WorldWideScience

Sample records for allosteric hot spots

  1. Are 'hot spots' hot spots?

    Science.gov (United States)

    Foulger, Gillian R.

    2012-07-01

    The term 'hot spot' emerged in the 1960s from speculations that Hawaii might have its origins in an unusually hot source region in the mantle. It subsequently became widely used to refer to volcanic regions considered to be anomalous in the then-new plate tectonic paradigm. It carried with it the implication that volcanism (a) is emplaced by a single, spatially restricted, mongenetic melt-delivery system, assumed to be a mantle plume, and (b) that the source is unusually hot. This model has tended to be assumed a priori to be correct. Nevertheless, there are many geological ways of testing it, and a great deal of work has recently been done to do so. Two fundamental problems challenge this work. First is the difficulty of deciding a 'normal' mantle temperature against which to compare estimates. This is usually taken to be the source temperature of mid-ocean ridge basalts (MORBs). However, Earth's surface conduction layer is ˜200 km thick, and such a norm is not appropriate if the lavas under investigation formed deeper than the 40-50 km source depth of MORB. Second, methods for estimating temperature suffer from ambiguity of interpretation with composition and partial melt, controversy regarding how they should be applied, lack of repeatability between studies using the same data, and insufficient precision to detect the 200-300 °C temperature variations postulated. Available methods include multiple seismological and petrological approaches, modelling bathymetry and topography, and measuring heat flow. Investigations have been carried out in many areas postulated to represent either (hot) plume heads or (hotter) tails. These include sections of the mid-ocean spreading ridge postulated to include ridge-centred plumes, the North Atlantic Igneous Province, Iceland, Hawaii, oceanic plateaus, and high-standing continental areas such as the Hoggar swell. Most volcanic regions that may reasonably be considered anomalous in the simple plate-tectonic paradigm have been

  2. Conserved allosteric hot spots in the transmembrane domains of cystic fibrosis transmembrane conductance regulator (CFTR) channels and multidrug resistance protein (MRP) pumps.

    Science.gov (United States)

    Wei, Shipeng; Roessler, Bryan C; Chauvet, Sylvain; Guo, Jingyu; Hartman, John L; Kirk, Kevin L

    2014-07-18

    ATP-binding cassette (ABC) transporters are an ancient family of transmembrane proteins that utilize ATPase activity to move substrates across cell membranes. The ABCC subfamily of the ABC transporters includes active drug exporters (the multidrug resistance proteins (MRPs)) and a unique ATP-gated ion channel (cystic fibrosis transmembrane conductance regulator (CFTR)). The CFTR channel shares gating principles with conventional ligand-gated ion channels, but the allosteric network that couples ATP binding at its nucleotide binding domains (NBDs) with conformational changes in its transmembrane helices (TMs) is poorly defined. It is also unclear whether the mechanisms that govern CFTR gating are conserved with the thermodynamically distinct MRPs. Here we report a new class of gain of function (GOF) mutation of a conserved proline at the base of the pore-lining TM6. Multiple substitutions of this proline promoted ATP-free CFTR activity and activation by the weak agonist, 5'-adenylyl-β,γ-imidodiphosphate (AMP-PNP). TM6 proline mutations exhibited additive GOF effects when combined with a previously reported GOF mutation located in an outer collar of TMs that surrounds the pore-lining TMs. Each TM substitution allosterically rescued the ATP sensitivity of CFTR gating when introduced into an NBD mutant with defective ATP binding. Both classes of GOF mutations also rescued defective drug export by a yeast MRP (Yor1p) with ATP binding defects in its NBDs. We conclude that the conserved TM6 proline helps set the energy barrier to both CFTR channel opening and MRP-mediated drug efflux and that CFTR channels and MRP pumps utilize similar allosteric mechanisms for coupling conformational changes in their translocation pathways to ATP binding at their NBDs.

  3. 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.

  4. The puzzling MILAGRO hot spots

    CERN Document Server

    Drury, Luke

    2008-01-01

    We discuss the reported detection by the MILAGRO experiment of localised hot spots in the cosmic ray arrival distribution and the difficulty of interpreting these observations. A model based on secondary neutron production in the heliotail is shown to fail. An alternative model based on loss-cone leakage through a magnetic trap from a local source region is proposed.

  5. 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

  6. A Hot Spot in Coma

    CERN Document Server

    Donnelly, R H; Forman, W R; Jones, C; Churazov, E; Gilfanov, M R

    1999-01-01

    We study the temperature structure of the central part (r<18' ~0.7 h50**-1 Mpc) of the Coma cluster of galaxies using ASCA data. Two different analysis methods produce results in good agreement with each other and reveal the presence of interesting structures in the gas temperature distribution. Globally, the average temperature in the center of the cluster is 9.0 +/- 0.6 keV in good agreement with previous results. Superimposed on this, we find a cool area with temperatures of 4-6 keV associated with a filament of X-ray emission extending southeast from the cluster center detected by Vikhlinin and coworkers. We also find a hot spot with a temperature of around 13 keV displaced north from the central peak of emission. The distribution of the gas temperatures and relative specific entropies suggests that the cool features are most likely gas stripped from a galaxy group centered on NGC 4874 falling toward the core from outside, while the hot spot located ``ahead'' of this in-falling gas is due to shock heat...

  7. 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.

  8. 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.

  9. Modeling deflagration waves out of hot spots

    Science.gov (United States)

    Partom, Yehuda

    2017-01-01

    It is widely accepted that shock initiation and detonation of heterogeneous explosives comes about by a two-step process known as ignition and growth. In the first step a shock sweeping through 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 the cell depends on the speed of those deflagration waves and on the average distance between neighboring 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 waves may depend on both pressure and temperature. It depends on pressure for quasistatic loading near ambient temperature, and on temperature at high temperatures resulting from shock loading. From the simulation we obtain deflagration fronts emanating out of the hot spots. For 8 to 13 GPa shocks, the emanating fronts propagate as deflagration waves to consume the explosive between hot spots. For higher shock levels deflagration waves may interact with the sweeping shock to become detonation waves on the mesoscale. From the simulation results we extract average deflagration wave speeds.

  10. 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.

  11. 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.

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

    CERN Document Server

    Choi, David S; 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 quasi-stable, 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...

  13. Magnetic spots on hot massive stars

    CERN Document Server

    Cantiello, Matteo

    2011-01-01

    Hot luminous stars show a variety of phenomena in their photospheres and winds which still lack clear physical explanation. Among these phenomena are photospheric turbulence, line profile variability (LPV), non-thermal emission, non-radial pulsations, discrete absorption components (DACs) and wind clumping. Cantiello et al. (2009) argued that a convection zone close to the stellar surface could be responsible for some of these phenomena. This convective zone is caused by a peak in the opacity associated with iron-group elements and is referred to as the "iron convection zone" (FeCZ). Assuming dynamo action producing magnetic fields at equipartition in the FeCZ, we investigate the occurrence of subsurface magnetism in OB stars. Then we study the surface emergence of these magnetic fields and discuss possible observational signatures of magnetic spots. Simple estimates are made using the subsurface properties of massive stars, as calculated in 1D stellar evolution models. We find that magnetic fields of suffici...

  14. 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.

  15. 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.

  16. 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.

  17. Models and methods for hot spot safety work

    OpenAIRE

    Vistisen, Dorte; Thyregod, Poul; LAURSEN, Jan Grubb

    2002-01-01

    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 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 ...

  18. Hot spots of perforated forest in the eastern United States.

    Science.gov (United States)

    Riitters, Kurt H; Coulston, John W

    2005-04-01

    National assessments of forest fragmentation satisfy international biodiversity conventions, but they do not identify specific places where ecological impacts are likely. In this article, we identify geographic concentrations (hot spots) of forest located near holes in otherwise intact forest canopies (perforated forest) in the eastern United States, and we describe the proximate causes in terms of the non-forest land-cover types contained in those hot spots. Perforated forest, defined as a 0.09-ha unit of forest that is located at the center of a 7.29-ha neighborhood containing 60-99% forest with relatively low connectivity, was mapped over the eastern United States by using land-cover maps with roads superimposed. Statistically significant (P forest) were then located by using a spatial scan statistic. Hot spots were widely distributed and covered 20.4% of the total area of the 10 ecological provinces examined, but 50.1% of the total hot-spot area was concentrated in only two provinces. In the central part of the study area, more than 90% of the forest edge in hot spots was attributed to anthropogenic land-cover types, whereas in the northern and southern parts it was more often associated with semi-natural land cover such as herbaceous wetlands.

  19. 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 ...

  20. SYSTEMATIC AND DYNAMIC PROPER-TIES OF CASTING HOT SPOT

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    The variation of casting hot spot with proceeding of solidification and components of casting-mold system is studied by the technique of numerical simulation of solidification.The result shows that the thickest part of casting is not exactly the last part of solidification in the casting, while the last part of solidification is not exactly casting hot spot at the early stage of solidification.The location, size, shape and number of casting hot spot change with geomitric, physical and technological factors of the casting-mold system such as thickness of the casting secondary wall and with the passage of time in the course of the solidification.The former is known as the systematic property of hot spot and the latter, dynamic property.Only when the properties of hot spot are grasped completely and accurately, can it be fed more effectively.By doing so, not only sound castings can be obtained, but also riser efficiency can be improved.

  1. 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.

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

    Directory of Open Access Journals (Sweden)

    John E Fa

    Full Text Available 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.

  3. 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...

  4. Analysis of structural hot-spot stress in orthotropic plates

    Institute of Scientific and Technical Information of China (English)

    Chen Ce; Ji Bohai; Xu Hanjiang

    2012-01-01

    On the basis of the actual steel deck structure of Taizhou Bridge, this paper carries out hot-spot stress analysis on some key spots by using the finite element model which simulates local structure of orthotropic steel bridge decks. A finite element model is established for local structure of orthotropic steel bridge decks, and in the analysis of linear elasticity of the structure, face load is employed to simulate the loads from vehicle wheels. Analysis results show that main stresses are relatively heavy at the joints between diaphragm plates, top plates and U-shaped ribs and the joints between diaphragm plates and U-shaped ribs. These joints shall be regarded as key points for hot-spot stress analysis. Different mesh densities are adopted in the finite element model and the main stresses at different hot spots are contrasted and linear extrapolation is carried out using extrapolation formulae. Results show that different mesh densities have different influences on the hot-spot stresses at the welded seams of U-shaped ribs. These influences shall be considered in calculation and analysis.

  5. Plasmonic electromagnetic hot spots temporally addressed by photoinduced molecular displacement.

    Energy Technology Data Exchange (ETDEWEB)

    Juan, M. L.; Plain, J.; Bachelot, R.; Vial, A.; Royer, P.; Gray, S. K.; Montgomery, J. M.; Wiederrecht, G. P.; Univ. de Technologie de Troyes

    2009-04-23

    We report the observation of temporally varying electromagnetic hot spots in plasmonic nanostructures. Changes in the field amplitude, position, and spatial features are induced by embedding plasmonic silver nanorods in the photoresponsive azo-polymer. This polymer undergoes cis?trans isomerization and wormlike transport within resonant optical fields, producing a time-varying local dielectric environment that alters the locations where electromagnetic hot spots are produced. Finite-difference time-domain and Monte Carlo simulations that model the induced field and corresponding material response are presented to aid in the interpretation of the experimental results. Evidence for propagating plasmons induced at the ends of the rods is also presented.

  6. 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.

  7. Thermal imaging of hot spots in nanostructured microstripes

    Science.gov (United States)

    Saïdi, E.; Lesueur, J.; Aigouy, L.; Labéguerie-Egéa, J.; Mortier, M.

    2010-03-01

    By scanning thermal microscopy, we study the behavior of nanostructured metallic microstripes heated by Joule effect. Regularly spaced indentations have been made along the thin film stripe in order to create hot spots. For the designed stripe geometry, we observe that heat remains confined in the wire and in particular at shrinkage points within ~1μm2. Thermal maps have been obtained with a good lateral resolution (< 300nm) and a good temperature sensitivity (~1K).

  8. Magnetic hot-spots in hollow silicon cylinders

    Science.gov (United States)

    Baryshnikova, K. V.; Evlyukhin, A. B.; Shalin, A. S.

    2016-08-01

    Silicon nanoparticles can possess magnetic Mie-resonant response in the visible and near infrared wavelength ranges. In this paper, we consider numerically the features of magnetic hot-spots realized inside silicon nanocylinders at the conditions of the optical magnetic resonances, and show that the intensity of the magnetic field inside nanoparticles with a coaxial through hole can be much stronger than the intensity of incident light waves.

  9. Hot Spots and Persistence of Nitrate in Aquifers Across Scales

    Directory of Open Access Journals (Sweden)

    Dipankar Dwivedi

    2016-01-01

    Full Text Available Nitrate-N (NO3 -- N is one of the most pervasive contaminants in groundwater. Nitrate in groundwater exhibits long-term behavior due to complex interactions at multiple scales among various geophysical factors, such as sources of nitrate-N, characteristics of the vadose zone and aquifer attributes. To minimize contamination of nitrate-N in groundwater, it is important to estimate hot spots (>10 mg/L of NO3 -- N, trends and persistence of nitrate-N in groundwater. To analyze the trends and persistence of nitrate-N in groundwater at multiple spatio-temporal scales, we developed and used an entropy-based method along with the Hurst exponent in two different hydrogeologic settings: the Trinity and Ogallala Aquifers in Texas at fine (2 km × 2 km, intermediate (10 km × 10 km and coarse (100 km × 100 km scales. Results show that nitrate-N exhibits long-term persistence at the intermediate and coarse scales. In the Trinity Aquifer, overall mean nitrate-N has declined with a slight increase in normalized marginal entropy (NME over each decade from 1940 to 2008; however, the number of hot spots has increased over time. In the Ogallala Aquifer, overall mean nitrate-N has increased with slight moderation in NME since 1940; however, the number of hot spots has significantly decreased for the same period at all scales.

  10. Climate impacts on global hot spots of marine biodiversity

    Science.gov (United States)

    Ramírez, Francisco; Afán, Isabel; Davis, Lloyd S.; Chiaradia, André

    2017-01-01

    Human activities drive environmental changes at scales that could potentially cause ecosystem collapses in the marine environment. We combined information on marine biodiversity with spatial assessments of the impacts of climate change to identify the key areas to prioritize for the conservation of global marine biodiversity. This process identified six marine regions of exceptional biodiversity based on global distributions of 1729 species of fish, 124 marine mammals, and 330 seabirds. Overall, these hot spots of marine biodiversity coincide with areas most severely affected by global warming. In particular, these marine biodiversity hot spots have undergone local to regional increasing water temperatures, slowing current circulation, and decreasing primary productivity. Furthermore, when we overlapped these hot spots with available industrial fishery data, albeit coarser than our estimates of climate impacts, they suggest a worrying coincidence whereby the world’s richest areas for marine biodiversity are also those areas mostly affected by both climate change and industrial fishing. In light of these findings, we offer an adaptable framework for determining local to regional areas of special concern for the conservation of marine biodiversity. This has exposed the need for finer-scaled fishery data to assist in the management of global fisheries if the accumulative, but potentially preventable, effect of fishing on climate change impacts is to be minimized within areas prioritized for marine biodiversity conservation. PMID:28261659

  11. Distinguishing black holes and wormholes with orbiting hot spots

    Science.gov (United States)

    Li, Zilong; Bambi, Cosimo

    2014-07-01

    The supermassive black hole candidates at the center of every normal galaxy might be wormholes created in the early Universe and connecting either two different regions of our Universe or two different universes in a multiverse model. Indeed, the origin of these supermassive objects is not well understood; topological nontrivial structures like wormholes are allowed both in general relativity and in alternative theories of gravity, and current observations cannot rule out such a possibility. In a few years, the VLTI instrument GRAVITY will have the capability to image blobs of plasma orbiting near the innermost stable circular orbit of SgrA*, the supermassive black hole candidate in the Milky Way. The secondary image of a hot spot orbiting around a wormhole is substantially different from that of a hot spot around a black hole, because the photon capture sphere of the wormhole is much smaller. The radius of the photon capture sphere is independent of the hot spot model, and therefore its possible detection, which is observationally challenging but not out of reach, can unambiguously test if the center of our Galaxy harbors a wormhole rather than a black hole.

  12. 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

  13. Variation in the Deep Gas Composition in Hot Spots on Jupiter

    Science.gov (United States)

    Bjoraker, Gordon; de Pater, Imke; Wong, Michael H.; Adamkovics, Mate; Hewagama, Tilak; Hesman, Brigette

    2015-11-01

    We used CSHELL on NASA’s Infrared Telescope Facility and NIRSPEC on the Keck telescope in the last two years to spectrally resolve line profiles of CH3D, NH3, PH3, and H2O in 5-micron Hot Spots on Jupiter. The profile of the CH3D lines at 4.66 microns is very broad in both NEB and SEB Hot Spots due to collisions with up to 8 bars of H2, where unit optical depth occurs due to collision-induced H2 opacity. The extreme width of these CH3D features implies that the Hot Spots that we observed do not have significant cloud opacity for P > 2 bars. We retrieved NH3, PH3, and gaseous H2O within Hot Spots in both the NEB and SEB. We had dry nights on Mauna Kea and a sufficient Doppler shift to detect H2O. We will compare line wings to derive H2O profiles in the 2 to 6-bar region. NEB Hot Spots are depleted in NH3 with respect to adjacent regions. Interestingly, SEB Hot Spots exhibit stronger NH3 absorption than NEB Hot Spots. In addition, SEB Hot Spots have very similar 5-micron spectra as neighboring longitudes in the SEB, implying similar deep gas composition. The dynamical origin of SEB Hot Spots is much less studied than that of NEB Hot Spots, so our observations of gas composition in both regions may constrain mechanisms for forming Hot Spots.

  14. Current-induced forces and hot spots in biased nanojunctions.

    Science.gov (United States)

    Lü, Jing-Tao; Christensen, Rasmus B; Wang, Jian-Sheng; Hedegård, Per; Brandbyge, Mads

    2015-03-06

    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-principles calculations on realistic biased nanojunctions illustrate the importance of the effect.

  15. 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.

  16. 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...... 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-principles calculations on realistic biased nanojunctions illustrate the importance of the effect....

  17. Microblog Hot Spot Mining Based on PAM Probabilistic Topic Model

    Directory of Open Access Journals (Sweden)

    Zheng Yaxin

    2015-01-01

    Full Text Available Microblogs are short texts carried with limited information, which will increase the difficulty of topic mining. This paper proposes the use of PAM (Pachinko Allocation Model probabilistic topic model to extract the generative model of text’s implicit theme for microblog hot spot mining. First, three categories of microblog and the main contribution of this paper are illustrated. Second, for there are four topic models which are respectively explained, the PAM model is introduced in detail in terms of how to generate a document, the accuracy of document classification and the topic correlation in PAM. Finally, MapReduce is described. For the number of microblogs is huge as well as the number of contactors, the totally number of words is relatively small. With MapReduce, microblogs data are split by contactor, document-topic count matrix and contactor-topic count matrix can be locally stored while the word-topic count matrix must be globally stored. Thus, the hot spot mining can be achieved on the basis of PAM probabilistic topic model.

  18. Detecting traffic hot spots using vehicle tracking data

    Science.gov (United States)

    Xu, Zhimin; Lin, Zhiyong; Zhou, Cheng; Huang, Changqing

    2016-03-01

    Vehicle tracking data for thousands of urban vehicles and the availability of digital map provide urban planners unprecedented opportunities for better understanding urban transportation. In this paper, we aim to detect traffic hot spots on urban road networks using vehicle tracking data. Our approach first proposes an integrated map-matching algorithm based on the road buffer and vehicle driving direction, to find out which road segment the vehicle is travelling on. Then, we estimate travel speed by calculating the average the speed of every vehicle on a certain road segment, which indicates traffic status, and create the spatial weights matrices based on the connectivity of road segments, which expresses the spatial dependence between each road segment. Finally, the measure of global and local spatial autocorrelation is used to evaluate the spatial distribution of the traffic condition and reveal the traffic hot spots on the road networks. Experiments based on the taxi tracking data and urban road network data from Wuhan have been performed to validate the detection effectiveness.

  19. 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...

  20. Hot spot-derived shock initiation phenomena in heterogeneous nitromethane

    Energy Technology Data Exchange (ETDEWEB)

    Dattelbaum, Dana M [Los Alamos National Laboratory; Sheffield, Stephen A [Los Alamos National Laboratory; Stahl, David B [Los Alamos National Laboratory; Dattelbaum, Andrew M [Los Alamos National Laboratory

    2009-01-01

    The addition of solid silica particles to gelled nitromethane offers a tractable model system for interrogating the role of impedance mismatches as one type of hot spot 'seed' on the initiation behaviors of explosive formulations. Gas gun-driven plate impact experiments are used to produce well-defined shock inputs into nitromethane-silica mixtures containing size-selected silica beads at 6 wt%. The Pop-plots or relationships between shock input pressure and rundistance (or time)-to-detonation for mixtures containing small (1-4 {micro}m) and large (40 {micro}m) beads are presented. Overall, the addition of beads was found to influence the shock sensitivity of the mixtures, with the smaller beads being more sensitizing than the larger beads, lowering the shock initiation threshold for the same run distance to detonation compared with neat nitromethane. In addition, the use of embedded electromagnetic gauges provides detailed information pertaining to the mechanism of the build-up to detonation and associated reactive flow. Of note, an initiation mechanism characteristic of homogeneous liquid explosives, such as nitromethane, was observed in the nitromethane-40 {micro}m diameter silica samples at high shock input pressures, indicating that the influence of hot spots on the initiation process was minimal under these conditions.

  1. Distinguishing black holes and wormholes with orbiting hot spots

    CERN Document Server

    Li, Zilong

    2014-01-01

    The supermassive black hole candidates at the center of every normal galaxy might be wormholes created in the early Universe and connecting either two different regions of our Universe or two different universes in a Multiverse model. Indeed, the origin of these supermassive objects is not well understood, topological non-trivial structures like wormholes are allowed both in general relativity and in alternative theories of gravity, and current observations cannot rule out such a possibility. In a few years, the VLTI instrument GRAVITY will have the capability to image blobs of plasma orbiting near the innermost stable circular orbit of SgrA$^*$, the supermassive black hole candidate in the Milky Way. The secondary image of a hot spot orbiting around a wormhole is substantially different from the one of a hot spot around a black hole, because the photon capture sphere of the wormhole is much smaller, and its detection could thus test if the center of our Galaxy harbors a wormhole rather then a black hole.

  2. Probing binding hot spots at protein-RNA recognition sites.

    Science.gov (United States)

    Barik, Amita; Nithin, Chandran; Karampudi, Naga Bhushana Rao; Mukherjee, Sunandan; Bahadur, Ranjit Prasad

    2016-01-29

    We use evolutionary conservation derived from structure alignment of polypeptide sequences along with structural and physicochemical attributes of protein-RNA interfaces to probe the binding hot spots at protein-RNA recognition sites. We find that the degree of conservation varies across the RNA binding proteins; some evolve rapidly compared to others. Additionally, irrespective of the structural class of the complexes, residues at the RNA binding sites are evolutionary better conserved than those at the solvent exposed surfaces. For recognitions involving duplex RNA, residues interacting with the major groove are better conserved than those interacting with the minor groove. We identify multi-interface residues participating simultaneously in protein-protein and protein-RNA interfaces in complexes where more than one polypeptide is involved in RNA recognition, and show that they are better conserved compared to any other RNA binding residues. We find that the residues at water preservation site are better conserved than those at hydrated or at dehydrated sites. Finally, we develop a Random Forests model using structural and physicochemical attributes for predicting binding hot spots. The model accurately predicts 80% of the instances of experimental ΔΔG values in a particular class, and provides a stepping-stone towards the engineering of protein-RNA recognition sites with desired affinity.

  3. Probing binding hot spots at protein–RNA recognition sites

    Science.gov (United States)

    Barik, Amita; Nithin, Chandran; Karampudi, Naga Bhushana Rao; Mukherjee, Sunandan; Bahadur, Ranjit Prasad

    2016-01-01

    We use evolutionary conservation derived from structure alignment of polypeptide sequences along with structural and physicochemical attributes of protein–RNA interfaces to probe the binding hot spots at protein–RNA recognition sites. We find that the degree of conservation varies across the RNA binding proteins; some evolve rapidly compared to others. Additionally, irrespective of the structural class of the complexes, residues at the RNA binding sites are evolutionary better conserved than those at the solvent exposed surfaces. For recognitions involving duplex RNA, residues interacting with the major groove are better conserved than those interacting with the minor groove. We identify multi-interface residues participating simultaneously in protein–protein and protein–RNA interfaces in complexes where more than one polypeptide is involved in RNA recognition, and show that they are better conserved compared to any other RNA binding residues. We find that the residues at water preservation site are better conserved than those at hydrated or at dehydrated sites. Finally, we develop a Random Forests model using structural and physicochemical attributes for predicting binding hot spots. The model accurately predicts 80% of the instances of experimental ΔΔG values in a particular class, and provides a stepping-stone towards the engineering of protein–RNA recognition sites with desired affinity. PMID:26365245

  4. Cold spots in neonatal incubators are hot spots for microbial contamination.

    Science.gov (United States)

    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

    2011-12-01

    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. We therefore investigated whether the level of microbial contamination (i.e., the bacterial load) inside neonatal incubators can be predicted on the basis of their average temperature and relative humidity settings, paying special attention to local temperature differences. Swab samples were taken from the warmest and coldest spots found within Caleo incubators, and these were plated to determine the number of microbial CFU per location. In incubators with high average temperature (≥ 34°C) and relative humidity (≥ 60%) values, the level of microbial contamination was significantly higher at cold spots than at hot spots. This relates to the fact that the local equilibrium relative humidity at cold spots is sufficiently high to sustain microbial growth. The abundance of staphylococci, which are the main causative agents of late-onset sepsis in preterm neonates, was found to be elevated significantly in cold areas. These findings can be used to improve basic incubator hygiene.

  5. 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.

  6. Vascular design for reducing hot spots and stresses

    Science.gov (United States)

    Rocha, L. A. O.; Lorente, S.; Bejan, A.

    2014-05-01

    This paper is a proposal to embed tree-shaped vasculatures in a wall designed such that the wall withstands without excessive hot spots and peak stresses the intense heating and pressure that impinge on it. The vasculature is a quilt of square-shaped panels, each panel having a tree vasculature that connects the center with the perimeter. The vascular designs for volumetric cooling can be complemented by the shaping and distributing of channels for maximum strength and thermal performance at the same time. Numerical simulations of heat flow and thermal stresses in three directions show that it is possible to determine the optimal geometric features of configurations with radial channels and trees with radial and one level of bifurcations. The global performance is evaluated in terms of the overall thermal resistance and peak von Mises stresses. The dendritic design is superior under the studied thermal condition.

  7. 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.

  8. 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.

  9. 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.

  10. Identification of retinal transformation hot spots in developing Drosophila epithelia.

    Directory of Open Access Journals (Sweden)

    Claire L Salzer

    Full Text Available BACKGROUND: The retinal determination (RD network is an evolutionarily conserved regulatory circuit that governs early events in the development of eyes throughout the animal kingdom. Ectopic expression of many members of this network leads to the transformation of non-retinal epithelia into eye tissue. An often-overlooked observation is that only particular cell-populations within a handful of tissues are capable of having their primary developmental instructions superseded and overruled. METHODOLOGY/PRELIMINARY FINDINGS: Here we confirm that indeed, only a discrete number of cell populations within the imaginal discs that give rise to the head, antenna, legs, wings and halteres have the cellular plasticity to have their developmental fates altered. In contrast to previous reports, we find that all transformable cell populations do not lie within the TGFbeta or Hedgehog signaling domains. Additionally neither signaling cascade alone is sufficient for non-retinal cell types to be converted into retinal tissue. The transformation "hot spots" that we have identified appear to coincide with several previously defined transdetermination "weak spots", suggesting that ectopic eye formation is less the result of one network overriding the orders of another, as previously thought, but rather is the physical manifestation of redirecting cell populations of enormous cellular plasticity. We also demonstrate that the initiation of eye formation in non-retinal tissues occurs asynchronously compared to that of the normal eye suggesting that retinal development is not under the control of a global developmental clock. CONCLUSIONS/SIGNIFICANCE: We conclude that the subregions of non-retinal tissues that are capable of supporting eye formation represent specialized cell-populations that have a different level of plasticity than other cells within these tissues and may be the founder cells of each tissue.

  11. 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

  12. Multi-stable dissipative structures pinned to dual hot spots

    CERN Document Server

    Tsang, Cheng Hou; Chow, Kwok Wing

    2011-01-01

    We analyze the formation of one-dimensional localized patterns in a nonlinear dissipative medium including a set of two narrow "hot spots" (HSs), which carry the linear gain, local potential, cubic self-interaction, and cubic loss, while the linear loss acts in the host medium. This system can be realized, as a spatial-domain one, in optics, and also in Bose-Einstein condensates of quasi-particles in solid-state settings. Recently, exact solutions were found for localized modes pinned to the single HS represented by the delta-function. The present paper reports analytical and numerical solutions for coexisting two- and multi-peak modes, which may be symmetric or antisymmetric with respect to the underlying HS pair. Stability of the modes is explored through simulations of their perturbed evolution. The sign of the cubic nonlinearity plays a crucial role: in the case of the self-focusing, only the fundamental symmetric and antisymmetric modes, with two local peaks tacked to the HSs, and no additional peaks bet...

  13. Wafer hot spot identification through advanced photomask characterization techniques

    Science.gov (United States)

    Choi, Yohan; Green, Michael; McMurran, Jeff; Ham, Young; Lin, Howard; Lan, Andy; Yang, Richer; Lung, Mike

    2016-10-01

    As device manufacturers progress through advanced technology nodes, limitations in standard 1-dimensional (1D) mask Critical Dimension (CD) metrics are becoming apparent. Historically, 1D metrics such as Mean to Target (MTT) and CD Uniformity (CDU) have been adequate for end users to evaluate and predict the mask impact on the wafer process. However, the wafer lithographer's process margin is shrinking at advanced nodes to a point that the classical mask CD metrics are no longer adequate to gauge the mask contribution to wafer process error. For example, wafer CDU error at advanced nodes is impacted by mask factors such as 3-dimensional (3D) effects and mask pattern fidelity on subresolution assist features (SRAFs) used in Optical Proximity Correction (OPC) models of ever-increasing complexity. These items are not quantifiable with the 1D metrology techniques of today. Likewise, the mask maker needs advanced characterization methods in order to optimize the mask process to meet the wafer lithographer's needs. These advanced characterization metrics are what is needed to harmonize mask and wafer processes for enhanced wafer hot spot analysis. In this paper, we study advanced mask pattern characterization techniques and their correlation with modeled wafer performance.

  14. Distinct Rayleigh scattering from hot spot mutant p53 proteins reveals cancer cells.

    Science.gov (United States)

    Jun, Ho Joon; Nguyen, Anh H; Kim, Yeul Hong; Park, Kyong Hwa; Kim, Doyoun; Kim, Kyeong Kyu; Sim, Sang Jun

    2014-07-23

    The scattering of light redirects and resonances when an electromagnetic wave interacts with electrons orbits in the hot spot core protein and oscillated electron of the gold nanoparticles (AuNP). This report demonstrates convincingly that resonant Rayleigh scattering generated from hot spot mutant p53 proteins is correspondence to cancer cells. Hot spot mutants have unique local electron density changes that affect specificity of DNA binding affinity compared with wild types. Rayleigh scattering changes introduced by hot-spot mutations were monitored by localized surface plasmon resonance (LSPR) shift changes. The LSPR λmax shift for hot-spot mutants ranged from 1.7 to 4.2 nm for mouse samples and from 0.64 nm to 2.66 nm for human samples, compared to 9.6 nm and 15 nm for wild type and mouse and human proteins, respectively with a detection sensitivity of p53 concentration at 17.9 nM. It is interesting that hot-spot mutants, which affect only interaction with DNA, launches affinitive changes as considerable as wild types. These changes propose that hot-spot mutants p53 proteins can be easily detected by local electron density alterations that disturbs the specificity of DNA binding of p53 core domain on the surface of the DNA probed-nanoplasmonic sensor.

  15. Hot spot detection for breast cancer in Ki-67 stained slides: image dependent filtering approach

    Science.gov (United States)

    Niazi, M. Khalid Khan; Downs-Kelly, Erinn; Gurcan, Metin N.

    2014-03-01

    We present a new method to detect hot spots from breast cancer slides stained for Ki67 expression. It is common practice to use centroid of a nucleus as a surrogate representation of a cell. This often requires the detection of individual nuclei. Once all the nuclei are detected, the hot spots are detected by clustering the centroids. For large size images, nuclei detection is computationally demanding. Instead of detecting the individual nuclei and treating hot spot detection as a clustering problem, we considered hot spot detection as an image filtering problem where positively stained pixels are used to detect hot spots in breast cancer images. The method first segments the Ki-67 positive pixels using the visually meaningful segmentation (VMS) method that we developed earlier. Then, it automatically generates an image dependent filter to generate a density map from the segmented image. The smoothness of the density image simplifies the detection of local maxima. The number of local maxima directly corresponds to the number of hot spots in the breast cancer image. The method was tested on 23 different regions of interest images extracted from 10 different breast cancer slides stained with Ki67. To determine the intra-reader variability, each image was annotated twice for hot spots by a boardcertified pathologist with a two-week interval in between her two readings. A computer-generated hot spot region was considered a true-positive if it agrees with either one of the two annotation sets provided by the pathologist. While the intra-reader variability was 57%, our proposed method can correctly detect hot spots with 81% precision.

  16. 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

  17. HOT SPOT RELIEF WITH EMBEDDED BEAM FOR CDMA SYSTEMS IN HAPS

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    This paper proposes a novel micro/macro beam coverage scheme used in High Altitude Platform System (HAPS) Code Division Multiple Access (CDMA) systems. A relief of traffic burden in hot spot areas is achieved by embedding micro-beams into the macro-beams at the hot spot locations, together with appropriate power ratio control and user ratio control. The simulation results show that the hot spot problem can be relieved efficiently with the presented configuration, and a higher and more stable system capacity is expectable despite the variation of user distribution.

  18. Features of surface enhanced Raman scattering in the systems with «hot spots»

    Directory of Open Access Journals (Sweden)

    Solovyeva E.V.

    2017-01-01

    Full Text Available In this work we demonstrate the features of SERS on the substrates with «hot spots» on the example of system «diaminostilbene - colloidal silver». We found that «hot spots» forming on aggregated nanoparticles exist on the metal substrates only at low concentration of ligand. This effect caused by the gradual filling of first monolayer by adsorbate molecules. Significantly higher enhancement factor is obtained for substrates with «hot spots», for which the participation of resonance processes in the formation of SERS signal is revealed also.

  19. Features of surface enhanced Raman scattering in the systems with «hot spots»

    Science.gov (United States)

    Solovyeva, E. V.; Khazieva, D. A.; Denisova, A. S.

    2016-12-01

    In this work we demonstrate the features of SERS on the substrates with «hot spots» on the example of system «diaminostilbene - colloidal silver». We found that «hot spots» forming on aggregated nanoparticles exist on the metal substrates only at low concentration of ligand. This effect caused by the gradual filling of first monolayer by adsorbate molecules. Significantly higher enhancement factor is obtained for substrates with «hot spots», for which the participation of resonance processes in the formation of SERS signal is revealed also.

  20. 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

  1. Prediction of protein interaction hot spots using rough set-based multiple criteria linear programming.

    Science.gov (United States)

    Chen, Ruoying; Zhang, Zhiwang; Wu, Di; Zhang, Peng; Zhang, Xinyang; Wang, Yong; Shi, Yong

    2011-01-21

    Protein-protein interactions are fundamentally important in many biological processes and it is in pressing need to understand the principles of protein-protein interactions. Mutagenesis studies have found that only a small fraction of surface residues, known as hot spots, are responsible for the physical binding in protein complexes. However, revealing hot spots by mutagenesis experiments are usually time consuming and expensive. In order to complement the experimental efforts, we propose a new computational approach in this paper to predict hot spots. Our method, Rough Set-based Multiple Criteria Linear Programming (RS-MCLP), integrates rough sets theory and multiple criteria linear programming to choose dominant features and computationally predict hot spots. Our approach is benchmarked by a dataset of 904 alanine-mutated residues and the results show that our RS-MCLP method performs better than other methods, e.g., MCLP, Decision Tree, Bayes Net, and the existing HotSprint database. In addition, we reveal several biological insights based on our analysis. We find that four features (the change of accessible surface area, percentage of the change of accessible surface area, size of a residue, and atomic contacts) are critical in predicting hot spots. Furthermore, we find that three residues (Tyr, Trp, and Phe) are abundant in hot spots through analyzing the distribution of amino acids.

  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. Controlling Surface-plasmon-polariton Launching with Hot Spot Cylindrical Waves in a Metallic Slit Structure

    CERN Document Server

    Yao, Wenjie; Chen, Jianjun; Gong, Qihuang

    2015-01-01

    Plasmonic nanostructures, which are used to generate surface plasmon polaritions (SPPs), always involve sharp corners where the charges can accumulate. This can result in strong localized electromagnetic fields at the metallic corners, forming hot spots. The influence of the hot spots on the propagating SPPs are investigated theoretically and experimentally in a metallic slit structure. It is found that the electromagnetic fields radiated from the hot spots, termed as the hot spot cylindrical wave (HSCW), can greatly manipulate the SPP launching in the slit structure. The physical mechanism behind the manipulation of the SPP launching with the HSCW is explicated by a semi-analytic model. By using the HSCW, unidirectional SPP launching is experimentally realized in an ultra-small metallic step-slit structure. The HSCW bridges the localized surface plasmons and the propagating surface plasmons in an integrated platform and thus may pave a new route to the design of plasmonic devices and circuits.

  4. Fireball ejection from a molten hot spot to air by localized microwaves.

    Science.gov (United States)

    Dikhtyar, Vladimir; Jerby, Eli

    2006-02-03

    A phenomenon of fireball ejection from hot spots in solid materials (silicon, germanium, glass, ceramics, basalt, etc.) to the atmosphere is presented. The hot spot is created in the substrate material by the microwave-drill mechanism [Jerby, Science 298, 587 (2002)10.1126/science.1077062]. The vaporized drop evolved from the hot spot is blown up, and forms a stable fireball buoyant in the air. The experimental observations of fireball ejection from silicate hot spots are referred to the Abrahamson-Dinniss theory [Nature (London) 403, 519 (2000)10.1038/35000525] suggesting a mechanism for ball-lightning initiation in nature. The fireballs observed in our experiments tend to absorb the available microwave power entirely, similarly to the plasmon resonance effect in submicron wavelengths [Nie and Emory, Science 275, 1102 (1997)10.1126/science.275.5303.1102].

  5. 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.

  6. Modeling Hot Spot Motor Vehicle Theft Crime in Relation to Landuse and Settlement Patterns

    Directory of Open Access Journals (Sweden)

    Djaka Marwasta

    2004-01-01

    Full Text Available The crowd of Yogyakarta urban has impacted its surrounding area, including Depok sub district, which is indicated by the rising of physical development, for example education facilities and settlements. The progress does not only bring positive impact, but also negative impact for instance the rising of crime number i.e. motor vehicle robbery. The aims of this research are 1 mapping motor vehicle robbery data as the distribution map and identifying motor vehicle robbery hot spot base on distrbution map; and 2 studying the correlation of motor vehicle robbery hot spot with physical environment phenomena, i.e. land use type and settlement pattern. The research method consists of two parts; they are motor vehicle robbery cluster analysis and the relation of motor vehicle robbery and physical environment analysis. Motor vehicle robbery cluster analysis is using distribution data, which analyzes the distribution into motor vehicle robbery hot spot with nearest neighbor tehnique. Contingency coefficient and frequency distribution analysis is used to analyze the correlation of motor vehicle robbery hot spot and physical environment. Contingency coefficient is used to study the relation of motor vehicle robbery hot spot polygon with physical environment condition, whereas frequency distribution is used to study the distribution of motor vehicle robbery in the hot spot with physical environment condition. Physical environment which consists of land use type, housing density, house regularity pattern, and the average of building size, are obtained from interpretation of black and white panchromatic aerial photograph year 2000, in the scale 1 : 20.000. the most motor vehicle robbery hot spot is found on the settlement area, 68,3% from 378 motor vehicle robbery cases in the hot spot. The seond level is found on the education area (16.4%. The most motor vehicle hot spot in the settlement is found on the hight density and irregular settlement, which have big

  7. 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.

  8. 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.

  9. Avoiding Carbon Bed Hot Spots in Thermal Process Off-Gas Systems

    Energy Technology Data Exchange (ETDEWEB)

    Nick Soelberg; Joe Enneking

    2011-05-01

    Mercury has had various uses in nuclear fuel reprocessing and other nuclear processes, and so is often present in radioactive and mixed (radioactive and hazardous) wastes. Test programs performed in recent years have shown that mercury in off-gas streams from processes that treat radioactive wastes can be controlled using fixed beds of activated sulfur-impregnated carbon, to levels low enough to comply with air emission regulations such as the Hazardous Waste Combustor (HWC) Maximum Achievable Control Technology (MACT) standards. Carbon bed hot spots or fires have occurred several times during these tests, and also during a remediation of tanks that contained mixed waste. Hot spots occur when localized areas in a carbon bed become heated to temperatures where oxidation occurs. This heating typically occurs due to heat of absoption of gas species onto the carbon, but it can also be caused through external means such as external heaters used to heat the carbon bed vessel. Hot spots, if not promptly mitigated, can grow into bed fires. Carbon bed hot spots and fires must be avoided in processes that treat radioactive and mixed waste. Hot spots are detected by (a) monitoring in-bed and bed outlet gas temperatures, and (b) more important, monitoring of bed outlet gas CO concentrations. Hot spots are mitigated by (a) designing for appropriate in-bed gas velocity, for avoiding gas flow maldistribution, and for sufficient but not excessive bed depth, (b) appropriate monitoring and control of gas and bed temperatures and compositions, and (c) prompt implementation of corrective actions if bed hot spots are detected. Corrective actions must be implemented quickly if bed hot spots are detected, using a graded approach and sequence starting with corrective actions that are simple, quick, cause the least impact to the process, and are easiest to recover from.

  10. 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.

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

    Science.gov (United States)

    Kane, Ronald J.; Tringe, Joseph W.; Klunder, Gregory L.; Baluyot, Emer V.; Densmore, John M.; Converse, Mark C.

    2017-01-01

    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 plume diameter as a function of time. 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.

  12. Understanding and controlling hot spots of crime: the importance of formal and informal social controls.

    Science.gov (United States)

    Weisburd, David; Groff, Elizabeth R; Yang, Sue-Ming

    2014-02-01

    Primary, secondary, and tertiary prevention programs that address opportunity or structural factors related to crime are usually delivered to entire cities, sections of cities or to specific neighborhoods, but our results indicate geographically targeting these programs to specific street segments may increase their efficacy. We link crime incidents to over 24,000 street segments (the two block faces on a street between two intersections) over a 16-year period, and identify distinct developmental patterns of crime at street segments using group-based trajectory analysis. One of these patterns, which we term chronic crime hot spots, includes just 1 % of street segments but is associated with 23 % of crime in the city during the study period. We then employ multinomial regression to identify the specific risk and protective factors that are associated with these crime hot spots. We find that both situational opportunities and social characteristics of places strongly distinguish chronic crime hot spots from areas with little crime. Our findings support recent efforts to decrease crime opportunities at crime hot spots through programs like hot spots policing, but they also suggest that social interventions directed at crime hot spots will be important if we are to do something about crime problems in the long run. We argue in concluding that micro level programs which focus crime prevention efforts on specific street segments have the potential to be less costly and more effective than those targeted at larger areas such as communities or neighborhoods.

  13. 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.

  14. 40 CFR 93.123 - Procedures for determining localized CO, PM10, and PM2.5 concentrations (hot-spot analysis).

    Science.gov (United States)

    2010-07-01

    ... ratio of future to current traffic and the ratio of future to current emission factors. (3) Hot-spot... CO, PM10, and PM2.5 concentrations (hot-spot analysis). 93.123 Section 93.123 Protection of... concentrations (hot-spot analysis). (a) CO hot-spot analysis. (1) The demonstrations required by §...

  15. Hot spot(s) of the lung in technetium-99m albumin colloid liver-spleen scintigraphy: case report

    Energy Technology Data Exchange (ETDEWEB)

    Shih, W.J.; Brandenburg, S.; Coupal, J.J.; Sullivan, J.D.; Beeler, J.A.; Magoun, S.; Ryo, U.Y.

    1988-06-01

    The authors replaced /sup 99m/Tc albumin colloid for /sup 99m/Tc sulfur colloid as a radiopharmaceutical for liver-spleen imaging and found two instances of hot spot(s) in the lung. The preparation procedure of albumin colloid is easier and more convenient as compared to that of sulfur colloid. Whereas replacement of /sup 99m/Tc sulfur colloid by /sup 99m/Tc albumin colloid is inevitable, it should be emphasized that one should avoid blood withdrawal in the syringe containing albumin colloid to prevent formation of clot(s) during the venous puncture for /sup 99m/Tc albumin colloid.

  16. Joule heating hot spot at high latitudes in the afternoon sector

    Science.gov (United States)

    Cai, L.; Aikio, A. T.; Milan, S. E.

    2016-07-01

    The afternoon Joule heating hot spot has been studied statistically by using the EISCAT Svalbard Radar (ESR) measurements at 75.4° Corrected Geomagnetic latitude (CGMLAT) and the OMNI solar wind data base. For a small subset of events, the Active Magnetosphere and Planetary Electrodynamics Response Experiment (AMPERE) field-aligned current distributions have been available. The main results are as follows. Afternoon Joule heating hot spots are associated with high values of ionospheric electric fields and slightly enhanced Pedersen conductances. The Joule heating hot spot values are larger in summer than in winter, which can be explained by the higher Pedersen conductances during summer than winter. The afternoon Joule heating hot spots are located close to the reversals of the large-scale field-aligned current systems. The most common location is close to the Region 1/Region 2 boundary and those events are associated with sunward convecting F region plasma. In a few cases, the hot spots take place close to the Region 1/Region 0 boundary and then the ionospheric plasma is convecting antisunward. The hot spots may occur both during slow (450 km/s) speed solar wind conditions. During slow-speed solar wind events, the dominant interplanetary magnetic field (IMF) direction is southward, which is the general requirement for the low-latitude magnetic merging at the dayside magnetopause. During high-speed solar wind, also northward IMF conditions appear, but those are associated with large values of the IMF |By| component, making again the dayside magnetopause merging possible. Finally, the measured afternoon hot spot Joule heating rates are not a linear function of the solar wind energy coupling function.

  17. What controls the distribution and tectono-magmatic features of oceanic hot spot volcanoes

    Science.gov (United States)

    Acocella, Valerio; Vezzoli, Luigina

    2016-04-01

    Hot spot oceanic volcanoes worldwide show significant deviations from the classic Hawaiian reference model; these mainly concern the distribution of edifices and overall tectono-magmatic features, as the development of the volcanic rift zones and extent of flank instability. Here we try to explain these deviations investigating and comparing the best-known hot spot oceanic volcanoes. At a general scale, these volcanoes show an age-distance progression ranging from focused to scattered. This is here explained as due to several independent factors, as the thermal or mechanical weakening of the plate (due to the lithosphere thickness or regional structures, respectively), or the plume structure. At a more detailed scale, hot spot volcanoes show recurrent features, including mafic shield edifices with summit caldera and volcanic rift zones, often at the head of an unstable flank. However, despite this recurrence, a widespread tectono-magmatic variability is often found. Here we show how this variability depends upon the magma supply and age of the oceanic crust (influencing the thickness of the overlying pelagic sediments). Well-developed rift zones and larger collapses are found on hot spot volcanoes with higher supply rate and older crust, as Hawaii and Canary Islands. Poorly-developed rift zones and limited collapses occur on hot spot volcanoes with lower supply rate and younger crust, as Easter Island and Ascension. Transitional features are observed at hot spots with intermediate productivity (Cape Verde, Reunion, Society Islands and, to a minor extent, the Azores), whereas the scarcity or absence of pelagic sediments may explain the lack of collapses and developed rift zones in the productive Galapagos hot spot.

  18. 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

  19. Postharvest Propionic Acid and Hot Water Treatment for the Control of Black Spot ntrol of Black Spot

    Directory of Open Access Journals (Sweden)

    Tao Liu

    2014-02-01

    Full Text Available Black spot disease caused by Alternaria alternata (Fr. is one of the main postharvest diseases of Chinese Ya pears and causes serious economic loss during storage. The fungi-toxicity of postharvest propionic acid and hot water treatment at different concentrations and temperatures was investigated in vitro and directly on Ya pears. The in vitro results showed that A. alternata was susceptible to propionic acid solutions at all tested temperatures. The toxicity of propionic acid increased linearly and the LC 99 decreased from 13.43 to 4.31 g/L with an increase in temperature from 20 to 45C. The results in Ya pears showed that propionic acid and hot water treatment dramatically controlled black spot disease and 99% inhibition was achieved upon treatment with 9 g/L propionic acid solution for 30 min at 45C. Furthermore, the treatment inhibited the respiration of fruits and did not cause any adverse effects on other quality parameters; however, slight surface injury was noted at 9 g/L. The safety of propionic acid treatment was further confirmed by residue analysis. The results of this study suggest that postharvest propionic acid and hot water treatment is an alternative method for the control of black spot disease in Ya pears.

  20. Allele-dependent recombination frequency: homology requirement in meiotic recombination at the hot spot in the mouse major histocompatibility complex.

    Science.gov (United States)

    Yoshino, M; Sagai, T; Lindahl, K F; Toyoda, Y; Moriwaki, K; Shiroishi, T

    1995-05-20

    Meiotic recombination break joints in the mouse major histocompatibility complex (MHC) are clustered within short segments known as hot spots. We systematically investigated the requirement for sequence homology between two chromosomes for recombination activity at the hot spot next to the Lmp2 gene. The results indicated that a high rate of recombination required a high degree of similarity of overall genome structure at the hot spot. In particular, the same copy number of repetitive sequences within the hot spot was essential for a high frequency of recombination, suggesting that recombination in mouse meiosis is more sensitive to heterozygous deletion or insertion of DNA than to mismatches of single-base substitutions.

  1. 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.

  2. Wavelength modulated SERS hot spot distribution in 1D nanostructures on metal film

    Science.gov (United States)

    Wang, Lili; Zeng, Xiping; Liu, Ting; Zhang, Xuemei; Wei, Hua; Huang, Yingzhou; Liu, Anping; Wang, Shuxia; Wen, Weijia

    2016-10-01

    Surface plasmons confining strong electromagnetic fields near metal surfaces, well-known as hot spots, provide an extremely efficient platform for surface-enhanced Raman scattering (SERS). In this work, SERS spectra of probing molecules in a silver particle-wire 1D nanostructure on a thin gold film are investigated. The Raman features of SERS spectra collected at the particle-wire joints exhibit an obvious wavelength dependence phenomenon. This result is confirmed electromagnetic field simulation, revealing that hot spot distribution is sensitively influenced by the wavelength of incident light at the joints. Further studies indicate this wavelength dependence of hot spot distribution is immune to influence from the geometric shape of the particle or the angle between wire and particle, which improves fabrication tolerance. This technology may have promising applications in surface plasmon related fields, such as ultrasensors, solar energy and selective surface catalysis.

  3. 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.

  4. Semi-automatic Epileptic Hot Spot Detection in ECD brain SPECT images

    Science.gov (United States)

    Papp, Laszlo; Zuhayra, Maaz; Henze, Eberhard

    A method is proposed to process ECD brain SPECT images representing epileptic hot spots inside the brain. For validation 35 ictal —interictal patient image data were processed. The images were registered by a normalized mutual information method, then the separation of the suspicious and normal brain areas were performed by two threshold-based segmentations. Normalization between the images was performed by local normal brain mean values. Based on the validation made by two medical physicians, minimal human intervention in the segmentation parameters was necessary to detect all epileptic spots and minimize the number of false spots inside the brain.

  5. Dissection of a circumscribed recombination hot spot in HIV-1 after a single infectious cycle.

    Science.gov (United States)

    Galetto, Román; Giacomoni, Véronique; Véron, Michel; Negroni, Matteo

    2006-02-03

    Recombination is a major source of genetic heterogeneity in the human immunodeficiency virus type 1 (HIV-1) population. The main mechanism responsible for the generation of recombinant viruses is a process of copy choice between the two copies of genomic RNA during reverse transcription. We previously identified, after a single cycle of infection of cells in culture, a recombination hot spot within the gp120 gene, corresponding to the top portion of a RNA hairpin. Here, we determine that the hot region is circumscribed to 18 nucleotides located in the descending strand of the stem, following the sense of reverse transcription. Three factors appeared to be important, albeit at different extents, for the high rate of recombination observed in this region. The position of the hot sequence in the context of the RNA structure appears crucial, because changing its location within this structure triggered differences in recombination up to 20-fold. Another pivotal factor is the presence of a perfectly identical sequence between donor and acceptor RNA in the region of transfer, because single or double nucleotide differences in the hot spot were sufficient to almost completely abolish recombination in the region. Last, the primary structure of the hot region also influenced recombination, although with effects only in the 2-3-fold range. Altogether, these results provide the first molecular dissection of a hot spot in infected cells and indicate that several factors contribute to the generation of a site of preferential copy choice.

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

    KAUST Repository

    Wang, Jim Jing-Yan

    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.

  7. 75 FR 29537 - Draft Transportation Conformity Guidance for Quantitative Hot-spot Analyses in PM2.5

    Science.gov (United States)

    2010-05-26

    ... Transportation Conformity Guidance for Quantitative Hot- spot Analyses in PM 2.5 and PM 10 Nonattainment and... Public Comment. SUMMARY: EPA is announcing the availability of a draft transportation conformity guidance... quantitative PM 2.5 and PM 10 hot-spot analyses for project- level transportation conformity determinations...

  8. THE PROBLEM OF HOT-SPOTS IN MICROWAVE EQUIPMENT USED FOR PREPARATORY TECHNIQUES - THEORY AND PRACTICE

    NARCIS (Netherlands)

    KOK, LP; BOON, ME; SMID, HM

    1993-01-01

    Electron microscopists who wants to use a microwave (MW) oven to stimulate preparatory processes are sooner or later confronted with the problem of hot spots. It soon becomes clear to the user of any MW oven that the energy distribution-thus the speed of absorbing energy, and hence warming up-varies

  9. Hot Spots and Trends in Developing China's Tourism Industry

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    It is stated in China's Tourism Development from 2002 to 2004: Analysis and Prediction, written by experts organized by Research Center of Tourism of China Academy of Social Science that eight hot spots have arisen and future trends in Chinese tourism development has been embodied in eight aspects since 2002.

  10. Piezo-Electric Hypothesis for Hot Spot Formation Leading to Detonation

    Science.gov (United States)

    Montgomery, D. S.; Cawkwell, M. J.; Ramos, K. J.

    2015-06-01

    The impact to detonation sequence has been a long standing mystery in high explosives (HE). It is widely recognized that detonation begins in spatially-localized ``hot spots'' where chemistry initiates, but the physical mechanisms leading to hot spot formation are unknown. Here we revisit an old hypothesis, first suggested by Maycock and Grabenstein, that piezo-electric effects may be the cause of hot spot formation since most solid HE materials are observed to be highly piezo-electric. In this scenario, shock-induced pressure leads to electric fields of 100's MV/m, sufficient for dielectric breakdown and breaking chemical bonds, rather than via thermal effects. Extrapolation of statically measured piezo-electric coefficients for several HE materials suggests that shock pressures > 100-kbar might lead to field strengths > 100 - 1000 MV/m, but no definitive experimental proof has been obtained to support this. Here we discuss possible experiments to test this hypothesis by measuring the electric field in dynamic HE experiments correlated with hot spot formation. Work performed under the auspices of DOE by LANL under contract DE-AC52-06NA25396.

  11. 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.

  12. 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 .

  13. Identification of hot spots of malaria transmission for targeted malaria control.

    NARCIS (Netherlands)

    Bousema, T.; Drakeley, C.; Gesase, S.; Hashim, R.; Magesa, S.; Mosha, F.; Otieno, S.; Carneiro, I.; Cox, J.; Msuya, E.; Kleinschmidt, I.; Maxwell, C.; Greenwood, B.; Riley, E.; Sauerwein, R.W.; Chandramohan, D.; Gosling, R.

    2010-01-01

    BACKGROUND: Variation in the risk of malaria within populations is a frequently described but poorly understood phenomenon. This heterogeneity creates opportunities for targeted interventions but only if hot spots of malaria transmission can be easily identified. METHODS: We determined spatial patte

  14. 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 opt...

  15. QPO emission from moving hot spots on the surface of neutron stars: a model

    CERN Document Server

    Bachetti, Matteo; Kulkarni, Akshay; Burderi, Luciano; di Salvo, Tiziana

    2009-01-01

    We present recent results of 3D magnetohydrodynamic simulations of neutron stars with small misalignment angles, as regards the features in light curves produced by regular movements of the hot spots during accretion onto the star. In particular, we show that the variation of position of the hot spot created by the infalling matter, as observed in 3D simulations, can produce high frequency Quasi Periodic Oscillations with frequencies associated with the inner zone of the disk. Simulations show that the usual assumption of a fixed hot spot near the polar region is valid only for misalignment angles relatively large. Otherwise, two phenomena challenge the assumption: one is the presence of Rayleigh-Taylor instabilities at the disk-magnetospheric boundary (e.g. Kulkarni & Romanova 2008), which produce tongues of accreting matter that can reach the star almost anywhere between the equator and the polar region; the other one is the motion of the hot spot around the magnetic pole during stable accretion (e.g. R...

  16. 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....... persimilis hot-spot treatments in commercial cut rose production, effectively reducing pest management costs with no loss in crop yield.......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 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...

  17. 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

  18. Galapagos-OIB signature in southern Central America: Mantle refertilization by arc-hot spot interaction

    Science.gov (United States)

    Gazel, Esteban; Carr, Michael J.; Hoernle, Kaj; Feigenson, Mark D.; Szymanski, David; Hauff, Folkmar; van den Bogaard, Paul

    2009-02-01

    Although most Central American magmas have a typical arc geochemical signature, magmas in southern Central America (central Costa Rica and Panama) have isotopic and trace element compositions with an ocean island basalt (OIB) affinity, similar to the Galapagos-OIB lavas (e.g., Ba/La 10, 206Pb/204Pb > 18.8). Our new data for Costa Rica suggest that this signature, unusual for a convergent margin, has a relatively recent origin (Late Miocene ˜6 Ma). We also show that there was a transition from typical arc magmas (analogous to the modern Nicaraguan volcanic front) to OIB-like magmas similar to the Galapagos hot spot. The geographic distribution of the Galapagos signature in recent lavas from southern Central America is present landward from the subduction of the Galapagos hot spot tracks (the Seamount Province and the Cocos/Coiba Ridge) at the Middle American Trench. The higher Pb isotopic ratios, relatively lower Sr and Nd isotopic ratios, and enriched incompatible-element signature of central Costa Rican magmas can be explained by arc-hot spot interaction. The isotopic ratios of central Costa Rican lavas require the subducting Seamount Province (Northern Galapagos Domain) component, whereas the isotopic ratios of the adakites and alkaline basalts from southern Costa Rica and Panama are in the geochemical range of the subducting Cocos/Coiba Ridge (Central Galapagos Domain). Geological and geochemical evidence collectively indicate that the relatively recent Galapagos-OIB signature in southern Central America represents a geochemical signal from subducting Galapagos hot spot tracks, which started to collide with the margin ˜8 Ma ago. The Galapagos hot spot contribution decreases systematically along the volcanic front from central Costa Rica to NW Nicaragua.

  19. Cassini VIMS Spectra of the Thermal Emission from Hot Spots Along Enceladus South Pole Fissures

    Science.gov (United States)

    Goguen, Jay D.; Buratti, Bonnie J.; Cassini VIMS Team

    2016-10-01

    Most of the south pole fissure region has not been directly illuminated by sunlight since the sub-solar point moved into the northern hemisphere in 2009, thereby eliminating the background of reflected sunlight at VIMS wavelengths and making the fissure thermal emission readily measureable. Since then, VIMS has measured spectra of at least 11 hot spots along the fissures. Most of these measurements were acquired in ride-along mode with CIRS as the prime instrument. During at least 2 encounters, VIMS and CIRS acquired simultaneous or near-simultaneous spectra of the same fissure location. VIMS spectra include multiple hot spots along Damascus, Baghdad, Cairo, and a likely hot spot on Alexandria.All of the VIMS spectra examined to date are consistent with this scenario of a self-regulating fissure maximum T~200 K with brighter VIMS emissions corresponding to fissures up to ~20 m wide. Emission from the warm fissure interior walls dominate the VIMS spectra with <15% contributed by conductive heating of the adjacent terrain at VIMS wavelengths.CIRS spectra report slightly cooler T's due to CIRS increased sensitivity to lower T emission at longer wavelengths and averaging over contributions from both the hottest and cooler areas. Combined analysis of the CIRS and VIMS spectra spanning 3 to 500 micron wavelengths promises to reveal the distribution of [T, area] near the fissures that cannot be spatially resolved. This [T, area] distribution holds the key to understanding how heat is transferred to the surface within a few 100 m of the fissures.The VIMS-detected emission is concentrated in localized hot spots along the fissures and does not seem to be distributed continuously along them. CIRS spectra suggest a more continuous distribution of the emission along the fissure length. Jets locations also are distributed along the fissure length and it appears that the VIMS-detected hot spots in general correlate with jet locations, but not all of the jet locations have been

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

    Energy Technology Data Exchange (ETDEWEB)

    Davidson, J.R.

    1994-10-01

    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.

  1. Exploring User Acceptance Of Free Wireless Fidelity Public Hot Spots: An Emperical Study

    Directory of Open Access Journals (Sweden)

    Ezejiofo Patrick Udeh

    2008-01-01

    Full Text Available Research regarding commercial and free wireless fidelity (Wi-Fi public hot spots acceptance and adoption is sketchy. Therefore, it has become imperative to understand the critical factors that affect their acceptance. The focus of this study is free Wi-Fi public hot spot users, with the objective to better understand their user acceptance. In doing so, this study integrated two well-established initial acceptance models, specifically, the technology acceptance model and the diffusion of innovation theory. This study was conducted using an on-line survey that collected data from 129 users. It uses the Partial Least Square (PLS technique to examine the relationship between variables. The results indicate that each critical factor has direct or indirect positive effects on current use and/or future use intention, which confirmed the majority of the proposed hypotheses. Relative advantage emerged as the only construct with a direct positive effect on both current use and future use intentions.

  2. STUDY ON LOCATION OF HOT SPOT AT TUBE WALL FOR FIRED CYLINDRICAL FURNACE COMBUSTION

    Institute of Scientific and Technical Information of China (English)

    Wang Taiyong; Lu Shizhong; Xü Zhixue

    2004-01-01

    Based on the analysis of heat radiation intensity from flame,a new mathematical model of the tube-wall temperature of heated tubes is devel-oped by taking down-fired,upright-tube cylindrical furnace for example.The proposed mathematical model can be employed to indicate both the position and size of the hot spot at fire-facing wall of heated tube of combustion chamber,and is characteristic of sim-plicity and efficiency.If coupled with thermoelectric couple or infrared viewer,the presented location method of com-bustion hot spot can offer engineers very valuable proposal to keep furnace running more safely.The same is true for any other type of tubular furnaces.

  3. Rapid experimental SAD phasing and hot-spot identification with halogenated fragments

    Directory of Open Access Journals (Sweden)

    Joseph D. Bauman

    2016-01-01

    Full Text Available Through X-ray crystallographic fragment screening, 4-bromopyrazole was discovered to be a `magic bullet' that is capable of binding at many of the ligand `hot spots' found in HIV-1 reverse transcriptase (RT. The binding locations can be in pockets that are `hidden' in the unliganded crystal form, allowing rapid identification of these sites for in silico screening. In addition to hot-spot identification, this ubiquitous yet specific binding provides an avenue for X-ray crystallographic phase determination, which can be a significant bottleneck in the determination of the structures of novel proteins. The anomalous signal from 4-bromopyrazole or 4-iodopyrazole was sufficient to determine the structures of three proteins (HIV-1 RT, influenza A endonuclease and proteinase K by single-wavelength anomalous dispersion (SAD from single crystals. Both compounds are inexpensive, readily available, safe and very soluble in DMSO or water, allowing efficient soaking into crystals.

  4. Influence of hot spot features on the initiation characteristics of heterogeneous nitromethane

    Energy Technology Data Exchange (ETDEWEB)

    Dattelbaum, Dana M [Los Alamos National Laboratory; Sheffield, Stephen A [Los Alamos National Laboratory; Stahl, David B [Los Alamos National Laboratory; Dattelbaum, Andrew M [Los Alamos National Laboratory; Engelke, Ray [Los Alamos National Laboratory

    2010-01-01

    To gain insights into the critical hot spot features influencing energetic materials initiation characteristics, well-defined micron-scale particles have been intentionally introduced into the homogeneous explosive nitromethane (NM). Two types of potential hot spot origins have been examined - shock impedance mismatches using solid silica beads, and porosity using hollow microballoons - as well as their sizes and inter-particle separations. Here, we present the results of several series of gas gun-driven plate impact experiments on NM/particle mixtures with well-controlled shock inputs. Detailed insights into the nature of the reactive flow during the build-up to detonation have been obtained from the response of in-situ electromagnetic gauges, and the data have been used to establish Pop-plots (run-distance-to-detonation vs. shock input pressure) for the mixtures. Comparisons of sensitization effects and energy release characteristics relative to the initial shock front between the solid and hollow beads are presented.

  5. Hot spot analysis for driving the development of hits into leads in fragment based drug discovery

    OpenAIRE

    Hall, David R.; Ngan, Chi Ho; Zerbe, Brandon S.; Kozakov, Dima; Vajda, Sandor

    2011-01-01

    Fragment based drug design (FBDD) starts with finding fragment-sized compounds that are highly ligand efficient and can serve as a core moiety for developing high affinity leads. Although the core-bound structure of a protein facilitates the construction of leads, effective design is far from straightforward. We show that protein mapping, a computational method developed to find binding hot spots and implemented as the FTMap server, provides information that complements the fragment screening...

  6. Characterization of hot spots in microstructured reactors for fast and exothermic reactions in mixing regime

    OpenAIRE

    Haber, Julien; Kashid, Madhavanand N.; Borhani, Navid; Jiang, Bo; Maeder, Thomas; Thome, John Richard; Renken, Albert; Kiwi-Minsker, Lioubov

    2012-01-01

    The intensification of fast exothermic reactions can be achieved by using microstructured reactors (MSR) which provide improved mass & heat transfer rates leading to higher overall reaction kinetics. But for highly exothermic reactions the heat evacuation becomes not efficient enough and unwanted hot spots are formed. In this study, first the mixing in MSR is quantified for different geometries and then temperature profiles are measured using a novel quantitative IR-thermometry method. The re...

  7. Predictions of hot spot residues at protein-protein interfaces using support vector machines.

    Directory of Open Access Journals (Sweden)

    Stefano Lise

    Full Text Available Protein-protein interactions are critically dependent on just a few 'hot spot' residues at the interface. Hot spots make a dominant contribution to the free energy of binding and they can disrupt the interaction if mutated to alanine. Here, we present HSPred, a support vector machine(SVM-based method to predict hot spot residues, given the structure of a complex. HSPred represents an improvement over a previously described approach (Lise et al, BMC Bioinformatics 2009, 10:365. It achieves higher accuracy by treating separately predictions involving either an arginine or a glutamic acid residue. These are the amino acid types on which the original model did not perform well. We have therefore developed two additional SVM classifiers, specifically optimised for these cases. HSPred reaches an overall precision and recall respectively of 61% and 69%, which roughly corresponds to a 10% improvement. An implementation of the described method is available as a web server at http://bioinf.cs.ucl.ac.uk/hspred. It is free to non-commercial users.

  8. Hot Spot Electron Temperature from X-Ray Continuum Measurements on the NIF

    Science.gov (United States)

    Jarrott, Leonard; Chen, Hui; Izumi, Nobuhiko; Khan, Shahab; Ma, Tammy; Nagel, Sabrina; Pak, Arthur; Patel, Pravesh; Schneider, Marilyn; Scott, Howard

    2015-11-01

    We report on direct measurements of the electron temperature within the hot spot of inertially confined, layered, spherical implosions on the National Ignition Facility using a new differential filtering diagnostic. Measurements of the DT and DD ion temperatures using neutron time-of-flight detectors are complicated by the contribution of hot spot motion to the peak width, which may produce an apparent temperature higher than the thermal temperature. The electron temperature is not sensitive to this non-thermal velocity and is thus a valuable input to interpreting the stagnated hot spot conditions. Here we discuss a new electron temperature measurement using the high energy (>15 keV) emitted continuum from the hotspot that can escape with minimal attenuation from the compressed fuel/shell. We will discuss the physics considerations for design of this new large-pinhole, hard x-ray imaging technique, and show preliminary data acquired from symcaps and DT-layered implosions. Validation of this technique against simulations and other diagnostics is performed to estimate the accuracy of the measurement. This work performed under the auspices of U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344.

  9. Resolving hot spot microstructure using x-ray penumbral imaging (invited)

    Science.gov (United States)

    Bachmann, B.; Hilsabeck, T.; Field, J.; Masters, N.; Reed, C.; Pardini, T.; Rygg, J. R.; Alexander, N.; Benedetti, L. R.; Döppner, T.; Forsman, A.; Izumi, N.; LePape, S.; Ma, T.; MacPhee, A. G.; Nagel, S.; Patel, P.; Spears, B.; Landen, O. L.

    2016-11-01

    We have developed and fielded x-ray penumbral imaging on the National Ignition Facility in order to enable sub-10 μm resolution imaging of stagnated plasma cores (hot spots) of spherically shock compressed spheres and shell implosion targets. By utilizing circular tungsten and tantalum apertures with diameters ranging from 20 μm to 2 mm, in combination with image plate and gated x-ray detectors as well as imaging magnifications ranging from 4 to 64, we have demonstrated high-resolution imaging of hot spot plasmas at x-ray energies above 5 keV. Here we give an overview of the experimental design criteria involved and demonstrate the most relevant influences on the reconstruction of x-ray penumbral images, as well as mitigation strategies of image degrading effects like over-exposed pixels, artifacts, and photon limited source emission. We describe experimental results showing the advantages of x-ray penumbral imaging over conventional Fraunhofer and photon limited pinhole imaging and showcase how internal hot spot microstructures can be resolved.

  10. 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.

  11. Magnetotransport of multiple-band nearly antiferromagnetic metals due to hot-spot scattering

    Science.gov (United States)

    Koshelev, A. E.

    2016-09-01

    Multiple-band electronic structure and proximity to antiferromagnetic (AF) instability are the key properties of iron-based superconductors. We explore the influence of scattering by the AF spin fluctuations on transport of multiple-band metals above the magnetic transition. A salient feature of scattering on the AF fluctuations is that it is strongly enhanced at the Fermi surface locations where the nesting is perfect ("hot spots" or "hot lines"). We review derivation of the collision integral for the Boltzmann equation due to AF-fluctuations scattering. In the paramagnetic state, the enhanced scattering rate near the hot lines leads to anomalous behavior of electronic transport in magnetic field. We explore this behavior by analytically solving the Boltzmann transport equation with approximate transition rates. This approach accounts for return scattering events and is more accurate than the relaxation-time approximation. The magnetic-field dependences are characterized by two very different field scales: the lower scale is set by the hot-spot width and the higher scale is set by the total scattering amplitude. A conventional magnetotransport behavior is limited to magnetic fields below the lower scale. In the wide range in-between these two scales, the longitudinal conductivity has linear dependence on the magnetic field and the Hall conductivity has quadratic dependence. The linear dependence of the diagonal component reflects growth of the Fermi-surface area affected by the hot spots proportional to the magnetic field. We discuss applicability of this theoretical framework for describing of anomalous magnetotransport properties in different iron pnictides and chalcogenides in the paramagnetic state.

  12. Magma production rate along the Ninetyeast Ridge and its relationship to Indian plate motion and Kerguelen hot spot activity

    Digital Repository Service at National Institute of Oceanography (India)

    Sreejith, K.M.; Krishna, K.S.

    The Ninetyeast Ridge, a linear trace of the Kerguelen hot spot in the Indian Ocean, was emplaced on a rapidly drifting Indian plate. Magma production rates along the ridge track are computed using gravity-derived excess crustal thickness data...

  13. Radiation-induced chromosomal hot spots at G 1 and G 2 stages of human lymphocytes in culture

    Directory of Open Access Journals (Sweden)

    Murugesan R

    2003-01-01

    Full Text Available Radiation-induced chromosomal break points in cultured lymphocytes of normal healthy individuals as well as of those with certain genetic disorders are reported to be localized at certain specific loci (hot spots. These reports are based on studies carried out in lymphocytes irradiated at G 1 stage. The present study examines whether the location of hot spots and the frequency seen in cells irradiated at G 1 are similar to those irradiated at G 2 stage of the cell cycle and also tests whether cells of patients exhibit hot spots on irradiation.The results showed that the radiation induced chromosomal break points to be similar in those irradiated are G 1 and G 2 stages of the cell cycle and also that cells of patients exhibited chromosomal hot spots.

  14. Visualization and detection of spatio-temporal hot-spot and cluster for dengue in Petaling district, Malaysia

    Science.gov (United States)

    Rizwan, M.; Dass, Sarat C.; Sagayan, Vijanth

    2016-11-01

    Hot-spot and cluster detection is a part of disease surveillance to find out which regions are effected most by the disease. Analysis of these clusters of disease used for longer periods of time can lead to future prediction of disease outbreaks. Dengue is one of the most important arboviral disease in Malaysia which needs proper surveillance and control strategies. Our current study presents hot-spot and cluster detection of dengue outbreaks in the district of Petaling, Selangor in Malaysia during the year 2014 using the registered cases of dengue in the district. Detected hot-spot from this spatio-temporal analysis of registered dengue could provide a trend for the future dengue outbreak predictions. Use of dengue registered cases for the future prediction could be more effective then using land use variables and climate data. R software is used for the hot-spots detection. Custom clustering definition is considered for the analysis.

  15. Turbulence and magnetic spots at the surface of hot massive stars

    CERN Document Server

    Cantiello, Matteo; Brandenburg, Axel; Del Sordo, Fabio; Käpylä, Petri; Langer, Norbert

    2010-01-01

    Hot luminous stars show a variety of phenomena in their photospheres and in their winds which still lack clear physical explanations at this time. Among these phenomena are non-thermal line broadening, line profile variability (LPVs), discrete absorption components (DACs), wind clumping and stochastically excited pulsations. Cantiello et al. (2009) argued that a convection zone close to the surface of hot, massive stars, could be responsible for some of these phenomena. This convective zone is caused by a peak in the opacity due to iron recombination and for this reason is referred as the "iron convection zone" (FeCZ). 3D MHD simulations are used to explore the possible effects of such subsurface convection on the surface properties of hot, massive stars. We argue that turbulence and localized magnetic spots at the surface are the likely consequence of subsurface convection in early type stars.

  16. 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

  17. 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...

  18. Process window and defect monitoring using high-throughput e-beam inspection guided by computational hot spot detection

    Science.gov (United States)

    Wang, Fei; Zhang, Pengcheng; Fang, Wei; Liu, Kevin; Jau, Jack; Wang, Lester; Wan, Alex; Hunsche, Stefan; Halder, Sandip; Leray, Philippe

    2016-03-01

    As design rules for leading edge devices have shrunk to 1x nm size and below, device patterns have become sensitive to sub-10nm size defects. Additionally, defectivity and yield are now increasingly dominated by systematic patterning defects. A method for identifying and inspecting these hot spot (HS) locations is necessary for both technology development and High Volume Manufacturing (HVM). In order to achieve sufficient statistical significance across the wafer for a specific product and layer, a guided, high-speed e-beam inspection system is needed to cover a significant amount of high-volume hot spot locations for process window monitoring. In this paper, we explore the capabilities of a novel, highthroughput e-beam hot spot inspection tool, SkyScanTM 5000, on a 10nm back-end-of-line (BEOL) wafer patterned using a triple lithography-etch process. ASML's high-resolution, design-aware computational hot spot inspection is used to identify relevant hot spot locations, including overlay-sensitive patterns. We guide the e-beam tool to these Points of Interest (POI) and obtain experimental data from inspection of 430k wafer locations. The large amount of data allows detection of wafer-level and intra-field defect signatures for a large number of hot spot patterns.

  19. Friction Stir Spot Welding of DP780 and Hot-Stamp Boron Steels

    Energy Technology Data Exchange (ETDEWEB)

    Santella, Michael L.; Frederick, Alan; Hovanski, Yuri; Grant, Glenn J.

    2008-05-16

    Friction stir spot welds were made in two high-strength steels: DP780, and a hot-stamp-boron steel with tensile strength of 1500 MPa. The spot welds were made at either 800 or 1600 rpm using either of two polycrystalline boron nitride tools. One stir tool, BN77, had the relatively common pin-tool shape. The second tool, BN46, had a convex rather than a concave shoulder profile and a much wider and shorter pin. The tools were plunged to preprogrammed depths either at a continuous rate (1-step schedule) or in two segments consisting of a relatively high rate followed by a slower rate. In all cases, the welds were completed in 4s. The range of lap-shear values were compared to values required for resistance spot welds on the same steels. The minimum value of 10.3 kN was exceeded for friction stir spot welding of DP780 using a 2-step schedule and either the BN77- or the BN46-type stir tool. The respective minimum value of 12 kN was also exceeded for the HSB steel using the 2-step process and the BN46 stir tool.

  20. Using spatial statistics to identify emerging hot spots of forest loss

    Science.gov (United States)

    Harris, Nancy L.; Goldman, Elizabeth; Gabris, Christopher; Nordling, Jon; Minnemeyer, Susan; Ansari, Stephen; Lippmann, Michael; Bennett, Lauren; Raad, Mansour; Hansen, Matthew; Potapov, Peter

    2017-02-01

    As sources of data for global forest monitoring grow larger, more complex and numerous, data analysis and interpretation become critical bottlenecks for effectively using them to inform land use policy discussions. Here in this paper, we present a method that combines big data analytical tools with Emerging Hot Spot Analysis (ArcGIS) to identify statistically significant spatiotemporal trends of forest loss in Brazil, Indonesia and the Democratic Republic of Congo (DRC) between 2000 and 2014. Results indicate that while the overall rate of forest loss in Brazil declined over the 14-year time period, spatiotemporal patterns of loss shifted, with forest loss significantly diminishing within the Amazonian states of Mato Grosso and Rondônia and intensifying within the cerrado biome. In Indonesia, forest loss intensified in Riau province in Sumatra and in Sukamara and West Kotawaringin regencies in Central Kalimantan. Substantial portions of West Kalimantan became new and statistically significant hot spots of forest loss in the years 2013 and 2014. Similarly, vast areas of DRC emerged as significant new hot spots of forest loss, with intensified loss radiating out from city centers such as Beni and Kisangani. While our results focus on identifying significant trends at the national scale, we also demonstrate the scalability of our approach to smaller or larger regions depending on the area of interest and specific research question involved. When combined with other contextual information, these statistical data models can help isolate the most significant clusters of loss occurring over dynamic forest landscapes and provide more coherent guidance for the allocation of resources for forest monitoring and enforcement efforts.

  1. Multiple modes of chromatin configuration at natural meiotic recombination hot spots in fission yeast.

    Science.gov (United States)

    Hirota, Kouji; Steiner, Walter W; Shibata, Takehiko; Ohta, Kunihiro

    2007-11-01

    The ade6-M26 meiotic recombination hot spot of fission yeast is defined by a cyclic AMP-responsive element (CRE)-like heptanucleotide sequence, 5'-ATGACGT-3', which acts as a binding site for the Atf1/Pcr1 heterodimeric transcription factor required for hot spot activation. We previously demonstrated that the local chromatin around the M26 sequence motif alters to exhibit higher sensitivity to micrococcal nuclease before the initiation of meiotic recombination. In this study, we have examined whether or not such alterations in chromatin occur at natural meiotic DNA double-strand break (DSB) sites in Schizosaccharomyces pombe. At one of the most prominent DSB sites, mbs1 (meiotic break site 1), the chromatin structure has a constitutively accessible configuration at or near the DSB sites. The establishment of the open chromatin state and DSB formation are independent of the CRE-binding transcription factor, Atf1. Analysis of the chromatin configuration at CRE-dependent DSB sites revealed both differences from and similarities to mbs1. For example, the tdh1+ locus, which harbors a CRE consensus sequence near the DSB site, shows a meiotically induced open chromatin configuration, similar to ade6-M26. In contrast, the cds1+ locus is similar to mbs1 in that it exhibits a constitutive open configuration. Importantly, Atf1 is required for the open chromatin formation in both tdh1+ and cds1+. These results suggest that CRE-dependent meiotic chromatin changes are intrinsic processes related to DSB formation in fission yeast meiosis. In addition, the results suggest that the chromatin configuration in natural meiotic recombination hot spots can be classified into at least three distinct categories: (i) an Atf1-CRE-independent constitutively open chromatin configuration, (ii) an Atf1-CRE-dependent meiotically induced open chromatin configuration, and (iii) an Atf1-CRE-dependent constitutively open chromatin configuration.

  2. 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

  3. The meaning of the UHECR Hot Spots: A Light Nuclei Nearby Astronomy

    CERN Document Server

    Fargion, Daniele

    2014-01-01

    We update all the recent UHECR events reported by AUGER, Telescope Array as well as by AGASA in common coordinate maps. We confirm our earliest (2008-2013) model where UHECR are mostly light nuclei (He,Be,B), explaining the Virgo absence and confirming M82 as the main source of North TA Hot Spot. Many more sources , as NGC 253 and galactic ones, are possibly source of most of the 376 UHECR events. Several correlated map, already considered in recent years, are shown with all the events

  4. 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...... of mutations within individual genomes were attributable to compound mutation or gene conversion. Hypermutability was a characteristic of genes involved in ASD and other diseases. In addition, genes impacted by mutations in this study were associated with ASD in independent exome-sequencing data sets. Our...

  5. Detection of spatial hot spots and variation for the neon flying squid Ommastrephes bartramii resources in the northwest Pacific Ocean

    Science.gov (United States)

    Feng, Yongjiu; Chen, Xinjun; Liu, Yan

    2016-08-01

    With the increasing effects of global climate change and fishing activities, the spatial distribution of the neon flying squid (Ommastrephes bartramii) is changing in the traditional fishing ground of 150°-160°E and 38°-45°N in the northwest Pacific Ocean. This research aims to identify the spatial hot and cold spots (i.e. spatial clusters) of O. bartramii to reveal its spatial structure using commercial fishery data from 2007 to 2010 collected by Chinese mainland squid-jigging fleets. A relatively strongly-clustered distribution for O. bartramii was observed using an exploratory spatial data analysis (ESDA) method. The results show two hot spots and one cold spot in 2007 while only one hot and one cold spots were identified each year from 2008 to 2010. The hot and cold spots in 2007 occupied 8.2% and 5.6% of the study area, respectively; these percentages for hot and cold spot areas were 5.8% and 3.1% in 2008, 10.2% and 2.9% in 2009, and 16.4% and 11.9% in 2010, respectively. Nearly half (>45%) of the squid from 2007 to 2009 reported by Chinese fleets were caught in hot spot areas while this percentage reached its peak at 68.8% in 2010, indicating that the hot spot areas are central fishing grounds. A further change analysis shows the area centered at 156°E/43.5°N was persistent as a hot spot over the whole period from 2007 to 2010. Furthermore, the hot spots were mainly identified in areas with sea surface temperature (SST) in the range of 15-20°C around warm Kuroshio Currents as well as with the chlorophyll-a (chl-a) concentration above 0.3 mg/m3. The outcome of this research improves our understanding of spatiotemporal hotspots and its variation for O. bartramii and is useful for sustainable exploitation, assessment, and management of this squid.

  6. Thermal analysis of continuous and patterned multilayer films in the presence of a nanoscale hot spot

    Directory of Open Access Journals (Sweden)

    Jia-Yang Juang

    2016-10-01

    Full Text Available Thermal responses of multilayer films play essential roles in state-of-the-art electronic systems, such as photo/micro-electronic devices, data storage systems, and silicon-on-insulator transistors. In this paper, we focus on the thermal aspects of multilayer films in the presence of a nanoscale hot spot induced by near field laser heating. The problem is set up in the scenario of heat assisted magnetic recording (HAMR, the next-generation technology to overcome the data storage density limit imposed by superparamagnetism. We characterized thermal responses of both continuous and patterned multilayer media films using transient thermal modeling. We observed that material configurations, in particular, the thermal barriers at the material layer interfaces crucially impact the temperature field hence play a key role in determining the hot spot geometry, transient response and power consumption. With a representative generic media model, we further explored the possibility of optimizing thermal performances by designing layers of heat sink and thermal barrier. The modeling approach demonstrates an effective way to characterize thermal behaviors of micro and nano-scale electronic devices with multilayer thin film structures. The insights into the thermal transport scheme will be critical for design and operations of such electronic devices.

  7. 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.

  8. Thermal analysis of continuous and patterned multilayer films in the presence of a nanoscale hot spot

    Science.gov (United States)

    Juang, Jia-Yang; Zheng, Jinglin

    2016-10-01

    Thermal responses of multilayer films play essential roles in state-of-the-art electronic systems, such as photo/micro-electronic devices, data storage systems, and silicon-on-insulator transistors. In this paper, we focus on the thermal aspects of multilayer films in the presence of a nanoscale hot spot induced by near field laser heating. The problem is set up in the scenario of heat assisted magnetic recording (HAMR), the next-generation technology to overcome the data storage density limit imposed by superparamagnetism. We characterized thermal responses of both continuous and patterned multilayer media films using transient thermal modeling. We observed that material configurations, in particular, the thermal barriers at the material layer interfaces crucially impact the temperature field hence play a key role in determining the hot spot geometry, transient response and power consumption. With a representative generic media model, we further explored the possibility of optimizing thermal performances by designing layers of heat sink and thermal barrier. The modeling approach demonstrates an effective way to characterize thermal behaviors of micro and nano-scale electronic devices with multilayer thin film structures. The insights into the thermal transport scheme will be critical for design and operations of such electronic devices.

  9. Biofilm models for the food industry: hot spots for plasmid transfer?

    Science.gov (United States)

    Van Meervenne, Eva; De Weirdt, Rosemarie; Van Coillie, Els; Devlieghere, Frank; Herman, Lieve; Boon, Nico

    2014-04-01

    Biofilms represent a substantial problem in the food industry, with food spoilage, equipment failure, and public health aspects to consider. Besides, biofilms may be a hot spot for plasmid transfer, by which antibiotic resistance can be disseminated to potential foodborne pathogens. This study investigated biomass and plasmid transfer in dual-species (Pseudomonas putida and Escherichia coli) biofilm models relevant to the food industry. Two different configurations (flow-through and drip-flow) and two different inoculation procedures (donor-recipient and recipient-donor) were tested. The drip-flow configuration integrated stainless steel coupons in the setup while the flow-through configuration included a glass flow cell and silicone tubing. The highest biomass density [10 log (cells cm-²)] was obtained in the silicone tubing when first the recipient strain was inoculated. High plasmid transfer ratios, up to 1/10 (transconjugants/total bacteria), were found. Depending on the order of inoculation, a difference in transfer efficiency between the biofilm models could be found. The ease by which the multiresistance plasmid was transferred highlights the importance of biofilms in the food industry as hot spots for the acquisition of multiresistance plasmids. This can impede the treatment of foodborne illnesses if pathogens acquire this multiresistance in or from the biofilm.

  10. Focal hot spot induced by a central subclavian line on bone scan

    Directory of Open Access Journals (Sweden)

    Masood Moslehi

    2014-01-01

    Full Text Available The diagnostic accuracy of nuclear medicine reporting can be improved by awareness of these instrument-related artifacts. Both awareness and experience are also important when it comes to detecting and identifying normal (and abnormal variants. We present a case of hot spot on the upper right chest in the region of right subclavicular region resulting from injection of radiotracer from central subclavian line. A 52-year-old woman with a history of left breast cancer and recent bone pain was referred to our nuclear medicine department for skeletal survey. Anterior views of chest show a focus of increased radiotracer uptake corresponding to anterior arch of one of the right second rib. The nuclear physician reported it as a focal rib bony lesion and recommended radiological evaluation. As technician later explained, physicians realized that injection site was a central subclavian line on the right side and hot spot on that region is due to injection site. The appearance of both skeletal and soft-tissue uptake depends heavily on imaging technique (such as the route of radiotracer administration and the interpreting physicians should be aware of the impact of technical factors on image quality.

  11. 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.

  12. A conserved TLR5 binding and activation hot spot on flagellin

    Science.gov (United States)

    Song, Wan Seok; Jeon, Ye Ji; Namgung, Byeol; Hong, Minsun; Yoon, Sung-il

    2017-01-01

    Flagellin is a bacterial protein that polymerizes into the flagellar filament and is essential for bacterial motility. When flagellated bacteria invade the host, flagellin is recognized by Toll-like receptor 5 (TLR5) as a pathogen invasion signal and eventually evokes the innate immune response. Here, we provide a conserved structural mechanism by which flagellins from Gram-negative γ-proteobacteria and Gram-positive Firmicutes bacteria bind and activate TLR5. The comparative structural analysis using our crystal structure of a complex between Bacillus subtilis flagellin (bsflagellin) and TLR5 at 2.1 Å resolution, combined with the alanine scanning analysis of the binding interface, reveals a common hot spot in flagellin for TLR5 activation. An arginine residue (bsflagellin R89) of the flagellin D1 domain and its adjacent residues (bsflagellin E114 and L93) constitute a hot spot that provides shape and chemical complementarity to a cavity generated by the loop of leucine-rich repeat 9 in TLR5. In addition to the flagellin D1 domain, the D0 domain also contributes to TLR5 activity through structurally dispersed regions, but not a single focal area. These results establish the groundwork for the future design of flagellin-based therapeutics. PMID:28106112

  13. 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.

  14. Grain-Scale Simulations of Hot-Spot Initiation for Shocked TATB

    Energy Technology Data Exchange (ETDEWEB)

    Najjar, F; Howard, W; Fried, L

    2009-07-31

    High-explosive (HE) material consists of large-sized grains with micron-sized embedded impurities and pores. Under various mechanical/thermal insults, these pores collapse generating high-temperature regions leading to ignition. A computational study has been performed to investigate the mechanisms of pore collapse and hot spot initiation in TATB crystals, employing the thermohydrodynamics arbitrary-Lagrange-Eulerian code ALE3D. This initial study includes non-reactive dynamics to isolate the thermal and hydrodynamical effects. Two-dimensional high-resolution large-scale meso-scale simulations have been undertaken. We study an axisymmetric configuration for pore radii ranging from 0.5 to 2{micro}m, with initial shock pressures in the range from 3 to 11 GPa. A Mie-Gruneisen Equation of State (EOS) model is used for TATB, and includes a constant yield strength and shear modulus; while the air in the pore invokes a Livermore Equation of State (LEOS) model. The parameter space is systematically studied by considering various shock strengths, pore diameters and material properties. We find that thermal diffusion from the collapsed pores has an important effect in generating high-temperature hot spots in the TATB.

  15. Hot-spot tectonics of Eistla Regio, Venus: Results from Magellan images and Pioneer Venus gravity

    Science.gov (United States)

    Grimm, Robert E.; Phillips, Roger J.

    1991-06-01

    Eistla Regio (ER) is a broad, low, discontinuous topographic rise striking roughly EW at low northern latitudes of Venus. Some 2000 x 7000 km in dimensions, it is the third largest rise in planform on Venus after Aphrodite Terra and Beta Phoebe Regiones. These rises are the key physiographic elements in a hot spot model of global tectonics including transient plume behavior. Since ER is the first such rise viewed by Magellan and the latitude is very favorable for Pioneer Venus gravity studies, some of the predictions of a time dependent hot spot model are tested. Western ER is defined as the rise including Gula and Sif Mons and central ER as that including Sappho Patera. Superior conjunction prevented Magellan from returning data on eastern ER (Pavlova) during the first mapping cycle. It is concluded that the western and central portions of ER, while part of the same broad topographic rise and tectonic framework, have distinctly different surface ages and gravity signatures. The western rise, including Gula and Sif Mons, is the expression of deep seated uplift with volcanism limited to the individual large shields. The eastern portion has been widely resurfaced more recently by thermal anomalies in the mantle.

  16. VLBI observations of 10 CSO candidates: expansion velocities of hot spots

    CERN Document Server

    An, Tao; Yang, Jun; Taylor, Gregory B; Hong, Xiaoyu; Baan, Willem A; Liu, Xiang; Wang, Min; Zhang, Hongbo; Wang, Weihua; Chen, Xi; Cui, Lang; Hao, Longfei; Zhu, Xinying

    2011-01-01

    Observations of ten Compact Symmetric Objects ({\\rm CSO}) candidates have been made with the Very Long Baseline Array at 8.4 GHz in 2005 and with a combined Chinese and European VLBI array at 8.4 GHz in 2009. The 2009 observations incorporate for the first time the two new Chinese telescopes at Miyun and Kunming for international astrophysical observations. The observational data, in combination with archival VLBA data from previous epochs, have been used to derive the proper motions of the VLBI components. Because of the long time baseline of $\\sim$16 years of the VLBI data sets, the expansion velocities of the hot spots can be measured at an accuracy as high as $\\sim$1.3 $\\mu$as yr$^{-1}$. Six of the ten sources are identified as CSOs with a typical double or triple morphology on the basis of both spectral index maps and their mirror-symmetry of proper motions of the terminal hot spots. The compact double source J1324+4048 is also identified as a CSO candidate. Among the three remaining sources, J1756+5748 ...

  17. Hot spots and future directions of research on the neuroprotective effects of nimodipine

    Institute of Scientific and Technical Information of China (English)

    Runhui Li

    2014-01-01

    Calcium antagonists are widely used in the clinical treatment of ischemic cerebrovascular disease because of their vascular and neuroprotective effects. Nimodipine, a typical calcium antagonist, can cross the blood-brain barrier and act selectively at neurons and blood vessels of target tis-sues, thus exerting neuroprotective effects. The aim of the present study was to explore the hot spots and future trends of research on the neuroprotective effects of nimodipine. We retrieved 425 articles on the neuroprotective effects of nimodipine that were indexed in the Web of the Science database between 2000 and 2014. The retrieved articles were analyzed using document analysis reporting and the derived information function in the Web of Science, and the infor-mation visualization software CiteSpace III. The reference co-citation network was plotted, and the high frequency key words in these publications were used to analyze the research fronts and development trends for nimodipine neuroprotection. According to these co-citation clusters, the research front of nimodipine neuroprotection is the use of randomized controlled trials to study nimodipine intervention of subarachnoid hemorrhage. Using time zone view analysis on hot spots labeled with a key word, the areas of interest in the ifeld of nimodipine neuroprotection are nimodipine pharmacology and therapeutics, blood-brain barrier, trials, and anti-angiospasm.

  18. Lack of mutational hot spots during decitabine-mediated HIV-1 mutagenesis.

    Science.gov (United States)

    Rawson, Jonathan M O; Landman, Sean R; Reilly, Cavan S; Bonnac, Laurent; Patterson, Steven E; Mansky, Louis M

    2015-11-01

    Decitabine has previously been shown to induce lethal mutagenesis of human immunodeficiency virus type 1 (HIV-1). However, the factors that determine the susceptibilities of individual sequence positions in HIV-1 to decitabine have not yet been defined. To investigate this, we performed Illumina high-throughput sequencing of multiple amplicons prepared from proviral DNA that was recovered from decitabine-treated cells infected with HIV-1. We found that decitabine induced an ≈4.1-fold increase in the total mutation frequency of HIV-1, primarily due to a striking ≈155-fold increase in the G-to-C transversion frequency. Intriguingly, decitabine also led to an ≈29-fold increase in the C-to-G transversion frequency. G-to-C frequencies varied substantially (up to ≈80-fold) depending upon sequence position, but surprisingly, mutational hot spots (defined as upper outliers within the mutation frequency distribution) were not observed. We further found that every single guanine position examined was significantly susceptible to the mutagenic effects of decitabine. Taken together, these observations demonstrate for the first time that decitabine-mediated HIV-1 mutagenesis is promiscuous and occurs in the absence of a clear bias for mutational hot spots. These data imply that decitabine-mediated G-to-C mutagenesis is a highly effective antiviral mechanism for extinguishing HIV-1 infectivity.

  19. Z-score biological significance of binding hot spots of protein interfaces by using crystal packing as the reference state.

    Science.gov (United States)

    Liu, Qian; Wong, Limsoon; Li, Jinyan

    2012-12-01

    Characterization of binding hot spots of protein interfaces is a fundamental study in molecular biology. Many computational methods have been proposed to identify binding hot spots. However, there are few studies to assess the biological significance of binding hot spots. We introduce the notion of biological significance of a contact residue for capturing the probability of the residue occurring in or contributing to protein binding interfaces. We take a statistical Z-score approach to the assessment of the biological significance. The method has three main steps. First, the potential score of a residue is defined by using a knowledge-based potential function with relative accessible surface area calculations. A null distribution of this potential score is then generated from artifact crystal packing contacts. Finally, the Z-score significance of a contact residue with a specific potential score is determined according to this null distribution. We hypothesize that residues at binding hot spots have big absolute values of Z-score as they contribute greatly to binding free energy. Thus, we propose to use Z-score to predict whether a contact residue is a hot spot residue. Comparison with previously reported methods on two benchmark datasets shows that this Z-score method is mostly superior to earlier methods. This article is part of a Special Issue entitled: Computational Methods for Protein Interaction and Structural Prediction.

  20. HotSpot Wizard 2.0: automated design of site-specific mutations and smart libraries in protein engineering.

    Science.gov (United States)

    Bendl, Jaroslav; Stourac, Jan; Sebestova, Eva; Vavra, Ondrej; Musil, Milos; Brezovsky, Jan; Damborsky, Jiri

    2016-07-01

    HotSpot Wizard 2.0 is a web server for automated identification of hot spots and design of smart libraries for engineering proteins' stability, catalytic activity, substrate specificity and enantioselectivity. The server integrates sequence, structural and evolutionary information obtained from 3 databases and 20 computational tools. Users are guided through the processes of selecting hot spots using four different protein engineering strategies and optimizing the resulting library's size by narrowing down a set of substitutions at individual randomized positions. The only required input is a query protein structure. The results of the calculations are mapped onto the protein's structure and visualized with a JSmol applet. HotSpot Wizard lists annotated residues suitable for mutagenesis and can automatically design appropriate codons for each implemented strategy. Overall, HotSpot Wizard provides comprehensive annotations of protein structures and assists protein engineers with the rational design of site-specific mutations and focused libraries. It is freely available at http://loschmidt.chemi.muni.cz/hotspotwizard.

  1. Ignition conditions relaxation for central hot-spot ignition with an ion-electron non-equilibrium model

    Science.gov (United States)

    Fan, Zhengfeng; Liu, Jie

    2016-10-01

    We present an ion-electron non-equilibrium model, in which the hot-spot ion temperature is higher than its electron temperature so that the hot-spot nuclear reactions are enhanced while energy leaks are considerably reduced. Theoretical analysis shows that the ignition region would be significantly enlarged in the hot-spot rhoR-T space as compared with the commonly used equilibrium model. Simulations show that shocks could be utilized to create and maintain non-equilibrium conditions within the hot spot, and the hot-spot rhoR requirement is remarkably reduced for achieving self-heating. In NIF high-foot implosions, it is observed that the x-ray enhancement factors are less than unity, which is not self-consistent and is caused by assuming Te =Ti. And from this non-consistency, we could infer that ion-electron non-equilibrium exists in the high-foot implosions and the ion temperature could be 9% larger than the equilibrium temperature.

  2. 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.

  3. Detection of direct and indirect noise generated by synthetic hot spots in a duct

    Science.gov (United States)

    De Domenico, Francesca; Rolland, Erwan O.; Hochgreb, Simone

    2017-04-01

    Sound waves in a combustor are generated from fluctuations in the heat release rate (direct noise) or the acceleration of entropy, vorticity or compositional perturbations through nozzles or turbine guide vanes (indirect or entropy noise). These sound waves are transmitted downstream as well as reflected upstream of the acceleration point, contributing to the overall noise emissions, or triggering combustion instabilities. Previous experiments attempted to isolate indirect noise by generating thermoacoustic hot spots electrically and measuring the transmitted acoustic waves, yet there are no measurements on the backward propagating entropy and acoustic waves. This work presents the first measurements which clearly separate the direct and indirect noise contributions to pressure fluctuations upstream of the acceleration point. Synthetic entropy spots are produced by unsteady electrical heating of a grid of thin wires located in a tube. Compression waves (direct noise) are generated from this heating process. The hot spots are then advected with the mean flow and finally accelerated through an orifice plate located at the end of the tube, producing a strong acoustic signature which propagates upstream (indirect noise). The convective time is selected to be longer than the heating pulse length, in order to obtain a clear time separation between direct and indirect noise in the overall pressure trace. The contribution of indirect noise to the overall noise is shown to be non-negligible either in subsonic or sonic throat conditions. However, the absolute amplitude of direct noise is larger than the corresponding fraction of indirect noise, explaining the difficulty in clearly identifying the two contributions when they are merged. Further, the work shows the importance of using appropriate pressure transducer instrumentation and correcting for the respective transfer functions in order to account for low frequency effects in the determination of pressure fluctuations.

  4. A reactive burn model for shock initiation in a PBX: scaling and separability based on the hot spot concept

    Energy Technology Data Exchange (ETDEWEB)

    Show, Milton S [Los Alamos National Laboratory; Menikoff, Ralph [Los Alamos National Laboratory

    2010-01-01

    In the formulation of a reactive burn model for shock initiation, we endeavor to incorporate a number of effects based on the underlying physical concept of hot spot ignition followed by the growth of reaction due to diverging deflagration fronts. The passage of a shock front sets the initial condition for reaction, leading to a fraction of the hot spots that completely burn while others will quench. The form of the rate model is chosen to incorporate approximations based on the physical picture. In particular, the approximations imply scaling relations that are then used to mathematically separate various contributions. That is, the model is modular and refinements can be applied separately without changing the other contributions. For example, the effect of initial temperature, porosity, etc. predominantly enter the characterization of the non-quenching hot spot distribution. A large collection of velocity gauge data is shown to be well represented by the model with a very small number of parameters.

  5. XMM-Newton observations of the hot spot galaxy NGC 2903

    CERN Document Server

    Perez-Ramirez, D; Ebrero, J; Leon, S

    2010-01-01

    We report on the first deeper X-ray broad-band observation of the hot spot galaxy NGC 2903 obtained with XMM-Newton. X-ray imaging and spectra of the spiral barred galaxy NGC 2903 were obtained from recently available XMM-Newton archival data in order to study its X-ray population and the conditions of the hot gas in its central region. We investigate the spectral properties for the discrete point-source population and give first estimations of their X-ray spectral parameters. By analysing the RGS spectra, we derive temperature and abundances for the hot gas located in its central region. A total of 6 X-ray point sources (4 of them ULX candidates) were detected in the energy range of 0.3-10.0 keV located within the galaxy D25 optical disk. 3 out of these sources are detected for the first time, and one of them, XMM-NGC2903 X2 with luminosity larger than 10^39 erg/s. After fitting three different models, we were able to estimate their luminosities which are compatible with binaries with a compact object in the...

  6. Multifocal hot spots demonstrated by whole-body 131I scintigraphy and SPECT/CT after transaxillary endoscopic thyroidectomy.

    Science.gov (United States)

    Kim, Ho Seong; Kim, Seok Hwi; Kim, Jung Han; Kim, Byung-Tae; Lee, Kyung-Han

    2015-03-01

    A 35-year-old woman received open thyroidectomy for a thyroid nodule that was confirmed as papillary carcinoma. Whole-body 131I scintigraphy during thyroid ablation demonstrated high uptake in the thyroid bed and multiple focal hot spots in the thorax. SPECT/CT localized the hot spots to the right chest wall and axilla, as well as to the left chest wall. The surgeon recognized these sites to concur with the transaxillary tract used during endoscopic thyroidectomy for nodular hyperplasia 8 years previously. Thus, this case illustrates how thyroidal tissue fragments seeded during endoscopic thyroidectomy can be mistaken for thyroid cancer metastasis on 131I scintigraphy.

  7. 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...

  8. 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.

  9. Analytical criterion for shock ignition of fusion reaction in hot spot

    Directory of Open Access Journals (Sweden)

    Ribeyre X.

    2013-11-01

    Full Text Available Shock ignition of DT capsules involves two major steps. First, the fuel is assembled by means of a low velocity conventional implosion. At stagnation, the central core has a temperature lower than the one needed for ignition. Then a second, strong spherical converging shock, launched from a high intensity laser spike, arrives to the core. This shock crosses the core, rebounds at the target center and increases the central pressure to the ignition conditions. In this work we consider this latter phase by using the Guderley self-similar solution for converging flows. Our model accounts for the fusion reaction energy deposition, thermal and radiation losses thus describing the basic physics of hot spot ignition. The ignition criterion derived from the analytical model is successfully compared with full scale hydrodynamic simulations.

  10. Integrative Analysis of Hot Spot Conditions in MagLIF Experiments

    Science.gov (United States)

    Knapp, Patrick; Gomez, Matthew; Harding, Eric; Hansen, Stephanie; Hahn, Kelly; Geissel, Matthias; Chandler, Gordon; Smith, Ian; Slutz, Steve; Jennings, Chris; Martin, Matthew; Schmit, Paul; Peterson, Kyle; Rochau, Gregory; McBride, Ryan; Sinars, Daniel

    2016-10-01

    A large data set incorporating all available neutron and x-ray data is used to analyze a broad range of Magnetized Liner Inertial Fusion (MagLIF) experiments conducted on the Z machine at Sandia National Laboratories over the past two years. Electron and ion temperatures, electron density, mix fraction, burn volume and duration, and neutron and x-ray yields are all measured on each experiment; several through multiple independent methods. Complementary methods are used to infer the hot spot energy and pressure, and trends are analyzed. The results are placed in the context of accepted performance metrics for Magneto-Inertial Fusion. Sandia National Laboratories is a multi-program laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under contract DE.

  11. Simulation of the radiation from the hot spot of an X-pinch

    Science.gov (United States)

    Oreshkin, V. I.; Artyomov, A. P.; Chaikovsky, S. A.; Oreshkin, E. V.; Rousskikh, A. G.

    2017-01-01

    The results of X-pinch experiments performed using a small-sized pulse generator are analyzed. The generator, capable of producing a 200-kA, 180-ns current, was loaded with an X-pinch made of four 35-μm-diameter aluminum wires. The analysis consists of a one-dimensional radiation magnetohydrodynamic simulation of the formation of a hot spot in an X-pinch, taking into account the outflow of material from the neck region. The radiation loss and the ion species composition of the pinch plasma are calculated based on a stationary collisional-radiative model, including balance equations for the populations of individual levels. With this model, good agreement between simulation predictions and experimental data has been achieved: the experimental and the calculated radiation power and pulse duration differ by no more than twofold. It has been shown that the x-ray pulse is formed in the radiative collapse region, near its boundary.

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

    Energy Technology Data Exchange (ETDEWEB)

    Teng, J. [Science and Technology on Plasma Physics Laboratory, Laser Fusion Research Center, China Academy of Engineering Physics, Mianyang 621900 (China); Gu, Y.Q., E-mail: yqgu@caep.cn [Science and Technology on Plasma Physics Laboratory, Laser Fusion Research Center, China Academy of Engineering Physics, Mianyang 621900 (China); Center for Applied Physics and Technology, HEDPS, Peking University, Beijing 100871 (China); Chen, J.; Zhu, B.; Zhang, B.; Zhang, T.K.; Tan, F.; Hong, W.; Zhang, B.H. [Science and Technology on Plasma Physics Laboratory, Laser Fusion Research Center, China Academy of Engineering Physics, Mianyang 621900 (China); Wang, X.Q. [Academy of Nuclear Science and Technology, University of Science and Technology of China, Hefei 230026 (China)

    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 10{sup 9} and the spectra width is within 10%.

  13. Treatability studies on F/H Area ``hot spot`` groundwater composite. Revision 1

    Energy Technology Data Exchange (ETDEWEB)

    Bibler, J.P.

    1993-08-30

    The data found in this report were collected from laboratory experiments that were conducted to characterize the ``hot spot`` groundwater before and after pH adjustment, to describe the settling behavior and particle size of the precipitates resulting from pH adjustment, and to compare several methods of pH adjustment. Although Decontamination Factors (DFs) for all precipitating agents are similar, the best settling characteristics and most manageable precipitate were produced when 25 ppM Al{sup 3+} was introduced as Al{sub 2}(SO{sub 4}){sub 3} and pH adjustment was made from 6--8 with NaOH. The resulting precipitate will not be a hazardous secondary waste.

  14. Chain of impact of the development of hot spots and hot rubbing in disk brakes of passenger cars; Wirkungskette der Entstehung von Hotspots und Heissrubbeln in Pkw-Scheibenbremsen

    Energy Technology Data Exchange (ETDEWEB)

    Sarda, Angelo

    2009-07-01

    Aspects coupled with brake comfort represent challenges with the development of brake systems. During the brake process, so-called hot spots on the surface of brake disks are developed under certain conditions. These hot spots result in an irregular thermal expansion and deformation of the brake disk. This results in vibrations impacting the comfort and being known as 'hot rubbing'. The author of the contribution under consideration describes the most important results from extensive benchmark tests and supplies experimentally secured realizations to the chain of impact of the development of hot spots and 'hot rubbing' in a disc brake.

  15. Is the Juan Fernandez Ridge (nazca Plate) a Deep-Mantle Hot SPOT Trail?

    Science.gov (United States)

    Lara, L. E.; Selles, D.; Díaz, A.; Piña-Gauthier, M.

    2011-12-01

    The Juan Fernández Ridge on the oceanic Nazca plate is thought to be a classic hot spot trail because of the apparent westward rejuvenation of the eruptive ages. Geochronological data is still scarce to prove this is the case, and other hypothesis should be taken into account. There are a few constrains, like the ca. 9 Ma Ar-Ar age of the O'Higgins seamount (115 km from the Chile-Perú trench), published K-Ar ages of ca. 3-4 Ma in Robinson Crusoe island (580 km from the trench) and ca. 1 Ma in Alejandro Selkirk (180 km further west). New reconnaissance K-Ar ages in Robinson Crusoe yield ca. 1-3 Ma, which partially overlap with the age of Alejandro Selkirk, breaking the expected age progression given that the Nazca plate moves eastwards at ca. 6-8 cm/yr. New geological mapping also shows a sharp unconformity between the older, strongly altered sequences and more recent, post-erosional volcanic piles, where only the vent facies have disappeared. A fixed deep-mantle plume origin for Pacific hot spots has been widely debated and concurrent phenomena arose as a possible explanation for non-linear age progressions and/or long-lived volcanic activity. In fact, intraplate regional tectonics, plume displacement, and mantle heterogeneities could be the main factor of the ridge architecture or the mask for a first-order linear trend. An ongoing mapping and dating effort is aimed to understand the evolution of the Juan Fernández Ridge, testing the main hypothesis. Fondecyt grant 110966 is acknowledged for financial support.

  16. 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....

  17. 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.

  18. 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

    ) or 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...

  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. Measurement of the hot spot electron temperature in NIF ICF implosions using Krypton x-ray emission spectroscopy

    Science.gov (United States)

    Ma, T.; Chen, H.; Patel, P. K.; Schneider, M.; Barrios, M.; Berzak Hopkins, L.; Casey, D.; Chung, H.-K.; Hammel, B.; Jarrott, C.; Nora, R.; Pak, A.; Scott, H.; Spears, B.; Weber, C.

    2015-11-01

    The inference of ion temperature from neutron spectral measurements in indirect-drive ICF implosions is known to be sensitive to non-thermal velocity distributions in the fuel. The electron temperature (Te) inferred from dopant line ratios should not be sensitive to these bulk motions and hence may be a better measure of the thermal temperature of the hot spot. Here we describe a series of experiments to be conducted on the NIF where a small concentration of a mid-Z dopant (Krypton) is added to the fuel gas. The x-ray spectra is measured and the electron temperature is inferred from Kr line ratios. We also quantify the level of radiative cooling in the hot spot due to this mid-Z dopant. These experiments represent the first direct measurement of hot spot Te using spectroscopy, and we will describe the considerations for applying x-ray spectroscopy in such dense and non-uniform hot spots. This work performed under the auspices of U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344.

  1. Evaluation of the influence of bypass flow gap distribution on the core hot spot in a prismatic VHTR core

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Min-Hwan, E-mail: mhkim@kaeri.re.kr [Korea Atomic Energy Research Institute, 1045 Daedeokdaero, Yoseong, Daejeon 304-353 (Korea, Republic of); Lim, Hong-Sik [Korea Atomic Energy Research Institute, 1045 Daedeokdaero, Yoseong, Daejeon 304-353 (Korea, Republic of)

    2011-08-15

    Highlights: > A procedure to evaluate the local gap size variation between graphite blocks was developed and applied to a prismatic core VHTR. > The analysis for the core bypass flow and hot spot was carried out based on the calculated gap distributions. > The predicted gap size is large enough to affect the flow distribution in the core. > The bypass gap and flow distributions are closely related to the local hot spot temperature and its location. > The core restraint mechanism preventing outward movement of graphite block reduces the bypass gap size and hot spot temperature. - Abstract: Core bypass flow in VHTR is one of the key issues for core thermal margins and efficiency. The bypass flow in the prismatic core varies during core cycles due to the irradiation shrinkage/swelling and thermal expansion of the graphite blocks. A procedure to evaluate the local gap size variation between graphite blocks was developed and applied to a prismatic core VHTR. The influence of the core restraint mechanism on the bypass flow gap was evaluated. The predicted gap size is as much as 8 mm when the graphite block is exposed to its allowable limit of fast neutron fluence. The analysis for the core bypass flow and hot spot was carried out based on the calculated gap distributions. The results indicate that the bypass gap and flow distributions are closely related to the local hot spot and its location and the core restraint mechanism preventing outward movement of the graphite block by a fastening device reduces the bypass gap size, which results in the decrease of maximum fuel temperature not less than 100 deg. C, when compared to the case without it.

  2. Effects of high shock pressures and pore morphology on hot spot mechanisms in HMX

    Science.gov (United States)

    Springer, H. K.; Tarver, C. M.; Bastea, S.

    2017-01-01

    The shock initiation and detonation behavior of heterogeneous solid explosives is governed by its microstructure and reactive properties. New additive manufacturing techniques offer unprecedented control of explosive microstructures previously impossible, enabling us to develop novel explosives with tailored shock sensitivity and detonation properties. Since microstructure-performance relationships are not well established for explosives, there is little material design guidance for these manufacturing techniques. In this study, we explore the effects of high shock pressures (15-38 GPa) with long shock durations and different pore morphologies on hot spot mechanisms in HMX. HMX is chosen as the model material because we have experimental data on many of the chemical-thermal-mechanical properties required for pore collapse simulations. Our simulations are performed using the multi-physics arbitrary Lagrangian Eulerian finite element hydrocode, ALE3D, with Cheetah-based models for the unreacted and the product equation-of-states. We use a temperature-dependent specific heat with the unreacted equation-of-state and a temperature-dependent viscosity model to ensure accurate shock temperatures for subsequent chemistry. The Lindemann Law model is used for shock melting in HMX. In contrast to previous pore collapse studies at lower shock pressures (≤10 GPa) in HMX and shorter post-collapse burning times, our calculations show that shock melting occurs above 15 GPa due to higher bulk heating and a prominent elongated ("jet-like") hot spot region forms at later times. The combination of the elongated, post-collapse hot spot region and the higher bulk heating with increasing pressure dramatically increases the growth rate of reaction. Our calculations show that the reaction rate, dF/dt, increases with increasing shock pressure. We decompose the reaction rate into ignition ((dF/dt)ig) and growth ((dF/dt)gr) phases to better analyze our results. We define the ignition phase

  3. Investigation of sources of atmospheric aerosol at a hot spot area in Dhaka, Bangladesh.

    Science.gov (United States)

    Begum, Bilkis A; Biswas, Swapan K; Kim, Eugene; Hopke, Philip K; Khaliquzzaman, Mohammed

    2005-02-01

    Samples of fine and coarse fractions of airborne particulate matter were collected at the Farm Gate area in Dhaka from July 2001 to March 2002. Dhaka is a hot spot area with very high pollutant concentrations because of the proximity of major roadways. The samples were collected using a "Gent" stacked filter unit in two fractions of 0- to 2.2-microm and 2.2- to 10-microm sizes. The samples were analyzed for elemental concentrations by particle-induced X-ray excitation (PIXE) and for black carbon by reflectivity methods, respectively. The data were analyzed by positive matrix factorization (PMF) to identify the possible sources of atmospheric aerosols in this area. Six sources were found for both the coarse and fine PM fractions. The data sets were also analyzed by an expanded model to explore additional sources. Seven and six factors were obtained for coarse and fine PM fractions, respectively, in these analyses. The identified sources are motor vehicle, soil dust, emissions from construction activities, sea salt, biomass burning/brick kiln, resuspended/fugitive Pb, and two-stroke engines. From the expanded modeling, approximately 50% of the total PM2.2 mass can be attributed to motor vehicles, including two-stroke engine vehicle in this hot spot in Dhaka, whereas the PMF modeling indicates that 45% of the total PM2.2 mass is from motor vehicles. The PMF2 and expanded models could resolve approximately 4% and 3% of the total PM2.2 mass as resuspended/fugitive Pb, respectively. Although, Pb has been eliminated from gasoline in Bangladesh since July 1999, there still may be substantial amounts of accumulated lead in the dust near roadways as well as fugitive Pb emissions from battery reclaimation and other industries. Soil dust is the largest component of the coarse particle fraction (PM2.2-10) accounting for approximately 71% of the total PM2.2-10 mass in the expanded model, whereas from the PMF modeling, the dust (undifferentiated) contribution is approximately 49%.

  4. The structure of HIV-1 genomic RNA in the gp120 gene determines a recombination hot spot in vivo.

    Science.gov (United States)

    Galetto, Román; Moumen, Abdeladim; Giacomoni, Véronique; Véron, Michel; Charneau, Pierre; Negroni, Matteo

    2004-08-27

    By frequently rearranging large regions of the genome, genetic recombination is a major determinant in the plasticity of the human immunodeficiency virus type I (HIV-1) population. In retroviruses, recombination mostly occurs by template switching during reverse transcription. The generation of retroviral vectors provides a means to study this process after a single cycle of infection of cells in culture. Using HIV-1-derived vectors, we present here the first characterization and estimate of the strength of a recombination hot spot in HIV-1 in vivo. In the hot spot region, located within the C2 portion of the gp120 envelope gene, the rate of recombination is up to ten times higher than in the surrounding regions. The hot region corresponds to a previously identified RNA hairpin structure. Although recombination breakpoints in vivo cluster in the top portion of the hairpin, the bias for template switching in this same region appears less marked in a cell-free system. By modulating the stability of this hairpin we were able to affect the local recombination rate both in vitro and in infected cells, indicating that the local folding of the genomic RNA is a major parameter in the recombination process. This characterization of reverse transcription products generated after a single cycle of infection provides insights in the understanding of the mechanism of recombination in vivo and suggests that specific regions of the genome might be prompted to yield different rates of evolution due to the presence of circumscribed recombination hot spots.

  5. 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

  6. 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

  7. New Caledonia: A 'Hot Spot' for Valuable Chemodiversity. Part 1: Gymnosperms.

    Science.gov (United States)

    Coulerie, Paul; Poullain, Cyril

    2015-06-01

    The flora of New Caledonia encompasses more than 3,000 species and almost 80% of them are endemic. New Caledonia is considered as a 'hot spot' for biodiversity. With the current global loss of biodiversity, and the fact that several drugs and pesticides are becoming obsolete, there is an urgent need to increase sampling and research on new natural products. In this context, we review the chemical information available on New Caledonian native flora from economical perspectives. We expect that a better knowledge of the economic potential will encourage the plantation of native plants for the development of a sustainable economy which will participate in the conservation of biodiversity. In the first part of this review, we discuss the results reported in 18 scientific articles on the chemicals isolated from 23 endemic conifers of New Caledonia. Several bioactive and original products, such as neocallitropsene or libocedrins, have been isolated from these conifers. This review also highlights several groups, such as Podocarpus spp., that are unexplored in New Caledonia despite the fact that they have been described in other countries to contain a wide range of original bioactive compounds. Those plants are considered as priority for future chemical investigations.

  8. 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

  9. 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.

  10. Suppressing local hot spots due to eddy currents in magnetic coil systems

    Science.gov (United States)

    Yao, Zhen; Shojinaga, Aaron; Wu, Yong; Shvartsman, Shmaryu; Eagan, Timothy; Chmielewski, Thomas; Brown, Robert

    2011-03-01

    A particular goal in magnetic field applications is to avoid eddy current heating in coils and shields. It is important, in MRI, for example, to avoid hot spots near the patient to be imaged as well as in the vicinity of soldering joints. We develop effective analytical formulas for the eddy current behavior of sources close to surrounding conductors, we verify these via numerical simulations, and we make successful comparisons to corresponding experimental temperature distributions. Optimized patterns of incisions made in the conductors are discovered for addressing particularly troublesome heating locations. The criteria include the need to minimize the number and length of the cuts. Theory and experiment are in agreement on the efficacy of this method for reducing steady-state temperatures. An example of results in the practical design of commercial coils and shields is that a single cut parallel to the long edge of rectangular conductors reduces the temperatures much more than making multiple cuts parallel to the short edge. Supported by Ohio Third Frontier Program

  11. Radio lobes and X-ray hot spots in the microquasar S26

    CERN Document Server

    Soria, Roberto; Broderick, Jess W; Corbel, Stephane; Motch, Christian

    2010-01-01

    We have studied the structure and energetics of the powerful microquasar/shock-ionized nebula S26 in NGC 7793, with particular focus on its radio and X-ray properties. Using the Australia Telescope Compact Array, we have resolved for the first time the radio lobe structure and mapped the spectral index of the radio cocoon. The steep spectral index of the radio lobes is consistent with optically-thin synchrotron emission; outside the lobes, the spectral index is flatter, suggesting an additional contribution from free-free emission, and perhaps ongoing ejections near the core. The radio core is not detected, while the X-ray core has a 0.3-8 keV luminosity ~6 x 10^{36} erg/s. The size of the radio cocoon matches that seen in the optical emission lines and diffuse soft X-ray emission. The total 5.5-GHz flux of cocoon and lobes is ~2.1 mJy, which at the assumed distance of 3.9 Mpc corresponds to about 3 times the luminosity of Cas A. The total 9.0-GHz flux is ~1.6 mJy. The X-ray hot spots (combined 0.3-8 keV lumi...

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

    Energy Technology Data Exchange (ETDEWEB)

    Pau, F. [Rotterdam School of Management, Erasmus Research Institute of Management ERIM, Rotterdam (Netherlands); Oremus, M.H.P. [Rolls Royce (BMW) Germany, Dahlewitz (Germany)

    2003-04-01

    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.

  13. 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.

  14. Mutation Hot Spots in Yeast Caused by Long-Range Clustering of Homopolymeric Sequences

    Directory of Open Access Journals (Sweden)

    Xin Ma

    2012-01-01

    Full Text Available Evolutionary theory assumes that mutations occur randomly in the genome; however, studies performed in a variety of organisms indicate the existence of context-dependent mutation biases. Sources of mutagenesis variation across large genomic contexts (e.g., hundreds of bases have not been identified. Here, we use high-coverage whole-genome sequencing of a conditional mismatch repair mutant line of diploid yeast to identify mutations that accumulated after 160 generations of growth. The vast majority of the mutations accumulated as insertion/deletions (in/dels in homopolymeric [poly(dA:dT] and repetitive DNA tracts. Surprisingly, the likelihood of an in/del mutation in a given poly(dA:dT tract is increased by the presence of nearby poly(dA:dT tracts in up to a 1,000 bp region centered on the given tract. Our work suggests that specific mutation hot spots can contribute disproportionately to the genetic variation that is introduced into populations and provides long-range genomic sequence context that contributes to mutagenesis.

  15. Direct simulations of homogeneous bubble nucleation: Agreement with classical nucleation theory and no local hot spots.

    Science.gov (United States)

    Diemand, Jürg; Angélil, Raymond; Tanaka, Kyoko K; Tanaka, Hidekazu

    2014-11-01

    We present results from direct, large-scale molecular dynamics simulations of homogeneous bubble (liquid-to-vapor) nucleation. The simulations contain half a billion Lennard-Jones atoms and cover up to 56 million time steps. The unprecedented size of the simulated volumes allows us to resolve the nucleation and growth of many bubbles per run in simple direct micro-canonical simulations while the ambient pressure and temperature remain almost perfectly constant. We find bubble nucleation rates which are lower than in most of the previous, smaller simulations. It is widely believed that classical nucleation theory (CNT) generally underestimates bubble nucleation rates by very large factors. However, our measured rates are within two orders of magnitude of CNT predictions; only at very low temperatures does CNT underestimate the nucleation rate significantly. Introducing a small, positive Tolman length leads to very good agreement at all temperatures, as found in our recent vapor-to-liquid nucleation simulations. The critical bubbles sizes derived with the nucleation theorem agree well with the CNT predictions at all temperatures. Local hot spots reported in the literature are not seen: Regions where a bubble nucleation event will occur are not above the average temperature, and no correlation of temperature fluctuations with subsequent bubble formation is seen.

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

    Directory of Open Access Journals (Sweden)

    Rita Melo

    2016-07-01

    Full Text Available 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.

  17. Hot spot model of MagLIF implosions: Nernst term effect on magnetic flux losses

    Science.gov (United States)

    Garcia Rubio, Fernando; Sanz Recio, Javier; Betti, Riccardo

    2016-10-01

    An analytical model of a collisional plasma being compressed by a cylindrical liner is proposed and solved in a magnetized liner inertial fusion-like context. The implosion is assumed to be isobaric, and the magnetic diffusion is confined to a thin layer near the liner. Both unmagnetized and magnetized plasma cases are considered. The model reduces to a system of two partial differential equations for temperature and magnetic field. Special attention is given to the effect of the Nernst term on the evolution of the magnetic field. Scaling laws for temperature, magnetic field, hot spot mass increase and magnetic field losses are obtained. The temperature and magnetic field spatial profiles tend to a self-similar state. It is found that when the Nernst term is taken into account, the magnetic field is advected towards the liner, and the magnetic flux losses are independent of the magnetic Lewis number. Research supported by the Spanish Ministerio de Economía y Competitividad, Project No. ENE2014-54960R. Acknowledgements to the Laboratory of Laser Energetics (Rochester) for its hospitality.

  18. Simulated impact of self-generated magnetic fields in the hot-spot of NIF implosions

    Science.gov (United States)

    Partha, M. A.; Haan, S. W.; Koning, J.; Marinak, M. M.; Weber, C. R.; Clark, D. S.

    2016-10-01

    Deviations from sphericity in an imploded hot-spot result in magnetic fields generated by the Biermann battery effect. The magnetic field can reduce thermal conductivity, affect α transport, change instability growth, and cause magnetic pressure. Previous estimates of these effects have indicated that they are not of great consequence, but have suggested that they could plausibly affect NIF observables such as yield and ion temperature by 5-25%. Using the MHD capability in the Hydra code, we evaluated the impact of these processes in a post-shot model for a typical NIF implosion. Various implosion asymmetries were implemented, with the goal of surveying plausible implosion configurations to find the geometry in which the MHD effects were the most significant. Magnetic fields are estimated to approach 104 Tesla, and to affect conductivity locally by more than 50%, but global impact on observables is small in most cases. Work performed under the auspices of the U.S. D.O.E. by Lawrence Livermore National Laboratory under Contract No. DE-AC52-07NA27344.

  19. 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

  20. “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.

  1. A comparison of Ki-67 counting methods in luminal Breast Cancer: The Average Method vs. the Hot Spot Method

    Science.gov (United States)

    Jang, Min Hye; Kim, Hyun Jung; Chung, Yul Ri; Lee, Yangkyu

    2017-01-01

    In spite of the usefulness of the Ki-67 labeling index (LI) as a prognostic and predictive marker in breast cancer, its clinical application remains limited due to variability in its measurement and the absence of a standard method of interpretation. This study was designed to compare the two methods of assessing Ki-67 LI: the average method vs. the hot spot method and thus to determine which method is more appropriate in predicting prognosis of luminal/HER2-negative breast cancers. Ki-67 LIs were calculated by direct counting of three representative areas of 493 luminal/HER2-negative breast cancers using the two methods. We calculated the differences in the Ki-67 LIs (ΔKi-67) between the two methods and the ratio of the Ki-67 LIs (H/A ratio) of the two methods. In addition, we compared the performance of the Ki-67 LIs obtained by the two methods as prognostic markers. ΔKi-67 ranged from 0.01% to 33.3% and the H/A ratio ranged from 1.0 to 2.6. Based on the receiver operating characteristic curve method, the predictive powers of the KI-67 LI measured by the two methods were similar (Area under curve: hot spot method, 0.711; average method, 0.700). In multivariate analysis, high Ki-67 LI based on either method was an independent poor prognostic factor, along with high T stage and node metastasis. However, in repeated counts, the hot spot method did not consistently classify tumors into high vs. low Ki-67 LI groups. In conclusion, both the average and hot spot method of evaluating Ki-67 LI have good predictive performances for tumor recurrence in luminal/HER2-negative breast cancers. However, we recommend using the average method for the present because of its greater reproducibility. PMID:28187177

  2. 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.

  3. 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.

  4. Seamount morphology in the Bowie and Cobb hot spot trails, Gulf of Alaska

    Science.gov (United States)

    Chaytor, Jason D.; Keller, Randall A.; Duncan, Robert A.; Dziak, Robert P.

    2007-09-01

    Full-coverage multibeam bathymetric mapping of twelve seamounts in the Gulf of Alaska reveals that they are characterized by flat-topped summits (rarely with summit craters) and by terraced, or step-bench, flanks. These summit plateaus contain relict volcanic features (e.g., flow levees, late-stage cones, and collapse craters) and as such must have been constructed by volcanic processes such as lava ponding above a central vent, rather than by erosion above sea level. The terraced flanks are composed of a sequence of stacked lava deltas and cones, probably tube-fed from a central lava pond, a morphology which is suggestive of long-lived, stable central lava sources and low to moderate eruption rates, indicative of significant time spent above a hot spot outlet. Most of these seamounts have summit plateaus surrounded, and cut into, by amphitheater headwall scarps, and flanks that are scarred by debris chutes, but lack visible debris accumulations at their base. We interpret the lack of blocky debris fields as evidence that the slope failures are mainly small-scale debris flows, rather than large-scale flank collapses. However, we cannot rule out the possibility that large flank-collapse blocks from early in the histories of these seamounts are now hidden beneath the thick glacio-fluvial fan deposits that cover the Gulf of Alaska seafloor. These slope failure features become smoother and longer and increase in size and abundance with increasing age of a seamount, suggesting that slope failure processes continue long after volcanic activity ceases.

  5. 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

  6. 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.

  7. Electric arc furnaces for steel-making: hot spots for persistent organic pollutants.

    Science.gov (United States)

    Odabasi, Mustafa; Bayram, Abdurrahman; Elbir, Tolga; Seyfioglu, Remzi; Dumanoglu, Yetkin; Bozlaker, Ayse; Demircioglu, Hulusi; Altiok, Hasan; Yatkin, Sinan; Cetin, Banu

    2009-07-15

    Persistent organic pollutant (POP) concentrations were measured in stack-gases of ferrous scrap processing steel plants with electric arc furnaces (EAFs) (n = 5) in Aliaga, Izmir, Turkey and in air (n = 11) at a site near those plants. Measured stack-gas concentrations for the four plants without scrap preheating (611 +/- 311, 165,000 +/- 285,000, and 33 +/- 3 ng m(-3), average +/- SD for sigma41PCBs, sigma16PAHs, and sigma7PBDEs, respectively) indicated that they are significant sources for polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs). POP emissions from the plant with scrap preheating were significantly higher (13 500, 445 000, and 91 ng m(-3) for sigma41PCBs, sigma16PAHs, and sigma7PBDEs, respectively). It was also shown that the steel plants emit considerable amounts of fugitive POPs in particle-phase. Estimated emissions using the emission factors generated in this study and the production amounts suggested that the steel plants with EAFs may significantly contribute to local and global PAH, PCB, and PBDE emissions. Several other compounds (aromatic and aliphatic hydrocarbons, oxygen, sulfur, nitrogen, and chlorine-containing organic compounds, n = 49) were identified and determined semiquantitatively in the stack-gas and ambient air samples. Ambient air concentrations (62 +/- 35, 320 +/- 134 ng m(-3), 1451 +/- 954 pg m(-3), for sigma41PCBs, sigma16PAHs, and sigma7PBDEs, respectively) were significantly higher than those measured previously around the world and in the region, further confirming that the steel plants with EAFs are "hot spots" for POPs.

  8. Relating Precipitation Phenomena with MODIS Detected Hot Spots in the Maritime Continent

    Science.gov (United States)

    Ramirez, E. M.; Reid, J. S.; Xian, P.; Hyer, E.; Turk, J.; Flatau, M.; Zhang, C.

    2009-12-01

    Recent studies of land use practices in SE Asia’s Maritime Continent (MC) have raised questions over potential meteorological implications including smoke-cloud interaction and changes in the regional radiation budget. Land management practices on Java, Sumatra, Sulawesi, Borneo, and the Malay Peninsula include biomass burning to clear primary forest as well as to maintain oil palm plantations. Burning is also employed for clearing unwanted remains from previous crops, rice stubble for example. However, burning activity is often dictated by weather, in particular precipitation. We studied 5 years of MODIS active fire hot spot and satellite precipitation data to investigate how observed burning activity correlated with precipitation features at four major scales: 1) Intraseasonal El Nino-Southern Oscillation (ENSO) and Indian Ocean Dipole (IOP); 2) Seasonal migration of the Intertropical Convergence Zone (ITCZ); 3) the 30-90 day Madden Julian Oscillation (MJO); and 4) regional convection from localized weather phenomenon (e.g., orographic, isolated thermal convection, sea breeze, etc…). It was found that observed burn patterns from each of the islands of the MC had differing responses to these four forcings. Observed burning activity on the islands of Borneo and Sulawesi correlated strongly with the ENSO and ITCZ indicies, whereas Sumatra was more influenced by the phase and strength of the MJO. Java, showing a mix of influence, exhibited strong fire activity in the morning rather than afternoon which is unusual for most burning regions. We hypothesize that these observed relationships reflect both physical land use differences and contextual bias/observability issues associated with the region’s heavy cloud cover. For further studies on smoke-meteorology interaction, our findings point to the need for a clear understanding of the meteorological context of satellite observations.

  9. Mutational hot spot in the DSPP gene causing dentinogenesis imperfecta type II.

    Science.gov (United States)

    Kim, Jung-Wook; Hu, Jan C-C; Lee, Jae-Il; Moon, Sung-Kwon; Kim, Young-Jae; Jang, Ki-Taeg; Lee, Sang-Hoon; Kim, Chong-Chul; Hahn, Se-Hyun; Simmer, James P

    2005-02-01

    The current system for the classification of hereditary defects of tooth dentin is based upon clinical and radiographic findings and consists of two types of dentin dysplasia (DD) and three types of dentinogenesis imperfecta (DGI). However, whether DGI type III should be considered a distinct phenotype or a variation of DGI type II is debatable. In the 30 years since the classification system was first proposed, significant advances have been made regarding the genetic etiologies of inherited dentin defects. DGI type II is recognized as an autosomal dominant disorder with almost complete penetrance and a low frequency of de novo mutations. We have identified a mutation (c.52G-->T, p.V18F) at the first nucleotide of exon 3 of the DSPP (dentin sialophosphoprotein) gene in a Korean family (de novo) and a Caucasian family. This mutation has previously been reported as causing DGI type II in a Chinese family. These findings suggest that this mutation site represents a mutational "hot spot" in the DSPP gene. The clinical and radiographic features of these two families include the classic phenotypes associated with both DGI type II and type III. Finding that a single mutation causes both phenotypic patterns strongly supports the conclusion that DGI type II and DGI type III are not separate diseases but rather the phenotypic variation of a single disease. We propose a modification of the current classification system such that the designation "hereditary opalescent dentin" or "DGI type II" should be used to describe both the DGI type II and type III phenotypes.

  10. 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.

  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. 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...

  13. Origin of the X-rays and Possible GeV-TeV Emission from the Western Hot Spot Of Pictor A

    CERN Document Server

    Zhang, Jin; Chen, Liang; Yang, Xian

    2009-01-01

    Pictor A is a nearby Fanaroff-Riley class II (FR II) radio galaxy with a bright hot spot, the western hot spot. Observation of high polarization in the optical emission of the hot spot indicates that the optical emission could be synchrotron radiation of relativistic electrons in the hot spot. These electrons may be able to produce high energy gamma-ray photons through inverse Compton (IC) scattering. We use single-zone and multi-zone synchrotron + synchrotron-self-Compton (SSC) models to fit the observed spectral energy distribution (SED) from the radio to the X-ray band of the hot spot. Our esults show that in the case of a much weaker magnetic field strength than the equipartition magnetic field, both the single-zone and multi-zone models can fit the SED, but the multi-zone model significantly improves the fit. The two models predict the hot spot as a GeV-TeV source, which might be marginally detectable with Fermi/LAT and HESS. The inverse Compton scattering of cosmic microwave background (IC/CMB) is also ...

  14. A Radio through X-ray Study of the Hot Spots, Active Nucleus, and Environment of the Nearby FR II Radio Galaxy 3C 33

    CERN Document Server

    Kraft, R P; Hardcastle, M J; Evans, D A; Croston, J H; Worrall, D M; Murray, S S

    2007-01-01

    We present results from {\\em Chandra}/ACIS-S, {\\em Spitzer}, {\\em XMM-Newton}, {\\em HST}, and VLA observations of the radio hot spots, extended environment, and nucleus of the nearby ($z$=0.0597) FR II radio galaxy 3C 33. This is a relatively low-power FR II radio galaxy, and so we expect, {\\it a priori}, to detect a significant X-ray synchrotron component to the emission from the hot spots. We detect X-ray emission coincident with the two knots of polarized optical emission from the southern hot spot (SHS), as well as along the northwest arm of this hot spot. We also detect X-ray emission from two compact regions of the northern hot spot (NHS), as well as diffuse emission behind the radio peak. The X-ray flux density of the region at the tip of the southern hot spot, the most compact radio feature of the southern lobe, is consistent with the synchrotron self-Compton (SSC) process. The X-ray flux densities of the other three regions of the SHS and the two compact regions of the NHS are an order of magnitude o...

  15. Metatranscriptomic Analysis Reveals Unexpectedly Diverse Microbial Metabolism in a Biogeochemical Hot Spot in an Alluvial Aquifer

    Science.gov (United States)

    Jewell, Talia N. M.; Karaoz, Ulas; Bill, Markus; Chakraborty, Romy; Brodie, Eoin L.; Williams, Kenneth H.; Beller, Harry R.

    2017-01-01

    Organic matter deposits in alluvial aquifers have been shown to result in the formation of naturally reduced zones (NRZs), which can modulate aquifer redox status and influence the speciation and mobility of metals, affecting groundwater geochemistry. In this study, we sought to better understand how natural organic matter fuels microbial communities within anoxic biogeochemical hot spots (NRZs) in a shallow alluvial aquifer at the Rifle (CO) site. We conducted a 20-day microcosm experiment in which NRZ sediments, which were enriched in buried woody plant material, served as the sole source of electron donors and microorganisms. The microcosms were constructed and incubated under anaerobic conditions in serum bottles with an initial N2 headspace and were sampled every 5 days for metagenome and metatranscriptome profiles in combination with biogeochemical measurements. Biogeochemical data indicated that the decomposition of native organic matter occurred in different phases, beginning with mineralization of dissolved organic matter (DOM) to CO2 during the first week of incubation, followed by a pulse of acetogenesis that dominated carbon flux after 2 weeks. A pulse of methanogenesis co-occurred with acetogenesis, but only accounted for a small fraction of carbon flux. The depletion of DOM over time was strongly correlated with increases in expression of many genes associated with heterotrophy (e.g., amino acid, fatty acid, and carbohydrate metabolism) belonging to a Hydrogenophaga strain that accounted for a relatively large percentage (~8%) of the metatranscriptome. This Hydrogenophaga strain also expressed genes indicative of chemolithoautotrophy, including CO2 fixation, H2 oxidation, S-compound oxidation, and denitrification. The pulse of acetogenesis appears to have been collectively catalyzed by a number of different organisms and metabolisms, most prominently pyruvate:ferredoxin oxidoreductase. Unexpected genes were identified among the most highly expressed

  16. 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

  17. 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.

  18. 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...

  19. Bear Creek Valley Floodplain Hot Spot Removal Action Project Plan, Oak Ridge Y-12 Plant, Oak Ridge, Tennessee

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-01-01

    The Bear Creek Valley Floodplain Hot Spot Removal Action Project Plan, Oak Ridge Y-12 Plant, Oak Ridge, Tennessee (Y/ER-301) was prepared (1) to safely, cost-effectively, and efficiently evaluate the environmental impact of solid material in the two debris areas in the context of industrial land uses (as defined in the Bear Creek Valley Feasibility Study) to support the Engineering Evaluation/Cost Assessment and (2) to evaluate, define, and implement the actions to mitigate these impacts. This work was performed under Work Breakdown Structure 1.x.01.20.01.08.

  20. 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

  1. Biological impacts of "hot-spot" mutations of hepatitis B virus X proteins are genotype B and C differentiated

    Institute of Scientific and Technical Information of China (English)

    Xu Lin; Xiao Xu; Qing-Ling Huang; Yu-Qing Liu; Da-Li Zheng; Wan-Nan Chen; Jian-Yin Lin

    2005-01-01

    AIM: To investigate the biological impacts of "hot-spot"mutations on genotype B and C HBV X proteins (HBx).METHODS: Five types of"hot-spot" mutations of genotype B or C HBV X genes, which sequentially lead to the amino acid substitutions of HBx as I127T, F132Y, K130M+V131I,I127T+K130M+V131I, or K130M+V131I+F132Y, respectively,were generated by means of site-directed mutagenesis.To evaluate the anti-proliferative effects, HBx or related mutants' expression vectors were transfected separately to the Chang cells by lipofectamine, and the cells were cultured in hygromycin selective medium for 14 d, drug-resistant colonies were fixed with cold methanol, stained with Giemsa dyes and scored (increase of the colonies indicated the reduction of the anti-proliferation activity,and vice versa). Different types of HBx expression vectors were co-transfected separately with the reporter plasmid pCMVβ to Chang cells, which were lysed 48 h post-transfection and the intra-cellular β-galactosidase activities were monitored (increase of the β-galactosidase activities indicated the reduction of the transactivation activity, and vice versa). All data obtained were calculated by paired-samples t-test.RESULTS: As compared to standard genotype B HBx,mutants of I127T and I127T+K130M+V131I showed higher transactivation and anti-proliferative activities, while the mutants of F132Y, K130M+V131I, and K130M+V131I+F132Y showed lower activities. As compared to standard genotype C HBx, I127T mutant showed higher transactivation activity, while the other four types of mutants showed no differences. With regard to anti-proliferative activity,compared to standard genotype C HBx, F132Y and K130M+V131I mutants showed lower activities, and K130M+V131I +F132Y mutant, on the other hand, showed higher activity,while the mutants of I127T and I127T+K130M+V131I showed no differences.CONCLUSION: "Hot-spot" mutations affect the antiproliferation and transactivation activities of genotype B and/or C HBx, and

  2. Temporary shielding of hot spots in the drainage areas of cutaneous melanoma improves accuracy of lymphoscintigraphic sentinel lymph node diagnostics

    Energy Technology Data Exchange (ETDEWEB)

    Maza, S.; Valencia, R.; Geworski, L.; Zander, A.; Munz, D.L. [Clinic for Nuclear Medicine, University Hospital Charite, Humboldt University of Berlin, Schumannstrasse 20-21, 10117 Berlin (Germany); Draeger, E.; Winter, H.; Sterry, W. [Clinic for Dermatology, Venereology and Allergology, University Hospital Charite, Humboldt University of Berlin, Berlin (Germany)

    2002-10-01

    Detection of the ''true'' sentinel lymph nodes, permitting correct staging of regional lymph nodes, is essential for management and prognostic assessment in malignant melanoma. In this study, it was prospectively evaluated whether simple temporary shielding of hot spots in lymphatic drainage areas could improve the accuracy of sentinel lymph node diagnostics. In 100 consecutive malignant melanoma patients (45 women, 55 men; age 11-91 years), dynamic and static lymphoscintigraphy in various views was performed after strict intracutaneous application of technetium-99m nanocolloid (40-150 MBq; 0.05 ml/deposit) around the tumour (31 patients) or the biopsy scar (69 patients, safety distance 1 cm). The images were acquired with and without temporary lead shielding of the most prominent hot spots in the drainage area. In 33/100 patients, one or two additional sentinel lymph nodes that showed less tracer accumulation or were smaller (<1.5 cm) were detected after shielding. Four of these patients had metastases in the sentinel lymph nodes; the non-sentinel lymph nodes were tumour negative. In 3/100 patients, hot spots in the drainage area proved to be lymph vessels, lymph vessel intersections or lymph vessel ectasias after temporary shielding; hence, a node interpreted as a non-sentinel lymph node at first glance proved to be the real sentinel lymph node. In two of these patients, lymph node metastasis was histologically confirmed; the non-sentinel lymph nodes were tumour free. In 7/100 patients the exact course of lymph vessels could be mapped after shielding. In one of these patients, two additional sentinel lymph nodes (with metastasis) were detected. Overall, in 43/100 patients the temporary shielding yielded additional information, with sentinel lymph node metastases in 7%. In conclusion, when used in combination with dynamic acquisition in various views, temporary shielding of prominent hot spots in the drainage area of a malignant melanoma of the

  3. 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.

  4. 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

  5. Hydrodynamic Mixing of Ablator Material into the Compressed Fuel and Hot Spot of Direct-Drive DT Cryogenic Implosions

    Science.gov (United States)

    Regan, S. P.; Goncharov, V. N.; Epstein, R.; Betti, R.; Bonino, M. J.; Cao, D.; Collins, T. J. B.; Campbell, E. M.; Forrest, C. J.; Glebov, V. Yu.; Harding, D. R.; Marozas, J. A.; Marshall, F. J.; McKenty, P. W.; Sangster, T. C.; Stoeckl, C.; Luo, R. W.; Schoff, M. E.; Farrell, M.

    2016-10-01

    Hydrodynamic mixing of ablator material into the compressed fuel and hot spot of direct-drive DT cryogenic implosions is diagnosed using time-integrated, spatially resolved xray spectroscopy. The laser drive ablates most of the 8- μm-thick CH ablator, which is doped with trace amounts of Ge ( 0.5 at.) and surrounds the cryogenic DT layer. A small fraction of the ablator material is mixed into the compressed shell and the hot spot by the ablation-front Rayleigh-Taylor hydrodynamic instability seeded by laser imprint, the target mounting stalk, and surface debris. The amount of mix mass inferred from spectroscopic analysis of the Ge K-shell emission will be presented. This material is based upon work supported by the Department Of Energy National Nuclear Security Administration under Award Number DE-NA0001944. Part of this work was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344.

  6. Identification of Interaction Hot Spots in Structures of Drug Targets on the Basis of Three-Dimensional Activity Cliff Information.

    Science.gov (United States)

    Furtmann, Norbert; Hu, Ye; Gütschow, Michael; Bajorath, Jürgen

    2015-12-01

    Activity cliffs are defined as pairs or groups of structurally similar or analogous compounds that share the same specific activity but have large differences in potency. Although activity cliffs are mostly studied in medicinal chemistry at the level of molecular graphs, they can also be assessed by comparing compound binding modes. If such three-dimensional activity cliffs (3D-cliffs) are studied on the basis of X-ray complex structures, experimental ligand-target interaction details can be taken into account. Rapid growth in the number of 3D-cliffs that can be derived from X-ray complex structures has made it possible to identify targets for which a substantial body of 3D-cliff information is available. Activity cliffs are typically studied to identify structure-activity relationship determinants and aid in compound optimization. However, 3D-cliff information can also be used to search for interaction hot spots and key residues, as reported herein. For six of seven drug targets for which more than 20 3D-cliffs were available, series of 3D-cliffs were identified that were consistently involved in interactions with different hot spots. These 3D-cliffs often encoded chemical modifications resulting in interactions that were characteristic of highly potent compounds but absent in weakly potent ones, thus providing information for structure-based design.

  7. An Analytical Model for Torus Networks in the Presence of Batch Message Arrivals with Hot-spot Destinations

    Institute of Scientific and Technical Information of China (English)

    Yulei Wu; Geyong Min; Mohamed Ould-Khaoua; Hao Yin

    2009-01-01

    Interconnection networks are hardware fabrics supporting communications between individual processors in multicomputers.The low-dimensional k-ary n-cubes (or torus) with adaptive wormhole switching have attracted significant research efforts to construct high-performance interconnection networks in contemporary multi-computers.The arrival process and destination distribution of messages have great effects on network performance.With the aim of capturing the characteristics of the realistic traffic pattern and obtaining a deep understanding of the performance behaviour of interconnection networks,this paper presents an analytical model to investigate the message latency in adaptive-routed wormhole-switched torus networks where there exists hot-spot nodes and the message arrivals follow a batch arrival process.Each generated message has a given probability to be directed to the hot-spot node.The average degree of virtual channel multiplexing is computed by the GE/G/1/V queueing system with finite buffer capacity.We compare analytical results of message latency with those obtained through the simulation experiments in order to validate the accuracy of the derived model.

  8. Three-Dimensional Analysis of the Hot-Spot Fuel Temperature in Pebble Bed and Prismatic Modular Reactors

    Energy Technology Data Exchange (ETDEWEB)

    In, W. K.; Lee, S. W.; Lim, H. S.; Lee, W. J. [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    2006-07-01

    High temperature gas-cooled reactors(HTGR) have been reviewed as potential sources for future energy needs, particularly for a hydrogen production. Among the HTGRs, the pebble bed reactor(PBR) and a prismatic modular reactor(PMR) are considered as the nuclear heat source in Korea's nuclear hydrogen development and demonstration project. PBR uses coated fuel particles embedded in spherical graphite fuel pebbles. The fuel pebbles flow down through the core during an operation. PMR uses graphite fuel blocks which contain cylindrical fuel compacts consisting of the fuel particles. The fuel blocks also contain coolant passages and locations for absorber and control material. The maximum fuel temperature in the core hot spot is one of the important design parameters for both a PBR and a PMR. The objective of this study is to predict the hot-spot fuel temperature distributions in a PBR and a PMR at a steady state. The computational fluid dynamics(CFD) code, CFX-10 is used to perform the three-dimensional analysis. The latest design data was used here based on the reference reactor designs, PBMR400 and GTMHR60.

  9. Environmental health risk assessment of dioxin exposure through foods in a dioxin hot spot-Bien Hoa City, Vietnam.

    Science.gov (United States)

    Tuyet-Hanh, Tran Thi; Vu-Anh, Le; Ngoc-Bich, Nguyen; Tenkate, Thomas

    2010-05-01

    This study used the Australian Environmental Health Risk Assessment Framework to assess the human health risk of dioxin exposure through foods for local residents in two wards of Bien Hoa City, Vietnam. These wards are known hot-spots for dioxin and a range of stakeholders from central government to local levels were involved in this process. Publications on dioxin characteristics and toxicity were reviewed and dioxin concentrations in local soil, mud, foods, milk and blood samples were used as data for this risk assessment. A food frequency survey of 400 randomly selected households in these wards was conducted to provide data for exposure assessment. Results showed that local residents who had consumed locally cultivated foods, especially fresh water fish and bottom-feeding fish, free-ranging chicken, duck, and beef were at a very high risk, with their daily dioxin intake far exceeding the tolerable daily intake recommended by the WHO. Based on the results of this assessment, a multifaceted risk management program was developed and has been recognized as the first public health program ever to have been implemented in Vietnam to reduce the risks of dioxin exposure at dioxin hot-spots.

  10. Effects of basal-plane thermal conductivity and interface thermal conductance on the hot spot temperature in graphene electronic devices

    Science.gov (United States)

    Choi, David; Poudel, Nirakar; Cronin, Stephen B.; Shi, Li

    2017-02-01

    Electrostatic force microscopy and scanning thermal microscopy are employed to investigate the electric transport and localized heating around defects introduced during transfer of graphene grown by chemical vapor deposition to an oxidized Si substrate. Numerical and analytical models are developed to explain the results based on the reported basal-plane thermal conductivity, κ, and interfacial thermal conductance, G, of graphene and to investigate their effects on the peak temperature. Irrespective of the κ values, increasing G beyond 4 × 107 W m-2 K-1 can reduce the peak temperature effectively for graphene devices made on sub-10 nm thick gate dielectric, but not for the measured device made on 300-nm-thick oxide dielectric, which yields a cross-plane thermal conductance (Gox) much smaller than the typical G of graphene. In contrast, for typical G values reported for graphene, increasing κ from 300 W m-1 K-1 toward 3000 W m-1 K-1 is effective in reducing the hot spot temperature for the 300-nm-thick oxide devices but not for the sub-10 nm gate dielectric case, because the heat spreading length (l) can be appreciably increased relative to the micron-scale localized heat generation spot size (r0) only when the oxide layer is sufficiently thick. As such, enhancement of κ increases the vertical heat transfer area above the gate dielectric only for the thick oxide case. In all cases considered, the hot spot temperature is sensitive to varying G and κ only when the G/Gox ratio and r0/l ratio are below about 5, respectively.

  11. 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.

  12. 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.

  13. 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

  14. Channeling at the base of the lithosphere during the lateral flow of plume material beneath flow line hot spots

    Science.gov (United States)

    Sleep, Norman H.

    2008-08-01

    Chains of volcanic edifices lie along flow lines between plume-fed hot spots and the thin lithosphere at ridge axes. Discovery and Euterpe/Musicians Seamounts are two examples. An attractive hypothesis is that buoyant plume material flows along the base of the lithosphere perpendicular to isochrons. The plume material may conceivably flow in a broad front or flow within channels convectively eroded into the base to the lithosphere. A necessary but not sufficient condition for convective channeling is that the expected stagnant-lid heat flow for the maximum temperature of the plume material is comparable to the half-space surface heat flow of the oceanic lithosphere. Two-dimensional and three-dimensional numerical calculations confirm this inference. A second criterion for significant convective erosion is that it needs to occur before the plume material thins by lateral spreading. Scaling relationships indicate spreading and convection are closely related. Mathematically, the Nusselt number (ratio of convective to conductive heat flow in the plume material) scales with the flux (volume per time per length of flow front) of the plume material. A blob of unconfined plume material thus spreads before the lithosphere thins much and evolves to a slowly spreading and slowly convecting warm region in equilibrium with conduction into the base of the overlying lithosphere. Three-dimensional calculations illustrate this long-lasting (and hence observable) state of plume material away from its plume source. A different flow domain occurs around a stationary hot plume that continuously supplies hot material. The plume convectively erodes the overlying lithosphere, trapping the plume material near its orifice. The region of lithosphere underlain by plume material grows toward the ridge axis and laterally by convective thinning of the lithosphere at its edges. The hottest plume material channels along flow lines. Geologically, the regions of lithosphere underlain by either warm

  15. 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

  16. DNase I-hypersensitive sites and transcription factor-binding motifs within the mouse E beta meiotic recombination hot spot.

    Science.gov (United States)

    Shenkar, R; Shen, M H; Arnheim, N

    1991-04-01

    The second intron of the E beta gene in the mouse major histocompatibility complex is the site of a meiotic recombination hot spot. We detected two DNase I-hypersensitive sites in this intron in meiotic cells isolated from mouse testes. One site appears to be constitutive and is found in other tissues regardless of whether or not they express the E beta gene. Near this hypersensitive site are potential binding motifs for H2TF1/KBF1, NF kappa B, and octamer transcription factors. Gel retardation studies with mouse lymphoma cell nuclear extracts confirmed that each of these motifs is capable of binding protein. The binding of transcription factors may contribute to the enhancement of recombination potential by altering chromatin structure and increasing the accessibility of the DNA to the recombination machinery.

  17. Particle Accelerators in the Hot Spots of the Radio Galaxy 3C445 Imaged With the VLT

    CERN Document Server

    Prieto, M A; Mack, K H; Brunetti, Gianfranco; Mack, Karl-Heinz

    2002-01-01

    Hot spots (HSs) are regions of enhanced radio emission produced by supersonic jets at the tip of the radio lobes of powerful radiosources. Obtained with the Very Large Telescope (VLT), images of the HSs in the radio galaxy 3C445 show bright knots embedded in diffuse optical emission distributed along the post shock region created by the impact of the jet into the intergalactic medium. The observations reported here confirm that relativistic electrons are accelerated by Fermi-I acceleration processes in HSs. Furthermore, both the diffuse emission tracing the rims of the front shock and the multiple knots demonstrate the presence of additional continuous re-acceleration processes of electrons (Fermi-II).

  18. 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.

  19. A Hot Spot and Mass Transfer of the Algol-type Binary System WZ Crv

    CERN Document Server

    Virnina, Natalia A; Mogorean, Maxim V

    2011-01-01

    We present the results of two color VR observation of the Algol-type binary system WZ Crv (12h44m15.19s, -21d25m35.4s) which were obtained using the remotely controlled telescope TOA-150 of Tzec Maun Observatory. We determined the moments of individual minima, the orbital period and its derivative, the initial epoch, color indices V-R and temperature estimates of the components. Also we noticed that the phase curve is asymmetric: the second maximum is higher than the first one. It indicates that there is a spot in the photosphere of one of the stars in this system.

  20. Infrared radiation emitted due to scanning of a hot spot as a probe of hidden defects

    Science.gov (United States)

    Woźny, Mariusz; Maś, Kinga; Prokhorenko, Serhiy; Ploch, Dariusz; Sheregii, E. M.

    2016-05-01

    Specially created subsurface defects in a sample are detected using a high resolution infrared camera FLIR SC7000. A scanning hot air (about 110 °C) nozzle is applied to introduce additional energy in a researched sample. The hidden defect has an increased temperature in comparison with the surrounding area that is a result of changed emissivity and thermal diffusivity. The suggested method is compared with pulse thermography which uses a xenon lamp for excitation.

  1. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Bondarenko, S., E-mail: sergeyb@ariel.ac.il; Komoshvili, K.; Prygarin, A.

    2016-06-15

    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.

  4. 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...

  5. Juan Fernández Ridge (Nazca Plate): petrology and thermochronology of a rejuvenated hot spot trail

    Science.gov (United States)

    Reyes, J.; Lara, L. E.

    2012-04-01

    The Juan Fernández Ridge on the oceanic Nazca plate is thought to be a classic hot spot trail because of the apparent westward rejuvenation of the eruptive ages. However, geochronological data is still scarce and there are a few constrains to support this hypothesis like the ca. 9 Ma Ar-Ar age of the O'Higgins seamount (115 km from the Chile-Perú trench), some published K-Ar ages of ca. 3-4 Ma in Robinson Crusoe island (580 km from the trench) and ca. 1 Ma in Alejandro Selkirk (180 km further west). New reconnaissance K-Ar ages and specially the ongoing Ar-Ar dating effort in Robinson Crusoe define a ca. 1-4 Ma time span, which partially overlap with the age of Alejandro Selkirk, breaking the expected age progression given that the Nazca plate moves eastwards at ca. 6-8 cm/yr. In addition, new geological mapping shows a sharp unconformity between the older (ca. 4 Ma), strongly altered sequences and the more recent (ca. 1 Ma), post-erosional volcanic piles, where the proximal facies are still preserved. Petrological evidence also supports this evolution pattern. In fact, the partially altered older sequence is tholeiitic (Ba/Yb=12.70; La/Yb=8.12; Ba/Y=6.51; Ba/Zr=0.89). The shield stage (ca. 1-3 Ma) is transicional from tholeiitic to alkaline (Ba/Yb=18.07-8.32; La/Yb=4.59-9.84; Ba/Y=4.24-8.18; Ba/Zr=0.73-1.09) and the younger (ca. 1 Ma) is mostly alkaline (Ba/Yb=38.15; La/Yb=15.66; Ba/Y=20.27; Ba/Zr=2.31). A fixed deep-mantle plume origin for Pacific hot spots has been widely debated and concurrent phenomena arose as a possible explanation for non-linear age progressions and/or long-lived volcanic activity. In fact, intraplate regional tectonics, plume displacement, and mantle heterogeneities could be the main factor of the ridge architecture or the mask for a first-order linear trend. An ongoing mapping and dating effort is aimed to understand the evolution of the Juan Fernández Ridge, testing the main hypothesis. This research is supported by FONDECYT Project

  6. Demonstration of 55 +/- 7-Gbar Hot-Spot Pressure in Direct-Drive Layered DT Cryogenic Implosions on OMEGA

    Science.gov (United States)

    Regan, S. P.

    2015-11-01

    Direct-drive ignition target designs for the National Ignition Facility (NIF) require hot-spot pressures in excess of 100 Gbar. Only one-third of the required pressure was inferred in earlier experimental campaigns conducted on the 60-beam, 30-kJ, 351-nm OMEGA laser with direct-drive implosions of layered DT cryogenic targets. Laser and target improvements were implemented on OMEGA to increase the stagnation pressure, including a set of phase plates to increase the laser irradiation uniformity on target and a purified fuel with isotope composition reaching a 50:50 DT ratio. Diagnostic improvements were made for a neutron burnwidth measurement with a 40-ps impulse response and a 16-channel Kirkpatrick-Baez microscope to measure gated (30-ps) x-ray images of the core near peak compression with 6- μm resolution. The inferred volume-averaged, peak pressure in the current campaign almost doubled to 55 +/- 7 Gbar with a neutron yield approaching 5 ×1013 . Further target performance improvements to reach hydrodynamic equivalence to ignition on OMEGA require mitigation of cross-beam energy transfer (CBET), which reduces the laser coupling. A proposed technique to reduce CBET by driving the spherical target with overlapping laser beams having individual focal spots smaller than the outside diameter of the target was investigated. The diameter of the target was discretely varied from 800 to 1000 μm, while the laser focal spot size was kept constant at 820 μm. The larger targets driven with up to 30 kJ of laser energy used dynamic bandwidth reduction, where the smoothing by spectral dispersion (SSD) is only applied to the pickets. The smaller targets driven with 26 kJ of laser energy had SSD on the entire pulse. This talk will summarize the results of this CBET mitigation campaign and describe a path forward to achieve ignition hydro-equivalence on OMEGA. This material is based upon work supported by the Department of Energy National Nuclear Security Administration under

  7. Mutual Occultation Observations of Volcanic Hot Spots on Io in 2015

    Science.gov (United States)

    Howell, Robert R.; Spencer, John R.; Rathbun, Julie A.; Goguen, Jay D.

    2015-11-01

    During spring 2015 we observed a series of mutual occultations and eclipses of Io using the SpeX instrument on the NASA Infrared Telescope Facility (IRTF). Mutual event lightcurves were obtained on 4 Feb., 18 Feb., 15 Mar., and 22 Mar. in the Lp (3.8 micron) filter, with observations on 11 Feb. and on 8 and 10 Mar. lost to weather. Such lightcurves can potentially provide the highest spatial resolution observations of Io's volcanic hotspots possible from ground-based observations. The geometry of the recent events was particularly favorable for studies of the Loki Patera region, but unfortunately Loki remained relatively faint during the 2015 series. An eruption of Pillan was observed on 18 Feb., and is discussed in more detail by de Pater et al. (2015) at this meeting. While the relative faintness of Loki during the recent series limits the value of the new observations for studying that source, recent improvements to the Galilean satellite ephemerides also allow us to significantly improve the analysis of previous Loki occultations from 1985, 1991, 1997, and 2003. In that earlier work it was necessary to allow adjustable offsets in the relative position of the satellites to accommodate ephemeris uncertainty. That in turn limited the accuracy with which hot regions within Loki Patera could be fixed, and limited the ability to test different models for Patera activity. Initial analysis of the most recent event series indicates that such arbitrary adjustments are no longer necessary. We will present the occultation lightcurves for the most recent series and the constraints on the location of Loki activity provided by those observations and from earlier occultation series.

  8. 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.

  9. The HIV-1 repeated sequence R as a robust hot-spot for copy-choice recombination

    Science.gov (United States)

    Moumen, Abdeladim; Polomack, Lucette; Roques, Bernard; Buc, Henri; Negroni, Matteo

    2001-01-01

    Template switching during reverse transcription is crucial for retroviral replication. While strand transfer on the terminal repeated sequence R is essential to achieve reverse transcription, template switching from internal regions of the genome (copy choice) leads to genetic recombination. We have developed an experimental system to study copy-choice recombination in vitro along the HIV-1 genome. We identify here several genomic regions, including the R sequence, where copy choice occurred at high rates. The frequency of copy choice occurring in a given region of template was strongly influenced by the surrounding sequences, an observation that suggests a pivotal role of the folding of template RNA in the process. The sequence R, instead, constituted an exception to this rule since it was a strong hot-spot for copy choice in the different sequence contexts tested. We suggest therefore that the structure of this region has been optimised during viral evolution to ensure efficient template switching independently from the sequences that might surround it. PMID:11557813

  10. 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.

  11. Unexpected climatological behavior of MLT gravity wave momentum flux in the lee of the Southern Andes hot spot

    Science.gov (United States)

    Wit, R. J.; Janches, D.; Fritts, D. C.; Stockwell, R. G.; Coy, L.

    2017-01-01

    The Southern Argentina Agile MEteor Radar (SAAMER), located at Tierra del Fuego (53.7°S, 67.7°W), has been providing near-continuous high-resolution measurements of winds and high-frequency gravity wave (GW) momentum fluxes of the mesopause region since May 2008. As SAAMER is located in the lee of the largest seasonal GW hot spot on Earth, this is a key location to study GWs and their interaction with large-scale motions. GW momentum flux climatologies are shown for the first time for this location and discussed in light of these unique dynamics. Particularly, the large eastward GW momentum fluxes during local winter are surprising, as these observations cannot be explained by the direct upward propagation of expected large-amplitude mountain waves (MWs) through the eastward stratospheric jet. Instead, these results are interpreted as secondary GWs propagating away from stratospheric sources over the Andes accompanying MW breaking over the Southern Andes.

  12. Study and Applications of Dynamic Resistance Profiles During Resistance Spot Welding of Coated Hot-Stamping Steels

    Science.gov (United States)

    Ighodaro, Osayande Lord-Rufus; Biro, Elliot; Zhou, Y. Norman

    2017-02-01

    This work compares the role of press hardened steel coating type (Al-Si and GA) on resistance spot welding by analyzing the dynamic resistance curves measured during the weld cycles of the respective materials. It was seen that the dynamic resistance profiles for GA- and Al-Si-coated steels are similar. But the GA specimens exhibited higher resistance than Al-Si-coated specimens in the as-received condition, while the Al-Si-coated specimens exhibited higher resistance after hot stamping. From the early stages of the dynamic resistance profiles, data were obtained and applied for computing the values of components of resistances associated with the different coatings since each coating exhibits characteristic value at the early stages. The results revealed that at the start of the welding cycle, the resistance of the electrode/sheet interface was significantly higher than that of the faying surface or the bulk resistance regardless of whether the steel was Al-Si- or GA-coated. The possible uses of these resistance values in studying welding current requirement and electrode tip life were discussed.

  13. Identification of an mtDNA mutation hot spot in UV-induced mouse skin tumors producing altered cellular biochemistry.

    Science.gov (United States)

    Jandova, Jana; Eshaghian, Alex; Shi, Mingjian; Li, Meiling; King, Lloyd E; Janda, Jaroslav; Sligh, James E

    2012-02-01

    There is increasing awareness of the role of mtDNA alterations in the development of cancer, as mtDNA point mutations are found at high frequency in a variety of human tumors. To determine the biological effects of mtDNA mutations in UV-induced skin tumors, hairless mice were irradiated to produce tumors, and the tumor mtDNAs were screened for single-nucleotide changes using temperature gradient capillary electrophoresis (TGCE), followed by direct sequencing. A mutation hot spot (9821insA) in the mitochondrially encoded tRNA arginine (mt-Tr) locus (tRNA(Arg)) was discovered in approximately one-third of premalignant and malignant skin tumors. To determine the functional relevance of this particular mutation in vitro, cybrid cell lines containing different mt-Tr (tRNA(Arg)) alleles were generated. The resulting cybrid cell lines contained the same nuclear genotype and differed only in their mtDNAs. The biochemical analysis of the cybrids revealed that the mutant haplotype is associated with diminished levels of complex I protein (CI), resulting in lower levels of baseline oxygen consumption and lower cellular adenosine triphosphate (ATP) production. We hypothesize that this specific mtDNA mutation alters cellular biochemistry, supporting the development of keratinocyte neoplasia.

  14. Improving the hot-spot pressure and demonstrating ignition hydrodynamic equivalence in cryogenic deuterium tritium implosions on OMEGA

    Energy Technology Data Exchange (ETDEWEB)

    Goncharov, V. N. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Sangster, T. C. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Betti, R. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Boehly, T. R. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Bonino, M. J. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Collins, T. J. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Craxton, R. S. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Delettrez, J. A. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Edgell, D. H. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Epstein, R. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Follett, R. K. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Forrest, C. J. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Froula, D. H. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Yu. Glebov, V. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Harding, D. R. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Henchen, R. J. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Hu, S. X. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Igumenshchev, I. V. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Janezic, R. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Kelly, J. H. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Kessler, T. J. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Kosc, T. Z. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Loucks, S. J. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Marozas, J. A. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Marshall, F. J. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Maximov, A. V. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; McCrory, R. L. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; McKenty, P. W. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Meyerhofer, D. D. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Michel, D. T. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Myatt, J. F. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Nora, R. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Radha, P. B. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Regan, S. P. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Seka, W. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Shmayda, W. T. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Short, R.W. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Shvydky, A. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Skupsky, S. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Stoeckl, C. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Yaakobi, B. [Univ. of Rochester, NY (United States). Lab. for Laser Energetics; Frenje, J. A. [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States). Plasma Science and Fusion Center; Gatu-Johnson, M. [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States). Plasma Science and Fusion Center; Petrasso, R. D. [Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States). Plasma Science and Fusion Center; Casey, D. T. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2014-05-01

    Reaching ignition in direct-drive (DD) inertial confinement fusion implosions requires achieving central pressures in excess of 100 Gbar. The OMEGA laser system [T. R. Boehly et al., Opt. Commun. 133, 495 (1997)] is used to study the physics of implosions that are hydrodynamically equivalent to the ignition designs on the National Ignition Facility (NIF) [J. A. Paisner et al., Laser Focus World 30, 75 (1994)]. It is shown that the highest hot-spot pressures (up to 40 Gbar) are achieved in target designs with a fuel adiabat of α ≅ 4, an implosion velocity of 3.8 × 10⁷ cm/s, and a laser intensity of ~10¹⁵ W/cm². These moderate-adiabat implosions are well understood using two-dimensional hydrocode simulations. The performance of lower-adiabat implosions is significantly degraded relative to code predictions, a common feature between DD implosions on OMEGA and indirect-drive cryogenic implosions on the NIF. Simplified theoretical models are developed to gain physical understanding of the implosion dynamics that dictate the target performance. These models indicate that degradations in the shell density and integrity (caused by hydrodynamic instabilities during the target acceleration) coupled with hydrodynamics at stagnation are the main failure mechanisms in low-adiabat designs. To demonstrate ignition hydrodynamic equivalence in cryogenic implosions on OMEGA, the target-design robustness to hydrodynamic instability growth must be improved by reducing laser-coupling losses caused by cross beam energy transfer.

  15. CTCF cis-regulates trinucleotide repeat instability in an epigenetic manner: a novel basis for mutational hot spot determination.

    Directory of Open Access Journals (Sweden)

    Randell T Libby

    2008-11-01

    Full Text Available At least 25 inherited disorders in humans result from microsatellite repeat expansion. Dramatic variation in repeat instability occurs at different disease loci and between different tissues; however, cis-elements and trans-factors regulating the instability process remain undefined. Genomic fragments from the human spinocerebellar ataxia type 7 (SCA7 locus, containing a highly unstable CAG tract, were previously introduced into mice to localize cis-acting "instability elements," and revealed that genomic context is required for repeat instability. The critical instability-inducing region contained binding sites for CTCF -- a regulatory factor implicated in genomic imprinting, chromatin remodeling, and DNA conformation change. To evaluate the role of CTCF in repeat instability, we derived transgenic mice carrying SCA7 genomic fragments with CTCF binding-site mutations. We found that CTCF binding-site mutation promotes triplet repeat instability both in the germ line and in somatic tissues, and that CpG methylation of CTCF binding sites can further destabilize triplet repeat expansions. As CTCF binding sites are associated with a number of highly unstable repeat loci, our findings suggest a novel basis for demarcation and regulation of mutational hot spots and implicate CTCF in the modulation of genetic repeat instability.

  16. Magma production rate along the Ninetyeast Ridge and its relationship to Indian plate motion and Kerguelen hot spot activity

    Science.gov (United States)

    Sreejith, K. M.; Krishna, K. S.

    2015-02-01

    The Ninetyeast Ridge, a linear trace of the Kerguelen hot spot in the Indian Ocean, was emplaced on a rapidly drifting Indian plate. Magma production rates along the ridge track are computed using gravity-derived excess crustal thickness data. The production rates change between 2 and 15 m3/s over timescales of 3-16 Myr. Major variations in magma production rates are primarily associated with significant changes in the Indian plate velocity with low-production phases linked to high plate velocity periods. The lowest magma production rate (2 m3/s) at 62 Ma is associated with the rapid northward drift of Indian plate under the influence of the Reunion mantle plume. The contemporaneous slowing of the African plate coincides with increase in magma production rate along the Walvis Ridge in the Atlantic Ocean. The present study suggests that variations in the Indian plate motion and frequent ridge jumps have a major role in controlling the magma production, particularly on long-period cycles (~16 Myr). Short-period variations (~5 Myr) in magma productions may be associated with intrinsic changes in the plume, possibly due to the presence of solitary waves in the plume conduit.

  17. Current dependence of the hot-spot response spectrum of superconducting single-photon detectors with different layouts

    Science.gov (United States)

    Charaev, I.; Semenov, A.; Doerner, S.; Gomard, G.; Ilin, K.; Siegel, M.

    2017-02-01

    We show that avoiding bends in a current-carrying superconducting nanowire enhances the probability for low energy photons to be detected and that this enhancement is entirely due to the increase in the experimentally achievable critical current. We studied nanowires shaped as either meander or spiral. The spirals had different layouts, a double-spiral layout with an S-turn in the middle and a single-spiral layout without such a turn. Nanowires were prepared from films of niobium nitride with a thickness of 5 nm. For specimens with each layout we measured the spectra of the single-photon response in the wavelength range from 400 nm to 1600 nm and defined the cut-off wavelength (λ c) beyond which the response rolls off. The largest and the smallest λ c were found for the single-spiral layout and for the meander, respectively. For all three layouts the relationship between λ c and the relative bias current falls onto a universal curve which has been predicted earlier in the framework of the modified hot-spot model. For the single-spiral layout, the efficiency of photon detection at wavelengths smaller than λ c reaches the expected absorbance of the spiral structure and the timing jitter per unit length of the nanowire has the smallest value.

  18. Hot Spots and Hot Moments of Methylmercury Production Associated With Agricultural and Non-agricultural Wetlands of the Yolo Bypass Wildlife Area, California

    Science.gov (United States)

    Marvin-Dipasquale, M.; Windham-Myers, L.; Agee, J. L.; Kakouros, E.; Cox, M. H.; Fleck, J.; Alpers, C. N.; Stephenson, M.

    2008-12-01

    The Yolo Bypass Wildlife Area (YBWA) is part of the larger Yolo Bypass floodwater protection zone associated with the Sacramento River and the Sacramento-San Joaquin Delta, in California. While mercury contamination is widespread throughout the region due to historic mining practices, the Yolo Bypass is responsible for a high proportion of the aqueous methylmercury (MeHg) entering the Delta, and biota from the Yolo Bypass are particularly elevated in toxic MeHg. Land use in the YBWA includes seasonally flooded agricultural fields (white rice, wild rice, fallow fields), and permanently and seasonally flooded non-agricultural wetlands used for resident and migratory waterfowl. Mercury biogeochemistry was examined in 0-2 cm surface sediment, as a function of habitat type, wetland management, and agricultural practices during the 2007-08 crop year. In permanently flooded wetlands, MeHg concentrations varied within a narrow range (ca. 0.5-1.5 ng/g dry wt) throughout the study period. In contrast, the three types of agricultural fields had higher MeHg concentrations throughout the rice-growing season (June-Sept; ca. 1.5-3.5 ng/g), and exhibited the highest levels (ca. 3.3-6.3 ng/g) in the post-harvest winter period (Dec-Feb). Further, naturally dried sediment, sampled during July '08 from post-harvest drained fallow agricultural fields (prior to reflooding) had MeHg concentrations that were also quite elevated (3.1 +/- 1.5 ng/g). This suggests that the initial elevated concentrations of overlying water MeHg, sometimes measured soon after flooding previously dried fields, may be related to the release of MeHg formed during the previous wet season and trapped in dried sediment, as opposed to being MeHg newly produced by bacteria upon soil rewetting. These results indicate that the 'hot spots and hot moments' associated with MeHg production in this system are linked to hydrologic manipulations (wetting and drying) in the agricultural fields, and that the practice of post

  19. Strategy to eliminate catalyst hot-spots in the partial oxidation of methane: enhancing its activity for direct hydrogen production by reducing the reactivity of lattice oxygen.

    Science.gov (United States)

    Wen, Cun; Liu, Yi; Guo, Yun; Wang, Yanqin; Lu, Guanzhong

    2010-02-14

    Hydrogen can be produced over Er(2)O(3) in methane oxidation (oxygen/methane = 26). The reactivity of lattice oxygen in the catalyst plays a main role in the conversion of surface hydroxyl species to hydrogen or water. Adding a rare earth element into a catalyst can reduce the reactivity of lattice oxygen, resulting in increased hydrogen production, to eliminate catalyst hot-spots.

  20. Three-dimensional (3D) plasmonic hot spots for label-free sensing and effective photothermal killing of multiple drug resistant superbugs.

    Science.gov (United States)

    Jones, Stacy; Sinha, Sudarson Sekhar; Pramanik, Avijit; Ray, Paresh Chandra

    2016-11-03

    Drug resistant superbug infection is one of the foremost threats to human health. Plasmonic nanoparticles can be used for ultrasensitive bio-imaging and photothermal killing by amplification of electromagnetic fields at nanoscale "hot spots". One of the main challenges to plasmonic imaging and photothermal killing is design of a plasmonic substrate with a large number of "hot spots". Driven by this need, this article reports design of a three-dimensional (3D) plasmonic "hot spot"-based substrate using gold nanoparticle attached hybrid graphene oxide (GO), free from the traditional 2D limitations. Experimental results show that the 3D substrate has capability for highly sensitive label-free sensing and generates high photothermal heat. Reported data using p-aminothiophenol conjugated 3D substrate show that the surface enhanced Raman spectroscopy (SERS) enhancement factor for the 3D "hot spot"-based substrate is more than two orders of magnitude greater than that for the two-dimensional (2D) substrate and five orders of magnitude greater than that for the zero-dimensional (0D) p-aminothiophenol conjugated gold nanoparticle. 3D-Finite-Difference Time-Domain (3D-FDTD) simulation calculations indicate that the SERS enhancement factor can be greater than 10(4) because of the bent assembly structure in the 3D substrate. Results demonstrate that the 3D-substrate-based SERS can be used for fingerprint identification of several multi-drug resistant superbugs with detection limits of 5 colony forming units per mL. Experimental data show that 785 nm near infrared (NIR) light generates around two times more photothermal heat for the 3D substrate with respect to the 2D substrate, and allows rapid and effective killing of 100% of the multi-drug resistant superbugs within 5 minutes.

  1. Bone Scan "Hot Spot" at the Superior Lateral Orbital Margin Fronto-zygomatic Suture Uptake Characterized with Tc-99m MDP SPECT/CT.

    Science.gov (United States)

    Thang, S P; Tan, A E H; Goh, A S W

    2011-07-01

    Findings of a solitary "hot spot" at the superior lateral orbital margin on bone scan scintigraphy is not uncommonly seen, and is often dismissed as a benign lesion. However, the exact etiology is indeterminate. We present two cases in which hybrid single photon emission computed tomography/computed tomography imaging was able to characterize and localize this uptake, demonstrating correlation to the right fronto-zygomatic suture.

  2. 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

    2016-07-08

    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.

  3. Hot Spot and THz Wave Generation in Bi2Sr2CaCu2O8 Intrinsic Josephson Junction Stacks

    Science.gov (United States)

    Kleiner, Reinhold

    2013-03-01

    Stacks of intrinsic Josephson junctions made of the high temperature superconductor Bi2Sr2CaCu2O8 have been shown to emit coherent radiation at THz frequencies. Emission is observed both in a low bias regime and a high bias regime. While at low bias the temperature of the stack is close to the bath temperature, at high bias a hot spot and a standing wave, formed in the ``cold'' part of the stack, coexist. THz radiation is very stable in this regime, exhibiting a linewidth which is much smaller than expected from a purely cavity-induced synchronization mechanism. We investigate the interaction of hot spots and THz waves using a combination of transport measurement, direct electromagnetic wave detection and low temperature scanning laser microscopy (LTSLM). In this talk recent developments will be presented, with a focus on the mechanism of hot spot formation. In collaboration with B. Gross, S. Guénon, M. Y. Li, J. Yuan, N. Kinev, J. Li, A. Ishii, K. Hirata, T. Hatano, R. G. Mints, D. Koelle, V. P. Koshelets, H. B. Wang and P. H. Wu.

  4. 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.

  5. 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.

  6. Sustainability of Public Health Interventions to Reduce the Risk of Dioxin Exposure at Severe Dioxin Hot Spots in Vietnam.

    Science.gov (United States)

    Tuyet-Hanh, Tran Thi; Vu-Anh, Le; Dunne, Michael; Toms, Leisa-Maree; Tenkate, Thomas; Harden, Fiona

    2015-08-01

    Severe dioxin contamination at Bien Hoa and Da Nang airbases, Vietnam is of international concern. Public Health risk reduction programs were implemented in Bien Hoa in 2007-2009 and in Da Nang in 2009-2011. In 2009 and 2011 we reported the encouraging results of these interventions in improving the knowledge, attitude and practices (KAP) of local residents in reducing the dioxin exposure risk through foods. In 2013 we revisited these dioxin hot spots, aimed to evaluate whether the results of the intervention were maintained and to identify factors affecting the sustainability of the programs. To assess this, 16 in-depth interviews, six focus group discussions, and pre and post intervention KAP surveys were undertaken. 800 respondents from six intervention wards and 200 respondents from Buu Long Ward (the control site) were randomly selected to participate in the surveys. The results showed that as of 2013, the programs were rated as "moderately sustained" with a score of 3.3 out of 5.0 (cut off points 2.5 to <3.5) for Bien Hoa, and "well sustained" with a score of 3.8 out of 5.0 (cut off points 3.5 to <4.5) for Da Nang. Most formal intervention program activities had ceased and dioxin risk communication activities were no longer integrated into local routine health education programs. However, the main outcomes were maintained and were better than that in the control ward. Migration, lack of official guidance from City People's Committees and local authorities as well as the politically sensitive nature of dioxin issues were the main challenges for the sustainability of the programs.

  7. Improving the hot-spot pressure and demonstrating ignition hydrodynamic equivalence in cryogenic deuterium–tritium implosions on OMEGA

    Energy Technology Data Exchange (ETDEWEB)

    Goncharov, V. N.; Sangster, T. C.; Betti, R.; Boehly, T. R.; Bonino, M. J.; Collins, T. J. B.; Craxton, R. S.; Delettrez, J. A.; Edgell, D. H.; Epstein, R.; Follett, R. K.; Forrest, C. J.; Froula, D. H.; Glebov, V. Yu.; Harding, D. R.; Henchen, R. J.; Hu, S. X.; Igumenshchev, I. V.; Janezic, R.; Kelly, J. H. [Laboratory for Laser Energetics, University of Rochester, Rochester, New York 14623 (United States); and others

    2014-05-15

    Reaching ignition in direct-drive (DD) inertial confinement fusion implosions requires achieving central pressures in excess of 100 Gbar. The OMEGA laser system [T. R. Boehly et al., Opt. Commun. 133, 495 (1997)] is used to study the physics of implosions that are hydrodynamically equivalent to the ignition designs on the National Ignition Facility (NIF) [J. A. Paisner et al., Laser Focus World 30, 75 (1994)]. It is shown that the highest hot-spot pressures (up to 40 Gbar) are achieved in target designs with a fuel adiabat of α ≃ 4, an implosion velocity of 3.8 × 10{sup 7} cm/s, and a laser intensity of ∼10{sup 15} W/cm{sup 2}. These moderate-adiabat implosions are well understood using two-dimensional hydrocode simulations. The performance of lower-adiabat implosions is significantly degraded relative to code predictions, a common feature between DD implosions on OMEGA and indirect-drive cryogenic implosions on the NIF. Simplified theoretical models are developed to gain physical understanding of the implosion dynamics that dictate the target performance. These models indicate that degradations in the shell density and integrity (caused by hydrodynamic instabilities during the target acceleration) coupled with hydrodynamics at stagnation are the main failure mechanisms in low-adiabat designs. To demonstrate ignition hydrodynamic equivalence in cryogenic implosions on OMEGA, the target-design robustness to hydrodynamic instability growth must be improved by reducing laser-coupling losses caused by cross beam energy transfer.

  8. 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

  9. Premutation huntingtin allele adopts a non-B conformation and contains a hot spot for DNA damage

    Energy Technology Data Exchange (ETDEWEB)

    Jarem, Daniel A. [Department of Chemistry, Brown University, Providence, RI 02912 (United States); Delaney, Sarah, E-mail: sarah_delaney@brown.edu [Department of Chemistry, Brown University, Providence, RI 02912 (United States)

    2011-12-09

    Highlights: Black-Right-Pointing-Pointer First structural and thermodynamic analysis of premutation allele of HD. Black-Right-Pointing-Pointer Premutation allele of HD adopts a stem-loop non-B conformation. Black-Right-Pointing-Pointer Healthy and premutation length stem-loops are hyper-susceptible to oxidative damage. Black-Right-Pointing-Pointer Stability of stem-loop structures increases linearly with repeat length. Black-Right-Pointing-Pointer Thermodynamic stability, not the ability to adopt non-B conformation, distinguishes DNA prone to expansion from stable DNA. -- Abstract: The expansion of a CAG trinucleotide repeat (TNR) sequence has been linked to several neurological disorders, for example, Huntington's disease (HD). In HD, healthy individuals have 5-35 CAG repeats. Those with 36-39 repeats have the premutation allele, which is known to be prone to expansion. In the disease state, greater than 40 repeats are present. Interestingly, the formation of non-B DNA conformations by the TNR sequence is proposed to contribute to the expansion. Here we provide the first structural and thermodynamic analysis of a premutation length TNR sequence. Using chemical probes of nucleobase accessibility, we found that similar to (CAG){sub 10}, the premutation length sequence (CAG){sub 36} forms a stem-loop hairpin and contains a hot spot for DNA damage. Additionally, calorimetric analysis of a series of (CAG){sub n} sequences, that includes repeat tracts in both the healthy and premutation ranges, reveal that thermodynamic stability increases linearly with the number of repeats. Based on these data, we propose that while non-B conformations can be formed by TNR tracts found in both the healthy and premutation allele, only sequences containing at least 36 repeats have sufficient thermodynamic stability to contribute to expansion.

  10. 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

  11. Introduction and evaluation of a hot spots priming kinetics in a two-dimensional code; Introduction et evaluation d`une cinetique d`amorcage par points chauds dans un code bidimensionnel

    Energy Technology Data Exchange (ETDEWEB)

    Vong, T.S.; Leroy, M. [CEA Vaujours-Moronvilliers, 77 - Courtry (France)

    1996-12-31

    In this paper, the kinetics of hot spots priming in heterogenous explosives is introduced into a 2D hydrodynamical code. The AMORC kinetics model takes into account the two priming phases (formation, firing of hot spots and combustion of grains) and is evaluated in various experimental configurations with 1D and 2D symmetries. A TATB-based composition was used for this first evaluation. (J.S.) 7 refs.

  12. 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

  13. Temperatures and CH4 mixing ratios near the homopause of the 8 μm north polar hot spot of Jupiter

    Science.gov (United States)

    Kim, Sang Joon; Geballe, Thomas R.; Greathouse, Thomas K.; Yung, Yuk L.; Miller, Steve; Orton, G. S.; Minh, Y. C.

    2017-01-01

    We have derived homopause temperatures of 180-250 K for the 8-μm north-polar hot spot (8NPHS) of Jupiter by fitting CH4 emission models to 3 and 8 μm spectra of the 8NPHS obtained 24 days apart in 2013. From the fits, we find that CH4 mixing ratios at the 8NPHS are consistent with those reported by Kim et al. (2014) in equatorial regions. We propose possible mechanisms to account for the temperature of the 8NPHS homopause, which is relatively cool compared with the temperatures of other auroral regions, including locally-fixed and transient but energetic auroral particle precipitation.

  14. 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.

  15. Validation of the DIFFAL, HPAC and HotSpot Dispersion Models Using the Full-Scale Radiological Dispersal Device (FSRDD) Field Trials Witness Plate Deposition Dataset.

    Science.gov (United States)

    Purves, Murray; Parkes, David

    2016-05-01

    Three atmospheric dispersion models--DIFFAL, HPAC, and HotSpot--of differing complexities have been validated against the witness plate deposition dataset taken during the Full-Scale Radiological Dispersal Device (FSRDD) Field Trials. The small-scale nature of these trials in comparison to many other historical radiological dispersion trials provides a unique opportunity to evaluate the near-field performance of the models considered. This paper performs validation of these models using two graphical methods of comparison: deposition contour plots and hotline profile graphs. All of the models tested are assessed to perform well, especially considering that previous model developments and validations have been focused on larger-scale scenarios. Of the models, HPAC generally produced the most accurate results, especially at locations within ∼100 m of GZ. Features present within the observed data, such as hot spots, were not well modeled by any of the codes considered. Additionally, it was found that an increase in the complexity of the meteorological data input to the models did not necessarily lead to an improvement in model accuracy; this is potentially due to the small-scale nature of the trials.

  16. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Bachmann, B., E-mail: bachmann2@llnl.gov; Kritcher, A. L.; Benedetti, L. R.; Glenn, S.; Hawreliak, J.; Izumi, N.; Landen, O. L.; Le Pape, S.; Ma, T.; Pérez, F.; Swift, D.; Döppner, T. [Lawrence Livermore National Laboratory, Livermore, California 94550 (United States); Falcone, R. W. [Department of Physics, University of California, Berkeley, California 94720 (United States); Lawrence Berkeley National Laboratory, Berkeley, California 94720 (United States); Kraus, D. [Department of Physics, University of California, Berkeley, California 94720 (United States)

    2014-11-15

    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/cm{sup 3}) 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.

  18. 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.

  19. The research of internet public opinion hot spot mining%网络舆情热点挖掘算法研究与实现

    Institute of Scientific and Technical Information of China (English)

    黄敏

    2012-01-01

    随着网络信息交互及传播的迅速与便捷,有效地对不断涌现的海量互联网信息进行采集并发现网络热点舆情具有十分重要的意义.研究网络舆情的表示及特征,提出采用网络化方法思想,结合Hits算法和PageRank算法进行舆情热点挖掘,并在此基础上设计了网络舆情热点挖掘系统.%With the speedy interaction and spread of the network information, it has great significance to collect emerging massive internet information and discover hot spots of network public opinion. This paper studied the characteristics of network public opinion and designed hot spot mining system on the basis of combination of Hits and PageRank algorithms.

  20. 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.

  1. Doubling the efficiency of third harmonic generation by positioning ITO nanocrystals into the hot-spot of plasmonic gap-antennas.

    Science.gov (United States)

    Metzger, Bernd; Hentschel, Mario; Schumacher, Thorsten; Lippitz, Markus; Ye, Xingchen; Murray, Christopher B; Knabe, Bastian; Buse, Karsten; Giessen, Harald

    2014-05-14

    We incorporate dielectric indium tin oxide nanocrystals into the hot-spot of gold nanogap-antennas and perform third harmonic spectroscopy on these hybrid nanostructure arrays. The combined system shows a 2-fold increase of the radiated third harmonic intensity when compared to bare gold antennas. In order to identify the origin of the enhanced nonlinear response we perform finite element simulations of the nanostructures, which are in excellent agreement with our measurements. We find that the third harmonic signal enhancement is mainly related to changes in the linear optical properties of the plasmonic antenna resonances when the ITO nanocrystals are incorporated. Furthermore, the dominant source of the third harmonic is found to be located in the gold volume of the plasmonic antennas.

  2. Controlling allosteric networks in proteins

    Science.gov (United States)

    Dokholyan, Nikolay

    2013-03-01

    We present a novel methodology based on graph theory and discrete molecular dynamics simulations for delineating allosteric pathways in proteins. We use this methodology to uncover the structural mechanisms responsible for coupling of distal sites on proteins and utilize it for allosteric modulation of proteins. We will present examples where inference of allosteric networks and its rewiring allows us to ``rescue'' cystic fibrosis transmembrane conductance regulator (CFTR), a protein associated with fatal genetic disease cystic fibrosis. We also use our methodology to control protein function allosterically. We design a novel protein domain that can be inserted into identified allosteric site of target protein. Using a drug that binds to our domain, we alter the function of the target protein. We successfully tested this methodology in vitro, in living cells and in zebrafish. We further demonstrate transferability of our allosteric modulation methodology to other systems and extend it to become ligh-activatable.

  3. Construction of a multiplex mutation hot spot PCR panel: the first step towards colorectal cancer genotyping on the GS Junior platform

    Science.gov (United States)

    Péterfia, Bálint; Kalmár, Alexandra; Patai, Árpád V.; Csabai, István; Bodor, András; Micsik, Tamás; Wichmann, Barnabás; Egedi, Krisztina; Hollósi, Péter; Kovalszky, Ilona; Tulassay, Zsolt; Molnár, Béla

    2017-01-01

    Background: To support cancer therapy, development of low cost library preparation techniques for targeted next generation sequencing (NGS) is needed. In this study we designed and tested a PCR-based library preparation panel with limited target area for sequencing the top 12 somatic mutation hot spots in colorectal cancer on the GS Junior instrument. Materials and Methods: A multiplex PCR panel was designed to amplify regions of mutation hot spots in 12 selected genes (APC, BRAF, CTNNB1, EGFR, FBXW7, KRAS, NRAS, MSH6, PIK3CA, SMAD2, SMAD4, TP53). Amplicons were sequenced on a GS Junior instrument using ligated and barcoded adaptors. Eight samples were sequenced in a single run. Colonic DNA samples (8 normal mucosa; 33 adenomas; 17 adenocarcinomas) as well as HT-29 and Caco-2 cell lines with known mutation profiles were analyzed. Variants found by the panel on APC, BRAF, KRAS and NRAS genes were validated by conventional sequencing. Results: In total, 34 kinds of mutations were detected including two novel mutations (FBXW7 c.1740:C>G and SMAD4 c.413C>G) that have not been recorded in mutation databases, and one potential germline mutation (APC). The most frequently mutated genes were APC, TP53 and KRAS with 30%, 15% and 21% frequencies in adenomas and 29%, 53% and 29% frequencies in carcinomas, respectively. In cell lines, all the expected mutations were detected except for one located in a homopolymer region. According to re-sequencing results sensitivity and specificity was 100% and 92% respectively. Conclusions: Our NGS-based screening panel denotes a promising step towards low cost colorectal cancer genotyping on the GS Junior instrument. Despite the relatively low coverage, we discovered two novel mutations and obtained mutation frequencies comparable to literature data. Additionally, as an advantage, this panel requires less template DNA than sequence capture colon cancer panels currently available for the GS Junior instrument.

  4. Identification of 'carbon hot-spots' and quantification of GHG intensities in the biodiesel supply chain using hybrid LCA and structural path analysis.

    Science.gov (United States)

    Acquaye, Adolf A; Wiedmann, Thomas; Feng, Kuishang; Crawford, Robert H; Barrett, John; Kuylenstierna, Johan; Duffy, Aidan P; Koh, S C Lenny; McQueen-Mason, Simon

    2011-03-15

    It is expected that biodiesel production in the EU will remain the dominant contributor as part of a 10% minimum binding target for biofuel in transportation fuel by 2020 within the 20% renewable energy target in the overall EU energy mix. Life cycle assessments (LCA) of biodiesel to evaluate its environmental impacts have, however, remained questionable, mainly because of the adoption of a traditional process analysis approach resulting in system boundary truncation and because of issues regarding the impacts of land use change and N(2)O emissions from fertilizer application. In this study, a hybrid LCA methodology is used to evaluate the life cycle CO(2) equivalent emissions of rape methyl ester (RME) biodiesel. The methodology uses input-output analysis to estimate upstream indirect emissions in order to complement traditional process LCA in a hybrid framework. It was estimated that traditional LCA accounted for 2.7 kg CO(2)-eq per kg of RME or 36.6% of total life cycle emissions of the RME supply chin. Further to the inclusion of upstream indirect impacts in the LCA system (which accounted for 23% of the total life cycle emissions), emissions due to direct land use change (6%) and indirect land use change (16.5%) and N(2)O emissions from fertilizer applications (17.9%) were also calculated. Structural path analysis is used to decompose upstream indirect emissions paths of the biodiesel supply chain in order to identify, quantify, and rank high carbon emissions paths or 'hot-spots' in the biodiesel supply chain. It was shown, for instance, that inputs from the 'Other Chemical Products' sector (identified as phosphoric acid, H(3)PO(4)) into the biodiesel production process represented the highest carbon emission path (or hot-spot) with 5.35% of total upstream indirect emissions of the RME biodiesel supply chain.

  5. 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.

  6. Optimization of Resistance Spot Weld Condition for Single Lap Joint of Hot Stamped 22MnB5 by Taking Heating Temperature and Heating Time into Consideration

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Hong Seok; Kim, Byung Min; Park, Geun Hwan [Pusan National University, Busan (Korea, Republic of); Lim, Woo Seung [Keimyung University, Daegu (Korea, Republic of)

    2010-10-15

    In this study, optimization of the process parameters of the resistance spot welding of a sheet of aluminum-coated boron alloyed steel, 22MnB5, used in hot stamping has been performed by a Taguchi method to increase the strength of the weld joint. The process parameters selected were current, electrode force, and weld time. The heating temperature and heating time of 22MnB5 are considered to be noise factors. It was known that the variation in the thickness of the intermetallic compound layer between the aluminum-coated layer and the substrate, which influences on the formation of nugget, was generated due to the difference of diffusion reaction according to heating conditions. From the results of spot weld experiment, the optimum weld condition was determined to be when the current, electrode force, and weld time were 8kA, 4kN, and 18 cycles, respectively. The result of a test performed to verify the optimized weld condition showed that the tensile strength of the weld joint was over 32kN, which is considerably higher than the required strength, i.e., 23kN.

  7. Internet Public Opinion Hot Spot Mining Base on Complex Network Theory%基于复杂网络方法的舆情热点挖掘

    Institute of Scientific and Technical Information of China (English)

    黄敏; 胡学钢

    2011-01-01

    This paper focused on the Internet public opinion hot spot mining based on the complex network theory and methods. Internet public opinion analysis techniques can be divided into content-based analytical methods and analyses based on data mining methods. Both are traditional technology and have no relation with the network. This paper gave the idea of public opinion analyses and proposed a network-based approach to resolve network problems. The public opinion web pages could be represented as nodes of complex networks and the sides were links of those pages. The public opinion network meets the complex network characteristics. Based on Hits algorithm and PageRank algorithm, we can find out the most popular public opinions in the network, which showed a hot public opinion. With a data set from Wikipedia, experimental results show that both methods can identify hot spots of public opinion networks. Because PageRank method focuses on the impact of link nodes and Hits algorithm focus on the core degree of the nodes, the mining results have some difference. We can combine the mining results of the two methods according to the field characteristics to get the Internet public opinion hot spots.%研究使用复杂网络理论和算法的网络舆情热点提取.网络舆情分析技术可以分为基于内容的分析方法和基于数据挖掘的分析方法,二者均是采用传统技术处理网络舆情,并未结合网络特性.针对上述问题,开拓了舆情分析的思路,提出采用网络化方法处理网络问题的思想,将舆情网络的页面视为节点,链接关系作为边,构建符合复杂网络特征的舆情传播网络.使用PageRank算法和Hits算法,可以挖掘出舆情网络中的重要节点,进而发现舆情热点.以维基百科数据为仿真数据集,采用新提出的方法,可以挖掘相关领域的热点条目.仿真结果表明,两种方法均可以完成网络舆情热点的发掘工作,从复杂网络的角度处理网络舆情

  8. 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.

  9. 国内网络舆情研究热点与趋势分析%Domestic Internet Public Opinion Research Hot Spot and Trend

    Institute of Scientific and Technical Information of China (English)

    卢卉; 黄建忠

    2011-01-01

    目的 了解国内网络舆情热点,提高舆情监测能力,为政府及相关部门决策提供服务.方法 通过下载CNKI收录的网络舆情论文(2005 - 2010年),借助于统计软件与科学计量方法对近6年来我国网络舆情的研究状况进行分析.结果 研究的热点问题为文本挖掘、引导、高校、突发事件、模型、舆情分析、预警、指标体系等;舆情研究已进入了发展阶段,形成了一批高产作者和出名的研究机构,部分阶段性研究成果已在网络舆情监测系统中得到应用.结论 舆情研究已进入了发展阶段,舆情监测工作应从实际需求出发,实时研究舆情发展趋势.%Objective To provide services for the decision meking of government and relevant departments by understanding the hot spot of the domestic internet public opinion and improving the monitoring capacity of public opinion. Methods Downloaded the domestic internet public opinion papers in CNKI (2005 -2010), with the situation of domestic internet public opinion in the past six years was analyzed by means of statistical software and scientific measurement methods. Results The research hot spot topics were the text mining, guide, college, emergency, models, public opinion analysis, early warning, indicator system and, etc. Public opinion research has entered the developing stage, with a group of high production authors and famous research institutions has formed. Part of initial findings of public opinion research has been applied in network monitoring system. Conclusion Public opinion research has entered the developing stage. Public opinion mornitoring should based on the actual demand to conduct real - time study of the developing trend.

  10. 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.

  11. Cell-free synthesis and multifold screening of Candida antarctica lipase B (CalB) variants after combinatorial mutagenesis of hot spots.

    Science.gov (United States)

    Park, Chang-Gil; Kwon, Min-A; Song, Jae-Kwang; Kim, Dong-Myung

    2011-01-01

    We have developed a strategy for rapid and combinatorial optimization of the hot spot residues of enzymes. After combinatorial randomization of target locations in the Candida antarctica lipase B (CalB) gene, the individual variant genes isolated in the E.coli cells were expressed in the cell-free protein synthesis system to analyze different parameters of the resulting CalB variants. The enzymatic assays for the hydrolysis of para-nitrophenyl-ester (pNP-ester) and triglyceride, synthesis of wax ester, and thermal stability of the variant enzymes were carried out simultaneously in 96-well microtiter plates. From the 1,000 variant genes tested in each assay, we were able to identify a series of the variant enzymes having markedly improved hydrolytic, synthetic activity, or thermal stability. The improved traits of the cell-free selected CalB variants were well reproduced when the corresponding genes were expressed in Pichia pastoris. Therefore, we expect that the proposed strategy of cell-free expression screening can serve as a viable option for rapid and precise tuning of enzyme molecules, not only for analytical purposes but also for industrial applications through large scale production using microbial cells transformed with variant genes selected from the cell-free expression screening.

  12. Folate deficiency facilitates recruitment of upstream binding factor to hot spots of DNA double-strand breaks of rRNA genes and promotes its transcription.

    Science.gov (United States)

    Xie, Qiu; Li, Caihua; Song, Xiaozhen; Wu, Lihua; Jiang, Qian; Qiu, Zhiyong; Cao, Haiyan; Yu, Kaihui; Wan, Chunlei; Li, Jianting; Yang, Feng; Huang, Zebing; Niu, Bo; Jiang, Zhengwen; Zhang, Ting

    2016-12-06

    The biogenesis of ribosomes in vivo is an essential process for cellular functions. Transcription of ribosomal RNA (rRNA) genes is the rate-limiting step in ribosome biogenesis controlled by environmental conditions. Here, we investigated the role of folate antagonist on changes of DNA double-strand breaks (DSBs) landscape in mouse embryonic stem cells. A significant DSB enhancement was detected in the genome of these cells and a large majority of these DSBs were found in rRNA genes. Furthermore, spontaneous DSBs in cells under folate deficiency conditions were located exclusively within the rRNA gene units, representing a H3K4me1 hallmark. Enrichment H3K4me1 at the hot spots of DSB regions enhanced the recruitment of upstream binding factor (UBF) to rRNA genes, resulting in the increment of rRNA genes transcription. Supplement of folate resulted in a restored UBF binding across DNA breakage sites of rRNA genes, and normal rRNA gene transcription. In samples from neural tube defects (NTDs) with low folate level, up-regulation of rRNA gene transcription was observed, along with aberrant UBF level. Our results present a new view by which alterations in folate levels affects DNA breakage through epigenetic control leading to the regulation of rRNA gene transcription during the early stage of development.

  13. Hot spots of sentinel node biopsy in breast cancer%乳腺癌前哨淋巴结活组织检查的研究

    Institute of Scientific and Technical Information of China (English)

    王永胜

    2009-01-01

    乳腺癌前哨淋巴结(SLN)活检代表着乳腺癌外科治疗的发展水平,但其广泛开展可能超越了已有的证据支持.目前乳腺癌SLN活检研究的热点包括SLN微转移的预后意义、SLN阳性患者非SLN(nSLN)转移预测及SLN术中分子诊断等,结合2008年圣·安东尼奥乳腺癌会议的最新研究结果对其进行述评.%Sentinel lymph node biopsy represents the state of the art of breast surgery, but its widely application might surpass the support of available evidences. The hot spots of sentinel lymph node biopsy in breast cancer include the prognosis of micrometastases in sentinel nodes, the prediction of non-sentinel nodes metastases in positive sentinel nodes patients, and the intraoperative molecular diagnosis of sentinel nodes.These are discussed accompanying with the updated results from the 31st SABCS held in December, 2008.

  14. 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.

  15. Spectral investigation of hot-spot and cavity resonance effects on the terahertz radiation emitted from high-Tc superconducting Bi2Sr2CaCu2O8+δ single crystal mesa structures

    Science.gov (United States)

    Kadowaki, Kazuo; Watanabe, Chiharu; Minami, Hidetoshi; Yamamoto, Takashi; Kashiwagi, Takanari; Klemm, Richard

    2014-03-01

    Terahertz (THz) electromagnetic radiation emitted from high-Tc superconducting Bi2Sr2CaCu2O8+δ mesa structures in the case of single mesa and series-connected mesas is investigated by the FTIR spectroscopic technique while observing its temperature distribution simultaneously by a SiC photoluminescence technique. Changing the bias level, sudden jumps of the hot-spot position were clearly observed. Although the radiation intensity changes drastically associated with the jump of the hot spot position, the frequency is unaffected as long as the voltage per junction is kept constant. Since the frequency of the intense radiation satisfies the cavity resonance condition, we confirmed that the cavity resonance is of primarily importance for the synchronization of whole intrinsic Josephson junctions in the mesa for high power radiation. This work was supported in part by the Grant-in-Aid for challenging Exploratory Research, the Ministry of Education, Culture, Sports, Science & Technology (MEXT).

  16. Improved Detection of Candida sp. fks Hot Spot Mutants by Using the Method of the CLSI M27-A3 Document with the Addition of Bovine Serum Albumin▿†

    Science.gov (United States)

    Garcia-Effron, Guillermo; Park, Steven; Perlin, David S.

    2011-01-01

    Echinocandins are highly bound to serum proteins, altering their antifungal properties. The addition of 50% human serum to the MIC assay improves the identification of echinocandin-resistant Candida spp. harboring fks hot spot mutations. However, this modification cannot readily be applied to the method of the CLSI M27-A3 document due to safety and standardization difficulties. The aim of this study was to evaluate commercial bovine serum albumin (BSA) as a safe and standardized alternative to human serum. A collection of 28 echinocandin-susceptible strains, 10 Candida parapsilosis sensu lato strains (with naturally reduced echinocandin susceptibility), and 40 FKS hot spot mutants was used in this work. When RPMI 1640 was used for susceptibility testing, wild-type strains and fks mutants showed MIC range overlaps (−2, −1, and −3 2-fold-dilution steps separated these populations for anidulafungin, caspofungin, and micafungin, respectively). On the other hand, the addition of BSA to RPMI 1640 differentially increased echinocandin MIC values for these groups of strains, allowing better separation between populations, with no MIC range overlaps for any of the echinocandin drugs tested. Moreover, the use of RPMI-BSA reduced the number of fks hot spot mutant isolates for which MIC values were less than or equal to the upper limit for the wild type (very major errors) from 9, 2, and 7 with RPMI alone to 3, 0, and 3 for anidulafungin, caspofungin, and micafungin, respectively. When RPMI-BSA was used to study the susceptibility of C. parapsilosis sensu lato species to echinocandins, the strains behaved as anidulafungin- and micafungin-resistant isolates (MIC, ≥8 μg/ml). These data support the need for a revision of the CLSI protocol for in vitro testing of echinocandin susceptibility in order to identify all or most of the fks hot spot mutants. Also, caspofungin could be used as a surrogate marker of reduced susceptibility to echinocandins. PMID:21383097

  17. Hunting for right and left parietal hot spots using single-pulse TMS: modulation of visuospatial perception during line bisection judgment in the healthy brain.

    Science.gov (United States)

    Salatino, Adriana; Poncini, Marisa; George, Mark S; Ricci, Raffaella

    2014-01-01

    A series of studies have consistently reproduced left neglect-like bias on line length estimation tasks in healthy participants by applying transcranial magnetic stimulation (TMS) over the right posterior parietal cortex (PPC), while no significant changes have been reported when stimulating the left PPC. However, a notable inter-individual variability in the right parietal site where TMS modulates visuospatial perception can be observed, and no general agreement exists on how to identify the optimal parietal site of stimulation. In the present study, we propose a new site-finding TMS protocol to easily identify the optimum parietal location, or "hot spot," where TMS may modulate visuospatial perception on a line length estimation task (the Landmark task). Single-pulse TMS at 115% of motor threshold was applied 150 ms after the visual stimulus onset over nine different sites of a 3 cm × 3 cm grid, centred over right or left PPC (P4 and P3 according to the 10-20 EEG system, respectively) in eight healthy participants. Stimulation of right PPC induced a significant left neglect-like bias, when the coil was applied over the most posterior and dorso-posterior sites. Unexpectedly, TMS over left PPC also produced left neglect-like bias. However, in this case significant effects were found when targeting the most anterior and dorso-anterior portions of the grid. These results are discussed in relation to recent findings on neural networks underlying spatial cognition. The hunting protocol we propose might offer an economical and easy-to-use tool to functionally identify the optimal parietal site where TMS can modulate visuospatial perception, in healthy subjects and possibly in post-stroke patients undergoing repetitive transcranial magnetic stimulation treatment.

  18. DNA barcoding in a biodiversity hot spot: potential value for the identification of Malagasy Euphorbia L. listed in CITES Appendices I and II.

    Science.gov (United States)

    Aubriot, Xavier; Lowry, Porter P; Cruaud, Corinne; Couloux, Arnaud; Haevermans, Thomas

    2013-01-01

    The island of Madagascar is a key hot spot for the genus Euphorbia, with at least 170 native species, almost all endemic. Threatened by habitat loss and illegal collection of wild plants, nearly all Malagasy Euphorbia are listed in CITES Appendices I and II. The absence of a reliable taxonomic revision makes it particularly difficult to identify these plants, even when fertile, and thereby compromises the application of CITES regulations. DNA barcoding, which can facilitate species-level identification irrespective of developmental stage and the presence of flowers or fruits, may be a promising tool for monitoring and controlling trade involving threatened species. In this study, we test the potential value of barcoding on 41 Euphorbia species representative of the genus in Madagascar, using the two widely adopted core barcode markers (matK and rbcL), along with two additional DNA regions, nuclear internal transcribed spacer (ITS) and the chloroplastic intergenic spacer psbA-trnH. For each marker and for selected marker combinations, inter- and intraspecific distance estimates and species discrimination rates are calculated. Results using just the 'official' barcoding markers yield overlapping inter- and intraspecific ranges and species discrimination rates below 60%. When ITS is used, whether alone or in combination with the core markers, species discrimination increases to nearly 100%, whereas the addition of psbA-trnH produces less satisfactory results. This study, the first ever to test barcoding on the large, commercially important genus Euphorbia shows that this method could be developed into a powerful identification tool and thereby contribute to more effective application of CITES regulations.

  19. Structure of the lithosphere-asthenosphere system in the vicinity of the Tristan da Cunha hot spot as seen by surface waves

    Science.gov (United States)

    Geissler, Wolfram; Bonadio, Raffaele; Lebedev, Sergei; Jokat, Wilfried; Jegen, Marion; Baba, Kiyoshi; Sens-Schönfelder, Christoph

    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 first results on the shear wave velocity structure of the lithosphere-asthenosphere system. We applied the classical two-station method; Rayleigh wave dispersion curves are determined by cross-correlation of seismograms from a pair of station. We measured interstation phase velocities of (earthquake-excited) fundamental-mode surface waves in a period range of 10 to 60 s. The selection of acceptable phase-velocity measurements in the frequency domain had to be done manually for each event. We present phase-velocity maps for the study area. Furthermore, we present 1D shear wave velocity models inverted from the highest-quality observations.

  20. DnaK as Antibiotic Target: Hot Spot Residues Analysis for Differential Inhibition of the Bacterial Protein in Comparison with the Human HSP70.

    Directory of Open Access Journals (Sweden)

    Federica Chiappori

    Full Text Available DnaK, the bacterial homolog of human Hsp70, plays an important role in pathogens survival under stress conditions, like antibiotic therapies. This chaperone sequesters protein aggregates accumulated in bacteria during antibiotic treatment reducing the effect of the cure. Although different classes of DnaK inhibitors have been already designed, they present low specificity. DnaK is highly conserved in prokaryotes (identity 50-70%, which encourages the development of a unique inhibitor for many different bacterial strains. We used the DnaK of Acinetobacter baumannii as representative for our analysis, since it is one of the most important opportunistic human pathogens, exhibits a significant drug resistance and it has the ability to survive in hospital environments. The E.coli DnaK was also included in the analysis as reference structure due to its wide diffusion. Unfortunately, bacterial DnaK and human Hsp70 have an elevated sequence similarity. Therefore, we performed a differential analysis of DnaK and Hsp70 residues to identify hot spots in bacterial proteins that are not present in the human homolog, with the aim of characterizing the key pharmacological features necessary to design selective inhibitors for DnaK. Different conformations of DnaK and Hsp70 bound to known inhibitor-peptides for DnaK, and ineffective for Hsp70, have been analysed by molecular dynamics simulations to identify residues displaying stable and selective interactions with these peptides. Results achieved in this work show that there are some residues that can be used to build selective inhibitors for DnaK, which should be ineffective for the human Hsp70.

  1. 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.

  2. 从文献分析看突发性耳聋的研究热点%Analysis the Hot Spots of Sudden Deafness by Researching Articles

    Institute of Scientific and Technical Information of China (English)

    向杰; 刘博

    2015-01-01

    Objective To better understand the hot spots and breakthrough on sudden deafness by searching and reading the papers in recent 5 years published in the PUBMED and the CNKI.Methods Use the Mesh term“Hearing Loss,Sudden”to search in the PUBMED.Use“sudden deafness”for the theme word to search in the CNKI.Results There are 381 articles in English,179 articles in Chinese.The article number of both database increase annually and the numbers are more than other years’in the 2012.(1)The top 3 countries published articles about sudden deafness in English are England,China,and Germany. The top 3 cities published articles about sudden deafness in Chinese are Guangdong,Henan,and Beijing.(2)There are 72(18.9%) articles about etiology of sudden deafness in English,61(16.0%) articles about diagnosis of sudden deafness in English,61(16.0%) articles about drug therapy.Articles about etiology and diagnosis in Chinese are less than in English.They focused in the therapy of sudden deafness. There are 61(34.1%) articles about drug therapy in Chinese,40(22.3%) articles about other therapy in Chinese,13(7.3%) about laboratory examination in Chinese.ConclusionThe hot spots of sudden deafness is significant different between home and abroad.The hot spots of sudden deafness is etiology,pathogenesis,and treatment.%目的:通过对PUBMED和CNKI数据库近5年收录的突聋研究文献检索、阅读和分析,了解近期突聋研究的热点问题和研究进展。方法在PUBMED数据库高级检索Mesh词表字段中检索“Hearing Loss,Sudden”,统计文献检索结果;在CNKI数据库主题字段中检索“突聋”,统计文献检索结果。结果 PUBMED及CNKI中近5年突聋文献发表数量呈逐年增加状态。共检索到英文文献381篇,中文文献179篇。①按地区分布看,英文文献数量前3位分别是英格兰、中国和德国。中文文献数量前3位分别是广东、河南和北京。②按文献研究方向看,英文文

  3. ASBench: benchmarking sets for allosteric discovery.

    Science.gov (United States)

    Huang, Wenkang; Wang, Guanqiao; Shen, Qiancheng; Liu, Xinyi; Lu, Shaoyong; Geng, Lv; Huang, Zhimin; Zhang, Jian

    2015-08-01

    Allostery allows for the fine-tuning of protein function. Targeting allosteric sites is gaining increasing recognition as a novel strategy in drug design. The key challenge in the discovery of allosteric sites has strongly motivated the development of computational methods and thus high-quality, publicly accessible standard data have become indispensable. Here, we report benchmarking data for experimentally determined allosteric sites through a complex process, including a 'Core set' with 235 unique allosteric sites and a 'Core-Diversity set' with 147 structurally diverse allosteric sites. These benchmarking sets can be exploited to develop efficient computational methods to predict unknown allosteric sites in proteins and reveal unique allosteric ligand-protein interactions to guide allosteric drug design.

  4. Identification of an Allosteric Binding Site on Human Lysosomal Alpha-Galactosidase Opens the Way to New Pharmacological Chaperones for Fabry Disease

    Science.gov (United States)

    den-Haan, Helena; Pérez-Sánchez, Horacio; Del Prete, Rosita; Liguori, Ludovica; Cimmaruta, Chiara; Lukas, Jan; Andreotti, Giuseppina

    2016-01-01

    Personalized therapies are required for Fabry disease due to its large phenotypic spectrum and numerous different genotypes. In principle, missense mutations that do not affect the active site could be rescued with pharmacological chaperones. At present pharmacological chaperones for Fabry disease bind the active site and couple a stabilizing effect, which is required, to an inhibitory effect, which is deleterious. By in silico docking we identified an allosteric hot-spot for ligand binding where a drug-like compound, 2,6-dithiopurine, binds preferentially. 2,6-dithiopurine stabilizes lysosomal alpha-galactosidase in vitro and rescues a mutant that is not responsive to a mono-therapy with previously described pharmacological chaperones, 1-deoxygalactonojirimycin and galactose in a cell based assay. PMID:27788225

  5. Equivalent hot spot stress approach for multiaxial fatigue strength assessment of complex welded joints%复杂焊接接头多轴疲劳强度评估的等效热点应力法

    Institute of Scientific and Technical Information of China (English)

    刘刚; 黄如旭; 黄一

    2012-01-01

    The current hot spot stress approach still has some limitations to the multiaxial fatigue strength assessment of complex welded joints.In this paper,an new stress estimation approach for the multiaxial fatigue strength assessment of complex welded joints is proposed,in which an equivalent hot spot stress is defined at a point(called Zero Point) in plate thickness direction where nonlinear distribution stress due to the notch effect of the weld is equal to zero.The proposed approach is based on that the nonlinear stress peak is not included in the hot spot stress and the nonlinear distribution stress is in self-equilibrium.First,influence factors and change laws of the Zero Point position were discussed,and a fitting equation for determining the Zero Point position was established.Then,published fatigue tests data and numerical stress results of some welded joints were used for comparison between the proposed equivalent hot spot stress approach and the current hot spot stress approach.The equivalent hot spot stress approach was verified to be consistent with the current hot spot stress approach and also have higher accuracy for considering the thickness effect on the fatigue strength to a certain extent.The merit of the proposed approach is that it can be used to estimate the multiaxial fatigue strength of welded joints through combining multiaxial fatigue theory.%基于焊缝本身引起的非线性分布应力自平衡的性质,在板厚方向非线性分布应力大小为零的位置(零点位置)定义等效热点应力,提出一种新的能够用于复杂焊接接头多轴疲劳应力评价方法.首先,分析了零点位置的影响因素和变化规律,建立了确定零点位置的拟合方程.然后,和公开发表的试验数据以及现有的热点应力法有限元计算结果进行了对比.结果表明,等效热点应力法和现有的热点应力法具有很好的一致性,而且能够在一定程度上考虑厚度效应对疲劳强度的影

  6. Statistical Mechanics of Allosteric Enzymes.

    Science.gov (United States)

    Einav, Tal; Mazutis, Linas; Phillips, Rob

    2016-07-07

    The concept of allostery in which macromolecules switch between two different conformations is a central theme in biological processes ranging from gene regulation to cell signaling to enzymology. Allosteric enzymes pervade metabolic processes, yet a simple and unified treatment of the effects of allostery in enzymes has been lacking. In this work, we take a step toward this goal by modeling allosteric enzymes and their interaction with two key molecular players-allosteric regulators and competitive inhibitors. We then apply this model to characterize existing data on enzyme activity, comment on how enzyme parameters (such as substrate binding affinity) can be experimentally tuned, and make novel predictions on how to control phenomena such as substrate inhibition.

  7. 利用卫星热点测报森林火灾的报准率统计分析%Accuracy Statistical Analysis of Forest Fire Forecasting by Using Satellite Hot Spot

    Institute of Scientific and Technical Information of China (English)

    黄甫则; 周汝良; 叶江霞; 丁琨

    2012-01-01

    卫星热点测报森林火灾的本质是测报地面高温热源,粗分辨率的遥感数据不能有效区别森林火灾与其非森林火灾,实地核查是卫星热点测报中的一个工作环节,利用GIS系统制定计算机辅助决策,提升热点处置的技术水平,是森林防火行业提出的一个应用研究课题,评估卫星热点测报森林火灾的报准率是解决问题的基础.通过收集云南省1998~2002年和2004年的卫星热点监测反馈数据11251条,按8种热源进行分类统计,进行大样本统计分析,利用总体比例估计模型进行比估计.结果表明,在90%可靠性条件下,云南的卫星热点中,森林火灾所占的比估计为29.3%,置信区间为{0.286,0.3001}.%The nature of satellite hot forest fires forecasting is measuring high-temperature heat source on the ground. Coarse-resolution remote sensing data can not distinguish between forest fires and non-forest fires. Field verification is a working link in satellite hot spot forecast. Using GIS system to develop computer-aided decision-making to enhance technical level of hot spot analysis is an applied research topic brought up by forest fire prevention profession. The assessment of accuracy of forest fires satellite hot spot forecasting is the basis of problem solving. This article collected 11 251 Satellite hot spot monitoring feedback data in Yunnan Province from 1998 to 2002 and in 2004. Classification statistics was made with eight kinds of heat source, and statistical analysis of large sample was made, the overall proportion estimated model was used for proportion estimation. The results showed that under 90% reliability condition, satellite hotspots in Yunnan, the share of forest fires proportion estimation was of 29. 3% , the confidence interval was 10. 286, 0. 300 11.

  8. 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

  9. "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

  10. 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

  11. Allosteric regulation of phenylalanine hydroxylase.

    Science.gov (United States)

    Fitzpatrick, Paul F

    2012-03-15

    The liver enzyme phenylalanine hydroxylase is responsible for conversion of excess phenylalanine in the diet to tyrosine. Phenylalanine hydroxylase is activated by phenylalanine; this activation is inhibited by the physiological reducing substrate tetrahydrobiopterin. Phosphorylation of Ser16 lowers the concentration of phenylalanine for activation. This review discusses the present understanding of the molecular details of the allosteric regulation of the enzyme.

  12. Allosteric Regulation of Phenylalanine Hydroxylase

    OpenAIRE

    Fitzpatrick, Paul F.

    2011-01-01

    The liver enzyme phenylalanine hydroxylase is responsible for conversion of excess phenylalanine in the diet to tyrosine. Phenylalanine hydroxylase is activated by phenylalanine; this activation is inhibited by the physiological reducing substrate tetrahydrobiopterin. Phosphorylation of Ser16 lowers the concentration of phenylalanine for activation. This review discusses the present understanding of the molecular details of the allosteric regulation of the enzyme.

  13. Research on the Dynamic Template Matching Method in Solar Energy Component Hot Spot Detection%太阳能组件热斑检测中的动态模板匹配方法研究

    Institute of Scientific and Technical Information of China (English)

    王阿勇; 杨静

    2012-01-01

    In order to decrease costs and effectively improve the component production qualities, thermal imagery is used to cany out the hot spot detection in solar energy components. The thermal images of solar energy components of large plate types are obtained in two times, and then they are spliced. In splicing thermal images, this paper suggests a splice algorithm based on the dynamic plate thermal images using the periodical properties shown by the component thermal images. Through corresponding tests, it can be proved that the algorithm can effectively improve component' s hot spot on-line detection efficiency. The designed detection scheme is adaptable to automatic hot spot detection with different specifications.%为了降低成本,有效提高组件的生产质量,利用热图像进行太阳能组件的热斑检测.分两次获取大板型太阳能组件热图像,然后进行图像拼接.在热图像的拼接中,利用组件热图像呈现周期性的特征,提出基于动态模板的热图像拼接算法.经过测试,动态模板的热图像拼接算法有效地提高了组件热斑在线检测效率,设计的检测方案适用于不同规格组件的热斑自动检测.

  14. Self-assembly of various Au nanocrystals on functionalized water-stable PVA/PEI nanofibers: a highly efficient surface-enhanced Raman scattering substrates with high density of "hot" spots.

    Science.gov (United States)

    Zhu, Han; Du, MingLiang; Zhang, Ming; Wang, Pan; Bao, ShiYong; Zou, Meiling; Fu, YaQin; Yao, JuMing

    2014-04-15

    We have demonstrated a facile approach for the fabrication of flexible and reliable sulfydryl functionalized PVA/PEI nanofibers with excellent water stability for the self-assembly of Au nanocrystals, such as Au nanoparticles (AuNPs), Au nanoflowers (AuNFs) and Au nanorods (AuNRs), used as the highly efficient surface-enhanced Raman scattering (SERS) substrates for the detection of rhodamine B (RhB). Various methods were employed to cross-link the PVA nanofibers with better morphology and porous structures after immersing in water for desired times. Various SERS-active Au nanocrystals, such as AuNPs, AuNFs, and AuNRs have been successfully synthesized. After the grafting of MPTES on the cross-linked PVA/PEI nanofibers, the Au nanocrystals can easily be self-assembled on the surfaces of the nanofibers because of the strong interactions of the Au-S chemical bondings. The Au nanocrystals self-assembled throughout the PVA/PEI nanofibers used as SERS substrates all exhibit enhanced SERS signals of RhB compared with their individual nanocrystals. It is mainly due to the close interparticle distance, mutual orientation and high density of "hot" spots, that can strongly affect the overall optical response and the SERS enhancement. By changing the amounts of the self-assembled AuNFs on the nanofibers, we can control the density of the "hot" spots. With the increased amounts of the AuNFs throughout the nanofibers, the SERS substrates show enhanced Raman signals of the RhB, indicating that the increased density of "hot" spots can directly lead to the SERS enhancement. The AuNFs/(PVA/PEI) SERS substrates show good sensitivity, reliability and low detection limit (10(-9) M). The presented approach can be broadly applicable to the assembly of different types of plasmonic nanostructures and these novel materials with strong SERS enhancement can be applied in bioanalysis and biosensors.

  15. 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

    FKS mutant isolates associated with breakthrough or failure cases are emerging in clinical settings. Discrimination of these from wild-type (wt) isolates in a routine laboratory setting is complicated. We evaluated the ability of caspofungin MIC determination using the new Vitek 2 AST-Y06 yeast...... 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...

  16. 多层套管燃料元件工程热点因子敏感性分析%Sensitivity Analysis of Engineering Hot Spot Factor for Multi-layer Tube Fuel Element

    Institute of Scientific and Technical Information of China (English)

    胡跃春; 邓才玉; 李海涛; 徐涛忠

    2014-01-01

    为保证反应堆的安全,并对燃料元件的制造加工提出合理可行的要求,从元件制造加工和反应堆运行测量两方面对多层套管燃料元件工程热点因子的敏感性进行了分析。结果表明:流道间隙偏差直接影响元件热源的导出,由此引起的工程热点因子造成的温升较大。%For ensuring reactor safety and putting forward reasonable requirements of fuel element manufacture , the sensitivity analysis of engineering hot spot factor for multi-layer tube fuel element was completed from both aspects of fuel manufacture and reactor operation measurement .The result shows that the flow channel deviation is of direct effect on fuel element heat transfer ,yielding a higher temperature rise caused by the relevant engineering hot spot factor .

  17. 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.

  18. HOT SPOT STRESS ANALYSIS OF DIFFERENT GIRTH BUTT WELD DETAILS OF CAST STEEL JOINT%不同焊接构造的铸钢节点环形对接焊缝的热点应力分析

    Institute of Scientific and Technical Information of China (English)

    韩庆华; 郭琪; 林允昶; 邢颖

    2014-01-01

    铸钢节点与主体构件的环形对接焊缝处存在材料差异、几何差异和焊接残余应力,因此环形对接焊缝是铸钢节点疲劳破坏的重要研究对象。目前,国内对铸钢节点焊缝疲劳问题的研究比较缺乏,传统名义应力方法并不适用于铸钢节点。采用热点应力方法对铸钢节点环形对接焊缝的疲劳问题进行探究,比较4种热点应力外推方法的计算结果。为减小铸钢节点与主体构件不等壁厚对接焊缝产生的应力集中对疲劳性能的影响,分析对比了3种不同的焊接构造,并分别研究在壁厚t、径厚比d/t、壁厚比T/t三种参数影响下的热点应力变化规律。%The girth butt weld attaching to the cast steel joint and the hot-rolled tube are the important object of the fatigue study of the cast steel joint due to the material nonlinearity and geometric nonlinearity across the weld . However , the research on this issue rarely saw in China and the nominal stress method was not applicable to it .In the paper, the hot spot stress method was used while the results of hot spot stress extrapolations were compared .To reduce the impact of the stress concentration , different weld details were designed .The hot spot stress curve was drawn under consideration of the tube ’ s thickness and the other two parameters .

  19. Age Spots

    Science.gov (United States)

    ... How to Choose the Best Skin Care Products Age Spots Treatment Options Learn more about treatment options ... or black, flat patches of skin. Why treat age spots Physical, emotional and social reasons for treating ...

  20. Allosteric enhancers, allosteric agonists and ago-allosteric modulators: where do they bind and how do they act?

    DEFF Research Database (Denmark)

    Schwartz, Thue W; Holst, Birgitte

    2007-01-01

    Many small-molecule agonists also display allosteric properties. Such ago-allosteric modulators act as co-agonists, providing additive efficacy--instead of partial antagonism--and they can affect--and often improve--the potency of the endogenous agonist. Surprisingly, the apparent binding sites...... different binding modes. In another, dimeric, receptor scenario, the endogenous agonist binds to one protomer while the ago-allosteric modulator binds to the other, 'allosteric' protomer. It is suggested that testing for ago-allosteric properties should be an integral part of the agonist drug discovery...... process because a compound that acts with--rather than against--the endogenous agonist could be an optimal agonist drug....

  1. Unraveling structural mechanisms of allosteric drug action.

    Science.gov (United States)

    Nussinov, Ruth; Tsai, Chung-Jung

    2014-05-01

    Orthosteric drugs block the active site to obstruct function; allosteric drugs modify the population of the active state, to modulate function. Available data lead us to propose that allosteric drugs can constitute anchors and drivers. The anchor docks into an allosteric pocket. The conformation with which it interacts is unchanged during the transition between the inactive and active states. The anchor provides the foundation that allows the driver to exert a 'pull' and/or 'push' action that shifts the receptor population from the inactive to the active state. The presence or absence of driver atom in an allosteric drug can exert opposite agonism. We map a strategy for driver identification and expect the allosteric trigger concept to transform agonist/antagonist drug discovery.

  2. Spatiotemporal distribution of the seismicity along the Mid-Atlantic Ridge north of the Azores from hydroacoustic data: Insights into seismogenic processes in a ridge-hot spot context

    Science.gov (United States)

    Goslin, J.; Perrot, J.; Royer, J.-Y.; Martin, C.; LourençO, N.; Luis, J.; Dziak, R. P.; Matsumoto, H.; Haxel, J.; Fowler, M. J.; Fox, C. G.; Lau, A. T.-K.; Bazin, S.

    2012-02-01

    The seismicity of the North Atlantic was monitored from May 2002 to September 2003 by the `SIRENA array' of autonomous hydrophones. The hydroacoustic signals provide a unique data set documenting numerous low-magnitude earthquakes along the section of the Mid-Atlantic Ridge (MAR) located in a ridge-hot spot interaction context. During the experiment, 1696 events were detected along the MAR axis between 40°N and 51°N, with a magnitude of completeness level ofmb≈ 2.4. Inside the array, location errors are in the order of 2 km, and errors in the origin time are less than 1 s. From this catalog, 15 clusters were detected. The distribution of source level (SL) versus time within each cluster is used to discriminate clusters occurring in a tectonic context from those attributed to non-tectonic (i.e. volcanic or hydrothermal) processes. The location of tectonic and non-tectonic sequences correlates well with regions with positive and negative Mantle Bouguer Anomalies (MBAs), indicating the presence of thinner/colder and thicker/warmer crust respectively. At the scale of the entire array, both the complete and declustered catalogs derived from the hydroacoustic signals show an increase of the seismicity rate from the Azores up to 43°30'N suggesting a diminishing influence of the Azores hot spot on the ridge-axis temperature, and well correlated with a similar increase in the along-axis MBAs. The comparison of the MAR seismicity with the Residual MBA (RMBA) at different scales leads us to think that the low-magnitude seismicity rates are directly related to along-axis variations in lithosphere rheology and temperatures.

  3. 肺癌患者SPECT/CT同机融合显像肋骨单发病灶影像分析%SPECT/CT fusion imaging analysis of costal single hot spots in patients with lung cancer

    Institute of Scientific and Technical Information of China (English)

    包贺菊; 陈刚; 陈燕燕

    2014-01-01

    Objective To analyze the imaging features and clinical significance of solitary costal hot spots in patient with lung cancer on SPECT/CT fusion imaging and the value of low-dose CT for diagnosis.Methods SPECT/CT scan was performed on 68 patients with lung cancer and costal single hot spots using whole body bone imaging.The sites of lesions were classified into four types:junction between costal cartilage and rib,frontal rib,lateral rib,posterior rib.The shapes of lesions were classified into two forms:punctiform and strip shapes,and were analyzed and classified.The differences of the diagnosis of whole body bone imaging and SPECT/CT scan were analyzed.Results Punctiform spots were mainly due to costal fractures(36/68,52.94%).The majority of spots in strip shape were costal metastases (21/23,91.30%).The lesions of junction between costal cartilage and rib were punctiform shape and benign.Hot spots in posterior ribs were mainly costal metastases (18/22,81.82%).Sensitivity of diagnosis of the metastatic bone tumor with whole body bone imaging and SPECT/CT in single hot spot of spine and rib was 69.23% (18/26) and 92.31%(24/26),specificity 59.52%(25/42) and 85.71%(36/42),accuracy 63.24%(43/68) and 88.24% (60/68),positive predictive value 51.43% (18/35) and 80.00% (24/30),negative predictive value 75.76% (25/33) and 94.74% (36/38).SPECT/CT scan had differences with whole body bone imaging in sensitivity (P < 0.05),SPECT/CT scan had significant differences with whole body bone imaging in coincidence and specificity (P < 0.01).Conclusions Useful imaging features can be obtained from SPECT/CT fusion imaging with single costal hot spots,being helpful to differential diagnosis of benign and malignant lesions.SPECT/CT fusion imaging may improve the accuracy to diagnose the rib disease.%目的 分析肺癌患者SPECT/CT同机融合显像肋骨单发病灶的特征和临床诊断之间的相互关系,并评价定位CT在诊断中的作用.方法

  4. Hot spot stress analysis of girth butt weld in cast steel joint%铸钢节点环形对接焊缝热点应力分析

    Institute of Scientific and Technical Information of China (English)

    韩庆华; 陈志钢; 芦燕

    2011-01-01

    铸钢节点的壁厚大于连接杆件,两者连接时壁厚方向存在几何形状的突变,引起焊缝附近的应力集中,降低其疲劳性能。目前现行规程或标准针对铸钢节点与主体结构连接处焊缝的疲劳问题没有明确的设计规定。本文选取两种焊接构造,采用热点应力的表面线性外推法对环形对接焊缝进行轴力作用下的疲劳性能有限元分析。同时选取结构杆件的壁厚t、径厚比d/t以及铸钢与普通杆件的壁厚比T/t作为热点应力的影响因素进行参数分析。分析结果表明:热点应力与厚度t关系不大,随着ln(d/t)的增大热点应力呈线性增加;随着T/t的增加,热点应力先增大后减小;ln(σ/(T/t))随着T/t的增加呈线性减小。%As cast steel joints are thicker than the hot-rolled tubes attached,sharp transition in the direction of thickness would cause stress concentration and weaken its fatigue performance.At present,there are no regulations or standards to guide the design of girth butt weld's fatigue behavior of cast steel joints.A hot-spot stress FEM analysis of weld's fatigue behavior was conducted based on the surface extrapolation method in this paper,considering two kinds of welding details under axial loads.Parametric analysis were carried out on the thickness(t) of hot-rolled tube,the ratio of tube's diameter to its thickness(d/t) and the ratio of cast steel joint's thickness to tube's(T/t).The results show that although the hot-spot stress is independent of the thickness of tubes(t),it will increase linearly with the increment of ln(d/t) and increase firstly then decrease with the increment of T/t.In addition,ln(σ/(T/t))(σ means the hot-spot stress) decreases linearly with the increment of T/t.

  5. 以箱壁温度为判据的油浸式变压器绕组热点温度计算模型及试验分析%Model of Hot Spot Temperature in Oil-immersed Transformers Using Temperature Estimation of Tank Wall

    Institute of Scientific and Technical Information of China (English)

    李剑; 刘兴鹏; 王有元; 陈伟根; 邓宗权

    2011-01-01

    电力变压器的热点温度是影响其绝缘寿命非常重要的因素,准确估计电力变压器热点温度,有助于提高电力变压器的经济与安全运行水平。为此,提出了一种估计变压器绕组热点温度的改进方法。该方法依据变压器热路模型,采用变压器油箱壁温度来估计绕组热点温度。为了验证该方法的准确性,在实验室的试验变压器上进行了负载试验,得到不同负载下的变压器绕组热点温度和油箱壁温度的实测值,并将热点温度的实测结果与该方法计算值以及IEEE负载导则公式的计算值进行了比较。分析结果表明,改进方法具有较小的热点温度估计误差,证明了改进方法估计变压器热点温度的有效性。%Hot spot temperature is a very important factor that influences lifetime of insulation in power transtormers. Accurate estimation of the hot spot temperatures of transformer windings is helpful to improving economic and safe operation levels of transformers. Consequently, an improved approach was presented to estimate hot spot temperatures of transformer windings. The improved approach was based on a thermal circuit of power transformers. Temperatures of transformer wails were used to estimate the hot spot temperature of transformer windings, and load of transformers was tested in laboratory to obtain the measurement data of temperatures of hot spot and transformer walls. The measurement results were compared with the estimated results of the improved approach and the calculated results of IEEE loading guide equations. The analysis results show that the improved approach has smaller estimation errors of hot spot temperature than the IEEE load guide equations. The improved approach is verified to be effective for estimation of hot spot temperature in transformers.

  6. Liver spots

    Science.gov (United States)

    Liver spots are changes in skin color that occur in older skin. The coloring may be due to aging, exposure to the sun or other sources of ultraviolet light, or causes that are not known. Liver spots are very common after age 40. They occur ...

  7. 非小细胞肺癌生物标志物新热点%New hot spots on biomarkers for non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    沈岚; 李子明; 陆舜

    2010-01-01

    As a hot topic, biomarkers can provide reliable evidence for the individualized treatment of non-small cell lung cancer. With the further study of molecular biology and development of new drugs,biomarkers have shown a broad prospect in clinical application. Combining with the research in recent years,this review describes the progress in biomarkers for non-small-cell lung cancer.%生物标志物是近年肺癌研究的热点之一,可为非小细胞肺癌(NSCLC)患者的个体化治疗提供可靠的依据.随着分子生物学研究的深入,其在临床上已显示出广阔的应用前景.文章结合近年来的研究对NSCLC生物标志物的新热点进行阐述.

  8. 国外足球耐力热点研究及其变化趋势分析%Research on the Hot Spots of Football Endurance in Foreign Countries and the Analysis of Its Changing Trend

    Institute of Scientific and Technical Information of China (English)

    陈小虎; 黄竹杭; 李春满

    2016-01-01

    以Web of ScienceTM核心合集数据库中(SCIE、SSCI和 A&HCI )收录的1997—2015年以足球耐力为主题的488篇文献信息作为数据源,运用科学知识图谱技术分析国外足球耐力研究的国家、机构和作者分布,并通过解析当前足球耐力研究的关键词,揭示国外足球耐力研究的相关热点以及其变化趋势。研究发现:美国的发文量最大,但英国所发文章的中心性更高,发文的机构主要集中在高等院校;来自各高等院校的Karim Chamari、Anis Chaoua‐chi、Peter Krustrup等教授是研究足球耐力的突出作者;研究的热点主要包括运动训练、竞技表现、训练方法和测试方法的可靠性、训练负荷及运动员的训练反应等;变化趋势以运动员训练和竞技表现为主线,由运动员身体反应过渡到检验测试方法的可靠性,再由关注训练方法的有效性过渡到利用先进技术分析运动员在训练和比赛中的表现。现阶段的足球耐力研究多为方法性研究,研究大多基于足球训练或比赛中的外在表现形成,缺乏支撑训练和比赛的基础性理论研究。%Selecting the literature from Web of ScienceTM core collection database (SCIE ,and SSCI and A&HCI) ,and taking the 488 articles during 1997—2015 with the theme of foot‐ball endurance as data source ,using knowledge map technology to analysis the football endur‐ance research study of foreign countries ,institutions and the distribution of authors ,and by re‐solving the current football endurance research keywords ,reveal the abroad study on the endur‐ance of football‐related hot spots and trends .The result shows that United States is issued much more than other countries ,but the most centrality is England .The institutions of issued mainly concentrated in university ;the professor of Karim Chamari ,Anis Chaouachi ,and Peter Krustrup from respective university are the highlight author to research

  9. An improved dynamic model of transformer hot spot temperature based on top oil temperature%基于顶层油温的变压器绕组热点温度计算改进模型

    Institute of Scientific and Technical Information of China (English)

    陈伟根; 苏小平; 周渠; 潘翀; 谢波

    2012-01-01

    油浸式电力变压器绕组热点温度是影响变压器绝缘寿命的重要参量,与变压器顶层油温密切相关。考虑非线性热阻一变压器断路阻抗、油粘滞度以及绕组损耗随温度的变化,引入粘滞度与损耗关于温度变化的修正因子,提出一种基于顶层油温的变压器绕组热点温度改进模型。模型参数选用Levenberg-Marquardt算法进行估算。对比实验室温升用试验变压器实测数据,该模型在欠负载(90%)、额定负载(100%)以及过负载(110%)下,显示了较好的一致性,特别在动态负载下,能够较好地描述各暂态温度变化情况,为变压器绕组热点温度计算提出了一种新方法。%The winding hot spot temperature of the oil-immersed power transformer is an important parameter. It has a great influence on the transformer insulation aging and a close relationship with the transformer top oil temperature. The changes of non-linear thermal resistance, open-circuit impedance, and oil viscosity and winding losses with temperature are also taken into account. An improved model added on the transformer top oil temperature to calculate transformer winding hot-spot temperature by using the viscosity and loss correction factors is proposed. Model parameters are estimated by Levenberg-Marquardt method. In the end, by comparing with the measured data tested under different conditions, the model shows good consistency under underload (90%), rated load (100%) and overload (110%) conditions respectively, and describes the temperature variation more accurately in the dynamic loading profiles.

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

    Energy Technology Data Exchange (ETDEWEB)

    Carvalho, Vanuildo S. de [Instituto de Física, Universidade Federal de Goiás, 74.001-970 Goiânia, GO (Brazil); Freire, Hermann, E-mail: hfreire@mit.edu [Instituto de Física, Universidade Federal de Goiás, 74.001-970 Goiânia, GO (Brazil); Department of Physics, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States)

    2013-10-21

    Motivated by a recent experimental observation of a nodal liquid on both single crystals and thin films of Bi{sub 2}Sr{sub 2}CaCu{sub 2}O{sub 8+} {sub 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.

  11. Plasmin Regulation through Allosteric, Sulfated, Small Molecules

    Directory of Open Access Journals (Sweden)

    Rami A. Al-Horani

    2015-01-01

    Full Text Available Plasmin, a key serine protease, plays a major role in clot lysis and extracellular matrix remodeling. Heparin, a natural polydisperse sulfated glycosaminoglycan, is known to allosterically modulate plasmin activity. No small allosteric inhibitor of plasmin has been discovered to date. We screened an in-house library of 55 sulfated, small glycosaminoglycan mimetics based on nine distinct scaffolds and varying number and positions of sulfate groups to discover several promising hits. Of these, a pentasulfated flavonoid-quinazolinone dimer 32 was found to be the most potent sulfated small inhibitor of plasmin (IC50 = 45 μM, efficacy = 100%. Michaelis-Menten kinetic studies revealed an allosteric inhibition of plasmin by these inhibitors. Studies also indicated that the most potent inhibitors are selective for plasmin over thrombin and factor Xa, two serine proteases in coagulation cascade. Interestingly, different inhibitors exhibited different levels of efficacy (40%–100%, an observation alluding to the unique advantage offered by an allosteric process. Overall, our work presents the first small, synthetic allosteric plasmin inhibitors for further rational design.

  12. SPOT Program

    Science.gov (United States)

    Smith, Jason T.; Welsh, Sam J.; Farinetti, Antonio L.; Wegner, Tim; Blakeslee, James; Deboeck, Toni F.; Dyer, Daniel; Corley, Bryan M.; Ollivierre, Jarmaine; Kramer, Leonard; Zimmerman, Patrick L.; Khatri, Reshma

    2010-01-01

    A Spacecraft Position Optimal Tracking (SPOT) program was developed to process Global Positioning System (GPS) data, sent via telemetry from a spacecraft, to generate accurate navigation estimates of the vehicle position and velocity (state vector) using a Kalman filter. This program uses the GPS onboard receiver measurements to sequentially calculate the vehicle state vectors and provide this information to ground flight controllers. It is the first real-time ground-based shuttle navigation application using onboard sensors. The program is compact, portable, self-contained, and can run on a variety of UNIX or Linux computers. The program has a modular objec-toriented design that supports application-specific plugins such as data corruption remediation pre-processing and remote graphics display. The Kalman filter is extensible to additional sensor types or force models. The Kalman filter design is also strong against data dropouts because it uses physical models from state and covariance propagation in the absence of data. The design of this program separates the functionalities of SPOT into six different executable processes. This allows for the individual processes to be connected in an a la carte manner, making the feature set and executable complexity of SPOT adaptable to the needs of the user. Also, these processes need not be executed on the same workstation. This allows for communications between SPOT processes executing on the same Local Area Network (LAN). Thus, SPOT can be executed in a distributed sense with the capability for a team of flight controllers to efficiently share the same trajectory information currently being computed by the program. SPOT is used in the Mission Control Center (MCC) for Space Shuttle Program (SSP) and International Space Station Program (ISSP) operations, and can also be used as a post -flight analysis tool. It is primarily used for situational awareness, and for contingency situations.

  13. 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

  14. 基于CiteSpace的教育大数据研究热点与趋势分析%The Analysis of Research Hot Spot and Trend on Big Data in Education based on CiteSpace

    Institute of Scientific and Technical Information of China (English)

    王娟; 陈世超; 王林丽; 杨现民

    2016-01-01

    With the era of big data coming, huge amount of data has been accumulated in education field. Taking CNKI and Google as research object, which including 924 and 204 journal papers about big Data in education respectively, adopting knowledge map of time and space and content knowledge map as main research methods, and applying the information visualization software CiteSpace, research hot spot and development trend of big data in education were revealed. It found the research of big data in education presented the following features: from the perspective of time, the research began to emerge centrally in 2013, and entered the stage of large-scale development in 2014-2015; from the view of content, the hot topic has “big data”, “big data era”, “study analysis and technology”, “data mining”, and etc. The further summary and reflection were given, in order to provide reference for deep study, practical exploration and industry promotion of big data in education.%大数据时代来临,教育领域积累了海量数据。文章以中国知网(CNKI)数据库收录的924篇及 Google学术收录的204篇与教育大数据相关的期刊论文为研究对象,运用信息可视化软件CiteSpace,以时空知识图谱及内容知识图谱分析为主要研究方法,揭示了国内外教育大数据的研究热点及发展趋势。分析发现,教育大数据研究呈现如下特点:从时间上看,研究在2013年开始集中涌现,2014~2015年进入大规模发展阶段;从内容上看,研究热点有“大数据”、“大数据时代”、“学习分析及技术”、“数据挖掘”等。为此,文章给出进一步的总结和思考,以期为教育大数据的深入研究、实践探索和产业推进提供参考。

  15. Visualization Analysis of Hot Spot and Cutting-Edge about Knowledge Sharing%知识共享研究热点与前沿的可视化分析

    Institute of Scientific and Technical Information of China (English)

    王伟军; 官思发; 李亚芳

    2012-01-01

    本文以ISIWebofScience数据库中收录的以知识共享为主题的文献信息作为数据源,然后运用CiteSpaceⅡ软件绘制了知识共享研究领域的国家或地区分布、机构分布、经典作品和研究热点与前沿的知识图谱,并进行了分析。研究发现,美国、英国、日本、德国和瑞典等在知识共享领域开展了广泛的合作研究,并且产出总量丰富。本文将研究热点与前沿分为知识共享相关的理论研究、技术方法研究和实践应用三个层面的内容。主要包括设计、交流、本体、网络、绩效、隐性知识、实践社区、知识建模、决策支持、人力资源开发、信息可视化、分布式案例推理和Web2.0等。%This paper selects ISI Web of Knowledge database to retrieve source data on the theme of knowledge sharing, and uses CiteSpaceⅡsoftware to draw knowledge domain map of national or regional distribution, institutional distribution, classic works, hot-spot and cutting-edge research content about knowledge sharing, then makes specific analyses. Study found that a wide range of collaborative research developed in the United States, Britain, Japan, Germany and Sweden etc. in the field of knowledge sharing, and the total output of papers of each country is comparatively rich. This paper divides the hot and cutting-edge research fields about knowledge sharing into three aspects including basic theories, methods and tech- nology support, and practical applications which are mainly consists of the design, communication, ontology, network, per- formance, tacit knowledge, communities of practice, knowledge modeling, decision support and human resources develop- ment, information visualization, distributed case reasoning and Web 2.0.

  16. 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

  17. 基于文献计量学的家庭照顾者相关研究现状及热点分析%Status quo and hot spots in studies on family caregivers:a bibliometric analysis

    Institute of Scientific and Technical Information of China (English)

    苏盼; 王安妮; 张杰

    2016-01-01

    Objective To analyze the status quo and hot spots in studies on family caregivers by bibliometric analy-sis. Methods PubMed-covered papers on family caregivers from 2011-01-01 to 2016-07-01 were retrieved and analyzed by BICOMS and gCLUTO to generate subject heading clustering curve, subject heading clustering matrix and subject heading tree. Results Six hot spots were detected in studies on family caregivers from 4945 papers from which 82 subject headings were extracted with a frequency≥36 , including social and psychological intervention of family caregivers for ischemic stroke patients, intervention of family caregivers for mental disease patients, mental health of family caregivers, mental health intervention of family caregivers for PD patients, mental health of family caregivers for AIDS patients, and mental health of family caregivers for tumor patients. Conclusion Importance is attached to the studies on family caregivers by foreign and domestic scholars with their studies focused on the inves-tigation and intervention of mental health in family caregivers.%目的::通过文献计量学方法探究近年来家庭照顾者相关的研究现状与热点。方法:计算机检索PubMed中与家庭照顾者研究相关的文献,检索范围为2011年1月1日-2016年7月1日,采用BICOMB和图形聚类工具gCLUTO对文献进行关键词词篇矩阵、双向聚类分析,形成主题词聚类曲线图、主题词聚类矩阵及主题词聚类树状图。结果:共4945篇文献纳入分析,抽取出现频次≥36次的主题词82个,聚类分析获得家庭照顾者相关研究的6个研究热点:脑卒中患者家庭照顾者的社会心理干预、精神疾病患者家庭照顾者的干预研究、家庭照顾者心理健康状况、阿尔茨海默病患者家庭照顾者心理健康干预、艾滋病患者家庭照顾者心理健康状况、肿瘤患者家庭照顾者心理健康干预。结论:近年来国外学者重视家庭照顾者

  18. Evaluation of CLSI M44-A2 Disk Diffusion and Associated Breakpoint Testing of Caspofungin and Micafungin Using a Well-Characterized Panel of Wild-Type and fks Hot Spot Mutant Candida Isolates▿

    Science.gov (United States)

    Arendrup, Maiken Cavling; Park, Steven; Brown, Steven; Pfaller, Michael; Perlin, David S.

    2011-01-01

    Disk diffusion testing has recently been standardized by the CLSI, and susceptibility breakpoints have been established for several antifungal compounds. For caspofungin, 5-μg disks are approved, and for micafungin, 10-μg disks are under evaluation. We evaluated the performances of caspofungin and micafungin disk testing using a panel of Candida isolates with and without known FKS echinocandin resistance mechanisms. Disk diffusion and microdilution assays were performed strictly according to CLSI documents M44-A2 and M27-A3. Eighty-nine clinical Candida isolates were included: Candida albicans (20 isolates/10 mutants), C. glabrata (19 isolates/10 mutants), C. dubliniensis (2 isolates/1 mutant), C. krusei (16 isolates/3 mutants), C. parapsilosis (14 isolates/0 mutants), and C. tropicalis (18 isolates/4 mutants). Quality control strains were C. parapsilosis ATCC 22019 and C. krusei ATCC 6258. The correlations between zone diameters and MIC results were good for both compounds, with identical susceptibility classifications for 93.3% of the isolates by applying the current CLSI breakpoints. However, the numbers of fks hot spot mutant isolates misclassified as being susceptible (S) (very major errors [VMEs]) were high (61% for caspofungin [S, ≥11 mm] and 93% for micafungin [S, ≥14 mm]). Changing the disk diffusion breakpoint to S at ≥22 mm significantly improved the discrimination. For caspofungin, 1 VME was detected (a C. tropicalis isolate with an F76S substitution) (3.5%), and for micafungin, 10 VMEs were detected, the majority of which were for C. glabrata (8/10). The broadest separation between zone diameter ranges for wild-type (WT) and mutant isolates was seen for caspofungin (6 to 12 mm versus −4 to 7 mm). In conclusion, caspofungin disk diffusion testing with a modified breakpoint led to excellent separation between WT and mutant isolates for all Candida species. PMID:21357293

  19. Computation of conformational coupling in allosteric proteins.

    Directory of Open Access Journals (Sweden)

    Brian A Kidd

    2009-08-01

    Full Text Available In allosteric regulation, an effector molecule binding a protein at one site induces conformational changes, which alter structure and function at a distant active site. Two key challenges in the computational modeling of allostery are the prediction of the structure of one allosteric state starting from the structure of the other, and elucidating the mechanisms underlying the conformational coupling of the effector and active sites. Here we approach these two challenges using the Rosetta high-resolution structure prediction methodology. We find that the method can recapitulate the relaxation of effector-bound forms of single domain allosteric proteins into the corresponding ligand-free states, particularly when sampling is focused on regions known to change conformation most significantly. Analysis of the coupling between contacting pairs of residues in large ensembles of conformations spread throughout the landscape between and around the two allosteric states suggests that the transitions are built up from blocks of tightly coupled interacting sets of residues that are more loosely coupled to one another.

  20. Allosteric small-molecule kinase inhibitors

    DEFF Research Database (Denmark)

    Wu, Peng; Clausen, Mads Hartvig; Nielsen, Thomas E.

    2015-01-01

    current barriers of kinase inhibitors, including poor selectivity and emergence of drug resistance. In spite of the small number of identified allosteric inhibitors in comparison with that of inhibitors targeting the ATP pocket, encouraging results, such as the FDA-approval of the first small...

  1. 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.

  2. Two CpG mutational hot spots in the X-linked interleukin-2 receptor gamma chain gene (IL2RG) may cause 15% of all human severe combined immunodeficiency

    Energy Technology Data Exchange (ETDEWEB)

    Pepper, A.E.; Puck, J.M. [National Center for Human Genome Research, Bethseda, MD (United States); Liu, X. [Univ. of Pennsylvania School of Medicine, Philadelphia, PA (United States)

    1994-09-01

    Severe combined immunodeficiency (SCID), a syndrome of profoundly impaired cellular and humoral immune function, is caused by various autosomal gene defects, including adenosine deaminase (ADA) deficiency, as well as mutations in the X-linked IL2RG gene encoding the gamma chain of the lymphocyte receptor for IL-2. Mutational analysis of IL2RG was performed using genomic DNA from males with SCID referred from genetics and immunology centers. Single strand conformation polymorphisms (SSCP) were sought by PCR amplification of each of the 8 IL2RG exons using labelled flanking primers. Sequence of exons with aberrant SSCP detected a majority of unique deleterious IL2RG mutations in 30 unrelated SCID patients. However, multiple mutations were seen at CpG dinucleotides, known to be C{yields}T transversion sites. cDNA 690-691 in exon 5 was mutated in 4 patients, 1 patient with each of the C{sub 690}{yields}T causing an Arg{yields}Cys substitution, and 1 with G{sub 691}{yields}A causing Arg{yields}His. Two other patients had SCID caused by a single mutation in IL2RG exon 7. This C{sub 879}{yields}T, also in a CpG, changed an Arg to STOP, resulting in loss of the SH2-related intracellular domain. In addition to our patients, 1 patient with each of the C{sub 690} and the C{sub 879} mutations have been reported by others, giving an overall incidence of 20% from our lab and 21% from all reported IL2RG SCID mutations. While ADA defects account for approximately 15% of SCID, a striking male SCID predominance suggest up to 70% of the cases are X-linked, due to IL2RG mutation. Thus, screening for mutations at the 2 CpG hot spots we have found in IL2RG can identify the genotype of as many SCID cases as are found by ADA testing.

  3. Status and Hot Spots of Resilience Research:A Bibliometric Analysis%基于文献计量学的心理弹性研究现状和热点分析

    Institute of Scientific and Technical Information of China (English)

    苏盼; 张静平; 张杰; 王安妮

    2016-01-01

    Objective To retrieve and analyze the status and hot spots of resilience research. Methods We made a retrieval in PubMed for literature with subject terms or key words concerning resilience published from January 1 2010 to September 15 2015. BICOMS was applied to conduct biliometric analysis on retrieval results including publishing time,source journals,subject terms,etc. According to the changing curve of accumulated times of subject terms,we found high-frequency subject terms by interception and obtained a subject term matrix. Then gCLUTO 1. 0 software was applied to conduct two-way cluster analysis,by which we made curves of subject term cluster,a matrix of subject term cluster,and a tree diagram of subject term cluster. At last, specific papers were referred to find research status and hotpots. Results A total of 3 241 pieces of literature relevant with resilience were collected,and there were 36 subject terms with frequency ≥40. We found 4 research hot spots through analysis,including the role of resilience on posttraumatic stress disorder( PTSD),the relation between resilience and mental health of the elderly,the resilience of caregivers for the patients,and the biochemistry mechanism of resilience in the aspect of stress coping. Conclusion In recent years, the academic circle in China and abroad attaches increasingly more importance on the research of resilience. The research emphasis is the effect of resilience on PTSD and the relation between resilience and mental health of the elderly. These subjects can be considered in further research,in order to find effective intervention scheme on resilience.%目的:检索并分析当前心理弹性研究的现状与热点。方法系统检索PubMed 2010-01-01至2015-09-15收录的国际上发表的主题或关键词中涉及心理弹性的文献。检索到的结果运用书目信息共现分析系统( BICOMS)进行文献计量分析,包括发表年份、来源期刊、主题词等。根据主题词累

  4. A literature review of epidemiological studies on mutation hot spots of Chinese population with non-syndromic hearing loss%非综合征性聋突变热点的流行病学分析

    Institute of Scientific and Technical Information of China (English)

    李海波; 李琼; 李红; 陈瑛

    2012-01-01

    Objective: To identify the regional mutation hot spots characteristics, and then to establish a regional genetic screening programs. Method; Molecular epidemiological literatures about Chinese deafness gene GJB2,SLC26A4,mitochondrial DNA mutations from 2006 to the first half of 2011 were retrieved in Wanfang and Pubmed literature database. The primary data of these studies including the number of samples, demographic characteristics, mutation frequencies and so on,were analyzed statiscally. Result:Of 46 papers, 42 were included in this study. The patients all had non-syndromic sensorineural hearing loss and lived in 20 regions of China. A total of 18094 were counted and the average mutation frequencies were approximately 42.0%. The mutation frequencies of 235 delC were 16. 34%, 299-300 delAT were 4. 75% in GJB2 gene and IVS7-2A>G were 12. 60% , 2168A>G were 2. 32% in SLC26A4 gene and the mutation frequencies of 1555A>G, 1494C>T in mtDNA were 5. 21 %, 1. 11% respectively. The statistical discrepancy was significant among mutation frequencies in different regions by χ2test(P<0. 05). Conclusion:Molecular epidemiological statistics show that the 6 locus are the mutation hot spots in Chinese people with non-syndromic hearing loss and can be used for genetic screening according to the specific regional mutation characteristics.%目的:了解耳聋基因突变热点在中国患者中的分布特征,以建立针对突变热点的区域性基因筛查方案.方法:运用万方和Pubmed等检索2006-2011年上半年国内报道的中国各地区人群耳聋相关基因GJB2、SLC26A4、mtDNA突变流行病学文献,对文献中的样本量、样本特征、地域分布、突变频率等多个因素进行统计分析.结果:检索到相关文献46篇,纳入该统计分析42篇,研究区域涉及中国20个省、市、自治区和直辖市,调查人群均为非综合征型感音神经性聋患者;样本总量18 094例,GJB2 235 delC突变频率为16.34%,GJB2 299-300 del

  5. The allosteric regulation of pyruvate kinase.

    Science.gov (United States)

    Valentini, G; Chiarelli, L; Fortin, R; Speranza, M L; Galizzi, A; Mattevi, A

    2000-06-16

    Pyruvate kinase (PK) is critical for the regulation of the glycolytic pathway. The regulatory properties of Escherichia coli were investigated by mutating six charged residues involved in interdomain salt bridges (Arg(271), Arg(292), Asp(297), and Lys(413)) and in the binding of the allosteric activator (Lys(382) and Arg(431)). Arg(271) and Lys(413) are located at the interface between A and C domains within one subunit. The R271L and K413Q mutant enzymes exhibit altered kinetic properties. In K413Q, there is partial enzyme activation, whereas R271L is characterized by a bias toward the T-state in the allosteric equilibrium. In the T-state, Arg(292) and Asp(297) form an intersubunit salt bridge. The mutants R292D and D297R are totally inactive. The crystal structure of R292D reveals that the mutant enzyme retains the T-state quaternary structure. However, the mutation induces a reorganization of the interface with the creation of a network of interactions similar to that observed in the crystal structures of R-state yeast and M1 PK proteins. Furthermore, in the R292D structure, two loops that are part of the active site are disordered. The K382Q and R431E mutations were designed to probe the binding site for fructose 1, 6-bisphosphate, the allosteric activator. R431E exhibits only slight changes in the regulatory properties. Conversely, K382Q displays a highly altered responsiveness to the activator, suggesting that Lys(382) is involved in both activator binding and allosteric transition mechanism. Taken together, these results support the notion that domain interfaces are critical for the allosteric transition. They couple changes in the tertiary and quaternary structures to alterations in the geometry of the fructose 1, 6-bisphosphate and substrate binding sites. These site-directed mutagenesis data are discussed in the light of the molecular basis for the hereditary nonspherocytic hemolytic anemia, which is caused by mutations in human erythrocyte PK gene.

  6. 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

  7. CMB Cold Spot from Inflationary Feature Scattering

    CERN Document Server

    Wang, Yi

    2015-01-01

    We propose a "feature-scattering" mechanism to explain the cosmic microwave background cold spot seen from {\\it WMAP} and {\\it Planck} maps. If there are hidden features in the potential of multi-field inflation, the inflationary trajectory can be scattered by such features. The scattering is controlled by the amount of isocurvature fluctuations, and thus can be considered as a mechanism to convert isocurvature fluctuations into curvature fluctuations. This mechanism predicts localized cold spots (instead of hot ones) on the CMB. In addition, it may also bridge a connection between the cold spot and a dip on the CMB power spectrum at $\\ell \\sim 20$.

  8. Rocky Mountain Spotted Fever

    Science.gov (United States)

    ... facebook share with twitter share with linkedin Rocky Mountain Spotted Fever Rocky Mountain spotted fever is a ... New Mexico. Why Is the Study of Rocky Mountain Spotted Fever a Priority for NIAID? Tickborne diseases ...

  9. International Union of Basic and Clinical Pharmacology. XC. multisite pharmacology: recommendations for the nomenclature of receptor allosterism and allosteric ligands.

    Science.gov (United States)

    Christopoulos, Arthur; Changeux, Jean-Pierre; Catterall, William A; Fabbro, Doriano; Burris, Thomas P; Cidlowski, John A; Olsen, Richard W; Peters, John A; Neubig, Richard R; Pin, Jean-Philippe; Sexton, Patrick M; Kenakin, Terry P; Ehlert, Frederick J; Spedding, Michael; Langmead, Christopher J

    2014-10-01

    Allosteric interactions play vital roles in metabolic processes and signal transduction and, more recently, have become the focus of numerous pharmacological studies because of the potential for discovering more target-selective chemical probes and therapeutic agents. In addition to classic early studies on enzymes, there are now examples of small molecule allosteric modulators for all superfamilies of receptors encoded by the genome, including ligand- and voltage-gated ion channels, G protein-coupled receptors, nuclear hormone receptors, and receptor tyrosine kinases. As a consequence, a vast array of pharmacologic behaviors has been ascribed to allosteric ligands that can vary in a target-, ligand-, and cell-/tissue-dependent manner. The current article presents an overview of allostery as applied to receptor families and approaches for detecting and validating allosteric interactions and gives recommendations for the nomenclature of allosteric ligands and their properties.

  10. Taking three typical nourished beaches for example to explore the character and mechanism of erosional hot spot at nourished beach%以3个典型个例探讨养护海滩侵蚀热点的特征及其成因类型

    Institute of Scientific and Technical Information of China (English)

    蔚广鑫; 蔡锋; 戚洪帅; 刘建辉

    2013-01-01

    Based on the data of multi-period topography survey, observation records and remote sensing images from 3 typical beach nourishment projects, i. e. Xiangshan—Changwei Reef beach in Xiamen, West Beach in Beidaihe and Longfengtou beach in Pingtan, the distribution and morphological characteristics of beach erosional hot spots were investigated, and their causes and control factors were further analyzed. The results show that the different scales of erosional hot spots are found at nourished beaches, ranging from 20 to 260m. This study shows that the main factors causing beach erosional hot spots are coastal underwater topography, sewage pipes or groins, headlands and the abrupt change of shoreline direction. They can be specially expressed as: ( 1 ) When there existed offshore submerged breakwaters, bars or continuous reefs with gaps under water, erosional hot spots would emerge as wave energy accumulation induced by wave diffraction. (2) Sewage pipes buried across the beach will block the sediment transport along the coast, causing erosional hot spots at its downstream. (3)The headlands at both ends of a bay coast could cause partially serious erosion surrounding the headland by wave refraction and reflection. (4) In the case of the shoreline direction of a nourished beach has an abrupt change, especially protruding seaward, it will be smoothed by wave action, resulting serious erosion at the abrupt point.%基于厦门香山—长尾礁海滩、北戴河西海滩和平潭龙凤头海滩3个典型海滩养护后多期地形地貌测量数据、观测记录和遥感影像等,分析了养护海滩侵蚀热点的分布和形态特征,探讨了各处侵蚀热点的形成原因和控制因素.从野外调查来看,侵蚀热点在各养护海滩皆有分布,热点宽度为20 ~260 m不等.研究表明沿岸水下地形、排污管道的布设、岬角和岸线走向突变是诱发侵蚀热点的主要因素,具体表现为:(1)沿岸水下地形分布有离岸潜堤、

  11. Friction Stir Spot Welding of Advanced High Strength Steels

    Energy Technology Data Exchange (ETDEWEB)

    Santella, M. L.; Hovanski, Yuri; Grant, Glenn J.; Carpenter, Joseph A.; Warren, C. D.; Smith, Mark T.

    2008-12-28

    Experiments are continuing to evaluate the feasibility of friction stir spot welding advanced high-strength steels including, DP780, martensitic hot-stamp boron steel, and TRIP steels. Spot weld lap-shear strengths can exceed those required by industry standards such as AWS D8.1.

  12. Calculated pKa Variations Expose Dynamic Allosteric Communication Networks.

    Science.gov (United States)

    Lang, Eric J M; Heyes, Logan C; Jameson, Geoffrey B; Parker, Emily J

    2016-02-17

    Allosteric regulation of protein function, the process by which binding of an effector molecule provokes a functional response from a distal site, is critical for metabolic pathways. Yet, the way the allosteric signal is communicated remains elusive, especially in dynamic, entropically driven regulation mechanisms for which no major conformational changes are observed. To identify these dynamic allosteric communication networks, we have developed an approach that monitors the pKa variations of ionizable residues over the course of molecular dynamics simulations performed in the presence and absence of an allosteric regulator. As the pKa of ionizable residues depends on their environment, it represents a simple metric to monitor changes in several complex factors induced by binding an allosteric effector. These factors include Coulombic interactions, hydrogen bonding, and solvation, as well as backbone motions and side chain fluctuations. The predictions that can be made with this method concerning the roles of ionizable residues for allosteric communication can then be easily tested experimentally by changing the working pH of the protein or performing single point mutations. To demonstrate the method's validity, we have applied this approach to the subtle dynamic regulation mechanism observed for Neisseria meningitidis 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase, the first enzyme of aromatic biosynthesis. We were able to identify key communication pathways linking the allosteric binding site to the active site of the enzyme and to validate these findings experimentally by reestablishing the catalytic activity of allosterically inhibited enzyme via modulation of the working pH, without compromising the binding affinity of the allosteric regulator.

  13. 研究热点探测的替代计量学方法和应用--以信息与计算科学为例%Detecting Research Hot-spots Using Altmetrics:A Case Study on Information & Computing Science

    Institute of Scientific and Technical Information of China (English)

    赵雅馨; 杨志萍

    2016-01-01

    Purpose/Significance] Research hot spots represent the topics to which researchers, policy makers and other stakeholders should pay attention. As for the approaches for detecting research hot spots, traditional approaches have certain disadvantages such as time lag and low efficiency, and the altmetrics way could be a feasible solution. [ Method/Process] In this paper, we explore the feasibility of applying altmetrics to hot spots detection. Using Altmetric Explorer provided by altmetric. com, we get a full set of Information&Compu-ting Science literatures' altmetric data, and then get a random sample of 2,500 records using SPSS random sampling. Based on these data, we explore the themes of the literatures with top 5% attention or mentioned in the past 1 month, then investigate whether the themes we get are hot topics of current research. [ Result/Conclusion] Empirical study shows that in the field of Information &Computing Science, the themes we get by altmetrics way are consistent with the actual ones, which demonstrates the feasibility of using altmetrics data in research hot spots detecting.%[目的/意义]识别研究热点,对掌握科学发展动态、加快推进科技创新、正确制定科学政策以及合理分配科研资源等具有重要意义。如今科研周期日益加快,传统的研究热点识别工作难免存在滞后于实际情况的问题;而基于在线数据的替代计量方法则可以较为有效地解决时滞问题,为研究热点探测工作提供新的思路。[方法/过程]借助altmetric. com工具进行数据下载,获取信息与计算科学大类下文献的全集数据,通过SPSS随机抽样得到2500条文献的Altmetric数据。在此基础上,分析综合关注度最高(Top5%)与关注度最新(2016年3月至4月)文献的主题,结合有关研究热点资料,探讨替代计量方法在研究热点探测中的可行性。[结果/结论]在信息与计算科学领域中,根据替代计量数据得

  14. 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.

  15. Untangling the glutamate dehydrogenase allosteric nightmare.

    Science.gov (United States)

    Smith, Thomas J; Stanley, Charles A

    2008-11-01

    Glutamate dehydrogenase (GDH) is found in all living organisms, but only animal GDH is regulated by a large repertoire of metabolites. More than 50 years of research to better understand the mechanism and role of this allosteric network has been frustrated by its sheer complexity. However, recent studies have begun to tease out how and why this complex behavior evolved. Much of GDH regulation probably occurs by controlling a complex ballet of motion necessary for catalytic turnover and has evolved concomitantly with a long antenna-like feature of the structure of the enzyme. Ciliates, the 'missing link' in GDH evolution, might have created the antenna to accommodate changing organelle functions and was refined in humans to, at least in part, link amino acid catabolism with insulin secretion.

  16. Rocky Mountain spotted fever

    Science.gov (United States)

    ... Mountain spotted fever is caused by the bacteria Rickettsia rickettsii (R. Rickettsii) , which is carried by ticks. ... Saunders; 2014:chap 212. Walker DH, Blaton LS. Rickettsia rickettsii and other spotted fever group rickettsiae (Rocky ...

  17. Hot microswimmers

    Science.gov (United States)

    Kroy, Klaus; Chakraborty, Dipanjan; Cichos, Frank

    2016-11-01

    Hot microswimmers are self-propelled Brownian particles that exploit local heating for their directed self-thermophoretic motion. We provide a pedagogical overview of the key physical mechanisms underlying this promising new technology. It covers the hydrodynamics of swimming, thermophoresis and -osmosis, hot Brownian motion, force-free steering, and dedicated experimental and simulation tools to analyze hot Brownian swimmers.

  18. 浅析社会热点问题和高校学生思想发展的关系%Analysis on the Relationship between Social Hot Spots and the Development of College Students'Ideology

    Institute of Scientific and Technical Information of China (English)

    黄兆凡

    2016-01-01

    社会热点问题的产生必定是与特定的时代特征和社会条件紧密联系的,高校大学生对社会热点问题的关注程度和价值态度侧面反映了其对于社会整体发展状况的态度。研究高校大学生思想动态必然离不开研究社会热点问题对于高校学生思想的影响,了解其影响,才可能进一步做好高校大学生的思想政治工作。%The hot social issues must be closely linked with the specific characteristics of the times and social conditions,the con-cern degree and value attitude of college students on the social hot issues reflects aside the attitude to the status of development of society as a whole.The research of university students'ideological trends can not be separated from the study of the social hot issues for the impact of college students'thinking,understanding of its impact,it is possible to further improve the ideolog-ical and political education of college students.

  19. ETA-receptor antagonists or allosteric modulators?

    DEFF Research Database (Denmark)

    De Mey, Jo G R; Compeer, Matthijs G; Lemkens, Pieter

    2011-01-01

    The paracrine signaling peptide endothelin-1 (ET1) is involved in cardiovascular diseases, cancer and chronic pain. It acts on class A G-protein-coupled receptors (GPCRs) but displays atypical pharmacology. It binds tightly to ET receptor type A (ET(A)) and causes long-lasting effects. In resista......The paracrine signaling peptide endothelin-1 (ET1) is involved in cardiovascular diseases, cancer and chronic pain. It acts on class A G-protein-coupled receptors (GPCRs) but displays atypical pharmacology. It binds tightly to ET receptor type A (ET(A)) and causes long-lasting effects....... In resistance arteries, the long-lasting contractile effects can only be partly and reversibly relaxed by low-molecular-weight ET(A) antagonists (ERAs). However, the neuropeptide calcitonin-gene-related peptide selectively terminates binding of ET1 to ET(A). We propose that ET1 binds polyvalently to ET(A......) and that ERAs and the physiological antagonist allosterically reduce ET(A) functions. Combining the two-state model and the two-domain model of GPCR function and considering receptor activation beyond agonist binding might lead to better anti-endothelinergic drugs. Future studies could lead to compounds...

  20. Allosteric regulation of deubiquitylase activity through ubiquitination

    Directory of Open Access Journals (Sweden)

    Serena eFaggiano

    2015-02-01

    Full Text Available Ataxin-3, the protein responsible for spinocerebellar ataxia type-3, is a cysteine protease that specifically cleaves poly-ubiquitin chains and participates in the ubiquitin proteasome pathway. The enzymatic activity resides in the N-terminal Josephin domain. An unusual feature of ataxin-3 is its low enzymatic activity especially for mono-ubiquitinated substrates and short ubiquitin chains. However, specific ubiquitination at lysine 117 in the Josephin domain activates ataxin-3 through an unknown mechanism. Here, we investigate the effects of K117 ubiquitination on the structure and enzymatic activity of the protein. We show that covalently linked ubiquitin rests on the Josephin domain, forming a compact globular moiety and occupying a ubiquitin binding site previously thought to be essential for substrate recognition. In doing so, ubiquitination enhances enzymatic activity by locking the enzyme in an activated state. Our results indicate that ubiquitin functions both as a substrate and as an allosteric regulatory factor. We provide a novel example in which a conformational switch controls the activity of an enzyme that mediates deubiquitination.

  1. Ryanodine receptors: allosteric ion channel giants.

    Science.gov (United States)

    Van Petegem, Filip

    2015-01-16

    The endoplasmic reticulum (ER) and sarcoplasmic reticulum (SR) form major intracellular Ca(2+) stores. Ryanodine receptors (RyRs) are large tetrameric ion channels in the SR and ER membranes that can release Ca(2+) upon triggering. With molecular masses exceeding 2.2MDa, they represent the pinnacle of ion channel complexity. RyRs have adopted long-range allosteric mechanisms, with pore opening resulting in conformational changes over 200Å away. Together with tens of protein and small molecule modulators, RyRs have adopted rich and complex regulatory mechanisms. Structurally related to inositol-1,4,5-trisphosphate receptors (IP3Rs), RyRs have been studied extensively using cryo-electron microscopy (cryo-EM). Along with more recent X-ray crystallographic analyses of individual domains, these have resulted in pseudo-atomic models. Over 500 mutations in RyRs have been linked to severe genetic disorders, which underscore their role in the contraction of cardiac and skeletal muscles. Most of these have been linked to gain-of-function phenotypes, resulting in premature or prolonged leak of Ca(2+) in the cytosol. This review outlines our current knowledge on the structure of RyRs at high and low resolutions, their relationship to IP3Rs, an overview of the most commonly studied regulatory mechanisms, and models that relate disease-causing mutations to altered channel function.

  2. Allosteric modulators for the treatment of schizophrenia: targeting glutamatergic networks.

    Science.gov (United States)

    Menniti, Frank S; Lindsley, Craig W; Conn, P Jeffrey; Pandit, Jayvardhan; Zagouras, Panayiotis; Volkmann, Robert A

    2013-01-01

    Schizophrenia is a highly debilitating mental disorder which afflicts approximately 1% of the global population. Cognitive and negative deficits account for the lifelong disability associated with schizophrenia, whose symptoms are not effectively addressed by current treatments. New medicines are needed to treat these aspects of the disease. Neurodevelopmental, neuropathological, genetic, and behavioral pharmacological data indicate that schizophrenia stems from a dysfunction of glutamate synaptic transmission, particularly in frontal cortical networks. A number of novel pre- and postsynaptic mechanisms affecting glutamatergic synaptic transmission have emerged as viable targets for schizophrenia. While developing orthosteric glutamatergic agents for these targets has proven extremely difficult, targeting allosteric sites of these targets has emerged as a promising alternative. From a medicinal chemistry perspective, allosteric sites provide an opportunity of finding agents with better drug-like properties and greater target specificity. Furthermore, allosteric modulators are better suited to maintaining the highly precise temporal and spatial aspects of glutamatergic synaptic transmission. Herein, we review neuropathological and genomic/genetic evidence underscoring the importance of glutamate synaptic dysfunction in the etiology of schizophrenia and make a case for allosteric targets for therapeutic intervention. We review progress in identifying allosteric modulators of AMPA receptors, NMDA receptors, and metabotropic glutamate receptors, all with the aim of restoring physiological glutamatergic synaptic transmission. Challenges remain given the complexity of schizophrenia and the difficulty in studying cognition in animals and humans. Nonetheless, important compounds have emerged from these efforts and promising preclinical and variable clinical validation has been achieved.

  3. HOT 2012

    DEFF Research Database (Denmark)

    Lund, Henriette Romme

    Undersøgelse af, hvad der er hot - og hvad der burde være hot på læseområdet med 21 læsekyndige. Undersøgelsen er gennemført siden 2010. HOT-undersøgelsen er foretaget af Nationalt Videncenter for Læsning - Professionshøjskolerne i samarb. med Dansklærerforeningen...

  4. 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.

  5. Allosteric dynamics of SAMHD1 studied by molecular dynamics simulations

    Science.gov (United States)

    Patra, K. K.; Bhattacharya, A.; Bhattacharya, S.

    2016-10-01

    SAMHD1 is a human cellular enzyme that blocks HIV-1 infection in myeloid cells and non-cycling CD4+T cells. The enzyme is an allosterically regulated triphosphohydrolase that modulates the level of cellular dNTP. The virus restriction is attributed to the lowering of the pool of dNTP in the cell to a point where reverse-transcription is impaired. Mutations in SAMHD1 are also implicated in Aicardi-Goutieres syndrome. A mechanistic understanding of the allosteric activation of the enzyme is still elusive. We have performed molecular dynamics simulations to examine the allosteric site dynamics of the protein and to examine the connection between the stability of the tetrameric complex and the Allosite occupancy.

  6. 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.

  7. How allosteric effectors can bind to the same protein residue and produce opposite shifts in the allosteric equilibrium.

    Science.gov (United States)

    Abraham, D J; Safo, M K; Boyiri, T; Danso-Danquah, R E; Kister, J; Poyart, C

    1995-11-21

    Monoaldehyde allosteric effectors of hemoglobin were designed, using molecular modeling software (GRID), to form a Schiff base adduct with the Val 1 alpha N-terminal nitrogens and interact via a salt bridge with Arg 141 alpha of the opposite subunit. The designed molecules were synthesized if not available. It was envisioned that the molecules, which are aldehyde acids, would produce a high-affinity hemoglobin with potential interest as antisickling agents similar to other aldehyde acids reported earlier. X-ray crystallographic analysis indicated that the aldehyde acids did bind as modeled de novo in symmetry-related pairs to the alpha subunit N-terminal nitrogens. However, oxygen equilibrium curves run on solutions obtained from T- (tense) state hemoglobin crystals of reacted effector molecules produced low-affinity hemoglobins. The shift in the allosteric equilibrium was opposite to that expected. We conclude that the observed shift in allosteric equilibrium was due to the acid group on the monoaldehyde aromatic ring that forms a salt bridge with the guanidinium ion of Arg 141 alpha on the opposite subunit. This added constraint to the T-state structure that ties two subunits across the molecular symmetry axis shifts the equilibrium further toward the T-state. We tested this idea by comparing aldehydes that form Schiff base interactions with the same Val 1 alpha residues but do not interact across the dimer subunit symmetry axis (a new one in this study with no acid group and others that have had determined crystal structures). The latter aldehydes shift the allosteric equilibrium toward the R-state. A hypothesis to predict the direction in shift of the allosteric equilibrium is made and indicates that it is not exclusively where the molecule binds but how it interacts with the protein to stabilize or destabilize the T- (tense) allosteric state.

  8. Functional Impact of Allosteric Agonist Activity of Selective Positive Allosteric Modulators of Metabotropic Glutamate Receptor Subtype 5 in Regulating Central Nervous System Function

    OpenAIRE

    Noetzel, Meredith J.; Rook, Jerri M.; Vinson, Paige N.; Cho, Hyekyung P.; Days, Emily; Zhou, Y.; Rodriguez, Alice L.; Lavreysen, Hilde; Stauffer, Shaun R.; Niswender, Colleen M.; Xiang, Zixiu; Daniels, J. Scott; Jones, Carrie K.; Lindsley, Craig W.; Weaver, C. David

    2012-01-01

    Positive allosteric modulators (PAMs) of metabotropic glutamate receptor subtype 5 (mGlu5) have emerged as an exciting new approach for the treatment of schizophrenia and other central nervous system (CNS) disorders. Of interest, some mGlu5 PAMs act as pure PAMs, only potentiating mGlu5 responses to glutamate whereas others [allosteric agonists coupled with PAM activity (ago-PAMs)] potentiate responses to glutamate and have intrinsic allosteric agonist activity in mGlu5-expressing cell lines....

  9. 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

    Energy Technology Data Exchange (ETDEWEB)

    Carvalho, Vanuildo S de [Instituto de Física, Universidade Federal de Goiás, 74.001-970, Goiânia-GO (Brazil); Freire, Hermann, E-mail: hfreire@mit.edu [Instituto de Física, Universidade Federal de Goiás, 74.001-970, Goiânia-GO (Brazil); Department of Physics, Massachusetts Institute of Technology, Cambridge, MA 2139 (United States)

    2014-09-15

    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{sup ′} 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.

  10. Ago-allosteric modulation and other types of allostery in dimeric 7TM receptors

    DEFF Research Database (Denmark)

    Schwartz, Thue W; Holst, Birgitte

    2006-01-01

    Conventionally, an allosteric modulator is neutral in respect of efficacy and binds to a receptor site distant from the orthosteric site of the endogenous agonist. However, recently compounds being ago-allosteric modulators have been described i.e., compounds acting both as agonists on their own...... 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 exogenous......, allosteric modulators. If the allosteric modulator is an agonist, it is an ago-allosteric modulator; if it is neutral, it is a classical enhancer. Molecular mapping in hetero-dimeric class-C receptors, where the endogenous agonist clearly binds only in one protomer, supports the notion that allosteric...

  11. Jupiter's Hot, Mushy Moon

    Science.gov (United States)

    Taylor, G. Jeffrey

    2003-01-01

    Jupiter's moon Io is the most volcanically active body in the Solar System. Observations by instruments on the Galileo spacecraft and on telescopes atop Mauna Kea in Hawai'i indicate that lava flows on Io are surprisingly hot, over 1200 oC and possibly as much as 1300 oC; a few areas might have lava flows as hot as 1500 oC. Such high temperatures imply that the lava flows are composed of rock that formed by a very large amount of melting of Io's mantle. This has led Laszlo Keszthelyi and Alfred S. McEwen of the University of Arizona and me to reawaken an old hypothesis that suggests that the interior of Io is a partially-molten mush of crystals and magma. The idea, which had fallen out of favor for a decade or two, explains high-temperature hot spots, mountains, calderas, and volcanic plains on Io. If correct, Io gives us an opportunity to study processes that operate in huge, global magma systems, which scientists believe were important during the early history of the Moon and Earth, and possibly other planetary bodies as well. Though far from proven, the idea that Io has a ocean of mushy magma beneath its crust can be tested with measurements by future spacecraft.

  12. An allosteric inhibitor of protein arginine methyltransferase 3.

    Science.gov (United States)

    Siarheyeva, Alena; Senisterra, Guillermo; Allali-Hassani, Abdellah; Dong, Aiping; Dobrovetsky, Elena; Wasney, Gregory A; Chau, Irene; Marcellus, Richard; Hajian, Taraneh; Liu, Feng; Korboukh, Ilia; Smil, David; Bolshan, Yuri; Min, Jinrong; Wu, Hong; Zeng, Hong; Loppnau, Peter; Poda, Gennadiy; Griffin, Carly; Aman, Ahmed; Brown, Peter J; Jin, Jian; Al-Awar, Rima; Arrowsmith, Cheryl H; Schapira, Matthieu; Vedadi, Masoud

    2012-08-01

    PRMT3, a protein arginine methyltransferase, has been shown to influence ribosomal biosynthesis by catalyzing the dimethylation of the 40S ribosomal protein S2. Although PRMT3 has been reported to be a cytosolic protein, it has been shown to methylate histone H4 peptide (H4 1-24) in vitro. Here, we report the identification of a PRMT3 inhibitor (1-(benzo[d][1,2,3]thiadiazol-6-yl)-3-(2-cyclohexenylethyl)urea; compound 1) with IC50 value of 2.5 μM by screening a library of 16,000 compounds using H4 (1-24) peptide as a substrate. The crystal structure of PRMT3 in complex with compound 1 as well as kinetic analysis reveals an allosteric mechanism of inhibition. Mutating PRMT3 residues within the allosteric site or using compound 1 analogs that disrupt interactions with allosteric site residues both abrogated binding and inhibitory activity. These data demonstrate an allosteric mechanism for inhibition of protein arginine methyltransferases, an emerging class of therapeutic targets.

  13. Structures of pyruvate kinases display evolutionarily divergent allosteric strategies.

    Science.gov (United States)

    Morgan, Hugh P; Zhong, Wenhe; McNae, Iain W; Michels, Paul A M; Fothergill-Gilmore, Linda A; Walkinshaw, Malcolm D

    2014-09-01

    The transition between the inactive T-state (apoenzyme) and active R-state (effector bound enzyme) of Trypanosoma cruzi pyruvate kinase (PYK) is accompanied by a symmetrical 8° rigid body rocking motion of the A- and C-domain cores in each of the four subunits, coupled with the formation of additional salt bridges across two of the four subunit interfaces. These salt bridges provide increased tetramer stability correlated with an enhanced specificity constant (k cat/S 0.5). A detailed kinetic and structural comparison between the potential drug target PYKs from the pathogenic protists T. cruzi, T. brucei and Leishmania mexicana shows that their allosteric mechanism is conserved. By contrast, a structural comparison of trypanosomatid PYKs with the evolutionarily divergent PYKs of humans and of bacteria shows that they have adopted different allosteric strategies. The underlying principle in each case is to maximize (k cat/S 0.5) by stabilizing and rigidifying the tetramer in an active R-state conformation. However, bacterial and mammalian PYKs have evolved alternative ways of locking the tetramers together. In contrast to the divergent allosteric mechanisms, the PYK active sites are highly conserved across species. Selective disruption of the varied allosteric mechanisms may therefore provide a useful approach for the design of species-specific inhibitors.

  14. The structure and allosteric regulation of glutamate dehydrogenase.

    Science.gov (United States)

    Li, Ming; Li, Changhong; Allen, Aron; Stanley, Charles A; Smith, Thomas J

    2011-09-01

    Glutamate dehydrogenase (GDH) has been extensively studied for more than 50 years. Of particular interest is the fact that, while considered by most to be a 'housekeeping' enzyme, the animal form of GDH is heavily regulated by a wide array of allosteric effectors and exhibits extensive inter-subunit communication. While the chemical mechanism for GDH has remained unchanged through epochs of evolution, it was not clear how or why animals needed to evolve such a finely tuned form of this enzyme. As reviewed here, recent studies have begun to elucidate these issues. Allosteric regulation first appears in the Ciliates and may have arisen to accommodate evolutionary changes in organelle function. The occurrence of allosteric regulation appears to be coincident with the formation of an 'antenna' like feature rising off the tops of the subunits that may be necessary to facilitate regulation. In animals, this regulation further evolved as GDH became integrated into a number of other regulatory pathways. In particular, mutations in GDH that abrogate GTP inhibition result in dangerously high serum levels of insulin and ammonium. Therefore, allosteric regulation of GDH plays an important role in insulin homeostasis. Finally, several compounds have been identified that block GDH-mediated insulin secretion that may be to not only find use in treating these insulin disorders but to kill tumors that require glutamine metabolism for cellular energy.

  15. 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

  16. 基于国际专利分类法的上海中药产业创新技术热点分析%Analysis on Hot Spots of Innovative Technology of Chinese Medicine Industry in Shanghai Based on The IPC Classification of Patents

    Institute of Scientific and Technical Information of China (English)

    张洋

    2015-01-01

    Objective To analysis the hot spots of innovative technology of Chinese medicine industry in Shanghai during the recent years.Methods Patent Database of State Intelletual Property Office was retrieved by IPC class numbers combined with keywords and the IPC classification of the Chinese medicine patents in Shanghai area during 2002-2013 were under statistical analysis.Results The hot spot distribution of therapeutic activity of TCM preparations:Antineoplastic is the most important activity of Chinese medicine development, followed by the activities of treatment of inadequate blood flow or cardiovascular system diseases, such as hyperglycemia, high cholesterol, and so on. The activity of treatment of the digestive tract or digestive system diseases, followed by the activities of anti infection, antiviral, antibacterial, anti-inflammatory treatment, etc. The hot spot distribution of dosage:Researches on new dosage of Chinese medicine were mainly reflected in the improvement of traditional dosage form and development of new formulations. The capsules, tablets, oral liquid, and injections were the new dosage forms under the most researches. The distribution of medical resources:Medicinal plants or animals mainly came from “angiosperm”. Medicinal animals were less than medicinal plants, which mainly belonged to insecta.ConclusionThe hot spots of innovative technology of Chinese medicine industry in Shanghai are mainly distributed in the medicine of anti-tumor, cardiocerebral vascular diseases, digestive system diseases and so on in recent years. The researches of new formulation focus on the traditional dosage form improvement and new formulations development. “Angiosperm” is the key to the development of medicinal plants.%目的:分析近年来我国上海地区中药产业创新技术研究热点。方法采用国际专利分类法(IPC)分类号结合关键词组合检索《国家知识产权局专利数据库》,对2002-2013年

  17. 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;

    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...

  18. 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...

  19. 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 ...

  20. VISUALIZATION ANALYSIS OF THEORY BASE AND RESEARCH HOT SPOTS OF DOMESTIC AND INTERNATIONAL ECOLOGICAL COMPENSATION%国内外生态补偿基础理论与研究热点的可视化分析

    Institute of Scientific and Technical Information of China (English)

    胡小飞; 傅春; 陈伏生; 廖志娟

    2012-01-01

    With the aggravation of the ecological and environmental problems faced by humanity,the ecological compensation has become a hot topic of widespread concerns amongst domestic and foreign scholars.In order to understand the advances of ecological compensation,we carries out statistical analysis about the time of its publication based on 929documents from Web of Science and the Chinese Social Science Citation Index(CSSCI) database on the subject of ecology compensation in the time period of 1998-2011,and analyzes co-citation of literary documents and keyword co-occurrence using the CiteSpace Ⅱ software.Meanwhile,the key scholarly documents are listed,and research topics of eco-compensation are briefly concluded using knowledge mapping visual tool.We found the number of ecological compensation paper presented the trend of fluctuation growth from 1998to 2011.Research on eco-compensation of carbon sinks and REDD in the context of global climate change,eco-compensation zones and evaluation on the implementation of ecological compensation,strengthening the ecological compensation standards of the wetlands,nature reserves,watersheds and other ecosystem,application of computer management software(such as GIS,SWAT,InVEST) would become the focus issues in the future research on eco-compensation.Our results also showed that the domestic scholars had made great progress in the theory of eco-compensation,and the practice researches in forests,watersheds,nature reserves and other areas were strengthened in recent years.%随着人类面临的生态环境问题加重,生态补偿已成为国内外学者广泛关注的热点问题。为清晰地了解国内外生态补偿的研究现状和未来发展,以Web of Science、中文社会科学引文索引(CSSCI)数据库中1998~2011年有关生态补偿的929篇文献为基础,应用CiteSpace Ⅱ软件分析了论文发表数量、文献共被引和关键词共现等特征,并以知识图谱可视化的方式,归纳了近年来

  1. 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...

  2. [G-protein-coupled receptors targeting: the allosteric approach].

    Science.gov (United States)

    Sebag, Julien A; Pantel, Jacques

    2012-10-01

    G-protein-coupled receptors (GPCR) are a major family of drug targets. Essentially all drugs targeting these receptors on the market compete with the endogenous ligand (agonists or antagonists) for binding the receptor. Recently, non-competitive compounds binding to distinct sites from the cognate ligand were documented in various classes of these receptors. These compounds, called allosteric modulators, generally endowed of a better selectivity are able to modulate specifically the endogenous signaling of the receptor. To better understand the promising potential of this class of GPCRs targeting compounds, this review highlights the properties of allosteric modulators, the strategies used to identify them and the challenges associated with the development of these compounds.

  3. An allosteric photoredox catalyst inspired by photosynthetic machinery.

    Science.gov (United States)

    Lifschitz, Alejo M; Young, Ryan M; Mendez-Arroyo, Jose; Stern, Charlotte L; McGuirk, C Michael; Wasielewski, Michael R; Mirkin, Chad A

    2015-03-30

    Biological photosynthetic machinery allosterically regulate light harvesting via conformational and electronic changes at the antenna protein complexes as a response to specific chemical inputs. Fundamental limitations in current approaches to regulating inorganic light-harvesting mimics prevent their use in catalysis. Here we show that a light-harvesting antenna/reaction centre mimic can be regulated by utilizing a coordination framework incorporating antenna hemilabile ligands and assembled via a high-yielding, modular approach. As in nature, allosteric regulation is afforded by coupling the conformational changes to the disruptions in the electrochemical landscape of the framework upon recognition of specific coordinating analytes. The hemilabile ligands enable switching using remarkably mild and redox-inactive inputs, allowing one to regulate the photoredox catalytic activity of the photosynthetic mimic reversibly and in situ. Thus, we demonstrate that bioinspired regulatory mechanisms can be applied to inorganic light-harvesting arrays displaying switchable catalytic properties and with potential uses in solar energy conversion and photonic devices.

  4. 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...

  5. Hot Tickets

    Science.gov (United States)

    Fox, Bette-Lee; Hoffert, Barbara; Kuzyk, Raya; McCormack, Heather; Williams, Wilda

    2008-01-01

    This article describes the highlights of this year's BookExpo America (BEA) held at the Los Angeles Convention Center. The attendees at BEA had not minded that the air was recycled, the lighting was fluorescent, and the food was bad. The first hot book sighting came courtesy of Anne Rice. Michelle Moran, author of newly published novel, "The…

  6. 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.

  7. Novel bivalent positive allosteric modulators of AMPA receptor.

    Science.gov (United States)

    Lavrov, M I; Grigor'ev, V V; Bachurin, S O; Palyulin, V A; Zefirov, N S

    2015-01-01

    A positive allosteric modulator of AMPA receptors has been designed using computer-aided molecular modeling techniques. It possessed a record high experimentally confirmed potency in the picomolar concentration range and belongs to a new type of bivalent AMPA receptor ligands containing bicyclo[3.3.1]nonane scaffold. The suggested structure could serve as a basis for further optimization and development of drugs for the treatment of neurodegenerative diseases, cognition enhancement, and improvement of memory.

  8. Inhibitory Mechanism of an Allosteric Antibody Targeting the Glucagon Receptor*

    OpenAIRE

    Mukund, Susmith; Shang, Yonglei; Clarke, Holly J.; Madjidi, Azadeh; Jacob E Corn; Kates, Lance; Kolumam, Ganesh; Chiang, Vicky; Luis, Elizabeth; Murray, Jeremy; Zhang, Yingnan; Hötzel, Isidro; Koth, Christopher M.; Allan, Bernard B.

    2013-01-01

    Elevated glucagon levels and increased hepatic glucagon receptor (GCGR) signaling contribute to hyperglycemia in type 2 diabetes. We have identified a monoclonal antibody that inhibits GCGR, a class B G-protein coupled receptor (GPCR), through a unique allosteric mechanism. Receptor inhibition is mediated by the binding of this antibody to two distinct sites that lie outside of the glucagon binding cleft. One site consists of a patch of residues that are surface-exposed on the face of the ext...

  9. Modeling the allosteric modulation of CCR5 function by Maraviroc.

    Science.gov (United States)

    Lagane, Bernard; Garcia-Perez, Javier; Kellenberger, Esther

    2013-01-01

    Maraviroc is a non-peptidic, low molecular weight CC chemokine receptor 5 (CCR5) ligand that has recently been marketed for the treatment of HIV infected individuals. This review discusses recent molecular modeling studies of CCR5 by homology to CXC chemokine receptor 4, their contribution to the understanding of the allosteric mode of action of the inhibitor and their potential for the development of future drugs with improved efficiency and preservation of CCR5 biological functions.

  10. Identification of the allosteric regulatory site of insulysin.

    Directory of Open Access Journals (Sweden)

    Nicholas Noinaj

    Full Text Available BACKGROUND: Insulin degrading enzyme (IDE is responsible for the metabolism of insulin and plays a role in clearance of the Aβ 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. PRINCIPAL FINDINGS: 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. CONCLUSIONS/SIGNIFICANCE: 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.

  11. 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

  12. 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.

  13. Zinc as Allosteric Ion Channel Modulator: Ionotropic Receptors as Metalloproteins

    Directory of Open Access Journals (Sweden)

    Francisco Andrés Peralta

    2016-07-01

    Full Text Available 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.

  14. Use of binding enthalpy to drive an allosteric transition.

    Science.gov (United States)

    Brown, Patrick H; Beckett, Dorothy

    2005-03-01

    The Escherichia coli biotin repressor is an allosteric DNA binding protein and is activated by the small molecule bio-5'-AMP. Binding of this small molecule promotes transcription repression complex assembly between the repressor and the biotin operator of the biotin biosynthetic operon. The ability of the adenylate to activate the assembly process reflects its effect on biotin repressor dimerization. Thus concomitant with small molecule binding the free energy of repressor dimerization becomes more favorable by approximately -4 kcal/mol. The structural, dynamic, and energetic changes in the repressor monomer that accompany allosteric activation are not known. In this work the thermodynamics of binding of four allosteric activators to the repressor have been characterized by isothermal titration calorimetry. While binding of two of the effectors results in relatively modest activation of the dimerization process, binding of the other two small molecules, including the physiological effector, leads to large changes in repressor dimerization energetics. Results of the calorimetric measurements indicate that strong effector binding is accompanied by an enthalpically costly transition in the protein. This transition is "paid for" by the enthalpy that would have otherwise been realized from the formation of noncovalent bonds between the ligand and repressor monomer.

  15. Inhibitory mechanism of an allosteric antibody targeting the glucagon receptor.

    Science.gov (United States)

    Mukund, Susmith; Shang, Yonglei; Clarke, Holly J; Madjidi, Azadeh; Corn, Jacob E; Kates, Lance; Kolumam, Ganesh; Chiang, Vicky; Luis, Elizabeth; Murray, Jeremy; Zhang, Yingnan; Hötzel, Isidro; Koth, Christopher M; Allan, Bernard B

    2013-12-13

    Elevated glucagon levels and increased hepatic glucagon receptor (GCGR) signaling contribute to hyperglycemia in type 2 diabetes. We have identified a monoclonal antibody that inhibits GCGR, a class B G-protein coupled receptor (GPCR), through a unique allosteric mechanism. Receptor inhibition is mediated by the binding of this antibody to two distinct sites that lie outside of the glucagon binding cleft. One site consists of a patch of residues that are surface-exposed on the face of the extracellular domain (ECD) opposite the ligand-binding cleft, whereas the second binding site consists of residues in the αA helix of the ECD. A docking model suggests that the antibody does not occlude the ligand-binding cleft. We solved the crystal structure of GCGR ECD containing a naturally occurring G40S mutation and found a shift in the register of the αA helix that prevents antibody binding. We also found that alterations in the αA helix impact the normal function of GCGR. We present a model for the allosteric inhibition of GCGR by a monoclonal antibody that may form the basis for the development of allosteric modulators for the treatment of diabetes and other class B GPCR-related diseases.

  16. 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.; Gerrard, Juliet Ann

    2011-06-24

    Background Insulin degrading enzyme (IDE) is responsible for the metabolism of insulin and plays a role in clearance of the Aβ 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. Principal Findings 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. Conclusions/Significance 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.

  17. 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.

  18. Glutamate dehydrogenase: structure, allosteric regulation, and role in insulin homeostasis.

    Science.gov (United States)

    Li, Ming; Li, Changhong; Allen, Aron; Stanley, Charles A; Smith, Thomas J

    2014-01-01

    Glutamate dehydrogenase (GDH) is a homohexameric enzyme that catalyzes the reversible oxidative deamination of L-glutamate to 2-oxoglutarate. Only in the animal kingdom is this enzyme heavily allosterically regulated by a wide array of metabolites. The major activators are ADP and leucine and inhibitors include GTP, palmitoyl CoA, and ATP. Spontaneous mutations in the GTP inhibitory site that lead to the hyperinsulinism/hyperammonemia (HHS) syndrome have shed light as to why mammalian GDH is so tightly regulated. Patients with HHS exhibit hypersecretion of insulin upon consumption of protein and concomitantly extremely high levels of ammonium in the serum. The atomic structures of four new inhibitors complexed with GDH complexes have identified three different allosteric binding sites. Using a transgenic mouse model expressing the human HHS form of GDH, at least three of these compounds blocked the dysregulated form of GDH in pancreatic tissue. EGCG from green tea prevented the hyper-response to amino acids in whole animals and improved basal serum glucose levels. The atomic structure of the ECG-GDH complex and mutagenesis studies is directing structure-based drug design using these polyphenols as a base scaffold. In addition, all of these allosteric inhibitors are elucidating the atomic mechanisms of allostery in this complex enzyme.

  19. The structure and allosteric regulation of mammalian glutamate dehydrogenase.

    Science.gov (United States)

    Li, Ming; Li, Changhong; Allen, Aron; Stanley, Charles A; Smith, Thomas J

    2012-03-15

    Glutamate dehydrogenase (GDH) is a homohexameric enzyme that catalyzes the reversible oxidative deamination of l-glutamate to 2-oxoglutarate. Only in the animal kingdom is this enzyme heavily allosterically regulated by a wide array of metabolites. The major activators are ADP and leucine, while the most important inhibitors include GTP, palmitoyl CoA, and ATP. Recently, spontaneous mutations in the GTP inhibitory site that lead to the hyperinsulinism/hyperammonemia (HHS) syndrome have shed light as to why mammalian GDH is so tightly regulated. Patients with HHS exhibit hypersecretion of insulin upon consumption of protein and concomitantly extremely high levels of ammonium in the serum. The atomic structures of four new inhibitors complexed with GDH complexes have identified three different allosteric binding sites. Using a transgenic mouse model expressing the human HHS form of GDH, at least three of these compounds were found to block the dysregulated form of GDH in pancreatic tissue. EGCG from green tea prevented the hyper-response to amino acids in whole animals and improved basal serum glucose levels. The atomic structure of the ECG-GDH complex and mutagenesis studies is directing structure-based drug design using these polyphenols as a base scaffold. In addition, all of these allosteric inhibitors are elucidating the atomic mechanisms of allostery in this complex enzyme.

  20. Analysis of hot spots of clinical psychological nursing research based on frequency analysis and co word clustering in recent 5 years%基于词频分析和共词聚类的近5年临床心理护理研究热点分析

    Institute of Scientific and Technical Information of China (English)

    赵娇; 韩世范

    2016-01-01

    [目的]揭示国际临床心理护理研究热点及临床心理护理研究现状,为我国临床心理护理研究提供参考。[方法]选取2011年—2015年PubMed数据库临床心理护理相关文献作为研究对象,利用书目共现分析系统(Bi-comb 2.0软件)对主题词进行词频分析,利用 SPSS 22.0统计软件对主题词进行系统聚类,并用双聚类软件(gCLUTO)进行双聚类分析对系统聚类结果进行调整。[结果]系统聚类得到3组聚类效果较好的主题词,双聚类有3个类团聚类较好,另外1个类团聚类效果较差。通过对高频主题词进行聚类分析,总结出近5年临床心理护理的3个主要研究热点:家庭在临床心理护理过程中越来越重要,精神、心理障碍成为临床心理护理重点关注的问题,肿瘤病人成为临床心理护理需要重点关注的群体。[结论]基于词频分析和共词聚类的近5年临床心理护理研究热点分析有助于了解目前国际临床心理护理研究热点,对我国临床心理护理研究起到一定的借鉴作用。%Objective:In order to provide a reference for clinical psychological nursing research in China,it re-vealed the hot spots of international clinical psychological nursing research and the status quo of clinical psycho-logical nursing research.Methods:The clinical psychological nursing related literatures were selected as the re-search object in PubMed database from 2011 to 2015.The bibliographic co occurrence analysis system (Bicomb 2)was used for frequency analysis of subject words.SPSS 22.0 statistical software was used to cluster the sub-j ect headings,and the double cluster software (gCLUTO)was used to adj ust the clustering results.Results:The systematic clustering had been used to get the 3 groups of subj ect headings with better clustering effect,and the double cluster had 3 better classes,and one poor cluster.Through cluster analysis of high frequency subj ect headings

  1. 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

  2. Recombination hot spot in 3.2-kb region of the Charcot-Marie Tooth type 1A repeat sequences: New tools for molecular diagnosis of hereditary neuropathy with liability to pressure palsies and of Charcot-Marie-Tooth type 1A

    Energy Technology Data Exchange (ETDEWEB)

    Lopes, J.; LeGuern, E.; Gouider, R.; Tardieu, S.; Abbas, N. [Hopital de la Salpetriere, Paris (France)] [and others

    1996-06-01

    Charcot-Marie-Tooth type 1A (CMT1A) disease and hereditary neuropathy with liability to pressure palsies (HNPP) are autosomal dominant neuropathies, associated, respectively, with duplications and deletions of the same 1.5-Mb region on 17p11.2-p12. These two rearrangements are the reciprocal products of an unequal meiotic crossover between the two chromosome 17 homologues, caused by the misalignment of the CMT1A repeat sequences (CMT1A-REPs), the homologous sequences flanking the 1.5-Mb CMT1A/HNPP monomer unit. In order to map recombination breakpoints within the CMT1A-REPs, a 12.9-kb restriction map was constructed from cloned EcoRI fragments of the proximal and distal CMT1A-REPs. Only 3 of the 17 tested restriction sites were present in the proximal CMT1A-REP but absent in the distal CMT1A-REP, indicating a high degree of homology between these sequences. The rearrangements were mapped in four regions of the CMT1A-REPs by analysis of 76 CMT1A index cases and 38 HNPP patients, who were unrelated. A hot spot of crossover breakpoints located in a 3.2-kb region accounted for three-quarters of the rearrangements, detected after EcoRI/SacI digestion, by the presence of 3.2-kb and 7.8-kb junction fragments in CMT1A and HNPP patients, respectively. These junction fragments, which can be detected on classical Southern blots, permit molecular diagnosis. Other rearrangements can also be detected by gene dosage on the same Southern blots. 25 refs., 4 figs., 2 tabs.

  3. Formation of super-resolution spot through nonlinear Fabry-Perot cavity structures: theory and simulation.

    Science.gov (United States)

    Wei, Jingsong; Wang, Rui; Yan, Hui; Fan, Yongtao

    2014-04-07

    This study explores how interference manipulation breaks through the diffraction limit and induces super-resolution nano-optical hot spots through the nonlinear Fabry-Perot cavity structure. The theoretical analytical model is established, and the numerical simulation results show that when the thickness of the nonlinear thin film inside the nonlinear Fabry-Perot cavity structure is adjusted to centain value, the constructive interference effect can be formed in the central point of the spot, which causes the nanoscale optical hot spot in the central region to be produced. The simulation results also tell us that the hot spot size is sensitive to nonlinear thin film thickness, and the accuracy is required to be up to nanometer or even subnanometer scale, which is very large challenging for thin film deposition technique, however, slightly changing the incident laser power can compensate for drawbacks of low thickness accuracy of nonlinear thin films. Taking As(2)S(3) as the nonlinear thin film, the central hot spot with a size of 40nm is obtained at suitable nonlinear thin film thickness and incident laser power. The central hot spot size is only about λ/16, which is very useful in super-high density optical recording, nanolithography, and high-resolving optical surface imaging.

  4. SpotADAPT

    DEFF Research Database (Denmark)

    Kaulakiene, Dalia; Thomsen, Christian; Pedersen, Torben Bach

    2015-01-01

    Having constantly increasing amounts of data, the analysis of it is often entrusted for a MapReduce framework. The execution of an analytical workload can be cheapened by adopting cloud computing resources, and in particular by using spot instances (cheap, fluctuating price instances) offered by ...

  5. Arc spot grouping: An entanglement of arc spot cells

    Energy Technology Data Exchange (ETDEWEB)

    Kajita, Shin, E-mail: kajita.shin@nagoya-u.jp [EcoTopia Science Institute, Nagoya University, Nagoya 464-8603 (Japan); Hwangbo, Dogyun; Ohno, Noriyasu [Graduate School of Engineering, Nagoya University, Nagoya 464-8603 (Japan); Tsventoukh, Mikhail M. [Lebedev Physical Institute, Russian Academy of Sciences, Moscow 119991 (Russian Federation); Barengolts, Sergey A. [Prokhorov General Physics Institute, Russian Academy of Sciences, Moscow 119991 (Russian Federation)

    2014-12-21

    In recent experiments, clear transitions in velocity and trail width of an arc spot initiated on nanostructured tungsten were observed on the boundary of the thick and thin nanostructured layer regions. The velocity of arc spot was significantly decreased on the thick nanostructured region. It was suggested that the grouping decreased the velocity of arc spot. In this study, we try to explain the phenomena using a simple random walk model that has properties of directionality and self-avoidance. And grouping feature was added by installing an attractive force between spot cells with dealing with multi-spots. It was revealed that an entanglement of arc spot cells decreased the spot velocity, and spot cells tend to stamp at the same location many times.

  6. Virtual Screening for Potential Allosteric Inhibitors of Cyclin-Dependent Kinase 2 from Traditional Chinese Medicine

    Directory of Open Access Journals (Sweden)

    Fang Lu

    2016-09-01

    Full Text Available Cyclin-dependent kinase 2 (CDK2, a member of Cyclin-dependent kinases (CDKs, plays an important role in cell division and DNA replication. It is regarded as a desired target to treat cancer and tumor by interrupting aberrant cell proliferation. Compared to lower subtype selectivity of CDK2 ATP-competitive inhibitors, CDK2 allosteric inhibitor with higher subtype selectivity has been used to treat CDK2-related diseases. Recently, the first crystal structure of CDK2 with allosteric inhibitor has been reported, which provides new opportunities to design pure allosteric inhibitors of CDK2. The binding site of the ATP-competition inhibitors and the allosteric inhibitors are partially overlapped in space position, so the same compound might interact with the two binding sites. Thus a novel screening strategy was essential for the discovery of pure CDK2 allosteric inhibitors. In this study, pharmacophore and molecular docking were used to screen potential CDK2 allosteric inhibitors and ATP-competition inhibitors from Traditional Chinese Medicine (TCM. In the docking result of the allosteric site, the compounds which can act with the CDK2 ATP site were discarded, and the remaining compounds were regarded as the potential pure allosteric inhibitors. Among the results, prostaglandin E1 and nordihydroguaiaretic acid (NDGA were available and their growth inhibitory effect on human HepG2 cell lines was determined by MTT assay. The two compounds could substantially inhibit the growth of HepG2 cell lines with an estimated IC50 of 41.223 μmol/L and 45.646 μmol/L. This study provides virtual screening strategy of allosteric compounds and a reliable method to discover potential pure CDK2 allosteric inhibitors from TCM. Prostaglandin E1 and NDGA could be regarded as promising candidates for CDK2 allosteric inhibitors.

  7. Sediment trapping by dams creates methane emission hot spots

    DEFF Research Database (Denmark)

    Maeck, A.; Delsontro, T.; McGinnis, Daniel F.

    2013-01-01

    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...... sedimentation in the latter is increased due to trapping by dams, revealed that the reservoir reaches are the major source of methane emissions (similar to 0.23 mmol CH4 m(-2) d(-1) vs similar to 19.7 mmol CH4 m(-2) d(-1), respectively) and that areal emission rates far exceed previous estimates for temperate...

  8. Plant cell nucleolus as a hot spot for iron.

    Science.gov (United States)

    Roschzttardtz, Hannetz; Grillet, Louis; Isaure, Marie-Pierre; Conéjéro, Geneviève; Ortega, Richard; Curie, Catherine; Mari, Stéphane

    2011-08-12

    Many central metabolic processes require iron as a cofactor and take place in specific subcellular compartments such as the mitochondrion or the chloroplast. Proper iron allocation in the different organelles is thus critical to maintain cell function and integrity. To study the dynamics of iron distribution in plant cells, we have sought to identify the different intracellular iron pools by combining three complementary imaging approaches, histochemistry, micro particle-induced x-ray emission, and synchrotron radiation micro X-ray fluorescence. Pea (Pisum sativum) embryo was used as a model in this study because of its large cell size and high iron content. Histochemical staining with ferrocyanide and diaminobenzidine (Perls/diaminobenzidine) strongly labeled a unique structure in each cell, which co-labeled with the DNA fluorescent stain DAPI, thus corresponding to the nucleus. The unexpected presence of iron in the nucleus was confirmed by elemental imaging using micro particle-induced x-ray emission. X-ray fluorescence on cryo-sectioned embryos further established that, quantitatively, the iron concentration found in the nucleus was higher than in the expected iron-rich organelles such as plastids or vacuoles. Moreover, within the nucleus, iron was particularly accumulated in a subcompartment that was identified as the nucleolus as it was shown to transiently disassemble during cell division. Taken together, our data uncover an as yet unidentified although abundant iron pool in the cell, which is located in the nuclei of healthy, actively dividing plant tissues. This result paves the way for the discovery of a novel cellular function for iron related to nucleus/nucleolus-associated processes.

  9. Project-Level Conformity and Hot-Spot Analyses

    Science.gov (United States)

    This page contains policy guidance issued by EPA and/or the U.S. Department of Transportation to assist state and local transportation and air quality agencies implement the transportation conformity program.

  10. Identifying and retargeting transcriptional hot spots in the human genome.

    Science.gov (United States)

    Cheng, Joseph K; Lewis, Amanda M; Kim, Do Soon; Dyess, Timothy; Alper, Hal S

    2016-08-01

    Mammalian cell line development requires streamlined methodologies that will reduce both the cost and time to identify candidate cell lines. Improvements in site-specific genomic editing techniques can result in flexible, predictable, and robust cell line engineering. However, an outstanding question in the field is the specific site of integration. Here, we seek to identify productive loci within the human genome that will result in stable, high expression of heterologous DNA. Using an unbiased, random integration approach and a green fluorescent reporter construct, we identify ten single-integrant, recombinant human cell lines that exhibit stable, high-level expression. From these cell lines, eight unique corresponding integration loci were identified. These loci are concentrated in non-protein coding regions or intronic regions of protein coding genes. Expression mapping of the surrounding genes reveals minimal disruption of endogenous gene expression. Finally, we demonstrate that targeted de novo integration at one of the identified loci, the 12(th) exon-intron region of the GRIK1 gene on chromosome 21, results in superior expression and stability compared to the standard, illegitimate integration approach at levels approaching 4-fold. The information identified here along with recent advances in site-specific genomic editing techniques can lead to expedited cell line development.

  11. 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.

  12. Denitrification 'hot spots' in soil following surface residue application

    Science.gov (United States)

    Kuntz, Marianne; Morley, Nicholas J.; Hallett, Paul D.; Watson, Christine; Baggs, Elizabeth M.

    2015-04-01

    The availability of organic C is an important driver for the production and reduction of the greenhouse gas nitrous oxide (N2O) during denitrification. Denitrification as a response to plant residue amendments to soil surfaces has been extensively researched. However, the nature of hotspot sites of N2O production and reduction within the soil profile, especially in relation to the location of applied residues, is unknown. In a laboratory experiment we investigated the relationship between denitrifier N2O surface fluxes and N2O production and reduction sites. Probes which equilibrate with the soil gas phase by diffusion were developed to quantify denitrification products and product ratios at 1-2 cm, 4.5-5.5 cm or 8-9 cm from the surface. 13C labelled barley straw was incorporated at rates of 0, 2 and 4 t ha-1 into the top 3 cm of soil and subsequently amended with 14NH415NO3. In a three week experiment the soil gas phase at the three depths was analysed for 15N-N2O, 15N-N2, 13C-CO2 and O2 concentrations. Additionally, cores were destructively sampled for mineral 15N as well as microbial C and dissolved C in the respective depths. 15N-N2O and CO2 surface fluxes peaked one day after N application, with residue application resulting in significantly higher 15N-N2O emission rates compared to the non-amended control. The timing of the 15N-N2O surface flux on day 1 was related to maximum 15N-N2O concentrations of 36.6 μg 15N L-1 within the pore space at 5 cm depth. Three days after fertilizer application 15N-N2O pore space concentrations had significantly increased to 193 μg 15N L-1 at 9 cm depth indicating denitrifier activity at greater depth. Denitrification below the soil surface could be explained by increased microbial activity, oxygen depletion with increasing depth and progressive downwards diffusion of fertilizer NO3-. However, C availability appeared to only affect denitrification in the surface layer in which the residue was incorporated. Our results provide insight into the nature and drivers of 'hotspots' of denitrifier activity within the soil profile. Such information can contribute to the development of sustainable management practices that lower net emissions of N2O from arable soils.

  13. Getting around the Cultural Hot Spots in Meetings.

    Science.gov (United States)

    Gardenswartz, Lee

    1993-01-01

    Suggestions are made for making meetings in a college or university setting more productive, particularly with regard to avoiding cultural misunderstanding. The cultural sources of some behaviors that may inhibit participation and effectiveness are outlined, and strategies for overcoming them are offered. (MSE)

  14. 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.

  15. 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

  16. Allosteric regulation of pyruvate kinase M2 isozyme involves a cysteine residue in the intersubunit contact.

    Science.gov (United States)

    Ikeda, Y; Noguchi, T

    1998-05-15

    Pyruvate kinase M2 isozyme mutants with amino acid substitutions in the subunit interface were prepared and characterized. The substitutions were made in the allosteric M2 isozyme by the corresponding residues of the nonallosteric M1 isozyme to identify the residue involved in the allosteric effects. The replacement of Cys-423 by Leu led to substantial loss of both homotropic and heterotropic allosteric effects while the substitutions at Phe-389, Arg-398, Ala-401, Pro-402, Thr-408, and Ile-427 did not. The altered kinetic properties of the Cys-423-substituted mutant resulted from the shift of the allosteric transition toward the active R-state since the mutant exhibits the allosteric properties in the presence of an allosteric inhibitor, L-phenylalanine. The inverse correlation between the hydrophobicity of residue 423 and the extent of stabilization of the R-state was found by analysis of mutants with un-ionizable amino acids at position 423. Furthermore, the modification of Cys-423 with methyl methanethiosulfonate led to a shift of the allosteric transition toward the R-state, probably the result of increased hydrophobicity of the residue. These results suggest that Cys-423 is involved in the allosteric regulation of the enzyme through hydrophobic interactions.

  17. 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.

  18. 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.

  19. Indole-based allosteric inhibitors of HIV-1 integrase.

    Science.gov (United States)

    Patel, Pratiq A; Kvaratskhelia, Nina; Mansour, Yara; Antwi, Janet; Feng, Lei; Koneru, Pratibha; Kobe, Mathew J; Jena, Nivedita; Shi, Guqin; Mohamed, Mosaad S; Li, Chenglong; Kessl, Jacques J; Fuchs, James R

    2016-10-01

    Employing a scaffold hopping approach, a series of allosteric HIV-1 integrase (IN) inhibitors (ALLINIs) have been synthesized based on an indole scaffold. These compounds incorporate the key elements utilized in quinoline-based ALLINIs for binding to the IN dimer interface at the principal LEDGF/p75 binding pocket. The most potent of these compounds displayed good activity in the LEDGF/p75 dependent integration assay (IC50=4.5μM) and, as predicted based on the geometry of the five- versus six-membered ring, retained activity against the A128T IN mutant that confers resistance to many quinoline-based ALLINIs.

  20. 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.

  1. El spot electoral negativo

    Directory of Open Access Journals (Sweden)

    Palma Peña-Jiménez

    2011-01-01

    Full Text Available l spot político tiene durante la campaña un objetivo final inequívoco: la consecución del voto favorable. Se dirige al cuerpo electoral a través de la televisión y de Internet, y presenta, en muchos casos, un planteamiento negativo, albergando mensajes destinados a la crítica frontal contra el adversario, más que a la exposición de propuestas propias. Este artículo se centra en el análisis del spot electoral negativo, en aquellas producciones audiovisuales construidas sin más causa que la reprobación del contrincante. Se trata de vídeos que, lejos de emplearse en difundir las potencialidades de la organización y las virtudes de su candidato –además de su programa electoral–, consumen su tiempo en descalificar al oponente mediante la transmisión de mensajes, muchas veces, ad hominem. Repasamos el planteamiento negativo del spot electoral desde su primera manifestación, que en España data de 1996, año de emisión del conocido como vídeo del dóberman, sin olvidar otros ejemplos que completan el objeto de estudio.

  2. 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.

  3. 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.

  4. Extracellular Loop 2 of the Free Fatty Acid Receptor 2 Mediates Allosterism of a Phenylacetamide Ago-Allosteric ModulatorS⃞

    Science.gov (United States)

    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.

    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 molecular mechanisms mediating the activity of 4-chloro-α-(1-methylethyl)-N-2-thiazolylbenzeneacetamide (4-CMTB), a recently described phenylacetamide allosteric agonist and allosteric modulator of endogenous ligand function at human FFA2, by combining our previous knowledge of the orthosteric binding site with targeted examination of 4-CMTB structure-activity relationships and mutagenesis and chimeric receptor generation. Here we show that 4-CMTB is a selective agonist for FFA2 that binds to a site distinct from the orthosteric site of the receptor. Ligand structure-activity relationship studies indicated that the N-thiazolyl amide is likely to provide hydrogen bond donor/acceptor interactions with the receptor. Substitution at Leu173 or the exchange of the entire extracellular loop 2 of FFA2 with that of FFA3 was sufficient to reduce or ablate, respectively, allosteric communication between the endogenous and allosteric agonists. Thus, we conclude that extracellular loop 2 of human FFA2 is required for transduction of cooperative signaling between the orthosteric and an as-yet-undefined allosteric binding site of the FFA2 receptor that is occupied by 4-CMTB. PMID:21498659

  5. 通电时间对热冲压高强钢点焊接头性能及失效方式的影响%Influence of welding time on performance and failure mode of hot stamping boron high strength steel spot-welded joints

    Institute of Scientific and Technical Information of China (English)

    陈树君; 郝素锋; 于洋; 白立来

    2013-01-01

    The characteristics of large resistivity, high peak temperature in welding thermal cycle, fast rising rate of temperature and uneven local cooling rate determined the heterogeneity in resistance spot-welded joints of hot stamping boron high strength steel, which resulted in three different failure modes of the joints. The effects of welding time on microhard-ness, bearing performance, failure modes of the resultant joints were studied, and the failure mechanism was investigated. The results show that the capacities of bearing and energy absorption between 400 ms and 600 ms of welding time were equivalent, and the nugget pull-out could not be the standard for evaluating the quality of joints. The welding defects, stress concentration and local toughness deterioration in HAZ were three main factors that affected the failure of the joints.%热冲压硼钢电阻率大、焊接热循环升温速度快、峰值温度高、局部冷却速率的不均匀,决定了点焊接头性能差别极大.点焊接头在剪切载荷作用下有界面断裂、焊核拔出和部分焊核拔出三种失效方式.以1.6mm厚的热冲压硼钢为对象,研究不同通电时间对接头显微硬度、承载性能、失效方式的影响规律,分析失效的形成原因和失效机理.结果表明,上述三种失效方式承载能力和破坏吸能力相差不大,焊核拔出并不能作为评判高强钢点焊接头质量好坏的标准.焊接缺陷、承载时的高度应力集中以及热影响区局部韧性恶化是影响热冲压高强钢点焊接头失效方式的三大主要因素.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. Allosteric Inhibition of Macrophage Migration Inhibitory Factor Revealed by Ibudilast

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Y.; Crichlow, G; Vermeire, J; Leng, L; Du, X; Hodsdon, M; Bucala, R; Cappello, M; Gross, M; et al.

    2010-01-01

    AV411 (ibudilast; 3-isobutyryl-2-isopropylpyrazolo-[1,5-a]pyridine) is an antiinflammatory drug that was initially developed for the treatment of bronchial asthma but which also has been used for cerebrovascular and ocular indications. It is a nonselective inhibitor of various phosphodiesterases (PDEs) and has varied antiinflammatory activity. More recently, AV411 has been studied as a possible therapeutic for the treatment of neuropathic pain and opioid withdrawal through its actions on glial cells. As described herein, the PDE inhibitor AV411 and its PDE-inhibition-compromised analog AV1013 inhibit the catalytic and chemotactic functions of the proinflammatory protein, macrophage migration inhibitory factor (MIF). Enzymatic analysis indicates that these compounds are noncompetitive inhibitors of the p-hydroxyphenylpyruvate (HPP) tautomerase activity of MIF and an allosteric binding site of AV411 and AV1013 is detected by NMR. The allosteric inhibition mechanism is further elucidated by X-ray crystallography based on the MIF/AV1013 binary and MIF/AV1013/HPP ternary complexes. In addition, our antibody experiments directed against MIF receptors indicate that CXCR2 is the major receptor for MIF-mediated chemotaxis of peripheral blood mononuclear cells.

  11. 我国高等医学教育慕课研究热点的共词聚类分析%Hot spots analysis for MOOC research of higher medical education in our country based on co-word clustering

    Institute of Scientific and Technical Information of China (English)

    李深情; 陈思达; 钱丽欢; 李静; 梁沛华; 方春平; 刘步平

    2016-01-01

    Objective To analyze the hot research spots of MOOC research of higher medical edu-cation in China. Methods We searched the database of China National Knowledge Infrastrucure (CNKI), VIP database of Chinese journal (VIP), Wanfang Database for published studies on MOOC research of higher medical education from 2005 to April 2015. The high frequency words were counted by an analysis program-Bibliographic Item Co-occurrence Matrix Builder (BICOMB). According to the ranking word frequency threshold formula by Donohue, we collected the high-frequency keywords. The corresponding co-word ma-trixes were constructed by Bibexcel, then the data was input into SPSS 19.0 software for hierarchical clus-tering analysis. Results Finally 2 459 articles were included. 11 177 keywords and 13 high frequency words (the number of the real selected was 24) were taken into account. The keywords “stanford” clus-tered with “education module”, “online education”, “online courses”, “distance education”, “learning pro-cess”, “self-regulated learning”, “information technology”, “classroom teaching”. The keywords “network course” clustered with “teaching design”. The keywords “online learning” clustered with itself. The key-words “challenge” clustered with “colleges and universities”. The keywords “flipped classroom” clustered with“micro-lecture”,“MOOC”,“higher education”, “library”, “teaching module”, “teaching reform”, “big data”,“open education”. The keywords“SPOC”clustered with itself. Conclusion The research of MOOC research of higher medical education in our country has formed the basic characteristics with six hot spots involving teaching design, the model of online learning, dispassion thinking, teaching reform, and develop-ment. And there are many potential areas.%目的:分析我国高等医学教育慕课研究的热点。方法检索中国学术期刊全文数据库(CNKI)、维普

  12. The mechanism of allosteric inhibition of protein tyrosine phosphatase 1B.

    Directory of Open Access Journals (Sweden)

    Shuai Li

    Full Text Available As the prototypical member of the PTP family, protein tyrosine phosphatase 1B (PTP1B is an attractive target for therapeutic interventions in type 2 diabetes. The extremely conserved catalytic site of PTP1B renders the design of selective PTP1B inhibitors intractable. Although discovered allosteric inhibitors containing a benzofuran sulfonamide scaffold offer fascinating opportunities to overcome selectivity issues, the allosteric inhibitory mechanism of PTP1B has remained elusive. Here, molecular dynamics (MD simulations, coupled with a dynamic weighted community analysis, were performed to unveil the potential allosteric signal propagation pathway from the allosteric site to the catalytic site in PTP1B. This result revealed that the allosteric inhibitor compound-3 induces a conformational rearrangement in helix α7, disrupting the triangular interaction among helix α7, helix α3, and loop11. Helix α7 then produces a force, pulling helix α3 outward, and promotes Ser190 to interact with Tyr176. As a result, the deviation of Tyr176 abrogates the hydrophobic interactions with Trp179 and leads to the downward movement of the WPD loop, which forms an H-bond between Asp181 and Glu115. The formation of this H-bond constrains the WPD loop to its open conformation and thus inactivates PTP1B. The discovery of this allosteric mechanism provides an overall view of the regulation of PTP1B, which is an important insight for the design of potent allosteric PTP1B inhibitors.

  13. Allosteric Modulation: An Alternate Approach Targeting the Cannabinoid CB1 Receptor.

    Science.gov (United States)

    Nguyen, Thuy; Li, Jun-Xu; Thomas, Brian F; Wiley, Jenny L; Kenakin, Terry P; Zhang, Yanan

    2016-11-23

    The cannabinoid CB1 receptor is a G protein coupled receptor and plays an important role in many biological processes and physiological functions. A variety of CB1 receptor agonists and antagonists, including endocannabinoids, phytocannabinoids, and synthetic cannabinoids, have been discovered or developed over the past 20 years. In 2005, it was discovered that the CB1 receptor contains allosteric site(s) that can be recognized by small molecules or allosteric modulators. A number of CB1 receptor allosteric modulators, both positive and negative, have since been reported and importantly, they display pharmacological characteristics that are distinct from those of orthosteric agonists and antagonists. Given the psychoactive effects commonly associated with CB1 receptor agonists and antagonists/inverse agonists, allosteric modulation may offer an alternate approach to attain potential therapeutic benefits while avoiding inherent side effects of orthosteric ligands. This review details the complex pharmacological profiles of these allosteric modulators, their structure-activity relationships, and efforts in elucidating binding modes and mechanisms of actions of reported CB1 allosteric modulators. The ultimate development of CB1 receptor allosteric ligands could potentially lead to improved therapies for CB1-mediated neurological disorders.

  14. Turbulent spots in hypervelocity flow

    Science.gov (United States)

    Jewell, Joseph S.; Leyva, Ivett A.; Shepherd, Joseph E.

    2017-04-01

    The turbulent spot propagation process in boundary layer flows of air, nitrogen, carbon dioxide, and air/carbon dioxide mixtures in thermochemical nonequilibrium at high enthalpy is investigated. Experiments are performed in a hypervelocity reflected shock tunnel with a 5-degree half-angle axisymmetric cone instrumented with flush-mounted fast-response coaxial thermocouples. Time-resolved and spatially demarcated heat transfer traces are used to track the propagation of turbulent bursts within the mean flow, and convection rates at approximately 91, 74, and 63% of the boundary layer edge velocity, respectively, are observed for the leading edge, peak, and trailing edge of the spots. A simple model constructed with these spot propagation parameters is used to infer spot generation rates from observed transition onset to completion distance. Spot generation rates in air and nitrogen are estimated to be approximately twice the spot generation rates in air/carbon dioxide mixtures.

  15. Cold-spotting: linking primary care and public health to create communities of solution.

    Science.gov (United States)

    Westfall, John M

    2013-01-01

    By providing enhanced primary care and social services to patients with high utilization of expensive emergency and hospital care, there is evidence that their health can improve and their costs can be lowered. This type of "hot-spotting" improves the care of individual patients. It may be that these patients live in communities with disintegrated social determinants of health, little community support, and poor access to primary care. These "cold spots" in the community may be amenable to interventions targeted at linking primary care and public health at broader community and population levels. Building local communities of solution that address the individual and population may help decrease these cold spots, thereby eliminating the hot spots as well.

  16. 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.

  17. 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, ...

  18. Enhancing NMDA Receptor Function: Recent Progress on Allosteric Modulators

    Science.gov (United States)

    2017-01-01

    The N-methyl-D-aspartate receptors (NMDARs) are subtype glutamate receptors that play important roles in excitatory neurotransmission and synaptic plasticity. Their hypo- or hyperactivation are proposed to contribute to the genesis or progression of various brain diseases, including stroke, schizophrenia, depression, and Alzheimer's disease. Past efforts in targeting NMDARs for therapeutic intervention have largely been on inhibitors of NMDARs. In light of the discovery of NMDAR hypofunction in psychiatric disorders and perhaps Alzheimer's disease, efforts in boosting NMDAR activity/functions have surged in recent years. In this review, we will focus on enhancing NMDAR functions, especially on the recent progress in the generation of subunit-selective, allosteric positive modulators (PAMs) of NMDARs. We shall also discuss the usefulness of these newly developed NMDAR-PAMs. PMID:28163934

  19. Enhancing NMDA Receptor Function: Recent Progress on Allosteric Modulators

    Directory of Open Access Journals (Sweden)

    Lulu Yao

    2017-01-01

    Full Text Available The N-methyl-D-aspartate receptors (NMDARs are subtype glutamate receptors that play important roles in excitatory neurotransmission and synaptic plasticity. Their hypo- or hyperactivation are proposed to contribute to the genesis or progression of various brain diseases, including stroke, schizophrenia, depression, and Alzheimer’s disease. Past efforts in targeting NMDARs for therapeutic intervention have largely been on inhibitors of NMDARs. In light of the discovery of NMDAR hypofunction in psychiatric disorders and perhaps Alzheimer’s disease, efforts in boosting NMDAR activity/functions have surged in recent years. In this review, we will focus on enhancing NMDAR functions, especially on the recent progress in the generation of subunit-selective, allosteric positive modulators (PAMs of NMDARs. We shall also discuss the usefulness of these newly developed NMDAR-PAMs.

  20. 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...

  1. The SPOT satellite

    Science.gov (United States)

    Fouquet, J.-P.

    1981-03-01

    The background, objectives and data products of the French SPOT remote sensing satellite system are presented. The system, which was developed starting in 1978 with the subsequent participation of Sweden and Belgium, is based on a standard multimission platform with associated ground control station and a mission-specific payload, which includes two High-Resolution Visible range instruments allowing the acquisition of stereoscopic views from different orbits. Mission objectives include the definition of future remote sensing systems, the compilation of a cartographic and resources data base, the study of species discrimination and production forecasting based on frequent access and off-nadir viewing, the compilation of a stereoscopic data base, and platform and instrument qualification, for possible applications in cartography, geology and agriculture. Standard data products will be available at three levels of preprocessing: radiometric correction only, precision processing for vertical viewing, and cartographic quality processing.

  2. Allosteric control in a metalloprotein dramatically alters function.

    Science.gov (United States)

    Baxter, Elizabeth Leigh; Zuris, John A; Wang, Charles; Vo, Phu Luong T; Axelrod, Herbert L; Cohen, Aina E; Paddock, Mark L; Nechushtai, Rachel; Onuchic, Jose N; Jennings, Patricia A

    2013-01-15

    Metalloproteins (MPs) comprise one-third of all known protein structures. This diverse set of proteins contain a plethora of unique inorganic moieties capable of performing chemistry that would otherwise be impossible using only the amino acids found in nature. Most of the well-studied MPs are generally viewed as being very rigid in structure, and it is widely thought that the properties of the metal centers are primarily determined by the small fraction of amino acids that make up the local environment. Here we examine both theoretically and experimentally whether distal regions can influence the metal center in the diabetes drug target mitoNEET. We demonstrate that a loop (L2) 20 Å away from the metal center exerts allosteric control over the cluster binding domain and regulates multiple properties of the metal center. Mutagenesis of L2 results in significant shifts in the redox potential of the [2Fe-2S] cluster and orders of magnitude effects on the rate of [2Fe-2S] cluster transfer to an apo-acceptor protein. These surprising effects occur in the absence of any structural changes. An examination of the native basin dynamics of the protein using all-atom simulations shows that twisting in L2 controls scissoring in the cluster binding domain and results in perturbations to one of the cluster-coordinating histidines. These allosteric effects are in agreement with previous folding simulations that predicted L2 could communicate with residues surrounding the metal center. Our findings suggest that long-range dynamical changes in the protein backbone can have a significant effect on the functional properties of MPs.

  3. Identification of black spots for traffic injury in road intersections dependence of injury definition

    DEFF Research Database (Denmark)

    Lund Hansen, Dennis; Lauritsen, Jens M

    2010-01-01

    accidents treated at three hospitals for a region covering roughly 0.5 mio persons were recorded routinely and subsequently geo-coded to exact location. For 8191 injured persons the traffic accident occurred in one of 2157 road intersections. In total the county holds 56.994 intersections. Hot spots were...... of intersections considered as a black spot. GIS methods must take this into consideration....

  4. Crystal structure of Sulfolobus acidocaldarius aspartate carbamoyltransferase in complex with its allosteric activator CTP.

    Science.gov (United States)

    De Vos, Dirk; Xu, Ying; Aerts, Tony; Van Petegem, Filip; Van Beeumen, Jozef J

    2008-07-18

    Aspartate carbamoyltransferase (ATCase) is a paradigm for allosteric regulation of enzyme activity. B-class ATCases display very similar homotropic allosteric behaviour, but differ extensively in their heterotropic patterns. The ATCase from the thermoacidophilic archaeon Sulfolobus acidocaldarius, for example, is strongly activated by its metabolic pathway's end product CTP, in contrast with Escherichia coli ATCase which is inhibited by CTP. To investigate the structural basis of this property, we have solved the crystal structure of the S. acidocaldarius enzyme in complex with CTP. Structure comparison reveals that effector binding does not induce similar large-scale conformational changes as observed for the E. coli ATCase. However, shifts in sedimentation coefficients upon binding of the bi-substrate analogue PALA show the existence of structurally distinct allosteric states. This suggests that the so-called "Nucleotide-Perturbation model" for explaining heterotropic allosteric behaviour, which is based on global conformational strain, is not a general mechanism of B-class ATCases.

  5. 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

    molecules often act more deeply in an allosteric mode. However, opposed to the well described molecular interaction of allosteric modulators in class C 7-transmembrane helix (7TM) receptors, the interaction in class A, to which the chemokine receptors belong, is more sparsely described. Using the CCR5...... chemokine receptor as a model system, we studied the molecular interaction and conformational interchange required for proper action of various orthosteric chemokines and allosteric small molecules, including the well known CCR5 antagonists TAK-779, SCH-C, and aplaviroc, and four novel CCR5 ago......-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...

  6. A Random Forest Model for Predicting Allosteric and Functional Sites on Proteins.

    Science.gov (United States)

    Chen, Ava S-Y; Westwood, Nicholas J; Brear, Paul; Rogers, Graeme W; Mavridis, Lazaros; Mitchell, John B O

    2016-04-01

    We created a computational method to identify allosteric sites using a machine learning method trained and tested on protein structures containing bound ligand molecules. The Random Forest machine learning approach was adopted to build our three-way predictive model. Based on descriptors collated for each ligand and binding site, the classification model allows us to assign protein cavities as allosteric, regular or orthosteric, and hence to identify allosteric sites. 43 structural descriptors per complex were derived and were used to characterize individual protein-ligand binding sites belonging to the three classes, allosteric, regular and orthosteric. We carried out a separate validation on a further unseen set of protein structures containing the ligand 2-(N-cyclohexylamino) ethane sulfonic acid (CHES).

  7. 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...

  8. 经导管消融选择性去肾交感神经治疗——未来心力衰竭治疗的热点%Catheter-based Selective Renal Artery Sympathetic Denervation-A Hot Spot of Managing Heart Failure in the Future

    Institute of Scientific and Technical Information of China (English)

    刘晓莉; 肖培林

    2013-01-01

    心力衰竭是各种心脏疾病的终末阶段.近几十年来,心力衰竭的治疗得到了一定的发展,但仍不能明显改善患者生存率,且需长期大量服药,严重影响患者生活质量.大量的研究显示:交感神经系统激活在心力衰竭的发生发展中扮演着重要角色.自上世纪40、50年代,学者们已开始进行去交感神经治疗心力衰竭的尝试,但碍于当时设备和技术的限制,治疗效果不尽人意.可喜的是,澳大利亚的权威学者近几年在美国心脏病学会/美国心脏协会心血管年会上介绍了一种安全、有效的新型去肾交感神经的方法,即经导管消融选择性去肾交感神经.该研究证实此方法可以明显降低全身交感活性.那么经导管消融去肾交感神经治疗能否成为未来心力衰竭治疗的热点呢?现将对去交感神经治疗心力衰竭的现状和进展做一综述.%Heart failure is the end-stage of serious heart disease. In recent decades, the heart failure treatment has gained some devel -opment, but still can' t significantly improve survival rate. The patients need to take a large amount of medication , and influence seriously the life quality of patients. Some study demonstrated that the somatic sympathetic nerves drive plays an important role in the development of heart failure. The sympathetic nerves denervation therapy has been researched since 1940 ~ 1950s, but the result is not satisfactory because of the restriction of poor technology. On the 2009 ACC/AHA cardiovascular annual conference , Krum MD introduced a new therapeutic method: the catheter-based renal artery ablation renal sympathetic nerves denervation . The HTN-2 Trail prove that the new method is safe and effective. The study (HTN-2) has been confirmed that the method can obviously reduce the whole body sympathetic activity . Will the catheter-based selective renal artery sympathetic denervation be a hot spot of managing heart failure in the future

  9. Detection and analysis of the hot spots of ATP7B gene mutation in the members of a family with an adult Wilson's disease%成人Wilson病一家系成员P型铜转运三磷酸腺苷酶基因突变热区的检测和分析

    Institute of Scientific and Technical Information of China (English)

    朱永豹; 黄元成; 郭威; 陈韬

    2012-01-01

    Objective To make a early gene diagnosis and analyze the mutation characteristics of ATP7B gene by detecting the hot spots of ATP7B gene mutation in Chinese family patients with Wilson's disease. Methods The genomic DNA of the family members were extracted from peripheral blood. The fragments of exon 8,1243 of ATP7B gene were amplified by polymerase chain reaction and PCR products were sequenced bidirectionally. Then we analyzed the results with BLAST software online. Results I 1N I 2( proband) , II1 and II2 have heterozygote missense mutation Arg778Leu(2333G > T) and heterozy-gote nonsense mutation Leu770Leu (2310C>G) on exon 8. I 1 、 I 2, I 3 and II1 have heterozygote mis-sense mutation Lys952Arg(2855A >G) on exon 12. All the subjects have no mutations on exon 13. Conclusion Exon 8、12,13 of ATP7B gene should be detected in the members of a family with a proband having Wilson' s disease, which will help to diagnose pre-symptomatic patients and carriers earlier.%目的 通过检测中国人Wilson病(WD)P型铜转运三磷酸腺苷酶(ATP7B)基因突变热区,对成人WD一家系成员进行早期基因诊断和突变特征分析.方法 提取该家系成员外周血基因组DNA,采用聚合酶链反应扩增ATP7B基因第8、12、13号外显子,并对扩增产物进行直接双向测序,然后应用在线BLAST软件分析.结果 Ⅰ1、Ⅰ2(先证者)、Ⅱ1和Ⅱ2第8号外显子存在Arg778Leu(2333G> T)错义杂合突变,且均伴有Leu770Leu( 2310C>G)同义杂合突变;Ⅰ1、Ⅰ 2、Ⅰ3和Ⅱ1第12号外显子存在Lys952Arg(2855A>G)错义杂合突变;所有受检者第13号外显子均未存在突变.结论 对有先证者的Wilson病家系成员应进行ATP7B基因第8、12、13号外显子检测,有助于早期发现症状前患者和携带者.

  10. 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、

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

    Science.gov (United States)

    Singer, Michael B.; Harrison, Lee R.; Donovan, Patrick M.; Blum, Joel D.; Marvin-DiPasquale, Mark C.

    2016-01-01

    The biogeochemical cycling of metals and other contaminants in river-floodplain corridors is controlled by microbial activity responding to dynamic redox conditions. Riverine flooding thus has the potential to affect speciation of redox-sensitive metals such as mercury (Hg). Therefore, inundation history over a period of decades potentially holds information on past production of bioavailable Hg. We investigate this within a Northern California river system with a legacy of landscape-scale 19th century hydraulic gold mining. We combine hydraulic modeling, Hg measurements in sediment and biota, and first-order calculations of mercury transformation to assess the potential role of river floodplains in producing monomethylmercury (MMHg), a neurotoxin which accumulates in local and migratory food webs. We identify frequently inundated floodplain areas, as well as floodplain areas inundated for long periods. We quantify the probability of MMHg production potential (MPP) associated with hydrology in each sector of the river system as a function of the spatial patterns of overbank inundation and drainage, which affect long-term redox history of contaminated sediments. Our findings identify river floodplains as periodic, temporary, yet potentially important, loci of biogeochemical transformation in which contaminants may undergo change during limited periods of the hydrologic record. We suggest that inundation is an important driver of MPP in river corridors and that the entire flow history must be analyzed retrospectively in terms of inundation magnitude and frequency in order to accurately assess biogeochemical risks, rather than merely highlighting the largest floods or low-flow periods. MMHg bioaccumulation within the aquatic food web in this system may pose a major risk to humans and waterfowl that eat migratory salmonids, which are being encouraged to come up these rivers to spawn. There is a long-term pattern of MPP under the current flow regime that is likely to be accentuated by increasingly common large floods with extended duration.

  12. 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:…

  13. 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...

  14. Divide and conquer spot noise

    NARCIS (Netherlands)

    Leeuw, W.C. de; Liere, R. van

    1997-01-01

    The design and implementation of an interactive spot noise algorithm is presented. Spot noise is a technique which utilizes texture for the visualization of flow fields. Various design tradeoffs are discussed that allow an optimal implementation on a range of high end graphical workstations. Two app

  15. Black-spot poison ivy.

    Science.gov (United States)

    Schram, Sarah E; Willey, Andrea; Lee, Peter K; Bohjanen, Kimberly A; Warshaw, Erin M

    2008-01-01

    In black-spot poison ivy dermatitis, a black lacquerlike substance forms on the skin when poison ivy resin is exposed to air. Although the Toxicodendron group of plants is estimated to be the most common cause of allergic contact dermatitis in the United States, black-spot poison ivy dermatitis is relatively rare.

  16. The therapeutic potential of allosteric ligands for free fatty acid sensitive GPCRs

    OpenAIRE

    Hudson, Brian D.; Ulven, Trond; Milligan, Graeme

    2013-01-01

    G protein coupled receptors (GPCRs) are the most historically successful therapeutic targets. Despite this success there are many important aspects of GPCR pharmacology and function that have yet to be exploited to their full therapeutic potential. One in particular that has been gaining attention in recent times is that of GPCR ligands that bind to allosteric sites on the receptor distinct from the orthosteric site of the endogenous ligand. As therapeutics, allosteric ligands possess many th...

  17. Change in allosteric network affects binding affinities of PDZ domains: analysis through perturbation response scanning.

    Directory of Open Access Journals (Sweden)

    Z Nevin Gerek

    2011-10-01

    Full Text Available The allosteric mechanism plays a key role in cellular functions of several PDZ domain proteins (PDZs and is directly linked to pharmaceutical applications; however, it is a challenge to elaborate the nature and extent of these allosteric interactions. One solution to this problem is to explore the dynamics of PDZs, which may provide insights about how intramolecular communication occurs within a single domain. Here, we develop an advancement of perturbation response scanning (PRS that couples elastic network models with linear response theory (LRT to predict key residues in allosteric transitions of the two most studied PDZs (PSD-95 PDZ3 domain and hPTP1E PDZ2 domain. With PRS, we first identify the residues that give the highest mean square fluctuation response upon perturbing the binding sites. Strikingly, we observe that the residues with the highest mean square fluctuation response agree with experimentally determined residues involved in allosteric transitions. Second, we construct the allosteric pathways by linking the residues giving the same directional response upon perturbation of the binding sites. The predicted intramolecular communication pathways reveal that PSD-95 and hPTP1E have different pathways through the dynamic coupling of different residue pairs. Moreover, our analysis provides a molecular understanding of experimentally observed hidden allostery of PSD-95. We show that removing the distal third alpha helix from the binding site alters the allosteric pathway and decreases the binding affinity. Overall, these results indicate that (i dynamics plays a key role in allosteric regulations of PDZs, (ii the local changes in the residue interactions can lead to significant changes in the dynamics of allosteric regulations, and (iii this might be the mechanism that each PDZ uses to tailor their binding specificities regulation.

  18. Volatile Abundances and the Deep Cloud Structure in Jupiter's Great Red Spot

    Science.gov (United States)

    Bjoraker, Gordon; de Pater, Imke; Wong, Michael H.; Adamkovics, Mate; Hewagama, Tilak; Hesman, Brigette

    2016-10-01

    Despite the presence of thick upper level clouds, Jupiter's Great Red Spot preserves the signature of physical conditions at much deeper levels in the troposphere. The Great Red Spot is dark at 5 microns due to thick clouds, but imaging alone does not reveal which cloud layers are responsible for attenuating this radiation. We used NIRSPEC on the Keck telescope and CSHELL on the Infrared Telescope Facility to spectrally resolve line profiles of CH3D and other molecules on Jupiter in order to derive the pressure of the line formation region in the 5-micron window. Variations in CH3D line shape with position on Jupiter are due to cloud structure rather than changes in gas mole fraction.By aligning the slit east/west on Jupiter, we sampled the Great Red Spot and a Hot Spot at the same latitude. The profile of the CH3D lines is very broad in the Hot Spot due to collisions with up to 8 bars of H2, where unit optical depth due to collision induced H2 opacity occurs. The extreme width of these CH3D features implies that Hot Spots do not have significant cloud opacity where water is expected to condense. Within the Great Red Spot, the line profiles are substantially narrower than in the Hot Spot. The best fit to the line shape of CH3D requires an opaque cloud at 5 bars, which we identify as being a water cloud. Thermal radiation from the 5-bar level is further attenuated by upper level clouds, but these colder clouds do not change the shape of the spectrum. Once we have established a cloud structure, gas mole fractions may then be retrieved. Gaseous H2O is clearly evident in the Great Red Spot, which provides independent evidence that we are sounding deep in Jupiter's atmosphere. A combination of Keck and IRTF data allows us to retrieve NH3, PH3, and gaseous H2O inside the Hot Spot and within the Great Red Spot. This technique can be applied to study the deep cloud structure anywhere on Jupiter whether or not upper level clouds are present. We will use this technique to

  19. An allosteric conduit facilitates dynamic multisite substrate recognition by the SCFCdc4 ubiquitin ligase

    Science.gov (United States)

    Csizmok, Veronika; Orlicky, Stephen; Cheng, Jing; Song, Jianhui; Bah, Alaji; Delgoshaie, Neda; Lin, Hong; Mittag, Tanja; Sicheri, Frank; Chan, Hue Sun; Tyers, Mike; Forman-Kay, Julie D.

    2017-01-01

    The ubiquitin ligase SCFCdc4 mediates phosphorylation-dependent elimination of numerous substrates by binding one or more Cdc4 phosphodegrons (CPDs). Methyl-based NMR analysis of the Cdc4 WD40 domain demonstrates that Cyclin E, Sic1 and Ash1 degrons have variable effects on the primary Cdc4WD40 binding pocket. Unexpectedly, a Sic1-derived multi-CPD substrate (pSic1) perturbs methyls around a previously documented allosteric binding site for the chemical inhibitor SCF-I2. NMR cross-saturation experiments confirm direct contact between pSic1 and the allosteric pocket. Phosphopeptide affinity measurements reveal negative allosteric communication between the primary CPD and allosteric pockets. Mathematical modelling indicates that the allosteric pocket may enhance ultrasensitivity by tethering pSic1 to Cdc4. These results suggest negative allosteric interaction between two distinct binding pockets on the Cdc4WD40 domain may facilitate dynamic exchange of multiple CPD sites to confer ultrasensitive dependence on substrate phosphorylation.

  20. Salvinorin A: allosteric interactions at the mu-opioid receptor.

    Science.gov (United States)

    Rothman, Richard B; Murphy, Daniel L; Xu, Heng; Godin, Jonathan A; Dersch, Christina M; Partilla, John S; Tidgewell, Kevin; Schmidt, Matthew; Prisinzano, Thomas E

    2007-02-01

    Salvinorin A [(2S,4aR,6aR,7R,9S,10aS,10bR)-9-(acetyloxy)-2-(3-furanyl)-dodecahydro-6a,10b-dimethyl-4,10-dioxo-2h-naphtho[2,1-c]pyran-7-carboxylic acid methyl ester] is a hallucinogenic kappa-opioid receptor agonist that lacks the usual basic nitrogen atom present in other known opioid ligands. Our first published studies indicated that Salvinorin A weakly inhibited mu-receptor binding, and subsequent experiments revealed that Salvinorin A partially inhibited mu-receptor binding. Therefore, we hypothesized that Salvinorin A allosterically modulates mu-receptor binding. To test this hypothesis, we used Chinese hamster ovary cells expressing the cloned human opioid receptor. Salvinorin A partially inhibited [(3)H]Tyr-D-Ala-Gly-N-Me-Phe-Gly-ol (DAMGO) (0.5, 2.0, and 8.0 nM) binding with E(MAX) values of 78.6, 72.1, and 45.7%, respectively, and EC(50) values of 955, 1124, and 4527 nM, respectively. Salvinorin A also partially inhibited [(3)H]diprenorphine (0.02, 0.1, and 0.5 nM) binding with E(MAX) values of 86.2, 64, and 33.6%, respectively, and EC(50) values of 1231, 866, and 3078 nM, respectively. Saturation binding studies with [(3)H]DAMGO showed that Salvinorin A (10 and 30 microM) decreased the mu-receptor B(max) and increased the K(d) in a dose-dependent nonlinear manner. Saturation binding studies with [(3)H]diprenorphine showed that Salvinorin A (10 and 40 microM) decreased the mu-receptor B(max) and increased the K(d) in a dose-dependent nonlinear manner. Similar findings were observed in rat brain with [(3)H]DAMGO. Kinetic experiments demonstrated that Salvinorin A altered the dissociation kinetics of both [(3)H]DAMGO and [(3)H]diprenorphine binding to mu receptors. Furthermore, Salvinorin A acted as an uncompetitive inhibitor of DAMGO-stimulated guanosine 5'-O-(3-[(35)S]thio)-triphosphate binding. Viewed collectively, these data support the hypothesis that Salvinorin A allosterically modulates the mu-opioid receptor.

  1. Coarse-grained molecular simulations of allosteric cooperativity

    Science.gov (United States)

    Nandigrami, Prithviraj; Portman, John J.

    2016-03-01

    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 Ca2+ 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 are treated implicitly within the grand canonical ensemble. 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 energies to the open and closed ensembles accurately describes the simulated binding thermodynamics. The simulations predict that the two domains of CaM have distinct binding affinity and cooperativity. In particular, the C-terminal domain binds Ca2+ with higher affinity and greater cooperativity than the N-terminal domain. From a structural point of view, the affinity of an individual binding loop depends sensitively on the loop's structural compatibility with the ligand in the bound ensemble, as well as the conformational flexibility of the binding site in the unbound ensemble.

  2. 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.

  3. 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.

  4. Functional impact of allosteric agonist activity of selective positive allosteric modulators of metabotropic glutamate receptor subtype 5 in regulating central nervous system function.

    Science.gov (United States)

    Noetzel, Meredith J; Rook, Jerri M; Vinson, Paige N; Cho, Hyekyung P; Days, Emily; Zhou, Y; Rodriguez, Alice L; Lavreysen, Hilde; Stauffer, Shaun R; Niswender, Colleen M; Xiang, Zixiu; Daniels, J Scott; Jones, Carrie K; Lindsley, Craig W; Weaver, C David; Conn, P Jeffrey

    2012-02-01

    Positive allosteric modulators (PAMs) of metabotropic glutamate receptor subtype 5 (mGlu(5)) have emerged as an exciting new approach for the treatment of schizophrenia and other central nervous system (CNS) disorders. Of interest, some mGlu(5) PAMs act as pure PAMs, only potentiating mGlu(5) responses to glutamate whereas others [allosteric agonists coupled with PAM activity (ago-PAMs)] potentiate responses to glutamate and have intrinsic allosteric agonist activity in mGlu(5)-expressing cell lines. All mGlu(5) PAMs previously shown to have efficacy in animal models act as ago-PAMs in cell lines, raising the possibility that allosteric agonist activity is critical for in vivo efficacy. We have now optimized novel mGlu(5) pure PAMs that are devoid of detectable agonist activity and structurally related mGlu(5) ago-PAMs that activate mGlu(5) alone in cell lines. Studies of mGlu(5) PAMs in cell lines revealed that ago-PAM activity is dependent on levels of mGlu(5) receptor expression in human embryonic kidney 293 cells, whereas PAM potency is relatively unaffected by levels of receptor expression. Furthermore, ago-PAMs have no agonist activity in the native systems tested, including cortical astrocytes and subthalamic nucleus neurons and in measures of long-term depression at the hippocampal Schaffer collateral-CA1 synapse. Finally, studies with pure PAMs and ago-PAMs chemically optimized to provide comparable CNS exposure revealed that both classes of mGlu(5) PAMs have similar efficacy in a rodent model predictive of antipsychotic activity. These data suggest that the level of receptor expression influences the ability of mGlu(5) PAMs to act as allosteric agonists in vitro and that ago-PAM activity observed in cell-based assays may not be important for in vivo efficacy.

  5. 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.

  6. Characteristic features of kynurenine aminotransferase allosterically regulated by (alpha-ketoglutarate in cooperation with kynurenine.

    Directory of Open Access Journals (Sweden)

    Ken Okada

    Full Text Available Kynurenine aminotransferase from Pyrococcus horikoshii OT3 (PhKAT, which is a homodimeric protein, catalyzes the conversion of kynurenine (KYN to kynurenic acid (KYNA. We analyzed the transaminase reaction mechanisms of this protein with pyridoxal-5'-phosphate (PLP, KYN and α-ketoglutaric acid (2OG or oxaloacetic acid (OXA. 2OG significantly inhibited KAT activities in kinetic analyses, suggesting that a KYNA biosynthesis is allosterically regulated by 2OG. Its inhibitions evidently were unlocked by KYN. 2OG and KYN functioned as an inhibitor and activator in response to changes in the concentrations of KYN and 2OG, respectively. The affinities of one subunit for PLP or 2OG were different from that of the other subunit, as confirmed by spectrophotometry and isothermal titration calorimetry, suggesting that the difference of affinities between subunits might play a role in regulations of the KAT reaction. Moreover, we identified two active and allosteric sites in the crystal structure of PhKAT-2OG complexes. The crystal structure of PhKAT in complex with four 2OGs demonstrates that two 2OGs in allosteric sites are effector molecules which inhibit the KYNA productions. Thus, the combined data lead to the conclusion that PhKAT probably is regulated by allosteric control machineries, with 2OG as the allosteric inhibitor.

  7. 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

  8. 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.

  9. Implication of spot position error on plan quality and patient safety in pencil-beam-scanning proton therapy

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Juan; Beltran, Chris J., E-mail: beltran.chris@mayo.edu; Herman, Michael G. [Division of Medical Physics, Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota 55905 (United States)

    2014-08-15

    Purpose: To quantitatively and systematically assess dosimetric effects induced by spot positioning error as a function of spot spacing (SS) on intensity-modulated proton therapy (IMPT) plan quality and to facilitate evaluation of safety tolerance limits on spot position. Methods: Spot position errors (PE) ranging from 1 to 2 mm were simulated. Simple plans were created on a water phantom, and IMPT plans were calculated on two pediatric patients with a brain tumor of 28 and 3 cc, respectively, using a commercial planning system. For the phantom, a uniform dose was delivered to targets located at different depths from 10 to 20 cm with various field sizes from 2{sup 2} to 15{sup 2} cm{sup 2}. Two nominal spot sizes, 4.0 and 6.6 mm of 1 σ in water at isocenter, were used for treatment planning. The SS ranged from 0.5 σ to 1.5 σ, which is 2–6 mm for the small spot size and 3.3–9.9 mm for the large spot size. Various perturbation scenarios of a single spot error and systematic and random multiple spot errors were studied. To quantify the dosimetric effects, percent dose error (PDE) depth profiles and the value of percent dose error at the maximum dose difference (PDE [ΔDmax]) were used for evaluation. Results: A pair of hot and cold spots was created per spot shift. PDE[ΔDmax] is found to be a complex function of PE, SS, spot size, depth, and global spot distribution that can be well defined in simple models. For volumetric targets, the PDE [ΔDmax] is not noticeably affected by the change of field size or target volume within the studied ranges. In general, reducing SS decreased the dose error. For the facility studied, given a single spot error with a PE of 1.2 mm and for both spot sizes, a SS of 1σ resulted in a 2% maximum dose error; a SS larger than 1.25 σ substantially increased the dose error and its sensitivity to PE. A similar trend was observed in multiple spot errors (both systematic and random errors). Systematic PE can lead to noticeable hot

  10. Hot-dome anemometry

    Science.gov (United States)

    Thompson, Brian E.

    1998-05-01

    Hot-dome anemometry obtains three components of flow velocity using an array of sensors, specifically five hot films in the present contribution, which are mounted around the hemispherical tip of a cylindrical support. Calibration for speed and angle resembles that of hot wires and split films except that the procedures accommodate heat transfer dominated by forced convection from the surface of a sphere rather than single or multiple cylinders. Measurements are obtained with hot domes, conventional hot wires, and impact probes in the wake of a wing to quantify measurement uncertainties.

  11. Dynamic Coupling and Allosteric Networks in the α Subunit of Heterotrimeric G Proteins*

    Science.gov (United States)

    Yao, Xin-Qiu; Malik, Rabia U.; Griggs, Nicholas W.; Skjærven, Lars; Traynor, John R.; Sivaramakrishnan, Sivaraj; Grant, Barry J.

    2016-01-01

    G protein α subunits cycle between active and inactive conformations to regulate a multitude of intracellular signaling cascades. Important structural transitions occurring during this cycle have been characterized from extensive crystallographic studies. However, the link between observed conformations and the allosteric regulation of binding events at distal sites critical for signaling through G proteins remain unclear. Here we describe molecular dynamics simulations, bioinformatics analysis, and experimental mutagenesis that identifies residues involved in mediating the allosteric coupling of receptor, nucleotide, and helical domain interfaces of Gαi. Most notably, we predict and characterize novel allosteric decoupling mutants, which display enhanced helical domain opening, increased rates of nucleotide exchange, and constitutive activity in the absence of receptor activation. Collectively, our results provide a framework for explaining how binding events and mutations can alter internal dynamic couplings critical for G protein function. PMID:26703464

  12. 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.

  13. 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

    G protein coupled receptors (GPCRs) are the most historically successful therapeutic targets. Despite this success there are many important aspects of GPCR pharmacology and function that have yet to be exploited to their full therapeutic potential. One in particular that has been gaining attention...... in recent times is that of GPCR ligands that bind to allosteric sites on the receptor distinct from the orthosteric site of the endogenous ligand. As therapeutics, allosteric ligands possess many theoretical advantages over their orthosteric counterparts, including more complex modes of action, improved...... safety, more physiologically appropriate responses, better target selectivity, and reduced likelihood of desensitisation and tachyphylaxis. Despite these advantages, the development of allosteric ligands is often difficult from a medicinal chemistry standpoint due to the more complex challenge...

  14. 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

    2015-01-20

    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.

  15. Theoretical Study on the Allosteric Regulation of an Oligomeric Protease from Pyrococcus horikoshii by Cl− Ion

    Directory of Open Access Journals (Sweden)

    Dongling Zhan

    2014-02-01

    Full Text Available The thermophilic intracellular protease (PH1704 from Pyrococcus horikoshii that functions as an oligomer (hexamer or higher forms has proteolytic activity and remarkable stability. PH1704 is classified as a member of the C56 family of peptidases. This study is the first to observe that the use of Cl− as an allosteric inhibitor causes appreciable changes in the catalytic activity of the protease. Theoretical methods were used for further study. Quantum mechanical calculations indicated the binding mode of Cl− with Arg113. A molecular dynamics simulation explained how Cl− stabilized distinct contact species and how it controls the enzyme activity. The new structural insights obtained from this study are expected to stimulate further biochemical studies on the structures and mechanisms of allosteric proteases. It is clear that the discovery of new allosteric sites of the C56 family of peptidases may generate opportunities for pharmaceutical development and increases our understanding of the basic biological processes of this peptidase family.

  16. Towards the identification of the allosteric Phe-binding site in phenylalanine hydroxylase.

    Science.gov (United States)

    Carluccio, Carla; Fraternali, Franca; Salvatore, Francesco; Fornili, Arianna; Zagari, Adriana

    2016-01-01

    The enzyme phenylalanine hydroxylase (PAH) is defective in the inherited disorder phenylketonuria. PAH, a tetrameric enzyme, is highly regulated and displays positive cooperativity for its substrate, Phe. Whether Phe binds to an allosteric site is a matter of debate, despite several studies worldwide. To address this issue, we generated a dimeric model for Phe-PAH interactions, by performing molecular docking combined with molecular dynamics simulations on human and rat wild-type sequences and also on a human G46S mutant. Our results suggest that the allosteric Phe-binding site lies at the dimeric interface between the regulatory and the catalytic domains of two adjacent subunits. The structural and dynamical features of the site were characterized in depth and described. Interestingly, our findings provide evidence for lower allosteric Phe-binding ability of the G46S mutant than the human wild-type enzyme. This also explains the disease-causing nature of this mutant.

  17. SAR studies on carboxylic acid series M(1) selective positive allosteric modulators (PAMs).

    Science.gov (United States)

    Kuduk, Scott D; Beshore, Douglas C

    2014-01-01

    There is mounting evidence from preclinical and early proof-of-concept studies suggesting that selective modulation of the M1 muscarinic receptor is efficacious in cognitive models of Alzheimer's disease (AD). A number of nonselective M1 muscarinic agonists have previously shown positive effects on cognitive function in AD patients, but were limited due to cholinergic adverse events thought to be mediated by pan activation of the M2 to M5 sub-types. Thus, there is a need to identify selective activators of the M1 receptor to evaluate their potential in cognitive disorders. One strategy to confer selectivity for M1 is the identification of allosteric agonists or positive allosteric modulators, which would target an allosteric site on the M1 receptor rather than the highly conserved orthosteric acetylcholine binding site. BQCA has been identified as a highly selective carboxylic acid M1 PAM and this review focuses on an extensive lead optimization campaign undertaken on this compound.

  18. Allosteric mechanism of pyruvate kinase from Leishmania mexicana uses a rock and lock model.

    Science.gov (United States)

    Morgan, Hugh P; McNae, Iain W; Nowicki, Matthew W; Hannaert, Véronique; Michels, Paul A M; Fothergill-Gilmore, Linda A; Walkinshaw, Malcolm D

    2010-04-23

    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 degrees rigid body rocking motion of the A- and C-domain cores in each of the four subunits. However, formation of the R-state in this way is only part of the mechanism; eight essential salt bridge locks that form across the C-C interface provide tetramer rigidity with a coupled 7-fold increase in rate. The results presented here illustrate how conformational changes coupled with effector binding correlate with loss of flexibility and increase in thermal stability providing a general mechanism for allosteric control.

  19. 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.

    2015-01-01

    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. PMID:26558346

  20. Allosteric activation of membrane-bound glutamate receptors using coordination chemistry within living cells

    Science.gov (United States)

    Kiyonaka, Shigeki; Kubota, Ryou; Michibata, Yukiko; Sakakura, Masayoshi; Takahashi, Hideo; Numata, Tomohiro; Inoue, Ryuji; Yuzaki, Michisuke; Hamachi, Itaru

    2016-10-01

    The controlled activation of proteins in living cells is an important goal in protein-design research, but to introduce an artificial activation switch into membrane proteins through rational design is a significant challenge because of the structural and functional complexity of such proteins. Here we report the allosteric activation of two types of membrane-bound neurotransmitter receptors, the ion-channel type and the G-protein-coupled glutamate receptors, using coordination chemistry in living cells. The high programmability of coordination chemistry enabled two His mutations, which act as an artificial allosteric site, to be semirationally incorporated in the vicinity of the ligand-binding pockets. Binding of Pd(2,2‧-bipyridine) at the allosteric site enabled the active conformations of the glutamate receptors to be stabilized. Using this approach, we were able to activate selectively a mutant glutamate receptor in live neurons, which initiated a subsequent signal-transduction pathway.

  1. The therapeutic promise of positive allosteric modulation of nicotinic receptors.

    Science.gov (United States)

    Uteshev, Victor V

    2014-03-15

    In the central nervous system, deficits in cholinergic neurotransmission correlate with decreased attention and cognitive impairment, while stimulation of neuronal nicotinic acetylcholine receptors improves attention, cognitive performance and neuronal resistance to injury as well as produces robust analgesic and anti-inflammatory effects. The rational basis for the therapeutic use of orthosteric agonists and positive allosteric modulators (PAMs) of nicotinic receptors arises from the finding that functional nicotinic receptors are ubiquitously expressed in neuronal and non-neuronal tissues including brain regions highly vulnerable to traumatic and ischemic types of injury (e.g., cortex and hippocampus). Moreover, functional nicotinic receptors do not vanish in age-, disease- and trauma-related neuropathologies, but their expression and/or activation levels decline in a subunit- and brain region-specific manner. Therefore, augmenting the endogenous cholinergic tone by nicotinic agents is possible and may offset neurological impairments associated with cholinergic hypofunction. Importantly, because neuronal damage elevates extracellular levels of choline (a selective agonist of α7 nicotinic acetylcholine receptors) near the site of injury, α7-PAM-based treatments may augment pathology-activated α7-dependent auto-therapies where and when they are most needed (i.e., in the penumbra, post-injury). Thus, nicotinic-PAM-based treatments are expected to augment the endogenous cholinergic tone in a spatially and temporally restricted manner creating the potential for differential efficacy and improved safety as compared to exogenous orthosteric nicotinic agonists that activate nicotinic receptors indiscriminately. In this review, I will summarize the existing trends in therapeutic applications of nicotinic PAMs.

  2. 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.

  3. Organism-adapted specificity of the allosteric regulation of pyruvate kinase in lactic acid bacteria.

    Directory of Open Access Journals (Sweden)

    Nadine Veith

    Full Text Available Pyruvate kinase (PYK is a critical allosterically regulated enzyme that links glycolysis, the primary energy metabolism, to cellular metabolism. Lactic acid bacteria rely almost exclusively on glycolysis for their energy production under anaerobic conditions, which reinforces the key role of PYK in their metabolism. These organisms are closely related, but have adapted to a huge variety of native environments. They include food-fermenting organisms, important symbionts in the human gut, and antibiotic-resistant pathogens. In contrast to the rather conserved inhibition of PYK by inorganic phosphate, the activation of PYK shows high variability in the type of activating compound between different lactic acid bacteria. System-wide comparative studies of the metabolism of lactic acid bacteria are required to understand the reasons for the diversity of these closely related microorganisms. These require knowledge of the identities of the enzyme modifiers. Here, we predict potential allosteric activators of PYKs from three lactic acid bacteria which are adapted to different native environments. We used protein structure-based molecular modeling and enzyme kinetic modeling to predict and validate potential activators of PYK. Specifically, we compared the electrostatic potential and the binding of phosphate moieties at the allosteric binding sites, and predicted potential allosteric activators by docking. We then made a kinetic model of Lactococcus lactis PYK to relate the activator predictions to the intracellular sugar-phosphate conditions in lactic acid bacteria. This strategy enabled us to predict fructose 1,6-bisphosphate as the sole activator of the Enterococcus faecalis PYK, and to predict that the PYKs from Streptococcus pyogenes and Lactobacillus plantarum show weaker specificity for their allosteric activators, while still having fructose 1,6-bisphosphate play the main activator role in vivo. These differences in the specificity of allosteric

  4. Computational modeling of allosteric communication reveals organizing principles of mutation-induced signaling in ABL and EGFR kinases.

    Directory of Open Access Journals (Sweden)

    Anshuman Dixit

    2011-10-01

    Full Text Available The emerging structural information about allosteric kinase complexes and the growing number of allosteric inhibitors call for a systematic strategy to delineate and classify mechanisms of allosteric regulation and long-range communication that control kinase activity. In this work, we have investigated mechanistic aspects of long-range communications in ABL and EGFR kinases based on the results of multiscale simulations of regulatory complexes and computational modeling of signal propagation in proteins. These approaches have been systematically employed to elucidate organizing molecular principles of allosteric signaling in the ABL and EGFR multi-domain regulatory complexes and analyze allosteric signatures of the gate-keeper cancer mutations. We have presented evidence that mechanisms of allosteric activation may have universally evolved in the ABL and EGFR regulatory complexes as a product of a functional cross-talk between the organizing αF-helix and conformationally adaptive αI-helix and αC-helix. These structural elements form a dynamic network of efficiently communicated clusters that may control the long-range interdomain coupling and allosteric activation. The results of this study have unveiled a unifying effect of the gate-keeper cancer mutations as catalysts of kinase activation, leading to the enhanced long-range communication among allosterically coupled segments and stabilization of the active kinase form. The results of this study can reconcile recent experimental studies of allosteric inhibition and long-range cooperativity between binding sites in protein kinases. The presented study offers a novel molecular insight into mechanistic aspects of allosteric kinase signaling and provides a quantitative picture of activation mechanisms in protein kinases at the atomic level.

  5. Biased signaling of lipids and allosteric actions of synthetic molecules for GPR119

    DEFF Research Database (Denmark)

    Hassing, Helle A; Fares, Suzan; Larsen, Olav;

    2016-01-01

    for 2h with the 2-MAG-lipase inhibitor JZL84 doubled the constitutive activity, indicating that endogenous lipids contribute to the apparent constitutive activity. Finally, besides being an agonist, AR231453 acted as a positive allosteric modulator of OEA and increased its potency by 54-fold at 100nM AR......231453. Our studies uncovering broad and biased signaling, masked constitutive activity by endogenous MAGs, and ago-allosteric properties of synthetic ligands may explain why many GPR119 drug-discovery programs have failed so far....

  6. 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.

  7. Laser reflection spot as a pattern in a diamond coating – a microscopic study

    Directory of Open Access Journals (Sweden)

    GORDANA S. RISTIĆ

    2009-07-01

    Full Text Available Diamond coatings were deposited by the synchronous and coupled action of a hot filament CVD method and a pulsed CO2 laser in spectro-absorbing and spectro-non-absorbing diamond precursor atmospheres. The obtained coatings were structured/patterned, i.e., they were comprised of uncovered, bare locations. An extra effect observed only in the spectro-active diamond precursor atmosphere was the creation of another laser spot in the coating – a reflection spot. In order to establish the practical usability of the latter one, extensive microscopic investigations were performed with consideration of the morphology changes in the spot of the direct laser beam. Normal incidence SEM images of this spot showed a smooth surface, without any pulse radiation damage. AFM imaging revealed the actual surface condition and gave precise data on the surface characteristics.

  8. 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.

  9. An Allosteric Receptor by Simultaneous "Casting" and "Molding" in a Dynamic Combinatorial Library

    NARCIS (Netherlands)

    Li, Jianwei; Nowak, Piotr; Otto, Sijbren

    2015-01-01

    Allosteric synthetic receptors are difficult to access by design. Herein we report a dynamic combinatorial strategy towards such systems based on the simultaneous use of two different templates. Through a process of simultaneous casting (the assembly of a library member around a template) and moldin

  10. Allosteric modulation of ATP-gated P2X receptor channels

    Science.gov (United States)

    Coddou, Claudio; Stojilkovic, Stanko S.; Huidobro-Toro, J. Pablo

    2013-01-01

    Seven mammalian purinergic receptor subunits, denoted P2X1 to P2X7, and several spliced forms of these subunits have been cloned. When heterologously expressed, these cDNAs encode ATP-gated non-selective cation channels organized as trimers. All activated receptors produce cell depolarization and promote Ca2+ influx through their pores and indirectly by activating voltage-gated calcium channels. However, the biophysical and pharmacological properties of these receptors differ considerably, and the majority of these subunits are also capable of forming heterotrimers with other members of the P2X receptor family, which confers further different properties. These channels have three ATP binding domains, presumably located between neighboring subunits, and occupancy of at least two binding sites is needed for their activation. In addition to the orthosteric binding sites for ATP, these receptors have additional allosteric sites that modulate the agonist action at receptors, including sites for trace metals, protons, neurosteroids, reactive oxygen species and phosphoinositides. The allosteric regulation of P2X receptors is frequently receptor-specific and could be a useful tool to identify P2X members in native tissues and their roles in signaling. The focus of this review is on common and receptor-specific allosteric modulation of P2X receptors and the molecular base accounting for allosteric binding sites. PMID:21639805

  11. Structural basis for cAMP-mediated allosteric control of the catabolite activator protein.

    Science.gov (United States)

    Popovych, Nataliya; Tzeng, Shiou-Ru; Tonelli, Marco; Ebright, Richard H; Kalodimos, Charalampos G

    2009-04-28

    The cAMP-mediated allosteric transition in the catabolite activator protein (CAP; also known as the cAMP receptor protein, CRP) is a textbook example of modulation of DNA-binding activity by small-molecule binding. Here we report the structure of CAP in the absence of cAMP, which, together with structures of CAP in the presence of cAMP, defines atomic details of the cAMP-mediated allosteric transition. The structural changes, and their relationship to cAMP binding and DNA binding, are remarkably clear and simple. Binding of cAMP results in a coil-to-helix transition that extends the coiled-coil dimerization interface of CAP by 3 turns of helix and concomitantly causes rotation, by approximately 60 degrees , and translation, by approximately 7 A, of the DNA-binding domains (DBDs) of CAP, positioning the recognition helices in the DBDs in the correct orientation to interact with DNA. The allosteric transition is stabilized further by expulsion of an aromatic residue from the cAMP-binding pocket upon cAMP binding. The results define the structural mechanisms that underlie allosteric control of this prototypic transcriptional regulatory factor and provide an illustrative example of how effector-mediated structural changes can control the activity of regulatory proteins.

  12. Anti-inflammatory lipoxin A4 is an endogenous allosteric enhancer of CB1 cannabinoid receptor.

    Science.gov (United States)

    Pamplona, Fabricio A; Ferreira, Juliano; Menezes de Lima, Octávio; Duarte, Filipe Silveira; Bento, Allisson Freire; Forner, Stefânia; Villarinho, Jardel G; Bellocchio, Luigi; Bellochio, Luigi; Wotjak, Carsten T; Lerner, Raissa; Monory, Krisztina; Lutz, Beat; Canetti, Claudio; Matias, Isabelle; Calixto, João Batista; Marsicano, Giovanni; Guimarães, Marilia Z P; Takahashi, Reinaldo N

    2012-12-18

    Allosteric modulation of G-protein-coupled receptors represents a key goal of current pharmacology. In particular, endogenous allosteric modulators might represent important targets of interventions aimed at maximizing therapeutic efficacy and reducing side effects of drugs. Here we show that the anti-inflammatory lipid lipoxin A(4) is an endogenous allosteric enhancer of the CB(1) cannabinoid receptor. Lipoxin A(4) was detected in brain tissues, did not compete for the orthosteric binding site of the CB(1) receptor (vs. (3)H-SR141716A), and did not alter endocannabinoid metabolism (as opposed to URB597 and MAFP), but it enhanced affinity of anandamide at the CB1 receptor, thereby potentiating the effects of this endocannabinoid both in vitro and in vivo. In addition, lipoxin A(4) displayed a CB(1) receptor-dependent protective effect against β-amyloid (1-40)-induced spatial memory impairment in mice. The discovery of lipoxins as a class of endogenous allosteric modulators of CB(1) receptors may foster the therapeutic exploitation of the endocannabinoid system, in particular for the treatment of neurodegenerative disorders.

  13. 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.

  14. Elucidation of a four-site allosteric network in fibroblast growth factor receptor tyrosine kinases

    Science.gov (United States)

    Chen, Huaibin; Marsiglia, William M; Cho, Min-Kyu; Huang, Zhifeng; Deng, Jingjing; Blais, Steven P; Gai, Weiming; Bhattacharya, Shibani; Neubert, Thomas A; Traaseth, Nathaniel J; Mohammadi, Moosa

    2017-01-01

    Receptor tyrosine kinase (RTK) signaling is tightly regulated by protein allostery within the intracellular tyrosine kinase domains. Yet the molecular determinants of allosteric connectivity in tyrosine kinase domain are incompletely understood. By means of structural (X-ray and NMR) and functional characterization of pathogenic gain-of-function mutations affecting the FGF receptor (FGFR) tyrosine kinase domain, we elucidated a long-distance allosteric network composed of four interconnected sites termed the ‘molecular brake’, ‘DFG latch’, ‘A-loop plug’, and ‘αC tether’. The first three sites repress the kinase from adopting an active conformation, whereas the αC tether promotes the active conformation. The skewed design of this four-site allosteric network imposes tight autoinhibition and accounts for the incomplete mimicry of the activated conformation by pathogenic mutations targeting a single site. Based on the structural similarity shared among RTKs, we propose that this allosteric model for FGFR kinases is applicable to other RTKs. DOI: http://dx.doi.org/10.7554/eLife.21137.001 PMID:28166054

  15. Molecular basis of positive allosteric modulation of GluN2B NMDA receptors by polyamines.

    Science.gov (United States)

    Mony, Laetitia; Zhu, Shujia; Carvalho, Stéphanie; Paoletti, Pierre

    2011-06-17

    NMDA receptors (NMDARs) form glutamate-gated ion channels that have central roles in neuronal communication and plasticity throughout the brain. Dysfunctions of NMDARs are involved in several central nervous system disorders, including stroke, chronic pain and schizophrenia. One hallmark of NMDARs is that their activity can be allosterically regulated by a variety of extracellular small ligands. While much has been learned recently regarding allosteric inhibition of NMDARs, the structural determinants underlying positive allosteric modulation of these receptors remain poorly defined. Here, we show that polyamines, naturally occurring polycations that selectively enhance NMDARs containing the GluN2B subunit, bind at a dimer interface between GluN1 and GluN2B subunit N-terminal domains (NTDs). Polyamines act by shielding negative charges present on GluN1 and GluN2B NTD lower lobes, allowing their close apposition, an effect that in turn prevents NTD clamshell closure. Our work reveals the mechanistic basis for positive allosteric modulation of NMDARs. It provides the first example of an intersubunit binding site in this class of receptors, a discovery that holds promise for future drug interventions.

  16. 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.

    2016-08-01

    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.

  17. Identification of the Allosteric Site for Phenylalanine in Rat Phenylalanine Hydroxylase.

    Science.gov (United States)

    Zhang, Shengnan; Fitzpatrick, Paul F

    2016-04-01

    Liver phenylalanine hydroxylase (PheH) is an allosteric enzyme that requires activation by phenylalanine for full activity. The location of the allosteric site for phenylalanine has not been established. NMR spectroscopy of the isolated regulatory domain (RDPheH(25-117) is the regulatory domain of PheH lacking residues 1-24) of the rat enzyme in the presence of phenylalanine is consistent with formation of a side-by-side ACT dimer. Six residues in RDPheH(25-117) were identified as being in the phenylalanine-binding site on the basis of intermolecular NOEs between unlabeled phenylalanine and isotopically labeled protein. The location of these residues is consistent with two allosteric sites per dimer, with each site containing residues from both monomers. Site-specific variants of five of the residues (E44Q, A47G, L48V, L62V, and H64N) decreased the affinity of RDPheH(25-117) for phenylalanine based on the ability to stabilize the dimer. Incorporation of the A47G, L48V, and H64N mutations into the intact protein increased the concentration of phenylalanine required for activation. The results identify the location of the allosteric site as the interface of the regulatory domain dimer formed in activated PheH.

  18. Allosteric modulators affect the internalization of human adenosine A1 receptors.

    NARCIS (Netherlands)

    Klaasse, E.C.; Hout, G. van den; Roerink, S.F.; Grip, W.J. de; IJzerman, A.P.; Beukers, M.W.

    2005-01-01

    To study the effect of allosteric modulators on the internalization of human adenosine A(1) receptors, the receptor was equipped with a C-terminal yellow fluorescent protein tag. The introduction of this tag did not affect the radioligand binding properties of the receptor. CHO cells stably expressi

  19. Thermodynamic Analysis of Allosteric and Chelate Cooperativity in Di- and Trivalent Ammonium/Crown-Ether Pseudorotaxanes.

    Science.gov (United States)

    Nowosinski, Karol; von Krbek, Larissa K S; Traulsen, Nora L; Schalley, Christoph A

    2015-10-16

    A detailed thermodynamic analysis of the axle-wheel binding in di- and trivalent secondary ammonium/[24]crown-8 pseudorotaxanes is presented. Isothermal titration calorimetry (ITC) data and double mutant cycle analyses reveal an interesting interplay of positive as well as negative allosteric and positive chelate cooperativity thus providing profound insight into the effects governing multivalent binding in these pseudorotaxanes.

  20. Allosteric Regulation of the Rotational Speed in a Light-Driven Molecular Motor

    NARCIS (Netherlands)

    Faulkner, Adele; van Leeuwen, Thomas; Feringa, Ben L; Wezenberg, Sander J

    2016-01-01

    The rotational speed of an overcrowded alkene-based molecular rotary motor, having an integrated 4,5-diazafluorenyl coordination motif, can be regulated allosterically via the binding of metal ions. DFT calculations have been used to predict the relative speed of rotation of three different (i.e. zi

  1. 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

    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...

  2. Nootropic alpha7 nicotinic receptor allosteric modulator derived from GABAA receptor modulators.

    Science.gov (United States)

    Ng, Herman J; Whittemore, Edward R; Tran, Minhtam B; Hogenkamp, Derk J; Broide, Ron S; Johnstone, Timothy B; Zheng, Lijun; Stevens, Karen E; Gee, Kelvin W

    2007-05-08

    Activation of brain alpha7 nicotinic acetylcholine receptors (alpha7 nAChRs) has broad therapeutic potential in CNS diseases related to cognitive dysfunction, including Alzheimer's disease and schizophrenia. In contrast to direct agonist activation, positive allosteric modulation of alpha7 nAChRs would deliver the clinically validated benefits of allosterism to these indications. We have generated a selective alpha7 nAChR-positive allosteric modulator (PAM) from a library of GABAA receptor PAMs. Compound 6 (N-(4-chlorophenyl)-alpha-[[(4-chloro-phenyl)amino]methylene]-3-methyl-5-isoxazoleacet-amide) evokes robust positive modulation of agonist-induced currents at alpha7 nAChRs, while preserving the rapid native characteristics of desensitization, and has little to no efficacy at other ligand-gated ion channels. In rodent models, it corrects sensory-gating deficits and improves working memory, effects consistent with cognitive enhancement. Compound 6 represents a chemotype for allosteric activation of alpha7 nAChRs, with therapeutic potential in CNS diseases with cognitive dysfunction.

  3. Allosteric Inhibition via R-state Destabilization in ATP Sulfurylase from Penicillium chrysogenum

    Energy Technology Data Exchange (ETDEWEB)

    MacRae, I. J.

    2002-01-01

    The structure of the cooperative hexameric enzyme ATP sulfurylase from Penicillium chrysogenum bound to its allosteric inhibitor, 3'-phosphoadenosine-5'-phosphosulfate (PAPS), was determined to 2.6 {angstrom} resolution. This structure represents the low substrate-affinity T-state conformation of the enzyme. Comparison with the high substrate-affinity R-state structure reveals that a large rotational rearrangement of domains occurs as a result of the R-to-T transition. The rearrangement is accompanied by the 17 {angstrom} movement of a 10-residue loop out of the active site region, resulting in an open, product release-like structure of the catalytic domain. Binding of PAPS is proposed to induce the allosteric transition by destabilizing an R-state-specific salt linkage between Asp 111 in an N-terminal domain of one subunit and Arg 515 in the allosteric domain of a trans-triad subunit. Disrupting this salt linkage by site-directed mutagenesis induces cooperative inhibition behavior in the absence of an allosteric effector, confirming the role of these two residues.

  4. 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

  5. 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 ...

  6. Improvements on analytic modelling of stellar sp