviations from the Kerr solution, that is out of reach for the near future for the Very Large Telescope Interferometer instrument GRAVITY. The Kerr black hole hypothesis could really be tested in the case of the discovery of a radio pulsar in a compact orbit around SgrA*. Radio observations of such a pulsar would provide precise estimates of the mass and the spin of SgrA*, and the combination of these measurements (probing the weak field) with the hot spot light curve information (probing the strong field) may constrain/find possible deviations from the Kerr solution with quite good precision.

  8. A spatial analysis of population dynamics and climate change in Africa: potential vulnerability hot spots emerge where precipitation declines and demographic pressures coincide

    Science.gov (United States)

    López-Carr, David; Pricope, Narcisa G.; Aukema, Juliann E.; Jankowska, Marta M.; Funk, Christopher C.; Husak, Gregory J.; Michaelsen, Joel C.

    2014-01-01

    We present an integrative measure of exposure and sensitivity components of vulnerability to climatic and demographic change for the African continent in order to identify “hot spots” of high potential population vulnerability. Getis-Ord Gi* spatial clustering analyses reveal statistically significant locations of spatio-temporal precipitation decline coinciding with high population density and increase. Statistically significant areas are evident, particularly across central, southern, and eastern Africa. The highly populated Lake Victoria basin emerges as a particularly salient hot spot. People located in the regions highlighted in this analysis suffer exceptionally high exposure to negative climate change impacts (as populations increase on lands with decreasing rainfall). Results may help inform further hot spot mapping and related research on demographic vulnerabilities to climate change. Results may also inform more suitable geographical targeting of policy interventions across the continent.

  9. Temperature Measurements on Hot Spots of Power Substations Utilizing Surface Acoustic Wave Sensors

    Science.gov (United States)

    Cavaco, M. A. M.; Benedet, M. E.; Neto, L. R.

    2011-12-01

    In several applications in the field of metrology, the direct connection of the sensor element with the respective signal-processing unit of the measurement system is not trivial. It can be mentioned, as an example, the measurement of hot points in electric power substations because of the high electrical potential. To solve that problem, two alternatives were studied, one using active surface acoustic wave (SAW) sensors and other using passive SAW tags. For the passive sensor, a SAW radio-frequency identification (RFID) temperature detector was used. That technology is widely applied for typical transport identification (grain transportation, road traffic control), but its application in the field of metrology is innovative. The variation in temperature makes an alteration in the characteristics of the piezoelectric material of the SAW matrix, changing mostly the resonance frequency. Using SAW-RFID, the problem of measuring temperature basically is directed to the identification of the frequency of resonance of the SAW. The use of active SAW sensors has been demonstrated to be much more satisfactory for the solution of such a problem because of the limitation in the range of the passive sensors.

  10. Can we detect hot/cold spots in the CMB with Minkowski Functionals?

    International Nuclear Information System (INIS)

    In this paper, we investigate the utility of Minkowski Functionals as a probe of cold/hot disk-like structures in the CMB. In order to construct an accurate estimator, we resolve a long-standing issue with the use of Minkowski Functionals as probes of the CMB sky — namely that of systematic differences (''residuals'') when numerical and analytical MF are compared. We show that such residuals are in fact by-products of binning, whereas it was originally attributed to pixelation or masking effects. We then derive a map-independent estimator that encodes the effects of binning, applicable to beyond our present work. Using this residual-free estimator, we show that small disk-like effects (as claimed by Vielva et al. [1,2]) can be detected only when a large sample of such maps are averaged over. In other words, our estimator is noise-dominated for small disk sizes at WMAP resolution. To confirm our suspicion, we apply our estimator to the WMAP7 data to obtain a null result

  11. Hot Spot Induced Cenozoic Volcanism in the Upper Rajang Valley, Sarawak - Is Borneo Rifting?

    Science.gov (United States)

    Taib, N.

    2010-12-01

    The Upper Rajang Valley covers a large area in the northern interior of the island of Borneo, in the Malaysian state of Sarawak . It is underlain by the Cretaceous to Late Eocene deep to shallow marine sediments of the Rajang Group. Within this area are several Cenozoic volcanic edifices, which to date have been sparsely studied. Two distinct episodes of volcanism are recognized - the first, dated early Eocene, consists of K-rich basalts, and is represented by the Bukit Mersing volcanics, which were erupted conformably onto deep water turbidites of the Rajang Group. The second, far more extensive, is dated Pliocene to Quaternary, and is bimodal, consisting mainly of early dacite and rhyodacite tuffs, with a smaller amount of later basalt, forming several volcanic plateaus and massifs (Hose Mountains, Usun Apau, Linau-Balui, Nieuwenhuis Mountains and others). They lie unconformably over pre-Miocene sediments, the Linau-Balui basalts having been erupted onto Quaternary river terraces. Mantle-normalized REE and incompatible trace element spider plots reveal that the Bukit Mersing basalts have geochemical affinity with Oceanic Island Basalts (OIB) and rift basalts, being enriched in LREEs and Most Incompatible Elements, and no Eu anomaly. Preliminary trace element data for several basalt samples from Usun Apau also show Oceanic Island/Rift affinity. Bimodal volcanism is most often associated with rift environments. Efforts are being made to radiometrically date the volcanics, in part to determine the possibility of future eruptions. The Upper Rajang Valley is remote, covered in tropical rainforest and is very sparsely populated. At this time, there is no information concerning signs of imminent volcanism, such as hot springs and microseismicity.

  12. The Hot Spot Analysis: Utilization as Customized Management Tool towards Sustainable Value Chains of Companies in the Food Sector

    Directory of Open Access Journals (Sweden)

    H. Rohn

    2014-12-01

    Full Text Available The food and agricultural sector will face numerous challenges in the next decades, arising from changing global production and consumption patterns, which currently go along with high resource use, causing ecological and socio-economic impacts. The aim of this paper is to illustrate and evaluate the practical applicability of the Hot Spot Analysis methodology in the context of supply chain management in companies. The HSA is a method to identify social and ecological problems along the entire life cycle of a product. Special emphasis is put on a customized implementation in the value chain beef of McDonald’s Germany. The HSA of McDonald’s beef value chain shows that the main ecological problems arise in the phase of raw material extraction, whereas the main social problems can be identified in the phase of slaughtering. Finally, the paper shows potentials and shortcomings of such a customized application and how the results can be implemented in the sustainability management of a company.

  13. Stabilization of large drainage basins over geological time scales: Cenozoic West Africa, hot spot swell growth, and the Niger River

    Science.gov (United States)

    Chardon, Dominique; Grimaud, Jean-Louis; Rouby, Delphine; Beauvais, Anicet; Christophoul, Frédéric

    2016-03-01

    Reconstructing the evolving geometry of large river catchments over geological time scales is crucial to constraining yields to sedimentary basins. In the case of Africa, it should further help deciphering the response of large cratonic sediment routing systems to Cenozoic growth of the basin-and-swell topography of the continent. Mapping of dated and regionally correlated lateritic paleolandscape remnants complemented by onshore sedimentological archives allows the reconstruction of two physiographic configurations of West Africa in the Paleogene. Those reconstructions show that the geometry of the drainage is stabilized by the late early Oligocene (29 Ma) and probably by the end of the Eocene (34 Ma), allowing to effectively link the inland morphoclimatic record to offshore sedimentation since that time, particularly in the case of the Niger catchment—delta system. Mid-Eocene paleogeography reveals the antiquity of the Senegambia catchment back to at least 45 Ma and suggests that a marginal upwarp forming a continental divide preexisted early Oligocene connection of the Niger and Volta catchments to the Equatorial Atlantic Ocean. Such a drainage rearrangement was primarily enhanced by the topographic growth of the Hoggar hot spot swell and caused a stratigraphic turnover along the Equatorial margin of West Africa.

  14. Septic systems as hot-spots of pollutants in the environment: Fate and mass balance of micropollutants in septic drainfields.

    Science.gov (United States)

    Yang, Yun-Ya; Toor, Gurpal S; Wilson, P Chris; Williams, Clinton F

    2016-10-01

    Septic systems, a common type of onsite wastewater treatment systems, can be an important source of micropollutants in the environment. We investigated the fate and mass balance of 17 micropollutants, including wastewater markers, hormones, pharmaceuticals and personal care products (PPCPs) in the drainfield of a septic system. Drainfields were replicated in lysimeters (1.5m length, 0.9m width, 0.9m height) and managed similar to the field practice. In each lysimeter, a drip line dispersed 9L of septic tank effluent (STE) per day (equivalent to 32.29L/m(2) per day). Fourteen micropollutants in the STE and 12 in the leachate from drainfields were detected over eight months. Concentrations of most micropollutants in the leachate were low (85% of the added micropollutants except for sucralose were attenuated in the drainfield. We discovered that sorption was the key mechanism for retention of carbamazepine and partially for sulfamethoxazole, whereas microbial degradation likely attenuated acetaminophen in the drainfield. This data suggests that sorption and microbial degradation limited transport of micropollutants from the drainfields. However, the leaching of small amounts of micropollutants indicate that septic systems are hot-spots of micropollutants in the environment and a better understanding of micropollutants in septic systems is needed to protect groundwater quality. PMID:27312276

  15. From science into practice: modelling hot spots for corporate flood risk and emergency management with high-resolution digital terrain data

    Science.gov (United States)

    Pfurtscheller, Clemens; Vetter, Michael; Werthmann, Markus

    2010-05-01

    In times of increasing scarcity of private or public resources and uncertain changes in natural environment caused by climate variations, prevention and risk management against floods and coherent processes in mountainous regions, like debris flows or log jams, should be faced as a main challenge for globalised enterprises whose production facilities are located in flood-prone areas. From an entrepreneurial perspective, vulnerability of production facilities which causes restrictions or a total termination of production processes has to be optimised by means of cost-benefit-principles. Modern production enterprises are subject to globalisation and accompanying aspects, like short order and delivery periods, interlinking production processes and just-in-time manufacturing, so a breakdown of production provokes substantial financial impacts, unemployment and a decline of gross regional product. The aim of the presented project is to identify weak and critical points of the corporate emergency planning ("hot spots") and to assess possible losses triggered by mountainous flood processes using high-resolution digital terrain models (DTM) from airborne LiDAR (ALS). We derive flood-hot spots and model critical locations where the risk of natural hazards is very high. To model those hot spots a flood simulation based on an ALS-DTM has to be calculated. Based on that flood simulation, the flood heights of the overflowed locations which are lower than a threshold are mapped as flood-hot-spots. Then the corporate critical infrastructure, e.g. production facilities or lifelines, which are affected by the flooding, can be figured out. After the identification of hot spots and possible damage potential, the implementation of the results into corporate risk and emergency management guarantees the transdisciplinary approach involving stakeholders, risk and safety management officers and corporate fire brigade. Thus, the interdisciplinary analysis, including remote sensing

  16. Identifying and Mitigating Potential Nutrient and Sediment Hot Spots under a Future Scenario in the Missouri River Basin

    Energy Technology Data Exchange (ETDEWEB)

    Wu, May [Argonne National Lab. (ANL), Argonne, IL (United States); Zhang, Zhonglong [Argonne National Lab. (ANL), Argonne, IL (United States)

    2015-09-01

    clearly attributable to the conversion of a large amount of land to switchgrass. The Middle Lower Missouri River and Lower Missouri River were identified as hot regions. Further analysis identified four subbasins (10240002, 10230007, 10290402, and 10300200) as being the most vulnerable in terms of sediment, nitrogen, and phosphorus loadings. Overall, results suggest that increasing the amount of switchgrass acreage in the hot spots should be considered to mitigate the nutrient loads. The study provides an analytical method to support stakeholders in making informed decisions that balance biofuel production and water sustainability.

  17. An allosteric synthetic DNA.

    OpenAIRE

    Wu, L.; Curran, J F

    1999-01-01

    Allosteric DNA oligonucleotides are potentially useful diagnostic reagents. Here we develop a model system for the study of allosteric interactions in DNAs. A DNA that binds either Cibacron blue or cholic acid was isolated and partially characterized. Isolation was performed using a multi-stage SELEX. First, short oligos that bind either Cibacron blue or cholic acid were enriched from random oligonucleotide pools. Then, members of the two pools were fused to form longer oligos, which were the...

  18. Established Companies meet Start-ups : Case: A service to research developing business models in start-up hot spots around the globe

    OpenAIRE

    Eisenblätter, Simon

    2016-01-01

    This thesis presents a business model with the aim to improve conversation between traditional companies and newly established start-ups. The assumption that such conversation can be facilitated by scouting for innovation in start-up hot spots around the world, will be discussed throughout the paper. The purpose of this work is to lay out a plan which can be presented to a first range of possible customers, with the goal of negotiating a trial cooperation. Before introducing the busi...

  19. New geologic evidence for additional 16.5-15.5 Ma silicic calderas in northwest Nevada related to initial impingement of the Yellowstone hot spot

    Energy Technology Data Exchange (ETDEWEB)

    Coble, Matthew A; Mahood, Gail A [Department Geological and Environmental Sciences, 450 Serra Mall, Bldg 320, Stanford University, Stanford, CA 94305-3115 (United States)

    2008-10-01

    Three silicic calderas have been newly identified in northwest Nevada west of McDermitt caldera. This volcanism is interpreted to have formed during a short interval at 16.5-15.5 Ma, during the waning stage of Steens flood basalt volcanism after the initial impingement of the Yellowstone hot spot. New mapping demonstrates that the area affected by this mid-Miocene silicic volcanism is significantly larger than previously appreciated in the western U.S.

  20. Rapid and Simple Detection of Hot Spot Point Mutations of Epidermal Growth Factor Receptor, BRAF, and NRAS in Cancers Using the Loop-Hybrid Mobility Shift Assay

    OpenAIRE

    Matsukuma, Shoichi; Yoshihara, Mitsuyo; Kasai, Fumio; Kato, Akinori; Yoshida, Akira; Akaike, Makoto; Kobayashi, Osamu; Nakayama, Haruhiko; Sakuma, Yuji; Yoshida , Tsutomu; Kameda, Yoichi; Tsuchiya, Eiju; Miyagi, Yohei

    2006-01-01

    A simple and rapid method to detect the epidermal growth factor receptor hot spot mutation L858R in lung adenocarcinoma was developed based on principles similar to the universal heteroduplex generator technology. A single-stranded oligonucleotide with an internal deletion was used to generate heteroduplexes (loop-hybrids) bearing a loop in the complementary strand derived from the polymerase chain reaction product of the normal or mutant allele. By placing deletion in the oligonucleotide adj...

  1. A novel LMNA mutation (R189W in familial dilated cardiomyopathy: evidence for a 'hot spot' region at exon 3: a case report

    Directory of Open Access Journals (Sweden)

    Biagini Andrea

    2010-03-01

    Full Text Available Abstract We describe a case of a patient with idiopathic dilated cardiomyopathy and cardiac conduction abnormalities who presented a strong family history of sudden cardiac death. Genetic screening of lamin A/C gene revealed in proband the presence of a novel missense mutation (R189W, near the most prevalent lamin A/C mutation (R190W, suggesting a "hot spot" region at exon 3.

  2. Mapping Publication Trends and Identifying Hot Spots of Research on Internet Health Information Seeking Behavior: A Quantitative and Co-Word Biclustering Analysis

    OpenAIRE

    Li, Fan; Min LI; Guan, Peng; Ma, Shuang; Cui, Lei

    2015-01-01

    Background The Internet has become an established source of health information for people seeking health information. In recent years, research on the health information seeking behavior of Internet users has become an increasingly important scholarly focus. However, there have been no long-term bibliometric studies to date on Internet health information seeking behavior. Objective The purpose of this study was to map publication trends and explore research hot spots of Internet health inform...

  3. Deletion of exons 3-9 encompassing a mutational hot spot in the DMD gene presents an asymptomatic phenotype, indicating a target region for multiexon skipping therapy.

    Science.gov (United States)

    Nakamura, Akinori; Fueki, Noboru; Shiba, Naoko; Motoki, Hirohiko; Miyazaki, Daigo; Nishizawa, Hitomi; Echigoya, Yusuke; Yokota, Toshifumi; Aoki, Yoshitsugu; Takeda, Shin'ichi

    2016-07-01

    Few cases of dystrophinopathy show an asymptomatic phenotype with mutations in the 5' (exons 3-7) hot spot in the Duchenne muscular dystrophy (DMD) gene. Our patient showed increased serum creatine kinase levels at 12 years of age. A muscle biopsy at 15 years of age led to a diagnosis of Becker muscular dystrophy. The patient showed a slight decrease in cardiac function at the age of 21 years and was administered a β-blocker, but there was no muscle involvement even at the age of 27 years. A deletion of exons 3-9 encompassing a mutational hot spot in the DMD gene was detected, and dystrophin protein expression was ∼15% that of control level. We propose that in-frame deletion of exons 3-9 may produce a functional protein, and that multiexon skipping therapy targeting these exons may be feasible for severe dystrophic patients with a mutation in the 5' hot spot of the DMD gene. PMID:27009627

  4. Development of core hot spot evaluation method for decay heat removal by natural circulation under transient conditions in sodium-cooled fast reactor

    International Nuclear Information System (INIS)

    Toward the commercialization of fast reactors, a design study of Japan Sodium Cooled Fast Reactor (JSFR) is being performed. In this design study, adoption of fully natural circulation system is being examined as the decay heat removal system from the viewpoints of economic competitiveness and passive safety. This paper describes a new evaluation method of core hot spot for decay heat removal by natural circulation under transient conditions that is necessary for confirming feasibility of the fully natural circulation system. The new method consists of three step analyses in order to include the effects of thermal hydraulic phenomena particular to natural circulation decay heat removal, inter-assembly heat transfer and flow redistribution in fuel assemblies and in the core by buoyancy force, and therefore enables more rational hot spot evaluation rather than conventional ones. The method was applied to an analysis of loss-of-extemal-power event and the result was compared with those by a conventional method and a detailed 3D simulation. It was confirmed that the proposed method can estimate the hot spot with a reasonable degree of conservativeness. (author)

  5. Mobile Launch Platform Vehicle Assembly Building Area (SWMU 056) Hot Spot 3 Bioremediation Interim Measures Work Plan, Kennedy Space Center, Florida

    Science.gov (United States)

    Whitney L. Morrison; Daprato, Rebecca C.

    2016-01-01

    This Interim Measures Work Plan (IMWP) presents an approach and design for the remediation of chlorinated volatile organic compound (CVOC) groundwater impacts using bioremediation (biostimulation and bioaugmentation) in Hot Spot 3, which is defined by the area where CVOC (trichloroethene [TCE], cis-1,2-dichloroethene [cDCE], and vinyl chloride [VC]) concentrations are greater than 10 times their respective Florida Department of Environmental Protection (FDEP) Natural Attenuation Default Concentration (NADC) [10xNADC] near the western Mobile Launch Platform (MLP) structure. The IM treatment area is the Hot Spot 3 area, which is approximately 0.07 acres and extends from approximately 6 to 22 and 41 to 55 feet below land surface (ft BLS). Within Hot Spot 3, a source zone (SZ; area with TCE concentrations greater than 1% solubility [11,000 micrograms per liter (micrograms/L)]) was delineated and is approximately 0.02 acres and extends from approximately 6 to 16 and 41 to 50 ft BLS.

  6. Demonstration of Fuel Hot-Spot Pressure in Excess of 50 Gbar for Direct-Drive, Layered Deuterium-Tritium Implosions on OMEGA.

    Science.gov (United States)

    Regan, S P; Goncharov, V N; Igumenshchev, I V; Sangster, T C; Betti, R; Bose, A; Boehly, T R; Bonino, M J; Campbell, E M; Cao, D; Collins, T J B; Craxton, R S; Davis, A K; Delettrez, J A; Edgell, D H; Epstein, R; Forrest, C J; Frenje, J A; Froula, D H; Gatu Johnson, M; Glebov, V Yu; Harding, D R; Hohenberger, M; Hu, S X; Jacobs-Perkins, D; Janezic, R; Karasik, M; Keck, R L; Kelly, J H; Kessler, T J; Knauer, J P; Kosc, T Z; Loucks, S J; Marozas, J A; Marshall, F J; McCrory, R L; McKenty, P W; Meyerhofer, D D; Michel, D T; Myatt, J F; Obenschain, S P; Petrasso, R D; Radha, P B; Rice, B; Rosenberg, M J; Schmitt, A J; Schmitt, M J; Seka, W; Shmayda, W T; Shoup, M J; Shvydky, A; Skupsky, S; Solodov, A A; Stoeckl, C; Theobald, W; Ulreich, J; Wittman, M D; Woo, K M; Yaakobi, B; Zuegel, J D

    2016-07-01

    A record fuel hot-spot pressure P_{hs}=56±7  Gbar was inferred from x-ray and nuclear diagnostics for direct-drive inertial confinement fusion cryogenic, layered deuterium-tritium implosions on the 60-beam, 30-kJ, 351-nm OMEGA Laser System. When hydrodynamically scaled to the energy of the National Ignition Facility, these implosions achieved a Lawson parameter ∼60% of the value required for ignition [A. Bose et al., Phys. Rev. E 93, 011201(R) (2016)], similar to indirect-drive implosions [R. Betti et al., Phys. Rev. Lett. 114, 255003 (2015)], and nearly half of the direct-drive ignition-threshold pressure. Relative to symmetric, one-dimensional simulations, the inferred hot-spot pressure is approximately 40% lower. Three-dimensional simulations suggest that low-mode distortion of the hot spot seeded by laser-drive nonuniformity and target-positioning error reduces target performance. PMID:27447511

  7. Multi-Scale Multi-physics Methods Development for the Calculation of Hot-Spots in the NGNP

    International Nuclear Information System (INIS)

    Radioactive gaseous fission products are released out of the fuel element at a significantly higher rate when the fuel temperature exceeds 1600°C in high-temperature gas-cooled reactors (HTGRs). Therefore, it is of paramount importance to accurately predict the peak fuel temperature during all operational and design-basis accident conditions. The current methods used to predict the peak fuel temperature in HTGRs, such as the Next-Generation Nuclear Plant (NGNP), estimate the average fuel temperature in a computational mesh modeling hundreds of fuel pebbles or a fuel assembly in a pebble-bed reactor (PBR) or prismatic block type reactor (PMR), respectively. Experiments conducted in operating HTGRs indicate considerable uncertainty in the current methods and correlations used to predict actual temperatures. The objective of this project is to improve the accuracy in the prediction of local 'hot' spots by developing multi-scale, multi-physics methods and implementing them within the framework of established codes used for NGNP analysis.The multi-scale approach which this project will implement begins with defining suitable scales for a physical and mathematical model and then deriving and applying the appropriate boundary conditions between scales. The macro scale is the greatest length that describes the entire reactor, whereas the meso scale models only a fuel block in a prismatic reactor and ten to hundreds of pebbles in a pebble bed reactor. The smallest scale is the micro scale--the level of a fuel kernel of the pebble in a PBR and fuel compact in a PMR--which needs to be resolved in order to calculate the peak temperature in a fuel kernel.

  8. Multi-Scale Multi-physics Methods Development for the Calculation of Hot-Spots in the NGNP

    Energy Technology Data Exchange (ETDEWEB)

    Downar, Thomas [Univ. of Michigan, Ann Arbor, MI (United States); Seker, Volkan [Univ. of Michigan, Ann Arbor, MI (United States)

    2013-04-30

    Radioactive gaseous fission products are released out of the fuel element at a significantly higher rate when the fuel temperature exceeds 1600°C in high-temperature gas-cooled reactors (HTGRs). Therefore, it is of paramount importance to accurately predict the peak fuel temperature during all operational and design-basis accident conditions. The current methods used to predict the peak fuel temperature in HTGRs, such as the Next-Generation Nuclear Plant (NGNP), estimate the average fuel temperature in a computational mesh modeling hundreds of fuel pebbles or a fuel assembly in a pebble-bed reactor (PBR) or prismatic block type reactor (PMR), respectively. Experiments conducted in operating HTGRs indicate considerable uncertainty in the current methods and correlations used to predict actual temperatures. The objective of this project is to improve the accuracy in the prediction of local "hot" spots by developing multi-scale, multi-physics methods and implementing them within the framework of established codes used for NGNP analysis.The multi-scale approach which this project will implement begins with defining suitable scales for a physical and mathematical model and then deriving and applying the appropriate boundary conditions between scales. The macro scale is the greatest length that describes the entire reactor, whereas the meso scale models only a fuel block in a prismatic reactor and ten to hundreds of pebbles in a pebble bed reactor. The smallest scale is the micro scale--the level of a fuel kernel of the pebble in a PBR and fuel compact in a PMR--which needs to be resolved in order to calculate the peak temperature in a fuel kernel.

  9. The acetabular fossa hot spot on {sup 18}F-FDG PET/CT: epidemiology, natural history, and proposed etiology

    Energy Technology Data Exchange (ETDEWEB)

    Kubicki, Shelby L. [Trinity University, San Antonio, TX (United States); Richardson, Michael L. [University of Washington, Department of Radiology, Seattle, WA (United States); Martin, Thomas [X-Ray Associates of New Mexico, Department of Radiology, Albuquerque, NM (United States); Rohren, Eric [The University of Texas M.D. Anderson Cancer Center, Department of Diagnostic Radiology, Division of Nuclear Medicine, Houston, TX (United States); Wei, Wei [The University of Texas M.D. Anderson Cancer Center, Department of Biostatistics, Houston, TX (United States); Amini, Behrang [The University of Texas M.D. Anderson Cancer Center, Department of Diagnostic Radiology, Division of Musculoskeletal Radiology, Houston, TX (United States)

    2015-01-15

    To describe a benign focus of increased activity in the acetabular fossa (the acetabular fossa hot spot, AFHS) on {sup 18}F-FDG PET/CT that can mimic a neoplasm. {sup 18}F-FDG PET/CT images from four patient populations were examined. Group 1 (n = 13) was collected from a search of radiology reports and used to define the AFHS and for hypothesis generation. Group 2 (n = 1,150) was used for prevalence of AFHS. Group 3 (n = 1,213) had PET/CT and MRI pelvis within a week of each other and was used to correlate metabolic and anatomic findings. Group 4 (n = 100) was used to generate the control group. Data were collected on demographics, common comorbidities, underlying cancer diagnosis and status, and hip symptoms. Prevalence of AFHS was 0.36 % (95 % CI 0.10-0.91 %). None progressed to malignancy or was associated with cancer status. The majority (71 %) were on the left, and 6 % were bilateral. Mean SUV{sub max} of the AFHS was 4.8 (range, 2.7-7.8). Male patients were more likely to have the AFHS (OR = 8.69, 95 % CI 1.88-40.13). There was no difference with respect to other collected data, including hip symptoms. Average minimum duration of AFHS was 346 days (range, 50-1,010 days). Readers did not detect corresponding hip abnormalities on MRIs. AFHS is a benign finding that may be caused by subclinical ligamentum teres injury, focal synovitis, or degeneration of acetabular fossa fat. Despite uncertainty regarding its etiology, recognition of AFHS as a benign finding can prevent morbidity associated with unnecessary biopsy or initiation of therapy. (orig.)

  10. Opening the research agenda for selection of hot spots for human biomonitoring research in Belgium: a participatory research project

    Directory of Open Access Journals (Sweden)

    Chovanova Hana

    2010-07-01

    Full Text Available Abstract Background In order to select priority hotspots for environment and health research in Flanders (Belgium, an open procedure was organized. Environment and health hotspots are strong polluting point sources with possible health effects for residents living in the vicinity of the hot spot. The selection procedure was part of the work of the Flemish Centre of Expertise for Environment and Health, which investigates the relation between environmental pollution and human health. The project is funded and steered by the Flemish government. Methods The involvement of other actors than merely experts is inspired by the 'analytical-deliberative' approach of the National Research Council in the United States and the extended peer community approach. These approaches stress the importance of involving different expert- and social perspectives in order to increase the knowledge base on complex issues. In the procedure used in the project a combination of expert and stakeholder input was essential. The final decision was supported by a multi-criteria analysis of expert assessment and stakeholder advice. Results The endeavour was challenging from the start because of the complicated ambition of including a diversity of actors, potential hotspots, concerns and assessment criteria, but nevertheless the procedure proved its value in both structuring and informing the decision-making process. Moreover the process gained the support of most actors participating in the process, even though the final selection could not satisfy all preferences. Conclusions Opening the research agenda exemplifies the value of inter- and transdisciplinary cooperation as well as the need for a well-structured and negotiated procedure that combines relevant factors and actors with pragmatism. The value of such a process also needs to prove itself in practice after the procedure has been completed: the tension between an ambition of openness on the one hand and a more closed

  11. The acetabular fossa hot spot on 18F-FDG PET/CT: epidemiology, natural history, and proposed etiology

    International Nuclear Information System (INIS)

    To describe a benign focus of increased activity in the acetabular fossa (the acetabular fossa hot spot, AFHS) on 18F-FDG PET/CT that can mimic a neoplasm. 18F-FDG PET/CT images from four patient populations were examined. Group 1 (n = 13) was collected from a search of radiology reports and used to define the AFHS and for hypothesis generation. Group 2 (n = 1,150) was used for prevalence of AFHS. Group 3 (n = 1,213) had PET/CT and MRI pelvis within a week of each other and was used to correlate metabolic and anatomic findings. Group 4 (n = 100) was used to generate the control group. Data were collected on demographics, common comorbidities, underlying cancer diagnosis and status, and hip symptoms. Prevalence of AFHS was 0.36 % (95 % CI 0.10-0.91 %). None progressed to malignancy or was associated with cancer status. The majority (71 %) were on the left, and 6 % were bilateral. Mean SUVmax of the AFHS was 4.8 (range, 2.7-7.8). Male patients were more likely to have the AFHS (OR = 8.69, 95 % CI 1.88-40.13). There was no difference with respect to other collected data, including hip symptoms. Average minimum duration of AFHS was 346 days (range, 50-1,010 days). Readers did not detect corresponding hip abnormalities on MRIs. AFHS is a benign finding that may be caused by subclinical ligamentum teres injury, focal synovitis, or degeneration of acetabular fossa fat. Despite uncertainty regarding its etiology, recognition of AFHS as a benign finding can prevent morbidity associated with unnecessary biopsy or initiation of therapy. (orig.)

  12. Catchments as heterogeneous and multi-species reactors: An integral approach for identifying biogeochemical hot-spots at the catchment scale

    Science.gov (United States)

    Weyer, Christina; Peiffer, Stefan; Schulze, Kerstin; Borken, Werner; Lischeid, Gunnar

    2014-11-01

    From a biogeochemical perspective, catchments can be regarded as reactors that transform the input of various substances via precipitation or deposition as they pass through soils and aquifers towards draining streams. Understanding and modeling the variability of solute concentrations in catchment waters require the identification of the prevailing processes, determining their respective contribution to the observed transformation of substances, and the localization of "hot spots", that is, the most reactive areas of catchments. For this study, we applied a non-linear variant of the Principle Component Analysis, the Isometric Feature Mapping (Isomap), to a data set composed of 1686 soil solution, groundwater and stream water samples and 16 variables (Al, Ca, Cl, Fe, K, Mg, Mn, Na, NH4, NO3, SO4, total S, Si, DOC, electric conductivity and pH values) from the Lehstenbach catchment in Germany. The aim was (i) to assess the contribution of the prevailing biogeochemical processes to the variability of solute concentrations in water samples taken from soils, in groundwater and in stream water in a catchment and (ii) to identify hot spots at the catchment scale with respect to 16 solutes along different flow paths. The first three dimensions of the Isomap analysis explained 48%, 30% and 11%, respectively, i.e. 89% of the variance in the data set. Scores of the first three dimensions could be ascribed to three predominating bundles of biogeochemical processes: (i) redox processes, (ii) acid-induced podzolization, and (iii) weathering processes. In general, the upper 1 m topsoil layer could be considered as hot spots along flow paths from upslope soils and in the wetland, although with varying extents for the different prevailing biogeochemical processes. Nearly 67% and 97% of the variance with respect to redox processes and acid induced podzolization could be traced back to hot spots, respectively, representing less than 2% of the total spatial volume of the catchment

  13. Spatial and Temporal Hot Spots of Aedes albopictus Abundance inside and outside a South European Metropolitan Area.

    Science.gov (United States)

    Manica, Mattia; Filipponi, Federico; D'Alessandro, Antonello; Screti, Alessia; Neteler, Markus; Rosà, Roberto; Solimini, Angelo; Della Torre, Alessandra; Caputo, Beniamino

    2016-06-01

    Aedes albopictus is a tropical invasive species which in the last decades spread worldwide, also colonizing temperate regions of Europe and US, where it has become a public health concern due to its ability to transmit exotic arboviruses, as well as severe nuisance problems due to its aggressive daytime outdoor biting behaviour. While several studies have been carried out in order to predict the potential limits of the species expansions based on eco-climatic parameters, few studies have so far focused on the specific effects of these variables in shaping its micro-geographic abundance and dynamics. The present study investigated eco-climatic factors affecting Ae. albopictus abundance and dynamics in metropolitan and sub-urban/rural sites in Rome (Italy), which was colonized in 1997 and is nowadays one of the most infested metropolitan areas in Southern Europe. To this aim, longitudinal adult monitoring was carried out along a 70 km-transect across and beyond the most urbanized and densely populated metropolitan area. Two fine scale spatiotemporal datasets (one with reference to a 20m circular buffer around sticky traps used to collect mosquitoes and the second to a 300m circular buffer within each sampling site) were exploited to analyze the effect of climatic and socio-environmental variables on Ae. albopictus abundance and dynamics along the transect. Results showed an association between highly anthropized habitats and high adult abundance both in metropolitan and sub-urban/rural areas, with "small green islands" corresponding to hot spots of abundance in the metropolitan areas only, and a bimodal seasonal dynamics with a second peak of abundance in autumn, due to heavy rains occurring in the preceding weeks in association with permissive temperatures. The results provide useful indications to prioritize public mosquito control measures in temperate urban areas where nuisance, human-mosquito contact and risk of local arbovirus transmission are likely higher

  14. Spatial and Temporal Hot Spots of Aedes albopictus Abundance inside and outside a South European Metropolitan Area.

    Directory of Open Access Journals (Sweden)

    Mattia Manica

    2016-06-01

    Full Text Available Aedes albopictus is a tropical invasive species which in the last decades spread worldwide, also colonizing temperate regions of Europe and US, where it has become a public health concern due to its ability to transmit exotic arboviruses, as well as severe nuisance problems due to its aggressive daytime outdoor biting behaviour. While several studies have been carried out in order to predict the potential limits of the species expansions based on eco-climatic parameters, few studies have so far focused on the specific effects of these variables in shaping its micro-geographic abundance and dynamics. The present study investigated eco-climatic factors affecting Ae. albopictus abundance and dynamics in metropolitan and sub-urban/rural sites in Rome (Italy, which was colonized in 1997 and is nowadays one of the most infested metropolitan areas in Southern Europe. To this aim, longitudinal adult monitoring was carried out along a 70 km-transect across and beyond the most urbanized and densely populated metropolitan area. Two fine scale spatiotemporal datasets (one with reference to a 20m circular buffer around sticky traps used to collect mosquitoes and the second to a 300m circular buffer within each sampling site were exploited to analyze the effect of climatic and socio-environmental variables on Ae. albopictus abundance and dynamics along the transect. Results showed an association between highly anthropized habitats and high adult abundance both in metropolitan and sub-urban/rural areas, with "small green islands" corresponding to hot spots of abundance in the metropolitan areas only, and a bimodal seasonal dynamics with a second peak of abundance in autumn, due to heavy rains occurring in the preceding weeks in association with permissive temperatures. The results provide useful indications to prioritize public mosquito control measures in temperate urban areas where nuisance, human-mosquito contact and risk of local arbovirus transmission are

  15. Nonlinear excitations match correlated motions unveiled by NMR in proteins: a new perspective on allosteric cross-talk

    International Nuclear Information System (INIS)

    In this paper we propose a novel theoretical framework for interpreting long-range dynamical correlations unveiled in proteins through NMR measurements. The theoretical rationale relies on the hypothesis that correlated motions in proteins may be reconstructed as large-scale, collective modes sustained by long-lived nonlinear vibrations known as discrete breathers (DB) localized at key, hot-spot sites. DBs are spatially localized modes, whose nonlinear nature hinders resonant coupling with the normal modes, thus conferring them long lifetimes as compared to normal modes. DBs have been predicted to exist in proteins, localized at few hot-spot residues typically within the stiffest portions of the structure. We compute DB modes analytically in the framework of the nonlinear network model, showing that the displacement patterns of many DBs localized at key sites match to a remarkable extent the experimentally uncovered correlation blueprint. The computed dispersion relations prove that it is physically possible for some of these DBs to be excited out of thermal fluctuations at room temperature. Based on our calculations, we speculate that transient energy redistribution among the vibrational modes in a protein might favor the emergence of DB-like bursts of long-lived energy at hot-spot sites with lifetimes in the ns range, able to sustain critical, function-encoding correlated motions. More generally, our calculations provide a novel quantitative tool to predict fold-spanning dynamical pathways of correlated residues that may be central to allosteric cross-talk in proteins. (paper)

  16. Fluorescence enhancement using Fano-resonant a plasmonic nanostructure with selective functionalization of molecules at the electromagnetic hot spot (Presentation Recording)

    Science.gov (United States)

    Wang, Xiaolong; Martin, Olivier J. F.

    2015-09-01

    In recent years, one has paid significant attention to plasmonic nanostructures due to their potential for practical applications. Especially, in most plasmonic nanostructures, the local density of optical states is strongly enhanced and confined in the nanogap region - like for example in plasmonic antennas - which results in the so-called electromagnetic hot spots. In this work, we use 4-nanorod structures made with silver to generate and tune Fano resonances exhibiting an asymmetric and narrow lineshape. In such a system, a strongly enhanced electromagnetic field is created in the nanogap when the two antenna modes undergo destructive interference, i.e. at the Fano resonance. The local near field is thus strongly enhanced since most of the energy is not radiated into the far field at that wavelength. We will show that using a 4-nanorod structure in silver, we can easily tune the Fano resonance through the fluorescence spectrum of the molecule under study, thus exploring the different resonance conditions between the molecule absorption/emission bands and the plasmonic nanostructure; both the excitation and emission rates of the molecule can be enhanced when it is placed within the hot spot. To this end, we have developed a double electron beam lithography process to fabricate the plasmonic nanostructures and then selectively immobilize the molecule in the hot spot, in order to investigate the fluorescence enhancement under well-controlled conditions. The fluorescence enhancement is demonstrated by measuring the fluorescence lifetime and the fluorescence count rate. The experimental results are supported by theoretical modelling and numerical calculations with the Green's tensor method.

  17. Allosteric modulation of caspases.

    Science.gov (United States)

    Häcker, Hans-Georg; Sisay, Mihiret Tekeste; Gütschow, Michael

    2011-11-01

    Caspases are proteolytic enzymes mainly involved in the induction and execution phases of apoptosis. This type of programmed cell death is an essential regulatory process required to maintain the integrity and homeostasis of multicellular organisms. Inappropriate apoptosis is attributed a key role in many human diseases, including neurodegenerative disorders, ischemic damage, autoimmune diseases and cancer. Allosteric modulation of the function of a protein occurs when the regulatory trigger, such as the binding of a small effector or inhibitor molecule, takes place some distance from the protein's active site. In recent years, several caspases have been identified that possess allosteric sites and binding of small molecule to these sites resulted in the modulation of enzyme activities. Regulation of caspase activity by small molecule allosteric modulators is believed to be of great therapeutic importance. In this review we give brief highlights on recent developments in identifying and characterizing natural and synthetic allosteric inhibitors as well as activators of caspases and discuss their potential in drug discovery and protein engineering. PMID:21807025

  18. Binding of hot spot mutant p53 proteins to supercoiled DNA, roles of p53 core domain and C-terminus

    Czech Academy of Sciences Publication Activity Database

    Němcová, Kateřina; Brázdová, Marie; Činčárová, Lenka; Fojta, Miroslav; Paleček, Emil

    Brno, 2008. s. 45-46. ISBN 978-80-210-4526-2. [Pracovní setkání biochemiků a molekulárních biologů /12./. 05.02.2008-06.02.2008, Brno] R&D Projects: GA ČR(CZ) GP204/06/P369; GA AV ČR(CZ) IAA500040701; GA MŠk(CZ) LC06035 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : hot spot mutant p53 proteins * SCS DNA-binding * effect of oxidation agent and monoclonal antibodies Subject RIV: BO - Biophysics

  19. Breakdown of Fermi liquid behavior near the hot spots in a two-dimensional model: A two-loop renormalization group analysis

    OpenAIRE

    de Carvalho, Vanuildo S.; Freire, Hermann

    2013-01-01

    Motivated by a recent experimental observation of a nodal liquid on both single crystals and thin films of Bi$_2$Sr$_2$CaCu$_2$O$_{8+\\delta}$ by Chatterjee \\emph{et al.} [Nature Physics \\textbf{6}, 99 (2010)], we perform a field-theoretical renormalization group (RG) analysis of a two-dimensional model consisting of eight points located near the "hot spots" on the Fermi surface which are directly connected by spin density wave ordering wave vector. We derive RG equations up to two-loop order ...

  20. Study on unified fatigue strength assessment method for welded structure. Hot spot stress evaluating method for various combinations of plate thickness and weld leg length; Yosetsu kozo no toitsutekina hiro kyodo hyokaho ni kansuru kenkyu. Itaatsu to yosetsu ashinaga no kumiawase ni taisuru hot spot oryoku sanshutsu ni tsuite

    Energy Technology Data Exchange (ETDEWEB)

    Nihei, K.; Inamura, F.; Koe, S. [Kawasaki Heavy Industries, Ltd., Kobe (Japan)

    1996-12-31

    There has been tried to apply unified assessment method using hot spot stress, which is effective to evaluate fatigue strength of fillet welded structures for ships and marine structures. This method can be applied to complicated structures and is independent of welding processes. In this study, first, stress analysis has been conducted for two-dimensional fillet welded joint models with various combinations of plate thickness and weld leg length of general fillet structures by means of boundary element method. Then, critical position, which is not affected by local stress concentration due to bead, was determined from the detailed stress distribution in the vicinity of weld toe. As a result, a general equation has been proposed to estimate the hot spot stress by one-point representative method. Second, the fatigue tests of typical fillet welded joints have been conducted by applying this method. Consequently, it was demonstrated that the unified fatigue strength can be evaluated by the S-N data based on hot spot stress range determined from the proposed equation, independent of structural stress concentration. 22 refs., 14 figs.

  1. Using penumbral imaging to measure micrometer size plasma hot spots in Gbar equation of state experiments on the National Ignition Facility

    Science.gov (United States)

    Bachmann, B.; Kritcher, A. L.; Benedetti, L. R.; Falcone, R. W.; Glenn, S.; Hawreliak, J.; Izumi, N.; Kraus, D.; Landen, O. L.; Le Pape, S.; Ma, T.; Pérez, F.; Swift, D.; Döppner, T.

    2014-11-01

    We have developed an experimental platform for absolute equation of state measurements up to Gbar pressures on the National Ignition Facility (NIF) within the Fundamental Science Program. We use a symmetry-tuned hohlraum drive to launch a spherical shock wave into a solid CH sphere. Streaked radiography is the primary diagnostic to measure the density change at the shock front as the pressure increases towards smaller radii. At shock stagnation in the center of the capsule, we observe a short and bright x-ray self emission from high density (˜50 g/cm3) plasma at ˜1 keV. Here, we present results obtained with penumbral imaging which has been carried out to characterize the size of the hot spot emission. This allows extending existing NIF diagnostic capabilities for spatial resolution (currently ˜10 μm) at higher sensitivity. At peak emission we find the hot spot radius to be as small as 5.8 +/- 1 μm, corresponding to a convergence ratio of 200.

  2. Presaging critical residues in protein interfaces-web server (PCRPi-W: a web server to chart hot spots in protein interfaces.

    Directory of Open Access Journals (Sweden)

    Joan Segura Mora

    Full Text Available BACKGROUND: It is well established that only a portion of residues that mediate protein-protein interactions (PPIs, the so-called hot spot, contributes the most to the total binding energy, and thus its identification is an important and relevant question that has clear applications in drug discovery and protein design. The experimental identification of hot spots is however a lengthy and costly process, and thus there is an interest in computational tools that can complement and guide experimental efforts. PRINCIPAL FINDINGS: Here, we present Presaging Critical Residues in Protein interfaces-Web server (http://www.bioinsilico.org/PCRPi, a web server that implements a recently described and highly accurate computational tool designed to predict critical residues in protein interfaces: PCRPi. PRCPi depends on the integration of structural, energetic, and evolutionary-based measures by using Bayesian Networks (BNs. CONCLUSIONS: PCRPi-W has been designed to provide an easy and convenient access to the broad scientific community. Predictions are readily available for download or presented in a web page that includes among other information links to relevant files, sequence information, and a Jmol applet to visualize and analyze the predictions in the context of the protein structure.

  3. The west side story: MEFV haplotype in Spanish FMF patients and controls, and evidence of high LD and a recombination "hot-spot" at the MEFV locus.

    Science.gov (United States)

    Aldea, Anna; Calafell, Francesc; Aróstegui, Juan I; Lao, Oscar; Rius, Josefa; Plaza, Susana; Masó, Montserrat; Vives, Jordi; Buades, Joan; Yagüe, Jordi

    2004-04-01

    Mutations at the MEFV gene cause, with various degrees of penetrance, familial Mediterranean fever (FMF). This disease is more prevalent in the Middle East than elsewhere, and most studies have focused on those populations. However, FMF occurs also in the Western Mediterranean and these populations should be taken into account for a complete view of FMF. We have analyzed intragenic MEFV SNPs in Spanish and Chueta (descendants of converted Jews) FMF patients and controls, and this constitutes the first systematic survey of normal MEFV SNP haplotype structure and variability. Our findings have allowed us to systematize the nomenclature of MEFV haplotypes and show that there is strong linkage disequilibrium (LD) at the MEFV locus and an intragenic recombination hot spot. The high local LD, regardless the recombination hot spot, is responsible for the limited diversity of the MEFV control haplotypes found in the Spanish population and it suggests that it may be a common feature to all Mediterranean populations. The MEFV mutation spectrum in Spain is quite diverse, and similar to those of France and Italy. On the contrary, the Chueta spectrum was poorer and closer to that of North African Jews, suggesting a direct connection with the Jewish diaspora. PMID:15024744

  4. Determination of site selectivity of different carcinogens for preferential mutational hot spots in oligonucleotide fragments by ion-pair reversed-phase nano liquid chromatography tandem mass spectrometry.

    Science.gov (United States)

    Sharma, Vaneet K; Xiong, Wennan; Glick, James; Vouros, Paul

    2014-01-01

    Ion-pair reversed-phase nano liquid chromatography coupled with nanospray ion trap mass spectrometry was used to investigate site selectivity of the known carcinogens N-acetoxy-2-acetylaminofluorene, N-hydroxy-4-aminobiphenyl and (+/-)-anti-benzo[a]pyrene diol epoxide with the synthetic double-strand 14-mer long oligonucleotide fragment of the p53 gene containing two mutational hot-spot codons (5'-P-ACC155 CGC156 GTC157 CGC158 GC/5'-GCG CGG ACG CGG GT). The investigation was performed using a monolithic polystyrene divinylbenzene capillary column and triethylammonium bicarbonate as an ion-pair reagent. The exact location of the carcinogen on the modified oligonucleotide backbone was determined using characteristic collision-induced dissociation fragmentation patterns obtained under negative-ion mode ionization. In all these cases, the adducted, isomeric oligonucleotides formed were chromatographically resolved and structural identification was performed without any prior deoxyribonucleic acid cleavage or hydrolysis. The knowledge of the site specificity of a carcinogen, especially at purported mutational hot spots, is of paramount importance (1) in establishing the identity of biomarkers for an early risk assessment of the formed DNA adducts, (2) developing repair mechanisms for the formed carcinogen adducted DNA, and (3) understanding the nature of the covalent bond formed and mapping the frequency of the adduction process. PMID:24881456

  5. Using multi-sensor satellite remote sensing and catch data to detect ocean hot spots for albacore ( Thunnus alalunga) in the northwestern North Pacific

    Science.gov (United States)

    Zainuddin, Mukti; Kiyofuji, Hidetada; Saitoh, Katsuya; Saitoh, Sei-Ichi

    2006-02-01

    To understand better and describe oceanic hot spots for albacore ( Thunnus alalunga), we linked remotely sensed data from multi-sensor satellite images of TRMM/TMI sea-surface temperature (SST), SeaWiFS chlorophyll- a concentration and photosynthetically active radiation (PAR), and AVISO mean sea-level anomaly (MSLA) with fisheries catch data from 1998 to 2003. A probability map was generated based on biophysical environmental variables (SST and chlorophyll- a) in relation to the catch data. The probability of environmental variables was combined with an eddy kinetic energy (EKE) map to describe the oceanographic features around fishing locations. Primary production was examined to assess the productivity of the fishing grounds and was calculated from chlorophyll- a, SST and PAR using the vertically generalized production model (VGPM). Results indicate that the greatest catches occurred mainly in November, and the catches were highest at warm SSTs (19.78±1.69°C) and relatively high chlorophyll- a concentrations (0.31±0.13 mg m -3). Highest catches occurred in areas where primary production rates ranged from 15.65 to 20.61 g C m -2 month -1 (18.12±4.98 g C m -2 month -1). Our analysis found that catch per unit efforts (CPUEs) tended to increase significantly in areas of increasing probability of environmental variables ( P<0.0001) during the season of high abundance. Albacore CPUEs were clearly higher during November 1998-2000 than during November 2002-2003. During 1998-2000, the congregating spots of albacore clearly showed that the probability and primary productivity rates were higher than during 2002-2003. It is likely that the area of high probability (preferred biophysical environmental factors) corresponds to the location of frontal zones, where albacore prey were abundant. Regions of high tuna abundance occurred in relatively high EKE and geostrophic currents, reflecting that tuna aggregations were associated with anticyclonic eddies. These eddies may

  6. Hot Water Treatment to Reduce Angular Leaf Spot of Strawberry, Caused by Xanthomonas fragariae, in Nursery Production

    Science.gov (United States)

    Angular leaf spot is an important disease in strawberry nursery production. The European and Mediterranean Plant Protection Organization (EPPO) lists X. fragariae as an A2 quarantine pathogen. Therefore, nurseries wishing to export plants to European countries must maintain certain phytosanitary sta...

  7. Analysis of Reactive Hot Spot for Thermite under Shock Waves%铝热剂反应性冲击热点分析

    Institute of Scientific and Technical Information of China (English)

    王新征; 张松林; 张庆明; 秦志桂; 陈旻; 李文杰

    2012-01-01

    采用激光粒度扫描仪测量了二元混合物铝热剂(Al+Fe2O3)原料的粒径分布,在电子显微镜下观察了铝颗粒、氧化铁颗粒的颗粒形状及两者按照化学配比混合后的颗粒接触状态。综合粒径分布和反应体系的化学配比关系,得到两种反应物的特征粒径和混合物的颗粒布局。根据特征粒径和颗粒布局,建立了该反应体系的等效细观模型,该细观模型能够保证得到与实际颗粒体系相一致的具有统计意义的孔穴结构。采用无网格粒子方法,数值模拟了铝热剂体系在不同冲击速度作用下,基本氧化铁颗粒排列形成的热点特征。研究表明,氧化铁三颗粒紧密排列的模式为形成单独热点的最基本排列,在平面冲击作用下,二元不同粒径的含能材料混合物形成热点的尺寸由初始孔穴尺寸确定,而热点温度受冲击速度影响较大。采用轻气炮对不同密度和配比的铝热剂进行了冲击点火实验,并将测量和数值计算结果进行了对比分析,结果表明,两者的定性结论吻合较好。%Using laser scaners to measure the size of binary mixture of energetic materials thermite (Al+Fe2O3 ) and get the particle size distribution,the particle shape of aluminum powder,iron oxide and the contact status of the mixtures meeting the standard chemical proportion are observed under the electron microscope. Combined the raw material particle size distribution and the mass ratio of chemical reaction,the particle characteristic size (equivalent volume radius) and arrangement of aluminum and iron oxide particle were obtained. Based on the above conditions, the mesoscopic model for the thermite mixtures was established. The mesoscopic model can be guaranteed to get the statistical cavities struc- ture consistent with that of the actual granular system. The features of "hot spot" for the thermite by impact were studied with the Smoothed Particle

  8. Relevance of hot spots in the evolution and transmission of Tn1546 in glycopeptide-resistant Enterococcus faecium (GREF) from broiler origin

    DEFF Research Database (Denmark)

    Migura, Lourdes Garcia; Hasman, Henrik; Svendsen, Christina Aaby;

    2008-01-01

    -resistant Enterococcus faecium isolated from broiler farms. Methods: Total DNA was digested, ligated and amplified using primers from inside Tn1546. The resulting amplicons were purified and sequenced. Two new primers were designed based on obtained sequences. Results: Two main insertion points have been repeatedly...... found in isolates from the UK (n = 150). The first insertion point revealed that 25 isolates harboured Tn1546 positioned in a sequence with 96% homology to a streptomycin adenyltransferase gene (AY604739) from a Staphylococcus intermedius plasmid. At this insertion point, a direct repeat (GTCCT......) was duplicated as previously described, indicating transposition at the target site. Furthermore, this 'hot spot' was also detected in isolates from Norway (2/8) and Denmark (17/20). The second insertion point detected in 45 isolates from the UK revealed integration into an Inc18-like plasmid, most likely...

  9. A hot-spot-active magnetic graphene oxide substrate for microRNA detection based on cascaded chemiluminescence resonance energy transfer

    Science.gov (United States)

    Bi, Sai; Chen, Min; Jia, Xiaoqiang; Dong, Ying

    2015-02-01

    Herein, a cascaded chemiluminescence resonance energy transfer (C-CRET) process was demonstrated from horseradish peroxidase (HRP)-mimicking DNAzyme-catalyzed luminol-H2O2 to fluorescein and further to graphene oxide (GO) when HRP-mimicking DNAzyme/fluorescein was in close proximity to the GO surface. The proposed C-CRET system was successfully implemented to construct three modes of C-CRET hot-spot-active substrates (modes I, II and III) by covalently immobilizing HRP-mimicking DNAzyme/fluorescein-labeled hairpin DNAs (hot-spot-generation probes) on magnetic GO (MGO), resulting in a signal ``off'' state due to the quenching of the luminol/H2O2/HRP-mimicking DNAzyme/fluorescein CRET system by GO. Upon the introduction of microRNA-122 (miRNA-122), the targets (mode I) or the new triggers that were generated through a strand displacement reaction (SDR) initiated by miRNA-122 (modes II and III) hybridized with the loop domains of hairpin probes on MGO to form double-stranded (modes I and II) or triplex-stem structures (mode III), causing an ``open'' configuration of the hairpin probe and a CRET signal ``on'' state, thus achieving sensitive and selective detection of miRNA-122. More importantly, the substrate exhibited excellent controllability, reversibility and reproducibility through SDR and magnetic separation (modes II and III), especially sequence-independence for hairpin probes in mode III, holding great potential for the development of a versatile platform for optical biosensing.Herein, a cascaded chemiluminescence resonance energy transfer (C-CRET) process was demonstrated from horseradish peroxidase (HRP)-mimicking DNAzyme-catalyzed luminol-H2O2 to fluorescein and further to graphene oxide (GO) when HRP-mimicking DNAzyme/fluorescein was in close proximity to the GO surface. The proposed C-CRET system was successfully implemented to construct three modes of C-CRET hot-spot-active substrates (modes I, II and III) by covalently immobilizing HRP-mimicking DNAzyme

  10. An outdoor investigation of the absorption degradation of single-junction amorphous silicon photovoltaic module due to localized heat/hot spot formation

    Indian Academy of Sciences (India)

    Osayemwenre Gilbert O; Meyer Edson L; Mamphweli Sampson

    2016-04-01

    This paper investigates the absorbance degradation of single-junction amorphous silicon (a-Si:H) photovoltaic (PV) module, due to the presence of localized heat. The decrease in optical density is a huge challenge due to the long-term degradation of PV modules. The reduction in solar cell optical density causes a decline in its conversion efficiency. This decreases the photogenerating current, hence reduces the effective efficiency of the PV device. An infrared thermography was used for mapping the module temperature profile. Fourier transform infrared spectroscopy (FTIR) was used for the absorption characterization. The rationale behind the outdoor deployment was to deduce a practical effect of hot spot formation on the module’s absorption ability.The results show a direct correlation between localized heat and the absorption degradation.

  11. Allosteric Mechanisms in Chaperonin Machines.

    Science.gov (United States)

    Gruber, Ranit; Horovitz, Amnon

    2016-06-01

    Chaperonins are nanomachines that facilitate protein folding by undergoing energy (ATP)-dependent movements that are coordinated in time and space owing to complex allosteric regulation. They consist of two back-to-back stacked oligomeric rings with a cavity at each end where protein substrate folding can take place. Here, we focus on the GroEL/GroES chaperonin system from Escherichia coli and, to a lesser extent, on the more poorly characterized eukaryotic chaperonin CCT/TRiC. We describe their various functional (allosteric) states and how they are affected by substrates and allosteric effectors that include ATP, ADP, nonfolded protein substrates, potassium ions, and GroES (in the case of GroEL). We also discuss the pathways of intra- and inter-ring allosteric communication by which they interconvert and the coupling between allosteric transitions and protein folding reactions. PMID:26726755

  12. A duchenne muscular dystrophy gene hot spot mutation in dystrophin-deficient cavalier king charles spaniels is amenable to exon 51 skipping.

    Directory of Open Access Journals (Sweden)

    Gemma L Walmsley

    Full Text Available BACKGROUND: Duchenne muscular dystrophy (DMD, which afflicts 1 in 3500 boys, is one of the most common genetic disorders of children. This fatal degenerative condition is caused by an absence or deficiency of dystrophin in striated muscle. Most affected patients have inherited or spontaneous deletions in the dystrophin gene that disrupt the reading frame resulting in unstable truncated products. For these patients, restoration of the reading frame via antisense oligonucleotide-mediated exon skipping is a promising therapeutic approach. The major DMD deletion "hot spot" is found between exons 45 and 53, and skipping exon 51 in particular is predicted to ameliorate the dystrophic phenotype in the greatest number of patients. Currently the mdx mouse is the most widely used animal model of DMD, although its mild phenotype limits its suitability in clinical trials. The Golden Retriever muscular dystrophy (GRMD model has a severe phenotype, but due to its large size, is expensive to use. Both these models have mutations in regions of the dystrophin gene distant from the commonly mutated DMD "hot spot". METHODOLOGY/PRINCIPAL FINDINGS: Here we describe the severe phenotype, histopathological findings, and molecular analysis of Cavalier King Charles Spaniels with dystrophin-deficient muscular dystrophy (CKCS-MD. The dogs harbour a missense mutation in the 5' donor splice site of exon 50 that results in deletion of exon 50 in mRNA transcripts and a predicted premature truncation of the translated protein. Antisense oligonucleotide-mediated skipping of exon 51 in cultured myoblasts from an affected dog restored the reading frame and protein expression. CONCLUSIONS/SIGNIFICANCE: Given the small size of the breed, the amiable temperament and the nature of the mutation, we propose that CKCS-MD is a valuable new model for clinical trials of antisense oligonucleotide-induced exon skipping and other therapeutic approaches for DMD.

  13. Characteristics of hot spots of melon fly, Bactrocera (Dacus) cucurbitae Coquillett (Diptera: Tephritidae) in sterile fly release areas on Okinawa island [Japan

    International Nuclear Information System (INIS)

    The spatio-temporal dynamics of populations of the melon fly, Bactrocera (Dacus) cucurbitae COQUILLETT, in the southern part of Okinawa Island where an eradication program using sterile flies has been conducted, were analyzed in relation to the seasonal succession and abundance of wild and cultivated host fruits. The study areas were classified into four major zones according to the seasonal abundance of flies caught by cue-lure traps and the availability of host fruits including Diplocyclos palmatus, Melothria liukiuensis and Momordica charantia var. pevel. Zone-I is characterized by the continuous presence of host fruits and a relatively-high population density of the melon fly indicated by the cue-lure trap catch of more than 1, 000 flies per 1, 000 traps per day throughout the year. Zone-II has a characteristic decline in both number of host fruits and fly density during the fall-winter period with an annual average of less than 1, 000 flies per 1, 000 traps per day. Zone-III includes areas where host fruits and flies (about 1 fly/trap/day) were relatively abundant only during the winter-spring period. Zone-IV is characterized by constantly low availability of host fruits and low fly density throughout the year. Hot spots, which are defined as areas where the ratio of sterile to wild flies hardly increases despite frequent and intensive release of sterile flies, were found in the Zone-I areas. Therefore, the continuous presence and abundance of host fruits appears to hot spots. For effective control of this species, it is essential to locate such areas and release sterile flies

  14. Evaluation of Caspofungin Susceptibility Testing by the New Vitek 2 AST-YS06 Yeast Card Using a Unique Collection of FKS Wild-Type and Hot Spot Mutant Isolates, Including the Five Most Common Candida Species

    DEFF Research Database (Denmark)

    Astvad, Karen M; Perlin, David S; Johansen, Helle K;

    2013-01-01

    susceptibility card to correctly identify the fks mutants from wt isolates and compared the performance to those of the CLSI and EUCAST reference methods. A collection of 98 Candida isolates, including 31 fks hot spot mutants, were included. Performance was evaluated using the FKS genotype as the "gold standard...

  15. A new assessment of combined geothermal electric generation and desalination in western Saudi Arabia: targeted hot spot development

    KAUST Repository

    Missimer, Thomas M.

    2014-07-17

    High heat flow associated with the tectonic spreading of the Red Sea make western Saudi Arabia a region with high potential for geothermal energy development. The hydraulic properties of the Precambrian-age rocks occurring in this region are not conducive to direct production of hot water for heat exchange, which will necessitate use of the hot dry rock (HDR) heat harvesting method. This would require the construction of coupled deep wells; one for water injection and the other for steam recovery. There are some technological challenges in the design, construction, and operation of HDR geothermal energy systems. Careful geotechnical evaluation of the heat reservoir must be conducted to ascertain the geothermal gradient at the chosen site to allow pre-design modeling of the system for assessment of operational heat flow maintenance. Also, naturally occurring fractures or faults must be carefully evaluated to make an assessment of the potential for induced seismicity. It is anticipated that the flow heat exchange capacity of the system will require enhancement by the use of horizontal drilling and hydraulic fracturing in the injection well with the production well drilled into the fracture zone to maximum water recovery efficiency and reduce operating pressure. The heated water must be maintained under pressure and flashed to steam at surface to produce to the most effective energy recovery. Most past evaluations of geothermal energy development in this region have been focused on the potential for solely electricity generation, but direct use of produced steam could be coupled with thermally driven desalination technologies such as multi-effect distillation, adsorption desalination, and/or membrane distillation to provide a continuous source of heat to allow very efficient operation of the plants. © 2014 © 2014 Balaban Desalination Publications. All rights reserved.

  16. Hydrothermal vents near a mantle hot spot: the Lucky Strike vent field at 37°N on the Mid-Atlantic Ridge

    Science.gov (United States)

    Langmuir, C.; Humphris, S.; Fornari, D.; Van Dover, C.; Von Damm, K.; Tivey, M. K.; Colodner, D.; Charlou, J.-L.; Desonie, D.; Wilson, C.; Fouquet, Y.; Klinkhammer, G.; Bougault, H.

    1997-04-01

    The Lucky Strike hydrothermal field occurs in the summit basin of a large seamount that forms the shallow center of a 65 km long ridge segment near 37°N on the Mid-Atlantic Ridge. The depth and chemistry of the ridge segment are influenced by the Azores hot spot, and this hydrothermal field is the first Atlantic site found on crust that is dominated by a hot spot signature. Multiple hydrothermal vents occur over an area of at least 300 m by 700 m. Vent morphologies range from flanges and chimneys with temperatures of 200-212°C, to black smoker chimneys with temperatures up to 333°C. Cooler fluids from northern vents have higher chlorinities and lower gas volumes, while hotter, southern fluids have chlorinities 20% below seawater with higher gas volumes, suggesting phase separation has influenced their compositions. All gas volumes in fluids are higher than those at TAG and Snake Pit hydrothermal fields. Black smokers exhibit their typical mineralogy, except that barite is a major mineral, particularly at lower-temperature sites, which contrasts with previously investigated Atlantic sites. The fluid chemistry, distribution of the relict sulfide deposits on the seamount summit in the areas investigated using DSV Alvin, and contact relationships between active vent sites and surrounding basaltic and sulfide substrate suggest that the hydrothermal system has a long history and may have recently been rejuvenated. Fauna at the Lucky Strike vent sites are dominated by a new species of mussel, and include the first reported sea urchins. The Lucky Strike biological community differs considerably from other vent fauna at the species level and appears to be a new biogeographic province. The Lucky Strike field helps to constrain how variations in the basaltic substrate influence the composition of hydrothermal fluids and solids, because basalt compositions at Lucky Strike are 10-30 times enriched in incompatible elements compared to other Atlantic hydrothermal sites such as

  17. Insights into the origin and distribution of biodiversity in the Brazilian Atlantic forest hot spot: a statistical phylogeographic study using a low-dispersal organism

    Science.gov (United States)

    Álvarez-Presas, M; Sánchez-Gracia, A; Carbayo, F; Rozas, J; Riutort, M

    2014-01-01

    The relative importance of the processes that generate and maintain biodiversity is a major and controversial topic in evolutionary biology with large implications for conservation management. The Atlantic Forest of Brazil, one of the world's richest biodiversity hot spots, is severely damaged by human activities. To formulate an efficient conservation policy, a good understanding of spatial and temporal biodiversity patterns and their underlying evolutionary mechanisms is required. With this aim, we performed a comprehensive phylogeographic study using a low-dispersal organism, the land planarian species Cephaloflexa bergi (Platyhelminthes, Tricladida). Analysing multi-locus DNA sequence variation under the Approximate Bayesian Computation framework, we evaluated two scenarios proposed to explain the diversity of Southern Atlantic Forest (SAF) region. We found that most sampled localities harbour high levels of genetic diversity, with lineages sharing common ancestors that predate the Pleistocene. Remarkably, we detected the molecular hallmark of the isolation-by-distance effect and little evidence of a recent colonization of SAF localities; nevertheless, some populations might result from very recent secondary contacts. We conclude that extant SAF biodiversity originated and has been shaped by complex interactions between ancient geological events and more recent evolutionary processes, whereas Pleistocene climate changes had a minor influence in generating present-day diversity. We also demonstrate that land planarians are an advantageous biological model for making phylogeographic and, particularly, fine-scale evolutionary inferences, and propose appropriate conservation policies. PMID:24549112

  18. Short-range incommensurate d-wave charge order from a two-loop renormalization group calculation of the ferm-ionic hot spot model

    Science.gov (United States)

    Freire, Hermann; de Carvalho, Vanuildo

    2015-03-01

    The two-loop renormalization group (RG) calculation is considerably extended here for a two-dimensional (2D) fermionic effective field theory model, which includes only the so-called ``hot spots'' that are connected by the spin-density-wave (SDW) ordering wavevector on a Fermi surface generated by the 2D t -t' Hubbard model at low hole doping. We compute the Callan-Symanzik RG equation up to two loops describing the flow of the single-particle Green's function, the corresponding spectral function, the Fermi velocity, and some of the most important order-parameter susceptibilities in the model at lower energies. As a result, we establish that - in addition to clearly dominant SDW correlations - an approximate (pseudospin) symmetry relating a short-range incommensurate d-wave charge order to the d-wave superconducting order indeed emerges at lower energy scales, which is in agreement with recent works available in the literature addressing the 2D spin-fermion model. We derive implications of this possible electronic phase in the ongoing attempt to describe the phenomenology of the pseudogap regime in underdoped cuprates. We acknowledge financial support from CNPq under Grant No. 245919/2012-0 and FAPEG under Grant No. 201200550050248 for this project.

  19. Accumulation of anthracotic particles along lymphatics of the human lung: Relevance to 'hot spot' formation after inhalation of poorly soluble radionuclides

    International Nuclear Information System (INIS)

    Large lung sections of humans of advanced adult age revealed a markedly nonuniform retention pattern of dense anthracotic particle aggregates, with an impressive accumulation of this material along pulmonary lymphatics, i.e. the deep (peribronchial), septal (perivenous) and superficial (pleural) networks. Conversely, the alveolar parenchyme contained only occasional, small aggregates of macrophages heavily loaded with carbon, representing little more than 2% of this material in lung tissue. Although translocation kinetics of anthracotic particles cannot readily be compared to those of highly toxic α-emitting, poorly soluble radionuclides such as 239PuO2, lymphatic drainage of the latter over the years may also be expected to lead to a concentration of radioactive material along lymph vessels. Since human data on the effects of inhaled 239PuO2 are virtually lacking, the above distribution pattern is apt to help in identifying cells and other tissue components most heavily at risk. Findings are also relevant to the problem of ''hot spot'' formation in vivo and its possible sequelae. The latter are briefly discussed with regard to both stochastic and non-stochastic effects. (orig.)

  20. The effect of hohlraum drive asymmetry on the observed in-flight momentum and hot spot emission non-uniformity in ICF implosions

    Science.gov (United States)

    Pak, Arthur; Field, J. E.; Kritcher, A.; Nora, R.; Berzak Hopkins, L. F.; Divol, L.; Khan, S. F.; Ma, T.; Tommasini, R.; Bradley, D. K.; Callahan, D.; Hinkel, D.; Hurricane, O. A.; Jones, O. S.; MacKinnon, A. J.; MacLaren, S. A.; Meezan, N. B.; Moody, J.; Patel, P.; Robey, H. F.; Smalyuk, V. A.; Spears, B. K.; Town, R. P. J.; Edwards, M. J.; LLNL Team

    2015-11-01

    At the National Ignition Facility indirectly driven inertial confinement fusion experiments are being conducted. In order to maximize the efficiency at which kinetic energy of the capsule ablator and fuel is converted to internal hot spot energy, asymmetries in the shape of the ablator and fuel momentum must be minimized. In this work an overview across different implosion experiments detailing the observed relationship between the in-flight ablator momentum symmetry and factors that modify the hohlraum radiation flux symmetry such as the density of the hohlraum gas fill, laser wavelength separation, and case to capsule ratio will be given. A measurement of the ablator momentum asymmetry at peak velocity can be made using the two-dimensional radiographs of the capsule ablator taken in-flight, at radii of 300 to 200 _m. Additionally the relationship between the morphology of the observed in-flight ablator and the x-ray self emission at stagnation will be examined. This work was performed under the auspices of the U. S. Department of Energy by Lawrence Livermore National Laboratory under contract DE-AC52-07NA27344.

  1. Uporaba prostorske statistike za določevanje zgostitev prometnih nesreč : Identification of Road Accident Hot Spots Using Spatial Statistics

    Directory of Open Access Journals (Sweden)

    Jure Kostanjšek

    2010-01-01

    Full Text Available SI: V prispevku predstavljamo prilagojeno metodo za odkrivanje nevarnih odsekov in krajev, ki temelji na uporabi indeksa Getis-Ord G*. Od klasične metode se razlikuje v tem, da poleg teže nezgod upoštevamo prometne obremenitve na kraju nezgode. Metodaje bila uporabljena na primeru omrežja slovenskih avtocest in hitrih cest. Prikazani so rezultati analiz z upoštevanjem prometnih obremenitev in brez njih oziroma primerjava z metodama določanja gostote jeder in lokalnega Anselin-Moranovega indeksa.ENG: This paper presents a modified spatial statistical method for identifying road accident hot spots. Our suggested method is based on the Getis-Ord G* index. It differs from the standard method, because in addition to the number of accidents and their consequences, we also consider traffic at the locations of these accidents. The method was tested on the Slovene motorway network. The results are presented with and without considering traffic volumes and are compared with both Kernel density method and Anselin-Moran local index method.

  2. Depth to Curie temperature or bottom of the magnetic sources in the volcanic zone of la Réunion hot spot

    Science.gov (United States)

    Gailler, Lydie-Sarah; Lénat, Jean-François; Blakely, Richard J.

    2016-09-01

    We present an innovative study to generalize Curie Point Depth (CPD) determinations at the scale of oceanic volcanic islands, an approach which has previously focused largely on continental areas. In order to determine the validity of this technique in oceanic environments, we first tested the approach on sets of sea-floor-spreading anomalies. Assuming that magnetic anomalies are concentrated within the oceanic crust and uppermost mantle, the Curie depth should deepen as oceanic lithosphere increases in age and thickness away from spreading centers. The calculated depths to the magnetic bottom are in agreement with this general pattern. On the basis of this test, we then applied the method to La Réunion Island and surrounding oceanic lithosphere. The calculated extent of magnetic sources lies at depths between 10 and 30 km and exhibits a complex topography, presumably caused by a combination of various magmatic and tectonic lithospheric structures. These calculations indicate that magnetic sources extend well below the crust-mantle interface at this location. To the first order, the bottom of the magnetic surface shallows beneath Réunion and Mauritius Islands due to the thermal effect of the hot spot, and deepens away from La Réunion edifice. On the scale of the Mascarene Basin, several discontinuities in the CPD correlate well with major fracture zones.

  3. High-resolution measurement of nitrous oxide in the Elbe estuary under hypoxia: Hot-spots of biological N2O production

    Science.gov (United States)

    Brase, Lisa; Lendt, Ralf; Sanders, Tina; Dähnke, Kirstin

    2016-04-01

    Nitrous oxide (N2O) is one of the most important greenhouse gases. Its global warming potential exceeds that of CO2 by a factor of ˜300. Estuaries, being sites of intense biological N-turnover, are one of the major natural sources of N2O emissions. On two ship cruises in April and June 2015, concentrations of N2O were measured in the surface water using equilibrator laser based on-line measurements. Based on these high-resolution N2O profiles along the Elbe estuary, N2O saturation and N2O-fluxes between surface water and air were calculated. Additionally, DIN concentrations and dual stable isotopes of nitrate (δ15N and δ18O) were analyzed. Concentration and water-to-air fluxes of N2O were highest in the Hamburg port region and dropped quickly further downstream. Highest water-to-air fluxes were up to 800μM/m2/d and 1600μM/m2/d in April and in June, respectively. Downstream of the port region, an N2O oversaturation of 150-200% was estimated over the entire estuary, with saturation approaching equilibrium (96-100%) only in the North Sea region. N2O production was much higher in June than in April 2015, likely coupled to lower oxygen saturation in the water column in June. Based on these measurements, the port of Hamburg region was identified as a hot-spot of N2O production. High N2O concentration and depleted values of nitrate isotopes suggest that nitrification is a significant source of N2O in the estuary, especially at low oxygen concentration. In the Elbe estuary, hypoxia obviously drastically increased the emissions of the greenhouse gas N2O.

  4. Allosterism and Structure in Thermally Activated Transient Receptor Potential Channels.

    Science.gov (United States)

    Diaz-Franulic, Ignacio; Poblete, Horacio; Miño-Galaz, Germán; González, Carlos; Latorre, Ramón

    2016-07-01

    The molecular sensors that mediate temperature changes in living organisms are a large family of proteins known as thermosensitive transient receptor potential (TRP) ion channels. These membrane proteins are polymodal receptors that can be activated by cold or hot temperatures, depending on the channel subtype, voltage, and ligands. The stimuli sensors are allosterically coupled to a pore domain, increasing the probability of finding the channel in its ion conductive conformation. In this review we first discuss the allosteric coupling between the temperature and voltage sensor modules and the pore domain, and then discuss the thermodynamic foundations of thermo-TRP channel activation. We provide a structural overview of the molecular determinants of temperature sensing. We also posit an anisotropic thermal diffusion model that may explain the large temperature sensitivity of TRP channels. Additionally, we examine the effect of several ligands on TRP channel function and the evidence regarding their mechanisms of action. PMID:27297398

  5. Allosteric Modulation of Muscarinic Receptors

    Czech Academy of Sciences Publication Activity Database

    Jakubík, Jan; El-Fakahany, E. E.

    New York: Springer, 2016 - (Mysliveček, J.; Jakubík, J.), s. 95-130. (Neuromethods. 107). ISBN 978-1-4939-2857-6 R&D Projects: GA ČR(CZ) GBP304/12/G069 Institutional support: RVO:67985823 Keywords : muscarinic receptors * allosteric modulation * radioligand binding functional response Subject RIV: ED - Physiology

  6. Liver spots

    Science.gov (United States)

    Sun-induced skin changes - liver spots; Senile or solar lentigines; Skin spots - aging; Age spots ... your skin by using skin bleaching lotions or creams. Most bleaching lotions use hydroquinone. This medicine is ...

  7. Converter Compressor Building, SWMU 089, Hot Spot Areas 1, 2, and 5 Operations, Maintenance, and Monitoring Report, Kennedy Space Center, Florida

    Science.gov (United States)

    Wilson, Deborah M.

    2015-01-01

    This Operations, Maintenance, and Monitoring Report (OMMR) presents the findings, observations, and results from operation of the air sparging (AS) interim measure (IM) for Hot Spot (HS) Areas 1, 2, and 5 at the Converter Compressor Building (CCB) located at Kennedy Space Center (KSC), Florida. The objective of the IM at CCB HS Areas 1, 2, and 5 is to decrease concentrations of volatile organic compounds (VOCs) in groundwater in the treatment zones via AS to levels that will enable a transition to a monitored natural attenuation (MNA) phase. This OMMR presents system operations and maintenance (O&M) information and performance monitoring results since full-scale O&M began in June 2014 (2 months after initial system startup in April 2014), including quarterly performance monitoring events in July and October 2014 and January and May 2015. Based on the results to date, the AS system is operating as designed and is meeting the performance criteria and IM objective. The performance monitoring network is adequately constructed for assessment of IM performance at CCB HS Areas 1, 2, and 5. At the March 2014 KSC Remediation Team (KSCRT) Meeting, team consensus was reached for the design prepared for expansion of the system to treat the HS 4 area, and at the November 2014 KSCRT Meeting, team consensus was reached that HS 3 was adequately delineated horizontally and vertically and for selection of AS for the remedial approach for HS 3. At the July 2015 KSCRT meeting, team consensus was reached to continue IM operations in all zones until HSs 3 and 4 is operational, once HS 3 and 4 zones are operational discontinue operations in HS 1, 2, and 5 zones where concentrations are less than GCTLs to observe whether rebounding conditions occur. Team consensus was also reached to continue quarterly performance monitoring to determine whether operational zones achieve GCTLs and to continue annual IGWM of CCB-MW0012, CCBMW0013, and CCB-MW0056, located south of the treatment area. The

  8. Finding malaria hot-spots in northern Angola: the role of individual, household and environmental factors within a meso-endemic area

    Directory of Open Access Journals (Sweden)

    Magalhães Ricardo J

    2012-11-01

    Full Text Available Abstract Background Identifying and targeting hyper-endemic communities within meso-endemic areas constitutes an important challenge in malaria control in endemic countries such like Angola. Recent national and global predictive maps of malaria allow the identification and quantification of the population at risk of malaria infection in Angola, but their small-scale accuracy is surrounded by large uncertainties. To observe the need to develop higher resolution malaria endemicity maps a predictive risk map of malaria infection for the municipality of Dande (a malaria endemic area in Northern Angola was developed and compared to existing national and global maps, the role of individual, household and environmental risk factors for malaria endemicity was quantified and the spatial variation in the number of children at-risk of malaria was estimated. Methods Bayesian geostatistical models were developed to predict small-scale spatial variation using data collected during a parasitological survey conducted from May to August 2010. Maps of the posterior distributions of predicted prevalence were constructed in a geographical information system. Results Malaria infection was significantly associated with maternal malaria awareness, households with canvas roofing, distance to health care centre and distance to rivers. The predictive map showed remarkable spatial heterogeneity in malaria risk across the Dande municipality in contrast to previous national and global spatial risk models; large high-risk areas of malaria infection (prevalence >50% were found in the northern and most eastern areas of the municipality, in line with the observed prevalence. Conclusions There is remarkable spatial heterogeneity of malaria burden which previous national and global spatial modelling studies failed to identify suggesting that the identification of malaria hot-spots within seemingly mesoendemic areas may require the generation of high resolution malaria maps

  9. Regional scale analysis of nitrous oxide emissions within the U.S. Corn Belt and the potential role of episodic hot spots

    Science.gov (United States)

    Griffis, T. J.; Lee, X.; Baker, J. M.; Russelle, M.; Zhang, X.; Millet, D. B.; Venterea, R. T.

    2012-12-01

    Nitrous oxide (N2O) is a long-lived greenhouse gas that has the third largest radiative forcing on the Earth-Atmosphere system and has become the most important stratospheric ozone depleting substance of the 21st century. The rapid increase in N2O concentrations over the last century is primarily attributed to the Haber-Bosch process and the green revolution. Predicting future concentrations and developing mitigation strategies for N2O is a critical environmental challenge as pressure mounts on agricultural ecosystems to deliver more products to a burgeoning population. Bottom-up (process/inventory) and top-down (global) strategies are used to constrain the global N2O budget, but have been inadequately tested by data collected at the appropriate spatial and temporal scales. Two-years of tall tower (regional-scale) high-frequency N2O concentration data and boundary layer budget techniques were used to quantify the regional budget and assess bottom-up and top-down emission factors within the U.S. Corn Belt. Here we show that regional flux estimates were 2 to 9-fold greater than bottom-up emission estimates provided by the EDGAR, IPCC, and GEIA assessments. Using our regional flux data we derived "internal" and "external" emission factors that relate directly to the bottom-up and top-down perspectives on constraining the global N2O cycle. The internal and external emission factors were 4.0 and 5.6%, respectively, and significantly larger than that derived from bottom-up approaches. It is hypothesized that this bias is caused by episodic leakage mechanisms that can only be accounted for at the appropriate spatial and temporal scales.N2O emission hot spots from agricultural drainage ditches are shown to exceed 60 nmol m-2 s-1 and, at times, are about 60-fold greater than typical field-scale fluxes. Our data and analyses suggest that many field-scale studies that quantify greenhouse gas emissions will significantly underestimate the true net radiative forcing of

  10. Four new WMO/GAW Observatories for the investigation of trace gas and aerosol variability in the Mediterranean hot-spot

    Science.gov (United States)

    Cristofanelli, Paolo; Marinoni, Angela; Duchi, Rocco; Busetto, Maurizio; Calzolari, Francescopiero; Bourcier, Laureline; Landi, Tony Christian; Calidonna, Claudia; Contini, Daniele; Ammoscato, Ivano; Gulli', Daniel; Dinoi, Adelaide; Sprovieri, Francesca; Carbone, Francesco; Naccarato, Attilio; Mannarino, Valentino; Pirrone, Nicola; Bonasoni, Paolo

    2016-04-01

    The Mediterranean Basin is considered a hot-spot region in term of air-quality and climate change due to the impact of anthropogenic and natural processes. Nevertheless, permanent infrastructures for the observations and the recognition of the atmospheric composition variability changes are still too sparse in this region. To contribute to a more accurate and wide-spread observation system, in the framework of the Project "I-AMICA" - Advanced Infrastructure for the Environmental-Climatic Monitoring (a three years Italian National Operative Program - PON, co-founded by the European Regional Development Fund), four permanent Climatic-Environmental Observatories have been set up in the southern Italy: Lecce (Apulia Region, 40° 20' 8" N, 18° 07' 28" E, 37 m a.s.l.), Lamezia Terme (Calabria Region, 38° 52' 34" N, 16° 13' 56" E, 6 m a.s.l.), Capo Granitola (Sicily, 37° 34' N, 12° 39' E, 5 m a.s.l.) and Mt. Curcio (Calabria, 39° 31' N, 16° 42' E, 1796 m a.s.l). These Observatories were equipped with homogeneous and standardized experimental set-up for measurements of aerosol properties (number size distribution, absorption and scattering coefficient, mass, equivalent black carbon), reactive and greenhouse gases (O3, NO, NO2, SO2, CO, CO2, CH4). The I-AMICA Observatories represent different conditions of the Mediterranean region, from suburban conditions at Lecce to costal background conditions at Lamezia Terme and Capo Granitola and high-mountain remote conditions at Mt. Curcio. The integration of the information from this high-quality observation network can be used for studies of aerosol transport from marine environment and Sahara desert, as well as for investigation of secondary pollutants formation in the gaseous and aerosol phase, investigation of continental outflow to Mediterranean Sea, impacts of vessel emissions on regional air quality and trans-boundary pollution. In this work, we provide a preliminary overview of gas and aerosol variability, together

  11. "Ladies and Gentlemen, start your engines!" Analysis codes waiting for the first JIRAM-Juno data of Jupiter hot-spots

    Science.gov (United States)

    Grassi, Davide; Sindoni, Giuseppe; D'Aversa, Emiliano; Oliva, Fabrizio; Filacchione, Gianrico; Adriani, Alberto; Mura, Alessandro; Moriconi, Maria Luisa; Noschese, Raffaella; Cicchetti, Andrea; Piccioni, Giuseppe; Ignatiev, Nikolai; Maestri, Tiziano

    2016-04-01

    In this contribution, we detail the retrieval scheme that has been developed in the last few years for the analysis of the spectral data expected from the JIRAM experiment on board of the Juno NASA mission [1], beginning from the second half of 2016. Our focus is on the analysis of the thermal radiation in the 5 micron transparency window, in regions of lesser cloud opacity (namely, hot-spots). Moving from the preliminary analysis presented in Grassi et al., 2010 [2], a retrieval scheme has been developed and implemented as a complete end-to-end processing software. Performances in terms of fit quality and retrieval errors are discussed from tests on simulated spectra. Few examples of usage on VIMS-Cassini flyby data are also presented. Following the suggestion originally presented in Irwin et al., 1998 [3] for the analysis of the NIMS data, the state vector to be retrieved has been drastically simplified on physically sounding basis, aiming mostly to distinguish between the 'deep' content of minor gaseous component (water, ammonia, phosphine) and their relative humidity or fractional scale height in the upper troposphere. The retrieval code is based on a Bayesian scheme [4], complemented by a Metropolis algorithm plus simulated thermal annealing [5] for most problematic cases. The key parameters retrievable from JIRAM individual spectra are the ammonia and phosphine deep content, the water vapour relative humidity as well as the total aerosol opacity. We discuss in extent also the technical aspects related to the forward radiative transfer scheme: completeness of line databases used to generate correlated-k tables, comparison of different schemes for the treatment of aerosol scattering, assumption on clouds radiative properties and issues related to the analysis of dayside data. This work has been funded through ASI grants: I/010/10/0 and 2014-050-R.0. [1] Adriani et al., 2008 doi:10.1089/ast.2007.0167 [2] Grassi et al., 2010, doi: 10.1016/j.pss.2010.05.003 [3

  12. Allosteric Modulation of Muscarinic Acetylcholine Receptors

    Directory of Open Access Journals (Sweden)

    Esam E. El-Fakahany

    2010-08-01

    Full Text Available An allosteric modulator is a ligand that binds to an allosteric site on the receptor and changes receptor conformation to produce increase (positive cooperativity or decrease (negative cooperativity in the binding or action of an orthosteric agonist (e.g., acetylcholine. Since the identification of gallamine as the first allosteric modulator of muscarinic receptors in 1976, this unique mode of receptor modulation has been intensively studied by many groups. This review summarizes over 30 years of research on the molecular mechanisms of allosteric interactions of drugs with the receptor and for new allosteric modulators of muscarinic receptors with potential therapeutic use. Identification of positive modulators of acetylcholine binding and function that enhance neurotransmission and the discovery of highly selective allosteric modulators are mile-stones on the way to novel therapeutic agents for the treatment of schizophrenia, Alzheimer’s disease and other disorders involving impaired cognitive function.

  13. Allosteric transition: a comparison of two models

    DEFF Research Database (Denmark)

    Bindslev, Niels

    2013-01-01

    Introduction Two recent models are in use for analysis of allosteric drug action at receptor sites remote from orthosteric binding sites. One is an allosteric two-state mechanical model derived in 2000 by David Hall. The other is an extended operational model developed in 2007 by Arthur Christopo......Introduction Two recent models are in use for analysis of allosteric drug action at receptor sites remote from orthosteric binding sites. One is an allosteric two-state mechanical model derived in 2000 by David Hall. The other is an extended operational model developed in 2007 by Arthur...

  14. IS186 Insertion at a Hot Spot in the lon Promoter as a Basis for Lon Protease Deficiency of Escherichia coli B: Identification of a Consensus Target Sequence for IS186 Transposition

    OpenAIRE

    SaiSree, L.; Reddy, Manjula; J.Gowrishankar

    2001-01-01

    The radiation sensitivity of Escherichia coli B was first described more than 50 years ago, and the genetic locus responsible for the trait was subsequently identified as lon (encoding Lon protease). We now show that both E. coli B and the first reported E. coli K-12 lon mutant, AB1899, carry IS186 insertions in opposite orientations at a single site in the lon promoter region and that this site represents a natural hot spot for transposition of the insertion sequence (IS) element. Our analys...

  15. Surface-Enhanced Raman Spectroscopy of Dye and Thiol Molecules Adsorbed on Triangular Silver Nanostructures: A Study of Near-Field Enhancement, Localization of Hot-Spots, and Passivation of Adsorbed Carbonaceous Species

    Directory of Open Access Journals (Sweden)

    Manuel R. Gonçalves

    2012-01-01

    Full Text Available Surface-enhanced Raman spectroscopy (SERS of thiols and dye molecules adsorbed on triangular silver nanostructures was investigated. The SERS hot-spots are localized at the edges and corners of the silver triangular particles. AFM and SEM measurements permit to observe many small clusters formed at the edges of triangular particles fabricated by nanosphere lithography. Finite-element calculations show that near-field enhancements can reach values of more than 200 at visible wavelengths, in the gaps between small spherical particles and large triangular particles, although for the later no plasmon resonance was found at the wavelengths investigated. The regions near the particles showing strong near-field enhancement are well correlated with spatial localization of SERS hot-spots done by confocal microscopy. Silver nanostructures fabricated by thermal evaporation present strong and fast fluctuating SERS activity, due to amorphous carbon contamination. Thiols and dye molecules seem to be able to passivate the undesired SERS activity on fresh evaporated silver.

  16. Numerical simulation of the unsteady heat-transfer in a turbine-rotor in consideration of hot-spot effects. Final report; AG-Turbo-Vorhaben 1.324: Numerische Simulation des instationaeren Waermeuebergangs an einem Turbinenrotor unter Einschluss von Heissstellen. Abschlussbericht

    Energy Technology Data Exchange (ETDEWEB)

    Nuernberger, D.

    2001-07-01

    In this research project the influence of hot-gas effects, so called hot-spots, to the thermal load of high pressure turbine rotors was investigated in. Generally the total process efficiency can massively be improved by an increase of the temperature level at turbine entrance. However the temperatures of modern gas turbines can only be realized by efficient cooling techniques of the turbine blade materials. Furthermore the turbine stages close to the combustion chamber are exposed to an additional thermal loading due to the so called hot-spots. These streaks of unburned fuel entering the first turbine passages can cause a dramatic increase of local temperature in their afterburning process. For an optimized thermal design a detailed knowledge of these hot-streaks and their interaction with the unsteady flow through the turbomachinery flow is necessary. With this research program time accurate numerical investigations were performed to analyze the interaction process between the occurring hot gases and the high loaded turbine rotors. The numerical simulations started with fundamental investigation of the hot-spot and heat transfer modeling. Based on these developements threedimensional time accurate simulations for a realistic high pressure turbine configuration were performed. Herein the unsteady mechanisms of the hot gases and their influence on the heat transfer of the blade material was analyzed. In total the hot-streaks lead to a massiv increase of the thermal loading mainly on the pressure sides. (orig.) [German] Im Rahmen dieses Forschungsvorhabens wurden der Einfluss von Heissgaseffekten, sogenannten Hot-Spots auf die thermische Belastung von Turbinenrotoren numerisch untersucht. Gemeinhin sind die sehr hohen Turbineneintrittstemperaturen, deren Erhoehung einen wesentlichen Beitrag zur Verbesserung des gesamten Prozesswirkungsgrades leisten, nur durch effektive Kuehlungsmassnahmen der Schaufelwerkstoffe realisierbar. Zudem erfahren diese unmittelbar dem

  17. Modeling amperometric biosensors based on allosteric enzymes

    Directory of Open Access Journals (Sweden)

    Liutauras Ričkus

    2013-09-01

    Full Text Available Computational modeling of a biosensor with allosteric enzyme layer was investigated in this study. The operation of the biosensor is modeled using non-stationary reaction-diffusion equations. The model involves three regions: the allosteric enzyme layer where the allosteric enzyme reactions as well as then mass transport by diffusion take place, the diffusion region where the mass transport by diffusion and non-enzymatic reactions take place and the convective region in which the analyte concentration is maintained constant. The biosensor response on dependency substrate concentration, cooperativity coefficient and the diffusion layer thickness on the same parameters have been studied.

  18. 时事热点在大学英语教学中的德育教育功能%The Moral Education Function of Current Event Hot Spots in College English Teaching

    Institute of Scientific and Technical Information of China (English)

    杨剑; 王欣

    2015-01-01

    Based on the characteristics, functions and status quo of moral education in college English teaching, this paper takes three practical exploration considering current event hot spots in college English teaching: to assist college students to establish correct outlook in life and cultivate firm and indomitable perseverance; to cultivate students’ patriotism and national pride;to cultivate students’ careful, serious dedication to work and study. Current event hot spots can not only improve students’ interest in learning English, expand horizons, increase knowledge, but can have greater moral education to students in life outlook, patriotism, national pride, morality, history, culture and politics. To combine the current event hot spots with moral education in college English teaching, it is necessary to change the practice from single, non-organized individual behavior to unified, organized collective and integrated promotion.%基于大学英语教学中德育教育的特点、作用和现状,现结合时事热点在大学英语教学中推进德育教育的7个方面的研究内容,进行了三个方面的实践探索,即如何利用时事热点在大学英语教学中帮助学生树立正确人生观,培养坚韧不拔的毅力;培养学生爱国主义情怀和和民族自豪感和培养学生细致认真进行工作和学习的敬业精神。时事热点在大学英语教学的德育教育中不但能够提高学生学习英语的兴趣,扩大视野,增长知识,而且能够对学生进行系统、全面的关于人生观、爱国、民族自豪感、品德、历史、文化、政治等方面的大德育教育,所以应该把结合时事热点在大学英语教学推进德育教育的实践从单一的、无组织的教师个体行为逐渐向统一的、有组织的集体统筹推广的方向发展。

  19. Supramolecular Allosteric Cofacial Porphyrin Complexes

    International Nuclear Information System (INIS)

    Nature routinely uses cooperative interactions to regulate cellular activity. For years, chemists have designed synthetic systems that aim toward harnessing the reactivity common to natural biological systems. By learning how to control these interactions in situ, one begins to allow for the preparation of man-made biomimetic systems that can efficiently mimic the interactions found in Nature. To this end, we have designed a synthetic protocol for the preparation of flexible metal-directed supramolecular cofacial porphyrin complexes which are readily obtained in greater than 90% yield through the use of new hemilabile porphyrin ligands with bifunctional ether-phosphine or thioether-phosphine substituents at the 5 and 15 positions on the porphyrin ring. The resulting architectures contain two hemilabile ligand-metal domains (RhI or CuI sites) and two cofacially aligned porphyrins (ZnII sites), offering orthogonal functionalities and allowing these multimetallic complexes to exist in two states, 'condensed' or 'open'. Combining the ether-phosphine ligand with the appropriate RhI or CuI transition-metal precursors results in 'open' macrocyclic products. In contrast, reacting the thioether-phosphine ligand with RhI or CuI precursors yields condensed structures that can be converted into their 'open' macrocyclic forms via introduction of additional ancillary ligands. The change in cavity size that occurs allows these structures to function as allosteric catalysts for the acyl transfer reaction between X-pyridylcarbinol (where X = 2, 3, or 4) and 1-acetylimidazole. For 3- and 4-pyridylcarbinol, the 'open' macrocycle accelerates the acyl transfer reaction more than the condensed analogue and significantly more than the porphyrin monomer. In contrast, an allosteric effect was not observed for 2-pyridylcarbinol, which is expected to be a weaker binder and is unfavorably constrained inside the macrocyclic cavity.

  20. Supramolecular Allosteric Cofacial Porphyrin Complexes

    Energy Technology Data Exchange (ETDEWEB)

    Oliveri, Christopher G.; Gianneschi, Nathan C.; Nguyen, Son Binh T.; Mirkin, Chad A.; Stern, Charlotte L.; Wawrzak, Zdzislaw; Pink, Maren (NWU); (Indiana)

    2008-04-12

    Nature routinely uses cooperative interactions to regulate cellular activity. For years, chemists have designed synthetic systems that aim toward harnessing the reactivity common to natural biological systems. By learning how to control these interactions in situ, one begins to allow for the preparation of man-made biomimetic systems that can efficiently mimic the interactions found in Nature. To this end, we have designed a synthetic protocol for the preparation of flexible metal-directed supramolecular cofacial porphyrin complexes which are readily obtained in greater than 90% yield through the use of new hemilabile porphyrin ligands with bifunctional ether-phosphine or thioether-phosphine substituents at the 5 and 15 positions on the porphyrin ring. The resulting architectures contain two hemilabile ligand-metal domains (Rh{sup I} or Cu{sup I} sites) and two cofacially aligned porphyrins (Zn{sup II} sites), offering orthogonal functionalities and allowing these multimetallic complexes to exist in two states, 'condensed' or 'open'. Combining the ether-phosphine ligand with the appropriate Rh{sup I} or Cu{sup I} transition-metal precursors results in 'open' macrocyclic products. In contrast, reacting the thioether-phosphine ligand with RhI or CuI precursors yields condensed structures that can be converted into their 'open' macrocyclic forms via introduction of additional ancillary ligands. The change in cavity size that occurs allows these structures to function as allosteric catalysts for the acyl transfer reaction between X-pyridylcarbinol (where X = 2, 3, or 4) and 1-acetylimidazole. For 3- and 4-pyridylcarbinol, the 'open' macrocycle accelerates the acyl transfer reaction more than the condensed analogue and significantly more than the porphyrin monomer. In contrast, an allosteric effect was not observed for 2-pyridylcarbinol, which is expected to be a weaker binder and is unfavorably constrained inside the

  1. 超高强度热成形钢电阻点焊的数值模拟%Numerical Simulation in Resistance Spot Welding of Ultra-High Strength Hot-Formed Steel

    Institute of Scientific and Technical Information of China (English)

    郑文; 王敏; 孔谅; 程轩挺; 孙游; 雷鸣

    2012-01-01

    Based on the software SORPAS, an axial symmetric finite element model for the resistance spot welding process (RSW) of ultra-high strength hot-formed steel (UHSS) was established. By numerical simulation, change rules of the temperature field, the nugget size, etc during the spot welding were dis-covered quantitatively. Comparing the numerical simulation results with the experimental measured ones, it was proved that the finite element model is feasible. It can also provide guidance for the RSW process of the UHSS.%利用SORPAS软件对超高强度热成形钢板建立了描述点焊熔核形成过程的轴对称有限元模型.通过数值模拟,定量揭示了热成形钢点焊过程中温度场、熔核直径等过程量的变化规律.对比模拟计算与实测结果表明,该模型是可行的,可为超高强度热成形钢的电阻点焊提供指导.

  2. Bier spots

    Directory of Open Access Journals (Sweden)

    Ahu Yorulmaz,

    2015-10-01

    Full Text Available Also called as physiologic anemic macules, Bier spots are small, hypopigmented irregularly shaped macules against a background of diffuse erythema, which creates an appearance of speckled vascular mottling of the skin. Bier spots most commonly appear on distal portions of the limbs though there are case reports describing diffuse involvement, which also affect trunk and mucous membranes of the patient. Although the exact pathophysiological mechanisms underlying Bier spots still need to be elucidated, Bier spots have been suggested to be a vascular anomaly caused by vasoconstriction of small vessels. In addition, several diseases have been proposed to be associated with Bier spots, including scleroderma renal crisis, cryoglobulinemia, Peutz-Jeghers syndrome, alopecia areata and hypoplasia of the aorta, although it has not been shown whether these associations are casual or coincidental. The clinical presentation of Bier spots is quite typical. These tiny whitish macules easily become prominent when the affected limb is placed in a dependent position and fade away when the limb is raised. Here we report a case of Bier spots in a 32-year-old male patient with characteristical clinical manifestations.

  3. Parameter optimization of dissimilar resistance spot welding on ultra-high strength hot-stamped steel and mild steel by numerical simulation

    Institute of Scientific and Technical Information of China (English)

    Wen ZHENG; Min WANG; Liang KONG; Xuanting CHENG; Ming LEI

    2012-01-01

    In this study,a coupled axisymmetric finite element model (FEM) was built to simulate the resistance spot welding (RSW) process between ultra-high strength hotstamped (UHSS) and mild steel by SORPAS software.Via simulating this process,the temperature distribution and dynamic temperature curves of the welding area were studied,and welding spatter phenomena were predicted and validated by comparing them with experimental results.By adjusting the welding parameters in numerical simulation,appropriate welding parameters were achieved.Moreover,the mechanical properties of the welding joints under the optimized conditions were also compared with those of not optimized.The study results have already been applied in a manufacturing production.It can also provide guidance for the RSW on UHSS and mild steel.

  4. Rational Engineering of Enzyme Allosteric Regulation through Sequence Evolution Analysis

    OpenAIRE

    Jae-Seong Yang; Sang Woo Seo; Sungho Jang; Gyoo Yeol Jung; Sanguk Kim

    2012-01-01

    Control of enzyme allosteric regulation is required to drive metabolic flux toward desired levels. Although the three-dimensional (3D) structures of many enzyme-ligand complexes are available, it is still difficult to rationally engineer an allosterically regulatable enzyme without decreasing its catalytic activity. Here, we describe an effective strategy to deregulate the allosteric inhibition of enzymes based on the molecular evolution and physicochemical characteristics of allosteric ligan...

  5. Breakdown of Fermi liquid behavior near the hot spots in a two-dimensional model: A two-loop renormalization group analysis

    International Nuclear Information System (INIS)

    Motivated by a recent experimental observation of a nodal liquid on both single crystals and thin films of Bi2Sr2CaCu2O8+δ by Chatterjee et al. [Nature Phys. 6 (2010) 99], we perform a field-theoretical renormalization group (RG) analysis of a two-dimensional model such that only eight points located near the “hot spots” on the Fermi surface are retained, which are directly connected by spin density wave ordering wavevector. We derive RG equations up to two-loop order describing the flow of renormalized couplings, quasiparticle weight, several order-parameter response functions, and uniform spin and charge susceptibilities of the model. We find that while the order-parameter susceptibilities investigated here become non-divergent at two loops, the quasiparticle weight vanishes in the low-energy limit, indicating a breakdown of Fermi liquid behavior at this RG level. Moreover, both uniform spin and charge susceptibilities become suppressed in the scaling limit which indicate gap openings in both spin and charge excitation spectra of the model

  6. Breakdown of Fermi liquid behavior near the hot spots in a two-dimensional model: A two-loop renormalization group analysis

    Science.gov (United States)

    de Carvalho, Vanuildo S.; Freire, Hermann

    2013-10-01

    Motivated by a recent experimental observation of a nodal liquid on both single crystals and thin films of Bi2Sr2CaCu2O8 + δ by Chatterjee et al. [Nature Phys. 6 (2010) 99], we perform a field-theoretical renormalization group (RG) analysis of a two-dimensional model such that only eight points located near the “hot spots” on the Fermi surface are retained, which are directly connected by spin density wave ordering wavevector. We derive RG equations up to two-loop order describing the flow of renormalized couplings, quasiparticle weight, several order-parameter response functions, and uniform spin and charge susceptibilities of the model. We find that while the order-parameter susceptibilities investigated here become non-divergent at two loops, the quasiparticle weight vanishes in the low-energy limit, indicating a breakdown of Fermi liquid behavior at this RG level. Moreover, both uniform spin and charge susceptibilities become suppressed in the scaling limit which indicate gap openings in both spin and charge excitation spectra of the model.

  7. Age Spots

    Science.gov (United States)

    ... for treating age spots include: Improved appearance. Enhanced self-esteem. Promotion of better skin health. What you need ... 480px View Render 320px View Connect with ASDS: Facebook LinkedIn YouTube Twitter Quick Links About ASDS Advocacy ...

  8. Allosteric modulation of caspase 3 through mutagenesis

    Directory of Open Access Journals (Sweden)

    Jad Walters

    2012-06-01

    Full Text Available A mutation in the allosteric site of the caspase 3 dimer interface of Val266 to histidine abolishes activity of the enzyme, and models predict that the mutation mimics the action of small molecule allosteric inhibitors by preventing formation of the active site. Mutations were coupled to His266 at two sites in the interface, E124A and Y197C. We present results from X-ray crystallography, enzymatic activity and molecular dynamics simulations for seven proteins, consisting of single, double and triple mutants. The results demonstrate that considering allosteric inhibition of caspase 3 as a shift between discrete ‘off-state’ or ‘on-state’ conformations is insufficient. Although His266 is accommodated in the interface, the structural defects are propagated to the active site through a helix on the protein surface. A more comprehensive view of allosteric regulation of caspase 3 requires the representation of an ensemble of inactive states and shows that subtle structural changes lead to the population of the inactive ensemble.

  9. Allosteric Modulation of Muscarinic Acetylcholine Receptors

    Czech Academy of Sciences Publication Activity Database

    Jakubík, Jan; El-Fakahany, E. E.

    2010-01-01

    Roč. 3, č. 9 (2010), s. 2838-2860. ISSN 1424-8247 R&D Projects: GA ČR GA305/09/0681 Institutional research plan: CEZ:AV0Z50110509 Keywords : muscarinic acetylcholine receptors * allosteric modulation * Alzheimer ´s disease Subject RIV: CE - Biochemistry

  10. Characterizing seasonal variability of storm events based on very high frequency monitoring of hydrological and chemical variables: comparing patterns in hot spots and hot moments for nutrient and sediment export

    Science.gov (United States)

    Fovet, Ophelie; Thelusma, Gilbert; Humbert, Guillaume; Dupas, Rémi; Faucheux, Mikael; Gilliet, Nicolas; Hamon, Yannick; Jaffrezic, Anne; Grimaldi, Catherine; Gruau, Gerard

    2016-04-01

    Storm events are critical hot moments of emission for several dissolved and particulate chemical species at major stake for water quality (e.g. dissolved organic carbon DOC, suspended sediments, phosphorus). During such events, the solutes or particles are exported from heterogeneous sources through various pathways to stream leading to specific integrated signals at the outlet characterized by very short dynamics. This is merely true in headwater catchments where the total duration of such events ranges over 10h to 3 days, with very quick variations in stream flow and concentrations at the outlet occurring in a few hours. Thus for investigating properly event processes, high frequency monitoring of flow and water quality is required. We analysed 103 storm events in a 5 km2 agricultural headwater catchment, part of the AgrHys Observatory, on the basis of a 3-year-long data set which combined meterological (Rainfall), hydrological (flow and piezometry), and water quality (turbidity, conductivity, DOC and NO3 concentrations) data recorded at very high frequencies (from 1 to 20 min) thanks to dedicated sensors. We proposed a range of quantitative storm descriptors for characterizing input (rainfall), antecedent and initial conditions (groundwater levels and saturated area), and stream response in terms of level and dynamics of flow (Q), groundwater levels, and concentrations (C) but also the C-Q relationships. Three intra annual periods have been previously defined for base flow dynamic according to shallow groundwater table variations so that they correspond to different connectivity status in the catchment. The seasonal and inter-annual variability of the storm events have been analysed using the descriptors and based on these predefined periods. Results show that the hydrological flowpaths and the consequent storm chemistry were controlled by the hydrological base flow regime rather than by the rain input characteristics. This highlights that the exports of NO3

  11. Thickness of the oceanic crust and the mantle transition zone in the vicinity of the Tristan da Cunha hot spot estimated from ocean-bottom and ocean-island seismometer receiver functions

    Science.gov (United States)

    Geissler, Wolfram; Jokat, Wilfried; Jegen, Marion; Baba, Kiyoshi

    2016-04-01

    According to classical plume theory, the Tristan da Cunha hotspot is thought to have played a major role in the rifting of the South Atlantic margins and the creation of the aseismic Walvis Ridge by impinging at the base of the continental lithosphere shortly before or during the breakup of the South Atlantic margins. However, Tristan da Cunha is enigmatic as it cannot be clearly identified as a hot spot but may also be classified as a more shallow type of anomaly that may actually have been caused by the opening of the South Atlantic. The equivocal character of Tristan da Cunha is largely due to a lack of geophysical and petrological data in this region. We therefore staged a multi-disciplinary geophysical study of the region by acquiring passive marine electromagnetic and seismic data, and bathymetric data within the framework of the SPP1375 South Atlantic Margin Processes and Links with onshore Evolution (SAMPLE) funded by the German Science foundation. The experiment included two ship expeditions onboard the German R/V MARIA S. MERIAN in 2012 and 2013. In our contribution we will present results on the thickness of the oceanic crust in the vicinity of the Tristan da Cunha archipelago derived from ocean-bottom seismometer data. Using the Ps receiver function method we estimate a thickness of 5 to 7 km for the oceanic crust at 17 ocean-bottom stations surrounding the islands in an area where the ocean floor has an age of approximately 10 to 30 Ma (from west to east). This indicates normal to slightly lowered magmatic activity at the mid-ocean ridge during the crust formation. There seems to be no major contribution of a mantle plume to the melting conditions at the ridge, which should cause the formation of thickened oceanic crust. The magmatic activity at the archipelago and surrounding seamounts seems to have only local effects on the crustal thickness. Furthermore, we imaged the mantle transition zone discontinuities analysing receiver functions at the

  12. Automated direct sequencing of the iduronate-2 sulfatase gene reveals a vast spectrum of mutations causing Hunter syndrome (mucopolysaccharidosis type II) and a {open_quotes}hot spot{close_quotes} at R468

    Energy Technology Data Exchange (ETDEWEB)

    Whitley, C.B; Jonsson, J.J.; Aronovich, E.L. [Univ. of Minnesota Medical School, Minneapolis, MN (United States)

    1994-09-01

    Hunter syndrome is an X-linked recessive, lethal disease resulting from deficiency of iduronate-2-sulfatase (IDS) catalytic activity. Because of low reproductive fitness, most affected individuals are expected to have new mutations. Most of such defects are anticipated to be single base pair (bp) changes; however, several previous studies utilizing Southern analysis of RT-PCR have identified numerous large gene deletions in patients having the {open_quotes}severe form{close_quotes} with neurologic disease. To investigate the spectrum of IDS mutations, we have developed a method of automated direct sequencing of RT-PCR products representing the entire IDS coding region. Of 19 patients studied by this approach, only 1 had an IDS coding region which did not contain a mutation; 1 had a single bp insertion; 1 had a 2 bp deletion; and 13 had single-base substitutions. Of the 13 having single base substitutions, 2 resulted in aberrant splicing. Only 1 patient had a complete gene deletion; in view of previous reports, there was a surprising lack of major gene deletions. Notably, a CpG dinucleotide at R468 was identified as a {open_quotes}hot spot{close_quotes} for mutation. Five unrelated individuals had substitutions at this site which thus accounted for 28% of all mutations in this series: R468W (3 patients) and R468Q (2 patients). MspI digestion provided a method of rapid diagnosis and determination of heterozygote status for such R468 mutations. Genotype-phenotype correlations in this R468 group are not yet possible because of confounding information, i.e., there are both {open_quotes}mild{close_quotes} and {open_quotes}severe{close_quotes} patients in this group and some have co-existing neurologic diseases. This approach of gene sequencing appears to be necessary, and sufficient, to characterize the vast spectrum of mutations in Hunter syndrome.

  13. 3-(imidazo[1,2-a:5,4-b']dipyridin-2-yl)aniline inhibits pestivirus replication by targeting a hot spot drug binding pocket in the RNA-dependent RNA polymerase.

    Science.gov (United States)

    Musiu, Simone; Leyssen, Pieter; Froeyen, Mathy; Chezal, Jean-Michel; Neyts, Johan; Paeshuyse, Jan

    2016-05-01

    The compound 3-(imidazo[1,2-a:5,4-b']dipyridin-2-yl)aniline (CF02334) was identified as a selective inhibitor of the cytopathic effect (CPE) caused by bovine viral diarrhea virus (BVDV) in a virus-cell-based assay. The EC50-values for inhibition of CPE, viral RNA synthesis and the production of infectious virus progeny were 13.0 ± 0.6 μM, 2.6 ± 0.9 μM and 17.8 ± 0.6 μM, respectively. CF02334 was found to be inactive in the hepatitis C subgenomic replicon system. CF02334-resistant BVDV was obtained and was found to carry the N264D mutation in the viral RNA-dependent RNA polymerase (RdRp). Molecular modeling revealed that N264D is located in a small cavity near the fingertip domain of the pestivirus polymerase. CF02334-resistant BVDV was proven to be cross-resistant to BPIP, AG110 and LZ37, inhibitors that have previously been described to target the same region of the BVDV RdRp. CF02334 did not inhibit the in vitro activity of recombinant BVDV RdRp, but did inhibit the activity of BVDV replication complexes. Taken together, these observations indicate that CF02334 likely interacts with the fingertip of the pestivirus RdRp at the same position as BPIP, AG110 and LZ37, which marks this region of the viral polymerase as a "hot spot" for inhibition of pestivirus replication. PMID:26970496

  14. 从医院管理几个热点问题谈医疗服务质量%Analysis of Medical Service Quality from Several Hot Spots of Hospital Management

    Institute of Scientific and Technical Information of China (English)

    易学明

    2011-01-01

    Medical service quality is the core and etemal theme of hospital management. The article deeply discussed the improvement of medical service quality from five aspects, which included correctly treat the conflict of social responsibility and self - profit so as to convert the thought of medical service; rightly recognize the problem of reasonable scale and exceed expansion so as to enhance inherent medical quality; erect the idea of service con-sciousness and service art so as to master the communication skiU; objectively handle the relationship of high - techand basic quality so as to fulfill the increasing requirement. We expect to focus on the improvement of medical serv-ice quality from the several hot spots to promote the hospital sustainable and healthy development.%医疗服务质量是医院管理的核心和永恒主题,本文从合理解决社会责任与自身利益的矛盾,转变医疗服务理念;正确看待过度扩张与适度规模的现象,加强内涵质量建设;科学树立以病为本与以人为本的理念,优化医疗服务流程;极力实现服务意识与服务艺术的交融,掌握医患沟通技巧;客观认识高新技术与基础质量的关系,满足持续发展需求五个方面就医疗服务质量建设进行了深入的探讨.以期从医院管理的几个热点问题来关注医疗服务质量,促进医院健康持续快速发展.

  15. 铜锌超氧化物歧化酶知识基础及前沿热点分析%Knowledge base, research front and hot spot analysis of Cu-Zn superoxide dismutase

    Institute of Scientific and Technical Information of China (English)

    邹昱; 李彦君; 杨爽; 张庆文

    2015-01-01

    genetics. So far more than 100 kinds of SOD1 gene mutations have been found. OBJECTIVE:To analyze the hot spot, research front and knowledge base of amyotrophic lateral sclerosis visualy. METHODS:Totaly 4 693 relevant articles published from 2005 to 2014 were retrieved from Web of Science in ISI with “Cu-Zn superoxide dismutase” or “SOD1” as search keywords. With the aid of CiteSpace III software, the visualization mapping of the network in co-cited articles and keywords was drawn to reveal knowledge base, hot spots and research front of SOD1. The parameters include the number of published papers and citations within 10 years, distribution of research countries and institutions, main source journals, research area of highly cited papers, keywords with high-frequency and emerging keywords with high-frequency in recent 5 years. RESULTS AND CONCLUSION:The number of published papers and citations in a year showed a trend of sustained growth. United State, China and Japan rank the top three in this area, in which Chinese Academy of Sciences has a great influence among the research institutions. The research fields of SOD1 focus on neurosciences and neurology, biochemistry and molecular biology and so on. The high impact factors of journals with a large number of articles reflect the importance and innovation of this research. Ten high-cited articles consist of the knowledge base on SOD1, directing to the finding of different sites of SOD1 mutation and the measurement of protein concentrations and activity of SOD. The hot spots of SOD1 mainly focus on oxidative stress, familial amyotrophic lateral sclerosis caused by SOD1 mutation and different types of transgenic animal models. The research fronts mainly focus on the finding of pathogenesis in amyotrophic lateral sclerosis, such as the aggregation of TDP-43, the interaction between astrocytes and motor neurons, optineurin and the inhibitor of nuclear factor-κB, hexanucleotide repeat expansion in C9ORF72 and autophagy.

  16. Mongolian spots

    Directory of Open Access Journals (Sweden)

    Divya Gupta

    2013-01-01

    Full Text Available Mongolian spots (MS are birthmarks that are present at birth and their most common location is sacrococcygeal or lumbar area. Lesions may be single or multiple and usually involve < 5% total body surface area. They are macular and round, oval or irregular in shape. The color varies from blue to greenish, gray, black or a combination of any of the above. The size varies from few to more than 20 centimetres. Pigmentation is most intense at the age of one year and gradually fades thereafter. It is rarely seen after the age of 6 years. Aberrant MS over occiput, temple, mandibular area, shoulders and limbs may be confused with other dermal melanocytoses and bruises secondary to child abuse, thus necessitating documentation at birth. Although regarded as benign, recent data suggest that MS may be associated with inborn errors of metabolism and neurocristopathies. Mongolian spots usually resolve by early childhood and hence no treatment is generally needed if they are located in the sacral area. However, sometimes it may be required for extrasacral lesions for cosmesis.

  17. Assesment methods for ammonia hot-spot

    Czech Academy of Sciences Publication Activity Database

    Cellier, P.; Theobald, M. R.; Asman, W.; Bealey, W.; Bittmann, S.; Dragosits, U.; Fudala, J.; Jones, M.; Loefstroem, P.; Loubet, B.; Misselbrook, T.; Rihm, B.; Smith, K.; Střižík, M.; van der Hoek, K.; van Jaarsveld, H.; Walker, J.; Zelinger, Zdeněk

    Dordrecht: Springer, 2009 - (Sutton, M.; Reis, S.; Baker, S.), s. 391-407 ISBN 978-1-4020-9120-9 R&D Projects: GA MŠk OC 111 Institutional research plan: CEZ:AV0Z40400503 Keywords : ammonia * NH3 dispersion * physical chemistry Subject RIV: CF - Physical ; Theoretical Chemistry

  18. "Hot Spots" of Land Atmosphere Coupling

    Science.gov (United States)

    Koster, Randal D.; Dirmeyer, Paul A.; Guo, Zhi-Chang; Bonan, Gordan; Chan, Edmond; Cox, Peter; Gordon, T. C.; Kanae, Shinjiro; Kowalczyk, Eva; Lawrence, David

    2004-01-01

    Previous estimates of land-atmosphere interaction (the impact of soil moisture on precipitation) have been limited by a severe paucity of relevant observational data and by the model-dependence of the various computational estimates. To counter this limitation, a dozen climate modeling groups have recently performed the same highly-controlled numerical experiment as part of a coordinated intercomparison project. This allows, for the first time ever, a superior multi-model approach to the estimation of the regions on the globe where precipitation is affected by soil moisture anomalies during Northern Hemisphere summer. Such estimation has many potential benefits; it can contribute, for example, to seasonal rainfall prediction efforts.

  19. Exploiting protein flexibility to predict the location of allosteric sites

    Directory of Open Access Journals (Sweden)

    Panjkovich Alejandro

    2012-10-01

    Full Text Available Abstract Background Allostery is one of the most powerful and common ways of regulation of protein activity. However, for most allosteric proteins identified to date the mechanistic details of allosteric modulation are not yet well understood. Uncovering common mechanistic patterns underlying allostery would allow not only a better academic understanding of the phenomena, but it would also streamline the design of novel therapeutic solutions. This relatively unexplored therapeutic potential and the putative advantages of allosteric drugs over classical active-site inhibitors fuel the attention allosteric-drug research is receiving at present. A first step to harness the regulatory potential and versatility of allosteric sites, in the context of drug-discovery and design, would be to detect or predict their presence and location. In this article, we describe a simple computational approach, based on the effect allosteric ligands exert on protein flexibility upon binding, to predict the existence and position of allosteric sites on a given protein structure. Results By querying the literature and a recently available database of allosteric sites, we gathered 213 allosteric proteins with structural information that we further filtered into a non-redundant set of 91 proteins. We performed normal-mode analysis and observed significant changes in protein flexibility upon allosteric-ligand binding in 70% of the cases. These results agree with the current view that allosteric mechanisms are in many cases governed by changes in protein dynamics caused by ligand binding. Furthermore, we implemented an approach that achieves 65% positive predictive value in identifying allosteric sites within the set of predicted cavities of a protein (stricter parameters set, 0.22 sensitivity, by combining the current analysis on dynamics with previous results on structural conservation of allosteric sites. We also analyzed four biological examples in detail, revealing

  20. Metastatic susceptibility locus, an 8p hot-spot for tumour progression disrupted in colorectal liver metastases: 13 candidate genes examined at the DNA, mRNA and protein level

    International Nuclear Information System (INIS)

    Mortality from colorectal cancer is mainly due to metastatic liver disease. Improved understanding of the molecular events underlying metastasis is crucial for the development of new methods for early detection and treatment of colorectal cancer. Loss of chromosome 8p is frequently seen in colorectal cancer and implicated in later stage disease and metastasis, although a single metastasis suppressor gene has yet to be identified. We therefore examined 8p for genes involved in colorectal cancer progression. Loss of heterozygosity analyses were used to map genetic loss in colorectal liver metastases. Candidate genes in the region of loss were investigated in clinical samples from 44 patients, including 6 with matched colon normal, colon tumour and liver metastasis. We investigated gene disruption at the level of DNA, mRNA and protein using a combination of mutation, semi-quantitative real-time PCR, western blotting and immunohistochemical analyses. We mapped a 2 Mb region of 8p21-22 with loss of heterozygosity in 73% of samples; 8/11 liver metastasis samples had loss which was not present in the corresponding matched primary colon tumour. 13 candidate genes were identified for further analysis. Both up and down-regulation of 8p21-22 gene expression was associated with metastasis. ADAMDEC1 mRNA and protein expression decreased during both tumourigenesis and tumour progression. Increased STC1 and LOXL2 mRNA expression occurred during tumourigenesis. Liver metastases with low DcR1/TNFRSF10C mRNA expression were more likely to present with extrahepatic metastases (p = 0.005). A novel germline truncating mutation of DR5/TNFRSF10B was identified, and DR4/TNFRSF10A SNP rs4872077 was associated with the development of liver metastases (p = 0.02). Our data confirm that genes on 8p21-22 are dysregulated during colorectal cancer progression. Interestingly, however, instead of harbouring a single candidate colorectal metastasis suppressor 8p21-22 appears to be a hot-spot for

  1. Metastatic susceptibility locus, an 8p hot-spot for tumour progression disrupted in colorectal liver metastases: 13 candidate genes examined at the DNA, mRNA and protein level

    Directory of Open Access Journals (Sweden)

    Hall David A

    2008-07-01

    colorectal metastasis suppressor 8p21-22 appears to be a hot-spot for tumour progression, encoding at least 13 genes with a putative role in carcinoma development. Thus, we propose that this region of 8p comprises a metastatic susceptibility locus involved in tumour progression whose disruption increases metastatic potential.

  2. Rational engineering of enzyme allosteric regulation through sequence evolution analysis.

    Directory of Open Access Journals (Sweden)

    Jae-Seong Yang

    Full Text Available Control of enzyme allosteric regulation is required to drive metabolic flux toward desired levels. Although the three-dimensional (3D structures of many enzyme-ligand complexes are available, it is still difficult to rationally engineer an allosterically regulatable enzyme without decreasing its catalytic activity. Here, we describe an effective strategy to deregulate the allosteric inhibition of enzymes based on the molecular evolution and physicochemical characteristics of allosteric ligand-binding sites. We found that allosteric sites are evolutionarily variable and comprised of more hydrophobic residues than catalytic sites. We applied our findings to design mutations in selected target residues that deregulate the allosteric activity of fructose-1,6-bisphosphatase (FBPase. Specifically, charged amino acids at less conserved positions were substituted with hydrophobic or neutral amino acids with similar sizes. The engineered proteins successfully diminished the allosteric inhibition of E. coli FBPase without affecting its catalytic efficiency. We expect that our method will aid the rational design of enzyme allosteric regulation strategies and facilitate the control of metabolic flux.

  3. Allosteric small-molecule kinase inhibitors

    DEFF Research Database (Denmark)

    Wu, Peng; Clausen, Mads Hartvig; Nielsen, Thomas E.

    2015-01-01

    Small-molecule kinase inhibitors are invaluable targeted therapeutics for the treatment of various human diseases, especially cancers. While the majority of approved and developed preclinical small-molecule inhibitors are characterized as type I or type II inhibitors that target the ATP......-binding pocket of kinases, the remarkable sequential and structural similarity among ATP pockets renders the selective inhibition of kinases a daunting challenge. Therefore, targeting allosteric pockets of kinases outside the highly conversed ATP pocket has been proposed as a promising alternative to overcome...

  4. Hot Money, Hot Potato

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    International hot money flowing into Chinese capital markets has caught the attention of Chinese watchdogs The Chinese are not the only ones feasting on the thriving property and stock markets. Apparently, these markets are the targets of international h

  5. Allosteric Regulation by a Critical Membrane

    CERN Document Server

    Kimchi, Ofer; Machta, Benjamin B

    2016-01-01

    Many of the processes that underly neural computation are carried out by ion channels embedded in the plasma membrane, a two-dimensional liquid that surrounds all cells. Recent experiments have demonstrated that this membrane is poised close to a liquid-liquid critical point in the Ising universality class. Here we use both exact and stochastic techniques on the lattice Ising model to explore the ramifications of proximity to criticality for proteins that are allosterically coupled to Ising composition modes. Owing to diverging generalized susceptibilities, such a protein's activity becomes strongly influenced by perturbations that influence the two relevant parameters of the critical point, especially the critical temperature. In addition, the protein's kinetics acquire a range of time scales from its surrounding membrane, naturally leading to non-Markovian dynamics.

  6. Allosteric modulation of G-protein coupled receptors

    DEFF Research Database (Denmark)

    Jensen, Anders A.; Spalding, Tracy A

    2004-01-01

    The superfamily of G-protein coupled receptors (GPCRs) has more than 1000 members and is the largest family of proteins in the body. GPCRs mediate signalling of stimuli as diverse as light, ions, small molecules, peptides and proteins and are the targets for many pharmaceuticals. Most GPCR ligands...... are believed to activate (agonists) or inhibit (competitive antagonists) receptor signalling by binding the receptor at the same site as the endogenous agonist, the orthosteric site. In contrast, allosteric ligands modulate receptor function by binding to different regions in the receptor, allosteric...... outlines the current status and perspectives of allosteric modulation of GPCR function with emphasis on the pharmacology of endogenous and synthesised modulators, their receptor interactions and the therapeutic prospects of allosteric ligands compared to orthosteric ligands....

  7. A unified framework and an alternative mechanism for allosteric regulation

    CERN Document Server

    Xing, J

    2007-01-01

    Allosteric regulation is an important property for many proteins. Several models have been proposed to explain the allosteric effect, such as the concerted MWC (Monod, Wyman, Changeux) model, the sequential KNF (Koshland, Nemethy, Filmer) model, and recent population shift models. Here we discuss a unified theoretical framework to describe allosteric effects. The existing models appear as special cases of the framework. The theoretical work also reveals an alternative mechanism currently overlooked. Theoretically it is possible that the reactivity of a protein is limited by some internal conformational change step (due to slow effective diffusion along rugged potential surfaces). Effector binding may modify the ruggedness and thus the protein dynamics and reactivity. Compared to conventional models, the new mechanism has less requirements on the mechanical properties of an allosteric protein to propagate mechanical signals over long distances. Thus some signal transduction proteins may adopt the new mechanism...

  8. Designing allosteric control into enzymes by chemical rescue of structure

    OpenAIRE

    Deckert, Katelyn; Budiardjo, S. Jimmy; Brunner, Luke C.; Lovell, Scott; Karanicolas, John

    2012-01-01

    Ligand-dependent activity has been engineered into enzymes for purposes ranging from controlling cell morphology to reprogramming cellular signaling pathways. Where these successes have typically fused a naturally allosteric domain to the enzyme of interest, here we instead demonstrate an approach for designing a de novo allosteric effector site directly into the catalytic domain of an enzyme. This approach is distinct from traditional chemical rescue of enzymes in that it relies on disruptio...

  9. Pathways of allosteric regulation in Hsp70 chaperones

    OpenAIRE

    Kityk, Roman; Vogel, Markus; Schlecht, Rainer; Bukau, Bernd; Mayer, Matthias P

    2015-01-01

    Central to the protein folding activity of Hsp70 chaperones is their ability to interact with protein substrates in an ATP-controlled manner, which relies on allosteric regulation between their nucleotide-binding (NBD) and substrate-binding domains (SBD). Here we dissect this mechanism by analysing mutant variants of the Escherichia coli Hsp70 DnaK blocked at distinct steps of allosteric communication. We show that the SBD inhibits ATPase activity by interacting with the NBD through a highly ...

  10. Positive allosteric action of eburnamonine on cardiac muscarinic acetylcholine receptors.

    Science.gov (United States)

    Proska, J; Tucek, S

    1996-06-01

    It was discovered recently that alcuronium and strychnine (which is a precursor of alcuronium) allosterically increase the affinity of cardiac muscarinic receptors for the antagonist, N-methylscopolamine. We have now investigated the effects of l-eburnamonine and vincamine, which are both closely related to strychnine. In experiments on rat heart atria, l-eburnamonine was found to increase the binding of [3H]N-methylscopolamine with Ehlert's cooperativity coefficient alpha = 0.35, which indicates that the strength of its allosteric action is close to that of alcuronium and strychnine (alpha = 0.31 and 0.44, respectively). However, the affinity of l-eburnamonine for the cardiac muscarinic receptors is lower than the affinities of alcuronium and strychnine (KAR = 22.6 microM, 0.15 microM, and 3.4 microM, respectively). In spite of its extremely close similarity to l-eburnamonine, vincamine has a negative allosteric effect on the binding of [3H]N-methylscopolamine (alpha = 4.1; KAR = 22.8 microM). It is likely that a systematic investigation of the allosteric effects of the analogues of strychnine will not only yield new allosteric effectors on muscarinic receptors, but also clarify the structural features responsible for the direction (positive or negative) of their allosteric effect. PMID:8813554

  11. Rocky Mountain spotted fever

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/000654.htm Rocky Mountain spotted fever To use the sharing features on this page, please enable JavaScript. Rocky Mountain spotted fever is a disease caused by a ...

  12. Study on the Model for Regulation of the Allosteric Enzyme Activity

    Institute of Scientific and Technical Information of China (English)

    LI,Qian-Zhong(李前忠); LUO,Liao-Fu(罗辽复); ZHANG,Li-Rong(张利绒)

    2002-01-01

    The effects of activator molecule and repressive molecule on binding process between allosteric enzyme and substrate are disused by considering the heterotropic effect of the regulating molecule that binds to allosteric enzyme. A model of allosteric enzyme with heterotropic effect is presented. The cooperativity and anticooperativity in the regulation process are studied.

  13. Pathways of allosteric regulation in Hsp70 chaperones.

    Science.gov (United States)

    Kityk, Roman; Vogel, Markus; Schlecht, Rainer; Bukau, Bernd; Mayer, Matthias P

    2015-01-01

    Central to the protein folding activity of Hsp70 chaperones is their ability to interact with protein substrates in an ATP-controlled manner, which relies on allosteric regulation between their nucleotide-binding (NBD) and substrate-binding domains (SBD). Here we dissect this mechanism by analysing mutant variants of the Escherichia coli Hsp70 DnaK blocked at distinct steps of allosteric communication. We show that the SBD inhibits ATPase activity by interacting with the NBD through a highly conserved hydrogen bond network, and define the signal transduction pathway that allows bound substrates to trigger ATP hydrolysis. We identify variants deficient in only one direction of allosteric control and demonstrate that ATP-induced substrate release is more important for chaperone activity than substrate-stimulated ATP hydrolysis. These findings provide evidence of an unexpected dichotomic allostery mechanism in Hsp70 chaperones and provide the basis for a comprehensive mechanical model of allostery in Hsp70s. PMID:26383706

  14. SpotADAPT

    DEFF Research Database (Denmark)

    Kaulakiene, Dalia; Thomsen, Christian; Pedersen, Torben Bach;

    2015-01-01

    Amazon Web Services (AWS). The users aiming for the spot market are presented with many instance types placed in multiple datacenters in the world, and thus it is difficult to choose the optimal deployment. In this paper, we propose the framework SpotADAPT (Spot-Aware (re-)Deployment of Analytical...... Processing Tasks) which is designed to help users by first, estimating the workload execution time on different AWS instance types, and, second, proposing the deployment (i.e., specific availability zone, instance type, pricing model) aligned with user-provided optimization goals (fastest or cheapest...... execution within boundaries). Moreover, during the execution of the workload, SpotADAPT suggests a redeployment if the current spot instance gets terminated by Amazon or a better deployment becomes possible due to fluctuations of the spot prices. The approach is evaluated using the actual execution times of...

  15. Talking on Current Situation and Selection of Strategies of Tourist Scenic Spot's Channel Managenent-Taking Mingyueshan&Hot Spring Scenic Spot as an Exanple%浅析旅游景区渠道管理的现状及策略选择——以明月山温泉风景名胜区为例

    Institute of Scientific and Technical Information of China (English)

    彭礴; 舒莉芬

    2011-01-01

    It's necessary to build sales channel that can make target customers knowing and buying the products of tourist scenic spot. However, the project of the channel management of the scenic spot was just carded out in many places, and it is in the exploratory stage, So, it's important for scenic spot marketing that how to build a scientific and effective sales channel. Intangibility of tourism products inevitably makes the difference of tourism products circulation fi'om physical products circulation, for the reason that we can't simply copy the theory and experience of physical products distribution. This paper will probe current situation and strategies of channel management of the scenic spot by learning the experience of Mingyueshan&Hot Spring Scenic spot's channel managements.%旅游景区产品要被目标顾客所接受和购买,渠道建设是必不可少的。然而,在许多地方景区渠道建设工作还刚刚起步,处在摸索阶段,如何构建一条科学有效的销售渠道,成为景区营销工作的一个重要内容。旅游产品的无形性,必然使得旅游产品流通与实体产品流通不同,在构建渠道过程中,这一特性应该体现出来,因而,简单照搬实体产品分销的理论和经验是不够的。借助对明月山温泉风景名胜区渠道工作的经验,本文探讨景区渠道管理的现状及策略的选择。

  16. Dark spots along slowly scaling chains of plasmonic nanoparticles

    CERN Document Server

    Zito, Gianluigi; Sasso, Antonio

    2016-01-01

    We numerically investigate the optical response of slowly scaling linear chains of mismatched silver nanoparticles. Hybridized plasmon chain resonances manifest unusual local field distributions around the nanoparticles that result from symmetry breaking of the geometry. Importantly, we find localization patterns characterized by bright hot-spots alternated by what we term \\textit{dark} spots. A dark spot is associated to dark plasmons that have collinear and antiparallel dipole moments along the chain. As a result, the field amplification in the dark interjunction gap is extinguished for incident polarization parallel to the chain axis. Despite the strong plasmonic coupling, the nanoparticles on the sides of this dark gap experience a dramatic asymmetric field amplification with amplitude gain contrast $> 2 \\times 10^2$. Remarkably, also for polarization orthogonal to the axis, gap hot-spots form on resonance.

  17. Metal ion coupled protein folding and allosteric motions

    Science.gov (United States)

    Wang, Wei

    2014-03-01

    Many proteins need the help of cofactors for their successful folding and functioning. Metal ions, i.e., Zn2+, Ca2+, and Mg2+ etc., are typical biological cofactors. Binding of metal ions can reshape the energy landscapes of proteins, thereby modifying the folding and allosteric motions. For example, such binding may make the intrinsically disordered proteins have funneled energy landscapes, consequently, ensures their spontaneous folding. In addition, the binding may activate certain biological processes by inducing related conformational changes of regulation proteins. However, how the local interactions involving the metal ion binding can induce the global conformational motions of proteins remains elusive. Investigating such question requires multiple models with different details, including quantum mechanics, atomistic models, and coarse grained models. In our recent work, we have been developing such multiscale methods which can reasonably model the metal ion binding induced charge transfer, protonation/deprotonation, and large conformational motions of proteins. With such multiscale model, we elucidated the zinc-binding induced folding mechanism of classical zinc finger and the calcium-binding induced dynamic symmetry breaking in the allosteric motions of calmodulin. In addition, we studied the coupling of folding, calcium binding and allosteric motions of calmodulin domains. In this talk, I will introduce the above progresses on the metal ion coupled protein folding and allosteric motions. We thank the finacial support from NSFC and the 973 project.

  18. Extracellular loop 2 of the free Fatty Acid receptor 2 mediates allosterism of a phenylacetamide ago-allosteric modulator

    DEFF Research Database (Denmark)

    Smith, Nicola J; Ward, Richard J; Stoddart, Leigh A; Hudson, Brian D; Kostenis, Evi; Ulven, Trond; Morris, Joanne C; Tränkle, Christian; Tikhonova, Irina G; Adams, David R; Milligan, Graeme

    2011-01-01

    Allosteric agonists are powerful tools for exploring the pharmacology of closely related G protein-coupled receptors that have nonselective endogenous ligands, such as the short chain fatty acids at free fatty acid receptors 2 and 3 (FFA2/GPR43 and FFA3/GPR41, respectively). We explored the molec...

  19. Watermarking spot colors

    Science.gov (United States)

    Alattar, Osama M.; Reed, Alastair M.

    2003-06-01

    Watermarking of printed materials has usually focused on process inks of cyan, magenta, yellow and black (CMYK). In packaging, almost three out of four printed materials include spot colors. Spot colors are special premixed inks, which can be produced in a vibrant range of colors, often outside the CMYK color gamut. In embedding a watermark into printed material, a common approach is to modify the luminance value of each pixel in the image. In the case of process color work pieces, the luminance change can be scaled to the C, M, Y and K channels using a weighting function, to produce the desired change in luminance. In the case of spot color art designs, there is only one channel available and the luminance change is applied to this channel. In this paper we develop a weighting function to embed the watermark signal across the range of different spot colors. This weighting function normalizes visibility effect and signal robustness across a wide range of different spot colors. It normalizes the signal robustness level over the range of an individual spot color"s intensity levels. Further, it takes into account the sensitivity of the capturing device to the different spot colors.

  20. Evidence of a short-range incommensurate d-wave charge order from a fermionic two-loop renormalization group calculation of a 2D model with hot spots

    International Nuclear Information System (INIS)

    The two-loop renormalization group (RG) calculation is considerably extended here for the two-dimensional (2D) fermionic effective field theory model, which includes only the so-called “hot spots” that are connected by the spin-density-wave (SDW) ordering wavevector on a Fermi surface generated by the 2D t−t′ Hubbard model at low hole doping. We compute the Callan–Symanzik RG equation up to two loops describing the flow of the single-particle Green’s function, the corresponding spectral function, the Fermi velocity, and some of the most important order-parameter susceptibilities in the model at lower energies. As a result, we establish that–in addition to clearly dominant SDW correlations–an approximate (pseudospin) symmetry relating a short-range incommensurated-wave charge order to the d-wave superconducting order indeed emerges at lower energy scales, which is in agreement with recent works available in the literature addressing the 2D spin-fermion model. We derive implications of this possible electronic phase in the ongoing attempt to describe the phenomenology of the pseudogap regime in underdoped cuprates

  1. Mononucleosis spot test

    Science.gov (United States)

    Monospot test; Heterophile antibody test; Heterophile agglutination test; Paul-Bunnell test; Forssman antibody test ... The mononucleosis spot test is done when symptoms of mononucleosis are ... Fatigue Fever Large spleen (possibly) Sore throat Tender ...

  2. Spotted Seal Distribution Map

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This dataset contains GIS layers that depict the known spatial distributions (i.e., ranges) and reported breeding areas of spotted seals (Phoca largha). It was...

  3. Arc cathode spots

    International Nuclear Information System (INIS)

    Arc spots are usually highly unstable and jump statistically over the cathode surface. In a magnetic field parallel to the surface, preferably they move in the retrograde direction; i.e., opposite to the Lorentzian rule. If the field is inclined with respect to the surface, the spots drift away at a certain angle with respect to the proper retrograde direction (Robson drift motion). These well-known phenomena are explained by one stability theory

  4. Experimental study of bulk storage ignition by hot points

    OpenAIRE

    Janes, Agnès; Carson, Douglas

    2013-01-01

    International audience An experimental study of ignition risk due to hot points in the storage of bulk materials is required to ensure fire safety. Many parameters are involved in this phenomenon: nature of the material, storage volume and temperature, type and size of hot point, etc. The aim of this study is to determine critical ignition temperatures of hot spots embedded in powder materials for different conditions and with several types of hot points. Materials selected for this study ...

  5. Transformation from “Carbon Valley” to a “Post-Carbon Society” in a Climate Change Hot Spot: the Coalfields of the Hunter Valley, New South Wales, Australia

    Directory of Open Access Journals (Sweden)

    Geoffrey R. Evans

    2008-06-01

    Full Text Available This paper examines the possibilities for transformation of a climate-change hot spot—the coal-producing Hunter Region of New South Wales, Australia—using complex adaptive systems (CAS theory. It uses CAS theory to understand the role of coal in the region’s history and efforts to strengthen the ecological, economic, and social resilience of the region’s coal industry in the face of demands for a shift from fossil fuel dependency to clean, renewable energy and genuine resilience and sustainability. It uses CAS theory to understand ways in which the resilience of two alternative futures, labeled “Carbon Valley” and “Post-Carbon Society” (Heinberg 2004, might evolve. The paper discusses ways in which changes implemented through the efforts of local communities at local, smaller scales of the nested systems seek to influence the evolution of adaptive cycles of the system at the local, national, and global scales. It identifies the influences of “attractors,” defined as factors driving the evolution of the system, that are influential across the panarchy. These include climate change threats, markets, regulatory regimes, political alliances, and local concerns about the environmental and social impacts of the Hunter’s coal dependency. These factors are weakening the apparent resilience of the coal industry, which is being propped up by the coal industry corporations, labor unions, and governments to maintain coal dependency in the Carbon Valley. Moreover, they are creating an alternative basin of attraction in which a Post-Carbon Society might emerge from the system’s evolutionary processes.

  6. Western Cultural and Creative Industry Research:Academic Community and Hot-spot Evolution%西方文化创意产业研究院学术群体与热点演进

    Institute of Scientific and Technical Information of China (English)

    马仁锋; 梁贤军; 姜炎鹏

    2015-01-01

    采用www.isiknowledge.com数据库收录的2001年~2013年期间2431篇文化创意产业相关文献,利用Citespace、Histcite两软件进行文献引用关系和知识图谱的可视化处理,分析热点文献的研究机构与研究领域,解读西方文化创意产业研究热点演进趋势。研究发现:①西方文化创意产业研究学术群体主要集中在澳大利亚、英国与美国,具体而言澳大利亚以昆士兰科技大学、昆士兰大学、麦考瑞大学、悉尼科技大学的艺术、设计与传媒为阵营的文化创意产业研究和以伍伦贡大学的文化地理学与城市文化经济等领域研究阵营,而英国则以利兹大学、格拉斯哥大学为首的艺术、设计、传媒和文化地理学二元并进的研究阵营,南加利亚福尼亚大学为代表的美国影视文化研究阵营;②文化创意产业研究力量与地方创意经济技发展水平存在两种匹配类型:澳大利亚呈协调发展,而美国、英国的文化创意产业研究机构与地方创意经济发展水平存在空间错位;③西方文化创意产业研究的高频作者是Chris Gibson、Jason Potts、Stuart Cunningham、Terry Flew,但单篇文献被引率最高的则是Florida R L、Caves R E、Scott A J、Hesmondhalgh D、Pratt AC;④文化创意产业研究热点是创意力、创意集群、创意阶层、创意城市、创意网络、国家创意产业政策等,且形成以Richard Florida为核心创意阶层理论派;以Charles Landry为核心创意城市假说派;以John Howkins、Stuart Cunningham等为核心的艺术、设计、媒介及其商业价值衍生派。%In order to explore the trend and hot issues objectively, a database has been set up from the source of www.isiknowledge.com with its 2431 papers about cultural and creative industry from 2001 to 2013.The institutes, country and cited reference citation relationship are visualized on the Cites-pace II and Histcite platform

  7. Prediction of allosteric sites and mediating interactions through bond-to-bond propensities

    CERN Document Server

    Amor, Benjamin R C; Yaliraki, Sophia N; Barahona, Mauricio

    2016-01-01

    Allosteric regulation is central to many biochemical processes. Allosteric sites provide a target to fine-tune protein activity, yet we lack computational methods to predict them. Here, we present an efficient graph-theoretical approach for identifying allosteric sites and the mediating interactions that connect them to the active site. Using an atomistic graph with edges weighted by covalent and non-covalent bond energies, we obtain a bond-to-bond propensity that quantifies the effect of instantaneous bond fluctuations propagating through the protein. We use this propensity to detect the sites and communication pathways most strongly linked to the active site, assessing their significance through quantile regression and comparison against a reference set of 100 generic proteins. We exemplify our method in detail with three well-studied allosteric proteins: caspase-1, CheY, and h-Ras, correctly predicting the location of the allosteric site and identifying key allosteric interactions. Consistent prediction of...

  8. Allosteric Pathways in the PPARγ-RXRα nuclear receptor complex

    Science.gov (United States)

    Ricci, Clarisse G.; Silveira, Rodrigo L.; Rivalta, Ivan; Batista, Victor S.; Skaf, Munir S.

    2016-01-01

    Understanding the nature of allostery in DNA-nuclear receptor (NR) complexes is of fundamental importance for drug development since NRs regulate the transcription of a myriad of genes in humans and other metazoans. Here, we investigate allostery in the peroxisome proliferator-activated/retinoid X receptor heterodimer. This important NR complex is a target for antidiabetic drugs since it binds to DNA and functions as a transcription factor essential for insulin sensitization and lipid metabolism. We find evidence of interdependent motions of Ω-loops and PPARγ-DNA binding domain with contacts susceptible to conformational changes and mutations, critical for regulating transcriptional functions in response to sequence-dependent DNA dynamics. Statistical network analysis of the correlated motions, observed in molecular dynamics simulations, shows preferential allosteric pathways with convergence centers comprised of polar amino acid residues. These findings are particularly relevant for the design of allosteric modulators of ligand-dependent transcription factors.

  9. The Allosteric Switching Mechanism in Bacteriophage MS2

    CERN Document Server

    Perkett, Matthew R

    2015-01-01

    In this article we use all-atom simulations to elucidate the mechanisms underlying conformational switching and allostery within the coat protein of the bacteriophage MS2. Assembly of most icosahedral virus capsids requires that the capsid protein adopt different conformations at precise locations within the capsid. It has been shown that a 19 nucleotide stem loop (TR) from the MS2 genome acts as an allosteric effector, guiding conformational switching of the coat protein during capsid assembly. Since the principal conformational changes occur far from the TR binding site, it is important to understand the molecular mechanism underlying this allosteric communication. To this end, we use all-atom simulations with explicit water combined with a path sampling technique to sample the MS2 coat protein conformational transition, in the presence and absence of TR-binding. The calculations find that TR binding strongly alters the transition free energy profile, leading to a switch in the favored conformation. We disc...

  10. Allosteric process of human glucokinase conducive to fight against diabetes

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ More than 200 million people worldwide have diabetes. In China alone, about 60 million people are suffering from the disease.Fortunately, scientists are pushing back its boundaries. For instance, a recent study by CAS researchers may shed new light on the treatment of the disease by making cutting-edge progress on studies of the allosteric process of human glucokinase, which has been published by the latest issue of the Proceedings of National Academy of Sciences.

  11. Are AMPA Receptor Positive Allosteric Modulators Potential Pharmacotherapeutics for Addiction?

    OpenAIRE

    Lucas R. Watterson; M. Foster Olive

    2013-01-01

    Positive allosteric modulators (PAMs) of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are a diverse class of compounds that increase fast excitatory transmission in the brain. AMPA PAMs have been shown to facilitate long-term potentiation, strengthen communication between various cortical and subcortical regions, and some of these compounds increase the production and release of brain-derived neurotrophic factor (BDNF) in an activity-dependent manner. Through these m...

  12. Allosteric activation of coagulation factor VIIa visualized by hydrogen exchange

    DEFF Research Database (Denmark)

    Rand, Kasper Dyrberg; Jørgensen, Thomas; Olsen, Ole H; Persson, Egon; Jensen, Ole; Stennicke, Henning R; Andersen, Mette

    2006-01-01

    Coagulation factor VIIa (FVIIa) is a serine protease that, after binding to tissue factor (TF), plays a pivotal role in the initiation of blood coagulation. We used hydrogen exchange monitored by mass spectrometry to visualize the details of FVIIa activation by comparing the exchange kinetics of ...... provide novel insights into the cofactor-induced activation of this important protease and reveal the potential for allosteric regulation in the trypsin family of proteases....

  13. Divergent allosteric patterns verify the regulatory paradigm for aspartate transcarbamylase.

    Science.gov (United States)

    Wales, M E; Madison, L L; Glaser, S S; Wild, J R

    1999-12-17

    The native Escherichia coli aspartate transcarbamoylase (ATCase, E.C. 2.1.3.2) provides a classic allosteric model for the feedback inhibition of a biosynthetic pathway by its end products. Both E. coli and Erwinia herbicola possess ATCase holoenzymes which are dodecameric (2(c3):3(r2)) with 311 amino acid residues per catalytic monomer and 153 and 154 amino acid residues per regulatory (r) monomer, respectively. While the quaternary structures of the two enzymes are identical, the primary amino acid sequences have diverged by 14 % in the catalytic polypeptide and 20 % in the regulatory polypeptide. The amino acids proposed to be directly involved in the active site and nucleotide binding site are strictly conserved between the two enzymes; nonetheless, the two enzymes differ in their catalytic and regulatory characteristics. The E. coli enzyme has sigmoidal substrate binding with activation by ATP, and inhibition by CTP, while the E. herbicola enzyme has apparent first order kinetics at low substrate concentrations in the absence of allosteric ligands, no ATP activation and only slight CTP inhibition. In an apparently important and highly conserved characteristic, CTP and UTP impose strong synergistic inhibition on both enzymes. The co-operative binding of aspartate in the E. coli enzyme is correlated with a T-to-R conformational transition which appears to be greatly reduced in the E. herbicola enzyme, although the addition of inhibitory heterotropic ligands (CTP or CTP+UTP) re-establishes co-operative saturation kinetics. Hybrid holoenzymes assembled in vivo with catalytic subunits from E. herbicola and regulatory subunits from E. coli mimick the allosteric response of the native E. coli holoenzyme and exhibit ATP activation. The reverse hybrid, regulatory subunits from E. herbicola and catalytic subunits from E. coli, exhibited no response to ATP. The conserved structure and diverged functional characteristics of the E. herbicola enzyme provides an opportunity

  14. The structural basis of ATP as an allosteric modulator.

    OpenAIRE

    Shaoyong Lu; Wenkang Huang; Qi Wang; Qiancheng Shen; Shuai Li; Ruth Nussinov; Jian Zhang

    2014-01-01

    Adenosine-5'-triphosphate (ATP) is generally regarded as a substrate for energy currency and protein modification. Recent findings uncovered the allosteric function of ATP in cellular signal transduction but little is understood about this critical behavior of ATP. Through extensive analysis of ATP in solution and proteins, we found that the free ATP can exist in the compact and extended conformations in solution, and the two different conformational characteristics may be responsible for ATP...

  15. The Structural Basis of ATP as an Allosteric Modulator

    OpenAIRE

    Lu, Shaoyong; Huang, Wenkang; Wang, Qi; Shen, Qiancheng; Li, Shuai; Nussinov, Ruth; Zhang, Jian

    2014-01-01

    Adenosine-5’-triphosphate (ATP) is generally regarded as a substrate for energy currency and protein modification. Recent findings uncovered the allosteric function of ATP in cellular signal transduction but little is understood about this critical behavior of ATP. Through extensive analysis of ATP in solution and proteins, we found that the free ATP can exist in the compact and extended conformations in solution, and the two different conformational characteristics may be responsible for ATP...

  16. Computational approaches to detect allosteric pathways in transmembrane molecular machines.

    Science.gov (United States)

    Stolzenberg, Sebastian; Michino, Mayako; LeVine, Michael V; Weinstein, Harel; Shi, Lei

    2016-07-01

    Many of the functions of transmembrane proteins involved in signal processing and transduction across the cell membrane are determined by allosteric couplings that propagate the functional effects well beyond the original site of activation. Data gathered from breakthroughs in biochemistry, crystallography, and single molecule fluorescence have established a rich basis of information for the study of molecular mechanisms in the allosteric couplings of such transmembrane proteins. The mechanistic details of these couplings, many of which have therapeutic implications, however, have only become accessible in synergy with molecular modeling and simulations. Here, we review some recent computational approaches that analyze allosteric coupling networks (ACNs) in transmembrane proteins, and in particular the recently developed Protein Interaction Analyzer (PIA) designed to study ACNs in the structural ensembles sampled by molecular dynamics simulations. The power of these computational approaches in interrogating the functional mechanisms of transmembrane proteins is illustrated with selected examples of recent experimental and computational studies pursued synergistically in the investigation of secondary active transporters and GPCRs. This article is part of a Special Issue entitled: Membrane Proteins edited by J.C. Gumbart and Sergei Noskov. PMID:26806157

  17. Allosteric indicator displacement enzyme assay for a cyanogenic glycoside.

    Science.gov (United States)

    Jose, D Amilan; Elstner, Martin; Schiller, Alexander

    2013-10-18

    Indicator displacement assays (IDAs) represent an elegant approach in supramolecular analytical chemistry. Herein, we report a chemical biosensor for the selective detection of the cyanogenic glycoside amygdalin in aqueous solution. The hybrid sensor consists of the enzyme β-glucosidase and a boronic acid appended viologen together with a fluorescent reporter dye. β-Glucosidase degrades the cyanogenic glycoside amygdalin into hydrogen cyanide, glucose, and benzaldehyde. Only the released cyanide binds at the allosteric site of the receptor (boronic acid) thereby inducing changes in the affinity of a formerly bound fluorescent indicator dye at the other side of the receptor. Thus, the sensing probe performs as allosteric indicator displacement assay (AIDA) for cyanide in water. Interference studies with inorganic anions and glucose revealed that cyanide is solely responsible for the change in the fluorescent signal. DFT calculations on a model compound revealed a 1:1 binding ratio of the boronic acid and cyanide ion. The fluorescent enzyme assay for β-glucosidase uses amygdalin as natural substrate and allows measuring Michaelis-Menten kinetics in microtiter plates. The allosteric indicator displacement assay (AIDA) probe can also be used to detect cyanide traces in commercial amygdalin samples. PMID:24123550

  18. Zinc as Allosteric Ion Channel Modulator: Ionotropic Receptors as Metalloproteins.

    Science.gov (United States)

    Peralta, Francisco Andrés; Huidobro-Toro, Juan Pablo

    2016-01-01

    Zinc is an essential metal to life. This transition metal is a structural component of many proteins and is actively involved in the catalytic activity of cell enzymes. In either case, these zinc-containing proteins are metalloproteins. However, the amino acid residues that serve as ligands for metal coordination are not necessarily the same in structural proteins compared to enzymes. While crystals of structural proteins that bind zinc reveal a higher preference for cysteine sulfhydryls rather than histidine imidazole rings, catalytic enzymes reveal the opposite, i.e., a greater preference for the histidines over cysteines for catalysis, plus the influence of carboxylic acids. Based on this paradigm, we reviewed the putative ligands of zinc in ionotropic receptors, where zinc has been described as an allosteric modulator of channel receptors. Although these receptors do not strictly qualify as metalloproteins since they do not normally bind zinc in structural domains, they do transitorily bind zinc at allosteric sites, modifying transiently the receptor channel's ion permeability. The present contribution summarizes current information showing that zinc allosteric modulation of receptor channels occurs by the preferential metal coordination to imidazole rings as well as to the sulfhydryl groups of cysteine in addition to the carboxyl group of acid residues, as with enzymes and catalysis. It is remarkable that most channels, either voltage-sensitive or transmitter-gated receptor channels, are susceptible to zinc modulation either as positive or negative regulators. PMID:27384555

  19. Zinc as Allosteric Ion Channel Modulator: Ionotropic Receptors as Metalloproteins

    Science.gov (United States)

    Peralta, Francisco Andrés; Huidobro-Toro, Juan Pablo

    2016-01-01

    Zinc is an essential metal to life. This transition metal is a structural component of many proteins and is actively involved in the catalytic activity of cell enzymes. In either case, these zinc-containing proteins are metalloproteins. However, the amino acid residues that serve as ligands for metal coordination are not necessarily the same in structural proteins compared to enzymes. While crystals of structural proteins that bind zinc reveal a higher preference for cysteine sulfhydryls rather than histidine imidazole rings, catalytic enzymes reveal the opposite, i.e., a greater preference for the histidines over cysteines for catalysis, plus the influence of carboxylic acids. Based on this paradigm, we reviewed the putative ligands of zinc in ionotropic receptors, where zinc has been described as an allosteric modulator of channel receptors. Although these receptors do not strictly qualify as metalloproteins since they do not normally bind zinc in structural domains, they do transitorily bind zinc at allosteric sites, modifying transiently the receptor channel’s ion permeability. The present contribution summarizes current information showing that zinc allosteric modulation of receptor channels occurs by the preferential metal coordination to imidazole rings as well as to the sulfhydryl groups of cysteine in addition to the carboxyl group of acid residues, as with enzymes and catalysis. It is remarkable that most channels, either voltage-sensitive or transmitter-gated receptor channels, are susceptible to zinc modulation either as positive or negative regulators. PMID:27384555

  20. Allosteric function and dysfunction of the prion protein.

    Science.gov (United States)

    Linden, Rafael; Cordeiro, Yraima; Lima, Luis Mauricio T R

    2012-04-01

    Transmissible spongiform encephalopathies (TSEs) are neurodegenerative diseases associated with progressive oligo- and multimerization of the prion protein (PrP(C)), its conformational conversion, aggregation and precipitation. We recently proposed that PrP(C) serves as a cell surface scaffold protein for a variety of signaling modules, the effects of which translate into wide-range functional consequences. Here we review evidence for allosteric functions of PrP(C), which constitute a common property of scaffold proteins. The available data suggest that allosteric effects among PrP(C) and its partners are involved in the assembly of multi-component signaling modules at the cell surface, impose upon both physiological and pathological conformational responses of PrP(C), and that allosteric dysfunction of PrP(C) has the potential to entail progressive signal corruption. These properties may be germane both to physiological roles of PrP(C), as well as to the pathogenesis of the TSEs and other degenerative/non-communicable diseases. PMID:21984610

  1. Identification of the Allosteric Regulatory Site of Insulysin

    Energy Technology Data Exchange (ETDEWEB)

    Noinaj, Nicholas; Bhasin, Sonia K.; Song, Eun Suk; Scoggin, Kirsten E.; Juliano, Maria A.; Juliano, Luiz; Hersh, Louis B.; Rodgers, David W. (U. Sao Paulo); (Kentucky)

    2012-05-25

    Insulin degrading enzyme (IDE) is responsible for the metabolism of insulin and plays a role in clearance of the A{beta} peptide associated with Alzheimer's disease. Unlike most proteolytic enzymes, IDE, which consists of four structurally related domains and exists primarily as a dimer, exhibits allosteric kinetics, being activated by both small substrate peptides and polyphosphates such as ATP. The crystal structure of a catalytically compromised mutant of IDE has electron density for peptide ligands bound at the active site in domain 1 and a distal site in domain 2. Mutating residues in the distal site eliminates allosteric kinetics and activation by a small peptide, as well as greatly reducing activation by ATP, demonstrating that this site plays a key role in allostery. Comparison of the peptide bound IDE structure (using a low activity E111F IDE mutant) with unliganded wild type IDE shows a change in the interface between two halves of the clamshell-like molecule, which may enhance enzyme activity by altering the equilibrium between closed and open conformations. In addition, changes in the dimer interface suggest a basis for communication between subunits. Our findings indicate that a region remote from the active site mediates allosteric activation of insulysin by peptides. Activation may involve a small conformational change that weakens the interface between two halves of the enzyme.

  2. PPR Great Red Spot Temperature Map

    Science.gov (United States)

    1996-01-01

    This map shows temperature for the region around Jupiter's Great Red Spot and an area to the northwest. It corresponds to a level in Jupiter's atmosphere where the pressure is 1/2 of the of the Earth's at sea level (500 millibars), the same as it is near 6000 meters (20,000 feet) above sea level on Earth. The center of Great Red Spot appears colder than the surrounding areas, where air from below is being brought up. The 'panhandle' to the northwest is warmer and drier, and the gases there are descending, so it is much clearer of clouds. Compare this map to one released earlier at a higher place in the atmosphere (250 millibars or 12000 meters). The center of the Great Red Spot is warmer lower in the atmosphere, and a white 'hot spot' appears in this image that is not present at the higher place. This map was made from data taken by the Photopolarimeter/Radiometer (PPR) instrument on June 26, 1996.Launched in October 1989, Galileo entered orbit around Jupiter on December 7, 1995. The spacecraft's mission is to conduct detailed studies of the giant planet, its largest moons and the Jovian magnetic environment.JPL manages the Galileo mission for NASA's Office of Space Science, Washington, D.C.This image and other images and data received from Galileo are posted on the World Wide Web, on the Galileo mission home page at URL http://galileo.jpl.nasa.gov.

  3. The therapeutic potential of allosteric ligands for free fatty acid sensitive GPCRs

    DEFF Research Database (Denmark)

    Hudson, Brian D; Ulven, Trond; Milligan, Graeme

    2013-01-01

    identifying allosteric leads and their often flat or confusing SAR. The present review will consider the advantages and challenges associated with allosteric GPCR ligands, and examine how the particular properties of these ligands may be exploited to uncover the therapeutic potential for free fatty acid...

  4. The satellite-based remote sensing of particulate matter (PM) in support to urban air quality: PM variability and hot spots within the Cordoba city (Argentina) as revealed by the high-resolution MAIAC-algorithm retrievals applied to a ten-years dataset (2

    Science.gov (United States)

    Della Ceca, Lara Sofia; Carreras, Hebe A.; Lyapustin, Alexei I.; Barnaba, Francesca

    2016-04-01

    some areas of the city (hot spots). These hot spots were put in relation with changes in vehicular traffic flows after the construction of new roads in the urban area. The monthly-resolved analysis showed a marked seasonal cycle, evidencing the influence of both meteorological conditions and season-dependent sources on the AOD parameter. For instance, in the Cordoba rural area an increase of AOD is observed during March-April, which is the soybean harvesting period, the main agricultural activity in the region. Furthermore, higher AOD signals were observed in the vicinity of main roads during summer months (December to February), likely related to the increase in vehicular traffic flow due to tourism. Long-range transport is also shown to play a role at the city scale, as high AODs throughout the study area are observed between August and November. In fact, this is the biomass-burning season over the Amazon region and over most of South America, with huge amounts of fire-related particles injected into the atmosphere and transported across the continent [4]. References [1] WHO, 2013; REVIHAAP, Project Technical Report [2] Lyapustin et al., 2011; doi: 10.1029/2010JD014986 [3] Holben et al., 1998, doi:10.1016/S0034-4257(98)00031-5 [4] Castro et al., 2013; doi:10.1016/j.atmosres.2012.10.026

  5. Activation and Allosteric Modulation of Human μ Opioid Receptor in Molecular Dynamics.

    Science.gov (United States)

    Bartuzi, Damian; Kaczor, Agnieszka A; Matosiuk, Dariusz

    2015-11-23

    Allosteric protein modulation has gained increasing attention in drug design. Its application as a mechanism of action could bring forth safer and more effective medicines. Targeting opioid receptors with allosteric modulators can result in better treatment of pain, depression, and respiratory and immune disorders. In this work we use recent reports on negative modulators of μ opioid receptor as a starting point for identification of allosteric sites and mechanisms of opioid receptor modulation using homology modeling and docking and molecular dynamics studies. An allosteric binding site description is presented. Results suggest a shared binding region for lipophilic allosteric ligands, reveal possible differences in the modulation mechanism between cannabinoids and salvinorin A, and show ambiguous properties of the latter. Also, they emphasize the importance of native-like environment in molecular dynamics simulations and uncover relationships between modulator and orthosteric ligand binding and receptor behavior. Relationships between ligands, transmission switch, and hydrophobic lock are analyzed. PMID:26517559

  6. Allosteric activation mechanism of the cys-loop receptors

    Institute of Scientific and Technical Information of China (English)

    Yong-chang CHANG; Wen WU; Jian-liang ZHANG; Yao HUANG

    2009-01-01

    Binding of a neurotransmitter to its ionotropic receptor opens a distantly located ion channel, a process termed allosteric activation. Here we review recent advances in the molecular mechanism by which the cys-loop receptors are activated with emphasis on the best studied nicotinic acetylcholine receptors (nAChRs). With a combination of affinity labeling, mutagenesis, electrophysiology, kinetic modeling, electron microscopy (EM), and crystal structure analysis, the allosteric activation mechanism is emerging. Specifically, the binding domain and gating domain are interconnected by an allosteric activation network. Agonist binding induces conformational changes, resulting in the rotation of a β sheet of amino-terminal domain and outward movement of loop 2, loop F, and cys-loop, which are coupled to the M2-M3 linker to pull the channel to open. However, there are still some controversies about the movement of the channel-lining domain M2. Nine angstrom resolution EM structure of a nAChR imaged in the open state suggests that channel opening is the result of rotation of the M2 domain. In contrast, recent crystal structures of bacterial homologues of the cys-loop receptor family in apparently open state have implied an M2 tilting model with pore dilation and quaternary twist of the whole pentameric receptor. An elegant study of the nAChR using protonation scanning of M2 domain supports a similar pore dilation activation mechanism with minimal rotation of M2. This remains to be validated with other approaches including high resolution structure determination of the mammalian cys-loop receptors in the open state.

  7. Bioinformatic scaling of allosteric interactions in biomedical isozymes

    Science.gov (United States)

    Phillips, J. C.

    2016-09-01

    Allosteric (long-range) interactions can be surprisingly strong in proteins of biomedical interest. Here we use bioinformatic scaling to connect prior results on nonsteroidal anti-inflammatory drugs to promising new drugs that inhibit cancer cell metabolism. Many parallel features are apparent, which explain how even one amino acid mutation, remote from active sites, can alter medical results. The enzyme twins involved are cyclooxygenase (aspirin) and isocitrate dehydrogenase (IDH). The IDH results are accurate to 1% and are overdetermined by adjusting a single bioinformatic scaling parameter. It appears that the final stage in optimizing protein functionality may involve leveling of the hydrophobic limits of the arms of conformational hydrophilic hinges.

  8. Allosteric modulators of the hERG K{sup +} channel

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Zhiyi, E-mail: z.yu@lacdr.leidenuniv.nl; Klaasse, Elisabeth, E-mail: elisabethklaasse@hotmail.com; Heitman, Laura H., E-mail: l.h.heitman@lacdr.leidenuniv.nl; IJzerman, Adriaan P., E-mail: ijzerman@lacdr.leidenuniv.nl

    2014-01-01

    Drugs that block the cardiac K{sup +} channel encoded by the human ether-à-go-go gene (hERG) have been associated with QT interval prolongation leading to proarrhythmia, and in some cases, sudden cardiac death. Because of special structural features of the hERG K{sup +} channel, it has become a promiscuous target that interacts with pharmaceuticals of widely varying chemical structures and a reason for concern in the pharmaceutical industry. The structural diversity suggests that multiple binding sites are available on the channel with possible allosteric interactions between them. In the present study, three reference compounds and nine compounds of a previously disclosed series were evaluated for their allosteric effects on the binding of [{sup 3}H]astemizole and [{sup 3}H]dofetilide to the hERG K{sup +} channel. LUF6200 was identified as an allosteric inhibitor in dissociation assays with both radioligands, yielding similar EC{sub 50} values in the low micromolar range. However, potassium ions increased the binding of the two radioligands in a concentration-dependent manner, and their EC{sub 50} values were not significantly different, indicating that potassium ions behaved as allosteric enhancers. Furthermore, addition of potassium ions resulted in a concentration-dependent leftward shift of the LUF6200 response curve, suggesting positive cooperativity and distinct allosteric sites for them. In conclusion, our investigations provide evidence for allosteric modulation of the hERG K{sup +} channel, which is discussed in the light of findings on other ion channels. - Highlights: • Allosteric modulators on the hERG K{sup +} channel were evaluated in binding assays. • LUF6200 was identified as a potent allosteric inhibitor. • Potassium ions were found to behave as allosteric enhancers. • Positive cooperativity and distinct allosteric sites for them were proposed.

  9. Spotting a fake

    International Nuclear Information System (INIS)

    Diamonds are highly prized for their dazzling appearance and hardness, but would you be able to spot one that had been created in the laboratory? Simon Lawson describes how physics-based techniques can distinguish between natural and synthetic stones. For the last 50 years or so we have been able to make synthetic diamonds that replicate the superlative physical and chemical properties of natural diamonds, and these are used largely for industrial applications. But in the mind of the consumer, there is far more to a diamond than its hardness or brilliance. Research commissioned by the Diamond Trading Company (DTC) has shown that 94% of women surveyed prefer natural diamonds over synthetic ones as a symbol of love, possibly as a result of the immense age of natural stones. One of the key research activities at the DTC is therefore to ensure that synthetic diamonds can be spotted easily. (U.K.)

  10. Poisson Spot with Magnetic Levitation

    Science.gov (United States)

    Hoover, Matthew; Everhart, Michael; D'Arruda, Jose

    2010-01-01

    In this paper we describe a unique method for obtaining the famous Poisson spot without adding obstacles to the light path, which could interfere with the effect. A Poisson spot is the interference effect from parallel rays of light diffracting around a solid spherical object, creating a bright spot in the center of the shadow.

  11. Hot particles - a hot topic

    International Nuclear Information System (INIS)

    The health effects of hot particles have remained largely unknown. The nuclear power plant accident in Chernobyl spread hot particles into the environment, and findings by a Finnish research team show that their health effects have generally been underestimated. The essential feature from the point of view of health effect is that hot particles cause a very high radiation dose in a very small area in the surrounding organ or tissue. Up to now it has generally been thought that a dose limited within a small area would be even less dangerous than the same dose distributed throughout the body. Hot particles, however, are very effective in causing malignant changes in cells. Beta radiation emitted by hot particles causes permanent mutations in the genetic constitution, or the DNA molecule, of cells. At the same time they effectively stimulate the multiplication of cells by first causing the death of cells in their vicinity. When this results in a chronic wound around the hot particle, cells that are further away from the particle try to heal the wound by dividing rapidly. These cells have received high radiation doses but managed to survive. The mutated cell is thus able to build a malignant clone, which can develop further into cancer. Exposure to hot particles takes place mostly through the skin and, in particular, through the respiratory tract Most of the particles that were carried to Finland from Chernobyl were small in both size and activity. They became deposited onto the ground within a few days, and thus disappeared quickly from breathing air (orig.)

  12. Flying spot scanner

    International Nuclear Information System (INIS)

    An improved flying spot x-ray scanning equipment is described which includes a grid controlled x-ray tube and associated collimators for producing a pencil beam of x-rays. It is possible to control the position of the scan field relative to the patient, to control the width of the scan field and also to independently achieve an arbitary variation in the longitudinal dimension of the scan field. (U.K.)

  13. Spot- Zombie Filtering System

    Directory of Open Access Journals (Sweden)

    Arathy Rajagopal

    2015-10-01

    Full Text Available A major security challenge on the Internet is the existence of the large number of compromised machines. Such machines have been increasingly used to launch various security attacks including spamming and spreading malware, DDoS, and identity theft. These compromised machines are called "Zombies". In general E-mail applications and providers uses spam filters to filter the spam messages. Spam filtering is a technique for discriminating the genuine message from the spam messages. The attackers send the spam messages to the targeted machine by exalting the filters, which causes the increase in false positives and false negatives. We develop an effective spam zombie detection system named SPOT by monitoring outgoing messages of a network. SPOT focuses on the number of outgoing messages that are originated or forwarded by each computer on a network to identify the presence of Zombies. SPOT is designed based on a powerful statistical tool called Sequential Probability Ratio Test, which has bounded false positive and false negative error rates.

  14. Spot- Zombie Filtering System

    Directory of Open Access Journals (Sweden)

    Arathy Rajagopal

    2014-01-01

    Full Text Available A major security challenge on the Internet is the existence of the large number of compromised machines. Such machines have been increasingly used to launch various security attacks including spamming and spreading malware, DDoS, and identity theft. These compromised machines are called “Zombies”. In general E-mail applications and providers uses spam filters to filter the spam messages. Spam filtering is a technique for discriminating the genuine message from the spam messages. The attackers send the spam messages to the targeted machine by exalting the filters, which causes the increase in false positives and false negatives. We develop an effective spam zombie detection system named SPOT by monitoring outgoing messages of a network. SPOT focuses on the number of outgoing messages that are originated or forwarded by each computer on a network to identify the presence of Zombies. SPOT is designed based on a powerful statistical tool called Sequential Probability Ratio Test, which has bounded false positive and false negative error rates.

  15. Copepod carcasses as microbial hot spots for pelagic denitrification

    DEFF Research Database (Denmark)

    Glud, Ronnie N.; Grossart, Hans-Peter; Larsen, Morten; Tang, Kam W.; Arendt, Kristine Engel; Rysgaard, Søren; Thamdrup, Bo; Nielsen, Torkel Gissel

    2015-01-01

    investigated carcass samples and thereby documented the potential for microbial denitrification in carcasses. The nirS gene was occasionally expressed in live copepods, but not as consistently as in carcasses. Incubations of sinking carcasses in 15NO2 3 amended seawater demonstrated denitrification, of which...... on average 34%617% (n528) was sustained by nitrification. However, the activity was highly variable and was strongly dependent on the ambient O2 levels. While denitrification was present even at air-saturation (302 lmol L21), the average carcass specific activity increased several orders of magnitude...... to 1 nmol d21 at 20% air-saturation (55 lmol O2 L21) at an ambient temperature of 78C. Sinking carcasses of C. inmarchicus therefore represent hotspots of pelagic denitrification, but the quantitative importance as a sink for bioavailable nitrogen is strongly dependent on the ambient O2 level. The...

  16. Environmental controls of marine productivity hot spots around Antarctica

    Science.gov (United States)

    Arrigo, Kevin R.; van Dijken, Gert L.; Strong, Aaron L.

    2015-08-01

    Antarctic coastal polynyas are biologically rich ecosystems that support large populations of mammals and birds and are globally significant sinks of atmospheric carbon dioxide. To support local phytoplankton blooms, these highly productive ecosystems require a large input of iron (Fe), the sources of which are poorly known. Here we assess the relative importance of six different environmental factors in controlling the amount of phytoplankton biomass and rates of net primary production (NPP) in 46 coastal polynyas around Antarctica. Data presented here suggest that melting ice shelves are a primary supplier of Fe to coastal polynyas, with basal melt rates explaining 59% of the between-polynya variance in mean chlorophyll a (Chl a) concentration. In a multiple regression analysis, which explained 78% of the variance in chlorophyll a (Chl a) between polynyas, basal melt rate explained twice as much of the variance as the next most important variable. Fe upwelled from sediments, which is partly controlled by continental shelf width, was also important in some polynyas. Of secondary importance to phytoplankton abundance and NPP were sea surface temperature and polynya size. Surprisingly, differences in light availability and the length of the open water season explained little or none of the variance in either Chl a or NPP between polynyas. If the productivity of coastal polynyas is indeed sensitive to the release of Fe from melting ice shelves, future changes in ice shelf melt rates could dramatically influence Antarctic coastal ecosystems and the ability of continental shelf waters to sequester atmospheric carbon dioxide. This article was corrected on 26 AUG 2015. See the end of the full text for details.

  17. Satellite magnetic modeling of north African hot spots

    Science.gov (United States)

    Phillips, R. J.; Brown, C. R.

    1985-01-01

    The primary objectives of the MAGSAT mission was to measure the intensity and direction of magnetization of the Earth's crust. A significant effort was directed to the large crustal anomalies first delineated by the POGO mission. The MAGSAT data are capable of spatial resolution of the crustal field to 250 km wavelength with reliability limits to less than 1 nT in the mean. The difficulties of dealing with less than the most robust of the MAGSAT anomalies is that often there is no more than the magnetic fields themselves to constrain geophysical models of the interior, and no independent means of assessing the quality of the crustal anomaly data in interpreting the subsurface are available.

  18. Traffic Engineering without Congestion Hot Spots in MPLS

    Directory of Open Access Journals (Sweden)

    A.Padmapriya,

    2010-10-01

    Full Text Available Traffic Engineering [1] broadly relates to optimization of the performance of the operational IP network. In networking, network congestion occurs when a link or node is carrying so much data that its quality of service deteriorates. Typical effects include queueing delay, packet loss or the blocking of new connections. A consequence of these latter two is that incremental increases in offered load lead either only to small increases in network throughput, or to an actual reduction in network throughput. This paper discusses methods like PNP approach [2] and HITS method for improving QoS [3], which are used for traffic engineering in MPLS. This paper will examine the two approaches; discuss solutions in both PNP approach and HITS method for improving QoS and point to topics for research and advanced development.

  19. Coral mucus is a hot spot for viral infections

    OpenAIRE

    Nguyen-Kim, Hanh; Bettarel, Yvan; Bouvier, Thierry; Bouvier, Corinne; Doan-Nhu, Hai; Nguyen-Ngoc, Lam; Nguyen-Thanh, Thuy; Tran-Quang, Huy; Brune, Justine

    2015-01-01

    There is increasing suspicion that viral communities play a pivotal role in maintaining coral health, yet their main ecological traits still remain poorly characterized. In this study, we examined the seasonal distribution and reproduction pathways of viruses inhabiting the mucus of the scleractinians Fungia repanda and Acropora formosa collected in Nha Trang Bay (Vietnam) during an 11-month survey. The strong coupling between epibiotic viral and bacterial abundance suggested that phages are ...

  20. Current-Induced Forces and Hot Spots in Biased Nanojunctions

    DEFF Research Database (Denmark)

    Lu, Jing Tao; Christensen, Rasmus Bjerregaard; Wang, Jian-Sheng;

    2015-01-01

    We investigate theoretically the interplay of current-induced forces (CIFs), Joule heating, and heat transport inside a current-carrying nanoconductor. We find that the CIFs, due to the electron-phonon coherence, can control the spatial heat dissipation in the conductor. This yields a significant...

  1. The Role of Viscosity in TATB Hot Spot Ignition

    Energy Technology Data Exchange (ETDEWEB)

    Fried, L E; Zepeda-Ruis, L; Howard, W M; Najjar, F; Reaugh, J E

    2011-08-02

    The role of dissipative effects, such as viscosity, in the ignition of high explosive pores is investigated using a coupled chemical, thermal, and hydrodynamic model. Chemical reactions are tracked with the Cheetah thermochemical code coupled to the ALE3D hydrodynamic code. We perform molecular dynamics simulations to determine the viscosity of liquid TATB. We also analyze shock wave experiments to obtain an estimate for the shock viscosity of TATB. Using the lower bound liquid-like viscosities, we find that the pore collapse is hydrodynamic in nature. Using the upper bound viscosity from shock wave experiments, we find that the pore collapse is closest to the viscous limit.

  2. Sediment trapping by dams creates methane emission hot spots

    DEFF Research Database (Denmark)

    Maeck, A.; Delsontro, T.; McGinnis, Daniel F.; Fischer, H.; Flury, Sabine; Schmidt, M.; Fietzek, P.; Lorke, A.

    2013-01-01

    reservoirs or rivers. We show that sediment accumulation correlates with methane production and subsequent ebullitive release rates and may therefore be an excellent proxy for estimating methane emissions from small reservoirs. Our results suggest that sedimentation-driven methane emissions from dammed river......Inland waters transport and transform substantial amounts of carbon and account for similar to 18% of global methane emissions. Large reservoirs with higher areal methane release rates than natural waters contribute significantly to freshwater emissions. However, there are millions of small dams...... worldwide that receive and trap high loads of organic carbon and can therefore potentially emit significant amounts of methane to the atmosphere. We evaluated the effect of damming on methane emissions in a central European impounded river. Direct comparison of riverine and reservoir reaches, where...

  3. Coral Mucus Is a Hot Spot for Viral Infections.

    Science.gov (United States)

    Nguyen-Kim, Hanh; Bettarel, Yvan; Bouvier, Thierry; Bouvier, Corinne; Doan-Nhu, Hai; Nguyen-Ngoc, Lam; Nguyen-Thanh, Thuy; Tran-Quang, Huy; Brune, Justine

    2015-09-01

    There is increasing suspicion that viral communities play a pivotal role in maintaining coral health, yet their main ecological traits still remain poorly characterized. In this study, we examined the seasonal distribution and reproduction pathways of viruses inhabiting the mucus of the scleractinians Fungia repanda and Acropora formosa collected in Nha Trang Bay (Vietnam) during an 11-month survey. The strong coupling between epibiotic viral and bacterial abundance suggested that phages are dominant among coral-associated viral communities. Mucosal viruses also exhibited significant differences in their main features between the two coral species and were also remarkably contrasted with their planktonic counterparts. For example, their abundance (inferred from epifluorescence counts), lytic production rates (KCN incubations), and the proportion of lysogenic cells (mitomycin C inductions) were, respectively, 2.6-, 9.5-, and 2.2-fold higher in mucus than in the surrounding water. Both lytic and lysogenic indicators were tightly coupled with temperature and salinity, suggesting that the life strategy of viral epibionts is strongly dependent upon environmental circumstances. Finally, our results suggest that coral mucus may represent a highly favorable habitat for viral proliferation, promoting the development of both temperate and virulent phages. Here, we discuss how such an optimized viral arsenal could be crucial for coral viability by presumably forging complex links with both symbiotic and adjacent nonsymbiotic microorganisms. PMID:26092456

  4. An evolving hot spot orbiting around Sgr A*

    Czech Academy of Sciences Publication Activity Database

    Zamaninasab, M.; Eckart, A.; Meyer, L.; Schoedel, R.; Dovčiak, Michal; Karas, Vladimír; Kunneriath, D.; Witzel, G.; Geissübel, R.; König, S.; Straubmeier, C.; Zensus, A.

    2008-01-01

    Roč. 131, - (2008), s. 1-7. ISSN 1742-6588. [The Universe under the Microscope – Astrophysics at High Angular Resolution. Bad Honnef, 21.04.2008-25.04.2008] Institutional research plan: CEZ:AV0Z10030501 Keywords : black holes Subject RIV: BN - Astronomy, Celestial Mechanics, Astrophysics

  5. On the flickering of hot spots in cataclysmic variables

    International Nuclear Information System (INIS)

    A flickering point source inside a scattering cloud will have its higher flicker frequencies attenuated because of delays caused by multiple scattering of photons in the cloud. The effect of this on the flicker spectrum of a cataclysmic variable is considered. (author)

  6. Structural Analysis of Iac Repressor Bound to Allosteric Effectors

    Energy Technology Data Exchange (ETDEWEB)

    Daber,R.; Stayrook, S.; Rosenberg, A.; Lewis, M.

    2007-01-01

    The lac operon is a model system for understanding how effector molecules regulate transcription and are necessary for allosteric transitions. The crystal structures of the lac repressor bound to inducer and anti-inducer molecules provide a model for how these small molecules can modulate repressor function. The structures of the apo repressor and the repressor bound to effector molecules are compared in atomic detail. All effectors examined here bind to the repressor in the same location and are anchored to the repressor through hydrogen bonds to several hydroxyl groups of the sugar ring. Inducer molecules form a more extensive hydrogen-bonding network compared to anti-inducers and neutral effector molecules. The structures of these effector molecules suggest that the O6 hydroxyl on the galactoside is essential for establishing a water-mediated hydrogen bonding network that bridges the N-terminal and C-terminal sub-domains. The altered hydrogen bonding can account in part for the different structural conformations of the repressor, and is vital for the allosteric transition.

  7. The allosteric switching mechanism in bacteriophage MS2

    Science.gov (United States)

    Perkett, Matthew R.; Mirijanian, Dina T.; Hagan, Michael F.

    2016-07-01

    We use all-atom simulations to elucidate the mechanisms underlying conformational switching and allostery within the coat protein of the bacteriophage MS2. Assembly of most icosahedral virus capsids requires that the capsid protein adopts different conformations at precise locations within the capsid. It has been shown that a 19 nucleotide stem loop (TR) from the MS2 genome acts as an allosteric effector, guiding conformational switching of the coat protein during capsid assembly. Since the principal conformational changes occur far from the TR binding site, it is important to understand the molecular mechanism underlying this allosteric communication. To this end, we use all-atom simulations with explicit water combined with a path sampling technique to sample the MS2 coat protein conformational transition, in the presence and absence of TR-binding. The calculations find that TR binding strongly alters the transition free energy profile, leading to a switch in the favored conformation. We discuss changes in molecular interactions responsible for this shift. We then identify networks of amino acids with correlated motions to reveal the mechanism by which effects of TR binding span the protein. We find that TR binding strongly affects residues located at the 5-fold and quasi-sixfold interfaces in the assembled capsid, suggesting a mechanism by which the TR binding could direct formation of the native capsid geometry. The analysis predicts amino acids whose substitution by mutagenesis could alter populations of the conformational substates or their transition rates.

  8. Differentiating a Ligand's Chemical Requirements for Allosteric Interactions from Those for Protein Binding. Phenylalanine Inhibition of Pyruvate Kinase

    International Nuclear Information System (INIS)

    The isoform of pyruvate kinase from brain and muscle of mammals (M1-PYK) is allosterically inhibited by phenylalanine. Initial observations in this model allosteric system indicate that Ala binds competitively with Phe, but elicits a minimal allosteric response. Thus, the allosteric ligand of this system must have requirements for eliciting an allosteric response in addition to the requirements for binding. Phe analogues have been used to dissect what chemical properties of Phe are responsible for eliciting the allosteric response. We first demonstrate that the L-2-aminopropanaldehyde substructure of the amino acid ligand is primarily responsible for binding to M1-PYK. Since the allosteric response to Ala is minimal and linear addition of methyl groups beyond the -carbon increase the magnitude of the allosteric response, we conclude that moieties beyond the -carbon are primarily responsible for allostery. Instead of an all-or-none mechanism of allostery, these findings support the idea that the bulk of the hydrophobic side chain, but not the aromatic nature, is the primary determinant of the magnitude of the observed allosteric inhibition. The use of these results to direct structural studies has resulted in a 1.65 Angstroms structure of M1-PYK with Ala bound. The coordination of Ala in the allosteric amino acid binding site confirms the binding role of the L-2-aminopropanaldehyde substructure of the ligand. Collectively, this study confirms that a ligand can have chemical regions specific for eliciting the allosteric signal in addition to the chemical regions necessary for binding

  9. The Spotting Distribution of Wildfires

    Directory of Open Access Journals (Sweden)

    Jonathan Martin

    2016-06-01

    Full Text Available In wildfire science, spotting refers to non-local creation of new fires, due to downwind ignition of brands launched from a primary fire. Spotting is often mentioned as being one of the most difficult problems for wildfire management, because of its unpredictable nature. Since spotting is a stochastic process, it makes sense to talk about a probability distribution for spotting, which we call the spotting distribution. Given a location ahead of the fire front, we would like to know how likely is it to observe a spot fire at that location in the next few minutes. The aim of this paper is to introduce a detailed procedure to find the spotting distribution. Most prior modelling has focused on the maximum spotting distance, or on physical subprocesses. We will use mathematical modelling, which is based on detailed physical processes, to derive a spotting distribution. We discuss the use and measurement of this spotting distribution in fire spread, fire management and fire breaching. The appendix of this paper contains a comprehensive review of the relevant underlying physical sub-processes of fire plumes, launching fire brands, wind transport, falling and terminal velocity, combustion during transport, and ignition upon landing.

  10. Cold Spots in Neonatal Incubators Are Hot Spots for Microbial Contamination

    NARCIS (Netherlands)

    de Goffau, Marcus C.; Bergman, Klasien A.; de Vries, Hendrik J.; Meessen, Nico E. L.; Degener, John E.; van Dijl, Jan Maarten; Harmsen, Hermie J. M.

    2011-01-01

    Thermal stability is essential for the survival and well-being of preterm neonates. This is achieved in neonatal incubators by raising the ambient temperature and humidity to sufficiently high levels. However, potentially pathogenic microorganisms also can thrive in such warm and humid environments.

  11. Hot Spots and Not Spots: Addressing Infrastructure and Service Provision through Combined Approaches in Rural Scotland

    OpenAIRE

    Sarah Skerratt

    2010-01-01

    There is widespread acceptance that the absence or presence of infrastructure and services in rural areas can lead to cycles of decline or resilience in these localities. It is also accepted that in remoter areas, population sparsity leads to a higher unit cost for delivery of services and infrastructure, and that private sector providers do not find such areas attractive for investment. At the same time, there is a reduction in spending capability within the public sector due to the signific...

  12. Allosteric and orthosteric sites in CC chemokine receptor (CCR5), a chimeric receptor approach

    DEFF Research Database (Denmark)

    Thiele, Stefanie; Steen, Anne; Jensen, Pia C;

    2011-01-01

    -allosteric molecules. A chimera was successfully constructed between CCR5 and the closely related CCR2 by transferring all extracellular regions of CCR2 to CCR5, i.e. a Trojan horse that resembles CCR2 extracellularly but signals through a CCR5 transmembrane unit. The chimera bound CCR2 (CCL2 and CCL7), but not CCR5...... preserved, the allosteric enhancement of chemokine binding was disrupted. In summary, the Trojan horse chimera revealed that orthosteric and allosteric sites could be structurally separated and still act together with transmission of agonism and antagonism across the different receptor units....

  13. Ago-allosteric modulation and other types of allostery in dimeric 7TM receptors

    DEFF Research Database (Denmark)

    Schwartz, Thue W; Holst, Birgitte

    concept for 7TM receptors, it is proposed that the ago-allosteric modulators bind in the orthosteric binding site, but-importantly-in the "other" or allosteric protomer of the dimer. Hereby, they can act both as additive co-agonists, and through intermolecular cooperative effects between the protomers......, they may influence the potency of the endogenous agonist. It is of interest that at least some endogenous agonists can only occupy one protomer of a dimeric 7TM receptor complex at a time and thereby they leave the orthosteric binding site in the allosteric protomer free, potentially for binding of...

  14. Analysis on hot spot mutations of GJB2 gene and mitochondrial DNA 12S rRNA among consanguineous induced deafness families%近亲婚配致聋家系中患者GJB2和线粒体DNA 12S rRNA基因突变热点分析

    Institute of Scientific and Technical Information of China (English)

    杨威; 付四清; 董家曙; 王春芳; 陈观明

    2011-01-01

    Objective: To analyze the frequencies of hot spot mutations of the two common deafness gene - GJB2 and mitochondrial DNA 12S rRNA in the consanguineous induced deafness families. Methods: 25 consanguineous induced deafness families received comprehensive physical examination and pure tone test, 48 cases were found, 3 mi venous blood samples were obtained to extract DNA, polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) targeted to specific genes were performed, the cases with mutation were confirmed by gene sequencing. Results: 1 case was found with 235delC homozygous mutation of GJB2 gene, 3 cases were found with heterozygous mutation; no A 1555G mutation was found in mitochondrial DNA 12S rRNA. Conclusion: The most of consanguineous induced deafness are autosomal recessive inheritance, but the incidence of 235delC mutation of GJB2 gene is low.%目的:分析GJB2和线粒体DNA 12S rRNA两种常见耳聋致病基因突变热点在近亲婚配致聋家系患者中的发生频率.方法:对25个近亲结婚致聋核心家系的后代进行全面的体格检查和纯音测试,共发现患者48例,采静脉血3 ml,提取DNA,针对特定基因,进行聚合酶链式反应(Polymerase chain reaction,PCR)及限制性片段长度多态性(Restriction fragmentlength polymorphism,RFLP)分析,发现突变者测序验证.结果:发现GJB2基因235delC纯合突变1例,杂合突变3例;未发现线粒体DNA 12S rRNA A1555G突变.结论:近亲结婚家系中遗传性聋多为常染色体隐性遗传,但GJB2基因235delc突变的发生率较低.

  15. To definition of activity of hot particles by a radiographic method

    International Nuclear Information System (INIS)

    The procedure of radiographic definition of low-active hot particles, including definition of parameters of radiographic spots, build-up of calibrating dependences and filtration of false spots is discussed. It was determined that the deviation of a dependence of a hot particle activity from a power function, which is observed in the small activity interval, is concerned to features of small radiographic spot formation. This is not sufficient basis for the assumption about differentiating of substance composition of hot particles depending on their activity

  16. Coarse-Grained Molecular Simulations of Allosteric Cooperativity

    CERN Document Server

    Nandigrami, Prithviraj

    2015-01-01

    Interactions between a protein and a ligand are often accompanied by a redistribution of the population of thermally accessible conformations. This dynamic response of the protein's functional energy landscape enables a protein to modulate binding affinities and control binding sensitivity to ligand concentration. In this paper, we investigate the structural origins of binding affinity and allosteric cooperativity of binding two calcium ions to each domain of calmodulin (CaM) through simulations of a simple coarse-grained model. In this model, the protein's conformational transitions between open and closed conformational ensembles are simulated explicitly and ligand binding and unbinding is treated implicitly at the mean field level. Ligand binding is cooperative because the binding sites are coupled through a shift in the dominant conformational ensemble upon binding. The classic Monod-Wyman-Changeux model of allostery with appropriate binding free energy to the open and closed ensembles accurately describe...

  17. Engineering an allosteric transcription factor to respond to new ligands.

    Science.gov (United States)

    Taylor, Noah D; Garruss, Alexander S; Moretti, Rocco; Chan, Sum; Arbing, Mark A; Cascio, Duilio; Rogers, Jameson K; Isaacs, Farren J; Kosuri, Sriram; Baker, David; Fields, Stanley; Church, George M; Raman, Srivatsan

    2016-02-01

    Genetic regulatory proteins inducible by small molecules are useful synthetic biology tools as sensors and switches. Bacterial allosteric transcription factors (aTFs) are a major class of regulatory proteins, but few aTFs have been redesigned to respond to new effectors beyond natural aTF-inducer pairs. Altering inducer specificity in these proteins is difficult because substitutions that affect inducer binding may also disrupt allostery. We engineered an aTF, the Escherichia coli lac repressor, LacI, to respond to one of four new inducer molecules: fucose, gentiobiose, lactitol and sucralose. Using computational protein design, single-residue saturation mutagenesis or random mutagenesis, along with multiplex assembly, we identified new variants comparable in specificity and induction to wild-type LacI with its inducer, isopropyl β-D-1-thiogalactopyranoside (IPTG). The ability to create designer aTFs will enable applications including dynamic control of cell metabolism, cell biology and synthetic gene circuits. PMID:26689263

  18. Orthosteric and Allosteric Regulation in Trypsin-Like Peptidases

    DEFF Research Database (Denmark)

    Kromann-Tofting, Tobias

    2015-01-01

    Trypsin-like serine peptidases play an important role in many physiological and pathophysiological processes, the latter including cardiovascular diseases and cancer. Binding of natural ligands to functional sites on the peptidase surface balances the level of activity and substrate specificity of...... peptidase and allosterically modulate the function of the active site, represents two important activity-regulating mechanisms in trypsin-like serine peptidases. Development of specific orthosteric agents as therapeutics is a challenge due to similar active site topology within the trypsin-like serine...... peptidase. The thesis describes how X-ray crystal structure analysis and biochemical analysis were used to demonstrate new concepts for orthosteric regulation of activity in the trypsin-like serine peptidase urokinase-type plasminogen activator (uPA), studying two types of orthosteric agents, namely cyclic...

  19. Architecture and Co-Evolution of Allosteric Materials

    CERN Document Server

    Yan, Le; Brito, Carolina; Wyart, Matthieu

    2016-01-01

    We introduce a numerical scheme to evolve functional materials that can accomplish a specified mechanical task. In this scheme, the number of solutions, their spatial architectures and the correlations among them can be computed. As an example, we consider an "allosteric" task, which requires the material to respond specifically to a stimulus at a distant active site. We find that functioning materials evolve a less-constrained trumpet-shaped region connecting the stimulus and active sites and that the amplitude of the elastic response varies non-monotonically along the trumpet. As previously shown for some proteins, we find that correlations appearing during evolution alone are sufficient to identify key aspects of this design. Finally, we show that the success of this architecture stems from the emergence of soft edge modes recently found to appear near the surface of marginally connected materials. Overall, our in silico evolution experiment offers a new window to study the relationship between structure, ...

  20. Hot Money,Hot Problems

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    After emerging from the economic doldrums, developing economies are now confronted with a new danger-a flood of international hot money. But how has the speculative capital circumvented regulatory controls and what are the consequences concerning the stability of the developing world? Zhao Zhongwei, a senior researcher with the Institute of World Politics and Economics at the Chinese Academy of Social Sciences, discussed these issues in an article recently published in the China Securities Journal. Edited excerpts follow

  1. Allosteric Optical Control of a Class B G-Protein-Coupled Receptor.

    Science.gov (United States)

    Broichhagen, Johannes; Johnston, Natalie R; von Ohlen, Yorrick; Meyer-Berg, Helena; Jones, Ben J; Bloom, Stephen R; Rutter, Guy A; Trauner, Dirk; Hodson, David J

    2016-05-01

    Allosteric regulation promises to open up new therapeutic avenues by increasing drug specificity at G-protein-coupled receptors (GPCRs). However, drug discovery efforts are at present hampered by an inability to precisely control the allosteric site. Herein, we describe the design, synthesis, and testing of PhotoETP, a light-activated positive allosteric modulator of the glucagon-like peptide-1 receptor (GLP-1R), a class B GPCR involved in the maintenance of glucose homeostasis in humans. PhotoETP potentiates Ca(2+) , cAMP, and insulin responses to glucagon-like peptide-1 and its metabolites following illumination of cells with blue light. PhotoETP thus provides a blueprint for the production of small-molecule class B GPCR allosteric photoswitches, and may represent a useful tool for understanding positive cooperativity at the GLP-1R. PMID:27059784

  2. Structure and allosteric effects of low-molecular-weight activators on the protein kinase PDK1

    DEFF Research Database (Denmark)

    Hindie, Valerie; Stroba, Adriana; Zhang, Hua;

    2009-01-01

    Protein phosphorylation transduces a large set of intracellular signals. One mechanism by which phosphorylation mediates signal transduction is by prompting conformational changes in the target protein or interacting proteins. Previous work described an allosteric site mediating phosphorylation-d...

  3. Positive allosteric feedback regulation of the stringent response enzyme RelA by its product

    OpenAIRE

    Shyp, Viktoriya; Tankov, Stoyan; Ermakov, Andrey; Kudrin, Pavel; English, Brian P.; Ehrenberg, Måns; Tenson, Tanel; Elf, Johan; Hauryliuk, Vasili

    2012-01-01

    This report identifies a new mechanism of enzyme activation—positive allosteric regulation by the product—in the context of the bacterial stringent response, which is essential for bacterial adaptation to environmental conditions.

  4. Allosteric Mechanism of Pyruvate Kinase from Leishmania mexicana Uses a Rock and Lock Model*

    OpenAIRE

    Morgan, Hugh P.; McNae, Iain W.; Matthew W Nowicki; Hannaert, Véronique; Michels, Paul A M; Fothergill-Gilmore, Linda A.; Walkinshaw, Malcolm D.

    2010-01-01

    Allosteric regulation provides a rate management system for enzymes involved in many cellular processes. Ligand-controlled regulation is easily recognizable, but the underlying molecular mechanisms have remained elusive. We have obtained the first complete series of allosteric structures, in all possible ligated states, for the tetrameric enzyme, pyruvate kinase, from Leishmania mexicana. The transition between inactive T-state and active R-state is accompanied by a simple symmetrical 6° rigi...

  5. Allosteric Partial Inhibition of Monomeric Proteases. Sulfated Coumarins Induce Regulation, not just Inhibition, of Thrombin

    OpenAIRE

    Stephen Verespy III; Mehta, Akul Y.; Daniel Afosah; Al-Horani, Rami A.; Desai, Umesh R.

    2016-01-01

    Allosteric partial inhibition of soluble, monomeric proteases can offer major regulatory advantages, but remains a concept on paper to date; although it has been routinely documented for receptors and oligomeric proteins. Thrombin, a key protease of the coagulation cascade, displays significant conformational plasticity, which presents an attractive opportunity to discover small molecule probes that induce sub-maximal allosteric inhibition. We synthesized a focused library of some 36 sulfated...

  6. Structure-Based Statistical Mechanical Model Accounts for the Causality and Energetics of Allosteric Communication.

    Science.gov (United States)

    Guarnera, Enrico; Berezovsky, Igor N

    2016-03-01

    Allostery is one of the pervasive mechanisms through which proteins in living systems carry out enzymatic activity, cell signaling, and metabolism control. Effective modeling of the protein function regulation requires a synthesis of the thermodynamic and structural views of allostery. We present here a structure-based statistical mechanical model of allostery, allowing one to observe causality of communication between regulatory and functional sites, and to estimate per residue free energy changes. Based on the consideration of ligand free and ligand bound systems in the context of a harmonic model, corresponding sets of characteristic normal modes are obtained and used as inputs for an allosteric potential. This potential quantifies the mean work exerted on a residue due to the local motion of its neighbors. Subsequently, in a statistical mechanical framework the entropic contribution to allosteric free energy of a residue is directly calculated from the comparison of conformational ensembles in the ligand free and ligand bound systems. As a result, this method provides a systematic approach for analyzing the energetics of allosteric communication based on a single structure. The feasibility of the approach was tested on a variety of allosteric proteins, heterogeneous in terms of size, topology and degree of oligomerization. The allosteric free energy calculations show the diversity of ways and complexity of scenarios existing in the phenomenology of allosteric causality and communication. The presented model is a step forward in developing the computational techniques aimed at detecting allosteric sites and obtaining the discriminative power between agonistic and antagonistic effectors, which are among the major goals in allosteric drug design. PMID:26939022

  7. Fumarate analogs act as allosteric inhibitors of the human mitochondrial NAD(P+-dependent malic enzyme.

    Directory of Open Access Journals (Sweden)

    Ju-Yi Hsieh

    Full Text Available Human mitochondrial NAD(P+-dependent malic enzyme (m-NAD(P-ME is allosterically activated by the four-carbon trans dicarboxylic acid, fumarate. Previous studies have suggested that the dicarboxylic acid in a trans conformation around the carbon-carbon double bond is required for the allosteric activation of the enzyme. In this paper, the allosteric effects of fumarate analogs on m-NAD(P-ME are investigated. Two fumarate-insensitive mutants, m-NAD(P-ME_R67A/R91A and m-NAD(P-ME_K57S/E59N/K73E/D102S, as well as c-NADP-ME, were used as the negative controls. Among these analogs, mesaconate, trans-aconitate, monomethyl fumarate and monoethyl fumarate were allosteric activators of the enzyme, while oxaloacetate, diethyl oxalacetate, and dimethyl fumarate were found to be allosteric inhibitors of human m-NAD(P-ME. The IC50 value for diethyl oxalacetate was approximately 2.5 mM. This paper suggests that the allosteric inhibitors may impede the conformational change from open form to closed form and therefore inhibit m-NAD(P-ME enzyme activity.

  8. Advances in spot curing technology

    International Nuclear Information System (INIS)

    A brief review of spot curing technology was presented. The process which a spot of energy of a specific wavelength bandwidth and irradiance is used to cause a coating, encapsulant or adhesive to change from a liquid to a solid state

  9. Perspective of International Research Hot Spot in the Field of Workplace Learning--Based on the Study of Literature from Seven Western Academic Journals Between 2005 and 2015%工作场所学习领域国际研究热点透视*--基于西方7本学术期刊文献(2005~2015)

    Institute of Scientific and Technical Information of China (English)

    张艳超; 黄健

    2016-01-01

    Workplace learning has become a new research territory of educational science in recent years. It has caused the wide attention from scholars both at home and abroad. With the help of Scopus database, based on the study of literature from seven academic journals between 2005 and 2015 in the West, the method of literature metrology, clustering analysis, mapping knowledge domain and so on have been used to do the data analysis and some results have been found. Firstly, the SCImago Journal Rank of these academic journals is generally low and the academic influence needs to be strengthened in the field of workplace learning. Secondly, the scholars have a clear gap between home and abroad concerning the research level and the achievements in this field. Actually, the United States, the Commonwealth and the Nordic countries have become the academic centers of international workplace learning research. Thirdly,"Human Resource Development"and"Workplace Learning"have become the two major mainstream research camps in the field of workplace learning, and the trend of their convergence and fusion is being strengthened. Fourthly, the characteristics of interdisciplinary research are obvious in the field of workplace learning. Interdisciplinary research from education, management, organization, psychology, sociology, etc. is benefit for academic innovation. Through the perspective of the international hot spot and development trend in the field of workplace learning, it can be expected that the studies of informal learning, gender, organizational learning, action learning and leadership development have important academic value and space to be explored in the future. It deserves the attention of scholars.%近年来工作场所学习领域已然成为教育科学研究的新疆域,引起了国内外学者的广泛关注。借助Scopus数据库,以西方工作场所学习领域7本学术期刊2005~2015年度收录的文献为研究样本,采用文献计量、聚类分析、

  10. Hot Spots and Hot Moments in Scientific Collaborations and Social Movements

    Science.gov (United States)

    Parker, John N.; Hackett, Edward J.

    2012-01-01

    Emotions are essential but little understood components of research; they catalyze and sustain creative scientific work and fuel the scientific and intellectual social movements (SIMs) that propel scientific change. Adopting a micro-sociological focus, we examine how emotions shape two intellectual processes central to all scientific work:…

  11. Hot spots and hot moments in riparian zones: potential for improved water quality management

    Science.gov (United States)

    Despite considerable heterogeneity over space and time, biogeochemical and hydrological processes in riparian zones regulate contaminant movement to receiving waters and often mitigate the impact of upland sources of contaminants on water quality. Recently, these heterogeneous processes have been co...

  12. Are AMPA receptor positive allosteric modulators potential pharmacotherapeutics for addiction?

    Science.gov (United States)

    Watterson, Lucas R; Olive, M Foster

    2013-01-01

    Positive allosteric modulators (PAMs) of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are a diverse class of compounds that increase fast excitatory transmission in the brain. AMPA PAMs have been shown to facilitate long-term potentiation, strengthen communication between various cortical and subcortical regions, and some of these compounds increase the production and release of brain-derived neurotrophic factor (BDNF) in an activity-dependent manner. Through these mechanisms, AMPA PAMs have shown promise as broad spectrum pharmacotherapeutics in preclinical and clinical studies for various neurodegenerative and psychiatric disorders. In recent years, a small collection of preclinical animal studies has also shown that AMPA PAMs may have potential as pharmacotherapeutic adjuncts to extinction-based or cue-exposure therapies for the treatment of drug addiction. The present paper will review this preclinical literature, discuss novel data collected in our laboratory, and recommend future research directions for the possible development of AMPA PAMs as anti-addiction medications. PMID:24380895

  13. Computational Investigation on the Allosteric Modulation of Androgen Receptor

    Institute of Scientific and Technical Information of China (English)

    OU Min-Rui; LI Jun-Qian

    2012-01-01

    Androgens have similar structures with different biological activities. To identify molecular determinants responsible for the activity difference, we have docked six steroidal androgens to the binding site or the surface of androgen receptor by using molecular docking with computational investigation. The energy was calculated respectively based on the QM (quantum mechanics) and MM (molecular mechanics) methods. The result shows that the allosteric modulation of androgen receptor plays an important role in the binding process between androgens and receptor. The open state receptor is less stable than the close state one, but the latter is more favorable for binding with androgens. It is worthy of note that when the androgen receptors binding or without binding with androgen are in close state, they are difficult to return to their open state. This phenomenon is an exception of the well known two-state model theory in which the two states are reversible. Whether the internal of close state androgen receptor has a combination of androgen or not, the androgen receptor surface can be combined with another androgen, and their surface binding energies could be very close. The result is consistent with the experimental observations, but this phenomenon of continuous combination from open state is also an exception of the two-state model theory.

  14. Are AMPA Receptor Positive Allosteric Modulators Potential Pharmacotherapeutics for Addiction?

    Directory of Open Access Journals (Sweden)

    Lucas R. Watterson

    2013-12-01

    Full Text Available Positive allosteric modulators (PAMs of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA receptors are a diverse class of compounds that increase fast excitatory transmission in the brain. AMPA PAMs have been shown to facilitate long-term potentiation, strengthen communication between various cortical and subcortical regions, and some of these compounds increase the production and release of brain-derived neurotrophic factor (BDNF in an activity-dependent manner. Through these mechanisms, AMPA PAMs have shown promise as broad spectrum pharmacotherapeutics in preclinical and clinical studies for various neurodegenerative and psychiatric disorders. In recent years, a small collection of preclinical animal studies has also shown that AMPA PAMs may have potential as pharmacotherapeutic adjuncts to extinction-based or cue-exposure therapies for the treatment of drug addiction. The present paper will review this preclinical literature, discuss novel data collected in our laboratory, and recommend future research directions for the possible development of AMPA PAMs as anti-addiction medications.

  15. Allosteric modulation of metabotropic glutamate receptors by chloride ions.

    Science.gov (United States)

    Tora, Amélie S; Rovira, Xavier; Dione, Ibrahima; Bertrand, Hugues-Olivier; Brabet, Isabelle; De Koninck, Yves; Doyon, Nicolas; Pin, Jean-Philippe; Acher, Francine; Goudet, Cyril

    2015-10-01

    Metabotropic glutamate receptors (mGluRs) play key roles in the modulation of many synapses. Chloride (Cl(-)) is known to directly bind and regulate the function of different actors of neuronal activity, and several studies have pointed to the possible modulation of mGluRs by Cl(-). Herein, we demonstrate that Cl(-) behaves as a positive allosteric modulator of mGluRs. For example, whereas glutamate potency was 3.08 ± 0.33 μM on metabotropic glutamate (mGlu) 4 receptors in high-Cl(-) buffer, signaling activity was almost abolished in low Cl(-) in cell-based assays. Cl(-) potency was 78.6 ± 3.5 mM. Cl(-) possesses a high positive cooperativity with glutamate (Hill slope ≈6 on mGlu4), meaning that small variations in [Cl(-)] lead to large variations in glutamate action. Using molecular modeling and mutagenesis, we have identified 2 well-conserved Cl(-) binding pockets in the extracellular domain of mGluRs. Moreover, modeling of activity-dependent Cl(-) variations at GABAergic synapses suggests that these variations may be compatible with a dynamic modulation of the most sensitive mGluRs present in these synapses. Taken together, these data reveal a necessary role of Cl(-) for the glutamate activation of many mGluRs. Exploiting Cl(-) binding pockets may yield to the development of innovative regulators of mGluR activity. PMID:26116702

  16. Allosteric receptor activation by the plant peptide hormone phytosulfokine.

    Science.gov (United States)

    Wang, Jizong; Li, Hongju; Han, Zhifu; Zhang, Heqiao; Wang, Tong; Lin, Guangzhong; Chang, Junbiao; Yang, Weicai; Chai, Jijie

    2015-09-10

    Phytosulfokine (PSK) is a disulfated pentapeptide that has a ubiquitous role in plant growth and development. PSK is perceived by its receptor PSKR, a leucine-rich repeat receptor kinase (LRR-RK). The mechanisms underlying the recognition of PSK, the activation of PSKR and the identity of the components downstream of the initial binding remain elusive. Here we report the crystal structures of the extracellular LRR domain of PSKR in free, PSK- and co-receptor-bound forms. The structures reveal that PSK interacts mainly with a β-strand from the island domain of PSKR, forming an anti-β-sheet. The two sulfate moieties of PSK interact directly with PSKR, sensitizing PSKR recognition of PSK. Supported by biochemical, structural and genetic evidence, PSK binding enhances PSKR heterodimerization with the somatic embryogenesis receptor-like kinases (SERKs). However, PSK is not directly involved in PSKR-SERK interaction but stabilizes PSKR island domain for recruitment of a SERK. Our data reveal the structural basis for PSKR recognition of PSK and allosteric activation of PSKR by PSK, opening up new avenues for the design of PSKR-specific small molecules. PMID:26308901

  17. How to Spot Health Fraud

    Science.gov (United States)

    ... Bioterrorism and Drug Preparedness How to Spot Health Fraud Share Tweet Linkedin Pin it More sharing options ... health fraud. --P.K. Joining Forces to Fight Fraud Health fraud isn't confined to the United ...

  18. Hot particles in industrial waste and mining tailings

    CERN Document Server

    Selchau-Hansen, K; Freyer, K; Treutler, C; Enge, W

    1999-01-01

    Industrial waste was studied concerning its radioactive pollution. Using known properties of the solid state nuclear track detector CR-39 we found among a high concentration of more or less homogeneously distributed single alpha-tracks discrete spots of very high enrichments of alpha-particles created by so called hot particles. We will report about the alpha-activity, the concentration of hot particles and about their ability to be air borne.

  19. Positive cooperativity of acetylcholine and other agonists with allosteric ligands on muscarinic acetylcholine receptors.

    Science.gov (United States)

    Jakubík, J; Bacáková, L; El-Fakahany, E E; Tucek, S

    1997-07-01

    It is well known that allosteric modulators of muscarinic acetylcholine receptors can both diminish and increase the affinity of receptors for their antagonists. We investigated whether the allosteric modulators can also increase the affinity of receptors for their agonists. Twelve agonists and five allosteric modulators were tested in experiments on membranes of CHO cells that had been stably transfected with genes for the M1-M4 receptor subtypes. Allosterically induced changes in the affinities for agonists were computed from changes in the ability of a fixed concentration of each agonist to compete with [3H]N-methylscopolamine for the binding to the receptors in the absence and the presence of varying concentrations of allosteric modulators. The effects of allosteric modulators varied greatly depending on the agonists and the subtypes of receptors. The affinity for acetylcholine was augmented by (-)-eburnamonine on the M2 and M4 receptors and by brucine on the M1 and M3 receptors. Brucine also enhanced the affinities for carbachol, bethanechol, furmethide, methylfurmethide, pilocarpine, 3-(3-pentylthio-1,2,5-thiadiazol-4-yl)-1,2,5,6-tetrahydro-1- methylpyridine (pentylthio-TZTP), oxotremorine-M, and McN-A-343 on the M1, M3, and M4 receptors, for pentylthio-TZTP on the M2 receptors, and for arecoline on the M3 receptors. (-)-Eburnamonine enhanced the affinities for carbachol, bethanechol, furmethide, methylfurmethide, pentylthio-TZTP, pilocarpine, oxotremorine and oxotremorine-M on the M2 receptors and for pilocarpine on the M4 receptors. Vincamine, strychnine, and alcuronium displayed fewer positive allosteric interactions with the agonists, but each allosteric modulator displayed positive cooperativity with at least one agonist on at least one muscarinic receptor subtype. The highest degrees of positive cooperativity were observed between (-)-eburnamonine and pilocarpine and (-)-eburnamonine and oxotremorine-M on the M2 receptors (25- and 7-fold increases in

  20. Structural basis for modulation of a G-protein-coupled receptor by allosteric drugs

    Science.gov (United States)

    Dror, Ron O.; Green, Hillary F.; Valant, Celine; Borhani, David W.; Valcourt, James R.; Pan, Albert C.; Arlow, Daniel H.; Canals, Meritxell; Lane, J. Robert; Rahmani, Raphaël; Baell, Jonathan B.; Sexton, Patrick M.; Christopoulos, Arthur; Shaw, David E.

    2013-11-01

    The design of G-protein-coupled receptor (GPCR) allosteric modulators, an active area of modern pharmaceutical research, has proved challenging because neither the binding modes nor the molecular mechanisms of such drugs are known. Here we determine binding sites, bound conformations and specific drug-receptor interactions for several allosteric modulators of the M2 muscarinic acetylcholine receptor (M2 receptor), a prototypical family A GPCR, using atomic-level simulations in which the modulators spontaneously associate with the receptor. Despite substantial structural diversity, all modulators form cation-π interactions with clusters of aromatic residues in the receptor extracellular vestibule, approximately 15Å from the classical, `orthosteric' ligand-binding site. We validate the observed modulator binding modes through radioligand binding experiments on receptor mutants designed, on the basis of our simulations, either to increase or to decrease modulator affinity. Simulations also revealed mechanisms that contribute to positive and negative allosteric modulation of classical ligand binding, including coupled conformational changes of the two binding sites and electrostatic interactions between ligands in these sites. These observations enabled the design of chemical modifications that substantially alter a modulator's allosteric effects. Our findings thus provide a structural basis for the rational design of allosteric modulators targeting muscarinic and possibly other GPCRs.

  1. Molecular Dynamics Simulations Reveal the Mechanisms of Allosteric Activation of Hsp90 by Designed Ligands

    Science.gov (United States)

    Vettoretti, Gerolamo; Moroni, Elisabetta; Sattin, Sara; Tao, Jiahui; Agard, David A.; Bernardi, Anna; Colombo, Giorgio

    2016-04-01

    Controlling biochemical pathways through chemically designed modulators may provide novel opportunities to develop therapeutic drugs and chemical tools. The underlying challenge is to design new molecular entities able to act as allosteric chemical switches that selectively turn on/off functions by modulating the conformational dynamics of their target protein. We examine the origins of the stimulation of ATPase and closure kinetics in the molecular chaperone Hsp90 by allosteric modulators through atomistic molecular dynamics (MD) simulations and analysis of protein-ligand interactions. In particular, we focus on the cross-talk between allosteric ligands and protein conformations and its effect on the dynamic properties of the chaperone’s active state. We examine the impact of different allosteric modulators on the stability, structural and internal dynamics properties of Hsp90 closed state. A critical aspect of this study is the development of a quantitative model that correlates Hsp90 activation to the presence of a certain compound, making use of information on the dynamic adaptation of protein conformations to the presence of the ligand, which allows to capture conformational states relevant in the activation process. We discuss the implications of considering the conformational dialogue between allosteric ligands and protein conformations for the design of new functional modulators.

  2. Allosteric inhibition of the NS2B-NS3 protease from dengue virus.

    Science.gov (United States)

    Yildiz, Muslum; Ghosh, Sumana; Bell, Jeffrey A; Sherman, Woody; Hardy, Jeanne A

    2013-12-20

    Dengue virus is the flavivirus that causes dengue fever, dengue hemorrhagic disease, and dengue shock syndrome, which are currently increasing in incidence worldwide. Dengue virus protease (NS2B-NS3pro) is essential for dengue virus infection and is thus a target of therapeutic interest. To date, attention has focused on developing active-site inhibitors of NS2B-NS3pro. The flat and charged nature of the NS2B-NS3pro active site may contribute to difficulties in developing inhibitors and suggests that a strategy of identifying allosteric sites may be useful. We report an approach that allowed us to scan the NS2B-NS3pro surface by cysteine mutagenesis and use cysteine reactive probes to identify regions of the protein that are susceptible to allosteric inhibition. This method identified a new allosteric site utilizing a circumscribed panel of just eight cysteine variants and only five cysteine reactive probes. The allosterically sensitive site is centered at Ala125, between the 120s loop and the 150s loop. The crystal structures of WT and modified NS2B-NS3pro demonstrate that the 120s loop is flexible. Our work suggests that binding at this site prevents a conformational rearrangement of the NS2B region of the protein, which is required for activation. Preventing this movement locks the protein into the open, inactive conformation, suggesting that this site may be useful in the future development of therapeutic allosteric inhibitors. PMID:24164286

  3. Allosteric inhibition of Aurora-A kinase by a synthetic vNAR domain.

    Science.gov (United States)

    Burgess, Selena G; Oleksy, Arkadiusz; Cavazza, Tommaso; Richards, Mark W; Vernos, Isabelle; Matthews, David; Bayliss, Richard

    2016-07-01

    The vast majority of clinically approved protein kinase inhibitors target the ATP-binding pocket directly. Consequently, many inhibitors have broad selectivity profiles and most have significant off-target effects. Allosteric inhibitors are generally more selective, but are difficult to identify because allosteric binding sites are often unknown or poorly characterized. Aurora-A is activated through binding of TPX2 to an allosteric site on the kinase catalytic domain, and this knowledge could be exploited to generate an inhibitor. Here, we generated an allosteric inhibitor of Aurora-A kinase based on a synthetic, vNAR single domain scaffold, vNAR-D01. Biochemical studies and a crystal structure of the Aurora-A/vNAR-D01 complex show that the vNAR domain overlaps with the TPX2 binding site. In contrast with the binding of TPX2, which stabilizes an active conformation of the kinase, binding of the vNAR domain stabilizes an inactive conformation, in which the αC-helix is distorted, the canonical Lys-Glu salt bridge is broken and the regulatory (R-) spine is disrupted by an additional hydrophobic side chain from the activation loop. These studies illustrate how single domain antibodies can be used to characterize the regulatory mechanisms of kinases and provide a rational basis for structure-guided design of allosteric Aurora-A kinase inhibitors. PMID:27411893

  4. Detection of allosteric signal transmission by information-theoretic analysis of protein dynamics

    Science.gov (United States)

    Pandini, Alessandro; Fornili, Arianna; Fraternali, Franca; Kleinjung, Jens

    2012-01-01

    Allostery offers a highly specific way to modulate protein function. Therefore, understanding this mechanism is of increasing interest for protein science and drug discovery. However, allosteric signal transmission is difficult to detect experimentally and to model because it is often mediated by local structural changes propagating along multiple pathways. To address this, we developed a method to identify communication pathways by an information-theoretical analysis of molecular dynamics simulations. Signal propagation was described as information exchange through a network of correlated local motions, modeled as transitions between canonical states of protein fragments. The method was used to describe allostery in two-component regulatory systems. In particular, the transmission from the allosteric site to the signaling surface of the receiver domain NtrC was shown to be mediated by a layer of hub residues. The location of hubs preferentially connected to the allosteric site was found in close agreement with key residues experimentally identified as involved in the signal transmission. The comparison with the networks of the homologues CheY and FixJ highlighted similarities in their dynamics. In particular, we showed that a preorganized network of fragment connections between the allosteric and functional sites exists already in the inactive state of all three proteins.—Pandini, A., Fornili, A., Fraternali, F., Kleinjung, J. Detection of allosteric signal transmission by information-theoretic analysis of protein dynamics. PMID:22071506

  5. Allosteric Partial Inhibition of Monomeric Proteases. Sulfated Coumarins Induce Regulation, not just Inhibition, of Thrombin.

    Science.gov (United States)

    Verespy Iii, Stephen; Mehta, Akul Y; Afosah, Daniel; Al-Horani, Rami A; Desai, Umesh R

    2016-01-01

    Allosteric partial inhibition of soluble, monomeric proteases can offer major regulatory advantages, but remains a concept on paper to date; although it has been routinely documented for receptors and oligomeric proteins. Thrombin, a key protease of the coagulation cascade, displays significant conformational plasticity, which presents an attractive opportunity to discover small molecule probes that induce sub-maximal allosteric inhibition. We synthesized a focused library of some 36 sulfated coumarins to discover two agents that display sub-maximal efficacy (~50%), high potency (150-fold). Michaelis-Menten, competitive inhibition, and site-directed mutagenesis studies identified exosite 2 as the site of binding for the most potent sulfated coumarin. Stern-Volmer quenching of active site-labeled fluorophore suggested that the allosteric regulators induce intermediate structural changes in the active site as compared to those that display ~80-100% efficacy. Antithrombin inactivation of thrombin was impaired in the presence of the sulfated coumarins suggesting that allosteric partial inhibition arises from catalytic dysfunction of the active site. Overall, sulfated coumarins represent first-in-class, sub-maximal inhibitors of thrombin. The probes establish the concept of allosteric partial inhibition of soluble, monomeric proteins. This concept may lead to a new class of anticoagulants that are completely devoid of bleeding. PMID:27053426

  6. A dynamically coupled allosteric network underlies binding cooperativity in Src kinase

    Science.gov (United States)

    Foda, Zachariah H.; Shan, Yibing; Kim, Eric T.; Shaw, David E.; Seeliger, Markus A.

    2015-01-01

    Protein tyrosine kinases are attractive drug targets because many human diseases are associated with the deregulation of kinase activity. However, how the catalytic kinase domain integrates different signals and switches from an active to an inactive conformation remains incompletely understood. Here we identify an allosteric network of dynamically coupled amino acids in Src kinase that connects regulatory sites to the ATP- and substrate-binding sites. Surprisingly, reactants (ATP and peptide substrates) bind with negative cooperativity to Src kinase while products (ADP and phosphopeptide) bind with positive cooperativity. We confirm the molecular details of the signal relay through the allosteric network by biochemical studies. Experiments on two additional protein tyrosine kinases indicate that the allosteric network may be largely conserved among these enzymes. Our work provides new insights into the regulation of protein tyrosine kinases and establishes a potential conduit by which resistance mutations to ATP-competitive kinase inhibitors can affect their activity.

  7. NMR Characterization of Information Flow and Allosteric Communities in the MAP Kinase p38γ

    Science.gov (United States)

    Aoto, Phillip C.; Martin, Bryan T.; Wright, Peter E.

    2016-01-01

    The intramolecular network structure of a protein provides valuable insights into allosteric sites and communication pathways. However, a straightforward method to comprehensively map and characterize these pathways is not currently available. Here we present an approach to characterize intramolecular network structure using NMR chemical shift perturbations. We apply the method to the mitogen activated protein kinase (MAPK) p38γ. p38γ contains allosteric sites that are conserved among eukaryotic kinases as well as unique to the MAPK family. How these regulatory sites communicate with catalytic residues is not well understood. Using our method, we observe and characterize for the first time information flux between regulatory sites through a conserved kinase infrastructure. This network is accessed, reinforced, and broken in various states of p38γ, reflecting the functional state of the protein. We demonstrate that the approach detects critical junctions in the network corresponding to biologically significant allosteric sites and pathways.

  8. Identifying Allosteric Hotspots with Dynamics: Application to Inter- and Intra-species Conservation.

    Science.gov (United States)

    Clarke, Declan; Sethi, Anurag; Li, Shantao; Kumar, Sushant; Chang, Richard W F; Chen, Jieming; Gerstein, Mark

    2016-05-01

    The rapidly growing volume of data being produced by next-generation sequencing initiatives is enabling more in-depth analyses of conservation than previously possible. Deep sequencing is uncovering disease loci and regions under selective constraint, despite the fact that intuitive biophysical reasons for such constraint are sometimes absent. Allostery may often provide the missing explanatory link. We use models of protein conformational change to identify allosteric residues by finding essential surface pockets and information-flow bottlenecks, and we develop a software tool that enables users to perform this analysis on their own proteins of interest. Though fundamentally 3D-structural in nature, our analysis is computationally fast, thereby allowing us to run it across the PDB and to evaluate general properties of predicted allosteric residues. We find that these tend to be conserved over diverse evolutionary time scales. Finally, we highlight examples of allosteric residues that help explain poorly understood disease-associated variants. PMID:27066750

  9. A dynamically coupled allosteric network underlies binding cooperativity in Src kinase.

    Science.gov (United States)

    Foda, Zachariah H; Shan, Yibing; Kim, Eric T; Shaw, David E; Seeliger, Markus A

    2015-01-01

    Protein tyrosine kinases are attractive drug targets because many human diseases are associated with the deregulation of kinase activity. However, how the catalytic kinase domain integrates different signals and switches from an active to an inactive conformation remains incompletely understood. Here we identify an allosteric network of dynamically coupled amino acids in Src kinase that connects regulatory sites to the ATP- and substrate-binding sites. Surprisingly, reactants (ATP and peptide substrates) bind with negative cooperativity to Src kinase while products (ADP and phosphopeptide) bind with positive cooperativity. We confirm the molecular details of the signal relay through the allosteric network by biochemical studies. Experiments on two additional protein tyrosine kinases indicate that the allosteric network may be largely conserved among these enzymes. Our work provides new insights into the regulation of protein tyrosine kinases and establishes a potential conduit by which resistance mutations to ATP-competitive kinase inhibitors can affect their activity. PMID:25600932

  10. Guanine nucleotide binding to the Bateman domain mediates the allosteric inhibition of eukaryotic IMP dehydrogenases

    Science.gov (United States)

    Buey, Rubén M.; Ledesma-Amaro, Rodrigo; Velázquez-Campoy, Adrián; Balsera, Mónica; Chagoyen, Mónica; de Pereda, José M.; Revuelta, José L.

    2015-11-01

    Inosine-5'-monophosphate dehydrogenase (IMPDH) plays key roles in purine nucleotide metabolism and cell proliferation. Although IMPDH is a widely studied therapeutic target, there is limited information about its physiological regulation. Using Ashbya gossypii as a model, we describe the molecular mechanism and the structural basis for the allosteric regulation of IMPDH by guanine nucleotides. We report that GTP and GDP bind to the regulatory Bateman domain, inducing octamers with compromised catalytic activity. Our data suggest that eukaryotic and prokaryotic IMPDHs might have developed different regulatory mechanisms, with GTP/GDP inhibiting only eukaryotic IMPDHs. Interestingly, mutations associated with human retinopathies map into the guanine nucleotide-binding sites including a previously undescribed non-canonical site and disrupt allosteric inhibition. Together, our results shed light on the mechanisms of the allosteric regulation of enzymes mediated by Bateman domains and provide a molecular basis for certain retinopathies, opening the door to new therapeutic approaches.

  11. NMR Characterization of Information Flow and Allosteric Communities in the MAP Kinase p38γ.

    Science.gov (United States)

    Aoto, Phillip C; Martin, Bryan T; Wright, Peter E

    2016-01-01

    The intramolecular network structure of a protein provides valuable insights into allosteric sites and communication pathways. However, a straightforward method to comprehensively map and characterize these pathways is not currently available. Here we present an approach to characterize intramolecular network structure using NMR chemical shift perturbations. We apply the method to the mitogen activated protein kinase (MAPK) p38γ. p38γ contains allosteric sites that are conserved among eukaryotic kinases as well as unique to the MAPK family. How these regulatory sites communicate with catalytic residues is not well understood. Using our method, we observe and characterize for the first time information flux between regulatory sites through a conserved kinase infrastructure. This network is accessed, reinforced, and broken in various states of p38γ, reflecting the functional state of the protein. We demonstrate that the approach detects critical junctions in the network corresponding to biologically significant allosteric sites and pathways. PMID:27353957

  12. Selective Negative Allosteric Modulation Of Metabotropic Glutamate Receptors - A Structural Perspective of Ligands and Mutants

    DEFF Research Database (Denmark)

    Harpsøe, Kasper; Isberg, Vignir; Tehan, Benjamin G;

    2015-01-01

    The metabotropic glutamate receptors have a wide range of modulatory functions in the central nervous system. They are among the most highly pursued drug targets, with relevance for several neurological diseases, and a number of allosteric modulators have entered clinical trials. However, so far...... this has not led to a marketed drug, largely because of the difficulties in achieving subtype-selective compounds with desired properties. Very recently the first crystal structures were published for the transmembrane domain of two metabotropic glutamate receptors in complex with negative allosteric...... modulators. In this analysis, we make the first comprehensive structural comparison of all metabotropic glutamate receptors, placing selective negative allosteric modulators and critical mutants into the detailed context of the receptor binding sites. A better understanding of how the different m...

  13. Hemoglobin and the origins of the concept of allosterism.

    Science.gov (United States)

    Edsall, J T

    1980-02-01

    heterotropic interactions. Brief final comments relate to the evolution of the concept of reversible conformational transitions as the basis for both homotropic and heterotropic interactions in allosteric proteins. PMID:6986293

  14. Optimization of a Dibenzodiazepine Hit to a Potent and Selective Allosteric PAK1 Inhibitor.

    Science.gov (United States)

    Karpov, Alexei S; Amiri, Payman; Bellamacina, Cornelia; Bellance, Marie-Helene; Breitenstein, Werner; Daniel, Dylan; Denay, Regis; Fabbro, Doriano; Fernandez, Cesar; Galuba, Inga; Guerro-Lagasse, Stephanie; Gutmann, Sascha; Hinh, Linda; Jahnke, Wolfgang; Klopp, Julia; Lai, Albert; Lindvall, Mika K; Ma, Sylvia; Möbitz, Henrik; Pecchi, Sabina; Rummel, Gabriele; Shoemaker, Kevin; Trappe, Joerg; Voliva, Charles; Cowan-Jacob, Sandra W; Marzinzik, Andreas L

    2015-07-01

    The discovery of inhibitors targeting novel allosteric kinase sites is very challenging. Such compounds, however, once identified could offer exquisite levels of selectivity across the kinome. Herein we report our structure-based optimization strategy of a dibenzodiazepine hit 1, discovered in a fragment-based screen, yielding highly potent and selective inhibitors of PAK1 such as 2 and 3. Compound 2 was cocrystallized with PAK1 to confirm binding to an allosteric site and to reveal novel key interactions. Compound 3 modulated PAK1 at the cellular level and due to its selectivity enabled valuable research to interrogate biological functions of the PAK1 kinase. PMID:26191365

  15. Laser based spot weld characterization

    Science.gov (United States)

    Jonietz, Florian; Myrach, Philipp; Rethmeier, Michael; Suwala, Hubert; Ziegler, Mathias

    2016-02-01

    Spot welding is one of the most important joining technologies, especially in the automotive industry. Hitherto, the quality of spot welded joints is tested mainly by random destructive tests. A nondestructive testing technique offers the benefit of cost reduction of the testing procedure and optimization of the fabrication process, because every joint could be examined. This would lead to a reduced number of spot welded joints, as redundancies could be avoided. In the procedure described here, the spot welded joint between two zinc-coated steel sheets (HX340LAD+Z100MB or HC340LA+ZE 50/50) is heated optically on one side. Laser radiation and flash light are used as heat sources. The melted zone, the so called "weld nugget" provides the mechanical stability of the connection, but also constitutes a thermal bridge between the sheets. Due to the better thermal contact, the spot welded joint reveals a thermal behavior different from the surrounding material, where the heat transfer between the two sheets is much lower. The difference in the transient thermal behavior is measured with time resolved thermography. Hence, the size of the thermal contact between the two sheets is determined, which is directly correlated to the size of the weld nugget, indicating the quality of the spot weld. The method performs well in transmission with laser radiation and flash light. With laser radiation, it works even in reflection geometry, thus offering the possibility of testing with just one-sided accessibility. By using heating with collimated laser radiation, not only contact-free, but also remote testing is feasible. A further convenience compared to similar thermographic approaches is the applicability on bare steel sheets without any optical coating for emissivity correction. For this purpose, a proper way of emissivity correction was established.

  16. Color tunable LED spot lighting

    Science.gov (United States)

    Hoelen, C.; Ansems, J.; Deurenberg, P.; van Duijneveldt, W.; Peeters, M.; Steenbruggen, G.; Treurniet, T.; Valster, A.; ter Weeme, J. W.

    2006-08-01

    A new trend in illumination is to use dynamic light to set or dynamically vary the ambience of a room or office. For this we need color tunable spots that can reliably vary over at least a wide range of color temperatures, and preferably also more saturated colors. LEDs are in principle ideally suited for this application thanks to their nature of emitting light in a relatively narrow band. For color tunable spot lighting based on the concept of mixing RGB LED colors, the key results have been presented before. Limitations of these 3-intrinsic-color mixing systems with high color rendering properties are found in a limited operating temperature range due to wavelength shifts, a limited color temperature range, and a low maximum operating temperature due to a strong flux decrease with increasing temperature. To overcome these limitations, a 3-color R pcGB system with phosphor-converted red (R pc) and a 4-color RAGB system have been investigated. With both systems, a CRI of at least 80 can be maintained over the relevant color temperature range of approximately 2700 K to 6500 K. In this paper we compare these concepts on overall system aspects and report on the performance of prototype spot lamps. The main features of the RAGB and R pcGB spot lamp concepts can be summarized as: 1) The RAGB spot overcomes CRI and gamut shortcomings of RGB light sources and gives much freedom in wavelength selection, but suffers from temperature sensitivity and complex controls; 2) The R pcGB spot overcomes shortcomings concerning CRI and thermal dependence of RGB sources and enables relatively simple controls, but needs an improved overall red efficacy. With both color concepts, prototype spot lamps have been built. The amber to red emitting nitridosilicate-based phosphors can be wavelength-tuned for optimal performance, which is found at a peak emission around 610 nm for high color quality systems. This results in a simple and very robust system with good color consistency. For the

  17. Is this Red Spot the Blue Spot (locus ceruleum)?

    Energy Technology Data Exchange (ETDEWEB)

    Choe, Won Sick; Lee, Yu Kyung; Lee, Min Kyung; Hwang, Kyung Hoon [Gachon University Gil Hospital, Incheon (Korea, Republic of)

    2010-06-15

    The authors report brain images of 18F-FDG-PET in a case of schizophrenia. The images showed strikingly increased bilateral uptake in the locus ceruleum. The locus ceruleum is called the blue spot and known to be a center of the norepinephrinergic system.

  18. Friction Stir Spot Welding of Advanced High Strength Steels

    Energy Technology Data Exchange (ETDEWEB)

    Hovanski, Yuri; Santella, M. L.; Grant, Glenn J.

    2009-12-28

    Friction stir spot welding was used to join two advanced high-strength steels using polycrystalline cubic boron nitride tooling. Numerous tool designs were employed to study the influence of tool geometry on weld joints produced in both DP780 and a hot-stamp boron steel. Tool designs included conventional, concave shouldered pin tools with several pin configurations; a number of shoulderless designs; and a convex, scrolled shoulder tool. Weld quality was assessed based on lap shear strength, microstructure, microhardness, and bonded area. Mechanical properties were functionally related to bonded area and joint microstructure, demonstrating the necessity to characterize processing windows based on tool geometry.

  19. Fatal Spotted Fever Rickettsiosis, Kenya

    OpenAIRE

    Rutherford, Jeremiah S.; Macaluso, Kevin; Smith, Nathaniel; Zaki, Sherif R.; Paddock, Christopher D.; Davis, Jon; Peterso, Norman; Azad, Abdu F.; Rosenberg, Ronald

    2004-01-01

    We report a fatal case of rickettsiosis in a woman from the United States living in Kenya, who had a history of tick exposure. Immunohistochemical staining of skin, kidney, and liver demonstrated spotted fever group rickettsiae. The clinical findings, severity, and fatal outcome are most consistent with Rickettsia conorii infection.

  20. Prediction of allosteric sites and mediating interactions through bond-to-bond propensities

    Science.gov (United States)

    Amor, B. R. C.; Schaub, M. T.; Yaliraki, S. N.; Barahona, M.

    2016-01-01

    Allostery is a fundamental mechanism of biological regulation, in which binding of a molecule at a distant location affects the active site of a protein. Allosteric sites provide targets to fine-tune protein activity, yet we lack computational methodologies to predict them. Here we present an efficient graph-theoretical framework to reveal allosteric interactions (atoms and communication pathways strongly coupled to the active site) without a priori information of their location. Using an atomistic graph with energy-weighted covalent and weak bonds, we define a bond-to-bond propensity quantifying the non-local effect of instantaneous bond fluctuations propagating through the protein. Significant interactions are then identified using quantile regression. We exemplify our method with three biologically important proteins: caspase-1, CheY, and h-Ras, correctly predicting key allosteric interactions, whose significance is additionally confirmed against a reference set of 100 proteins. The almost-linear scaling of our method renders it suitable for high-throughput searches for candidate allosteric sites. PMID:27561351

  1. Elastic network model of allosteric regulation in protein kinase PDK1

    Directory of Open Access Journals (Sweden)

    Williams Gareth

    2010-05-01

    Full Text Available Abstract Background Structural switches upon binding of phosphorylated moieties underpin many signalling networks. The ligand activation is a form of allosteric modulation of the protein, where the binding site is remote from the structural change in the protein. Recently this structural switch has been elegantly demonstrated with the crystallisation of the activated form of 3-phosphoinositide-dependent protein kinase-1 (PDK1. The purpose of the present work is to determine whether the allosteric coupling in PDK1 emerges at the level of a simple coarse grained model of protein dynamics. Results It is shown here that the allosteric effects of the agonist binding to the small lobe upon the activation loop in the large lobe of PDK1 are explainable within a simple 'ball and spring' elastic network model (ENM of protein dynamics. In particular, the model shows that the bound phospho peptide mimetic fluctuations have a high degree of correlation with the activation loop of PDK1. Conclusions The ENM approach to small molecule activation of proteins may offer a first pass predictive methodology where affinity is encoded in residues remote from the active site, and aid in the design of specific protein agonists that enhance the allosteric coupling and antagonist that repress it.

  2. Mutations in Antibody Fragments Modulate Allosteric Response Via Hydrogen-Bond Network Fluctuations.

    Science.gov (United States)

    Srivastava, Amit; Tracka, Malgorzata B; Uddin, Shahid; Casas-Finet, Jose; Livesay, Dennis R; Jacobs, Donald J

    2016-05-10

    A mechanical perturbation method that locally restricts conformational entropy along the protein backbone is used to identify putative allosteric sites in a series of antibody fragments. The method is based on a distance constraint model that integrates mechanical and thermodynamic viewpoints of protein structure wherein mechanical clamps that mimic substrate or cosolute binding are introduced. Across a set of six single chain-Fv fragments of the anti-lymphotoxin-β receptor antibody, statistically significant responses are obtained by averaging over 10 representative structures sampled from a molecular dynamics simulation. As expected, the introduced clamps locally rigidify the protein, but long-ranged increases in both rigidity and flexibility are also frequently observed. Expanding our analysis to every molecular dynamics frame demonstrates that the allosteric responses are modulated by fluctuations within the hydrogen-bond network where the native ensemble is comprised of conformations that both are, and are not, affected by the perturbation in question. Population shifts induced by the mutations alter the allosteric response by adjusting which hydrogen-bond networks are the most probable. These effects are compared using response maps that track changes across each single chain-Fv fragment, thus providing valuable insight into how sensitive allosteric mechanisms are to mutations. PMID:27166802

  3. Coevolutionary analysis enabled rational deregulation of allosteric enzyme inhibition in Corynebacterium glutamicum for lysine production.

    Science.gov (United States)

    Chen, Zhen; Meyer, Weiqian; Rappert, Sugima; Sun, Jibin; Zeng, An-Ping

    2011-07-01

    Product feedback inhibition of allosteric enzymes is an essential issue for the development of highly efficient microbial strains for bioproduction. Here we used aspartokinase from Corynebacterium glutamicum (CgAK), a key enzyme controlling the biosynthesis of industrially important aspartate family amino acids, as a model to demonstrate a fast and efficient approach to the deregulation of allostery. In the last 50 years many researchers and companies have made considerable efforts to deregulate this enzyme from allosteric inhibition by lysine and threonine. However, only a limited number of positive mutants have been identified so far, almost exclusively by random mutation and selection. In this study, we used statistical coupling analysis of protein sequences, a method based on coevolutionary analysis, to systematically clarify the interaction network within the regulatory domain of CgAK that is essential for allosteric inhibition. A cluster of interconnected residues linking different inhibitors' binding sites as well as other regions of the protein have been identified, including most of the previously reported positions of successful mutations. Beyond these mutation positions, we have created another 14 mutants that can partially or completely desensitize CgAK from allosteric inhibition, as shown by enzyme activity assays. The introduction of only one of the inhibition-insensitive CgAK mutations (here Q298G) into a wild-type C. glutamicum strain by homologous recombination resulted in an accumulation of 58 g/liter L-lysine within 30 h of fed-batch fermentation in a bioreactor. PMID:21531824

  4. Rational design of allosteric regulation of homoserine dehydrogenase by a nonnatural inhibitor L-lysine.

    Science.gov (United States)

    Chen, Zhen; Rappert, Sugima; Zeng, An-Ping

    2015-02-20

    Allosteric proteins, which can sense different signals, are interesting biological parts for synthetic biology. In particular, the design of an artificial allosteric enzyme to sense an unnatural signal is both challenging and highly desired, for example, for a precise and dynamical control of fluxes of growth-essential but byproduct pathways in metabolic engineering of industrial microorganisms. In this work, we used homoserine dehydrogenase (HSDH) of Corynebacterium glutamicum, which is naturally allosterically regulated by threonine and isoleucine, as an example to demonstrate the feasibility of reengineering an allosteric enzyme to respond to an unnatural inhibitor L-lysine. For this purpose, the natural threonine binding sites of HSD were first predicted and verified by mutagenesis experiments. The threonine binding sites were then engineered to a lysine binding pocket. The reengineered HSD only responds to lysine inhibition but not to threonine. This is a significant step toward the construction of artificial molecular circuits for dynamic control of growth-essential byproduct formation pathway for lysine biosynthesis. PMID:24344690

  5. Allosteric ligands for the pharmacologically dark receptors GPR68 and GPR65.

    Science.gov (United States)

    Huang, Xi-Ping; Karpiak, Joel; Kroeze, Wesley K; Zhu, Hu; Chen, Xin; Moy, Sheryl S; Saddoris, Kara A; Nikolova, Viktoriya D; Farrell, Martilias S; Wang, Sheng; Mangano, Thomas J; Deshpande, Deepak A; Jiang, Alice; Penn, Raymond B; Jin, Jian; Koller, Beverly H; Kenakin, Terry; Shoichet, Brian K; Roth, Bryan L

    2015-11-26

    At least 120 non-olfactory G-protein-coupled receptors in the human genome are 'orphans' for which endogenous ligands are unknown, and many have no selective ligands, hindering the determination of their biological functions and clinical relevance. Among these is GPR68, a proton receptor that lacks small molecule modulators for probing its biology. Using yeast-based screens against GPR68, here we identify the benzodiazepine drug lorazepam as a non-selective GPR68 positive allosteric modulator. More than 3,000 GPR68 homology models were refined to recognize lorazepam in a putative allosteric site. Docking 3.1 million molecules predicted new GPR68 modulators, many of which were confirmed in functional assays. One potent GPR68 modulator, ogerin, suppressed recall in fear conditioning in wild-type but not in GPR68-knockout mice. The same approach led to the discovery of allosteric agonists and negative allosteric modulators for GPR65. Combining physical and structure-based screening may be broadly useful for ligand discovery for understudied and orphan GPCRs. PMID:26550826

  6. Allosteric transition and binding of small molecule effectors causes curvature change in central β-sheets of selected enzymes.

    Science.gov (United States)

    Tolonen, Ellen; Bueno, Brenda; Kulshreshta, Sanjeev; Cieplak, Piotr; Argáez, Miguel; Velázquez, Leticia; Stec, Boguslaw

    2011-04-01

    A quantitative description of allosteric transition remains a significant science challenge. Many allosteric enzymes contain a central β-sheet in their catalytic domain. When an allosteric protein undergoes the transition between T (tense) and R (relaxed) allosteric states, this central β-sheet undergoes a conformational change. A traditional method of measuring this change, the root mean square deviation (RMSD), appears to be inadequate to describe such changes in meaningful quantitative manner. We designed a novel quantitative method to demonstrate this conformational transition by measuring the change in curvature of the central β-sheet when enzymes transition between allosteric states. The curvature was established by calculating the semiaxes of a 3-D hyperboloid fitted by least squares to the Cα atomic positions of the β-sheet. The two enzymes selected for this study, fructose 1,6-bisphosphatase (FBPase) from pig kidney and aspartate carbamoyltransferase (ATCase) from E. coli, showed while transitioning between the allosteric states (T ⇔ R) a notable change in β-sheet curvature (∼5%) that results in a large lateral shift at the sheet's edge, which is necessary to convey the signal. The results suggest that the β-sheet participates in storing elastic energy associated with the transition. Establishing a tentative link between the energetics of the β-sheet in different allosteric states provides a more objective basis for the naming convention of allosteric states (tense or relaxed), and provides insight into the hysteretic nature of the transition. The approach presented here allows for a better understanding of the internal dynamics of allosteric enzymes by defining the domains that directly participate in the transition. PMID:20602244

  7. LED downlights with non-circular spots

    Science.gov (United States)

    Parkyn, William A.; Pelka, David G.

    2005-09-01

    The ubiquitous downlight inhabits our ceilings by the millions. Hot, inefficient, and electrically wasteful, it is next in line for replacement by the latest high-brightness, high-efficacy white LEDs. The conventional downlight configuration of a large incandescent spotlight in a low-cost, ceiling-recessed metal can, represents the culmination of old technology, fated never to improve significantly. Incandescent downlights add greatly both to direct and indirect electrical consumption, with the lamps requiring relatively frequent replacement. The small size of LED emitters means small optical elements can produce much higher-quality beams than incandescent spotlight-lamps can produce. Herein we introduce compact high-luminosity LED downlights with lenses that deliver uniform illumination to delimited targets such as tables. One version utilizes circular lenses and micro-diffuser films to deliver square outputs. The other uses lenses cut to the target shape. In particular, one of these lenses is the first to offer a semicircular spot suitable for gambling tables.

  8. Heat Capacity Changes and Disorder-to-Order Transitions in Allosteric Activation.

    Science.gov (United States)

    Cressman, William J; Beckett, Dorothy

    2016-01-19

    Allosteric coupling in proteins is ubiquitous but incompletely understood, particularly in systems characterized by coupling over large distances. Binding of the allosteric effector, bio-5'-AMP, to the Escherichia coli biotin protein ligase, BirA, enhances the protein's dimerization free energy by -4 kcal/mol. Previous studies revealed that disorder-to-order transitions at the effector binding and dimerization sites, which are separated by 33 Å, are integral to functional coupling. Perturbations to the transition at the ligand binding site alter both ligand binding and coupled dimerization. Alanine substitutions in four loops on the dimerization surface yield a range of energetic effects on dimerization. A glycine to alanine substitution at position 142 in one of these loops results in a complete loss of allosteric coupling, disruption of the disorder-to-order transitions at both functional sites, and a decreased affinity for the effector. In this work, allosteric communication between the effector binding and dimerization surfaces in BirA was further investigated by performing isothermal titration calorimetry measurements on nine proteins with alanine substitutions in three dimerization surface loops. In contrast to BirAG142A, at 20 °C all variants bind to bio-5'-AMP with free energies indistinguishable from that measured for wild-type BirA. However, the majority of the variants exhibit altered heat capacity changes for effector binding. Moreover, the ΔCp values correlate with the dimerization free energies of the effector-bound proteins. These thermodynamic results, combined with structural information, indicate that allosteric activation of the BirA monomer involves formation of a network of intramolecular interactions on the dimerization surface in response to bio-5'-AMP binding at the distant effector binding site. PMID:26678378

  9. Rocky Mountain Spotted Fever: Statistics and Epidemiology

    Science.gov (United States)

    ... The CDC Cancel Submit Search The CDC Rocky Mountain Spotted Fever (RMSF) Note: Javascript is disabled or ... please visit this page: About CDC.gov . Rocky Mountain Spotted Fever (RMSF) Symptoms, Diagnosis, and Treatment Statistics ...

  10. Improvements on analytic modelling of stellar spots

    CERN Document Server

    Montalto, M; Oshagh, M; Boisse, I; Bruno, G; Santos, N C

    2014-01-01

    In this work we present the solution of the stellar spot problem using the Kelvin-Stokes theorem. Our result is applicable for any given location and dimension of the spots on the stellar surface. We present explicitely the result up to the second degree in the limb darkening law. This technique can be used to calculate very efficiently mutual photometric effects produced by eclipsing bodies occulting stellar spots and to construct complex spot shapes.

  11. Interpreting spotted dolphin age distributions

    OpenAIRE

    Barlow, Jay; Hohn, Aleta A.

    1984-01-01

    Previous work has determined the age distribution from a sample of spotted dolphins (Stenella attenuata) killed in the eastern Pacific tuna purse-seine fishery. In this paper we examine the usefulness of this age distribution for estimating natural mortality rates. The observed age distribution has a deficiency of individuals from 5-15 years and cannot represent a stable age distribution. Sampling bias and errors in age interpretation are examined as possible causes of the "dip" in the obs...

  12. Probing the Sophisticated Synergistic Allosteric Regulation of Aromatic Amino Acid Biosynthesis in Mycobacterium tuberculosis Using ᴅ-Amino Acids

    Science.gov (United States)

    Reichau, Sebastian; Blackmore, Nicola J.; Jiao, Wanting; Parker, Emily J.

    2016-01-01

    Chirality plays a major role in recognition and interaction of biologically important molecules. The enzyme 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase (DAH7PS) is the first enzyme of the shikimate pathway, which is responsible for the synthesis of aromatic amino acids in bacteria and plants, and a potential target for the development of antibiotics and herbicides. DAH7PS from Mycobacterium tuberculosis (MtuDAH7PS) displays an unprecedented complexity of allosteric regulation, with three interdependent allosteric binding sites and a ternary allosteric response to combinations of the aromatic amino acids l-Trp, l-Phe and l-Tyr. In order to further investigate the intricacies of this system and identify key residues in the allosteric network of MtuDAH7PS, we studied the interaction of MtuDAH7PS with aromatic amino acids that bear the non-natural d-configuration, and showed that the d-amino acids do not elicit an allosteric response. We investigated the binding mode of d-amino acids using X-ray crystallography, site directed mutagenesis and isothermal titration calorimetry. Key differences in the binding mode were identified: in the Phe site, a hydrogen bond between the amino group of the allosteric ligands to the side chain of Asn175 is not established due to the inverted configuration of the ligands. In the Trp site, d-Trp forms no interaction with the main chain carbonyl group of Thr240 and less favourable interactions with Asn237 when compared to the l-Trp binding mode. Investigation of the MtuDAH7PSN175A variant further supports the hypothesis that the lack of key interactions in the binding mode of the aromatic d-amino acids are responsible for the absence of an allosteric response, which gives further insight into which residues of MtuDAH7PS play a key role in the transduction of the allosteric signal. PMID:27128682

  13. Structural Determinants Defining the Allosteric Inhibition of an Essential Antibiotic Target.

    Science.gov (United States)

    Soares da Costa, Tatiana P; Desbois, Sebastien; Dogovski, Con; Gorman, Michael A; Ketaren, Natalia E; Paxman, Jason J; Siddiqui, Tanzeela; Zammit, Leanne M; Abbott, Belinda M; Robins-Browne, Roy M; Parker, Michael W; Jameson, Geoffrey B; Hall, Nathan E; Panjikar, Santosh; Perugini, Matthew A

    2016-08-01

    Dihydrodipicolinate synthase (DHDPS) catalyzes the first committed step in the lysine biosynthesis pathway of bacteria. The pathway can be regulated by feedback inhibition of DHDPS through the allosteric binding of the end product, lysine. The current dogma states that DHDPS from Gram-negative bacteria are inhibited by lysine but orthologs from Gram-positive species are not. The 1.65-Å resolution structure of the Gram-negative Legionella pneumophila DHDPS and the 1.88-Å resolution structure of the Gram-positive Streptococcus pneumoniae DHDPS bound to lysine, together with comprehensive functional analyses, show that this dogma is incorrect. We subsequently employed our crystallographic data with bioinformatics, mutagenesis, enzyme kinetics, and microscale thermophoresis to reveal that lysine-mediated inhibition is not defined by Gram staining, but by the presence of a His or Glu at position 56 (Escherichia coli numbering). This study has unveiled the molecular determinants defining lysine-mediated allosteric inhibition of bacterial DHDPS. PMID:27427481

  14. Common Internal Allosteric Network Links Anesthetic Binding Sites in a Pentameric Ligand-Gated Ion Channel.

    Science.gov (United States)

    Joseph, Thomas T; Mincer, Joshua S

    2016-01-01

    General anesthetics bind reversibly to ion channels, modifying their global conformational distributions, but the underlying atomic mechanisms are not completely known. We examine this issue by way of the model protein Gloeobacter violaceous ligand-gated ion channel (GLIC) using computational molecular dynamics, with a coarse-grained model to enhance sampling. We find that in flooding simulations, both propofol and a generic particle localize to the crystallographic transmembrane anesthetic binding region, and that propofol also localizes to an extracellular region shared with the crystallographic ketamine binding site. Subsequent simulations to probe these binding modes in greater detail demonstrate that ligand binding induces structural asymmetry in GLIC. Consequently, we employ residue interaction correlation analysis to describe the internal allosteric network underlying the coupling of ligand and distant effector sites necessary for conformational change. Overall, the results suggest that the same allosteric network may underlie the actions of various anesthetics, regardless of binding site. PMID:27403526

  15. Watermarking spot colors in packaging

    Science.gov (United States)

    Reed, Alastair; Filler, TomáÅ.¡; Falkenstern, Kristyn; Bai, Yang

    2015-03-01

    In January 2014, Digimarc announced Digimarc® Barcode for the packaging industry to improve the check-out efficiency and customer experience for retailers. Digimarc Barcode is a machine readable code that carries the same information as a traditional Universal Product Code (UPC) and is introduced by adding a robust digital watermark to the package design. It is imperceptible to the human eye but can be read by a modern barcode scanner at the Point of Sale (POS) station. Compared to a traditional linear barcode, Digimarc Barcode covers the whole package with minimal impact on the graphic design. This significantly improves the Items per Minute (IPM) metric, which retailers use to track the checkout efficiency since it closely relates to their profitability. Increasing IPM by a few percent could lead to potential savings of millions of dollars for retailers, giving them a strong incentive to add the Digimarc Barcode to their packages. Testing performed by Digimarc showed increases in IPM of at least 33% using the Digimarc Barcode, compared to using a traditional barcode. A method of watermarking print ready image data used in the commercial packaging industry is described. A significant proportion of packages are printed using spot colors, therefore spot colors needs to be supported by an embedder for Digimarc Barcode. Digimarc Barcode supports the PANTONE spot color system, which is commonly used in the packaging industry. The Digimarc Barcode embedder allows a user to insert the UPC code in an image while minimizing perceptibility to the Human Visual System (HVS). The Digimarc Barcode is inserted in the printing ink domain, using an Adobe Photoshop plug-in as the last step before printing. Since Photoshop is an industry standard widely used by pre-press shops in the packaging industry, a Digimarc Barcode can be easily inserted and proofed.

  16. Spotted hyena from north China

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    @@ Acomplete fossil skeleton of spotted hyena unearthed on 26 July, 2008 in nearly perfect preservation, exhilarates CAS paleontologists, as the discovery in north China might offer new clues about the interactions between prehistoric faunas of Africa and Eurasia, and meanwhile afford a clue to the big extinction of large amount of species occurring about 11,000 years ago. Hinting at possible connections between species from Africa and Eurasia, the discovery would even provide new insights into the "out-of-Africa" model of human origins.

  17. Targeted Chemical Wedges Reveal the Role of Allosteric DNA Modulation in Protein — DNA Assembly

    OpenAIRE

    Moretti, Rocco; Donato, Leslie J.; Brezinski, Mary L.; Stafford, Ryan L.; Hoff, Helena; Thorson, Jon S.; Dervan, Peter B.; Ansari, Aseem Z.

    2008-01-01

    The cooperative assembly of multiprotein complexes results from allosteric modulations of DNA structure as well as direct intermolecular contacts between proteins. Such cooperative binding plays a critical role in imparting exquisite sequence specificity on the homeobox transcription factor (Hox) family of developmental transcription factors. A well-characterized example includes the interaction of Hox proteins with extradenticle (Exd), a highly conserved DNA binding transcription factor. Alt...

  18. Markov propagation of allosteric effects in biomolecular systems: application to GroEL–GroES

    OpenAIRE

    Chennubhotla, Chakra; Bahar, Ivet

    2006-01-01

    We introduce a novel approach for elucidating the potential pathways of allosteric communication in biomolecular systems. The methodology, based on Markov propagation of ‘information' across the structure, permits us to partition the network of interactions into soft clusters distinguished by their coherent stochastics. Probabilistic participation of residues in these clusters defines the communication patterns inherent to the network architecture. Application to bacterial chaperonin complex ...

  19. Coupled Dynamics and Entropic Contribution to the Allosteric Mechanism of Pin1.

    Science.gov (United States)

    Barman, Arghya; Hamelberg, Donald

    2016-08-25

    Allosteric communication in proteins regulates a plethora of downstream processes in subcellular signaling pathways. Describing the effects of cooperative ligand binding on the atomic level is a key to understanding many regulatory processes involving biomolecules. Here, we use microsecond-long molecular dynamics simulations to investigate the allosteric mechanism of Pin1, a potential therapeutic target and a phosphorylated-Ser/Thr dependent peptidyl-prolyl cis-trans isomerase that regulates several subcellular processes and has been implicated in many diseases, including cancer and Alzheimer's. Experimental studies suggest that the catalytic domain and the noncatalytic WW domain are allosterically coupled; however, an atomic level description of the dynamics associated with the interdomain communication is lacking. We show that binding of the substrate to the WW domain is directly coupled to the dynamics of the catalytic domain, causing rearrangement of the residue-residue contact dynamics from the WW domain to the catalytic domain. The binding affinity of the substrate in the catalytic domain is also enhanced upon binding of the substrate to the WW domain. Modulation of the dynamics of the catalytic domain upon binding of the substrate to the WW domain leads to prepayment of the entropic cost of binding the substrate to the catalytic domain. This study shows that Ile 28 at the interfacial region between the catalytic and WW domains is certainly one of the residues responsible for bridging the communication between the two domains. The results complement previous experiments and provide valuable atomistic insights into the role of dynamics and possible entropic contribution to the allosteric mechanism of proteins. PMID:27077947

  20. FR258900, a potential anti-hyperglycemic drug, binds at the allosteric site of glycogen phosphorylase

    OpenAIRE

    Tiraidis, C.; Alexacou, K. M.; Zographos, Spyros E.; Leonidas, Demetres D.; Gimisis, T.; Oikonomakos, Nikos G.

    2007-01-01

    FR258900 has been discovered as a novel inhibitor of human liver glycogen phosphorylase a and proved to suppress hepatic glycogen breakdown and reduce plasma glucose concentrations in diabetic mice models. To elucidate the mechanism of inhibition, we have determined the crystal structure of the cocrystallized rabbit muscle glycogen phosphorylase b–FR258900 complex and refined it to 2.2 Å resolution. The structure demonstrates that the inhibitor binds at the allosteric activator site, where th...

  1. Coevolutionary Analysis Enabled Rational Deregulation of Allosteric Enzyme Inhibition in Corynebacterium glutamicum for Lysine Production ▿

    OpenAIRE

    Chen, Zhen; Meyer, Weiqian; Rappert, Sugima; Sun, Jibin; Zeng, An-Ping

    2011-01-01

    Product feedback inhibition of allosteric enzymes is an essential issue for the development of highly efficient microbial strains for bioproduction. Here we used aspartokinase from Corynebacterium glutamicum (CgAK), a key enzyme controlling the biosynthesis of industrially important aspartate family amino acids, as a model to demonstrate a fast and efficient approach to the deregulation of allostery. In the last 50 years many researchers and companies have made considerable efforts to deregul...

  2. Characterization of an allosteric citalopram-binding site at the serotonin transporter

    DEFF Research Database (Denmark)

    Chen, Fenghua; Breum Larsen, Mads; Neubauer, Henrik Amtoft;

    2005-01-01

    -citalopram, sertraline,       serotonin and paroxetine. EC50 values for S- and R-citalopram are 3.6 +/-       0.4 microm and 19.4 +/- 2.3 microm, respectively. Fluoxetine, venlafaxine       and duloxetine have no significant effect on the dissociation of       [3H]S-citalopram. Allosteric modulation of dissociation is...

  3. Molecular Mechanism of Allosteric Communication in Hsp70 Revealed by Molecular Dynamics Simulations

    OpenAIRE

    Chiappori, Federica; Merelli, Ivan; Colombo, Giorgio; Milanesi, Luciano; Morra, Giulia

    2012-01-01

    Author Summary Allostery, or the capability of proteins to respond to ligand binding events with a variation in structure or dynamics at a distant site, is a common feature for biomolecular function and regulation in a large number of proteins. Intra-protein connections and inter-residue coordinations underlie allosteric mechanisms and react to binding primarily through a finely tuned modulation of motions and structures at the microscopic scale. Hence, all-atom molecular dynamics simulations...

  4. TOWARD UNDERSTANDING ALLOSTERIC SIGNALING MECHANISMS IN THE ATPASE DOMAIN OF MOLECULAR CHAPERONES

    OpenAIRE

    Liu, Ying; Bahar, Ivet

    2010-01-01

    The ATPase cycle of the heat shock protein 70 (HSP70) is largely dependent on the ability of its nucleotide binding domain (NBD), also called ATPase domain, to undergo structural changes between its open and closed conformations. We present here a combined study of the Hsp70 NBD sequence, structure and dynamic features to identify the residues that play a crucial role in mediating the allosteric signaling properties of the ATPase domain. Specifically, we identify the residues involved in the ...

  5. Allosteric Regulation of Histidine Kinases by Their Cognate Response Regulator Determines Cell Fate

    OpenAIRE

    Paul, Ralf; Jaeger, Tina; Abel, Sören; Wiederkehr, Irene; Folcher, Marc; Biondi, Emanuele G.; Laub, Michael T.; Jenal, Urs

    2008-01-01

    The two-component phosphorylation network is of critical importance for bacterial growth and physiology. Here, we address plasticity and interconnection of distinct signal transduction pathways within this network. In Caulobacter crescentus antagonistic activities of the PleC phosphatase and DivJ kinase localized at opposite cell poles control the phosphorylation state and subcellular localization of the cell fate determinator protein DivK. We show that DivK functions as an allosteric regulat...

  6. Structural basis for drug-induced allosteric changes to human β-cardiac myosin motor activity

    Science.gov (United States)

    Winkelmann, Donald A.; Forgacs, Eva; Miller, Matthew T.; Stock, Ann M.

    2015-08-01

    Omecamtiv Mecarbil (OM) is a small molecule allosteric effector of cardiac myosin that is in clinical trials for treatment of systolic heart failure. A detailed kinetic analysis of cardiac myosin has shown that the drug accelerates phosphate release by shifting the equilibrium of the hydrolysis step towards products, leading to a faster transition from weak to strong actin-bound states. The structure of the human β-cardiac motor domain (cMD) with OM bound reveals a single OM-binding site nestled in a narrow cleft separating two domains of the human cMD where it interacts with the key residues that couple lever arm movement to the nucleotide state. In addition, OM induces allosteric changes in three strands of the β-sheet that provides the communication link between the actin-binding interface and the nucleotide pocket. The OM-binding interactions and allosteric changes form the structural basis for the kinetic and mechanical tuning of cardiac myosin.

  7. FR258900, a potential anti-hyperglycemic drug, binds at the allosteric site of glycogen phosphorylase.

    Science.gov (United States)

    Tiraidis, Costas; Alexacou, Kyra-Melinda; Zographos, Spyros E; Leonidas, Demetres D; Gimisis, Thanasis; Oikonomakos, Nikos G

    2007-08-01

    FR258900 has been discovered as a novel inhibitor of human liver glycogen phosphorylase a and proved to suppress hepatic glycogen breakdown and reduce plasma glucose concentrations in diabetic mice models. To elucidate the mechanism of inhibition, we have determined the crystal structure of the cocrystallized rabbit muscle glycogen phosphorylase b-FR258900 complex and refined it to 2.2 A resolution. The structure demonstrates that the inhibitor binds at the allosteric activator site, where the physiological activator AMP binds. The contacts from FR258900 to glycogen phosphorylase are dominated by nonpolar van der Waals interactions with Gln71, Gln72, Phe196, and Val45' (from the symmetry-related subunit), and also by ionic interactions from the carboxylate groups to the three arginine residues (Arg242, Arg309, and Arg310) that form the allosteric phosphate-recognition subsite. The binding of FR258900 to the protein promotes conformational changes that stabilize an inactive T-state quaternary conformation of the enzyme. The ligand-binding mode is different from those of the potent phenoxy-phthalate and acyl urea inhibitors, previously described, illustrating the broad specificity of the allosteric site. PMID:17600143

  8. Peptide- and proton-driven allosteric clamps catalyze anthrax toxin translocation across membranes.

    Science.gov (United States)

    Das, Debasis; Krantz, Bryan A

    2016-08-23

    Anthrax toxin is an intracellularly acting toxin in which sufficient information is available regarding the structure of its transmembrane channel, allowing for detailed investigation of models of translocation. Anthrax toxin, comprising three proteins-protective antigen (PA), lethal factor (LF), and edema factor-translocates large proteins across membranes. Here we show that the PA translocase channel has a transport function in which its catalytic active sites operate allosterically. We find that the phenylalanine clamp (ϕ-clamp), the known conductance bottleneck in the PA translocase, gates as either a more closed state or a more dilated state. Thermodynamically, the two channel states have >300-fold different binding affinities for an LF-derived peptide. The change in clamp thermodynamics requires distant α-clamp and ϕ-clamp sites. Clamp allostery and translocation are more optimal for LF peptides with uniform stereochemistry, where the least allosteric and least efficiently translocated peptide had a mixed stereochemistry. Overall, the kinetic results are in less agreement with an extended-chain Brownian ratchet model but, instead, are more consistent with an allosteric helix-compression model that is dependent also on substrate peptide coil-to-helix/helix-to-coil cooperativity. PMID:27506790

  9. Hot Dry Rock; Geothermal Energy

    Energy Technology Data Exchange (ETDEWEB)

    None

    1990-01-01

    The commercial utilization of geothermal energy forms the basis of the largest renewable energy industry in the world. More than 5000 Mw of electrical power are currently in production from approximately 210 plants and 10 000 Mw thermal are used in direct use processes. The majority of these systems are located in the well defined geothermal generally associated with crustal plate boundaries or hot spots. The essential requirements of high subsurface temperature with huge volumes of exploitable fluids, coupled to environmental and market factors, limit the choice of suitable sites significantly. The Hot Dry Rock (HDR) concept at any depth originally offered a dream of unlimited expansion for the geothermal industry by relaxing the location constraints by drilling deep enough to reach adequate temperatures. Now, after 20 years intensive work by international teams and expenditures of more than $250 million, it is vital to review the position of HDR in relation to the established geothermal industry. The HDR resource is merely a body of rock at elevated temperatures with insufficient fluids in place to enable the heat to be extracted without the need for injection wells. All of the major field experiments in HDR have shown that the natural fracture systems form the heat transfer surfaces and that it is these fractures that must be for geothermal systems producing from naturally fractured formations provide a basis for directing the forthcoming but, equally, they require accepting significant location constraints on HDR for the time being. This paper presents a model HDR system designed for commercial operations in the UK and uses production data from hydrothermal systems in Japan and the USA to demonstrate the reservoir performance requirements for viable operations. It is shown that these characteristics are not likely to be achieved in host rocks without stimulation processes. However, the long term goal of artificial geothermal systems developed by systematic

  10. Energy is not Coffee. An assessment of blind spots on energy spot-markets

    Energy Technology Data Exchange (ETDEWEB)

    Jepma, C.J.; Spijker, E.; Van der Gaast, W.; De Jong, F. [Foundation Joint Implementation Network JIN, Paterswolde (Netherlands); Overmars, P. (ed.) [Energy Delta Institute EDI, Groningen (Netherlands)

    2006-01-15

    This study was to be the first in a series of studies on the title subject. It specifically focuses on the differences and similarities with a number of other spot-markets and aims to frame the energy spot markets and their potential development into a broader perspective. Main conclusion is that energy spot-markets differ from several other physical and non-physical spot-markets in many ways. This implies that 'perfect' energy spot-markets may inherently be (much) less perfect than other spot-markets that have approximated the stage of theoretical perfection.

  11. Energy is not Coffee. An assessment of blind spots on energy spot-markets

    International Nuclear Information System (INIS)

    This study was to be the first in a series of studies on the title subject. It specifically focuses on the differences and similarities with a number of other spot-markets and aims to frame the energy spot markets and their potential development into a broader perspective. Main conclusion is that energy spot-markets differ from several other physical and non-physical spot-markets in many ways. This implies that 'perfect' energy spot-markets may inherently be (much) less perfect than other spot-markets that have approximated the stage of theoretical perfection

  12. Thermomechanical finite element analysis of hot water boiler structure

    OpenAIRE

    Živković Dragoljub S.; Milčić Dragan S.; Banić Milan S.; Milosavljević Peđa M.

    2012-01-01

    The paper presents an application of the Finite Elements Method for stress and strain analysis of the hot water boiler structure. The aim of the research was to investigate the influence of the boiler scale on the thermal stresses and strains of the structure of hot water boilers. Results show that maximum thermal stresses appear in the zone of the pipe carrying wall of the first reversing chamber. This indicates that the most critical part of the boiler are weld spots of the smoke pipe...

  13. Optimizing glycosyltransferase specificity via ‘hot spot’ saturation mutagenesis presents a new catalyst for novobiocin glycorandomization

    OpenAIRE

    Williams, Gavin J.; Goff, Randal D.; Zhang, Changsheng; Thorson, Jon S.

    2008-01-01

    A comprehensive two phase ‘hot spot’ saturation mutagenesis strategy to rapidly evolve glycosyltransferase specificity for non-natural acceptors is described. Specifically, the application of a high throughput screen (based upon the fluorescent acceptor umbelliferone) was used to identify key amino acid ‘hot spots’ that contribute to GT proficiency and/or promiscuity. Saturation mutagenesis of the corresponding hot spots facilitated the utilization of a lower throughput screen to provide OleD...

  14. Spot Market Power and Future Market Trading

    OpenAIRE

    Muermann, Alexander; Shore, Stephen H.

    2005-01-01

    When a spot market monopolist participates in the futures market, he has an incentive to adjust spot prices to make his futures market position more pro…table. Rational futures market makers take this into account when they set prices. Spot market power thus creates a moral hazard problem which parallels the adverse selection problem in models with inside information. This moral hazard not only reduces the optimal amount of hedging for those with and without market power, but also makes compl...

  15. A spot market for electricity

    International Nuclear Information System (INIS)

    Electric utilities in many parts of the world are being transformed from regulated monopolies to competitive enterprises. They are buying power from sources they don't control, and experiencing new competitive pressures in selling. In response, utilities have begun to use such techniques as ''active demand-side management'' and ''real-time pricing'' to improve their responsiveness to customers and to create new opportunities for revenue. As an extension of the industry's evolution so far, this article describes how the utilities industry might develop a ''spot market'' for electricity, with the utility providing value in the form of a service for arbitrating requests and demands from various generators and users. The author presents a possible future organization of the electricity market, for which there is no model currently known. Most of its elements do exist in some form at one or more power companies around the world

  16. Ambystoma maculatum (spotted salamander). Reproduction

    Science.gov (United States)

    Glorioso, Brad M.; Waddle, Hardin; Hefner, Jeromi

    2012-01-01

    The Spotted Salamander is a wide-ranging salamander of the eastern United States that typically breeds in winter or early spring in ephemeral pools in lowland forests. Ambystoma maculatum is known to deposit 2-4 egg masses per year, each containing 1-250 eggs. As part of ongoing research into the ecology and reproductive biology of Spotted Salamanders in the Kisatchie District of Kisatchie National Forest in Natchitoches Parish, Louisiana, USA, we have been counting the number of embryos per egg mass. We captured seven female A. maculatum in a small pool, six of which were still gravid. We took standard measurements, including SVL, and then implanted a Passive Integrated Transponder (PIT tag) into each adult female as was the protocol. About an hour after processing these animals we marked new A. maculatum egg masses found in the same small pool using PVC pin flags pushed carefully through the outer jelly. We did not have enough time to process them that evening, and it was not until a few days later that we photographed those masses. We discovered that one of the masses contained a PIT tag in the outer jelly that corresponded to one of the six gravid females that were marked that same evening. To our knowledge, this is the first report of PIT tags being the means, albeit coincidentally, by which a particular egg mass of Ambystoma maculatum has been assigned to a particular female. For our purposes, losing the PIT tag from the adult female is counter to the goals of our study of this population, and we will no longer be implanting PIT tags into gravid females.

  17. Methane hydrate dissociation using inverted five-spot water flooding method in cubic hydrate simulator

    International Nuclear Information System (INIS)

    The combination forms of the hydrate dissociation methods in different well systems are divided into 6 main patterns. Dissociation processes of methane hydrate in porous media using the inverted five-spot water flooding method (Pattern 4) are investigated by the experimental observation and numerical simulation. In situ methane hydrate is synthesized in the Cubic Hydrate Simulator (CHS), a 5.832-L cubic reactor. A center vertical well is used as the hot water injection well, while the four vertical wells at the corner are the gas and water production wells. The gas production begins simultaneously with the hot water injection, while after approximately 20 min of compression, the water begins to be produced. One of the common characteristics of the inverted five-spot water flooding method is that both the gas and water production rates decrease with the reduction of the hydrate dissociation rate. The evaluation of the energy efficiency ratio might indicate the inverted five-spot water flooding as a promising gas producing method from the hydrate reservoir. - Highlights: • A three-dimensional 5.8-L cubic pressure vessel is developed. • Gas production of hydrate using inverted five-spot flooding method is studied. • Water/gas production rate and energy efficiency ratio are evaluated. • Temperature distributions of numerical simulation and experiment agree well. • Hydrate dissociation process is a moving boundary problem in this study

  18. Investigation of allosteric modulation mechanism of metabotropic glutamate receptor 1 by molecular dynamics simulations, free energy and weak interaction analysis

    Science.gov (United States)

    Bai, Qifeng; Yao, Xiaojun

    2016-02-01

    Metabotropic glutamate receptor 1 (mGlu1), which belongs to class C G protein-coupled receptors (GPCRs), can be coupled with G protein to transfer extracellular signal by dimerization and allosteric regulation. Unraveling the dimer packing and allosteric mechanism can be of great help for understanding specific regulatory mechanism and designing more potential negative allosteric modulator (NAM). Here, we report molecular dynamics simulation studies of the modulation mechanism of FITM on the wild type, T815M and Y805A mutants of mGlu1 through weak interaction analysis and free energy calculation. The weak interaction analysis demonstrates that van der Waals (vdW) and hydrogen bonding play an important role on the dimer packing between six cholesterol molecules and mGlu1 as well as the interaction between allosteric sites T815, Y805 and FITM in wild type, T815M and Y805A mutants of mGlu1. Besides, the results of free energy calculations indicate that secondary binding pocket is mainly formed by the residues Thr748, Cys746, Lys811 and Ser735 except for FITM-bound pocket in crystal structure. Our results can not only reveal the dimer packing and allosteric regulation mechanism, but also can supply useful information for the design of potential NAM of mGlu1.

  19. Experimental and simulated strength of spot welds

    DEFF Research Database (Denmark)

    Nielsen, Chris Valentin; Bennedbæk, Rune A.K.; Larsen, Morten B.;

    2014-01-01

    Weld strength testing of single spots in DP600 steel is presented for the three typical testing procedures, i.e. tensile-shear, cross-tension and peel testing. Spot welds are performed at two sets of welding parameters and strength testing under these conditions is presented by load-elongation cu...

  20. Rocky Mountain spotted fever in Argentina

    Science.gov (United States)

    Cases of epidemic typhus have been documented in Argentina since 1919; however, no confirmed reports of spotted fever rickettsiosis were described in this country until 1999. We describe the first molecular confirmation of Rickettsia rickettsii, the etiologic agent of Rocky Mountain spotted fever (R...