Science.gov

Sample records for large regional domain

  1. Testing a time-domain regional momtent tensor inversion program for large worldwide earthquakes

    NASA Astrophysics Data System (ADS)

    Richter, G.; Hoffmann, M.; Hanka, W.; Saul, J.

    2009-04-01

    After gaining an accurate source location and magnitude estimate of large earthquakes the direction of plate movement is the next important information for reliable hazard assessment. For this purpose rapid moment tensor inversions are necessary. In this study the time-domain moment tensor inversion program by Dreger (2001) is tested. This program for regional moment tensor solutions is applied to seismic data from regional stations of the GEOFON net and international cooperating partner networks (InaTEWS, IRIS, GEOFON Extended Virtual Network) to obtain moment tensor solutions for large earthquakes worldwide. The motivation of the study is to have rapid information on the plate motion direction for the verification of tsunami generation hazard by earthquakes. A special interest lies on the application in the Indonesian archipelago to integrate the program in German-Indonesian Tsunami Early Warning System (GITEWS). Performing the inversion on a single CPU of a normal PC most solutions are achieved within half an hour after origin time. The program starts automatically for large earthquakes detected by the seismic analysis tool SeisComP3 (Hanka et al, 2008). The data from seismic stations in the distance range up to 2000 km are selected, prepared and quality controlled. First the program searches the best automatic solution by varying the source depth. Testing different stations combinations for the inversion enables to identify the stability of the solution. For further optimization of the solution the interactive selection of available stations is facilitated. The results of over 200 events are compared to centroid moment tensor solutions from the Global CMT-Project, from MedNet/INGV and NEID to evaluate the accuracy of the results. The inversion in the time-domain is sensitive to uncertainties in the velocity model and in the source location. These resolution limits are visible in the waveform fits. Another reason for misfits are strong structural inhomogeneities

  2. Large-scale electromagnetic modeling for multiple inhomogeneous domains

    NASA Astrophysics Data System (ADS)

    Zhdanov, M. S.; Endo, M.; Cuma, M.

    2008-12-01

    We develop a new formulation of the integral equation (IE) method for three-dimensional (3D) electromagnetic (EM) field computation in large-scale models with multiple inhomogeneous domains. This problem arises in many practical applications including modeling the EM fields within the complex geoelectrical structures in geophysical exploration. In geophysical applications, it is difficult to describe an earth structure using a horizontally layered background conductivity model, which is required for the efficient implementation of the conventional IE approach. As a result, a large domain of interest with anomalous conductivity distribution needs to be discretized, which complicates the computations. The new method allows us to consider multiple inhomogeneous domains, where the conductivity distribution is different from that of the background, and to use independent discretizations for different domains. This reduces dramatically the computational resources required for large-scale modeling. In addition, by using this method, we can analyze the response of each domain separately without an inappropriate use of the superposition principle for the EM field calculations. The method was carefully tested for modeling the marine controlled-source electromagnetic (MCSEM) fields for complex geoelectrical structures with multiple inhomogeneous domains, such as a seafloor with rough bathymetry, salt domes, and reservoirs. We have also used this technique to investigate the return induction effects from regional geoelectrical structures, e.g., seafloor bathymetry and salt domes, which can distort the EM response from the geophysical exploration target.

  3. Multiple domains of the large fibroblast proteoglycan, versican.

    PubMed Central

    Zimmermann, D R; Ruoslahti, E

    1989-01-01

    The primary structure of a large chondroitin sulfate proteoglycan expressed by human fibroblasts has been determined. Overlapping cDNA clones code for the entire 2389 amino acid long core protein and the 20-residue signal peptide. The sequence predicts a potential hyaluronic acid-binding domain in the amino-terminal portion. This domain contains sequences virtually identical to partial peptide sequences from a glial hyaluronate-binding protein. Putative glycosaminoglycan attachment sites are located in the middle of the protein. The carboxy-terminal portion includes two epidermal growth factor (EGF)-like repeats, a lectin-like sequence and a complement regulatory protein-like domain. The same set of binding elements has also been identified in a new class of cell adhesion molecules. Amino- and carboxy-terminal portions of the fibroblast core protein are closely related to the core protein of a large chondroitin sulfate proteoglycan of chondrosarcoma cells. However, the glycosaminoglycan attachment regions in the middle of the core proteins are different and only the fibroblast core protein contains EGF-like repeats. Based on the similarities of its domains with various binding elements of other proteins, we suggest that the large fibroblast proteoglycan, herein referred to as versican, may function in cell recognition, possibly by connecting extracellular matrix components and cell surface glycoproteins. Images PMID:2583089

  4. Atomic structure of the sweet-tasting protein thaumatin I at pH 8.0 reveals the large disulfide-rich region in domain II to be sensitive to a pH change

    SciTech Connect

    Masuda, Tetsuya; Ohta, Keisuke; Mikami, Bunzo; Kitabatake, Naofumi; Tani, Fumito

    2012-03-02

    Highlights: Black-Right-Pointing-Pointer Structure of a recombinant thaumatin at pH 8.0 determined at a resolution of 1.0 A. Black-Right-Pointing-Pointer Substantial fluctuations of a loop in domain II was found in the structure at pH 8.0. Black-Right-Pointing-Pointer B-factors for Lys137, Lys163, and Lys187 were significantly affected by pH change. Black-Right-Pointing-Pointer An increase in mobility might play an important role in the heat-induced aggregation. -- Abstract: Thaumatin, an intensely sweet-tasting plant protein, elicits a sweet taste at 50 nM. Although the sweetness remains when thaumatin is heated at 80 Degree-Sign C for 4 h under acid conditions, it rapidly declines when heating at a pH above 6.5. To clarify the structural difference at high pH, the atomic structure of a recombinant thaumatin I at pH 8.0 was determined at a resolution of 1.0 A. Comparison to the crystal structure of thaumatin at pH 7.3 and 7.0 revealed the root-mean square deviation value of a C{alpha} atom to be substantially greater in the large disulfide-rich region of domain II, especially residues 154-164, suggesting that a loop region in domain II to be affected by solvent conditions. Furthermore, B-factors of Lys137, Lys163, and Lys187 were significantly affected by pH change, suggesting that a striking increase in the mobility of these lysine residues, which could facilitate a reaction with a free sulfhydryl residue produced via the {beta}-elimination of disulfide bonds by heating at a pH above 7.0. The increase in mobility of lysine residues as well as a loop region in domain II might play an important role in the heat-induced aggregation of thaumatin above pH 7.0.

  5. Identification of a large bent DNA domain and binding sites for serum response factor adjacent to the NFI repeat cluster and enhancer region in the major IE94 promoter from simian cytomegalovirus.

    PubMed Central

    Chang, Y N; Jeang, K T; Chiou, C J; Chan, Y J; Pizzorno, M; Hayward, G S

    1993-01-01

    The major immediate-early (MIE) transactivator proteins of cytomegaloviruses (CMV) play a pivotal role in the initiation of virus-host cell interactions. Therefore, cis- and trans-acting factors influencing the expression of these proteins through their upstream promoter-enhancer regions are important determinants of the outcome of virus infection. S1 nuclease analysis and in vitro transcription assays with the MIE (or IE94) transcription unit of simian CMV (SCMV) (Colburn) revealed a single prominent mRNA start site associated with a canonical TATATAA motif. This initiator region lies adjacent to a 2,400-bp 5'-upstream noncoding sequence that encompasses a newly identified 1,000-bp (A+T)-rich segment containing intrinsically bent DNA (domain C), together with the previously described proximal cyclic AMP response element locus (domain A) and a tandemly repeated nuclear factor I binding site cluster (domain B). Deleted MIE reporter gene constructions containing domain A sequences only yield up to 4-fold stronger basal expression in Vero cells than the intact simian virus 40 promoter-enhancer region, and sequences from position -405 to -69 (ENH-A1) added to a minimal heterologous promoter produced a 50-fold increase of basal expression in an enhancer assay. In contrast, neither the nuclear factor I cluster nor the bent DNA region possessed basal enhancer properties and neither significantly modulated the basal activity of the ENH-A1 segment. A second segment of domain A from position -580 to -450 was also found to possess basal enhancer activity in various cell types. This ENH-A2 region contains three copies of a repeated element that includes the 10-bp palindromic sequence CCATATATGG, which resembles the core motif of serum response elements and proved to bind specifically to the cellular nuclear protein serum response transcription factor. Reporter gene constructions containing four tandem copies of these elements displayed up to 13-fold increased basal enhancer

  6. Domain nesting for multi-scale large eddy simulation

    NASA Astrophysics Data System (ADS)

    Fuka, Vladimir; Xie, Zheng-Tong

    2016-04-01

    The need to simulate city scale areas (O(10 km)) with high resolution within street canyons in certain areas of interests necessitates different grid resolutions in different part of the simulated area. General purpose computational fluid dynamics codes typically employ unstructured refined grids while mesoscale meteorological models more often employ nesting of computational domains. ELMM is a large eddy simulation model for the atmospheric boundary layer. It employs orthogonal uniform grids and for this reason domain nesting was chosen as the approach for simulations in multiple scales. Domains are implemented as sets of MPI processes which communicate with each other as in a normal non-nested run, but also with processes from another (outer/inner) domain. It should stressed that the duration of solution of time-steps in the outer and in the inner domain must be synchronized, so that the processes do not have to wait for the completion of their boundary conditions. This can achieved by assigning an appropriate number of CPUs to each domain, and to gain high efficiency. When nesting is applied for large eddy simulation, the inner domain receives inflow boundary conditions which lack turbulent motions not represented by the outer grid. ELMM remedies this by optional adding of turbulent fluctuations to the inflow using the efficient method of Xie and Castro (2008). The spatial scale of these fluctuations is in the subgrid-scale of the outer grid and their intensity will be estimated from the subgrid turbulent kinetic energy in the outer grid.

  7. Interannual Behavior of Large Regional Dust Storms

    NASA Astrophysics Data System (ADS)

    Kass, D. M.; Kleinboehl, A.; McCleese, D. J.; Schofield, J. T.; Smith, M. D.

    2014-07-01

    We examine large regional dust storms in MCS and TES retrieved temperature profiles. There is significant repeatability with three regional storms (A, B and C) each Mars year. Each type of storm is distinct seasonally and in its behavior.

  8. Time-Domain Filtering for Spatial Large-Eddy Simulation

    NASA Technical Reports Server (NTRS)

    Pruett, C. David

    1997-01-01

    An approach to large-eddy simulation (LES) is developed whose subgrid-scale model incorporates filtering in the time domain, in contrast to conventional approaches, which exploit spatial filtering. The method is demonstrated in the simulation of a heated, compressible, axisymmetric jet, and results are compared with those obtained from fully resolved direct numerical simulation. The present approach was, in fact, motivated by the jet-flow problem and the desire to manipulate the flow by localized (point) sources for the purposes of noise suppression. Time-domain filtering appears to be more consistent with the modeling of point sources; moreover, time-domain filtering may resolve some fundamental inconsistencies associated with conventional space-filtered LES approaches.

  9. Calcineurin B-like domains in the large regulatory alpha/beta subunits of phosphorylase kinase.

    PubMed

    Carrière, Cathelène; Mornon, Jean-Paul; Venien-Bryan, Catherine; Boisset, Nicolas; Callebaut, Isabelle

    2008-06-01

    Phosphorylase kinase (PhK) is a large hexadecameric complex that catalyzes the phosphorylation and activation of glycogen phosphorylase (GP). It consists in four copies each of a catalytic subunit (gamma) and three regulatory subunits (alpha beta delta). Delta corresponds to endogenous calmodulin, whereas little is known on the molecular architecture of the large alpha and beta subunits, which probably arose from gene duplication. Here, using sensitive methods of sequence analysis, we show that the C-terminal domain (named domain D) of these alpha and beta subunits can be significantly related to calcineurin B-like (CBL) proteins. CBL are members of the EF-hand family that are involved in the regulation of plant-specific kinases of the CIPK/PKS family, and relieve autoinhibition of their target kinases by binding to their regulatory region. The relationship highlighted here suggests that PhK alpha and/or beta domain D may be involved in a similar regulation mechanism, a hypothesis which is supported by the experimental observation of a direct interaction between domain D of PhKalpha and the regulatory region of the Gamma subunit. This finding, together the identification of significant similarities of domain D with the preceding domain C, may help to understand the molecular mechanism by which PhK alpha and/or beta domain D might regulate PhK activity. PMID:18320589

  10. DomHR: Accurately Identifying Domain Boundaries in Proteins Using a Hinge Region Strategy

    PubMed Central

    Zhang, Xiao-yan; Lu, Long-jian; Song, Qi; Yang, Qian-qian; Li, Da-peng; Sun, Jiang-ming; Li, Tong-hua; Cong, Pei-sheng

    2013-01-01

    Motivation The precise prediction of protein domains, which are the structural, functional and evolutionary units of proteins, has been a research focus in recent years. Although many methods have been presented for predicting protein domains and boundaries, the accuracy of predictions could be improved. Results In this study we present a novel approach, DomHR, which is an accurate predictor of protein domain boundaries based on a creative hinge region strategy. A hinge region was defined as a segment of amino acids that covers part of a domain region and a boundary region. We developed a strategy to construct profiles of domain-hinge-boundary (DHB) features generated by sequence-domain/hinge/boundary alignment against a database of known domain structures. The DHB features had three elements: normalized domain, hinge, and boundary probabilities. The DHB features were used as input to identify domain boundaries in a sequence. DomHR used a nonredundant dataset as the training set, the DHB and predicted shape string as features, and a conditional random field as the classification algorithm. In predicted hinge regions, a residue was determined to be a domain or a boundary according to a decision threshold. After decision thresholds were optimized, DomHR was evaluated by cross-validation, large-scale prediction, independent test and CASP (Critical Assessment of Techniques for Protein Structure Prediction) tests. All results confirmed that DomHR outperformed other well-established, publicly available domain boundary predictors for prediction accuracy. Availability The DomHR is available at http://cal.tongji.edu.cn/domain/. PMID:23593247

  11. Large-scale regions of antimatter

    SciTech Connect

    Grobov, A. V. Rubin, S. G.

    2015-07-15

    Amodified mechanism of the formation of large-scale antimatter regions is proposed. Antimatter appears owing to fluctuations of a complex scalar field that carries a baryon charge in the inflation era.

  12. The Smad3 linker region contains a transcriptional activation domain.

    PubMed

    Wang, Guannan; Long, Jianyin; Matsuura, Isao; He, Dongming; Liu, Fang

    2005-02-15

    Transforming growth factor-beta (TGF-beta)/Smads regulate a wide variety of biological responses through transcriptional regulation of target genes. Smad3 plays a key role in TGF-beta/Smad-mediated transcriptional responses. Here, we show that the proline-rich linker region of Smad3 contains a transcriptional activation domain. When the linker region is fused to a heterologous DNA-binding domain, it activates transcription. We show that the linker region physically interacts with p300. The adenovirus E1a protein, which binds to p300, inhibits the transcriptional activity of the linker region, and overexpression of p300 can rescue the linker-mediated transcriptional activation. In contrast, an adenovirus E1a mutant, which cannot bind to p300, does not inhibit the linker-mediated transcription. The native Smad3 protein lacking the linker region is unable to mediate TGF-beta transcriptional activation responses, although it can be phosphorylated by the TGF-beta receptor at the C-terminal tail and has a significantly increased ability to form a heteromeric complex with Smad4. We show further that the linker region and the C-terminal domain of Smad3 synergize for transcriptional activation in the presence of TGF-beta. Thus our findings uncover an important function of the Smad3 linker region in Smad-mediated transcriptional control. PMID:15588252

  13. Magnetization process and domain structure in the near-surface region of conventional amorphous wires

    NASA Astrophysics Data System (ADS)

    Chiriac, Horia; Lostun, Mihaela; Óvári, Tibor-Adrian

    2011-04-01

    Results on the study of the surface magnetization process and domain structure by magneto-optical Kerr effect in conventional rapidly quenched amorphous magnetic wires are reported. Domain imaging confirms the presence of a bamboo-type structure in the near-surface region of these materials. Surface Kerr loops show that the overall magnetization in the near-surface region has a large axial component, besides the circular one. A bistable magnetic behavior on the axial direction has been emphasized. A circularly applied field leads to the disappearance of axial magnetic bistability. Kerr loops are changed by the presence of 180° interdomain walls in the near-surface region.

  14. Chapter 4: Regional magnetic domains of the Circum-Arctic: A framework for geodynamic interpretation

    USGS Publications Warehouse

    Saltus, R.W.; Miller, E.L.; Gaina, C.; Brown, P.J.

    2011-01-01

    We identify and discuss 57 magnetic anomaly pattern domains spanning the Circum-Arctic. The domains are based on analysis of a new Circum-Arctic data compilation. The magnetic anomaly patterns can be broadly related to general geodynamic classification of the crust into stable, deformed (magnetic and nonmagnetic), deep magnetic high, oceanic and large igneous province domains. We compare the magnetic domains with topography/bathymetry, regional geology, regional free air gravity anomalies and estimates of the relative magnetic 'thickness' of the crust. Most of the domains and their geodynamic classification assignments are consistent with their topographic/bathymetric and geological expression. A few of the domains are potentially controversial. For example, the extent of the Iceland Faroe large igneous province as identified by magnetic anomalies may disagree with other definitions for this feature. Also the lack of definitive magnetic expression of oceanic crust in Baffin Bay, the Norwegian-Greenland Sea and the Amerasian Basin is at odds with some previous interpretations. The magnetic domains and their boundaries provide clues for tectonic models and boundaries within this poorly understood portion of the globe. ?? 2011 The Geological Society of London.

  15. Frequency domain identification for robust large space structure control design

    NASA Technical Reports Server (NTRS)

    Yam, Y.; Bayard, D. S.; Scheid, R. E.

    1991-01-01

    A methodology is demonstrated for frequency domain identification of large space structures which systematically transforms experimental raw data into a form required for synthesizing H(infinity) controllers using modern robust control design software (e.g., Matlab Toolboxes). A unique feature of this approach is that the additive uncertainty is characterized to a specified statistic confidence rather than with hard bounds. In this study, the difference in robust performance is minimal between the two levels of confidence. In general cases, the present methodology provides a tool for performance/confidence level tradeoff studies. For simplicity, the additive uncertainty on a frequency grid is considered and the interpolation error in between grid points is neglected.

  16. A domain decomposition algorithm for solving large elliptic problems

    SciTech Connect

    Nolan, M.P.

    1991-01-01

    AN algorithm which efficiently solves large systems of equations arising from the discretization of a single second-order elliptic partial differential equation is discussed. The global domain is partitioned into not necessarily disjoint subdomains which are traversed using the Schwarz Alternating Procedure. On each subdomain the multigrid method is used to advance the solution. The algorithm has the potential to decrease solution time when data is stored across multiple levels of a memory hierarchy. Results are presented for a virtual memory, vector multiprocessor architecture. A study of choice of inner iteration procedure and subdomain overlap is presented for a model problem, solved with two and four subdomains, sequentially and in parallel. Microtasking multiprocessing results are reported for multigrid on the Alliant FX-8 vector-multiprocessor. A convergence proof for a class of matrix splittings for the two-dimensional Helmholtz equation is given. 70 refs., 3 figs., 20 tabs.

  17. Oriented Liquid Crystalline Polymer Semiconductor Films with Large Ordered Domains.

    PubMed

    Xue, Xiao; Chandler, George; Zhang, Xinran; Kline, R Joseph; Fei, Zhuping; Heeney, Martin; Diemer, Peter J; Jurchescu, Oana D; O'Connor, Brendan T

    2015-12-01

    Large strains are applied to liquid crystalline poly(2,5-bis(3-tetradecylthiophen-2yl)thieno(3,2-b)thiophene) (pBTTT) films when held at elevated temperatures resulting in in-plane polymer alignment. We find that the polymer backbone aligns significantly in the direction of strain, and that the films maintain large quasi-domains similar to that found in spun-cast films on hydrophobic surfaces, highlighted by dark-field transmission electron microscopy imaging. The highly strained films also have nanoscale holes consistent with dewetting. Charge transport in the films is then characterized in a transistor configuration, where the field effect mobility is shown to increase in the direction of polymer backbone alignment, and decrease in the transverse direction. The highest saturated field-effect mobility was found to be 1.67 cm(2) V(-1) s(-1), representing one of the highest reported mobilities for this material system. The morphology of the oriented films demonstrated here contrast significantly with previous demonstrations of oriented pBTTT films that form a ribbon-like morphology, opening up opportunities to explore how differences in molecular packing features of oriented films impact charge transport. Results highlight the role of grain boundaries, differences in charge transport along the polymer backbone and π-stacking direction, and structural features that impact the field dependence of charge transport. PMID:26552721

  18. Large Ensembles of Regional Climate Projections

    NASA Astrophysics Data System (ADS)

    Massey, Neil; Allen, Myles; Hall, Jim

    2016-04-01

    Projections of regional climate change have great utility for impact assessment at a local scale. The CORDEX climate projection framework presents a method of providing these regional projections by driving a regional climate model (RCM) with output from CMIP5 climate projection runs of global climate models (GCM). This produces an ensemble of regional climate projections, sampling the model uncertainty, the forcing uncertainty and the uncertainty of the response of the climate system to the increase in greenhouse gas (GHG) concentrations. Using the weather@home project to compute large ensembles of RCMs via volunteer distributed computing presents another method of generating projections of climate variables and also allows the sampling of the uncertainty due to internal variability. weather@home runs both a RCM and GCM on volunteer's home computers, with the free-running GCM driving the boundaries of the RCM. The GCM is an atmosphere only model and requires forcing at the lower boundary with sea-surface temperature (SST) and sea-ice concentration (SIC) data. By constructing SST and SIC projections, using projections of GHG and other atmospheric gases, and running the weather@home RCM and GCM with these forcings, large ensembles of projections of climate variables at regional scales can be made. To construct the SSTs and SICs, a statistical model is built to represent the response of SST and SIC to increases in GHG concentrations in the CMIP5 ensemble, for both the RCP4.5 and RCP8.5 scenarios. This statistical model uses empirical orthogonal functions (EOFs) to represent the change in the long term trend of SSTs in the CMIP5 projections. A multivariate distribution of the leading principle components (PC) is produced using a copula and sampled to produce a timeseries of PCs which are recombined with the EOFs to generate a timeseries of SSTs, with internal variability added from observations. Hence, a large ensemble of SST projections is generated, with each SST

  19. Assessing the effect of domain size over the Caribbean region using the PRECIS regional climate model

    NASA Astrophysics Data System (ADS)

    Centella-Artola, Abel; Taylor, Michael A.; Bezanilla-Morlot, Arnoldo; Martinez-Castro, Daniel; Campbell, Jayaka D.; Stephenson, Tannecia S.; Vichot, Alejandro

    2015-04-01

    This study investigates the sensitivity of the one-way nested PRECIS regional climate model (RCM) to domain size for the Caribbean region. Simulated regional rainfall patterns from experiments using three domains with horizontal resolution of 50 km are compared with ERA reanalysis and observed datasets to determine if there is an optimal RCM configuration with respect to domain size and the ability to reproduce important observed climate features in the Caribbean. Results are presented for the early wet season (May-July) and late wet season (August-October). There is a relative insensitivity to domain size for simulating some important features of the regional circulation and key rainfall characteristics e.g. the Caribbean low level jet and the mid summer drought (MSD). The downscaled precipitation has a systematically negative precipitation bias, even when the domain was extended to the African coast to better represent circulation associated with easterly waves and tropical cyclones. The implications for optimizing modelling efforts within resource-limited regions like the Caribbean are discussed especially in the context of the region's participation in global initiatives such as CORDEX.

  20. Large conformational fluctuations of the multi-domain xylanase Z of Clostridium thermocellum.

    PubMed

    Różycki, Bartosz; Cieplak, Marek; Czjzek, Mirjam

    2015-07-01

    The cellulosome is a multi-enzyme machinery which efficiently degrades plant cell-wall polysaccharides. The multiple domains of the cellulosome complexes are often tethered to one another by intrinsically disordered regions. The properties and functions of these disordered linkers are unknown to a large extent. In this work, we study the conformational variability of one component of the cellulosome - the multi-domain xylanase Z (XynZ) of Clostridium thermocellum. We use a coarse-grained protein model to efficiently simulate conformations of the enzyme. Our simulation results are in excellent agreement with data from small angle X-ray scattering experiments, which validates the simulation outcome. Both in the presence and absence of the cohesin domain, the XynZ enzyme appears to be flexible in the sense that it takes various compact and extended conformations. The physical interactions between the individual domains are rather weak and transient, and the XynZ enzyme is held together mainly by the flexible linkers connecting the domains. The end-to-end distance distributions for the flexible linkers can be rationalized by the excluded volume effect. Taken together, our results provide a detailed picture of the conformational ensemble of the XynZ enzyme in solution. PMID:26008791

  1. Robust All-quad Meshing of Domains with Connected Regions

    PubMed Central

    Rushdi, Ahmad A.; Mitchell, Scott A.; Bajaj, Chandrajit L.; Ebeida, Mohamed S.

    2016-01-01

    In this paper, we present a new algorithm for all-quad meshing of non-convex domains, with connected regions. Our method starts with a strongly balanced quadtree. In contrast to snapping the grid points onto the geometric boundaries, we move points a slight distance away from the common boundaries. Then we intersect the moved grid with the geometry. This allows us to avoid creating any flat quads, and we are able to handle two-sided regions and more complex topologies than prior methods. The algorithm is provably correct, robust, and cleanup-free; meaning we have angle and edge length bounds, without the use of any pillowing, swapping, or smoothing. Thus, our simple algorithm is also more predictable than prior art.

  2. Atypical regions in large genomic DNA sequences

    SciTech Connect

    Scherer, S. |; McPeek, M.S.; Speed, T.P.

    1994-07-19

    Large genomic DNA sequences contain regions with distinctive patterns of sequence organization. The authors describe a method using logarithms of probabilities based on seventh-order Markov chains to rapidly identify genomic sequences that do not resemble models of genome organization built from compilations of octanucleotide usage. Data bases have been constructed from Escherichia coli and Saccharomyces cerevisiae DNA sequences of >1000 nt and human sequences of >10,000 nt. Atypical genes and clusters of genes have been located in bacteriophage, yeast, and primate DNA sequences. The authors consider criteria for statistical significance of the results, offer possible explanations for the observed variation in genome organization, and give additional applications of these methods in DNA sequence analysis.

  3. ENDLESS: An extended nonperiodic domain large-eddy simulation approach for scalar plumes

    NASA Astrophysics Data System (ADS)

    Chen, Bicheng; Yang, Di; Meneveau, Charles; Chamecki, Marcelo

    2016-05-01

    Large-eddy simulation (LES) has proven to be a valuable tool for high-fidelity modeling of environmental and geophysical turbulent flows. An important application of LES is to study the transport of effluents (e.g. oils from a subsea blowout) in the ocean mixed layer (OML). Oil plumes being transported in the OML experience the action of shear-generated turbulence, Langmuir circulations, Ekman transport and submesoscale quasi-geostrophic eddies. To resolve such turbulent processes, grid sizes of a few meters are desirable while horizontal domain sizes of LES are typically restricted from hundreds of meters to a few kilometers, for LES to remain practically affordable. Yet transported oil plumes evolve to large scales extending to tens or even hundreds of kilometers. In this study, the Extended Nonperiodic Domain LES for Scalar transport (ENDLESS) is proposed as a multi-scale approach to tackle this challenge while being computationally affordable. The basic idea is to simulate the shear turbulence and Langmuir circulations on a small horizontal domain with periodic boundary conditions while the resulting transport velocity field is replicated periodically following adaptively the large-scale plume as it evolves spatially towards much larger scales. This approach also permits the superposition of larger-scale quasi two-dimensional flow motions on the oil advection, allowing for coupling with regional circulation models. A validation case and two sample applications to oil plume evolution in the OML are presented in order to demonstrate key features and computational speedup associated with the ENDLESS method.

  4. Binding to retinoblastoma pocket domain does not alter the inter-domain flexibility of the J domain of SV40 large T antigen.

    PubMed

    Williams, Christina K; Vaithiyalingam, Sivaraja; Hammel, Michal; Pipas, James; Chazin, Walter J

    2012-02-15

    Simian Virus 40 uses the large T antigen (Tag) to bind and inactivate retinoblastoma tumor suppressor proteins (Rb), which can result in cellular transformation. Tag is a modular protein with four domains connected by flexible linkers. The N-terminal J domain of Tag is necessary for Rb inactivation. Binding of Rb is mediated by an LXCXE consensus motif immediately C-terminal to the J domain. Nuclear magnetic resonance (NMR) and small angle X-ray scattering (SAXS) were used to study the structural dynamics and interaction of Rb with the LXCXE motif, the J domain and a construct (N(260)) extending from the J domain through the origin binding domain (OBD). NMR and SAXS data revealed substantial flexibility between the domains in N(260). Binding of pRb to a construct containing the LXCXE motif and the J domain revealed weak interactions between pRb and the J domain. Analysis of the complex of pRb and N(260) indicated that the OBD is not involved and retains its dynamic independence from the remainder of Tag. These results support a 'chaperone' model in which the J domain of Tag changes its orientation as it acts upon different protein complexes. PMID:22227098

  5. Packed domain Rayleigh-Sommerfeld wavefield propagation for large targets.

    PubMed

    Wuttig, Andreas; Kanka, Mario; Kreuzer, Hans Jürgen; Riesenberg, Rainer

    2010-12-20

    For applications in the domain of digital holographic microscopy, we present a fast algorithm to propagate scalar wave fields from a small source area to an extended, parallel target area of coarser sampling pitch, using the first Rayleigh-Sommerfeld diffraction formula. Our algorithm can take full advantage of the fast Fourier transform by decomposing the convolution kernel of the propagation into several convolution kernel patches. Using partial overlapping of the patches together with a soft blending function, the Fourier spectrum of these patches can be reduced to a low number of significant components, which can be stored in a compact sparse array structure. This allows for rapid evaluation of the partial convolution results by skipping over negligible components through the Fourier domain pointwise multiplication and direct mapping of the remaining multiplication results into a Fourier domain representation of the coarsly sampled target patch. The algorithm has been verified experimentally at a numerical aperture of 0.62, not showing any significant resolution limitations. PMID:21196980

  6. Large domains of apparent delayed replication timing associated with triplet repeat expansion at FRAXA and FRAXE.

    PubMed Central

    Subramanian, P. S.; Nelson, D. L.; Chinault, A. C.

    1996-01-01

    Trinucleotide repeat expansions have been implicated in the causation of a number of neurodegenerative disorders. In the case of fragile X syndrome, full expansion of the FMR1 repeat element (CGG)n has also been correlated with replication timing delay of the locus and proximal flanking sequences in male lymphoblasts. To define more extensively this altered region of DNA replication, as well as to extend these studies to female cells containing premutant and mutant alleles, study of the replication timing properties of a >2-Mb zone in the FRAXA region (Xq27.3-q28) was undertaken by using a FISH technique. In this assay, relative times of replication of specific loci are inferred from the ratios of singlet and doublet hybridization signals in interphase nuclei. In all individuals with a full expansion of the trinucleotide repeat, a large (1-1.2-Mb) region of delayed timing was observed; the apparent timing of the earlier-replicating allele in female cells in this region was intermediate between normal and affected alleles in males, which is in accordance with expectations of a mixed population of cells resulting from random X inactivation. In addition, expansion of the nearby FRAXE locus also was found to correlate with replication timing delay, although the extent of the altered region was somewhat less. Trinucleotide repeat expansion thus may be acting in the Xq27.3-q28 region to alter long-range chromatin structure that could influence transcription of gene sequences within the affected domain. PMID:8755928

  7. Single SQUID frequency-domain multiplexer for large bolometer arrays

    SciTech Connect

    Yoon, Jongsoo; Clarke, John; Gildemeister, J.M.; Lee, Adrian T.; Myers, M.J.; Skidmore, J.T.; Richards, P.L.; Spieler, H.G.

    2001-08-20

    We describe the development of a frequency-domain superconducting quantum interference device (SQUID) multiplexer which monitors a row of low-temperature sensors simultaneously with a single SQUID. Each sensor is ac biased with a unique frequency and all the sensor currents are added in a superconducting summing loop. A single SQUID measures the current in the summing loop, and the individual signals are lock-in detected after the room temperature SQUID electronics. The current in the summing loop is nulled by feedback to eliminate direct crosstalk. We have built an eight-channel prototype and demonstrated channel separation and signal recovery.

  8. Packaging of a large capacity magnetic bubble domain spacecraft recorder

    NASA Technical Reports Server (NTRS)

    Becker, F. J.; Stermer, R. L.

    1977-01-01

    A Solid State Spacecraft Data Recorder (SSDR), based on bubble domain technology, having a storage capacity of 10 to the 8th power bits, was designed and is being tested. The recorder consists of two memory modules each having 32 cells, each cell containing sixteen 100 kilobit serial bubble memory chips. The memory modules are interconnected to a Drive and Control Unit (DCU) module containing four microprocessors, 500 integrated circuits, a RAM core memory and two PROM's. The two memory modules and DCU are housed in individual machined aluminum frames, are stacked in brick fashion and through bolted to a base plate assembly which also houses the power supply.

  9. Unassisted translocation of large polypeptide domains across phospholipid bilayers

    PubMed Central

    Brambillasca, Silvia; Yabal, Monica; Makarow, Marja; Borgese, Nica

    2006-01-01

    Although transmembrane proteins generally require membrane-embedded machinery for integration, a few can insert spontaneously into liposomes. Previously, we established that the tail-anchored (TA) protein cytochrome b(5) (b5) can posttranslationally translocate 28 residues downstream to its transmembrane domain (TMD) across protein-free bilayers (Brambillasca, S., M. Yabal, P. Soffientini, S. Stefanovic, M. Makarow, R.S. Hegde, and N. Borgese. 2005. EMBO J. 24:2533–2542). In the present study, we investigated the limits of this unassisted translocation and report that surprisingly long (85 residues) domains of different sequence and charge placed downstream of b5's TMD can posttranslationally translocate into mammalian microsomes and liposomes at nanomolar nucleotide concentrations. Furthermore, integration of these constructs occurred in vivo in translocon-defective yeast strains. Unassisted translocation was not unique to b5 but was also observed for another TA protein (protein tyrosine phosphatase 1B) whose TMD, like the one of b5, is only moderately hydrophobic. In contrast, more hydrophobic TMDs, like synaptobrevin's, were incapable of supporting unassisted integration, possibly because of their tendency to aggregate in aqueous solution. Our data resolve long-standing discrepancies on TA protein insertion and are relevant to membrane evolution, biogenesis, and physiology. PMID:17130291

  10. Fabrication of Large Domain YBa2Cu3O(x) for Magnetic Suspension Applications

    NASA Technical Reports Server (NTRS)

    Sengupta, S.; Corpus, J.; Gaines, J. R., Jr.; Todt, V. R.; Zhang, X.; Miller, D. J.

    1996-01-01

    Large domain YBa2Cu3O(x) levitators have been fabricated using a seeded melt processing technique. Depending upon the seed, either a single or five domained sample can be obtained. The grain boundaries separating each domains in the five domain levitator are found to be 90 degrees. Similar levitation forces can be observed for single and five domained samples. After thermal cycling, however, a small decrease in the levitation force of the five domain levitator was observed as a function of thermal cycles while nearly no change in force was observed in the single domain levitator. Finally, it is shown that both, single and five domain YBCO, behave similarly as a function of sample thickness.

  11. Frequency domain identification experiment on a large flexible structure

    NASA Technical Reports Server (NTRS)

    Bayard, D. S.; Hadaegh, F. Y.; Yam, Y.; Scheid, R. E.; Mettler, E.; Milman, M. H.

    1989-01-01

    Recent experiences in the field of flexible structure control in space have indicated a need for on-orbit system identification to support robust control redesign to avoid in-flight instabilities and maintain high spacecraft performance. The authors highlight an automated frequency domain system identification methodology recently developed to fill this need. The methodology supports (1) the estimation of system quantities useful for robust control analysis and design, (2) experiment design tailored to performing system identification in a typically constrained on-orbit environment, and (3) the automation of operations to reduce human-in-the-loop requirements. A basic overview of the methodology is presented first, followed by an experimental verification of the approach performed on the JPL/AFAL testbed facility.

  12. The Invariance Hypothesis Implies Domain-Specific Regions in Visual Cortex

    PubMed Central

    Leibo, Joel Z.; Liao, Qianli; Anselmi, Fabio; Poggio, Tomaso

    2015-01-01

    Is visual cortex made up of general-purpose information processing machinery, or does it consist of a collection of specialized modules? If prior knowledge, acquired from learning a set of objects is only transferable to new objects that share properties with the old, then the recognition system’s optimal organization must be one containing specialized modules for different object classes. Our analysis starts from a premise we call the invariance hypothesis: that the computational goal of the ventral stream is to compute an invariant-to-transformations and discriminative signature for recognition. The key condition enabling approximate transfer of invariance without sacrificing discriminability turns out to be that the learned and novel objects transform similarly. This implies that the optimal recognition system must contain subsystems trained only with data from similarly-transforming objects and suggests a novel interpretation of domain-specific regions like the fusiform face area (FFA). Furthermore, we can define an index of transformation-compatibility, computable from videos, that can be combined with information about the statistics of natural vision to yield predictions for which object categories ought to have domain-specific regions in agreement with the available data. The result is a unifying account linking the large literature on view-based recognition with the wealth of experimental evidence concerning domain-specific regions. PMID:26496457

  13. Automated frequency domain system identification of a large space structure

    NASA Technical Reports Server (NTRS)

    Yam, Y.; Bayard, D. S.; Hadaegh, F. Y.; Mettler, E.; Milman, M. H.

    1989-01-01

    This paper presents the development and experimental results of an automated on-orbit system identification method for large flexible spacecraft that yields estimated quantities to support on-line design and tuning of robust high performance control systems. The procedure consists of applying an input to the plant, obtaining an output, and then conducting nonparametric identification to yield the spectral estimate of the system transfer function. A parametric model is determined by curve fitting the spectral estimate to a rational transfer function. The identification method has been demonstrated experimentally on the Large Spacecraft Control Laboratory in JPL.

  14. Sonic hedgehog lineage in the mouse hypothalamus: from progenitor domains to hypothalamic regions

    PubMed Central

    2012-01-01

    Background The hypothalamus is a brain region with essential functions for homeostasis and energy metabolism, and alterations of its development can contribute to pathological conditions in the adult, like hypertension, diabetes or obesity. However, due to the anatomical complexity of the hypothalamus, its development is not well understood. Sonic hedgehog (Shh) is a key developmental regulator gene expressed in a dynamic pattern in hypothalamic progenitor cells. To obtain insight into hypothalamic organization, we used genetic inducible fate mapping (GIFM) to map the lineages derived from Shh-expressing progenitor domains onto the four rostrocaudally arranged hypothalamic regions: preoptic, anterior, tuberal and mammillary. Results Shh-expressing progenitors labeled at an early stage (before embryonic day (E)9.5) contribute neurons and astrocytes to a large caudal area including the mammillary and posterior tuberal regions as well as tanycytes (specialized median eminence glia). Progenitors labeled at later stages (after E9.5) give rise to neurons and astrocytes of the entire tuberal region and in particular the ventromedial nucleus, but not to cells in the mammillary region and median eminence. At this stage, an additional Shh-expressing domain appears in the preoptic area and contributes mostly astrocytes to the hypothalamus. Shh-expressing progenitors do not contribute to the anterior region at any stage. Finally, we show a gradual shift from neurogenesis to gliogenesis, so that progenitors expressing Shh after E12.5 generate almost exclusively hypothalamic astrocytes. Conclusions We define a fate map of the hypothalamus, based on the dynamic expression of Shh in the hypothalamic progenitor zones. We provide evidence that the large neurogenic Shh-expressing progenitor domains of the ventral diencephalon are continuous with those of the midbrain. We demonstrate that the four classical transverse zones of the hypothalamus have clearly defined progenitor domains

  15. Large Silicon Abundance in Photodissociation Regions

    NASA Astrophysics Data System (ADS)

    Okada, Yoko; Onaka, Takashi; Nakagawa, Takao; Shibai, Hiroshi; Tomono, Daigo; Yui, Yukari Y.

    2006-03-01

    We have made one-dimensional raster scan observations of the ρ Oph and σ Sco star-forming regions with two spectrometers (SWS and LWS) on board the ISO. In the ρ Oph region, [Si II] 35 μm, [O I] 63 μm, 146 μm, [C II] 158 μm, and the H2 pure rotational transition lines S(0) to S(3) are detected, and the photodissociation region (PDR) properties are derived as the radiation field scaled by the solar neighborhood value G0~30-500, the gas density n~250-2500 cm-3, and the surface temperature T~100-400 K. The ratio of [Si II] 35 μm to [O I] 146 μm indicates that silicon of 10%-20% of the solar abundance must be in the gaseous form in the PDR, suggesting that efficient dust destruction is ongoing even in the PDR and that a fraction of the silicon atoms may be contained in volatile forms in dust grains. The [O I] 63 μm and [C II] 158 μm emissions are too weak relative to [O I] 146 μm to be accounted for by standard PDR models. We propose a simple model, in which overlapping PDR clouds along the line of sight absorb the [O I] 63 μm and [C II] 158 μm emissions, and show that the proposed model reproduces the observed line intensities fairly well. In the σ Sco region, we have detected three fine-structure lines, [O I] 63 μm, [N II] 122 μm, and [C II] 158 μm, and derived that 30%-80% of the [C II] emission comes from the ionized gas. The upper limit of the [Si II] 35 μm is compatible with the solar abundance relative to nitrogen, and no useful constraint on the gaseous Si is obtained for the σ Sco region. Based on observations with ISO, an ESA project with instruments funded by ESA member states (especially the PI countries: France, Germany, the Netherlands, and the UK) and with the participation of ISAS and NASA.

  16. Spectral multi-domain for large-scale fluid dynamic simulations

    NASA Technical Reports Server (NTRS)

    Streett, C. L.; Macaraeg, M. G.

    1989-01-01

    A number of successful applications of a spectral collocation method extended by a multi-domain patching technique are shown. The multi-domain technique can be used to improve resolution for problems with widely disparate scales, and to reduce the ill-conditioning of the spectral operators for problems in which a large number of points are required for distributed resolution. A new nonreflecting outflow boundary treatment for unsteady transition-to-turbulence simulations is also presented, which relies on the multi-domain technique. The role of multi-domain in improving the efficiency of such calculations is discussed.

  17. Large, Male Germ Cell-Specific Hypomethylated DNA Domains With Unique Genomic and Epigenomic Features on the Mouse X Chromosome

    PubMed Central

    Ikeda, Rieko; Shiura, Hirosuke; Numata, Koji; Sugimoto, Michihiko; Kondo, Masayo; Mise, Nathan; Suzuki, Masako; Greally, John M.; Abe, Kuniya

    2013-01-01

    To understand the epigenetic regulation required for germ cell-specific gene expression in the mouse, we analysed DNA methylation profiles of developing germ cells using a microarray-based assay adapted for a small number of cells. The analysis revealed differentially methylated sites between cell types tested. Here, we focused on a group of genomic sequences hypomethylated specifically in germline cells as candidate regions involved in the epigenetic regulation of germline gene expression. These hypomethylated sequences tend to be clustered, forming large (10 kb to ∼9 Mb) genomic domains, particularly on the X chromosome of male germ cells. Most of these regions, designated here as large hypomethylated domains (LoDs), correspond to segmentally duplicated regions that contain gene families showing germ cell- or testis-specific expression, including cancer testis antigen genes. We found an inverse correlation between DNA methylation level and expression of genes in these domains. Most LoDs appear to be enriched with H3 lysine 9 dimethylation, usually regarded as a repressive histone modification, although some LoD genes can be expressed in male germ cells. It thus appears that such a unique epigenomic state associated with the LoDs may constitute a basis for the specific expression of genes contained in these genomic domains. PMID:23861320

  18. Insights into Hox Protein Function from a Large Scale Combinatorial Analysis of Protein Domains

    PubMed Central

    Karlsson, Daniel; Dixit, Richa; Saadaoui, Mehdi; Monier, Bruno; Brun, Christine; Thor, Stefan; Vijayraghavan, K.; Perrin, Laurent; Pradel, Jacques; Graba, Yacine

    2011-01-01

    Protein function is encoded within protein sequence and protein domains. However, how protein domains cooperate within a protein to modulate overall activity and how this impacts functional diversification at the molecular and organism levels remains largely unaddressed. Focusing on three domains of the central class Drosophila Hox transcription factor AbdominalA (AbdA), we used combinatorial domain mutations and most known AbdA developmental functions as biological readouts to investigate how protein domains collectively shape protein activity. The results uncover redundancy, interactivity, and multifunctionality of protein domains as salient features underlying overall AbdA protein activity, providing means to apprehend functional diversity and accounting for the robustness of Hox-controlled developmental programs. Importantly, the results highlight context-dependency in protein domain usage and interaction, allowing major modifications in domains to be tolerated without general functional loss. The non-pleoitropic effect of domain mutation suggests that protein modification may contribute more broadly to molecular changes underlying morphological diversification during evolution, so far thought to rely largely on modification in gene cis-regulatory sequences. PMID:22046139

  19. Insights into Hox protein function from a large scale combinatorial analysis of protein domains.

    PubMed

    Merabet, Samir; Litim-Mecheri, Isma; Karlsson, Daniel; Dixit, Richa; Saadaoui, Mehdi; Monier, Bruno; Brun, Christine; Thor, Stefan; Vijayraghavan, K; Perrin, Laurent; Pradel, Jacques; Graba, Yacine

    2011-10-01

    Protein function is encoded within protein sequence and protein domains. However, how protein domains cooperate within a protein to modulate overall activity and how this impacts functional diversification at the molecular and organism levels remains largely unaddressed. Focusing on three domains of the central class Drosophila Hox transcription factor AbdominalA (AbdA), we used combinatorial domain mutations and most known AbdA developmental functions as biological readouts to investigate how protein domains collectively shape protein activity. The results uncover redundancy, interactivity, and multifunctionality of protein domains as salient features underlying overall AbdA protein activity, providing means to apprehend functional diversity and accounting for the robustness of Hox-controlled developmental programs. Importantly, the results highlight context-dependency in protein domain usage and interaction, allowing major modifications in domains to be tolerated without general functional loss. The non-pleoitropic effect of domain mutation suggests that protein modification may contribute more broadly to molecular changes underlying morphological diversification during evolution, so far thought to rely largely on modification in gene cis-regulatory sequences. PMID:22046139

  20. Highly heterologous region in the N-terminal extracellular domain of reptilian follitropin receptors.

    PubMed

    Akazome, Y; Ogasawara, O; Park, M K; Mori, T

    1996-12-01

    The primary structure of the N-terminal extracellular region of the follitropin receptor (FSH-R), which is thought to be responsible for hormone binding specificity, was determined in three reptilian species (tortoise, gecko, and lizard). Remarkably low sequence homologies were detected in the C-terminal part of the extracellular domain. This region was estimated to be a part of exon 10, which is the last exon of the FSH-R gene. In this region, not only were low homologies detected among the three reptilian species, but also specific deletions and/or insertions were found. In particular, large deletions were detected in squamate (gecko and lizard) FSH-Rs. Phylogenetic analysis indicated that these large deletions occurred recently, i.e., after the Triassic period. In another region characterized, sequence homologies were high, with tortoise-rat homology 78.4%, gecko-rat 64.7%, and lizard-rat 69.1%. In this highly conserved region, however, some reptile-specific alterations were detected, such as the loss of a cysteine residue in putative exon 7 and the existence of potential N-linked glycosylation sites in putative exon 9. PMID:8954771

  1. The human insulin gene is part of a large open chromatin domain specific for human islets

    PubMed Central

    Mutskov, Vesco; Felsenfeld, Gary

    2009-01-01

    Knowledge of how insulin (INS) gene expression is regulated will lead to better understanding of normal and abnormal pancreatic β cell function. We have mapped histone modifications over the INS region, coupled with an expression profile, in freshly isolated islets from multiple human donors. Unlike many other human genes, in which active modifications tend to be concentrated within 1 kb around the transcription start site, these marks are distributed over the entire coding region of INS as well. Moreover, a region of ≈80 kb around the INS gene, which contains the {tyrosine hydroxylase (TH)–(INS)–insulin-like growth factor 2 antisense (IGF2AS)–insulin-like growth factor 2 (IGF2)} gene cluster, unusually is marked by almost uniformly elevated levels of histone acetylation and H3K4 dimethylation, extending both downstream into IGF2 and upstream beyond the TH gene. This is accompanied by islet specific coordinate expression with INS of the neighboring TH and IGF2 genes. The presence of islet specific intergenic transcripts suggests their possible function in the maintenance of this unusual large open chromatin domain. PMID:19805079

  2. A dynamic domain partitioning strategy for parallel two-dimensional, large-scale and fine resolution flood inundation modeling

    NASA Astrophysics Data System (ADS)

    De Almeida, G. M.; Bates, P. D.

    2013-12-01

    and tests two parallel strategies in which the non-regular domain re-partitioning is performed dynamically to restore the load balance. The first method is an extension of the regular row partitioning method that adjusts the size of the sub-domains as a function of the number of wet and dry cells as well as of the respective cost of computations over wet and dry areas. The second method is similar to the first, but computations are performed only in wet regions. This is accomplished by using dynamic data structures that store the indexes to the wet cells and edges of the domain, which updated dynamically. The advantages and disadvantages of each of the two methods are examined analytically and through a set of idealized and real-world test cases that illustrate their performance. The results of the study provide useful guidance for future implementation and application of parallel 2-D flood inundation models; and sheds light onto a powerful tool to speed-up model computations over large high-resolution domains.

  3. Functional analysis of the NH{sub 2}-terminal hydrophobic region and BRICHOS domain of GKN1

    SciTech Connect

    Yoon, Jung Hwan; Choi, Yoo Jin; Choi, Won Suk; Nam, Suk Woo; Lee, Jung Young; Park, Won Sang

    2013-11-01

    Highlights: •NH{sub 2}-terminal and BRICHOS domain of GKN1 inhibited tumor cell growth. •NH{sub 2}-terminal and BRICHOS domain of GKN1 regulated cell cycle. •NH{sub 2}-terminal and BRICHOS domain of GKN1 inhibited epigenetic regulators. -- Abstract: Gastrokine 1 (GKN1) protects the gastric antral mucosa and promotes healing by facilitating restitution and proliferation after injury. GKN1 is down-regulated in Helicobacter pylori-infected gastric epithelial cells and loss of GKN1 expression is tightly associated with gastric carcinogenesis. However, the underlying mechanisms as a tumor suppressor are largely unknown. Presently, the hydrophobic region and BRICHOS domain of GKN1, pGKN1{sup D13N}, pGKN1{sup Δ68–199}, and pGKN1{sup Δ1–67,165–199} were shown to suppress gastric cancer cell growth and recapitulate GKN1 functions. As well, the hydrophobic region and BRICHOS domain of GKN1 had a synergistic anti-cancer effect with 5-FU on tumor cell growth, implying that the NH{sub 2}-terminal hydrophobic region and BRICHOS domain of GKN1 are sufficient for tumor suppression, thereby suggesting a therapeutic intervention for gastric cancer. Also, its domain inducing endogenous miR-185 directly targeted the epigenetic effectors DNMT1 and EZH2 in gastric cancer cells. Our results suggest that the NH{sub 2}-terminal hydrophobic region and BRICHOS domain of GKN1 are sufficient for its tumor suppressor activities.

  4. Domain structure of the large subunit of Escherichia coli carbamoyl phosphate synthetase. Location of the binding site for the allosteric inhibitor UMP in the COOH-terminal domain

    SciTech Connect

    Rubio, V.; Cervera, J.; Bendala, E. ); Lusty, C.J. ); Britton, H.G. )

    1991-01-29

    The large subunit of Escherichia coli carbamoyl phosphate synthetase is responsible for carbamoyl phosphate synthesis from NH{sub 3} and for the binding of the allosteric activators ornithine and IMP and of the inhibitor UMP. Elastase, trypsin, and chymotrypsin inactivate the enzyme and cleave the large subunit at a site approximately 15 kDa from the COOH terminus UMP, IMP, and ornithine prevent this cleavage and the inactivation. Upon irradiation with ultraviolet light in the presence of ({sup 14}C)UMP, the large subunit is labeled selectively and specifically. The labeling is inhibited by ornithine and IMP. Cleavage of the 15-kDa COOH-terminal region by prior treatment of the enzyme with trypsin prevents the labeling on subsequent irradation with ({sup 14}C)UMP. The ({sup 14}C)UMP-labeled large subunit is resistant to proteolytic cleavage, but if it is treated with SDS the resistance is lost, indicating that UMP is cross-linked to its binding site and that the protection is due to conformational factors. Since the binding sites for IMP and UMP overlap, most probably IMP also binds in this domain. The protection from proteolysis by ornithine suggests that ornithine binds in the same domain. To account for the effects of the allosteric effectors on the binding of ATP, the authors propose a scheme where the two halves of the large subunit form a pseudohomodimer by complementary isologous association, thus placing the NH{sub 2} half, which is involved in the binding of the molecule of ATP that yields P{sub i}, close to the regulatory domain.

  5. Large-scale 3D inversion of frequency domain controlled-source electromagnetic data

    NASA Astrophysics Data System (ADS)

    Miller, C. R.; Routh, P. S.; Donaldson, P.; Oldenburg, D. W.

    2005-05-01

    Controlled Source Audio-Frequency Magnetotellurics (CSAMT) is a frequency domain EM sounding technique. The CSAMT source is a grounded horizontal electric dipole approximately one to two kilometers in length. This dipole source generates both inductive and galvanic currents so that the observed electric field arises due to both the static the vector potentials. At low frequencies, the behavior of the fields is similar to that observed in a geometric sounding such as a direct current experiment. At higher frequencies, the inductive character of the source modifies the behavior of the fields so that the experiment becomes more like a frequency sounding. Higher frequency data are useful for imaging near-surface features and lower frequency data are sensitive to deeper structure. Inversion of controlled source EM data provides a means to image the subsurface electrical conductivity structure. We consider a 3D CSAMT data set acquired over a known geothermal resource area in Western Idaho. The data are amplitudes and phases of the electric and magnetic fields acquired at 25 frequencies. The conductivity contrast between the geothermal fluid conduits and the resistive host material allows us to relate the inverted conductivity image to the distribution of fluid flow pathways in the geothermal system. Our 1D CSAMT inversion of the 3D data set indicates regions of conductive fluid pathways in the subsurface. Our next step is to invert these data using the full Maxwell's equations in 3D. Inversion of a single frequency data set at 2 Hz using the 3D frequency domain inversion algorithm (Haber et. al, 2004) shows regions of fluid circulation indicated by zones of higher conductivity. Comparing the images from different single frequency inversions allows us to identify persistent features in the conductivity image that adequately satisfy the data. With the aid of synthetic modeling we are investigating what frequencies? and what geometries? are appropriate to better resolve

  6. Large exchange-dominated domain wall velocities in antiferromagnetically coupled nanowires

    NASA Astrophysics Data System (ADS)

    Kuteifan, Majd; Lubarda, M. V.; Fu, S.; Chang, R.; Escobar, M. A.; Mangin, S.; Fullerton, E. E.; Lomakin, V.

    2016-04-01

    Magnetic nanowires supporting field- and current-driven domain wall motion are envisioned for methods of information storage and processing. A major obstacle for their practical use is the domain-wall velocity, which is traditionally limited for low fields and currents due to the Walker breakdown occurring when the driving component reaches a critical threshold value. We show through numerical and analytical modeling that the Walker breakdown limit can be extended or completely eliminated in antiferromagnetically coupled magnetic nanowires. These coupled nanowires allow for large domain-wall velocities driven by field and/or current as compared to conventional nanowires.

  7. Sensitivity of systematic biases in South Asian summer monsoon simulations to regional climate model domain size and implications for downscaled regional process studies

    NASA Astrophysics Data System (ADS)

    Karmacharya, J.; Levine, R. C.; Jones, R.; Moufouma-Okia, W.; New, M.

    2015-07-01

    Global climate models (GCMs) have good skill in simulating climate at the global scale yet they show significant systematic errors at regional scale. For example, many GCMs exhibit significant biases in South Asian summer monsoon (SASM) simulations. Those errors not only limit application of such GCM output in driving regional climate models (RCMs) over these regions but also raise questions on the usefulness of RCMs derived from those GCMs. We focus on process studies where the RCM is driven by realistic lateral boundary conditions from atmospheric re-analysis which prevents remote systematic errors from influencing the regional simulation. In this context it is pertinent to investigate whether RCMs also suffer from similar errors when run over regions where their parent models show large systematic errors. Furthermore, the general sensitivity of the RCM simulation to domain size is informative in understanding remote drivers of systematic errors in the GCM and in choosing a suitable RCM domain that minimizes those errors. We investigate Met Office Unified Model systematic errors in SASM by comparing global and regional model simulations with targeted changes to the domain and forced with atmospheric re-analysis. We show that excluding remote drivers of systematic errors from the direct area of interest allows the application of RCMs for process studies of the SASM, despite the large errors in the parent global model. The findings in this study are also relevant to other models, many of which suffer from a similar pattern of systematic errors in global model simulations of the SASM.

  8. Large landslides lie low: Vertical domains of denudation processes in the arid Himalaya-Karakoram orogen

    NASA Astrophysics Data System (ADS)

    Blöthe, Jan Henrik

    2014-05-01

    glaciers and rock glaciers dominates higher elevation bands. Given a SE-ward decreasing topographic amplitude and increasing median elevation, bedrock landslides tend to affect higher portions of the landscape, while their vertical drop heights decrease accordingly. We conclude that these vertical domains of denudation processes conflict with the view that large bedrock landslides contribute to limiting relief in active mountain belts, unless (a) more frequent and smaller rock falls take on this role, and/or (b) evidence of large bedrock landslides above the permanent snow line is being censored rapidly. In either case, our data favour a model where large rock-slope failures undermine the lower portions of arid high-relief landscapes near the limits of Pleistocene glaciations, potentially signalling a regional postglacial hillslope adjustment. We thus call for a more detailed and refined view on how large rock-slope failures contribute to shaping arid mountain belts.

  9. Speed of field-driven domain walls in nanowires with large transverse magnetic anisotropy

    NASA Astrophysics Data System (ADS)

    Depassier, M. C.

    2015-07-01

    Recent analytical and numerical work on field-driven domain wall propagation in nanowires and thin films has shown that for large transverse anisotropy and sufficiently large applied fields the Walker profile becomes unstable before the breakdown field, giving way to a domain wall whose speed increases at a slower rate with the applied field. We perform an asymptotic expansion of the Landau-Lifshitz-Gilbert equation for large transverse magnetic anisotropy and show that the asymptotic dynamics reproduces this behavior. The appearance of a different regime in the asymptotic dynamics is due to a transition from a pushed to a pulled front of a reaction diffusion equation in which the speed of the domain wall increases with the square root of the applied field

  10. Human heterochromatin proteins form large domains containing KRAB-ZNF genes

    PubMed Central

    Vogel, Maartje J.; Guelen, Lars; de Wit, Elzo; Hupkes, Daniel Peric; Lodén, Martin; Talhout, Wendy; Feenstra, Marike; Abbas, Ben; Classen, Anne-Kathrin; van Steensel, Bas

    2006-01-01

    Heterochromatin is important for gene regulation and chromosome structure, but the genes that are occupied by heterochromatin proteins in the mammalian genome are largely unknown. We have adapted the DamID method to systematically identify target genes of the heterochromatin proteins HP1 and SUV39H1 in human and mouse cells. Unexpectedly, we found that CBX1 (formerly HP1β) and SUV39H1 bind to genes encoding KRAB domain containing zinc finger (KRAB-ZNF) transcriptional repressors. These genes constitute one of the largest gene families and are organized in clusters in the human genome. Preference of CBX1 for this gene family was observed in both human and mouse cells. High-resolution mapping on human chromosome 19 revealed that CBX1 coats large domains 0.1–4 Mb in size, which coincide with the position of KRAB-ZNF gene clusters. These domains show an intricate CBX1 binding pattern: While CBX1 is globally elevated throughout the domains, it is absent from the promoters and binds more strongly to the 3′ ends of KRAB-ZNF genes. KRAB-ZNF domains contain large numbers of LINE elements, which may contribute to CBX1 recruitment. These results uncover a surprising link between heterochromatin and a large family of regulatory genes in mammals. We suggest a role for heterochromatin in the evolution of the KRAB-ZNF gene family. PMID:17038565

  11. Human heterochromatin proteins form large domains containing KRAB-ZNF genes.

    PubMed

    Vogel, Maartje J; Guelen, Lars; de Wit, Elzo; Peric-Hupkes, Daniel; Lodén, Martin; Talhout, Wendy; Feenstra, Marike; Abbas, Ben; Classen, Anne-Kathrin; van Steensel, Bas

    2006-12-01

    Heterochromatin is important for gene regulation and chromosome structure, but the genes that are occupied by heterochromatin proteins in the mammalian genome are largely unknown. We have adapted the DamID method to systematically identify target genes of the heterochromatin proteins HP1 and SUV39H1 in human and mouse cells. Unexpectedly, we found that CBX1 (formerly HP1beta) and SUV39H1 bind to genes encoding KRAB domain containing zinc finger (KRAB-ZNF) transcriptional repressors. These genes constitute one of the largest gene families and are organized in clusters in the human genome. Preference of CBX1 for this gene family was observed in both human and mouse cells. High-resolution mapping on human chromosome 19 revealed that CBX1 coats large domains 0.1-4 Mb in size, which coincide with the position of KRAB-ZNF gene clusters. These domains show an intricate CBX1 binding pattern: While CBX1 is globally elevated throughout the domains, it is absent from the promoters and binds more strongly to the 3' ends of KRAB-ZNF genes. KRAB-ZNF domains contain large numbers of LINE elements, which may contribute to CBX1 recruitment. These results uncover a surprising link between heterochromatin and a large family of regulatory genes in mammals. We suggest a role for heterochromatin in the evolution of the KRAB-ZNF gene family. PMID:17038565

  12. Advanced Ecosystem Mapping Techniques for Large Arctic Study Domains Using Calibrated High-Resolution Imagery

    NASA Astrophysics Data System (ADS)

    Macander, M. J.; Frost, G. V., Jr.

    2015-12-01

    Regional-scale mapping of vegetation and other ecosystem properties has traditionally relied on medium-resolution remote sensing such as Landsat (30 m) and MODIS (250 m). Yet, the burgeoning availability of high-resolution (<=2 m) imagery and ongoing advances in computing power and analysis tools raises the prospect of performing ecosystem mapping at fine spatial scales over large study domains. Here we demonstrate cutting-edge mapping approaches over a ~35,000 km² study area on Alaska's North Slope using calibrated and atmospherically-corrected mosaics of high-resolution WorldView-2 and GeoEye-1 imagery: (1) an a priori spectral approach incorporating the Satellite Imagery Automatic Mapper (SIAM) algorithms; (2) image segmentation techniques; and (3) texture metrics. The SIAM spectral approach classifies radiometrically-calibrated imagery to general vegetation density categories and non-vegetated classes. The SIAM classes were developed globally and their applicability in arctic tundra environments has not been previously evaluated. Image segmentation, or object-based image analysis, automatically partitions high-resolution imagery into homogeneous image regions that can then be analyzed based on spectral, textural, and contextual information. We applied eCognition software to delineate waterbodies and vegetation classes, in combination with other techniques. Texture metrics were evaluated to determine the feasibility of using high-resolution imagery to algorithmically characterize periglacial surface forms (e.g., ice-wedge polygons), which are an important physical characteristic of permafrost-dominated regions but which cannot be distinguished by medium-resolution remote sensing. These advanced mapping techniques provide products which can provide essential information supporting a broad range of ecosystem science and land-use planning applications in northern Alaska and elsewhere in the circumpolar Arctic.

  13. Observations of Large Amplitude, Monochromatic Whistlers at Stream Interaction Regions

    NASA Astrophysics Data System (ADS)

    Breneman, A. W.; Cattell, C. A.; Kersten, K.; Wilson, L. B., III; Kellogg, P. J.; Schreiner, S.; Goetz, K.

    2009-12-01

    We present the first solar wind observations of monochromatic waveforms in the frequency range 10-100 Hz, consistent with the whistler mode. These waveforms are only observable in the high time resolution waveform data provided by the Time Domain Sampler (TDS) instrument on STEREO. The whistlers occur in groups that are strongly correlated with stream interaction regions (SIRs). The groups persist from a few seconds to minutes and are observed at 90% of SIRs and 20% of shocks from available 2007 data. A more detailed look shows that the whistler groups are closely related to sudden disturbances of the solar wind magnetic field and plasma. An example is presented of whistlers in association with a small reverse shock upstream of a SIR. Wave amplitudes range from a few to >25mV/m peak-to-peak, one to four orders of magnitude larger than any previous observations of whistler mode waves near SIRs or shocks. The whistlers are oblique by propagating with a large electrostatic component and are right-handed elliptically polarized in the spacecraft frame. We suggest that, due to the oblique and monochromatic nature of these waves, an electron or ion beam instability may be responsible for their creation. Test particle simulations show that the waves can interact strongly with halo (>60 eV) electrons. Test electrons were scattered by 10s of degrees and energized/de-energized by up to 50% in a few 10s of msec. Thus these whistlers may play an important role in the dynamics of solar wind electrons within SIRs and near some shocks.

  14. Large-area formation of self-aligned crystalline domains of organic semiconductors on transistor channels using CONNECT

    PubMed Central

    Park, Steve; Giri, Gaurav; Shaw, Leo; Pitner, Gregory; Ha, Jewook; Koo, Ja Hoon; Gu, Xiaodan; Park, Joonsuk; Lee, Tae Hoon; Nam, Ji Hyun; Hong, Yongtaek; Bao, Zhenan

    2015-01-01

    The electronic properties of solution-processable small-molecule organic semiconductors (OSCs) have rapidly improved in recent years, rendering them highly promising for various low-cost large-area electronic applications. However, practical applications of organic electronics require patterned and precisely registered OSC films within the transistor channel region with uniform electrical properties over a large area, a task that remains a significant challenge. Here, we present a technique termed “controlled OSC nucleation and extension for circuits” (CONNECT), which uses differential surface energy and solution shearing to simultaneously generate patterned and precisely registered OSC thin films within the channel region and with aligned crystalline domains, resulting in low device-to-device variability. We have fabricated transistor density as high as 840 dpi, with a yield of 99%. We have successfully built various logic gates and a 2-bit half-adder circuit, demonstrating the practical applicability of our technique for large-scale circuit fabrication. PMID:25902502

  15. Allosteric role of the large-scale domain opening in biological catch-binding

    NASA Astrophysics Data System (ADS)

    Pereverzev, Yuriy V.; Prezhdo, Oleg V.; Sokurenko, Evgeni V.

    2009-05-01

    The proposed model demonstrates the allosteric role of the two-domain region of the receptor protein in the increased lifetimes of biological receptor/ligand bonds subjected to an external force. The interaction between the domains is represented by a bounded potential, containing two minima corresponding to the attached and separated conformations of the two protein domains. The dissociative potential with a single minimum describing receptor/ligand binding fluctuates between deep and shallow states, depending on whether the domains are attached or separated. A number of valuable analytic expressions are derived and are used to interpret experimental data for two catch bonds. The P-selectin/P-selectin-glycoprotein-ligand-1 (PSGL-1) bond is controlled by the interface between the epidermal growth factor (EGF) and lectin domains of P-selectin, and the type 1 fimbrial adhesive protein (FimH)/mannose bond is governed by the interface between the lectin and pilin domains of FimH. Catch-binding occurs in these systems when the external force stretches the receptor proteins and increases the interdomain distance. The allosteric effect is supported by independent measurements, in which the domains are kept separated by attachment of another ligand. The proposed model accurately describes the experimentally observed anomalous behavior of the lifetimes of the P-selectin/PSGL-1 and FimH/mannose complexes as a function of applied force and provides valuable insights into the mechanism of catch-binding.

  16. Different evolutionary patterns of SNPs between domains and unassigned regions in human protein-coding sequences.

    PubMed

    Pang, Erli; Wu, Xiaomei; Lin, Kui

    2016-06-01

    Protein evolution plays an important role in the evolution of each genome. Because of their functional nature, in general, most of their parts or sites are differently constrained selectively, particularly by purifying selection. Most previous studies on protein evolution considered individual proteins in their entirety or compared protein-coding sequences with non-coding sequences. Less attention has been paid to the evolution of different parts within each protein of a given genome. To this end, based on PfamA annotation of all human proteins, each protein sequence can be split into two parts: domains or unassigned regions. Using this rationale, single nucleotide polymorphisms (SNPs) in protein-coding sequences from the 1000 Genomes Project were mapped according to two classifications: SNPs occurring within protein domains and those within unassigned regions. With these classifications, we found: the density of synonymous SNPs within domains is significantly greater than that of synonymous SNPs within unassigned regions; however, the density of non-synonymous SNPs shows the opposite pattern. We also found there are signatures of purifying selection on both the domain and unassigned regions. Furthermore, the selective strength on domains is significantly greater than that on unassigned regions. In addition, among all of the human protein sequences, there are 117 PfamA domains in which no SNPs are found. Our results highlight an important aspect of protein domains and may contribute to our understanding of protein evolution. PMID:26833483

  17. How do disordered regions achieve comparable functions to structured domains?

    PubMed Central

    Latysheva, Natasha S; Flock, Tilman; Weatheritt, Robert J; Chavali, Sreenivas; Babu, M Madan

    2015-01-01

    The traditional structure to function paradigm conceives of a protein's function as emerging from its structure. In recent years, it has been established that unstructured, intrinsically disordered regions (IDRs) in proteins are equally crucial elements for protein function, regulation and homeostasis. In this review, we provide a brief overview of how IDRs can perform similar functions to structured proteins, focusing especially on the formation of protein complexes and assemblies and the mediation of regulated conformational changes. In addition to highlighting instances of such functional equivalence, we explain how differences in the biological and physicochemical properties of IDRs allow them to expand the functional and regulatory repertoire of proteins. We also discuss studies that provide insights into how mutations within functional regions of IDRs can lead to human diseases. PMID:25752799

  18. Development of a regional macroinvertebrate index for large river bioassessment

    EPA Science Inventory

    Large river bioassessment protocols lag far behind those of wadeable streams and often rely on fish assemblages of individual rivers. We developed a regional macroinvertebrate index and assessed relative condition of six large river tributaries to the upper Mississippi and Ohio r...

  19. Graphene films with large domain size by a two-step chemical vapor deposition process.

    PubMed

    Li, Xuesong; Magnuson, Carl W; Venugopal, Archana; An, Jinho; Suk, Ji Won; Han, Boyang; Borysiak, Mark; Cai, Weiwei; Velamakanni, Aruna; Zhu, Yanwu; Fu, Lianfeng; Vogel, Eric M; Voelkl, Edgar; Colombo, Luigi; Ruoff, Rodney S

    2010-11-10

    The fundamental properties of graphene are making it an attractive material for a wide variety of applications. Various techniques have been developed to produce graphene and recently we discovered the synthesis of large area graphene by chemical vapor deposition (CVD) of methane on Cu foils. We also showed that graphene growth on Cu is a surface-mediated process and the films were polycrystalline with domains having an area of tens of square micrometers. In this paper, we report on the effect of growth parameters such as temperature, and methane flow rate and partial pressure on the growth rate, domain size, and surface coverage of graphene as determined by Raman spectroscopy, and transmission and scanning electron microscopy. On the basis of the results, we developed a two-step CVD process to synthesize graphene films with domains having an area of hundreds of square micrometers. Scanning electron microscopy and Raman spectroscopy clearly show an increase in domain size by changing the growth parameters. Transmission electron microscopy further shows that the domains are crystallographically rotated with respect to each other with a range of angles from about 13 to nearly 30°. Electrical transport measurements performed on back-gated FETs show that overall films with larger domains tend to have higher carrier mobility up to about 16,000 cm(2) V(-1) s(-1) at room temperature. PMID:20957985

  20. Contribution of large region joint associations to complex traits genetics.

    PubMed

    Paré, Guillaume; Asma, Senay; Deng, Wei Q

    2015-04-01

    A polygenic model of inheritance, whereby hundreds or thousands of weakly associated variants contribute to a trait's heritability, has been proposed to underlie the genetic architecture of complex traits. However, relatively few genetic variants have been positively identified so far and they collectively explain only a small fraction of the predicted heritability. We hypothesized that joint association of multiple weakly associated variants over large chromosomal regions contributes to complex traits variance. Confirmation of such regional associations can help identify new loci and lead to a better understanding of known ones. To test this hypothesis, we first characterized the ability of commonly used genetic association models to identify large region joint associations. Through theoretical derivation and simulation, we showed that multivariate linear models where multiple SNPs are included as independent predictors have the most favorable association profile. Based on these results, we tested for large region association with height in 3,740 European participants from the Health and Retirement Study (HRS) study. Adjusting for SNPs with known association with height, we demonstrated clustering of weak associations (p = 2x10-4) in regions extending up to 433.0 Kb from known height loci. The contribution of regional associations to phenotypic variance was estimated at 0.172 (95% CI 0.063-0.279; p < 0.001), which compared favorably to 0.129 explained by known height variants. Conversely, we showed that suggestively associated regions are enriched for known height loci. To extend our findings to other traits, we also tested BMI, HDLc and CRP for large region associations, with consistent results for CRP. Our results demonstrate the presence of large region joint associations and suggest these can be used to pinpoint weakly associated SNPs. PMID:25856144

  1. Sensitivity of Domain Size of a Regional Climate Model on the Indian Summer Monsoon Simulations

    NASA Astrophysics Data System (ADS)

    Pattnayak, K. C.; Panda, S. K.; Vaddi, D.; Mamgain, A.; Dash, S. K.

    2013-12-01

    The characteristics of Indian Summer Monsoon circulation and rainfall simulated by Regional Climate Model version 4.2 (RegCM4.2) using two domains: the smaller domain over India and the larger one over South Asia (SA) domain have been examined. The larger domain over the South Asia has been identified in the framework of World Climate Research Programme (WCRP) coordinated experiment known as the COordinated Regional climate Downscaling Experiment (CORDEX). This study is made over a period of 36 years starting from 1st January 1970 to 31st December 2005 at 50 km horizontal resolution of the model over both the domains using RegCM version 4.2. The UK Met Office Hadley Centre Global Circulation Model Version 2.0 (HadGEM2) outputs obtained from the Coupled Model Inter-comparison Project Phase 5 (CMIP5) for IPCC AR5 have been used as the initial and lateral boundary conditions. The model simulated precipitation has been compared with the IMD 0.5°x0.5° gridded rainfall which is available over the Indian land mass. Results show that the total precipitation is reduced significantly when the domain size is reduced from South Asia to smaller Indian domain. The simulated Indian precipitation obtained in the South Asian domain has a good agreement with the corresponding IMD observations. It is also seen that the domain size has dominant impact on the convective precipitation simulated by the model whereas there is no significant change in the non-convective precipitation. The wind field at 850hPa over the Arabian Sea is close to the NCEP/NCAR reanalysis in SA domain as compared against that obtained in the Indian domain. The cross-equatorial flow and the Somali Jet are better simulated in the SA than the Indian domain. Thus both the wind and rainfall fields' simulated by RegCM4 over India in case of SA domain are closer to the respective observations as compared to those obtained using the Indian domain. Since, the vertically integrated moisture flux over the Arabian Sea is

  2. The PHD Domain of Np95 (mUHRF1) Is Involved in Large-Scale Reorganization of Pericentromeric Heterochromatin

    PubMed Central

    Papait, Roberto; Pistore, Christian; Grazini, Ursula; Babbio, Federica; Cogliati, Sara; Pecoraro, Daniela; Brino, Laurent; Morand, Anne-Laure; Dechampesme, Anne-Marie; Spada, Fabio; Leonhardt, Heinrich; McBlane, Fraser; Oudet, Pierre

    2008-01-01

    Heterochromatic chromosomal regions undergo large-scale reorganization and progressively aggregate, forming chromocenters. These are dynamic structures that rapidly adapt to various stimuli that influence gene expression patterns, cell cycle progression, and differentiation. Np95-ICBP90 (m- and h-UHRF1) is a histone-binding protein expressed only in proliferating cells. During pericentromeric heterochromatin (PH) replication, Np95 specifically relocalizes to chromocenters where it highly concentrates in the replication factories that correspond to less compacted DNA. Np95 recruits HDAC and DNMT1 to PH and depletion of Np95 impairs PH replication. Here we show that Np95 causes large-scale modifications of chromocenters independently from the H3:K9 and H4:K20 trimethylation pathways, from the expression levels of HP1, from DNA methylation and from the cell cycle. The PHD domain is essential to induce this effect. The PHD domain is also required in vitro to increase access of a restriction enzyme to DNA packaged into nucleosomal arrays. We propose that the PHD domain of Np95-ICBP90 contributes to the opening and/or stabilization of dense chromocenter structures to support the recruitment of modifying enzymes, like HDAC and DNMT1, required for the replication and formation of PH. PMID:18508923

  3. Seamless continental-domain hydrologic model parameter estimations with Multi-Scale Parameter Regionalization

    NASA Astrophysics Data System (ADS)

    Mizukami, Naoki; Clark, Martyn; Newman, Andrew; Wood, Andy

    2016-04-01

    Estimation of spatially distributed parameters is one of the biggest challenges in hydrologic modeling over a large spatial domain. This problem arises from methodological challenges such as the transfer of calibrated parameters to ungauged locations. Consequently, many current large scale hydrologic assessments rely on spatially inconsistent parameter fields showing patchwork patterns resulting from individual basin calibration or spatially constant parameters resulting from the adoption of default or a-priori estimates. In this study we apply the Multi-scale Parameter Regionalization (MPR) framework (Samaniego et al., 2010) to generate spatially continuous and optimized parameter fields for the Variable Infiltration Capacity (VIC) model over the contiguous United States(CONUS). The MPR method uses transfer functions that relate geophysical attributes (e.g., soil) to model parameters (e.g., parameters that describe the storage and transmission of water) at the native resolution of the geophysical attribute data and then scale to the model spatial resolution with several scaling functions, e.g., arithmetic mean, harmonic mean, and geometric mean. Model parameter adjustments are made by calibrating the parameters of the transfer function rather than the model parameters themselves. In this presentation, we first discuss conceptual challenges in a "model agnostic" continental-domain application of the MPR approach. We describe development of transfer functions for the soil parameters, and discuss challenges associated with extending MPR for VIC to multiple models. Next, we discuss the "computational shortcut" of headwater basin calibration where we estimate the parameters for only 500 headwater basins rather than conducting simulations for every grid box across the entire domain. We first performed individual basin calibration to obtain a benchmark of the maximum achievable performance in each basin, and examined their transferability to the other basins. We then

  4. The charged region of Hsp90 modulates the function of the N-terminal domain

    PubMed Central

    Scheibel, Thomas; Siegmund, Heiko Ingo; Jaenicke, Rainer; Ganz, Peter; Lilie, Hauke; Buchner, Johannes

    1999-01-01

    Hsp90, an abundant heat shock protein that is highly expressed even under physiological conditions, is involved in the folding of key molecules of the cellular signal transduction system such as kinases and steroid receptors. It seems to contain two chaperone sites differing in substrate specificity. Binding of ATP or the antitumor drug geldanamycin alters the substrate affinity of the N-terminal chaperone site, whereas both substances show no influence on the C-terminal one. In wild-type Hsp90 the fragments containing the chaperone sites are connected by a highly charged linker of various lengths in different organisms. As this linker region represents the most striking difference between bacterial and eukaryotic Hsp90s, it may be involved in a gain of function of eukaryotic Hsp90s. Here, we have analyzed a fragment of yeast Hsp90 consisting of the N-terminal domain and the charged region (N272) in comparison with the isolated N-terminal domain (N210). We show that the charged region causes an increase in the affinity of the N-terminal domain for nonnative protein and establishes a crosstalk between peptide and ATP binding. Thus, the binding of peptide to N272 decreases its affinity for ATP and geldanamycin, whereas the ATP-binding properties of the monomeric N-terminal domain N210 are not influenced by peptide binding. We propose that the charged region connecting the two chaperone domains plays an important role in regulating chaperone function of Hsp90. PMID:9990018

  5. On the domain-specificity of the visual and non-visual face-selective regions.

    PubMed

    Axelrod, Vadim

    2016-08-01

    What happens in our brains when we see a face? The neural mechanisms of face processing - namely, the face-selective regions - have been extensively explored. Research has traditionally focused on visual cortex face-regions; more recently, the role of face-regions outside the visual cortex (i.e., non-visual-cortex face-regions) has been acknowledged as well. The major quest today is to reveal the functional role of each this region in face processing. To make progress in this direction, it is essential to understand the extent to which the face-regions, and particularly the non-visual-cortex face-regions, process only faces (i.e., face-specific, domain-specific processing) or rather are involved in a more domain-general cognitive processing. In the current functional MRI study, we systematically examined the activity of the whole face-network during face-unrelated reading task (i.e., written meaningful sentences with content unrelated to faces/people and non-words). We found that the non-visual-cortex (i.e., right lateral prefrontal cortex and posterior superior temporal sulcus), but not the visual cortex face-regions, responded significantly stronger to sentences than to non-words. In general, some degree of sentence selectivity was found in all non-visual-cortex cortex. Present result highlights the possibility that the processing in the non-visual-cortex face-selective regions might not be exclusively face-specific, but rather more or even fully domain-general. In this paper, we illustrate how the knowledge about domain-general processing in face-regions can help to advance our general understanding of face processing mechanisms. Our results therefore suggest that the problem of face processing should be approached in the broader scope of cognition in general. PMID:27255921

  6. The carboxyl-terminal domain of large T antigen rescues SV40 host range activity in trans independent of acetylation.

    PubMed

    Poulin, Danielle L; DeCaprio, James A

    2006-05-25

    The host range activity of SV40 has been described as the inability of mutant viruses with deletions in the C terminal region of large T Ag to replicate in certain types of African green monkey kidney cells. We constructed new mutant viruses expressing truncated T Ag proteins and found that these mutant viruses exhibited the host range phenotype. The host range phenotype was independent of acetylation of T Ag at lysine 697. Co-expression of the C terminal domain of T Ag (aa 627-708) in trans increased both T Ag and VP1 mRNA as well as protein levels for host range mutant viruses in the restrictive cell type. In addition, the T Ag 627-708 fragment promoted the productive lytic infection of host range mutant viruses in the nonpermissive cell type. The carboxyl-terminal region of T Ag contains a biological function essential for the SV40 viral life cycle. PMID:16510165

  7. MODFLOW-LGR: Practical application to a large regional dataset

    NASA Astrophysics Data System (ADS)

    Barnes, D.; Coulibaly, K. M.

    2011-12-01

    In many areas of the US, including southwest Florida, large regional-scale groundwater models have been developed to aid in decision making and water resources management. These models are subsequently used as a basis for site-specific investigations. Because the large scale of these regional models is not appropriate for local application, refinement is necessary to analyze the local effects of pumping wells and groundwater related projects at specific sites. The most commonly used approach to date is Telescopic Mesh Refinement or TMR. It allows the extraction of a subset of the large regional model with boundary conditions derived from the regional model results. The extracted model is then updated and refined for local use using a variable sized grid focused on the area of interest. MODFLOW-LGR, local grid refinement, is an alternative approach which allows model discretization at a finer resolution in areas of interest and provides coupling between the larger "parent" model and the locally refined "child." In the present work, these two approaches are tested on a mining impact assessment case in southwest Florida using a large regional dataset (The Lower West Coast Surficial Aquifer System Model). Various metrics for performance are considered. They include: computation time, water balance (as compared to the variable sized grid), calibration, implementation effort, and application advantages and limitations. The results indicate that MODFLOW-LGR is a useful tool to improve local resolution of regional scale models. While performance metrics, such as computation time, are case-dependent (model size, refinement level, stresses involved), implementation effort, particularly when regional models of suitable scale are available, can be minimized. The creation of multiple child models within a larger scale parent model makes it possible to reuse the same calibrated regional dataset with minimal modification. In cases similar to the Lower West Coast model, where a

  8. Fabrication of large domain YBa{sub 2}Cu{sub 3}O{sub x} for magnetic suspension applications

    SciTech Connect

    Todt, V.R.; Zhang, X.; Miller, D.J.; Sengupta, S.; Corpus, J.; Gains, J.R. Jr.

    1995-12-31

    Large domain YBa{sub 2}Cu{sub 3}O{sub x} levitators have been fabricated using a seeded melt processing technique. Depending upon the seed, either a single or five domained sample can be obtained. The grain boundaries separating each domains in the five domain levitator are found to be 90 degrees. Similar levitation forces can be observed for single and five domained samples. After thermal cycling, however, a small decrease in the levitation force of the five domain levitator was observed as a function of thermal cycles while nearly no change in force was observed in the single domain levitator. Finally it is shown that both, single and five domain YBCO, behave similarly as a function of sample thickness.

  9. Systematic large-scale secondary circulations in a regional climate model

    NASA Astrophysics Data System (ADS)

    Becker, Nico; Ulbrich, Uwe; Klein, Rupert

    2015-05-01

    Regional climate models (RCMs) are used to add the effects of nonresolved scales to coarser resolved model simulations by using a finer grid within a limited domain. We identify large-scale secondary circulations (SCs) relative to the driving global climate model (GCM) in an RCM simulation over Europe. By applying a clustering technique, we find that the SC depends on the large-scale flow prescribed by the driving GCM data. Evidence is presented that the SC is caused by the different representations of orographic effects in the RCM and the GCM. Flow modifications in the RCM caused by the Alps lead to large-scale vortices in the SC fields. These vortices are limited by the RCM boundaries, causing artificial boundary-parallel flows. The SC is associated with geopotential height and temperature anomalies between RCM and GCM and has the potential to produce systematic large-scale biases in RCMs.

  10. Parallel Domain Decomposition Formulation and Software for Large-Scale Sparse Symmetrical/Unsymmetrical Aeroacoustic Applications

    NASA Technical Reports Server (NTRS)

    Nguyen, D. T.; Watson, Willie R. (Technical Monitor)

    2005-01-01

    The overall objectives of this research work are to formulate and validate efficient parallel algorithms, and to efficiently design/implement computer software for solving large-scale acoustic problems, arised from the unified frameworks of the finite element procedures. The adopted parallel Finite Element (FE) Domain Decomposition (DD) procedures should fully take advantages of multiple processing capabilities offered by most modern high performance computing platforms for efficient parallel computation. To achieve this objective. the formulation needs to integrate efficient sparse (and dense) assembly techniques, hybrid (or mixed) direct and iterative equation solvers, proper pre-conditioned strategies, unrolling strategies, and effective processors' communicating schemes. Finally, the numerical performance of the developed parallel finite element procedures will be evaluated by solving series of structural, and acoustic (symmetrical and un-symmetrical) problems (in different computing platforms). Comparisons with existing "commercialized" and/or "public domain" software are also included, whenever possible.

  11. The Evolution of Regional Seismicity Between Large Earthquakes

    NASA Astrophysics Data System (ADS)

    Bowman, D.; King, G.

    We describe a simple model that links static stress (Coulomb) modeling to the re- gional seismicity around a major fault. Unlike conventional Coulomb stress tech- niques, which calculate stress changes, we model the evolution of the stress field rela- tive to the failure stress. Background seismicity is attributed to inhomogeneities in the stress field which are created by adding a random field that creates local regions above the failure stress. The inhomogeneous field is chosen such that when these patches fail, the resulting earthquake size distribution follows a Gutenburg-Richter law. Im- mediately following a large event, the model produces regions of increased seismicity where the overall stress field has been elevated (aftershocks) and regions of reduced seismicity where the stress field has been reduced (stress shadows). The high stress levels in the aftershock regions decrease due to loading following the main event. Combined with the stress shadow from the main event, this results in a broad seismi- cally quiet region of lowered stress around the epicenter. Pre-event seismicity appears as the original stress shadows finally fill as a result of loading. The increase in seismic- ity initially occurs several fault lengths away from the main fault and moves inward as the event approaches. As a result of this effect, the seismic moment release in the region around the future epicenter increases as the event approaches. Synthetic cat- alogues generated by this model are virtually indistinguishable from real earthquake sequences in California and Washington.

  12. Frequency-Domain Models for Nonlinear Microwave Devices Based on Large-Signal Measurements

    PubMed Central

    Jargon, Jeffrey A.; DeGroot, Donald C.; Gupta, K. C.

    2004-01-01

    In this paper, we introduce nonlinear large-signal scattering ( S) parameters, a new type of frequency-domain mapping that relates incident and reflected signals. We present a general form of nonlinear large-signal S-parameters and show that they reduce to classic S-parameters in the absence of nonlinearities. Nonlinear large-signal impedance ( Z) and admittance ( D) parameters are also introduced, and equations relating the different representations are derived. We illustrate how nonlinear large-signal S-parameters can be used as a tool in the design process of a nonlinear circuit, specifically a single-diode 1 GHz frequency-doubler. For the case where a nonlinear model is not readily available, we developed a method of extracting nonlinear large-signal S-parameters obtained with artificial neural network models trained with multiple measurements made by a nonlinear vector network analyzer equipped with two sources. Finally, nonlinear large-signal S-parameters are compared to another form of nonlinear mapping, known as nonlinear scattering functions. The nonlinear large-signal S-parameters are shown to be more general. PMID:27366621

  13. Radio Coronal Magnetography of a Large Active Region

    NASA Astrophysics Data System (ADS)

    Bastian, Timothy S.; Gary, Dale E.; White, Stephen; Fleishman, Gregory; Chen, Bin

    2015-04-01

    Quantitative knowledge of coronal magnetic fields is fundamental to understanding energetic phenomena such as solar flares. Flares occur in solar active regions where strong, non-potential magnetic fields provide free energy. While constraints on the coronal magnetic field topology are readily available through high resolution SXR and EUV imaging of solar active regions, useful quantitative measurements of coronal magnetic fields have thus far been elusive. Recent progress has been made at infrared (IR) wavelengths in exploiting both the Zeeman and Hanle effects to infer the line-of-sight magnetic field strength or the orientation of the magnetic field vector in the plane of the sky above the solar limb. However, no measurements of coronal magnetic fields against the solar disk are possible using IR observations. Radio observations of gyroresonance emission from active regions offer the means of measuring coronal magnetic fields above the limb and on the solar disk. In particular, for plasma plasma conditions in the solar corona, active regions typically become optically thick to emission over a range of radio frequencies through gyroresonance absorption at a low harmonic of the electron gyrofrequency. The specific range of resonant frequencies depends on the range of coronal magnetic field strengths present in the active region.The Karl G. Jansky Very Large Array was used in November 2014 to image NOAA/USAF active region AR12209 over a continuous frequency range of 1-8 GHz, corresponding to a wavelength range of 3.75-30 cm. This frequency range is sensitive to coronal magnetic field strengths ranging from ~120-1400G. The active region was observed on four different dates - November 18, 20, 22, and 24 - during which the active region longitude ranged from -15 to +70 degrees, providing a wide range of aspect angles. In this paper we provide a preliminary description of the coronal magnetic field measurements derived from the radio observations.

  14. Relative Movements of Domains in Large Molecules of the Immune System

    PubMed Central

    Schreiner, Wolfgang; Karch, Rudolf; Ribarics, Reiner; Cibena, Michael; Ilieva, Nevena

    2015-01-01

    Molecular dynamics was used to simulate large molecules of the immune system (major histocompatibility complex class I, presented epitope, T-cell receptor, and a CD8 coreceptor.) To characterize the relative orientation and movements of domains local coordinate systems (based on principal component analysis) were generated and directional cosines and Euler angles were computed. As a most interesting result, we found that the presence of the coreceptor seems to influence the dynamics within the protein complex, in particular the relative movements of the two α-helices, Gα1 and Gα2. PMID:26798660

  15. Light domain walls, massive neutrinos and the large scale structure of the Universe

    NASA Technical Reports Server (NTRS)

    Massarotti, Alessandro

    1991-01-01

    Domain walls generated through a cosmological phase transition are considered, which interact nongravitationally with light neutrinos. At a redshift z greater than or equal to 10(exp 4), the network grows rapidly and is virtually decoupled from the matter. As the friction with the matter becomes dominant, a comoving network scale close to that of the comoving horizon scale at z of approximately 10(exp 4) gets frozen. During the later phases, the walls produce matter wakes of a thickness d of approximately 10h(exp -1)Mpc, that may become seeds for the formation of the large scale structure observed in the Universe.

  16. Influence of the hinge region and its adjacent domains on binding and signaling patterns of the thyrotropin and follitropin receptor.

    PubMed

    Schaarschmidt, Jörg; Huth, Sandra; Meier, René; Paschke, Ralf; Jaeschke, Holger

    2014-01-01

    Glycoprotein hormone receptors (GPHR) have a large extracellular domain (ECD) divided into the leucine rich repeat (LRR) domain for binding of the glycoprotein hormones and the hinge region (HinR), which connects the LRR domain with the transmembrane domain (TMD). Understanding of the activation mechanism of GPHRs is hindered by the unknown interaction of the ECD with the TMD and the structural changes upon ligand binding responsible for receptor activation. Recently, our group showed that the HinR of the thyrotropin receptor (TSHR) can be replaced by those of the follitropin (FSHR) and lutropin receptor (LHCGR) without effects on surface expression and hTSH signaling. However, differences in binding characteristics for bovine TSH at the various HinRs were obvious. To gain further insights into the interplay between LRR domain, HinR and TMD we generated chimeras between the TSHR and FSHR. Our results obtained by the determination of cell surface expression, ligand binding and G protein activation confirm the similar characteristics of GPHR HinRs but they also demonstrate an involvement of the HinR in ligand selectivity indicated by the observed promiscuity of some chimeras. While the TSHR HinR contributes to specific binding of TSH and its variants, no such contribution is observed for FSH and its analog TR4401 at the HinR of the FSHR. Furthermore, the charge distribution at the poorly characterized LRR domain/HinR transition affected ligand binding and signaling even though this area is not in direct contact with the ligand. In addition our results also demonstrate the importance of the TMD/HinR interface. Especially the combination of the TSHR HinR with the FSHR-TMD resulted in a loss of cell surface expression of the respective chimeras. In conclusion, the HinRs of GPHRs do not only share similar characteristics but also behave as ligand specific structural and functional entities. PMID:25340405

  17. Influence of the Hinge Region and Its Adjacent Domains on Binding and Signaling Patterns of the Thyrotropin and Follitropin Receptor

    PubMed Central

    Schaarschmidt, Jörg; Huth, Sandra; Meier, René; Paschke, Ralf; Jaeschke, Holger

    2014-01-01

    Glycoprotein hormone receptors (GPHR) have a large extracellular domain (ECD) divided into the leucine rich repeat (LRR) domain for binding of the glycoprotein hormones and the hinge region (HinR), which connects the LRR domain with the transmembrane domain (TMD). Understanding of the activation mechanism of GPHRs is hindered by the unknown interaction of the ECD with the TMD and the structural changes upon ligand binding responsible for receptor activation. Recently, our group showed that the HinR of the thyrotropin receptor (TSHR) can be replaced by those of the follitropin (FSHR) and lutropin receptor (LHCGR) without effects on surface expression and hTSH signaling. However, differences in binding characteristics for bovine TSH at the various HinRs were obvious. To gain further insights into the interplay between LRR domain, HinR and TMD we generated chimeras between the TSHR and FSHR. Our results obtained by the determination of cell surface expression, ligand binding and G protein activation confirm the similar characteristics of GPHR HinRs but they also demonstrate an involvement of the HinR in ligand selectivity indicated by the observed promiscuity of some chimeras. While the TSHR HinR contributes to specific binding of TSH and its variants, no such contribution is observed for FSH and its analog TR4401 at the HinR of the FSHR. Furthermore, the charge distribution at the poorly characterized LRR domain/HinR transition affected ligand binding and signaling even though this area is not in direct contact with the ligand. In addition our results also demonstrate the importance of the TMD/HinR interface. Especially the combination of the TSHR HinR with the FSHR-TMD resulted in a loss of cell surface expression of the respective chimeras. In conclusion, the HinRs of GPHRs do not only share similar characteristics but also behave as ligand specific structural and functional entities. PMID:25340405

  18. A case study of the intraseasonal oscillation traversing the TOGA-COARE LSD. [large-scale domain

    NASA Technical Reports Server (NTRS)

    Vincent, Dayton G.; Schrage, Jon M.; Sliwinski, L. D.

    1993-01-01

    The paper presents examination of tree intraseasonal (30-60 day) oscillations (ISOs) that occurred during the southern summer season (December 1, 1985 - February 28, 1986) traversing the Large-Scale Domain (LSD) TOGA-COARE, the region which also plays an important role in ENSO, Australian monsoon, and extratropical circulations. Data presented include Hovmoeller diagrams of 5-day running means of 250-mb velocity potential anomalies and OLR anomalies; graphs of five-day running means of OLR in precipitable water (W) per sq m, averaged over 10 x 10 deg boxes centered on 5 S and (1) 145 E, (2) 155 E, (3) 165 E, and (4) 165 D, indicating the midpoint of each ISO; and vertical profiles of zonal wind in m/s averaged over the time period that each ISO spends in the 10 x 10 deg box centered at 5 S, and 175 E and 145 E.

  19. Absence of remotely triggered large earthquakes beyond the mainshock region

    USGS Publications Warehouse

    Parsons, T.; Velasco, A.A.

    2011-01-01

    Large earthquakes are known to trigger earthquakes elsewhere. Damaging large aftershocks occur close to the mainshock and microearthquakes are triggered by passing seismic waves at significant distances from the mainshock. It is unclear, however, whether bigger, more damaging earthquakes are routinely triggered at distances far from the mainshock, heightening the global seismic hazard after every large earthquake. Here we assemble a catalogue of all possible earthquakes greater than M 5 that might have been triggered by every M 7 or larger mainshock during the past 30 years. We compare the timing of earthquakes greater than M 5 with the temporal and spatial passage of surface waves generated by large earthquakes using a complete worldwide catalogue. Whereas small earthquakes are triggered immediately during the passage of surface waves at all spatial ranges, we find no significant temporal association between surface-wave arrivals and larger earthquakes. We observe a significant increase in the rate of seismic activity at distances confined to within two to three rupture lengths of the mainshock. Thus, we conclude that the regional hazard of larger earthquakes is increased after a mainshock, but the global hazard is not.

  20. Predicting binding within disordered protein regions to structurally characterised peptide-binding domains.

    PubMed

    Khan, Waqasuddin; Duffy, Fergal; Pollastri, Gianluca; Shields, Denis C; Mooney, Catherine

    2013-01-01

    Disordered regions of proteins often bind to structured domains, mediating interactions within and between proteins. However, it is difficult to identify a priori the short disordered regions involved in binding. We set out to determine if docking such peptide regions to peptide binding domains would assist in these predictions.We assembled a redundancy reduced dataset of SLiM (Short Linear Motif) containing proteins from the ELM database. We selected 84 sequences which had an associated PDB structures showing the SLiM bound to a protein receptor, where the SLiM was found within a 50 residue region of the protein sequence which was predicted to be disordered. First, we investigated the Vina docking scores of overlapping tripeptides from the 50 residue SLiM containing disordered regions of the protein sequence to the corresponding PDB domain. We found only weak discrimination of docking scores between peptides involved in binding and adjacent non-binding peptides in this context (AUC 0.58).Next, we trained a bidirectional recurrent neural network (BRNN) using as input the protein sequence, predicted secondary structure, Vina docking score and predicted disorder score. The results were very promising (AUC 0.72) showing that multiple sources of information can be combined to produce results which are clearly superior to any single source.We conclude that the Vina docking score alone has only modest power to define the location of a peptide within a larger protein region known to contain it. However, combining this information with other knowledge (using machine learning methods) clearly improves the identification of peptide binding regions within a protein sequence. This approach combining docking with machine learning is primarily a predictor of binding to peptide-binding sites, and is not intended as a predictor of specificity of binding to particular receptors. PMID:24019881

  1. Asymmetric Assembly of Merkel Cell Polyomavirus Large T-Antigen Origin Binding Domains at the Viral Origin

    SciTech Connect

    C Harrison; G Meinke; H Kwun; H Rogalin; P Phelan; P Bullock; Y Chang; P Moore; A Bohm

    2011-12-31

    The double-stranded DNA polyomavirus Merkel cell polyomavirus (MCV) causes Merkel cell carcinoma, an aggressive but rare human skin cancer that most often affects immunosuppressed and elderly persons. As in other polyomaviruses, the large T-antigen of MCV recognizes the viral origin of replication by binding repeating G(A/G)GGC pentamers. The spacing, number, orientation, and necessity of repeats for viral replication differ, however, from other family members such as SV40 and murine polyomavirus. We report here the 2.9 {angstrom} crystal structure of the MCV large T-antigen origin binding domain (OBD) in complex with a DNA fragment from the MCV origin of replication. Consistent with replication data showing that three of the G(A/G)GGC-like binding sites near the center of the origin are required for replication, the crystal structure contains three copies of the OBD. This stoichiometry was verified using isothermal titration calorimetry. The affinity for G(A/G)GGC-containing double-stranded DNA was found to be {approx} 740 nM, approximately 8-fold weaker than the equivalent domain in SV40 for the analogous region of the SV40 origin. The difference in affinity is partially attributable to DNA-binding residue Lys331 (Arg154 in SV40). In contrast to SV40, a small protein-protein interface is observed between MCV OBDs when bound to the central region of the origin. This protein-protein interface is reminiscent of that seen in bovine papilloma virus E1 protein. Mutational analysis indicates, however, that this interface contributes little to DNA binding energy.

  2. A dual-field domain-decomposition method for the time-domain finite-element analysis of large finite arrays

    SciTech Connect

    Lou, Zheng; Jin, Jian-Ming . E-mail: j-jin1@uiuc.edu

    2007-03-01

    A novel dual-field time-domain finite-element domain-decomposition method is presented for an efficient and broadband numerical simulation of electromagnetic properties of large finite arrays. Instead of treating the entire array as a single computation domain, the method considers each array element as a smaller subdomain and computes both the electric and magnetic fields inside each subdomain. Adjacent subdomains are related to each other by the equivalent surface currents on the subdomain interfaces in an explicit manner. Furthermore, the method exploits the identical geometry of the array elements and further reduces the memory requirement and CPU time. The proposed method is highly efficient for the simulation of large finite arrays. Numerical stability and computational performance of the method are discussed. Several radiation examples are presented to demonstrate the accuracy and efficiency of the method.

  3. Design of the large hadron electron collider interaction region

    NASA Astrophysics Data System (ADS)

    Cruz-Alaniz, E.; Newton, D.; Tomás, R.; Korostelev, M.

    2015-11-01

    The large hadron electron collider (LHeC) is a proposed upgrade of the Large Hadron Collider (LHC) within the high luminosity LHC (HL-LHC) project, to provide electron-nucleon collisions and explore a new regime of energy and luminosity for deep inelastic scattering. The design of an interaction region for any collider is always a challenging task given that the beams are brought into crossing with the smallest beam sizes in a region where there are tight detector constraints. In this case integrating the LHeC into the existing HL-LHC lattice, to allow simultaneous proton-proton and electron-proton collisions, increases the difficulty of the task. A nominal design was presented in the the LHeC conceptual design report in 2012 featuring an optical configuration that focuses one of the proton beams of the LHC to β*=10 cm in the LHeC interaction point to reach the desired luminosity of L =1033 cm-2 s-1 . This value is achieved with the aid of a new inner triplet of quadrupoles at a distance L*=10 m from the interaction point. However the chromatic beta beating was found intolerable regarding machine protection issues. An advanced chromatic correction scheme was required. This paper explores the feasibility of the extension of a novel optical technique called the achromatic telescopic squeezing scheme and the flexibility of the interaction region design, in order to find the optimal solution that would produce the highest luminosity while controlling the chromaticity, minimizing the synchrotron radiation power and maintaining the dynamic aperture required for stability.

  4. Temperature-sensitive mutants identify crucial structural regions of simian virus 40 large T antigen.

    PubMed Central

    Loeber, G; Tevethia, M J; Schwedes, J F; Tegtmeyer, P

    1989-01-01

    We have completed the cloning and sequencing of all known temperature-sensitive, amino acid substitution mutants of simian virus 40 large T antigen (tsA mutants). Surprisingly, many of the mutants isolated from distinct viral strains by different laboratories are identical. Thus, 17 independently isolated mutants represent only eight distinct genotypes. This remarkable clustering of tsA mutations in a few "hot spots" in the amino acid sequence of T antigen and the temperature-sensitive phenotypes of the mutations strongly suggest that these amino acids play crucial roles in organizing the structure of one or more functional domains. Most of the mutations are located in highly conserved regions of T antigen that correlate with DNA binding, protein-protein interactions, or ATP binding. With the exception of one mutant with a lesion in the putative ATP-binding region, all the mutants are temperature sensitive for DNA replication. PMID:2778883

  5. Wavefront reconstruction for extremely large telescopes via CuRe with domain decomposition.

    PubMed

    Rosensteiner, Matthias

    2012-11-01

    The Cumulative Reconstructor is an accurate, extremely fast reconstruction algorithm for Shack-Hartmann wavefront sensor data. But it has shown an unacceptable high noise propagation for large apertures. Therefore, in this paper we describe a domain decomposition approach to deal with this drawback. We show that this adaptation of the algorithm gives the same reconstruction quality as the original algorithm and leads to a significant improvement with respect to noise propagation. The method is combined with an integral control and compared to the classical matrix vector multiplication algorithm on an end-to-end simulation of a single conjugate adaptive optics system. The reconstruction time is 20n (number of subapertures), and the method is parallelizable. PMID:23201793

  6. A bifurcation analysis of boiling water reactor on large domain of parametric spaces

    NASA Astrophysics Data System (ADS)

    Pandey, Vikas; Singh, Suneet

    2016-09-01

    The boiling water reactors (BWRs) are inherently nonlinear physical system, as any other physical system. The reactivity feedback, which is caused by both moderator density and temperature, allows several effects reflecting the nonlinear behavior of the system. Stability analyses of BWR is done with a simplified, reduced order model, which couples point reactor kinetics with thermal hydraulics of the reactor core. The linear stability analysis of the BWR for steady states shows that at a critical value of bifurcation parameter (i.e. feedback gain), Hopf bifurcation occurs. These stable and unstable domains of parametric spaces cannot be predicted by linear stability analysis because the stability of system does not include only stability of the steady states. The stability of other dynamics of the system such as limit cycles must be included in study of stability. The nonlinear stability analysis (i.e. bifurcation analysis) becomes an indispensable component of stability analysis in this scenario. Hopf bifurcation, which occur with one free parameter, is studied here and it formulates birth of limit cycles. The excitation of these limit cycles makes the system bistable in the case of subcritical bifurcation whereas stable limit cycles continues in an unstable region for supercritical bifurcation. The distinction between subcritical and supercritical Hopf is done by two parameter analysis (i.e. codimension-2 bifurcation). In this scenario, Generalized Hopf bifurcation (GH) takes place, which separates sub and supercritical Hopf bifurcation. The various types of bifurcation such as limit point bifurcation of limit cycle (LPC), period doubling bifurcation of limit cycles (PD) and Neimark-Sacker bifurcation of limit cycles (NS) have been identified with the Floquet multipliers. The LPC manifests itself as the region of bistability whereas chaotic region exist because of cascading of PD. This region of bistability and chaotic solutions are drawn on the various

  7. Structure of the dimerization domain of DiGeorge critical region 8

    SciTech Connect

    Senturia, R.; Faller, M.; Yin, S.; Loo, J.A.; Cascio, D.; Sawaya, M.R.; Hwang, D.; Clubb, R.T.; Guo, F.

    2010-09-27

    Maturation of microRNAs (miRNAs, {approx}22nt) from long primary transcripts [primary miRNAs (pri-miRNAs)] is regulated during development and is altered in diseases such as cancer. The first processing step is a cleavage mediated by the Microprocessor complex containing the Drosha nuclease and the RNA-binding protein DiGeorge critical region 8 (DGCR8). We previously reported that dimeric DGCR8 binds heme and that the heme-bound DGCR8 is more active than the heme-free form. Here, we identified a conserved dimerization domain in DGCR8. Our crystal structure of this domain (residues 298-352) at 1.7 {angstrom} resolution demonstrates a previously unknown use of a WW motif as a platform for extensive dimerization interactions. The dimerization domain of DGCR8 is embedded in an independently folded heme-binding domain and directly contributes to association with heme. Heme-binding-deficient DGCR8 mutants have reduced pri-miRNA processing activity in vitro. Our study provides structural and biochemical bases for understanding how dimerization and heme binding of DGCR8 may contribute to regulation of miRNA biogenesis.

  8. The neck region of the myosin motor domain acts as a lever arm to generate movement.

    PubMed Central

    Uyeda, T Q; Abramson, P D; Spudich, J A

    1996-01-01

    The myosin head consists of a globular catalytic domain that binds actin and hydrolyzes ATP and a neck domain that consists of essential and regulatory light chains bound to a long alpha-helical portion of the heavy chain. The swinging neck-level model assumes that a swinging motion of the neck relative to the catalytic domain is the origin of movement. This model predicts that the step size, and consequently the sliding velocity, are linearly related to the length of the neck. We have tested this point by characterizing a series of mutant Dictyostelium myosins that have different neck lengths. The 2xELCBS mutant has an extra binding site for essential light chain. The delta RLCBS mutant myosin has an internal deletion that removes the regulatory light chain binding site. The delta BLCBS mutant lacks both light chain binding sites. Wild-type myosin and these mutant myosins were subjected to the sliding filament in vitro motility assay. As expected, mutants with shorter necks move slower than wild-type myosin in vitro. Most significantly, a mutant with a longer neck moves faster than the wild type, and the sliding velocities of these myosins are linearly related to the neck length, as predicted by the swinging neck-lever model. A simple extrapolation to zero speed predicts that the fulcrum point is in the vicinity of the SH1-SH2 region in the catalytic domain. Images Fig. 1 Fig. 2 Fig. 3 PMID:8633089

  9. Flood Hazard Mapping over Large Regions using Geomorphic Approaches

    NASA Astrophysics Data System (ADS)

    Samela, Caterina; Troy, Tara J.; Manfreda, Salvatore

    2016-04-01

    Historically, man has always preferred to settle and live near the water. This tendency has not changed throughout time, and today nineteen of the twenty most populated agglomerations of the world (Demographia World Urban Areas, 2015) are located along watercourses or at the mouth of a river. On one hand, these locations are advantageous from many points of view. On the other hand, they expose significant populations and economic assets to a certain degree of flood hazard. Knowing the location and the extent of the areas exposed to flood hazards is essential to any strategy for minimizing the risk. Unfortunately, in data-scarce regions the use of traditional floodplain mapping techniques is prevented by the lack of the extensive data required, and this scarcity is generally most pronounced in developing countries. The present work aims to overcome this limitation by defining an alternative simplified procedure for a preliminary, but efficient, floodplain delineation. To validate the method in a data-rich environment, eleven flood-related morphological descriptors derived from DEMs have been used as linear binary classifiers over the Ohio River basin and its sub-catchments, measuring their performances in identifying the floodplains at the change of the topography and the size of the calibration area. The best performing classifiers among those analysed have been applied and validated across the continental U.S. The results suggest that the classifier based on the index ln(hr/H), named the Geomorphic Flood Index (GFI), is the most suitable to detect the flood-prone areas in data-scarce environments and for large-scale applications, providing good accuracy with low requirements in terms of data and computational costs. Keywords: flood hazard, data-scarce regions, large-scale studies, binary classifiers, DEM, USA.

  10. Large cutting tools in the Danjiangkou Reservoir Region, central China.

    PubMed

    Kuman, Kathleen; Li, Chaorong; Li, Hao

    2014-11-01

    Handaxe-bearing sites in China are currently known to occur in a number of alluvial basins, the best known being Dingcun, Bose and Luonan. Bose in the south and Luonan in central China on the northern margin of the Qinling Mountains are most familiar to English-speaking researchers. Here we document the Danjiangkou Reservoir Region (DRR) as another major area for large cutting tools (LCTs), located in central China on the southeastern edge of the Qinling Mountains. Large cutting tools are preserved in three terraces of the Han and Dan Rivers in Hubei and Henan Provinces, with dates from ca. 0.8 Ma (millions of years ago) (Terrace 4) to the first half of the Middle Pleistocene (Terrace 3), and possibly to the Late Pleistocene (Terrace 2). This paper reports on LCTs discovered in Terraces 3 and 2, with a majority from the older terrace (and one specimen from Terrace 4). Regional environments during the Middle Pleistocene were relatively warm, humid and stable. Despite the poor quality of raw materials (predominantly quartz phyllite and trachyte for the LCTs), good examples of both handaxes and cleavers are present, plus two types of picks. The LCT technology is compared and contrasted with other Asian industries and with the Acheulean. Overall the DRR LCTs show both technological and morphological similarities with Acheulean LCTs, with some differences that are mainly attributed to raw material properties, subsistence ecology, and 'cultural drift.' The DRR LCTs expand the range of morphological variability of the East Asian material and highlight the need for greater reliance on technological analysis and raw material evaluation for best comparison of Chinese assemblages with the Acheulean tradition. PMID:25223718

  11. Molecular Insights into the Coding Region Determinant-binding Protein-RNA Interaction through Site-directed Mutagenesis in the Heterogeneous Nuclear Ribonucleoprotein-K-homology Domains*

    PubMed Central

    Barnes, Mark; van Rensburg, Gerrit; Li, Wai-Ming; Mehmood, Kashif; Mackedenski, Sebastian; Chan, Ching-Man; King, Dustin T.; Miller, Andrew L.; Lee, Chow H.

    2015-01-01

    The ability of its four heterogeneous nuclear RNP-K-homology (KH) domains to physically associate with oncogenic mRNAs is a major criterion for the function of the coding region determinant-binding protein (CRD-BP). However, the particular RNA-binding role of each of the KH domains remains largely unresolved. Here, we mutated the first glycine to an aspartate in the universally conserved GXXG motif of the KH domain as an approach to investigate their role. Our results show that mutation of a single GXXG motif generally had no effect on binding, but the mutation in any two KH domains, with the exception of the combination of KH3 and KH4 domains, completely abrogated RNA binding in vitro and significantly retarded granule formation in zebrafish embryos, suggesting that any combination of at least two KH domains cooperate in tandem to bind RNA efficiently. Interestingly, we found that any single point mutation in one of the four KH domains significantly impacted CRD-BP binding to mRNAs in HeLa cells, suggesting that the dynamics of the CRD-BP-mRNA interaction vary over time in vivo. Furthermore, our results suggest that different mRNAs bind preferentially to distinct CRD-BP KH domains. The novel insights revealed in this study have important implications on the understanding of the oncogenic mechanism of CRD-BP as well as in the future design of inhibitors against CRD-BP function. PMID:25389298

  12. Large system change challenges: addressing complex critical issues in linked physical and social domains

    NASA Astrophysics Data System (ADS)

    Waddell, Steve; Cornell, Sarah; Hsueh, Joe; Ozer, Ceren; McLachlan, Milla; Birney, Anna

    2015-04-01

    Most action to address contemporary complex challenges, including the urgent issues of global sustainability, occurs piecemeal and without meaningful guidance from leading complex change knowledge and methods. The potential benefit of using such knowledge is greater efficacy of effort and investment. However, this knowledge and its associated tools and methods are under-utilized because understanding about them is low, fragmented between diverse knowledge traditions, and often requires shifts in mindsets and skills from expert-led to participant-based action. We have been engaged in diverse action-oriented research efforts in Large System Change for sustainability. For us, "large" systems can be characterized as large-scale systems - up to global - with many components, of many kinds (physical, biological, institutional, cultural/conceptual), operating at multiple levels, driven by multiple forces, and presenting major challenges for people involved. We see change of such systems as complex challenges, in contrast with simple or complicated problems, or chaotic situations. In other words, issues and sub-systems have unclear boundaries, interact with each other, and are often contradictory; dynamics are non-linear; issues are not "controllable", and "solutions" are "emergent" and often paradoxical. Since choices are opportunity-, power- and value-driven, these social, institutional and cultural factors need to be made explicit in any actionable theory of change. Our emerging network is sharing and building a knowledge base of experience, heuristics, and theories of change from multiple disciplines and practice domains. We will present our views on focal issues for the development of the field of large system change, which include processes of goal-setting and alignment; leverage of systemic transitions and transformation; and the role of choice in influencing critical change processes, when only some sub-systems or levels of the system behave in purposeful ways

  13. Structure of the DBL3X-DBL4ε region of the VAR2CSA placental malaria vaccine candidate: insight into DBL domain interactions.

    PubMed

    Gangnard, Stéphane; Lewit-Bentley, Anita; Dechavanne, Sébastien; Srivastava, Anand; Amirat, Faroudja; Bentley, Graham A; Gamain, Benoît

    2015-01-01

    The human malaria parasite, Plasmodium falciparum, is able to evade spleen-mediated clearing from blood stream by sequestering in peripheral organs. This is due to the adhesive properties conferred by the P. falciparum Erythrocyte Membrane Protein 1 (PfEMP1) family exported by the parasite to the surface of infected erythrocytes. Expression of the VAR2CSA variant of PfEMP1 leads to pregnancy-associated malaria, which occurs when infected erythrocytes massively sequester in the placenta by binding to low-sulfated Chondroitin Sulfate A (CSA) present in the intervillous spaces. VAR2CSA is a 350 kDa protein that carries six Duffy-Binding Like (DBL) domains, one Cysteine-rich Inter-Domain Regions (CIDR) and several inter-domain regions. In the present paper, we report for the first time the crystal structure at 2.9 Å of a VAR2CSA double domain, DBL3X-DBL4ε, from the FCR3 strain. DBL3X and DBL4ε share a large contact interface formed by residues that are invariant or highly conserved in VAR2CSA variants, which suggests that these two central DBL domains (DBL3X-DBL4ε) contribute significantly to the structuring of the functional VAR2CSA extracellular region. We have also examined the antigenicity of peptides corresponding to exposed loop regions of the DBL4ε structure. PMID:26450557

  14. Structure of the DBL3X-DBL4ε region of the VAR2CSA placental malaria vaccine candidate: insight into DBL domain interactions

    PubMed Central

    Gangnard, Stéphane; Lewit-Bentley, Anita; Dechavanne, Sébastien; Srivastava, Anand; Amirat, Faroudja; Bentley, Graham A.; Gamain, Benoît

    2015-01-01

    The human malaria parasite, Plasmodium falciparum, is able to evade spleen-mediated clearing from blood stream by sequestering in peripheral organs. This is due to the adhesive properties conferred by the P. falciparum Erythrocyte Membrane Protein 1 (PfEMP1) family exported by the parasite to the surface of infected erythrocytes. Expression of the VAR2CSA variant of PfEMP1 leads to pregnancy-associated malaria, which occurs when infected erythrocytes massively sequester in the placenta by binding to low-sulfated Chondroitin Sulfate A (CSA) present in the intervillous spaces. VAR2CSA is a 350 kDa protein that carries six Duffy-Binding Like (DBL) domains, one Cysteine-rich Inter-Domain Regions (CIDR) and several inter-domain regions. In the present paper, we report for the first time the crystal structure at 2.9 Å of a VAR2CSA double domain, DBL3X-DBL4ε, from the FCR3 strain. DBL3X and DBL4ε share a large contact interface formed by residues that are invariant or highly conserved in VAR2CSA variants, which suggests that these two central DBL domains (DBL3X-DBL4ε) contribute significantly to the structuring of the functional VAR2CSA extracellular region. We have also examined the antigenicity of peptides corresponding to exposed loop regions of the DBL4ε structure. PMID:26450557

  15. A three-dimensional domain decomposition method for large-scale DFT electronic structure calculations

    NASA Astrophysics Data System (ADS)

    Duy, Truong Vinh Truong; Ozaki, Taisuke

    2014-03-01

    With tens of petaflops supercomputers already in operation and exaflops machines expected to appear within the next 10 years, efficient parallel computational methods are required to take advantage of such extreme-scale machines. In this paper, we present a three-dimensional domain decomposition scheme for enabling large-scale electronic structure calculations based on density functional theory (DFT) on massively parallel computers. It is composed of two methods: (i) the atom decomposition method and (ii) the grid decomposition method. In the former method, we develop a modified recursive bisection method based on the moment of inertia tensor to reorder the atoms along a principal axis so that atoms that are close in real space are also close on the axis to ensure data locality. The atoms are then divided into sub-domains depending on their projections onto the principal axis in a balanced way among the processes. In the latter method, we define four data structures for the partitioning of grid points that are carefully constructed to make data locality consistent with that of the clustered atoms for minimizing data communications between the processes. We also propose a decomposition method for solving the Poisson equation using the three-dimensional FFT in Hartree potential calculation, which is shown to be better in terms of communication efficiency than a previously proposed parallelization method based on a two-dimensional decomposition. For evaluation, we perform benchmark calculations with our open-source DFT code, OpenMX, paying particular attention to the O(N) Krylov subspace method. The results show that our scheme exhibits good strong and weak scaling properties, with the parallel efficiency at 131,072 cores being 67.7% compared to the baseline of 16,384 cores with 131,072 atoms of the diamond structure on the K computer.

  16. Inactivation of pRB-related proteins p130 and p107 mediated by the J domain of simian virus 40 large T antigen.

    PubMed Central

    Stubdal, H; Zalvide, J; Campbell, K S; Schweitzer, C; Roberts, T M; DeCaprio, J A

    1997-01-01

    Inactivation of the retinoblastoma tumor suppressor protein (pRB) contributes to tumorigenesis in a wide variety of cancers. In contrast, the role of the two pRB-related proteins, p130 and p107, in oncogenic transformation is unclear. The LXCXE domain of simian virus 40 large T antigen (TAg) specifically binds to pRB, p107, and p130. We have previously shown that the N terminus and the LXCXE domain of TAg cooperate to alter the phosphorylation state of p130 and p107. Here, we demonstrate that TAg promotes the degradation of p130 and that the N terminus of TAg is required for this activity. The N terminus of TAg has homology to the J domain of the DnaJ family of molecular chaperone proteins. Mutants with mutations in the J-domain homology region of TAg are defective for altering p130 and p107 phosphorylation and for p130 degradation. A heterologous J-domain from a human DnaJ protein can functionally substitute for the N terminus of TAg in the effect on p107 and p130 phosphorylation and p130 stability. We further demonstrate that the J-domain homology region of TAg confers a growth advantage to wild-type mouse embryo fibroblasts (MEFs) but is dispensable in the case of MEFs lacking both p130 and p107. This indicates that p107 and p130 have overlapping growth-suppressing activities whose inactivation is mediated by the J domain of TAg. PMID:9271376

  17. Coordinated Multi-layer Multi-domain Optical Network (COMMON) for Large-Scale Science Applications (COMMON)

    SciTech Connect

    Vokkarane, Vinod

    2013-09-01

    We intend to implement a Coordinated Multi-layer Multi-domain Optical Network (COMMON) Framework for Large-scale Science Applications. In the COMMON project, specific problems to be addressed include 1) anycast/multicast/manycast request provisioning, 2) deployable OSCARS enhancements, 3) multi-layer, multi-domain quality of service (QoS), and 4) multi-layer, multidomain path survivability. In what follows, we outline the progress in the above categories (Year 1, 2, and 3 deliverables).

  18. On the blow-up rate of large solutions for a porous media logistic equation on radial domain

    NASA Astrophysics Data System (ADS)

    Feng, Peng

    2007-05-01

    In this paper we establish the exact blow-up rate of the large solutions of a porous media logistic equation. We consider the carrying capacity function with a general decay rate at the boundary instead of the usual cases when it can be approximated by a distant function. Obtaining the accurate blow-up rate allows us to establish the uniqueness result. Our result covers all previous results on the ball domain and can be further adapted in a more general domain.

  19. Calculus of variations in the large, existence of trajectories in a domain with boundary, and Whitney's inverted pendulum problem

    NASA Astrophysics Data System (ADS)

    Bolotin, S. V.; Kozlov, V. V.

    2015-10-01

    For non-autonomous Lagrangian systems we introduce the notion of a dynamically convex domain with respect to the Lagrangian. We establish the solubility of boundary-value problems in compact dynamically convex domains. If the Lagrangian is time-periodic, then such a domain contains a periodic trajectory. The proofs use the Hamilton principle and known tools of the calculus of variations in the large. Our general results are applied to Whitney's problem on the existence of motions of an inverted pendulum without falls.

  20. SURF_ER—surface electron spin resonance (ESR) of the surface domain of large objects

    NASA Astrophysics Data System (ADS)

    Herrling, Th.; Rehberg, J.; Jung, K.; Groth, N.

    2002-04-01

    SURF_ER is a method for spectral and spatial electron spin resonance measurements on the surface of large objects which extension is only restricted by the width of the pole gap of the magnet and the homogeneity of the magnetic field and not by the cavity dimensions. The application of several techniques like SURF_ER for spectroscopic measurements, SURF_ERM for spatial scanning and SURF_ERI for spatial measurements of the depth of the surface region are discussed and represented for the skin of a human being as an example.

  1. Rendering Future Vegetation Change across Large Regions of the US

    NASA Astrophysics Data System (ADS)

    Sant'Anna Dias, Felipe; Gu, Yuting; Agarwalla, Yashika; Cheng, Yiwei; Patil, Sopan; Stieglitz, Marc; Turk, Greg

    2015-04-01

    We use two Machine Learning techniques, Decision Trees (DT) and Neural Networks (NN), to provide classified images and photorealistic renderings of future vegetation cover at three large regions in the US. The training data used to generate current vegetation cover include Landsat surface reflectance images, USGS Land Cover maps, 50 years of mean annual temperature and precipitation for the period 1950 - 2000, elevation, aspect and slope data. Present vegetation cover was generated on a 100m grid. Future vegetation cover for the period 2061- 2080 was predicted using the 1 km resolution bias corrected data from the NASA Goddard Institute for Space Studies Global Climate Model E simulation. The three test regions encompass a wide range of climatic gradients, topographic variation, and vegetation cover. The central Oregon site covers 19,182 square km and includes the Ochoco and Malheur National Forest. Vegetation cover is 50% evergreen forest and 50% shrubs and scrubland. The northwest Washington site covers 14,182 square km. Vegetation cover is 60% evergreen forest, 14% scrubs, 7% grassland, and 7% barren land. The remainder of the area includes deciduous forest, perennial snow cover, and wetlands. The third site, the Jemez mountain region of north central New Mexico, covers 5,500 square km. Vegetation cover is 47% evergreen forest, 31% shrubs, 13% grasses, and 3% deciduous forest. The remainder of the area includes developed and cultivated areas and wetlands. Using the above mentioned data sets we first trained our DT and NN models to reproduce current vegetation. The land cover classified images were compared directly to the USGS land cover data. The photorealistic generated vegetation images were compared directly to the remotely sensed surface reflectance maps. For all three sites, similarity between generated and observed vegetation cover was quite remarkable. The three trained models were then used to explore what the equilibrium vegetation would look like for

  2. Large conserved domains of low DNA methylation maintained by Dnmt3a

    PubMed Central

    Jeong, Mira; Sun, Deqiang; Luo, Min; Huang, Yun; Challen, Grant A.; Rodriguez, Benjamin; Zhang, Xiaotian; Chavez, Lukas; Wang, Hui; Hannah, Rebecca; Kim, Sang-Bae; Yang, Liubin; Ko, Myunggon; Chen, Rui; Göttgens, Berthold; Lee, Ju-Seog; Gunaratne, Preethi; Godley, Lucy A.; Darlington, Gretchen J.; Rao, Anjana; Li, Wei; Goodell, Margaret A.

    2014-01-01

    Gains and losses in DNA methylation are prominent features of mammalian cell types. To gain insight into mechanisms that could promote shifts in DNA methylation and contribute to cell fate changes, including malignant transformation, we performed genome-wide mapping of 5-methylcytosine and 5-hydroxymethylcytosine in purified murine hematopoietic stem cells. We discovered extended regions of low methylation (Canyons) that span conserved domains frequently containing transcription factors and are distinct from CpG islands and shores. The genes in about half of these methylation Canyons are coated with repressive histone marks while the remainder are covered by activating histone marks and are highly expressed in HSCs. Canyon borders are demarked by 5-hydroxymethylcytosine and become eroded in the absence of DNA methyltransferase 3a (Dnmt3a). Genes dysregulated in human leukemias are enriched for Canyon-associated genes. The novel epigenetic landscape we describe may provide a mechanism for the regulation of hematopoiesis and may contribute to leukemia development. PMID:24270360

  3. Considerations on domain location according to the jump of resolution between the driving data and the nested regional climate model within the Big-Brother experiment.

    NASA Astrophysics Data System (ADS)

    Matte, D.; Laprise, R.; Theriault, J. M.; Lucas-Picher, P.

    2015-12-01

    Many studies have shown the importance of choosing the domain size adequately for dynamical downscaling with nested regional climate models. It is well known that domain should not be too large to avoid large departure from the driving data, and not be too small to provide sufficient distance from the lateral inflow to allow a full development of the small-scale features resolved by the increase resolution. Although practitioners of dynamical downscaling are well aware that the jump of resolution between the driving data and the nested regional climate model impacts the simulated climate, the issue has never been properly study. Larger is the jump of resolution, larger is the distance from the lateral inflow to fully develop the small-scale features permitted by the increase resolution. Our investigation compares direct nesting to achieve a grid mesh of 0.15o from driving data at 3.6°, 1.8o, 0.45° and 0.15° using the perfect-prognostic approach of the Big-Brother protocol. The results show that the small-scale transient-eddy component struggles to be fully developed with reduced resolution of the driving data. Overall, this study suggests that domain location (i.e. domain of interest or subsequent nested domains) must be chosen carefully according to the jump of resolution to allow the optimal development of small-scale features allowed by the increase resolution of the nested model.

  4. Building Large-Domain Twisted Bilayer Graphene with van Hove Singularity.

    PubMed

    Tan, Zhenjun; Yin, Jianbo; Chen, Cheng; Wang, Huan; Lin, Li; Sun, Luzhao; Wu, Jinxiong; Sun, Xiao; Yang, Haifeng; Chen, Yulin; Peng, Hailin; Liu, Zhongfan

    2016-07-26

    Twisted bilayer graphene (tBLG) with van Hove Singularity (VHS) has exhibited novel twist-angle-dependent chemical and physical phenomena. However, scalable production of high-quality tBLG is still in its infancy, especially lacking the angle controlled preparation methods. Here, we report a facile approach to prepare tBLG with large domain sizes (>100 μm) and controlled twist angles by a clean layer-by-layer transfer of two constituent graphene monolayers. The whole process without interfacial polymer contamination in two monolayers guarantees the interlayer interaction of the π-bond electrons, which gives rise to the existence of minigaps in electronic structures and the consequent formation of VHSs in density of state. Such perturbation on band structure was directly observed by angle-resolved photoemission spectroscopy with submicrometer spatial resolution (micro-ARPES). The VHSs lead to a strong light-matter interaction and thus introduce ∼20-fold enhanced intensity of Raman G-band, which is a characteristic of high-quality tBLG. The as-prepared tBLG with strong light-matter interaction was further fabricated into high-performance photodetectors with selectively enhanced photocurrent generation (up to ∼6 times compared with monolayer in our device). PMID:27163879

  5. Analysis of the Linker Region Joining the Adenylation and Carrier Protein Domains of the Modular Non-Ribosomal Peptide Synthetases

    PubMed Central

    Miller, Bradley R.; Sundlov, Jesse A.; Drake, Eric J.; Makin, Thomas A.; Gulick, Andrew M.

    2014-01-01

    Non-Ribosomal Peptide Synthetases (NRPSs) are multi-modular proteins capable of producing important peptide natural products. Using an assembly-line process the amino acid substrate and peptide intermediates are passed between the active sites of different catalytic domains of the NRPS while bound covalently to a peptidyl carrier protein (PCP) domain. Examination of the linker sequences that join the NRPS adenylation and PCP domains identified several conserved proline residues that are not found in standalone adenylation domains. We examined the roles of these proline residues and neighboring conserved sequences through mutagenesis and biochemical analysis of the reaction catalyzed by the adenylation domain and the fully reconstituted NRPS pathway. In particular, we identified a conserved LPxP motif at the start of the adenylation-PCP linker. The LPxP motif interacts with a region on the adenylation domain to stabilize a critical catalytic lysine residue belonging to the A10 motif that immediately precedes the linker. Further, this interaction with the C-terminal sub-domain of the adenylation domain may coordinate movement of the PCP with the conformational change of the adenylation domain. Through this work, we extend the conserved A10 motif of the adenylation domain and identify residues that enable proper adenylation domain function. PMID:24975514

  6. Structural basis of empathy and the domain general region in the anterior insular cortex

    PubMed Central

    Mutschler, Isabella; Reinbold, Céline; Wankerl, Johanna; Seifritz, Erich; Ball, Tonio

    2013-01-01

    Empathy is key for healthy social functioning and individual differences in empathy have strong implications for manifold domains of social behavior. Empathy comprises of emotional and cognitive components and may also be closely linked to sensorimotor processes, which go along with the motivation and behavior to respond compassionately to another person's feelings. There is growing evidence for local plastic change in the structure of the healthy adult human brain in response to environmental demands or intrinsic factors. Here we have investigated changes in brain structure resulting from or predisposing to empathy. Structural MRI data of 101 healthy adult females was analyzed. Empathy in fictitious as well as real-life situations was assessed using a validated self-evaluation measure. Furthermore, empathy-related structural effects were also put into the context of a functional map of the anterior insular cortex (AIC) determined by activation likelihood estimate (ALE) meta-analysis of previous functional imaging studies. We found that gray matter (GM) density in the left dorsal AIC correlates with empathy and that this area overlaps with the domain general region (DGR) of the anterior insula that is situated in-between functional systems involved in emotion–cognition, pain, and motor tasks as determined by our meta-analysis. Thus, we propose that this insular region where we find structural differences depending on individual empathy may play a crucial role in modulating the efficiency of neural integration underlying emotional, cognitive, and sensorimotor information which is essential for global empathy. PMID:23675334

  7. First steps of the regional climate model MAR over the Euro-CORDEX domain

    NASA Astrophysics Data System (ADS)

    Scholzen, Chloé; Fettweis, Xavier

    2016-04-01

    In the framework of the Euro-CORDEX initiative, the Laboratory of Climatology of the University of Liège, Belgium, is currently using the regional climate model MAR (for "Modèle Atmosphérique Régional") to simulate the past, present and future climate over Europe. Simulations are being performed for both available resolutions over the Euro-CORDEX domain, namely 0.11 deg. (12.5 km) and 0.44 deg. (50 km). Historical and present-day runs (1979-2015) use the ERA-Interim and the NCEP/NCAR-v1 reanalyses as boundary conditions, whereas future projections are driven by two selected GCMs from the CMIP5 database: NorESM1-M and MIROC5. All CMIP5-GCMs were previously compared against ERA-Interim reanalysis data in terms of their ability to represent the current mean climate over Europe. The GCMs also underwent a statistical classification based on the calculation of skill-scores evaluating for instance 850 hPa temperature and 500 hPa geopotential height. Several settings and parameters were tested in order to calibrate the regional climate model MAR over the Euro-CORDEX domain. MAR was validated with respect to observations from the European Climate Assessment & Dataset (ECA&D). The aim of this study is to assess the performance of MAR in comparing its results to other RCMs used within the Euro-CORDEX initiative.

  8. Genetic analysis of the cell binding domain region of the chicken fibronectin gene.

    PubMed

    Kubomura, S; Obara, M; Karasaki, Y; Taniguchi, H; Gotoh, S; Tsuda, T; Higashi, K; Ohsato, K; Hirano, H

    1987-11-20

    We have determined the nucleotide sequence of the cell binding domain region of the chicken fibronectin gene and analyzed it evolutionaly. We present here the complete nucleotide sequence of 4.3 kb HindIII/EcoRI segment from the clone lambda FC23 of the chicken fibronectin gene. There were five exons in this segment. When we lined up the amino acid of exons 28, 29 and 31, three alignments, known as the Type III repeat, appeared. Tetrapeptide, -RGDS-, called the cell binding domain, existed in the second repeat, coding exon 30. It was presumed that the Type III repeats were composed of two exons in the chicken gene, the same as in the rat and humans. We found repeatedly appearing amino-acid sequences such as -TIT- (three arrays in these Type III repeats) but also found one of the amino acids substituted in the tripeptide in these Type III repeats (seven arrays). We analyzed these repeats from the point of view of evolution. We used three of the nucleotide sequences (12-18 bp) coding such -TIT- repeats as a unit length for comparing the various homologies after dividing the coding region into 56 segments. The mutual homology of the divided segments to each one of three showed 53% on average. On the other hand, the mutual nucleotide homology of the Type III repeat was 44%. This suggested that the Type III repeat may have been developed by frequent duplication of small gene units. PMID:2823899

  9. Atmospheric Impact of Large Methane Emission in the Arctic Region

    NASA Astrophysics Data System (ADS)

    Bhattacharyya, S.; Cameron-Smith, P. J.; Bergmann, D.; Reagan, M. T.; Collins, W.; Elliott, S. M.; Maltrud, M. E.

    2011-12-01

    A highly potent greenhouse gas, methane, is locked in the solid phase as ice-like deposits containing a mixture of water and gas (mostly methane) called clathrates, in ocean sediments and underneath permafrost regions. Clathrates are stable under high pressure and low temperatures. Recent estimates suggest that about 1600 - 2000GtC of clathrates are present in oceans and 400GtC in Arctic permafrost (Archer et al.2009) which is about 4000 times that of current annual emissions. In a warming climate, increase in ocean temperatures could alter the geothermal gradient, which in turn could lead to dissociation of the clathrates and release of methane into the ocean and subsequently into the atmosphere as well. This could be of particular importance in the shallow part of the Arctic Ocean where the clathrates are found in depths of only 300m. In this presentation, we shall show results from our ongoing simulation of a scenario of large scale methane outgassing from clathrate dissociation due to warming ocean temperatures in the Arctic based on ocean sediment modeling. To that end we use the CESM (Community Earth System Model) version 1 with fully active coupled atmosphere-ocean-land model together with fast atmospheric chemistry module to simulate the response to increasing methane emissions in the Barents Sea, Canadian Archipelago and the Sea of Okhotsk. The simulation shows the effect these methane emissions could have on global surface methane, surface ozone, surface air temperature and other related indices. This work was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344. LLNL-ABS-491764

  10. Consistency of mixing height retrieved over a large spatial domain from different data sources

    NASA Astrophysics Data System (ADS)

    Biavati, Gionata; Feist, Dietrich G.

    2014-05-01

    The monitoring of GreenHouse Gases (GHG) fluxes over large domains is performed coupling measurements with transport models. A key parameter, for successfully quantifying the fluxes is the altitude of the capping inversion, or the mixing height (MH). This parameter is commonly estimated as a diagnostic variable within global models, or estimated using radiosonde data. Both these methods have problems in representing the MH. In particular the time evolution and the spatial representation are the weakest aspects. Within the context of the Integrated Carbon Observation System (ICOS), a network of measurement stations is going to be created. Together with a complete equipment of instruments for measuring GHG concentrations and meteorological quantities, it is planed to monitor the MH using ceilometers and lidars. Ceilometers are a less expensive version of lidars, they are capable to estimate aerosolic load and within almost the first two kilometers the molecular density. The estimations are obtained looking for relevant time and space fluctuations of aerosol concentration. This is equivalent to placing the MH over an strong variation of the measured signal. So the most of the algorithms for locating MH are edge detection algorithms. The evaluation of the MH, estimated with different algorithms applied to optical data, shows bad agreement with the estimate performed on radiosonde data. However, a deeper study on the automated methods used on radiosonde data reveals that the commonly used algorithms, based on different implementations of Richardson Bulk Number method, are not reliable or suitable for evaluating results of other methods. The use of optical instruments for estimating MH has several limitations: multiple edges are commonly detected and a selection criteria is required; depending on the stability of the boundary layer MH can be outside the detection limits of the instrument; clouds and other water condensations phenomena can prevent the estimation of MH

  11. Identification of a Receptor-Binding Region within Domain 4 of the Protective Antigen Component of Anthrax Toxin

    PubMed Central

    Varughese, Mini; Teixeira, Avelino V.; Liu, Shihui; Leppla, Stephen H.

    1999-01-01

    Anthrax toxin from Bacillus anthracis is a three-component toxin consisting of lethal factor (LF), edema factor (EF), and protective antigen (PA). LF and EF are the catalytic components of the toxin, whereas PA is the receptor-binding component. To identify residues of PA that are involved in interaction with the cellular receptor, two solvent-exposed loops of domain 4 of PA (amino acids [aa] 679 to 693 and 704 to 723) were mutagenized, and the altered proteins purified and tested for toxicity in the presence of LF. In addition to the intended substitutions, novel mutations were introduced by errors that occurred during PCR. Substitutions within the large loop (aa 704 to 723) had no effect on PA activity. A mutated protein, LST-35, with three substitutions in the small loop (aa 679 to 693), bound weakly to the receptor and was nontoxic. A mutated protein, LST-8, with changes in three separate regions did not bind to receptor and was nontoxic. Toxicity was greatly decreased by truncation of the C-terminal 3 to 5 aa, but not by their substitution with nonnative residues or the extension of the terminus with nonnative sequences. Comparison of the 28 mutant proteins described here showed that the large loop (aa 704 to 722) is not involved in receptor binding, whereas residues in and near the small loop (aa 679 to 693) play an important role in receptor interaction. Other regions of domain 4, in particular residues at the extreme C terminus, appear to play a role in stabilizing a conformation needed for receptor-binding activity. PMID:10085028

  12. Regional Triggering of Volcanic Activity Following Large Magnitude Earthquakes

    NASA Astrophysics Data System (ADS)

    Hill-Butler, Charley; Blackett, Matthew; Wright, Robert

    2015-04-01

    There are numerous reports of a spatial and temporal link between volcanic activity and high magnitude seismic events. In fact, since 1950, all large magnitude earthquakes have been followed by volcanic eruptions in the following year - 1952 Kamchatka M9.2, 1960 Chile M9.5, 1964 Alaska M9.2, 2004 & 2005 Sumatra-Andaman M9.3 & M8.7 and 2011 Japan M9.0. While at a global scale, 56% of all large earthquakes (M≥8.0) in the 21st century were followed by increases in thermal activity. The most significant change in volcanic activity occurred between December 2004 and April 2005 following the M9.1 December 2004 earthquake after which new eruptions were detected at 10 volcanoes and global volcanic flux doubled over 52 days (Hill-Butler et al. 2014). The ability to determine a volcano's activity or 'response', however, has resulted in a number of disparities with <50% of all volcanoes being monitored by ground-based instruments. The advent of satellite remote sensing for volcanology has, therefore, provided researchers with an opportunity to quantify the timing, magnitude and character of volcanic events. Using data acquired from the MODVOLC algorithm, this research examines a globally comparable database of satellite-derived radiant flux alongside USGS NEIC data to identify changes in volcanic activity following an earthquake, February 2000 - December 2012. Using an estimate of background temperature obtained from the MODIS Land Surface Temperature (LST) product (Wright et al. 2014), thermal radiance was converted to radiant flux following the method of Kaufman et al. (1998). The resulting heat flux inventory was then compared to all seismic events (M≥6.0) within 1000 km of each volcano to evaluate if changes in volcanic heat flux correlate with regional earthquakes. This presentation will first identify relationships at the temporal and spatial scale, more complex relationships obtained by machine learning algorithms will then be examined to establish favourable

  13. Transcription forms and remodels supercoiling domains unfolding large-scale chromatin structures

    PubMed Central

    Naughton, Catherine; Avlonitis, Nicolaos; Corless, Samuel; Prendergast, James G.; Mati, Ioulia K.; Eijk, Paul P.; Cockroft, Scott L.; Bradley, Mark; Ylstra, Bauke; Gilbert, Nick

    2013-01-01

    DNA supercoiling is an inherent consequence of twisting DNA and is critical for regulating gene expression and DNA replication. However, DNA supercoiling at a genomic scale in human cells is uncharacterized. To map supercoiling we used biotinylated-trimethylpsoralen as a DNA structure probe to show the genome is organized into supercoiling domains. Domains are formed and remodeled by RNA polymerase and topoisomerase activities and are flanked by GC-AT boundaries and CTCF binding sites. Under-wound domains are transcriptionally active, enriched in topoisomerase I, “open” chromatin fibers and DNaseI sites, but are depleted of topoisomerase II. Furthermore DNA supercoiling impacts on additional levels of chromatin compaction as under-wound domains are cytologically decondensed, topologically constrained, and decompacted by transcription of short RNAs. We suggest that supercoiling domains create a topological environment that facilitates gene activation providing an evolutionary purpose for clustering genes along chromosomes. PMID:23416946

  14. Transcription forms and remodels supercoiling domains unfolding large-scale chromatin structures.

    PubMed

    Naughton, Catherine; Avlonitis, Nicolaos; Corless, Samuel; Prendergast, James G; Mati, Ioulia K; Eijk, Paul P; Cockroft, Scott L; Bradley, Mark; Ylstra, Bauke; Gilbert, Nick

    2013-03-01

    DNA supercoiling is an inherent consequence of twisting DNA and is critical for regulating gene expression and DNA replication. However, DNA supercoiling at a genomic scale in human cells is uncharacterized. To map supercoiling, we used biotinylated trimethylpsoralen as a DNA structure probe to show that the human genome is organized into supercoiling domains. Domains are formed and remodeled by RNA polymerase and topoisomerase activities and are flanked by GC-AT boundaries and CTCF insulator protein-binding sites. Underwound domains are transcriptionally active and enriched in topoisomerase I, 'open' chromatin fibers and DNase I sites, but they are depleted of topoisomerase II. Furthermore, DNA supercoiling affects additional levels of chromatin compaction as underwound domains are cytologically decondensed, topologically constrained and decompacted by transcription of short RNAs. We suggest that supercoiling domains create a topological environment that facilitates gene activation, providing an evolutionary purpose for clustering genes along chromosomes. PMID:23416946

  15. Simultaneous Solar Maximum Mission (SMM) and Very Large Array (VLA) observations of solar active regions

    NASA Technical Reports Server (NTRS)

    Willson, Robert F.

    1991-01-01

    Very Large Array observations at 20 cm wavelength can detect the hot coronal plasma previously observed at soft x ray wavelengths. Thermal cyclotron line emission was detected at the apex of coronal loops where the magnetic field strength is relatively constant. Detailed comparison of simultaneous Solar Maximum Mission (SMM) Satellite and VLA data indicate that physical parameters such as electron temperature, electron density, and magnetic field strength can be obtained, but that some coronal loops remain invisible in either spectral domain. The unprecedent spatial resolution of the VLA at 20 cm wavelength showed that the precursor, impulsive, and post-flare components of solar bursts originate in nearby, but separate loops or systems of loops.. In some cases preburst heating and magnetic changes are observed from loops tens of minutes prior to the impulsive phase. Comparisons with soft x ray images and spectra and with hard x ray data specify the magnetic field strength and emission mechanism of flaring coronal loops. At the longer 91 cm wavelength, the VLA detected extensive emission interpreted as a hot 10(exp 5) K interface between cool, dense H alpha filaments and the surrounding hotter, rarefield corona. Observations at 91 cm also provide evidence for time-correlated bursts in active regions on opposite sides of the solar equator; they are attributed to flare triggering by relativistic particles that move along large-scale, otherwise-invisible, magnetic conduits that link active regions in opposite hemispheres of the Sun.

  16. The cardiac-specific N-terminal region of troponin I positions the regulatory domain of troponin C

    PubMed Central

    Hwang, Peter M.; Cai, Fangze; Pineda-Sanabria, Sandra E.; Corson, David C.; Sykes, Brian D.

    2014-01-01

    The cardiac isoform of troponin I (cTnI) has a unique 31-residue N-terminal region that binds cardiac troponin C (cTnC) to increase the calcium sensitivity of the sarcomere. The interaction can be abolished by cTnI phosphorylation at Ser22 and Ser23, an important mechanism for regulating cardiac contractility. cTnC contains two EF–hand domains (the N and C domain of cTnC, cNTnC and cCTnC) connected by a flexible linker. Calcium binding to either domain favors an “open” conformation, exposing a large hydrophobic surface that is stabilized by target binding, cTnI[148–158] for cNTnC and cTnI[39–60] for cCTnC. We used multinuclear multidimensional solution NMR spectroscopy to study cTnI[1–73] in complex with cTnC. cTnI[39–60] binds to the hydrophobic face of cCTnC, stabilizing an alpha helix in cTnI[41–67] and a type VIII turn in cTnI[38–41]. In contrast, cTnI[1–37] remains disordered, although cTnI[19–37] is electrostatically tethered to the negatively charged surface of cNTnC (opposite its hydrophobic surface). The interaction does not directly affect the calcium binding affinity of cNTnC. However, it does fix the positioning of cNTnC relative to the rest of the troponin complex, similar to what was previously observed in an X-ray structure [Takeda S, et al. (2003) Nature 424(6944):35–41]. Domain positioning impacts the effective concentration of cTnI[148–158] presented to cNTnC, and this is how cTnI[19–37] indirectly modulates the calcium affinity of cNTnC within the context of the cardiac thin filament. Phosphorylation of cTnI at Ser22/23 disrupts domain positioning, explaining how it impacts many other cardiac regulatory mechanisms, like the Frank–Starling law of the heart. PMID:25246568

  17. Structure-based design of a disulfide-linked oligomeric form of the simian virus 40 (SV40) large T antigen DNA-binding domain

    SciTech Connect

    Meinke, Gretchen; Phelan, Paul; Fradet-Turcotte, Amélie; Archambault, Jacques; Bullock, Peter A.

    2011-06-01

    With the aim of forming the ‘lock-washer’ conformation of the origin-binding domain of SV40 large T antigen in solution, using structure-based analysis an intermolecular disulfide bridge was engineered into the origin-binding domain to generate higher order oligomers in solution. The 1.7 Å resolution structure shows that the mutant forms a spiral in the crystal and has the de novo disulfide bond at the protein interface, although structural rearrangements at the interface are observed relative to the wild type. The modular multifunctional protein large T antigen (T-ag) from simian virus 40 orchestrates many of the events needed for replication of the viral double-stranded DNA genome. This protein assembles into single and double hexamers on specific DNA sequences located at the origin of replication. This complicated process begins when the origin-binding domain of large T antigen (T-ag ODB) binds the GAGGC sequences in the central region (site II) of the viral origin of replication. While many of the functions of purified T-ag OBD can be studied in isolation, it is primarily monomeric in solution and cannot assemble into hexamers. To overcome this limitation, the possibility of engineering intermolecular disulfide bonds in the origin-binding domain which could oligomerize in solution was investigated. A recent crystal structure of the wild-type T-ag OBD showed that this domain forms a left-handed spiral in the crystal with six subunits per turn. Therefore, we analyzed the protein interface of this structure and identified two residues that could potentially support an intermolecular disulfide bond if changed to cysteines. SDS–PAGE analysis established that the mutant T-ag OBD formed higher oligomeric products in a redox-dependent manner. In addition, the 1.7 Å resolution crystal structure of the engineered disulfide-linked T-ag OBD is reported, which establishes that oligomerization took place in the expected manner.

  18. The ICTP Regional System Model (RESM) to simulate the monsoon in the South Asia CORDEX domain

    NASA Astrophysics Data System (ADS)

    Di Sante, Fabio; Coppola, Erika; Farneti, Riccardo; Giorgi, Filippo

    2016-04-01

    South Asian climate is characterized mainly by the wet and dry dipole that divides the annual cycle in two seasons: the monsoon season and the dry season. The life and the economy of those regions is very much influenced by the climate variability and the monsoon variability therefore is crucial to understand the physical mechanism associated with them. The spatial and temporal representation of the monsoons over the South Asian region is one of the main challenge of global and regional climate models principally because they fail to represent the SST (sea surface temperature) induced rainfall when forced with observed SST resulting in a poor representation of the monsoon cycle (Fu et al. 2002). The coupling with the ocean is essential to be able to simulate the correct air-sea interaction; the results are in general much improved and the monsoon patterns and the time representation (like the onset for example) are closer to the observations (Fu et al. 2002; Fu et al. 2007; Ratnam et Al. 2008; Seo et Al. 2009). Here we present a Regional Earth System Model (RESM) composed by a regional climate model RegCM4 (Giorgi et al, 2012) coupled with the regional oceanic model MITgcm (Marshall et al, 1997) and two hydrological model: ChyM (Cetemps Hydrological Model, Coppola et al, 2007) and HD model (Max-Planck's HD model; Hagemann and Dümenil, 1998). We simulate the Southern Asian Climate taking into account the whole hydrological cycle. Wind stress, water fluxes and heat fluxes are exchanged from the atmosphere to the ocean, SST are exchanged from ocean to the atmosphere and in order to conserve mass, the river discharge is calculated from the Hydrological model and sent to the ocean. The main goal of this work is to evaluate the impacts of local air-sea interaction in the simulation of the interannual variability, over the Indian CORDEX (Giorgi et al, 2009) domain through regionally ocean-atmosphere-river coupled and uncoupled simulations, with a focus on monsoon season

  19. Appearance of large crystalline domains in VO{sub 2} films grown on sapphire (001) and their phase transition characteristics

    SciTech Connect

    Azhan, Nurul Hanis; Su, Kui; Okimura, Kunio; Zaghrioui, Mustapha; Sakai, Joe

    2015-06-28

    We report the first observation of large crystalline domains of several μm-size in VO{sub 2} films deposited on Al{sub 2}O{sub 3} (001) substrates by rf-biased reactive sputtering technique. The large crystalline domains, dominated with random in-plane oriented growth of (011){sub M1}-orientation, appear only under adequate substrate biasing, such as 10 W, while most biasing conditions result in conventional nanosized grains of highly oriented (010){sub M1}-orientation. Two temperature-controlled analyses, x-ray diffraction and micro-Raman spectroscopy, have revealed that some parts of large crystalline domains undergo intermediate monoclinic (M2) phase during the thermally-induced structural phase transition from monoclinic (M1) to rutile-tetragonal (R) phase. As an effect of the appearance of large crystalline domains, the film showed in-plane tensile stress, resulting in high T{sub IMT} of 69 °C due to the elongation of the V-V distance in its low-temperature monoclinic phase.

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

    SciTech Connect

    Yuchi, Zhiguang; Lau, Kelvin; Van Petegem, Filip

    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.

  1. Anisotropic aberration correction using region of interest based digital adaptive optics in Fourier domain OCT

    PubMed Central

    Kumar, Abhishek; Kamali, Tschackad; Platzer, René; Unterhuber, Angelika; Drexler, Wolfgang; Leitgeb, Rainer A.

    2015-01-01

    In this paper a numerical technique is presented to compensate for anisotropic optical aberrations, which are usually present across the lateral field of view in the out of focus regions, in high resolution optical coherence tomography and microscopy (OCT/OCM) setups. The recorded enface image field at different depths in the tomogram is digitally divided into smaller sub-regions or the regions of interest (ROIs), processed individually using subaperture based digital adaptive optics (DAO), and finally stitched together to yield a final image with a uniform diffraction limited resolution across the entire field of view (FOV). Using this method, a sub-micron lateral resolution is achieved over a depth range of 218 μmfor a nano-particle phantom sample imaged using a fiber based point scanning spectral domain (SD) OCM system with a limited depth of focus (DOF) of ~7 μmat a numerical aperture (NA) of 0.6. Thus, an increase in DOF by ~30x is demonstrated in this case. The application of this method is also shown in ex vivo mouse adipose tissue. PMID:25908999

  2. Some Uniform Estimates and Large-Time Behavior of Solutions to One-Dimensional Compressible Navier-Stokes System in Unbounded Domains with Large Data

    NASA Astrophysics Data System (ADS)

    Li, Jing; Liang, Zhilei

    2016-06-01

    We study the large-time behavior of solutions to the initial and initial boundary value problems with large initial data for the compressible Navier-Stokes system describing the one-dimensional motion of a viscous heat-conducting perfect polytropic gas in unbounded domains. The temperature is proved to be bounded from below and above, independent of both time and space. Moreover, it is shown that the global solution is asymptotically stable as time tends to infinity. Note that the initial data can be arbitrarily large. This result is proved by using elementary energy methods.

  3. Conservation voltage reduction: Estimating methodology for a large regional application

    SciTech Connect

    De Steese, J.G.; Kennedy, B.W.; Merrick, S.B.

    1992-04-01

    Conservation Voltage Reduction (CVR) is an established and cost-effective practice that has motivated many utilities to investigate its application on individual systems. This paper describes a supply-curve methodology that can determine the conservation value of CVR applied to many distribution systems in a region. In the area served by Bonneville Power Administration involving approximately 150 utilities, the systematic implementations of CVR could conserve between 170 and 268 Average Megawatts at a cost of 5 cents/kWh. This was shown to be a larger resource than might be achievable by applying more conventional efficiency improvements to transmission and distribution (T&D) systems in the region.

  4. Conservation voltage reduction: Estimating methodology for a large regional application

    SciTech Connect

    De Steese, J.G. ); Kennedy, B.W. ); Merrick, S.B. )

    1992-04-01

    Conservation Voltage Reduction (CVR) is an established and cost-effective practice that has motivated many utilities to investigate its application on individual systems. This paper describes a supply-curve methodology that can determine the conservation value of CVR applied to many distribution systems in a region. In the area served by Bonneville Power Administration involving approximately 150 utilities, the systematic implementations of CVR could conserve between 170 and 268 Average Megawatts at a cost of 5 cents/kWh. This was shown to be a larger resource than might be achievable by applying more conventional efficiency improvements to transmission and distribution (T D) systems in the region.

  5. The C-terminal region of Drosophila heat shock factor (HSF) contains a constitutively functional transactivation domain.

    PubMed Central

    Wisniewski, J; Orosz, A; Allada, R; Wu, C

    1996-01-01

    The heat shock transcription factor (HSF) is constitutively expressed in Drosophila cells as an inactive monomer. Upon heat shock HSF undergoes trimerization and acquires high affinity DNA binding ability leading to specific interaction with its cognate elements in heat shock promoters. Here we show that the transactivation function of HSF is conferred by the extreme C-terminal region of the protein. Deletion analysis of HSF fragments fused to the GAL4 DNA-binding domain demonstrates that transactivation is dependent on HSF residues 610-691. This domain is located beyond the C-terminal heptad repeat (leucine zipper 4) whose presence or integrity is dispensable for transactivation. The transactivation domain is functional in the absence of heat shock and can be replaced by the extreme C-terminal region of human HSF1. The Drosophila and human HSF transactivation domains are both rich in hydrophobic and acidic residues and may be structurally conserved, despite limited sequence identity. PMID:8628664

  6. Thrombospondin Type-1 Repeat Domain-Containing Proteins Are Strongly Expressed in the Head Region of Hydra.

    PubMed

    Hamaguchi-Hamada, Kayoko; Kurumata-Shigeto, Mami; Minobe, Sumiko; Fukuoka, Nozomi; Sato, Manami; Matsufuji, Miyuki; Koizumi, Osamu; Hamada, Shun

    2016-01-01

    The head region of Hydra, the hypostome, is a key body part for developmental control and the nervous system. We herein examined genes specifically expressed in the head region of Hydra oligactis using suppression subtractive hybridization (SSH) cloning. A total of 1414 subtracted clones were sequenced and found to be derived from at least 540 different genes by BLASTN analyses. Approximately 25% of the subtracted clones had sequences encoding thrombospondin type-1 repeat (TSR) domains, and were derived from 17 genes. We identified 11 TSR domain-containing genes among the top 36 genes that were the most frequently detected in our SSH library. Whole-mount in situ hybridization analyses confirmed that at least 13 out of 17 TSR domain-containing genes were expressed in the hypostome of Hydra oligactis. The prominent expression of TSR domain-containing genes suggests that these genes play significant roles in the hypostome of Hydra oligactis. PMID:27043211

  7. Thrombospondin Type-1 Repeat Domain-Containing Proteins Are Strongly Expressed in the Head Region of Hydra

    PubMed Central

    Hamaguchi-Hamada, Kayoko; Kurumata-Shigeto, Mami; Minobe, Sumiko; Fukuoka, Nozomi; Sato, Manami; Matsufuji, Miyuki; Koizumi, Osamu; Hamada, Shun

    2016-01-01

    The head region of Hydra, the hypostome, is a key body part for developmental control and the nervous system. We herein examined genes specifically expressed in the head region of Hydra oligactis using suppression subtractive hybridization (SSH) cloning. A total of 1414 subtracted clones were sequenced and found to be derived from at least 540 different genes by BLASTN analyses. Approximately 25% of the subtracted clones had sequences encoding thrombospondin type-1 repeat (TSR) domains, and were derived from 17 genes. We identified 11 TSR domain-containing genes among the top 36 genes that were the most frequently detected in our SSH library. Whole-mount in situ hybridization analyses confirmed that at least 13 out of 17 TSR domain-containing genes were expressed in the hypostome of Hydra oligactis. The prominent expression of TSR domain-containing genes suggests that these genes play significant roles in the hypostome of Hydra oligactis. PMID:27043211

  8. Effective crop evapotranspiration measurement using time-domain reflectometry technique in a sub-humid region

    NASA Astrophysics Data System (ADS)

    Srivastava, R. K.; Panda, R. K.; Halder, Debjani

    2016-06-01

    The primary objective of this study was to evaluate the performance of the time-domain reflectometry (TDR) technique for daily evapotranspiration estimation of peanut and maize crop in a sub-humid region. Four independent methods were used to estimate crop evapotranspiration (ETc), namely, soil water balance budgeting approach, energy balance approach—(Bowen ratio), empirical methods approach, and Pan evaporation method. The soil water balance budgeting approach utilized the soil moisture measurement by gravimetric and TDR method. The empirical evapotranspiration methods such as combination approach (FAO-56 Penman-Monteith and Penman), temperature-based approach (Hargreaves-Samani), and radiation-based approach (Priestley-Taylor, Turc, Abetw) were used to estimate the reference evapotranspiration (ET0). The daily ETc determined by the FAO-56 Penman-Monteith, Priestley-Taylor, Turc, Pan evaporation, and Bowen ratio were found to be at par with the ET values derived from the soil water balance budget; while the methods Abetw, Penman, and Hargreaves-Samani were not found to be ideal for the determination of ETc. The study illustrates the in situ applicability of the TDR method in order to make it possible for a user to choose the best way for the optimum water consumption for a given crop in a sub-humid region. The study suggests that the FAO-56 Penman-Monteith, Turc, and Priestley-Taylor can be used for the determination of crop ETc using TDR in comparison to soil water balance budget.

  9. Structural basis of ligand interactions of the large extracellular domain of tetraspanin CD81.

    PubMed

    Rajesh, Sundaresan; Sridhar, Pooja; Tews, Birke Andrea; Fénéant, Lucie; Cocquerel, Laurence; Ward, Douglas G; Berditchevski, Fedor; Overduin, Michael

    2012-09-01

    Hepatitis C virus (HCV) causes chronic liver disease, cirrhosis, and primary liver cancer. Despite 130 million people being at risk worldwide, no vaccine exists, and effective therapy is limited by drug resistance, toxicity, and high costs. The tetraspanin CD81 is an essential entry-level receptor required for HCV infection of hepatocytes and represents a critical target for intervention. In this study, we report the first structural characterization of the large extracellular loop of CD81, expressed in mammalian cells and studied in physiological solutions. The HCV E2 glycoprotein recognizes CD81 through a dynamic loop on the helical bundle, which was shown by nuclear magnetic resonance (NMR) spectroscopy to adopt a conformation distinct from that seen in crystals. A novel membrane binding interface was revealed adjacent to the exposed HCV interaction site in the extracellular loop of CD81. The binding pockets for two proposed inhibitors of the CD81-HCV interaction, namely, benzyl salicylate and fexofenadine, were shown to overlap the HCV and membrane interaction sites. Although the dynamic loop region targeted by these compounds presents challenges for structure-based design, the NMR assignments enable realistic screening and validation of ligands. Together, these data provide an improved avenue for developing potent agents that specifically block CD81-HCV interaction and also pave a way for elucidating the recognition mechanisms of diverse tetraspanins. PMID:22740401

  10. Interlocked chiral/polar domain walls and large optical rotation in Ni{sub 3}TeO{sub 6}

    SciTech Connect

    Wang, Xueyun; Huang, Fei-Ting; Yang, Junjie; Oh, Yoon Seok; Cheong, Sang-Wook

    2015-07-01

    Chirality, i.e., handedness, pervades much of modern science from elementary particles, DNA-based biology to molecular chemistry; however, most of the chirality-relevant materials have been based on complex molecules. Here, we report inorganic single-crystalline Ni{sub 3}TeO{sub 6}, forming in a corundum-related R3 structure with both chirality and polarity. These chiral Ni{sub 3}TeO{sub 6} single crystals exhibit a large optical specific rotation (α)—1355° dm{sup −1} cm{sup 3} g{sup −1}. We demonstrate, for the first time, that in Ni{sub 3}TeO{sub 6}, chiral and polar domains form an intriguing domain pattern, resembling a radiation warning sign, which stems from interlocked chiral and polar domain walls through lowering of the wall energy.

  11. Non-Linear and Flexible Regions of the Human Notch1 Extracellular Domain Revealed by High-Resolution Structural Studies

    PubMed Central

    Weisshuhn, Philip C.; Sheppard, Devon; Taylor, Paul; Whiteman, Pat; Lea, Susan M.; Handford, Penny A.; Redfield, Christina

    2016-01-01

    Summary The Notch receptor is a key component of a core metazoan signaling pathway activated by Delta/Serrate/Lag-2 ligands expressed on an adjacent cell. This results in a short-range signal with profound effects on cell-fate determination, cell proliferation, and cell death. Key to understanding receptor function is structural knowledge of the large extracellular portion of Notch which contains multiple repeats of epidermal growth factor (EGF)-like domains. Here we investigate the EGF4-13 region of human Notch1 (hN1) using a multidisciplinary approach. Ca2+-binding measurements, X-ray crystallography, {1H}-15N heteronuclear nuclear Overhauser effects, and residual dipolar couplings support a non-linear organization for the EGF4-13 region with a rigid, bent conformation for EGF4-7 and a single flexible linkage between EGF9 and EGF10. These data allow us to construct an informed model for EGF10-13 which, in conjunction with comparative binding studies, demonstrates that EGF10 has an important role in determining Notch receptor sensitivity to Dll-4. PMID:26996961

  12. Large-scale interaction profiling of PDZ domains through proteomic peptide-phage display using human and viral phage peptidomes.

    PubMed

    Ivarsson, Ylva; Arnold, Roland; McLaughlin, Megan; Nim, Satra; Joshi, Rakesh; Ray, Debashish; Liu, Bernard; Teyra, Joan; Pawson, Tony; Moffat, Jason; Li, Shawn Shun-Cheng; Sidhu, Sachdev S; Kim, Philip M

    2014-02-18

    The human proteome contains a plethora of short linear motifs (SLiMs) that serve as binding interfaces for modular protein domains. Such interactions are crucial for signaling and other cellular processes, but are difficult to detect because of their low to moderate affinities. Here we developed a dedicated approach, proteomic peptide-phage display (ProP-PD), to identify domain-SLiM interactions. Specifically, we generated phage libraries containing all human and viral C-terminal peptides using custom oligonucleotide microarrays. With these libraries we screened the nine PSD-95/Dlg/ZO-1 (PDZ) domains of human Densin-180, Erbin, Scribble, and Disks large homolog 1 for peptide ligands. We identified several known and putative interactions potentially relevant to cellular signaling pathways and confirmed interactions between full-length Scribble and the target proteins β-PIX, plakophilin-4, and guanylate cyclase soluble subunit α-2 using colocalization and coimmunoprecipitation experiments. The affinities of recombinant Scribble PDZ domains and the synthetic peptides representing the C termini of these proteins were in the 1- to 40-μM range. Furthermore, we identified several well-established host-virus protein-protein interactions, and confirmed that PDZ domains of Scribble interact with the C terminus of Tax-1 of human T-cell leukemia virus with micromolar affinity. Previously unknown putative viral protein ligands for the PDZ domains of Scribble and Erbin were also identified. Thus, we demonstrate that our ProP-PD libraries are useful tools for probing PDZ domain interactions. The method can be extended to interrogate all potential eukaryotic, bacterial, and viral SLiMs and we suggest it will be a highly valuable approach for studying cellular and pathogen-host protein-protein interactions. PMID:24550280

  13. Observations of large-amplitude, narrowband whistlers at stream interaction regions

    NASA Astrophysics Data System (ADS)

    Breneman, A.; Cattell, C.; Schreiner, S.; Kersten, K.; Wilson, L. B., III; Kellogg, P.; Goetz, K.; Jian, L. K.

    2010-08-01

    We present the first solar wind observations of large-amplitude, narrowband waveforms in the frequency range 10-100 Hz, consistent with the whistler mode. These whistlers are only observable in high time resolution electric field waveform data provided by the Time Domain Sampler (TDS) instrument on STEREO. Amplitudes range from a few to >40 mV/m peak-to-peak, one to three orders of magnitude larger than any previous observations of whistler mode waves in the solar wind. The whistlers are obliquely propagating with a large electrostatic component and are right-hand elliptically polarized in the spacecraft frame. The whistlers occur in groups that are strongly correlated with stream interaction regions (SIRs). The groups persist from a few seconds to minutes and are observed at 88% of SIRs and 17% of shocks from available data. A more detailed look shows that the whistler groups are observed near sudden disturbances of the solar wind magnetic field and plasma. We suggest that, owing to the oblique and narrowband nature of these waves, an electron or ion beam instability may be responsible for their creation. Test particle simulations show that the waves can interact strongly with halo (>60 eV) electrons. Test electrons were scattered by tens of degrees and energized/deenergized by up to 50% in a few tens of milliseconds. Thus these whistlers may play an important role in the dynamics of solar wind electrons within SIRs and near some shocks.

  14. Structural Domains within the 3′ Untranslated Region of Turnip Crinkle Virus▿

    PubMed Central

    McCormack, John C.; Yuan, Xuefeng; Yingling, Yaroslava G.; Kasprzak, Wojciech; Zamora, Rodolfo E.; Shapiro, Bruce A.; Simon, Anne E.

    2008-01-01

    The genomes of positive-strand RNA viruses undergo conformational shifts that complicate efforts to equate structures with function. We have initiated a detailed analysis of secondary and tertiary elements within the 3′ end of Turnip crinkle virus (TCV) that are required for viral accumulation in vivo. MPGAfold, a massively parallel genetic algorithm, suggested the presence of five hairpins (H4a, H4b, and previously identified hairpins H4, H5, and Pr) and one H-type pseudoknot (Ψ3) within the 3′-terminal 194 nucleotides (nt). In vivo compensatory mutagenesis analyses confirmed the existence of H4a, H4b, Ψ3 and a second pseudoknot (Ψ2) previously identified in a TCV satellite RNA. In-line structure probing of the 194-nt fragment supported the coexistence of H4, H4a, H4b, Ψ3 and a pseudoknot that connects H5 and the 3′ end (Ψ1). Stepwise replacements of TCV elements with the comparable elements from Cardamine chlorotic fleck virus indicated that the complete 142-nt 3′ end, and subsets containing Ψ3, H4a, and H4b or Ψ3, H4a, H4b, H5, and Ψ2, form functional domains for virus accumulation in vivo. A new 3-D molecular modeling protocol (RNA2D3D) predicted that H4a, H4b, H5, Ψ3, and Ψ2 are capable of simultaneous existence and bears some resemblance to a tRNA. The related Japanese iris necrotic ring virus does not have comparable domains. These results provide a framework for determining how interconnected elements participate in processes that require 3′ untranslated region sequences such as translation and replication. PMID:18579599

  15. Structure-based Design of a Disulfide-lined Oligomeric Form of the Simian Virus 40 (SV40) Large T Antigen DNA-Binding Domain

    SciTech Connect

    G Meinke; P Phelan; A Fradet-Turcotte; J Archambault; P Bullock

    2011-12-31

    The modular multifunctional protein large T antigen (T-ag) from simian virus 40 orchestrates many of the events needed for replication of the viral double-stranded DNA genome. This protein assembles into single and double hexamers on specific DNA sequences located at the origin of replication. This complicated process begins when the origin-binding domain of large T antigen (T-ag ODB) binds the GAGGC sequences in the central region (site II) of the viral origin of replication. While many of the functions of purified T-ag OBD can be studied in isolation, it is primarily monomeric in solution and cannot assemble into hexamers. To overcome this limitation, the possibility of engineering intermolecular disulfide bonds in the origin-binding domain which could oligomerize in solution was investigated. A recent crystal structure of the wild-type T-ag OBD showed that this domain forms a left-handed spiral in the crystal with six subunits per turn. Therefore, we analyzed the protein interface of this structure and identified two residues that could potentially support an intermolecular disulfide bond if changed to cysteines. SDS-PAGE analysis established that the mutant T-ag OBD formed higher oligomeric products in a redox-dependent manner. In addition, the 1.7 {angstrom} resolution crystal structure of the engineered disulfide-linked T-ag OBD is reported, which establishes that oligomerization took place in the expected manner.

  16. The Effect of Regional Climate Model Domain Choice on the Simulation of Tropical Cyclone-Like Vortices in the Southwestern Indian Ocean.

    NASA Astrophysics Data System (ADS)

    Landman, Willem A.; Seth, Anji; Camargo, Suzana J.

    2005-04-01

    A regional climate model is tested for several domain configurations over the southwestern Indian Ocean to examine the ability of the model to reproduce observed cyclones and their landfalling tracks. The interaction between large-scale and local terrain forcing of tropical storms approaching and transiting the island landmass of Madagascar makes the southwestern Indian Ocean a unique and interesting study area. In addition, tropical cyclones across the southern Indian Ocean are likely to be significantly affected by the large-scale zonal flow. Therefore, the effects of model domain size and the positioning of its lateral boundaries on the simulation of tropical cyclone-like vortices and their tracks on a seasonal time scale are investigated. Four tropical cyclones, which occurred over the southwestern Indian Ocean in January of the years 1995-97, are studied, and four domains are tested. The regional climate model is driven by atmospheric lateral boundary conditions that are derived from large-scale meteorological analyses. The use of analyzed boundary forcing enables comparison with observed cyclones in these tests. Simulations are performed using a 60-km horizontal resolution and for an extended time integration of about 6 weeks. Results show that the positioning of the eastern boundary of the regional model domain is of major importance in the life cycle of simulated tropical cyclone-like vortices: a vortex entering through the eastern boundary of the regional model is generally well simulated. The size of the domain also has a bearing on the ability of the regional model to simulate vortices in the Mozambique Channel, and the island landmass of Madagascar additionally influences storm tracks. These results show that the regional model can produce cyclonelike vortices and their tracks (with some deficiencies) given analyzed lateral boundary forcing. Statistical analyses of GCM-driven nested model ensemble integrations are now required to further address

  17. Normal Activation of Discoidin Domain Receptor 1 Mutants with Disulfide Cross-links, Insertions, or Deletions in the Extracellular Juxtamembrane Region

    PubMed Central

    Xu, Huifang; Abe, Takemoto; Liu, Justin K. H.; Zalivina, Irina; Hohenester, Erhard; Leitinger, Birgit

    2014-01-01

    The discoidin domain receptors, DDR1 and DDR2, are receptor tyrosine kinases that are activated by collagen. DDR activation does not appear to occur by the common mechanism of ligand-induced receptor dimerization: the DDRs form stable noncovalent dimers in the absence of ligand, and ligand-induced autophosphorylation of cytoplasmic tyrosines is unusually slow and sustained. Here we sought to identify functionally important dimer contacts within the extracellular region of DDR1 by using cysteine-scanning mutagenesis. Cysteine substitutions close to the transmembrane domain resulted in receptors that formed covalent dimers with high efficiency, both in the absence and presence of collagen. Enforced covalent dimerization did not result in constitutive activation and did not affect the ability of collagen to induce receptor autophosphorylation. Cysteines farther away from the transmembrane domain were also cross-linked with high efficiency, but some of these mutants could no longer be activated. Furthermore, the extracellular juxtamembrane region of DDR1 tolerated large deletions as well as insertions of flexible segments, with no adverse effect on activation. These findings indicate that the extracellular juxtamembrane region of DDR1 is exceptionally flexible and does not constrain the basal or ligand-activated state of the receptor. DDR1 transmembrane signaling thus appears to occur without conformational coupling through the juxtamembrane region, but requires specific receptor interactions farther away from the cell membrane. A plausible mechanism to explain these findings is signaling by DDR1 clusters. PMID:24671415

  18. Properties of the DNA-binding domain of the simian virus 40 large T antigen.

    PubMed Central

    McVey, D; Strauss, M; Gluzman, Y

    1989-01-01

    T antigen (Tag) from simian virus 40 binds specifically to two distinct sites in the viral origin of replication and to single-stranded DNA. Analysis of the protein domain responsible for these activities revealed the following. (i) The C-terminal boundary of the origin-specific and single-strand-specific DNA-binding domain is at or near amino acid 246; furthermore, the maximum of these DNA-binding activities coincides with a narrow C-terminal boundary, spanning 4 amino acids (246 to 249) and declines sharply in proteins with C termini which differ by a few (4 to 10) amino acids; (ii) a polypeptide spanning residues 132 to 246 of Tag is an independent domain responsible for origin-specific DNA binding and presumably for single-stranded DNA binding; and (iii) a comparison of identical N-terminal fragments of Tag purified from mammalian and bacterial cells revealed differential specificity and levels of activity between the two sources of protein. A role for posttranslational modification (phosphorylation) in controlling the DNA-binding activity of Tag is discussed. Images PMID:2555700

  19. Mutations in N-terminal Flanking Region of Blue Light-sensing Light-Oxygen and Voltage 2 (LOV2) Domain Disrupt Its Repressive Activity on Kinase Domain in the Chlamydomonas Phototropin*

    PubMed Central

    Aihara, Yusuke; Yamamoto, Takaharu; Okajima, Koji; Yamamoto, Kazuhiko; Suzuki, Tomomi; Tokutomi, Satoru; Tanaka, Kazuma; Nagatani, Akira

    2012-01-01

    Phototropin is a light-regulated kinase that mediates a variety of photoresponses such as phototropism, chloroplast positioning, and stomata opening in plants to increase the photosynthetic efficiency. Blue light stimulus first induces local conformational changes in the chromophore-bearing light-oxygen and voltage 2 (LOV2) domain of phototropin, which in turn activates the serine/threonine (Ser/Thr) kinase domain in the C terminus. To examine the kinase activity of full-length phototropin conventionally, we employed the budding yeast Saccharomyces cerevisiae. In this organism, Ser/Thr kinases (Fpk1p and Fpk2p) that show high sequence similarity to the kinase domain of phototropins exist. First, we demonstrated that the phototropin from Chlamydomonas reinhardtii (CrPHOT) could complement loss of Fpk1p and Fpk2p to allow cell growth in yeast. Furthermore, this reaction was blue light-dependent, indicating that CrPHOT was indeed light-activated in yeast cells. We applied this system to a large scale screening for amino acid substitutions in CrPHOT that elevated the kinase activity in darkness. Consequently, we identified a cluster of mutations located in the N-terminal flanking region of LOV2 (R199C, L202L, D203N/G/V, L204P, T207I, and R210H). An in vitro phosphorylation assay confirmed that these mutations substantially reduced the repressive activity of LOV2 on the kinase domain in darkness. Furthermore, biochemical analyses of the representative T207I mutant demonstrated that the mutation affected neither spectral nor multimerization properties of CrPHOT. Hence, the N-terminal flanking region of LOV2, as is the case with the C-terminal flanking Jα region, appears to play a crucial role in the regulation of kinase activity in phototropin. PMID:22291022

  20. Structural insights into the specific binding of huntingtin proline-rich region with the SH3 and WW domains.

    PubMed

    Gao, Yong-Guang; Yan, Xian-Zhong; Song, Ai-Xin; Chang, Yong-Gang; Gao, Xue-Chao; Jiang, Nan; Zhang, Qi; Hu, Hong-Yu

    2006-12-01

    The interactions of huntingtin (Htt) with the SH3 domain- or WW domain-containing proteins have been implicated in the pathogenesis of Huntington's disease (HD). We report the specific interactions of Htt proline-rich region (PRR) with the SH3GL3-SH3 domain and HYPA-WW1-2 domain pair by NMR. The results show that Htt PRR binds with the SH3 domain through nearly its entire chain, and that the binding region on the domain includes the canonical PxxP-binding site and the specificity pocket. The C terminus of PRR orients to the specificity pocket, whereas the N terminus orients to the PxxP-binding site. Htt PRR can also specifically bind to WW1-2; the N-terminal portion preferentially binds to WW1, while the C-terminal portion binds to WW2. This study provides structural insights into the specific interactions between Htt PRR and its binding partners as well as the alteration of these interactions that involve PRR, which may have implications for the understanding of HD. PMID:17161366

  1. The Receptor-Binding Domain in the VP1u Region of Parvovirus B19

    PubMed Central

    Leisi, Remo; Di Tommaso, Chiarina; Kempf, Christoph; Ros, Carlos

    2016-01-01

    Parvovirus B19 (B19V) is known as the human pathogen causing the mild childhood disease erythema infectiosum. B19V shows an extraordinary narrow tissue tropism for erythroid progenitor cells in the bone marrow, which is determined by a highly restricted uptake. We have previously shown that the specific internalization is mediated by the interaction of the viral protein 1 unique region (VP1u) with a yet unknown cellular receptor. To locate the receptor-binding domain (RBD) within the VP1u, we analyzed the effect of truncations and mutations on the internalization capacity of the recombinant protein into UT7/Epo cells. Here we report that the N-terminal amino acids 5–80 of the VP1u are necessary and sufficient for cellular binding and internalization; thus, this N-terminal region represents the RBD required for B19V uptake. Using site-directed mutagenesis, we further identified a cluster of important amino acids playing a critical role in VP1u internalization. In silico predictions and experimental results suggest that the RBD is structured as a rigid fold of three α-helices. Finally, we found that dimerization of the VP1u leads to a considerably enhanced cellular binding and internalization. Taken together, we identified the RBD that mediates B19V uptake and mapped functional and structural motifs within this sequence. The findings reveal insights into the uptake process of B19V, which contribute to understand the pathogenesis of the infection and the neutralization of the virus by the immune system. PMID:26927158

  2. The Receptor-Binding Domain in the VP1u Region of Parvovirus B19.

    PubMed

    Leisi, Remo; Di Tommaso, Chiarina; Kempf, Christoph; Ros, Carlos

    2016-03-01

    Parvovirus B19 (B19V) is known as the human pathogen causing the mild childhood disease erythema infectiosum. B19V shows an extraordinary narrow tissue tropism for erythroid progenitor cells in the bone marrow, which is determined by a highly restricted uptake. We have previously shown that the specific internalization is mediated by the interaction of the viral protein 1 unique region (VP1u) with a yet unknown cellular receptor. To locate the receptor-binding domain (RBD) within the VP1u, we analyzed the effect of truncations and mutations on the internalization capacity of the recombinant protein into UT7/Epo cells. Here we report that the N-terminal amino acids 5-80 of the VP1u are necessary and sufficient for cellular binding and internalization; thus, this N-terminal region represents the RBD required for B19V uptake. Using site-directed mutagenesis, we further identified a cluster of important amino acids playing a critical role in VP1u internalization. In silico predictions and experimental results suggest that the RBD is structured as a rigid fold of three α-helices. Finally, we found that dimerization of the VP1u leads to a considerably enhanced cellular binding and internalization. Taken together, we identified the RBD that mediates B19V uptake and mapped functional and structural motifs within this sequence. The findings reveal insights into the uptake process of B19V, which contribute to understand the pathogenesis of the infection and the neutralization of the virus by the immune system. PMID:26927158

  3. The auto-inhibitory domain and ATP-independent microtubule-binding region of Kinesin heavy chain are major functional domains for transport in the Drosophila germline

    PubMed Central

    Williams, Lucy S.; Ganguly, Sujoy; Loiseau, Philippe; Ng, Bing Fu; Palacios, Isabel M.

    2014-01-01

    The major motor Kinesin-1 provides a key pathway for cell polarization through intracellular transport. Little is known about how Kinesin works in complex cellular surroundings. Several cargos associate with Kinesin via Kinesin light chain (KLC). However, KLC is not required for all Kinesin transport. A putative cargo-binding domain was identified in the C-terminal tail of fungal Kinesin heavy chain (KHC). The tail is conserved in animal KHCs and might therefore represent an alternative KLC-independent cargo-interacting region. By comprehensive functional analysis of the tail during Drosophila oogenesis we have gained an understanding of how KHC achieves specificity in its transport and how it is regulated. This is, to our knowledge, the first in vivo structural/functional analysis of the tail in animal Kinesins. We show that the tail is essential for all functions of KHC except Dynein transport, which is KLC dependent. These tail-dependent KHC activities can be functionally separated from one another by further characterizing domains within the tail. In particular, our data show the following. First, KHC is temporally regulated during oogenesis. Second, the IAK domain has an essential role distinct from its auto-inhibitory function. Third, lack of auto-inhibition in itself is not necessarily detrimental to KHC function. Finally, the ATP-independent microtubule-binding motif is required for cargo localization. These results stress that two unexpected highly conserved domains, namely the auto-inhibitory IAK and the auxiliary microtubule-binding motifs, are crucial for transport by Kinesin-1 and that, although not all cargos are conserved, their transport involves the most conserved domains of animal KHCs. PMID:24257625

  4. Large mining blasts from the Kursk Mining Region, Russia

    SciTech Connect

    Leith, W. Adushkin, V.; Spivak, A.

    1997-01-01

    Monitoring the Comprehensive Nuclear Test Ban Treaty (CTBT) by seismic means will require identification of seismic sources at magnitude levels where industrial explosions (primarily, mining blasts) may comprise a significant fraction of the total number of events recorded, and may for some countries dominate the seismicity. Thus, data on blasting practice have both political significance for the negotiation of treaties involving seismic monitoring of nuclear tests, and operational applications in terms of establishing monitoring and inspection needs on a mine-by-mine basis. While it is generally accepted that mining explosions contribute to seismicity at lower seismic magnitudes (less than about magnitude 3.5), the rate of mining seismicity as a function of seismic magnitude is unknown for most countries outside the U.S. This results in a large uncertainty when estimating the task of discriminating nuclear explosions from chemical explosions and earthquakes, by seismic means, under a comprehensive nuclear test ban. This uncertainty directly affects estimates of seismic network enhancements required to achieve treaty verification requirements at magnitudes less than about 3.5. 24 refs., 64 figs., 11 tabs.

  5. Development and use of domain-specific antibodies in a characterization of the large subunits of soybean photosystem 1

    NASA Technical Reports Server (NTRS)

    Henry, R. L.; Takemoto, L. J.; Murphy, J.; Gallegos, G. L.; Guikema, J. A.; Spooner, B. S. (Principal Investigator)

    1992-01-01

    The molecular architecture of the soybean photosystem 1 reaction center complex was examined using a combination of surface labeling and immunological methodology on isolated thylakoid membranes. Synthetic peptides (12 to 14 amino acids in length) were prepared which correspond to the N-terminal regions of the 83 and 82.4 kDa subunits of photosystem 1 (the PsaA and PsaB proteins, respectively). Similarly, a synthetic peptide was prepared corresponding to the C-terminal region of the PsaB subunit. These peptides were conjugated to a carrier protein, and were used for the production of polyclonal antibodies in rabbits. The resulting sera could distinguish between the PsaA and PsaB photosystem 1 subunits by Western blot analysis, and could identify appropriate size classes of cyanogen bromide cleavage fragments as predicted from the primary sequences of these two subunits. When soybean thylakoid membranes were surface-labeled with N-hydroxysuccinimidobiotin, several subunits of the complete photosystem 1 lipid/protein complex incorporated label. These included the light harvesting chlorophyll proteins of photosystem 1, and peptides thought to aid in the docking of ferredoxin to the complex during photosynthetic electron transport. However, the PsaA and PsaB subunits showed very little biotinylation. When these subunits were examined for the domains to which biotin did attach, most of the observed label was associated with the N-terminal domain of the PsaA subunit, as identified using a domain-specific polyclonal antisera.

  6. Multiscale method for modeling binding phenomena involving large objects: application to kinesin motor domains motion along microtubules.

    PubMed

    Li, Lin; Alper, Joshua; Alexov, Emil

    2016-01-01

    Many biological phenomena involve the binding of proteins to a large object. Because the electrostatic forces that guide binding act over large distances, truncating the size of the system to facilitate computational modeling frequently yields inaccurate results. Our multiscale approach implements a computational focusing method that permits computation of large systems without truncating the electrostatic potential and achieves the high resolution required for modeling macromolecular interactions, all while keeping the computational time reasonable. We tested our approach on the motility of various kinesin motor domains. We found that electrostatics help guide kinesins as they walk: N-kinesins towards the plus-end, and C-kinesins towards the minus-end of microtubules. Our methodology enables computation in similar, large systems including protein binding to DNA, viruses, and membranes. PMID:26988596

  7. Multiscale method for modeling binding phenomena involving large objects: application to kinesin motor domains motion along microtubules

    NASA Astrophysics Data System (ADS)

    Li, Lin; Alper, Joshua; Alexov, Emil

    2016-03-01

    Many biological phenomena involve the binding of proteins to a large object. Because the electrostatic forces that guide binding act over large distances, truncating the size of the system to facilitate computational modeling frequently yields inaccurate results. Our multiscale approach implements a computational focusing method that permits computation of large systems without truncating the electrostatic potential and achieves the high resolution required for modeling macromolecular interactions, all while keeping the computational time reasonable. We tested our approach on the motility of various kinesin motor domains. We found that electrostatics help guide kinesins as they walk: N-kinesins towards the plus-end, and C-kinesins towards the minus-end of microtubules. Our methodology enables computation in similar, large systems including protein binding to DNA, viruses, and membranes.

  8. Multiscale method for modeling binding phenomena involving large objects: application to kinesin motor domains motion along microtubules

    PubMed Central

    Li, Lin; Alper, Joshua; Alexov, Emil

    2016-01-01

    Many biological phenomena involve the binding of proteins to a large object. Because the electrostatic forces that guide binding act over large distances, truncating the size of the system to facilitate computational modeling frequently yields inaccurate results. Our multiscale approach implements a computational focusing method that permits computation of large systems without truncating the electrostatic potential and achieves the high resolution required for modeling macromolecular interactions, all while keeping the computational time reasonable. We tested our approach on the motility of various kinesin motor domains. We found that electrostatics help guide kinesins as they walk: N-kinesins towards the plus-end, and C-kinesins towards the minus-end of microtubules. Our methodology enables computation in similar, large systems including protein binding to DNA, viruses, and membranes. PMID:26988596

  9. Fast analysis of wide-band scattering from electrically large targets with time-domain parabolic equation method

    NASA Astrophysics Data System (ADS)

    He, Zi; Chen, Ru-Shan

    2016-03-01

    An efficient three-dimensional time domain parabolic equation (TDPE) method is proposed to fast analyze the narrow-angle wideband EM scattering properties of electrically large targets. The finite difference (FD) of Crank-Nicolson (CN) scheme is used as the traditional tool to solve the time-domain parabolic equation. However, a huge computational resource is required when the meshes become dense. Therefore, the alternating direction implicit (ADI) scheme is introduced to discretize the time-domain parabolic equation. In this way, the reduced transient scattered fields can be calculated line by line in each transverse plane for any time step with unconditional stability. As a result, less computational resources are required for the proposed ADI-based TDPE method when compared with both the traditional CN-based TDPE method and the finite-different time-domain (FDTD) method. By employing the rotating TDPE method, the complete bistatic RCS can be obtained with encouraging accuracy for any observed angle. Numerical examples are given to demonstrate the accuracy and efficiency of the proposed method.

  10. A Domain Decomposition Approach for Large-Scale Simulations of Flow Processes in Hydrate-Bearing Geologic Media

    SciTech Connect

    Zhang, Keni; Moridis, G.J.; Wu, Y.-S.; Pruess, K.

    2008-07-01

    Simulation of the system behavior of hydrate-bearing geologic media involves solving fully coupled mass- and heat-balance equations. In this study, we develop a domain decomposition approach for large-scale gas hydrate simulations with coarse-granularity parallel computation. This approach partitions a simulation domain into small subdomains. The full model domain, consisting of discrete subdomains, is still simulated simultaneously by using multiple processes/processors. Each processor is dedicated to following tasks of the partitioned subdomain: updating thermophysical properties, assembling mass- and energy-balance equations, solving linear equation systems, and performing various other local computations. The linearized equation systems are solved in parallel with a parallel linear solver, using an efficient interprocess communication scheme. This new domain decomposition approach has been implemented into the TOUGH+HYDRATE code and has demonstrated excellent speedup and good scalability. In this paper, we will demonstrate applications for the new approach in simulating field-scale models for gas production from gas-hydrate deposits.

  11. Multipactor radiation analysis within a waveguide region based on a frequency-domain representation of the dynamics of charged particles.

    PubMed

    Gimeno, B; Sorolla, E; Anza, S; Vicente, C; Gil, J; Pérez, A M; Boria, V E; Pérez-Soler, F J; Quesada, F; Alvarez, A; Raboso, D

    2009-04-01

    A technique for the accurate computation of the electromagnetic fields radiated by a charged particle moving within a parallel-plate waveguide is presented. Based on a transformation of the time-varying current density of the particle into a time-harmonic current density, this technique allows the evaluation of the radiated electromagnetic fields both in the frequency and time domains, as well as in the near- and far-field regions. For this purpose, several accelerated versions of the parallel-plate Green's function in the frequency domain have been considered. The theory has been successfully applied to the multipactor discharge occurring within a two metal-plates region. The proposed formulation has been tested with a particle-in-cell code based on the finite-difference time-domain method, obtaining good agreement. PMID:19518368

  12. Automated on-orbit frequency domain identification for large space structures

    NASA Technical Reports Server (NTRS)

    Bayard, D. S.; Hadaegh, F. Y.; Yam, Y.; Scheid, R. E.; Mettler, E.; Milman, M. H.

    1991-01-01

    Recent experiences in the field of flexible structure control in space have indicated a need for on-orbit system identification to support robust control redesign to avoid in-flight instabilities and maintain high spacecraft performance. This paper highlights an automated frequency domain system identification methodology recently developed to fulfill this need. The methodology is focused to support (1) the estimation of system quantities useful for robust control analysis and design; (2) experiment design tailored to performing system identification in a typically constrained on-orbit environment; and (3) the automation of operations to reduce 'human in the loop' requirements.

  13. Defining the functional domains in the control region of the adenovirus type 2 specific VARNA1 gene.

    PubMed

    Wu, G J; Railey, J F; Cannon, R E

    1987-04-01

    The outer boundaries of the internal transcriptional control region in the VARNA1 gene have been located from positions +10 to +69. To further define the detailed organization of the functional domains in this region and the function(s) of the 5' flanking sequence, and to obtain a more detailed insight into other transcriptionally important sequences, we have constructed 77 mutants with deletion endpoints at almost every one to five base-pairs in the entire region from -30 to +160 for transcriptional studies. Using our highly active crude extract under our assay conditions, and quantitatively measuring the transcriptional efficiency and competing strength of each mutant, we have revealed new features of important transcriptional control sequences and defined the transcriptional functions of several functional domains in this gene. The essential domain is from +59/+63 to +66/+68, which corresponds to the B block sequence. This is smaller than that defined previously. The second most important domain is the region from +12/14 to +40, which includes the A block sequence that dictates the wild-type major start site and amplifies the events started by the B block region, mediated through factors and RNA polymerase III. Furthermore, the domain from -5 to +11 affects the use of certain start site(s). Moreover, the 5' flanking region from -30 to +1 contributes 80 to 90% of the overall transcriptional efficiency of the gene. Finally, our transcriptional studies of mutants deleted of the A block sequence and all of the upstream sequence indicated that an intimate interaction between the two blocks is essential for initiation of transcription. Furthermore, the B block sequence is more important than the A block sequence in the transcription reaction. The mechanism and control of transcriptional initiation in the VARNA1 gene is similar to that in some tRNA genes, but differs from that in others. PMID:3625769

  14. Contributions of the Complementarity Determining Regions to the Thermal Stability of a Single-Domain Antibody

    PubMed Central

    Zabetakis, Dan; Anderson, George P.; Bayya, Nikhil; Goldman, Ellen R.

    2013-01-01

    Single domain antibodies (sdAbs) are the recombinantly-expressed variable domain from camelid (or shark) heavy chain only antibodies and provide rugged recognition elements. Many sdAbs possess excellent affinity and specificity; most refold and are able to bind antigen after thermal denaturation. The sdAb A3, specific for the toxin Staphylococcal enterotoxin B (SEB), shows both sub-nanomolar affinity for its cognate antigen (0.14 nM) and an unusually high melting point of 85°C. Understanding the source of sdAb A3’s high melting temperature could provide a route for engineering improved melting temperatures into other sdAbs. The goal of this work was to determine how much of sdAb A3’s stability is derived from its complementarity determining regions (CDRs) versus its framework. Towards answering this question we constructed a series of CDR swap mutants in which the CDRs from unrelated sdAbs were integrated into A3’s framework and where A3’s CDRs were integrated into the framework of the other sdAbs. All three CDRs from A3 were moved to the frameworks of sdAb D1 (a ricin binder that melts at 50°C) and the anti-ricin sdAb C8 (melting point of 60°C). Similarly, the CDRs from sdAb D1 and sdAb C8 were moved to the sdAb A3 framework. In addition individual CDRs of sdAb A3 and sdAb D1 were swapped. Melting temperature and binding ability were assessed for each of the CDR-exchange mutants. This work showed that CDR2 plays a critical role in sdAb A3’s binding and stability. Overall, results from the CDR swaps indicate CDR interactions play a major role in the protein stability. PMID:24143255

  15. Validation of the regional climate model MAR over the CORDEX Africa domain and comparison with other regional models using unpublished data set

    NASA Astrophysics Data System (ADS)

    Prignon, Maxime; Agosta, Cécile; Kittel, Christoph; Fettweis, Xavier; Michel, Erpicum

    2016-04-01

    In the framework of the CORDEX project, we have applied the regional model MAR over the Africa domain at a resolution of 50 km. ERA-Interim and NCEP-NCAR reanalysis have been used as 6 hourly forcing at the MAR boundaries over 1950-2015. While MAR was already been validated over the West Africa, it is the first time that MAR simulations are carried out at the scale of the whole continent. Unpublished daily measurements, covering the Sahel and more areas up South, with a large set of variables, are used as validation of MAR, other CORDEX-Africa RCMs and both reanalyses. Comparisons with the CRU and the ECA&D databases are also performed. The unpublished daily data set covers the period 1884-2006 and comes from 1460 stations. The measured variables are wind, evapotranspiration, relative humidity, insolation, rain, surface pressure, temperature, vapour pressure and visibility. It covers 23 countries: Algeria, Benin, Burkina, Canary Islands, Cap Verde, Central Africa, Chad, Congo, Ivory Coast, Gabon, Gambia, Ghana, Guinea, Guinea-Bissau, Mali, Mauritania, Morocco, Niger, Nigeria, Senegal, Sudan and Togo.

  16. Large-scale analysis of NBS domain-encoding resistance gene analogs in Triticeae.

    PubMed

    Bouktila, Dhia; Khalfallah, Yosra; Habachi-Houimli, Yosra; Mezghani-Khemakhem, Maha; Makni, Mohamed; Makni, Hanem

    2014-09-01

    Proteins containing nucleotide binding sites (NBS) encoded by plant resistance genes play an important role in the response of plants to a wide array of pathogens. In this paper, an in silico search was conducted in order to identify and characterize members of NBS-encoding gene family in the tribe of Triticeae. A final dataset of 199 sequences was obtained by four search methods. Motif analysis confirmed the general structural organization of the NBS domain in cereals, characterized by the presence of the six commonly conserved motifs: P-loop, RNBS-A, Kinase-2, Kinase-3a, RNBS-C and GLPL. We revealed the existence of 11 distinct distribution patterns of these motifs along the NBS domain. Four additional conserved motifs were shown to be significantly present in all 199 sequences. Phylogenetic analyses, based on genetic distance and parsimony, revealed a significant overlap between Triticeae sequences and Coiled coil-Nucleotide binding site-Leucine rich repeat (CNL)-type functional genes from monocotyledons. Furthermore, several Triticeae sequences belonged to clades containing functional homologs from non Triticeae species, which has allowed for these sequences to be functionally assigned. The findings reported, in this study, will provide a strong groundwork for the isolation of candidate R-genes in Triticeae crops and the understanding of their evolution. PMID:25249784

  17. Large-scale analysis of NBS domain-encoding resistance gene analogs in Triticeae

    PubMed Central

    Bouktila, Dhia; Khalfallah, Yosra; Habachi-Houimli, Yosra; Mezghani-Khemakhem, Maha; Makni, Mohamed; Makni, Hanem

    2014-01-01

    Proteins containing nucleotide binding sites (NBS) encoded by plant resistance genes play an important role in the response of plants to a wide array of pathogens. In this paper, an in silico search was conducted in order to identify and characterize members of NBS-encoding gene family in the tribe of Triticeae. A final dataset of 199 sequences was obtained by four search methods. Motif analysis confirmed the general structural organization of the NBS domain in cereals, characterized by the presence of the six commonly conserved motifs: P-loop, RNBS-A, Kinase-2, Kinase-3a, RNBS-C and GLPL. We revealed the existence of 11 distinct distribution patterns of these motifs along the NBS domain. Four additional conserved motifs were shown to be significantly present in all 199 sequences. Phylogenetic analyses, based on genetic distance and parsimony, revealed a significant overlap between Triticeae sequences and Coiled coil-Nucleotide binding site-Leucine rich repeat (CNL)-type functional genes from monocotyledons. Furthermore, several Triticeae sequences belonged to clades containing functional homologs from non Triticeae species, which has allowed for these sequences to be functionally assigned. The findings reported, in this study, will provide a strong groundwork for the isolation of candidate R-genes in Triticeae crops and the understanding of their evolution. PMID:25249784

  18. Structural and functional studies of a large winged Z-DNA-binding domain of Danio rerio protein kinase PKZ.

    PubMed

    Subramani, Vinod Kumar; Kim, Doyoun; Yun, Kyunghee; Kim, Kyeong Kyu

    2016-07-01

    The Z-DNA-binding domain of PKZ from zebrafish (Danio rerio; drZαPKZ ) contains the largest β-wing among known Z-DNA-binding domains. To elucidate the functional implication of the β-wing, we solved the crystal structure of apo-drZαPKZ . Structural comparison with its Z-DNA-bound form revealed a large conformational change within the β-wing during Z-DNA binding. Biochemical studies of protein mutants revealed that two basic residues in the β-wing are responsible for Z-DNA recognition as well as fast B-Z transition. Therefore, the extra basic residues in the β-wing of drZαPKZ are necessary for the fast B-Z transition activity. PMID:27265117

  19. Large-eddy simulation in complex domains using the finite element method

    SciTech Connect

    McCallen, R.C.; Kornblum, B.T.; Kollman, W.

    1996-11-12

    Finite element methods (FEM) are demonstrated in combination with large-eddy simulations (LES) as a valuable tool for the study of turbulent, separating channel flows, specifically the flow over a backward facing step.

  20. Synthesis of feedback systems with large plant ignorance for prescribed time domain tolerances

    NASA Technical Reports Server (NTRS)

    Horowitz, I. M.; Sidi, M.

    1971-01-01

    There is given a minimum-phase plant transfer function, with prescribed bounds on its parameter values. The plant is imbedded in a two-degree-of freedom feedback system, which is to be designed such that the system time response to a deterministic input lies within specified boundaries. Subject to the above, the design should be such as to minimize the effect of sensor noise at the input to the plant. This report presents a design procedure for this purpose, based on frequency response concepts. The time-domain tolerances are translated into equivalent frequency response tolerances. The latter lead to bounds on the loop transmission function in the form of continuous curves on the Nichols chart. The properties of the loop transmission function which satisfy these bounds with minimum effect of sensor noise, are derived.

  1. Peculiar long-range supercurrent in superconductor-ferromagnet-superconductor junction containing a noncollinear magnetic domain in the ferromagnetic region

    NASA Astrophysics Data System (ADS)

    Meng, Hao; Wu, Xiuqiang; Ren, Yajie

    2015-01-01

    We study the supercurrent in clean superconductor-ferromagnet-superconductor heterostructure containing a noncollinear magnetic domain in the ferromagnetic region. It is demonstrated that the magnetic domain can lead to a spin-flip scattering process, which reverses the spin orientations of the singlet Cooper pair and simultaneously changes the sign of the corresponding electronic momentum. If the ferromagnetic layers on both sides of magnetic domain have the same features, the long-range proximity effect will take place. That is because the singlet Cooper pair will create an exact phase-cancellation effect and gets an additional π phase shift as it passes through the entire ferromagnetic region. Then, the equal spin triplet pair only exists in the magnetic domain region and can not diffuse into the other two ferromagnetic layers. So, the supercurrent mostly arises from the singlet Cooper pairs, and the equal spin triplet pairs are not involved. This result can provide a approach for generating the long-range supercurrent.

  2. Peculiar long-range supercurrent in superconductor-ferromagnet-superconductor junction containing a noncollinear magnetic domain in the ferromagnetic region

    SciTech Connect

    Meng, Hao; Wu, Xiuqiang; Ren, Yajie

    2015-01-14

    We study the supercurrent in clean superconductor-ferromagnet-superconductor heterostructure containing a noncollinear magnetic domain in the ferromagnetic region. It is demonstrated that the magnetic domain can lead to a spin-flip scattering process, which reverses the spin orientations of the singlet Cooper pair and simultaneously changes the sign of the corresponding electronic momentum. If the ferromagnetic layers on both sides of magnetic domain have the same features, the long-range proximity effect will take place. That is because the singlet Cooper pair will create an exact phase-cancellation effect and gets an additional π phase shift as it passes through the entire ferromagnetic region. Then, the equal spin triplet pair only exists in the magnetic domain region and can not diffuse into the other two ferromagnetic layers. So, the supercurrent mostly arises from the singlet Cooper pairs, and the equal spin triplet pairs are not involved. This result can provide a approach for generating the long-range supercurrent.

  3. Liberation of an interaction domain from the phosphotransfer region of CheA, a signaling kinase of Escherichia coli.

    PubMed Central

    Morrison, T B; Parkinson, J S

    1994-01-01

    The CheA protein of Escherichia coli is a histidine autokinase that donates its phosphate groups to two target proteins, CheY and CheB, to regulate flagellar rotation and sensory adaptation during chemotactic responses. The amino-terminal third of CheA contains the autophosphorylation site, determinants needed to interact with the catalytic center of the molecule, and determinants needed for specific recognition of its phosphorylation targets. To understand the structural basis for these activities, we examined the domain organization of the CheA phosphotransfer region by using DNA sequence analysis, limited proteolytic digestion, and a genetic technique called domain liberation. Comparison of the functionally interchangeable CheA proteins of E. coli and Salmonella typhimurium revealed two extensively mismatched segments within the phosphotransfer region, 22 and 25 aa long, with sequences characteristic of domain linkers. Both segments were readily susceptible to proteases, implying that they have an extended, flexible structure. In contrast, the intervening segments of the phosphotransfer region, designated P1 and P2 (roughly 140 and 65 aa, respectively), were relatively insensitive, suggesting they correspond to more compactly folded structural domains. Their functional properties were explored by identifying portions of the cheA coding region capable of interfering with chemotactic behavior when "liberated" and expressed as polypeptides. P1 fragments were not inhibitory, but P2 fragments blocked the interaction of CheY with the rotational switch at the flagellar motor, leading to incessant forward swimming. These results suggest that P2 contains CheY-binding determinants which are normally responsible for phosphotransfer specificity. Domain-liberation approaches should prove generally useful for analyzing multidomain proteins and their interaction targets. Images PMID:8202513

  4. The Bel1 protein of human foamy virus contains one positive and two negative control regions which regulate a distinct activation domain of 30 amino acids.

    PubMed Central

    Lee, C W; Chang, J; Lee, K J; Sung, Y C

    1994-01-01

    The Bel1 transactivator is essential for the replication of human foamy virus (HFV). To define the functional domains of HFV Bel1, we generated random missense mutations throughout the entire coding sequence of Bel1. Functional analyses of 24 missense mutations have revealed the presence of at least two functional domains in Bel1. One domain corresponds to a basic amino acid-rich motif which acts as a bipartite nuclear targeting sequence. A second, central domain corresponds to a presumed effector region which, when mutated, leads to dominant-negative mutants and/or lacks transactivating ability. In addition, deletion analyses and domain-swapping experiments further showed that Bel1 protein contains a strong carboxy-terminal activation domain. The activating region is also capable of functioning as a transcription-activating domain in yeast cells, although it does not bear any significant sequence homology to the well-characterized acidic activation domain which is known to function only in yeast and mammalian cells. We also demonstrated that the regions of Bel1 from residues 1 to 76 and from residues 153 to 225 repressed transcriptional activation exerted by the Bel1 activation domain. In contrast, the region from residues 82 to 150 appears to overcome an inhibitory effect. These results indicate that Bel1 contains one positive and two negative regulatory domains that modulate a distinct activation domain of Bel1. These regulatory domains of Bel1 cannot affect the function of the VP16 activation domain, suggesting that these domains specifically regulate the activation domain of Bel1. Furthermore, in vivo competition experiments showed that the positive regulatory domain acts in trans. Thus, our results demonstrate that Bel1-mediated transactivation appears to undergo a complex regulatory pathway which provides a novel mode of regulation for a transcriptional activation domain. Images PMID:8139046

  5. CnaA domains in bacterial pili are efficient dissipaters of large mechanical shocks

    PubMed Central

    Echelman, Daniel J.; Alegre-Cebollada, Jorge; Badilla, Carmen L.; Chang, Chungyu; Ton-That, Hung; Fernández, Julio M.

    2016-01-01

    Pathogenic bacteria adhere despite severe mechanical perturbations induced by the host, such as coughing. In Gram-positive bacteria, extracellular protein appendages termed pili are necessary for adherence under mechanical stress. However, little is known about the behavior of Gram-positive pili under force. Here, we demonstrate a mechanism by which Gram-positive pili are able to dissipate mechanical energy through mechanical unfolding and refolding of isopeptide bond-delimited polypeptide loops present in Ig-type CnaA domains. Using single-molecule force spectroscopy, we find that these loops of the pilus subunit SpaA of the SpaA-type pilus from Corynebacterium diphtheriae and FimA of the type 2 pilus from Actinomyces oris unfold and extend at forces that are the highest yet reported for globular proteins. Loop refolding is limited by the hydrophobic collapse of the polypeptide and occurs in milliseconds. Remarkably, both SpaA and FimA initially refold to mechanically weaker intermediates that recover strength with time or ligand binding. Based on the high force extensibility, CnaA-containing pili can dissipate ∼28-fold as much energy compared with their inextensible counterparts before reaching forces sufficient to cleave covalent bonds. We propose that efficient mechanical energy dissipation is key for sustained bacterial attachment against mechanical perturbations. PMID:26884173

  6. Exploring Symmetry as an Avenue to the Computational Design of Large Protein Domains

    SciTech Connect

    Fortenberry, Carie; Bowman, Elizabeth Anne; Proffitt, Will; Dorr, Brent; Combs, Steven; Harp, Joel; Mizoue, Laura; Meiler, Jens

    2012-03-15

    It has been demonstrated previously that symmetric, homodimeric proteins are energetically favored, which explains their abundance in nature. It has been proposed that such symmetric homodimers underwent gene duplication and fusion to evolve into protein topologies that have a symmetric arrangement of secondary structure elements - 'symmetric superfolds'. Here, the ROSETTA protein design software was used to computationally engineer a perfectly symmetric variant of imidazole glycerol phosphate synthase and its corresponding symmetric homodimer. The new protein, termed FLR, adopts the symmetric ({beta}{alpha}){sub 8} TIM-barrel superfold. The protein is soluble and monomeric and exhibits two-fold symmetry not only in the arrangement of secondary structure elements but also in sequence and at atomic detail, as verified by crystallography. When cut in half, FLR dimerizes readily to form the symmetric homodimer. The successful computational design of FLR demonstrates progress in our understanding of the underlying principles of protein stability and presents an attractive strategy for the in silico construction of larger protein domains from smaller pieces.

  7. Degenerate specificity of PDZ domains from RhoA-specific nucleotide exchange factors PDZRhoGEF and LARG.

    PubMed

    Smietana, Katarzyna; Kasztura, Monika; Paduch, Marcin; Derewenda, Urszula; Derewenda, Zygmunt S; Otlewski, Jacek

    2008-01-01

    PDZ domains are ubiquitous protein-protein interaction modules which bind short, usually carboxyterminal fragments of receptors, other integral or membrane-associated proteins, and occasionally cytosolic proteins. Their role in organizing multiprotein complexes at the cellular membrane is crucial for many signaling pathways, but the rules defining their binding specificity are still poorly understood and do not readily explain the observed diversity of their known binding partners. Two homologous RhoA-specific, multidomain nucleotide exchange factors PDZRhoGEF and LARG contain PDZ domains which show a particularly broad recognition profile, as suggested by the identification of five diverse biological targets. To investigate the molecular roots of this phenomenon, we constructed a phage display library of random carboxyterminal hexapeptides. Peptide variants corresponding to the sequences identified in library selection were synthesized and their affinities for both PDZ domains were measured and compared with those of peptides derived from sequences of natural partners. Based on the analysis of the binding sequences identified for PDZRhoGEF, we propose a sequence for an 'optimal' binding partner. Our results support the hypothesis that PDZ-peptide interactions may be best understood when one considers the sum of entropic and dynamic effects for each peptide as a whole entity, rather than preferences for specific residues at a given position. PMID:18542831

  8. Lineament Domain of Regional Strike-Slip Corridor: Insight from the Neogene Transtensional De Geer Transform Fault in NW Spitsbergen

    NASA Astrophysics Data System (ADS)

    Cianfarra, P.; Salvini, F.

    2015-05-01

    Lineaments on regional scale images represent controversial features in tectonic studies. Published models explain the presence of the lineament domains in most geodynamic environments as resulting from the enhanced erosion along strikes normal to the upper crustal regional extension. Despite their success in many tectonic frameworks, these models fail to explain the existing lineament domains in the regional strike-slip corridors that separate regional blocks, including the transform faults. The present paper investigates the lineament distribution in such environments, and specifically presents the results from a study along the shear corridor of the De Geer Transform Fault in the North Atlantic, responsible for the separation and drifting away between Northern Greenland and the Svalbard Archipelago since Oligocene times. The study spans from satellite image analysis and outcrop scale investigations to a more regional analysis on a digital bathymetric model of the North Atlantic-Arctic Ocean. Lineaments were automatically detected in the spectral band 8 (0.52-0.9 μm) of a Landsat 7 image (15 m/pixel resolution). A total of 320 image lineaments were extracted from both the regional and the local scale investigations and statistically analyzed. Results from the multi-scalar lineament analyses revealed the existence of a main N-S lineament domain regionally persistent from the De Geer corridor to the western margin of northern Spitsbergen where it relates to the youngest, post-Oligocene, tectonics observed onshore. This is confirmed by field observations showing that the N-S faults represent the youngest brittle deformation system and systematically cut the deformations associated with the building of the Tertiary West Spitsbergen fold and thrust belt. The N-S lineament domain is the result of the activity of a larger, regional scale tectonic feature, NW-SE oriented and responsible for the localized extension within its deformation corridor, the De Geer Transform

  9. Immunoadhesins Containing Pre-S Domains of Hepatitis B Virus Large Envelope Protein Are Secreted and Inhibit Virus Infection▿

    PubMed Central

    Chai, Ning; Gudima, Severin; Chang, Jinhong; Taylor, John

    2007-01-01

    Hepatitis B virus (HBV) replication produces three envelope proteins (L, M, and S) that have a common C terminus. L, the largest, contains a domain, pre-S1, not present on M. Similarly M contains a domain, pre-S2, not present on S. The pre-S1 region has important functions in the HBV life cycle. Thus, as an approach to studying these roles, the pre-S1 and/or pre-S2 sequences of HBV (serotype adw2, genotype A) were expressed as N-terminal fusions to the Fc domain of a rabbit immunoglobulin G chain. Such proteins, known as immunoadhesins (IA), were highly expressed following transfection of cultured cells and, when the pre-S1 region was present, >80% were secreted. The IA were myristoylated at a glycine penultimate to the N terminus, although mutation studies showed that this modification was not needed for secretion. As few as 30 amino acids from the N terminus of pre-S1 were both necessary and sufficient to drive secretion of IA. Even expression of pre-S1 plus pre-S2, in the absence of an immunoglobulin chain, led to efficient secretion. Overall, these studies demonstrate an unexpected ability of the N terminus of pre-S1 to promote protein secretion. In addition, some of these secreted IA, at nanomolar concentrations, inhibited infection of primary human hepatocytes either by hepatitis delta virus (HDV), a subviral agent that uses HBV envelope proteins, or HBV. These IA have potential to be part of antiviral therapies against chronic HDV and HBV, and may help understand the attachment and entry mechanisms used by these important human pathogens. PMID:17329331

  10. 11q23 Translocations split the [open quotes]AT-hook[close quotes] cruciform DNA-binding region and the transcriptional repression domain from the activation domain of the mixed-lineage leukemia (MLL) gene

    SciTech Connect

    Zeleznik-Le, N.J.; Harden, A.M.; Rowley, J.D. )

    1994-10-25

    Translocations involving chromosome band 11q23, found in acute lymphoid and myeloid leukemias, disrupt the MLL gene. This gene encodes a putative transcription factor with homology to the zinc fingers and other domains of the Drosophila trithorax gene product and to the [open quotes]AT-hook[close quotes] motif of high mobility group proteins. To map potential transcriptional activation or repression domains of the MLL protein, yeast GAL4 DNA-binding domain and MLL hybrid protein-expressing plasmids were cotransfected with chloramphenicol acetyltransferase reporter plasmids in a transient transfection system. We found that MLL contains a strong activation domain and a repression domain. The former, located telomeric (3[prime]) to the breakpoint region, activated transcription 18-fold to >200-fold, depending on the promoter and cell line used for transfection. A repression domain that repressed transcription 4-fold was located centromeric (5[prime]) to the breakpoint region of MLL. The MLL AT-hook domain protein was expressed in bacteria and was utilized in a gel mobility shift assay to assess DNA-binding activity. The MLL AT-hook domain could bind cruciform DNA, recognizing structure rather than sequence of the target DNA. In translocations involving MLL, loss of an activation domain with retention of a repression domain and a DNA-binding domain on the der(11) chromosome could alter the expression of downstream target genes, suggesting a potential mechanism of action for MLL in leukemia. 35 refs., 5 figs., 1 tab.

  11. Identification of a region in the coiled-coil domain of Smc3 that is essential for cohesin activity.

    PubMed

    Orgil, Ola; Mor, Hadar; Matityahu, Avi; Onn, Itay

    2016-07-27

    The cohesin complex plays an important role in sister chromatin cohesion. Cohesin's core is composed of two structural maintenance of chromosome (SMC) proteins, called Smc1 and Smc3. SMC proteins are built from a globular hinge domain, a rod-shaped domain composed of long anti-parallel coiled-coil (CC), and a second globular adenosine triphosphatase domain called the head. The functions of both head and hinge domains have been studied extensively, yet the function of the CC region remains elusive. We identified a mutation in the CC of smc3 (L217P) that disrupts the function of the protein. Cells carrying the smc3-L217P allele have a strong cohesion defect and complexes containing smc3-L217P are not loaded onto the chromosomes. However, the mutation does not affect inter-protein interactions in either the core complex or with the Scc2 loader. We show by molecular dynamics and biochemistry that wild-type Smc3 can adopt distinct conformations, and that adenosine triphosphate (ATP) induces the conformational change. The L217P mutation restricts the ability of the mutated protein to switch between the conformations. We suggest that the function of the CC is to transfer ATP binding/hydrolysis signals between the head and the hinge domains. The results provide a new insight into the mechanism of cohesin activity. PMID:27307603

  12. The NMDA Receptor NR1 C1 Region Bound to Calmodulin: Structural Insights into Functional Differences between Homologous Domains

    SciTech Connect

    Ataman, Zeynep Akyol; Gakhar, Lokesh; Sorensen, Brenda R.; Hell, Johannes W.; Shea, Madeline A.

    2008-09-17

    Calmodulin (CaM) regulates tetrameric N-methyl-D-aspartate receptors (NMDARs) by binding tightly to the C0 and C1 regions of its NR1 subunit. A crystal structure (2HQW; 1.96 {angstrom}) of calcium-saturated CaM bound to NR1C1 (peptide spanning 875-898) showed that NR1 S890, whose phosphorylation regulates membrane localization, was solvent protected, whereas the endoplasmic reticulum retention motif was solvent exposed. NR1 F880 filled the CaM C-domain pocket, whereas T886 was closest to the N-domain pocket. This 1-7 pattern was most similar to that in the CaM-MARCKS complex. Comparison of CaM-ligand wrap-around conformations identified a core tetrad of CaM C-domain residues (FLMM{sub C}) that contacted all ligands consistently. An identical tetrad of N-domain residues (FLMM{sub N}) made variable sets of contacts with ligands. This CaM-NR1C1 structure provides a foundation for designing mutants to test the role of CaM in NR1 trafficking as well as insights into how the homologous CaM domains have different roles in molecular recognition.

  13. The N-terminal side of the origin-binding domain of simian virus 40 large T antigen is involved in A/T untwisting.

    PubMed Central

    Chen, L; Joo, W S; Bullock, P A; Simmons, D T

    1997-01-01

    We investigated the role of the N-terminal side of simian virus 40 (SV40) large T antigen's origin-binding domain in the initiation of virus DNA replication by analyzing the biochemical activities of mutants containing single point substitutions or deletions in this region. Four mutants with substitutions at residues between 121 and 135 were partially defective in untwisting the A/T-rich track on the late side of the origin but were normal in melting the imperfect palindrome (IP) region on the early side. Deletion of the N-terminal 109 amino acids had no effect on either activity, whereas a longer deletion, up to residue 123, greatly reduced A/T untwisting but not IP melting. These results indicate that the region from residue 121 to 135 is important for A/T untwisting but not for IP melting and demonstrate that these activities are separable. Two point substitution mutants (126PS and 135PL) were characterized further by testing them for origin DNA binding, origin unwinding, oligomerization, and helicase activity. These two mutants were completely defective in origin (form U(R)) unwinding but normal in the other activities. Our results demonstrate that a failure to normally untwist the A/T track is correlated with a defect in origin unwinding. Further, they indicate that some mutants with substitutions in the region from residue 121 to 135 interact with origin DNA incorrectly, perhaps by failing to make appropriate contacts with the A/T-rich DNA. PMID:9343233

  14. Time-domain solution for transient dynamic response of a large-diameter thin-walled pipe pile

    NASA Astrophysics Data System (ADS)

    Ding, Xuanming; Liu, Hanlong; Chu, Jian; Cheng, Ke

    2015-06-01

    The propagation of stress waves in a large-diameter pipe pile for low strain dynamic testing cannot be explained properly by traditional 1D wave theories. A new computational model is established to obtain a wave equation that can describe the dynamic response of a large-diameter thin-walled pipe pile to a transient point load during a low strain integrity test. An analytical solution in the time domain is deduced using the separation of variables and variation of constant methods. The validity of this new solution is verified by an existing analytical solution under free boundary conditions. The results of this time domain solution are also compared with the results of a frequency domain solution and field test data. The comparisons indicate that the new solution agrees well with the results of previous solutions. Parametric studies using the new solution with reference to a case study are also carried out. The results show that the mode number affects the accuracy of the dynamic response. A mode number greater than 10 is required to enable the calculated dynamic responses to be independent of the mode number. The dynamic response is also greatly affected by soil properties. The larger the side resistance, the smaller the displacement response and the smaller the reflected velocity wave crest. The displacement increases as the stress waves propagate along the pile when the pile shaft is free. The incident waves of displacement and velocity responses of the pile are not the same among different points in the circumferential direction on the pile top. However, the arrival time and peak value of the pile tip reflected waves are almost the same among different points on the pile top.

  15. A large-domain approach for calculating ship boundary layers and wakes and wave fields for nonzero Froude number

    SciTech Connect

    Tahara, Y.; Stern, F.

    1996-09-01

    A large-domain approach is developed for calculating ship boundary layers and wakes and wave fields for nonzero Froude number. The Reynolds-averaged Navier-Stokes and continuity equations are solved with the Baldwin-Lomax turbulence model, exact nonlinear kinematic and approximate dynamic free-surface boundary conditions, and a body/free-surface conforming grid. The results are validated through comparisons with data for the Series 60 C{sub B} = 0.6 ship model at low and high Froude numbers and results of a precursory interactive approach. Both approaches yield satisfactory results; however, the large-domain results indicate improved resolution of the flow close to the hull and wake centerplane and of the Froucle number differences due to near-wall turbulence modeling and non-linear free-surface boundary conditions. Additional evaluation is provided through discussion of the recent CFD Workshop Tokyo 1994, where both methods were among the best. Last, some concluding remarks are made. 20 refs., 7 figs.

  16. Using addition to solve large subtractions in the number domain up to 20.

    PubMed

    Peters, Greet; De Smedt, Bert; Torbeyns, Joke; Ghesquière, Pol; Verschaffel, Lieven

    2010-02-01

    This study examined 25 university students' use of addition to solve large single-digit subtractions by contrasting performance in the standard subtraction format (12-9=.) and in the addition format (9+.=12). In particular, we investigated the effect of the relative size of the subtrahend on performance in both formats. We found a significant interaction between format, the magnitude of the subtrahend (S) compared to the difference (D) (S>D vs. Slarge single-digit subtractions, but select either addition-based or subtraction-based strategies depending on the relative size of the subtrahend. PMID:19963199

  17. The finite element model for the propagation of light in scattering media: a direct method for domains with nonscattering regions.

    PubMed

    Arridge, S R; Dehghani, H; Schweiger, M; Okada, E

    2000-01-01

    We present a method for handling nonscattering regions within diffusing domains. The method develops from an iterative radiosity-diffusion approach using Green's functions that was computationally slow. Here we present an improved implementation using a finite element method (FEM) that is direct. The fundamental idea is to introduce extra equations into the standard diffusion FEM to represent nondiffusive light propagation across a nonscattering region. By appropriate mesh node ordering the computational time is not much greater than for diffusion alone. We compare results from this method with those from a discrete ordinate transport code, and with Monte Carlo calculations. The agreement is very good, and, in addition, our scheme allows us to easily model time-dependent and frequency domain problems. PMID:10659765

  18. Interfacial partitioning of a loop hinge residue contributes to diacylglycerol affinity of conserved region 1 domains.

    PubMed

    Stewart, Mikaela D; Cole, Taylor R; Igumenova, Tatyana I

    2014-10-01

    Conventional and novel isoenzymes of PKC are activated by the membrane-embedded second messenger diacylglycerol (DAG) through its interactions with the C1 regulatory domain. The affinity of C1 domains to DAG varies considerably among PKCs. To gain insight into the origin of differential DAG affinities, we conducted high-resolution NMR studies of C1B domain from PKCδ (C1Bδ) and its W252Y variant. The W252Y mutation was previously shown to render C1Bδ less responsive to DAG (Dries, D. R., Gallegos, L. L., and Newton, A. C. (2007) A single residue in the C1 domain sensitizes novel protein kinase C isoforms to cellular diacylglycerol production. J. Biol. Chem. 282, 826-830) and thereby emulate the behavior of C1B domains from conventional PKCs that have a conserved Tyr at the equivalent position. Our data revealed that W252Y mutation did not perturb the conformation of C1Bδ in solution but significantly reduced its propensity to partition into a membrane-mimicking environment in the absence of DAG. Using detergent micelles doped with a paramagnetic lipid, we determined that both the residue identity at position 252 and complexation with diacylglycerol influence the geometry of C1Bδ-micelle interactions. In addition, we identified the C-terminal helix α1 of C1Bδ as an interaction site with the head groups of phosphatidylserine, a known activator of PKCδ. Taken together, our studies (i) reveal the identities of C1Bδ residues involved in interactions with membrane-mimicking environment, DAG, and phosphatidylserine, as well as the affinities associated with each event and (ii) suggest that the initial ligand-independent membrane recruitment of C1B domains, which is greatly facilitated by the interfacial partitioning of Trp-252, is responsible, at least in part, for the differential DAG affinities. PMID:25124034

  19. Interfacial Partitioning of a Loop Hinge Residue Contributes to Diacylglycerol Affinity of Conserved Region 1 Domains*

    PubMed Central

    Stewart, Mikaela D.; Cole, Taylor R.; Igumenova, Tatyana I.

    2014-01-01

    Conventional and novel isoenzymes of PKC are activated by the membrane-embedded second messenger diacylglycerol (DAG) through its interactions with the C1 regulatory domain. The affinity of C1 domains to DAG varies considerably among PKCs. To gain insight into the origin of differential DAG affinities, we conducted high-resolution NMR studies of C1B domain from PKCδ (C1Bδ) and its W252Y variant. The W252Y mutation was previously shown to render C1Bδ less responsive to DAG (Dries, D. R., Gallegos, L. L., and Newton, A. C. (2007) A single residue in the C1 domain sensitizes novel protein kinase C isoforms to cellular diacylglycerol production. J. Biol. Chem. 282, 826–830) and thereby emulate the behavior of C1B domains from conventional PKCs that have a conserved Tyr at the equivalent position. Our data revealed that W252Y mutation did not perturb the conformation of C1Bδ in solution but significantly reduced its propensity to partition into a membrane-mimicking environment in the absence of DAG. Using detergent micelles doped with a paramagnetic lipid, we determined that both the residue identity at position 252 and complexation with diacylglycerol influence the geometry of C1Bδ-micelle interactions. In addition, we identified the C-terminal helix α1 of C1Bδ as an interaction site with the head groups of phosphatidylserine, a known activator of PKCδ. Taken together, our studies (i) reveal the identities of C1Bδ residues involved in interactions with membrane-mimicking environment, DAG, and phosphatidylserine, as well as the affinities associated with each event and (ii) suggest that the initial ligand-independent membrane recruitment of C1B domains, which is greatly facilitated by the interfacial partitioning of Trp-252, is responsible, at least in part, for the differential DAG affinities. PMID:25124034

  20. Simulation of Electron Diffusion Region processes in magnetospheric current layers with the new semi-implicit adaptive Multi Level Multi Domain method

    NASA Astrophysics Data System (ADS)

    Innocenti, M. E.; Beck, A.; Markidis, S.; Lapenta, G.

    2014-12-01

    Magnetic reconnection is the magnetosphere is characterized by the complex interplay of microscopic and macroscopic scale: processes originating at the electron scales may eventually produce noticeable effects at the macroscopic scales also. A suitable example is the acceleration of electron jets to electron Alfvén speed in the inner Electron Diffusion Region (EDR) (Drake08): the accelerated electrons then evolve into an outer EDR with length of the order of the ion skin depth (Karimabadi07).This same example highlights the challenges entailed in numerical simulations of magnetic reconnection. Large domains have to be simulated to appreciate the large scale reconnection dynamics, but at the same time electron scale resolution has to be used, at least locally, to allow microscale processes to develop. This dramatically increases the computational costs of simulations, especially if a realistic mass ratio between the particle species is used. We show here simulations of large domain magnetic reconnection processes with electron scale resolution. These simulations are made possible at a moderate computational cost by the use of the newly developed semi-implicit Multi Level Multi Domain method (Innocenti13, Beck13), which combines the advantages of implicit algorithms (Vu92) and adaptivity. With the MLMD method, a domain larger than the Ion Diffusion Region is simulated with realistic mass ratio and with ion scale resolution. The EDR is then simulated also with higher spatial and temporal resolution, to allow electron scale, faster processes to develop there. Since electron scale resolution is used only in a small part of the total domain, the computational cost of MLMD simulations is dramatically lowered with respect to fully resolved simulations. Comparable levels of physical details is delivered (Innocenti14, submitted). To prove this, we show here that the MLMD method can capture characteristic EDR electron scale processes such as the formation of an inversion

  1. Two distinct regions of the BPV1 E1 replication protein interact with the activation domain of E2.

    PubMed

    Moscufo, N; Sverdrup, F; Breiding, D E; Androphy, E J

    1999-12-15

    Papillomavirus E1 and E2 proteins co-operation in viral DNA replication is mediated by protein-protein interactions that lead to formation of an E1-E2 complex. To identify the domains involved, portions of the two proteins were expressed as fusions to the DNA-binding protein LexA or the transactivation domain of VP16 and analyzed by the yeast two-hybrid system. The C-terminal 266 amino acids of BPV1 E1 (E1C266) interacted strongly with E2 in the yeast system and in a mammalian two-hybrid assay. VP16-E1C266 interacted with a region encompassing amino acids 1-200 of the transactivation domain of E2 that was fused to LexA. The interaction between E1 full length and E2 was clearly observed only when E1 was expressed as LexA-E1 chimera. In addition, we found that in the LexA context also the N-terminal region encompassing the first 340 amino acids of E1 (E1N340) interacted with E2 full length. The interactions of E1N340 and E1C266 with E2 were confirmed also by in vitro binding studies. These observations demonstrate that two distinct regions of E1 mediate the interaction with E2 in vivo. PMID:10581387

  2. Understanding the link between large-scale climate variability and regional hydrologic variability using weather patterns as intermediate variables

    NASA Astrophysics Data System (ADS)

    Renard, Benjamin; Lall, Upmanu

    2013-04-01

    Climate naturally follows specific modes of variability, quantified by some climate indices (e.g. North Atlantic Oscillation NAO, Southern Oscillation Index SOI, Atlantic Multidecadal Oscillation AMO, etc.). These modes of variability are due to large-scale climatic processes affecting large areas, and whose temporal scales range from a few months to a few decades. The temporal variability of hydrological regimes depends on such modes of variability, as has been reported in several regions worldwide. However, this relationship is more difficult to observe in some other regions, for several possible reasons: (i) the large natural variability of hydrological regimes, especially in the extreme domain, might strongly restrict the ability to detect weak or moderate relationships; (ii) Standard modes of variability like the NAO, SOI, etc. might not be the most relevant for some regions. This presentation explores an approach which, instead of directly seeking links between large-scale climate variability and regional hydrologic variability, decomposes the problem into two transitive "sub-problems" involving weather patterns as intermediate variables. Weather patterns are used to describe the atmospheric situation over a region as a categorical variable. As region-specific indices, they are potentially more explanatory than larger-scale indices like the NAO or SOI to explain the regional variability of hydrologic regimes. Consequently, two probabilistic models are derived: (1) a model to predict the frequency of weather patterns using large-scale climate indices (NAO, SOI, etc.) as predictors; (2) a model to predict the regional distribution of some hydrologic variable (e.g. number of flood events) using the frequencies of weather patterns as predictors. A case study based on French flood data is used to illustrate the application of this approach. It shows that each sub-model has some predictive ability: for instance, the annual number of flood events can be predicted

  3. Protein kinase domain of twitchin has protein kinase activity and an autoinhibitory region.

    PubMed

    Lei, J; Tang, X; Chambers, T C; Pohl, J; Benian, G M

    1994-08-19

    Twitchin is a 753-kDa polypeptide located in the muscle A-bands of the nematode, Caenorhabditis elegans. It consists of multiple copies of both fibronectin III and immunoglobulin C2 domains and, near the C terminus, a protein kinase domain with greatest homology to the catalytic domains of myosin light chain kinases. We have expressed and purified from Escherichia coli twitchin's protein kinase catalytic core and flanking sequences that do not include fibronectin III and immunoglobulin C2 domains. The protein was shown to phosphorylate a model substrate and to undergo autophosphorylation. The autophosphorylation occurs at a slow rate, attaining a maximum at 3 h with a stoichiometry of about 1.0 mol of phosphate/mol of protein, probably through an intramolecular mechanism. Sequence analysis of proteolytically derived phosphopeptides revealed that autophosphorylation occurred N-terminal to the catalytic core, predominantly at Thr-5910, with possible minor sites at Ser5912 and/or Ser-5913. This portion of twitchin (residues 5890-6268) was also phosphorylated in vitro by protein kinase C in the absence of calcium and phosphotidylserine, but not by cAMP-dependent protein kinase. By comparing the activities of three twitchin segments, the enzyme appears to be inhibited by the 60-amino acid residues lying just C-terminal to the kinase catalytic core. Thus, like a number of other protein kinases including myosin light chain kinases, the twitchin kinase appears to be autoregulated. PMID:8063727

  4. A novel keratan sulphate domain preferentially expressed on the large aggregating proteoglycan from human articular cartilage is recognized by the monoclonal antibody 3D12/H7.

    PubMed Central

    Fischer, D C; Haubeck, H D; Eich, K; Kolbe-Busch, S; Stöcker, G; Stuhlsatz, H W; Greiling, H

    1996-01-01

    Monoclonal antibodies (mAbs) were prepared against aggrecan which has been isolated from human articular cartilage and purified by several chromatographic steps. One of these mAbs, the aggrecan-specific mAb 3D12/H7, was selected for further characterization. The data presented indicate that this mAb recognizes a novel domain of keratan sulphate chains from aggrecan: (1) immunochemical staining of aggrecan is abolished by treatment with keratanase/keratanase II, but not with keratanase or chondroitin sulphate lyase AC/ABC; (2) after chemical deglycosylation of aggrecan no staining of the core-protein was observed; (3) different immunochemical reactivity was observed against keratan sulphates from articular cartilage, intervertebral disc and cornea for the mAbs 3D12/H7 and 5D4. For further characterization of the epitope, reduced and 3H-labelled keratan sulphate chains were prepared. In an IEF-gel-shift assay it was shown that the 3H-labelled oligosaccharides obtained after keratanase digestion of reduced and 3H-labelled keratan sulphate chains were recognized by the mAb 3D12/H7. Thus it can be concluded that the mAb 3D12/H7 recognizes an epitope in the linkage region present in, at least some, keratan sulphate chains of the large aggregating proteoglycan from human articular cartilage. Moreover, this domain seems to be expressed preferentially on those keratan sulphate chains which occur in the chondroitin sulphate-rich region of aggrecan, since the antibody does not recognize the keratan sulphate-rich region obtained after combined chondroitinase AC/ABC and trypsin digestion of aggrecan. PMID:8836155

  5. A novel keratan sulphate domain preferentially expressed on the large aggregating proteoglycan from human articular cartilage is recognized by the monoclonal antibody 3D12/H7.

    PubMed

    Fischer, D C; Haubeck, H D; Eich, K; Kolbe-Busch, S; Stöcker, G; Stuhlsatz, H W; Greiling, H

    1996-09-15

    Monoclonal antibodies (mAbs) were prepared against aggrecan which has been isolated from human articular cartilage and purified by several chromatographic steps. One of these mAbs, the aggrecan-specific mAb 3D12/H7, was selected for further characterization. The data presented indicate that this mAb recognizes a novel domain of keratan sulphate chains from aggrecan: (1) immunochemical staining of aggrecan is abolished by treatment with keratanase/keratanase II, but not with keratanase or chondroitin sulphate lyase AC/ABC; (2) after chemical deglycosylation of aggrecan no staining of the core-protein was observed; (3) different immunochemical reactivity was observed against keratan sulphates from articular cartilage, intervertebral disc and cornea for the mAbs 3D12/H7 and 5D4. For further characterization of the epitope, reduced and 3H-labelled keratan sulphate chains were prepared. In an IEF-gel-shift assay it was shown that the 3H-labelled oligosaccharides obtained after keratanase digestion of reduced and 3H-labelled keratan sulphate chains were recognized by the mAb 3D12/H7. Thus it can be concluded that the mAb 3D12/H7 recognizes an epitope in the linkage region present in, at least some, keratan sulphate chains of the large aggregating proteoglycan from human articular cartilage. Moreover, this domain seems to be expressed preferentially on those keratan sulphate chains which occur in the chondroitin sulphate-rich region of aggrecan, since the antibody does not recognize the keratan sulphate-rich region obtained after combined chondroitinase AC/ABC and trypsin digestion of aggrecan. PMID:8836155

  6. Role of the Outer Pore Domain in Transient Receptor Potential Vanilloid 1 Dynamic Permeability to Large Cations*

    PubMed Central

    Munns, Clare H.; Chung, Man-Kyo; Sanchez, Yuly E.; Amzel, L. Mario; Caterina, Michael J.

    2015-01-01

    Transient receptor potential vanilloid 1 (TRPV1) has been shown to alter its ionic selectivity profile in a time- and agonist-dependent manner. One hallmark of this dynamic process is an increased permeability to large cations such as N-methyl-d-glucamine (NMDG). In this study, we mutated residues throughout the TRPV1 pore domain to identify loci that contribute to dynamic large cation permeability. Using resiniferatoxin (RTX) as the agonist, we identified multiple gain-of-function substitutions within the TRPV1 pore turret (N628P and S629A), pore helix (F638A), and selectivity filter (M644A) domains. In all of these mutants, maximum NMDG permeability was substantially greater than that recorded in wild type TRPV1, despite similar or even reduced sodium current density. Two additional mutants, located in the pore turret (G618W) and selectivity filter (M644I), resulted in significantly reduced maximum NMDG permeability. M644A and M644I also showed increased and decreased minimum NMDG permeability, respectively. The phenotypes of this panel of mutants were confirmed by imaging the RTX-evoked uptake of the large cationic fluorescent dye YO-PRO1. Whereas none of the mutations selectively altered capsaicin-induced changes in NMDG permeability, the loss-of-function phenotypes seen with RTX stimulation of G618W and M644I were recapitulated in the capsaicin-evoked YO-PRO1 uptake assay. Curiously, the M644A substitution resulted in a loss, rather than a gain, in capsaicin-evoked YO-PRO1 uptake. Modeling of our mutations onto the recently determined TRPV1 structure revealed several plausible mechanisms for the phenotypes observed. We conclude that side chain interactions at a few specific loci within the TRPV1 pore contribute to the dynamic process of ionic selectivity. PMID:25568328

  7. Real-time display with large field of view on fourier domain optical coherence tomography at 1310 nm wavelength for dermatology

    NASA Astrophysics Data System (ADS)

    Xiao, Qing; Hou, Jue; Fu, Ling

    2012-06-01

    A Fourier domain optical coherence tomography (OCT) system with 1310 nm light was demonstrated to study inflammatory human skin and the skin coated with a moisturizer in vivo. By using a graphics processing unit (GPU), the display rate could reach 20 frames/s with 1000 A-scans contained in one image. The field of view (FOV) of the cross-sectional image is 7 mm in the lateral direction and the penetration depth is ˜1 mm in skin. The result shows that, in inflammatory skin, the epidermis became thicker and had a decreased scattering; furthermore, the region of the severe lesion present an uneven thickness of the epidermis compared with the peripheral area. For the result of a finger tip coated with the moisturizer, the antireflection effect was significant and the stratum corneum became more transparent. In this letter, we demonstrated that real-time display with a large FOV could enable screening of a large tissue area; thereby increasing the dermatologic diagnostic potential of the method by permitting a comparison of the lesion and the normal peripheral region.

  8. Pectin Homogalacturonans: Nanostructural Characterization of Methylesterified Domains

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Functionality of pectic hydrocolloids is largely dependent on the two major domains commonly found in their homogalacturonan (HG) regions, i.e., methylester protected domains (MPDs)and non methylesterified domains (NMDs). MPDs can participate in hydrogen bonding and hydrophobic interactions but unli...

  9. Deep-tow magnetic survey above large exhumed mantle domains of the eastern Southwest Indian ridge

    NASA Astrophysics Data System (ADS)

    Bronner, A.; Munschy, M.; Carlut, J. H.; Searle, R. C.; Sauter, D.; Cannat, M.

    2011-12-01

    The recent discovery of a new type of seafloor, the "smooth seafloor", formed with no or very little volcanic activity along the ultra-slow spreading Southwest Indian ridge (SWIR) shows an unexpected complexity in processes of generation of the oceanic lithosphere. There, detachment faulting is thought to be a mechanism for efficient exhumation of deep-seated mantle rocks. We present here a deep-tow geological-geophysical survey over smooth seafloor at the eastern SWIR (62-64°N) combining magnetic data, geology mapping from side-scan sonar images and results from dredge sampling. We introduce a new type of calibration approach for deep-tow fluxgate magnetometer. We show that magnetic data can be corrected from the magnetic effect of the vehicle with no recourse to its attitude (pitch, roll and heading) but only using the 3 components recorded by the magnetometer and an approximation of the scalar intensity of the Earth magnetic field. The collected dredge samples as well as the side-scan images confirm the presence of large areas of exhumed mantle-derived peridodites surrounded by a few volcanic constructions. This allows us to hypothesis that magnetic anomalies are caused by serpentinized peridotites or magmatic intrusions. We show that the magnetic signature of the smooth seafloor is clearly weaker than the surrounding volcanic areas. Moreover, the calculated magnetization of a source layer as well as the comparison between deep-tow and sea-surface magnetic data argue for strong East-West variability in the distribution of the magnetized sources. This variability may results from fluid-rocks interaction along the detachment faults as well as from the repartition of the volcanic material and thus questions the seafloor spreading origin of the corresponding magnetic anomalies. Finally, we provide magnetic arguments, as calculation of block rotation or spreading asymmetry in order to better constrain tectonic mechanisms that occur during the formation of this

  10. Identification of the minimal binding region of a Plasmodium falciparum IgM binding PfEMP1 domain

    PubMed Central

    Semblat, Jean-Philippe; Ghumra, Ashfaq; Czajkowsky, Daniel M.; Wallis, Russell; Mitchell, Daniel A.; Raza, Ahmed; Rowe, J.Alexandra

    2015-01-01

    Binding of host immunoglobulin is a common immune evasion mechanism demonstrated by microbial pathogens. Previous work showed that the malaria parasite Plasmodium falciparum binds the Fc-region of human IgM molecules, resulting in a coating of IgM on the surface of infected erythrocytes. IgM binding is a property of P. falciparum strains showing virulence-related phenotypes such as erythrocyte rosetting. The parasite ligands for IgM binding are members of the diverse P. falciparum Erythrocyte Membrane Protein One (PfEMP1) family. However, little is known about the amino acid sequence requirements for IgM binding. Here we studied an IgM binding domain from a rosette-mediating PfEMP1 variant, DBL4ζ of TM284var1, and found that the minimal IgM binding region mapped to the central region of the DBL domain, comprising all of subdomain 2 and adjoining parts of subdomains 1 and 3. Site-directed mutagenesis of charged amino acids within subdomain 2, predicted by molecular modelling to form the IgM binding site, showed no marked effect on IgM binding properties. Overall, this study identifies the minimal IgM binding region of a PfEMP1 domain, and indicates that the existing homology model of PfEMP1-IgM interaction is incorrect. Further work is needed to identify the specific interaction site for IgM within the minimal binding region of PfEMP1. PMID:26094597

  11. Deep-tow geophysical survey above large exhumed mantle domains of the eastern Southwest Indian ridge

    NASA Astrophysics Data System (ADS)

    Bronner, A.; Munschy, M.; Sauter, D.; Carlut, J.; Searle, R.; Cannat, M.

    2012-04-01

    The recent discovery of a new type of seafloor, the "smooth seafloor", formed with no or very little volcanic activity along the easternmost part of the ultra-slow spreading Southwest Indian ridge (SWIR) shows an unexpected complexity in processes of generation of the oceanic lithosphere. There, detachment faulting is thought to be a mechanism for efficient exhumation of deep-seated mantle rocks. We present here a deep-tow geological-geophysical survey over smooth seafloor at the eastern SWIR (62-64°N) combining multibeam bathymetric data, magnetic data, geology mapping from sidescan sonar (TOBI) images and results from dredge sampling. We introduce a new type of calibration approach for deep-tow fluxgate magnetometer. We show that magnetic data can be corrected from the magnetic effect of the vehicle with no recourse to its attitude (pitch, roll and heading) but only using the 3 components recorded by the magnetometer and an approximation of the scalar intensity of the Earth magnetic field. The collected dredge samples as well as the sidescan sonar images confirm the presence of large areas of exhumed mantle-derived peridodites surrounded by a few volcanic constructions. We investigate the possibility that magnetic anomalies are either caused by serpentinized peridotites and/or magmatic intrusions. We show that the magnetic signature of the smooth seafloor is clearly weaker than the surrounding volcanic areas. Moreover, the calculated magnetization of a source layer as well as the comparison between deep-tow and sea-surface magnetic data argue for strong East-West variability in the distribution of the magnetized sources. This variability may result from fluid-rock interactions along the detachment faults as well as from the occurrence of small sized and thin volcanic patches and thus questions the seafloor spreading origin of the corresponding magnetic anomalies. Finally, we provide magnetic arguments, as calculation of block rotation or spreading asymmetry in

  12. REGIONAL METHODS INITIATIVE: DEVELOPMENT OF LARGE RIVER BIOASSESSMENT PROTOCOLS (LRBP) FOR BENTHIC MACROINVERTEBRATES

    EPA Science Inventory

    We are developing the Large River Bioassessment Protocol (LRBP) for assessment of benthic macroinvertebrate assemblages. This multi-habitat method is currently being used in support of a REMAP project for probabilistic assessment of large rivers in USEPA Region 5. Six rivers, r...

  13. Nucleation Control for Large, Single Crystalline Domains of Monolayer Hexagonal Boron Nitride via Si-Doped Fe Catalysts

    PubMed Central

    2015-01-01

    The scalable chemical vapor deposition of monolayer hexagonal boron nitride (h-BN) single crystals, with lateral dimensions of ∼0.3 mm, and of continuous h-BN monolayer films with large domain sizes (>25 μm) is demonstrated via an admixture of Si to Fe catalyst films. A simple thin-film Fe/SiO2/Si catalyst system is used to show that controlled Si diffusion into the Fe catalyst allows exclusive nucleation of monolayer h-BN with very low nucleation densities upon exposure to undiluted borazine. Our systematic in situ and ex situ characterization of this catalyst system establishes a basis for further rational catalyst design for compound 2D materials. PMID:25664483

  14. Effects of large-scale deforestation on precipitation in the monsoon regions: Remote versus local effects

    PubMed Central

    Devaraju, N.; Bala, Govindasamy; Modak, Angshuman

    2015-01-01

    In this paper, using idealized climate model simulations, we investigate the biogeophysical effects of large-scale deforestation on monsoon regions. We find that the remote forcing from large-scale deforestation in the northern middle and high latitudes shifts the Intertropical Convergence Zone southward. This results in a significant decrease in precipitation in the Northern Hemisphere monsoon regions (East Asia, North America, North Africa, and South Asia) and moderate precipitation increases in the Southern Hemisphere monsoon regions (South Africa, South America, and Australia). The magnitude of the monsoonal precipitation changes depends on the location of deforestation, with remote effects showing a larger influence than local effects. The South Asian Monsoon region is affected the most, with 18% decline in precipitation over India. Our results indicate that any comprehensive assessment of afforestation/reforestation as climate change mitigation strategies should carefully evaluate the remote effects on monsoonal precipitation alongside the large local impacts on temperatures. PMID:25733889

  15. Effects of large-scale deforestation on precipitation in the monsoon regions: remote versus local effects.

    PubMed

    Devaraju, N; Bala, Govindasamy; Modak, Angshuman

    2015-03-17

    In this paper, using idealized climate model simulations, we investigate the biogeophysical effects of large-scale deforestation on monsoon regions. We find that the remote forcing from large-scale deforestation in the northern middle and high latitudes shifts the Intertropical Convergence Zone southward. This results in a significant decrease in precipitation in the Northern Hemisphere monsoon regions (East Asia, North America, North Africa, and South Asia) and moderate precipitation increases in the Southern Hemisphere monsoon regions (South Africa, South America, and Australia). The magnitude of the monsoonal precipitation changes depends on the location of deforestation, with remote effects showing a larger influence than local effects. The South Asian Monsoon region is affected the most, with 18% decline in precipitation over India. Our results indicate that any comprehensive assessment of afforestation/reforestation as climate change mitigation strategies should carefully evaluate the remote effects on monsoonal precipitation alongside the large local impacts on temperatures. PMID:25733889

  16. Design and experimental investigation of highly efficient resonance-domain diffraction gratings in the visible spectral region.

    PubMed

    Barlev, Omri; Golub, Michael A; Friesem, Asher A; Nathan, Menachem

    2012-12-01

    Surface-relief resonance-domain diffraction gratings with deep and dense grooves provide considerable changes in light propagation direction, wavefront curvature, and nearly 100% Bragg diffraction efficiency usually attributed only to volume optical holograms. In this paper, we present design, computer simulation, fabrication, and experimental results of binary resonance-domain diffraction gratings in the visible spectral region. Performance of imperfectly fabricated diffraction groove profiles was optimized by controlling the DC and the depth of the grooves. Indeed, more than 97% absolute Bragg diffraction efficiency was measured at the 635 nm wavelength with binary gratings having periods of 520 nm and groove depths of about 1000 nm, fabricated by direct electron-beam lithography and reactive ion etching. PMID:23207376

  17. Characterization of regions within the N-terminal 6-kilodalton domain of phytochrome A that modulate its biological activity.

    PubMed Central

    Jordan, E T; Marita, J M; Clough, R C; Vierstra, R D

    1997-01-01

    Phytochrome A (phyA) is a red/far-red (FR) light photoreceptor responsible for initiating numerous light-mediated plant growth and developmental responses, especially in FR light-enriched environments. We previously showed that the first 70 amino acids of the polypeptide contain at least two regions with potentially opposite functions (E.T. Jordan, J.R. Cherry, J.M. Walker, R.D. Vierstra [1996] Plant J 9: 243-257). One region is required for activity and correct apoprotein/chromophore interactions, whereas the second appears to regulate phytochrome activity. We have further resolved these functional regions by analysis of N-terminal deletion and alanine-scanning mutants of oat (Avena sativa) phyA in transgenic tobacco (Nicotiana tabacum). The results indicate that the region involved in chromophore/apoprotein interactions contains two separate segments (residues 25-33 and 50-62) also required for biological activity. The region that regulates phyA activity requires only five adjacent serines (Sers) (residues 8-12). Removal or alteration of these Sers generates a photoreceptor that increases the sensitivity of transgenic seedlings to red and FR light more than intact phyA. Taken together, these data identify three distinct regions in the N-terminal domain necessary for photoreceptor activity, and further define the Ser-rich region as an important site for phyA regulation. PMID:9342873

  18. Multiple Interactions of the Intrinsically Disordered Region between the Helicase and Nuclease Domains of the Archaeal Hef Protein*

    PubMed Central

    Ishino, Sonoko; Yamagami, Takeshi; Kitamura, Makoto; Kodera, Noriyuki; Mori, Tetsuya; Sugiyama, Shyogo; Ando, Toshio; Goda, Natsuko; Tenno, Takeshi; Hiroaki, Hidekazu; Ishino, Yoshizumi

    2014-01-01

    Hef is an archaeal protein that probably functions mainly in stalled replication fork repair. The presence of an unstructured region was predicted between the two distinct domains of the Hef protein. We analyzed the interdomain region of Thermococcus kodakarensis Hef and demonstrated its disordered structure by CD, NMR, and high speed atomic force microscopy (AFM). To investigate the functions of this intrinsically disordered region (IDR), we screened for proteins interacting with the IDR of Hef by a yeast two-hybrid method, and 10 candidate proteins were obtained. We found that PCNA1 and a RecJ-like protein specifically bind to the IDR in vitro. These results suggested that the Hef protein interacts with several different proteins that work together in the pathways downstream from stalled replication fork repair by converting the IDR structure depending on the partner protein. PMID:24947516

  19. Multiple interactions of the intrinsically disordered region between the helicase and nuclease domains of the archaeal Hef protein.

    PubMed

    Ishino, Sonoko; Yamagami, Takeshi; Kitamura, Makoto; Kodera, Noriyuki; Mori, Tetsuya; Sugiyama, Shyogo; Ando, Toshio; Goda, Natsuko; Tenno, Takeshi; Hiroaki, Hidekazu; Ishino, Yoshizumi

    2014-08-01

    Hef is an archaeal protein that probably functions mainly in stalled replication fork repair. The presence of an unstructured region was predicted between the two distinct domains of the Hef protein. We analyzed the interdomain region of Thermococcus kodakarensis Hef and demonstrated its disordered structure by CD, NMR, and high speed atomic force microscopy (AFM). To investigate the functions of this intrinsically disordered region (IDR), we screened for proteins interacting with the IDR of Hef by a yeast two-hybrid method, and 10 candidate proteins were obtained. We found that PCNA1 and a RecJ-like protein specifically bind to the IDR in vitro. These results suggested that the Hef protein interacts with several different proteins that work together in the pathways downstream from stalled replication fork repair by converting the IDR structure depending on the partner protein. PMID:24947516

  20. Improving Teaching and Learning in a Regional University Campus through a Focus on the Affective Domain

    ERIC Educational Resources Information Center

    Sawyer, Janet; Zianian, Tahereh; Evans, Nina; Gillham, David

    2012-01-01

    This paper describes the research process undertaken in a pilot study conducted at the University of South Australia's Centre for Regional Engagement (CRE), and reports the feedback collected in relation to this process and the project overall. Academic staff and students from CRE's two sites located in the rural and regional cities of Whyalla and…

  1. Importance of Hypervariable Region 2 for Stability and Affinity of a Shark Single-Domain Antibody Specific for Ebola Virus Nucleoprotein

    PubMed Central

    Anderson, George P.; Teichler, Daniel D.; Zabetakis, Dan; Shriver-Lake, Lisa C.; Liu, Jinny L.; Lonsdale, Stephen G.; Goodchild, Sarah A.; Goldman, Ellen R.

    2016-01-01

    Single-domain antibodies derived from the unique New Antigen Receptor found in sharks have numerous potential applications, ranging from diagnostic reagents to therapeutics. Shark-derived single-domain antibodies possess the same characteristic ability to refold after heat denaturation found in single-domain antibodies derived from camelid heavy-chain-only antibodies. Recently, two shark derived single-domain antibodies specific for the nucleoprotein of Ebola virus were described. Our evaluation confirmed their high affinity for the nucleoprotein, but found their melting temperatures to be low relative to most single-domain antibodies. Our first approach towards improving their stability was grafting antigen-binding regions (complementarity determining regions) of one of these single-domain antibodies onto a high melting temperature shark single-domain antibody. This resulted in two variants: one that displayed excellent affinity with a low melting temperature, while the other had poor affinity but a higher melting temperature. These new proteins, however, differed in only 3 amino acids within the complementarity determining region 2 sequence. In shark single-domain antibodies, the complementarity determining region 2 is often referred to as hypervariable region 2, as this segment of the antibody domain is truncated compared to the sequence in camelid single-domain antibodies and conventional heavy chain variable domains. To elucidate which of the three amino acids or combinations thereof were responsible for the affinity and stability we made the 6 double and single point mutants that covered the intermediates between these two clones. We found a single amino acid change that achieved a 10°C higher melting temperature while maintaining sub nM affinity. This research gives insights into the impact of the shark sdAb hypervariable 2 region on both stability and affinity. PMID:27494523

  2. Importance of Hypervariable Region 2 for Stability and Affinity of a Shark Single-Domain Antibody Specific for Ebola Virus Nucleoprotein.

    PubMed

    Anderson, George P; Teichler, Daniel D; Zabetakis, Dan; Shriver-Lake, Lisa C; Liu, Jinny L; Lonsdale, Stephen G; Goodchild, Sarah A; Goldman, Ellen R

    2016-01-01

    Single-domain antibodies derived from the unique New Antigen Receptor found in sharks have numerous potential applications, ranging from diagnostic reagents to therapeutics. Shark-derived single-domain antibodies possess the same characteristic ability to refold after heat denaturation found in single-domain antibodies derived from camelid heavy-chain-only antibodies. Recently, two shark derived single-domain antibodies specific for the nucleoprotein of Ebola virus were described. Our evaluation confirmed their high affinity for the nucleoprotein, but found their melting temperatures to be low relative to most single-domain antibodies. Our first approach towards improving their stability was grafting antigen-binding regions (complementarity determining regions) of one of these single-domain antibodies onto a high melting temperature shark single-domain antibody. This resulted in two variants: one that displayed excellent affinity with a low melting temperature, while the other had poor affinity but a higher melting temperature. These new proteins, however, differed in only 3 amino acids within the complementarity determining region 2 sequence. In shark single-domain antibodies, the complementarity determining region 2 is often referred to as hypervariable region 2, as this segment of the antibody domain is truncated compared to the sequence in camelid single-domain antibodies and conventional heavy chain variable domains. To elucidate which of the three amino acids or combinations thereof were responsible for the affinity and stability we made the 6 double and single point mutants that covered the intermediates between these two clones. We found a single amino acid change that achieved a 10°C higher melting temperature while maintaining sub nM affinity. This research gives insights into the impact of the shark sdAb hypervariable 2 region on both stability and affinity. PMID:27494523

  3. Generating extreme weather event sets from very large ensembles of regional climate models

    NASA Astrophysics Data System (ADS)

    Massey, Neil; Guillod, Benoit; Otto, Friederike; Allen, Myles; Jones, Richard; Hall, Jim

    2015-04-01

    Generating extreme weather event sets from very large ensembles of regional climate models Neil Massey, Benoit P. Guillod, Friederike E. L. Otto, Myles R. Allen, Richard Jones, Jim W. Hall Environmental Change Institute, University of Oxford, Oxford, UK Extreme events can have large impacts on societies and are therefore being increasingly studied. In particular, climate change is expected to impact the frequency and intensity of these events. However, a major limitation when investigating extreme weather events is that, by definition, only few events are present in observations. A way to overcome this issue it to use large ensembles of model simulations. Using the volunteer distributed computing (VDC) infrastructure of weather@home [1], we run a very large number (10'000s) of RCM simulations over the European domain at a resolution of 25km, with an improved land-surface scheme, nested within a free-running GCM. Using VDC allows many thousands of climate model runs to be computed. Using observations for the GCM boundary forcings we can run historical "hindcast" simulations over the past 100 to 150 years. This allows us, due to the chaotic variability of the atmosphere, to ascertain how likely an extreme event was, given the boundary forcings, and to derive synthetic event sets. The events in these sets did not actually occur in the observed record but could have occurred given the boundary forcings, with an associated probability. The event sets contain time-series of fields of meteorological variables that allow impact modellers to assess the loss the event would incur. Projections of events into the future are achieved by modelling projections of the sea-surface temperature (SST) and sea-ice boundary forcings, by combining the variability of the SST in the observed record with a range of warming signals derived from the varying responses of SSTs in the CMIP5 ensemble to elevated greenhouse gas (GHG) emissions in three RCP scenarios. Simulating the future with a

  4. Human domain antibodies to conserved sterically restricted regions on gp120 as exceptionally potent cross-reactive HIV-1 neutralizers

    PubMed Central

    Chen, Weizao; Zhu, Zhongyu; Feng, Yang; Dimitrov, Dimiter S.

    2008-01-01

    The antibody access to some conserved structures on the HIV-1 envelope glycoprotein (Env) is sterically restricted. We have hypothesized that the smallest independently folded antibody fragments (domains) could exhibit exceptionally potent and broadly cross-reactive neutralizing activity by targeting hidden conserved epitopes that are not accessible by larger antibodies. To test this hypothesis, we constructed a large (size 2.5 × 1010), highly diversified library of human antibody variable domains (domain antibodies) and used it for selection of binders to conserved Env structures by panning sequentially against Envs from different isolates. The highest affinity binder, m36, neutralized all tested HIV-1 isolates from clades A– D with an activity on average higher than that of C34, a peptide similar to the fusion inhibitor T20, which is in clinical use, and that of m9, which exhibits a neutralizing activity superior to known potent cross-reactive antibodies. Large-size fusion proteins of m36 exhibited diminished neutralizing activity but preincubation of virions with soluble CD4 restored it, suggesting that m36 epitope is sterically restricted and induced by CD4 (CD4i). M36 bound to gp120-CD4 complexes better than to gp120 alone and competed with CD4i antibodies. M36 is the only reported representative of a promising class of potent, broadly cross-reactive HIV-1 inhibitors based on human domain antibodies. It has potential for prevention and therapy and as an agent for exploration of the closely guarded conserved Env structures with implications for design of small molecule inhibitors and elucidation of mechanisms of virus entry and evasion of immune responses. PMID:18957538

  5. Time-Domain Techniques to Automatically Detect Local Earthquakes in the Wavetrain of Large Remote Teleseseismic Events Using Data within the Continental United States

    NASA Astrophysics Data System (ADS)

    Alfaro-Diaz, R. A.; Velasco, A. A.; Kilb, D.; Pankow, K.; Linville, L. M.

    2014-12-01

    Technology advances in combination with the onslaught of data availability now allow for large seismic data streams to automatically and systematically be processed. This processing allows for the detection of unique seismic events, including events triggered by the passage of seismic waves created by large, distant earthquakes. We develop an automated approach to identify small, locally recorded earthquakes on a single station within continuous seismic data. We apply a time domain short-term average (STA) to long-term-average (LTA) ratio algorithm to create a catalog of "detections" (a signal above the noise level, which may, or may not be an earthquake) at each station recorded on three components, and then remove any spurious detections by requiring that a detection is real only if recorded on a minimum of two channels. To calibrate the algorithm, we use a set of ~900 small earthquakes in the December 2008 Yellowstone Swarm. Of the four STA/LTA algorithms we tested (e.g., 1 s/10 s; 4 s/40 s; 8 s/80 s; 16 s/160s), the 4/40s method is the most effective at identifying the majority of events in the swarm. We apply this preferred method to data from 165 M≥7 earthquakes (±5-hours of data centered on the mainshock origin times) recorded at >400 seismic stations in EarthScope's USArray Transportable Array (TA) and regional seismic networks within the continental United States. Our algorithm nets, on average, hundreds of detections for each mainshock, and we find we can detect small events within the network. The 4/40s method is successful at identifying local earthquakes within the TA and regional networks. We find STA/LTA algorithms can successfully identify small local earthquakes within large datasets.

  6. On the need for long-term, on the order of a decade, hydro-climatic forecasts over large domains

    NASA Astrophysics Data System (ADS)

    Burges, S. J.

    2012-12-01

    All problems of hydrology have been influenced to some extent by the need to describe delivery of water to, and its movement through, the critical zone. The nature of the questions and the level of required quantitative description have changed with time, but all involve accurate accounting of all components of the hydrologic cycle. The broadest issues involve the temporal and spatial distributions of excess (floods) or too little (droughts) water. The spatial domains can range from small catchments to major fractions of continents. The temporal domains range from relatively short-term, on the order of hours to days to a few months, to multiple decades. Hydrologic engineers have long recognized the need to offer designs for human occupied catchments that accommodate hydrologic extremes (principally floods and droughts) that affect human and animal safety, for example, through disruptions to infrastructure and supply chains, food supplies, and water supplies. As more has been learned about the criticality of ecosystems to the well-being of the planet, water allocation issues have become those of "water for people" and "water for ecology". These latter requirements have emphasized the need for increased accuracy of estimating water budgets, and how water (and pollutants) moves through the associated critical domain. Given the now large physical demand for societal water use (it exceeds 50% of the mean annual river flow in most conterminous US river basins) hydrologic balances that include the operation of water resource infrastructure (flood damage mitigation dams and levees, storage reservoirs for municipal and industrial water, irrigation and ecological preservation) have become the norm. In most basins the storage reservoirs are relatively small (few store more than the mean annual flow of rivers) and long-term hydrological forecasting has become a major issue. Whether the issue is floods or droughts, there is now a pressing need for societally useful forecasts

  7. A new RE + 011 TSIG method for the fabrication of high quality and large size single domain YBCO bulk superconductors

    NASA Astrophysics Data System (ADS)

    Yang, W. M.; Chen, L. P.; Wang, X. J.

    2016-02-01

    High quality single domain YBCO bulk superconductors, 20 mm in diameter, have been fabricated using a new top seeded infiltration and growth method (called the RE + 011 TSIG method), with a new solid phase (Y2O3 + xBaCuO2) instead of the conventional Y2BaCuO5 solid phase, x = 0, 0.5, 1.0, 1.2, 1.5, 1.8, 2.0, 2.5, 3.0. The effects of different BaCuO2 contents x on the growth morphology, microstructure, and levitation force have been investigated. The results show that the levitation force of the YBCO bulks first increases and then decreases with increasing x, and reaches maximum levitation forces of about 49.2 N (77 K, 0.5 T, with the traditional liquid phase of YBa2Cu3O y + 3 BaCuO2 + 2 CuO) and 47 N (77.3 K, 0.5 T, with the new liquid phase of Y2O3 + 10 BaCuO2 + 6 CuO) when x = 1.2, which is much higher than that of the samples fabricated with the conventional solid phases (23 N). The average Y2BaCuO5 particle size is about 1 μm, which is much smaller than the 3.4 μm in the samples prepared with the conventional Y2BaCuO5 solid phase; this means that the flux pinning force of the sample can be improved by using the new solid phase. Based on this method, single domain YBCO bulks 40 mm, 59 mm, and 93 mm in diameter have also been fabricated using the TSIG process with the new solid phases (Y2O3 + 1.2BaCuO2). These results indicate that the new TSIG process developed by our lab is a very important and practical method for the fabrication of low cost, large size, and high quality single domain REBCO bulk superconductors.

  8. The Transferability of Regional Climate Models to Non-native Domains at Varying Time- scales

    NASA Astrophysics Data System (ADS)

    Kothavala, Z.; Jones, C.; Rockel, B.; Paquin, D.; Roads, J. O.; Zadra, A.

    2008-05-01

    Five Regional Climate Models (RCMs) were implemented over seven different regions of the globe with the objective of assessing their transferability to different climate regimes. That is, the ability of RCMs to simulate the variability of continental scale climates over different regions of the world with minimal parameter changes. To fully assess the ability of the RCMs to represent the observed variability, field observations collected as part of the Coordinated Enhanced Observation Period (CEOP) program over the same period, were used as a baseline. To gauge the transferability to other continents, we have evaluated their performance separately against CEOP observations taken from coastal, continental, polar and sub-tropical and equatorial sites. The exercise was conducted at the annual, seasonal and diurnal time-scales. We present time-series, frequency distributions, bias estimates and mean diurnal cycle results for these stations, highlighting geographic areas and the time-frames when the RCMs perform well or where they diverge. Most regional climate models simulated the annual cycle of surface temperature close to the observations over mid-latitude regions of Europe and North America. The largest deviations were identified at high altitude sites, Arctic regions, and in the tropics for different reasons. The simulations diverged from the observations at finer time-scales. The analysis yields an insight about how the models simulate the timing of convection or frontal progression in different regions of the world. Where possible we use extra CEOP observations to determine the cause of a given model deviation and make recommendations for improvements for the RCM concerned.

  9. Tilt Angle and Footpoint Separation of Small and Large Bipolar Sunspot Regions Observed with HMI

    NASA Astrophysics Data System (ADS)

    McClintock, B. H.; Norton, A. A.

    2016-02-01

    We investigate bipolar sunspot regions and how tilt angle and footpoint separation vary during emergence and decay. The Helioseismic and Magnetic Imager on board the Solar Dynamic Observatory collects data at a higher cadence than historical records and allows for a detailed analysis of regions over their lifetimes. We sample the umbral tilt angle, footpoint separation, and umbral area of 235 bipolar sunspot regions in Helioseismic and Magnetic Imager—Debrecen Data with an hourly cadence. We use the time when the umbral area peaks as time zero to distinguish between the emergence and decay periods of each region and we limit our analysis of tilt and separation behavior over time to within ±96 hr of time zero. Tilt angle evolution is distinctly different for regions with small (≈30 MSH), midsize (≈50 MSH), and large (≈110 MSH) maximum umbral areas, with 45 and 90 MSH being useful divisions for separating the groups. At the peak umbral area, we determine median tilt angles for small (7.°6), midsize (5.°9), and large (9.°3) regions. Within ±48 hr of the time of peak umbral area, large regions steadily increase in tilt angle, midsize regions are nearly constant, and small regions show evidence of negative tilt during emergence. A period of growth in footpoint separation occurs over a 72-hr period for all of the regions from roughly 40 to 70 Mm. The smallest bipoles (<9 MSH) are outliers in that they do not obey Joy's law and have a much smaller footpoint separation. We confirm the Muñoz-Jaramillo et al. (2015) results that the sunspots appear to be two distinct populations.

  10. Applying the Time-Domain Moment Tensor Inversion technique to Regional Earthquake Data in the Puerto Rico-Virgin Island Region

    NASA Astrophysics Data System (ADS)

    Martinez-Torres, F. A.; Lopez, A. M.

    2015-12-01

    The quick determination of an earthquake's moment tensor, whose description relate to centroid depth, faulting geometry and size, is crucial for tsunami warning systems. Whether an event possesses the critical parameters to produce a devastating tsunami, tsunami warning centers must knowThis research project seeks to test, well-formulated time-domain moment tensor inversion code in order to obtain in quasi real-time faulting parameters of significant regional earthquakes in the Puerto Rico-Virgin Islands region. The inversion code has been developed by researchers at the Berkeley Seismological Laboratory, whose main attractive is to decrease the time it takes to have an estimate calculation of a moment tensor for any major earthquake using regional data, approximately less than 7 minutes of an earthquake's origin time. Four seismic events in the region have been used as testbed to the inversion code configured for this area. In order to compare our results, previously computed and published moment tensor inversions from the Global CMT and USGS for the same events were used to assess the deviations from results obtained in this study. Our results indicate the inversion method is capable of reproducing the regional and teleseismic solutions, and thus can be incorporated into daily earthquake location operations at the Puerto Rico Seismic Network (PRSN) for quick estimation of faulting mechanisms and tsunami warning purposes.

  11. An adaptive subspace trust-region method for frequency-domain seismic full waveform inversion

    NASA Astrophysics Data System (ADS)

    Zhang, Huan; Li, Xiaofan; Song, Hanjie; Liu, Shaolin

    2015-05-01

    Full waveform inversion is currently considered as a promising seismic imaging method to obtain high-resolution and quantitative images of the subsurface. It is a nonlinear ill-posed inverse problem, the main difficulty of which that prevents the full waveform inversion from widespread applying to real data is the sensitivity to incorrect initial models and noisy data. Local optimization theories including Newton's method and gradient method always lead the convergence to local minima, while global optimization algorithms such as simulated annealing are computationally costly. To confront this issue, in this paper we investigate the possibility of applying the trust-region method to the full waveform inversion problem. Different from line search methods, trust-region methods force the new trial step within a certain neighborhood of the current iterate point. Theoretically, the trust-region methods are reliable and robust, and they have very strong convergence properties. The capability of this inversion technique is tested with the synthetic Marmousi velocity model and the SEG/EAGE Salt model. Numerical examples demonstrate that the adaptive subspace trust-region method can provide solutions closer to the global minima compared to the conventional Approximate Hessian approach and the L-BFGS method with a higher convergence rate. In addition, the match between the inverted model and the true model is still excellent even when the initial model deviates far from the true model. Inversion results with noisy data also exhibit the remarkable capability of the adaptive subspace trust-region method for low signal-to-noise data inversions. Promising numerical results suggest this adaptive subspace trust-region method is suitable for full waveform inversion, as it has stronger convergence and higher convergence rate.

  12. Normal Myeloid Development Requires Both the Glutamine-Rich Transactivation Domain and the PEST Region of Transcription Factor PU.1 but Not the Potent Acidic Transactivation Domain

    PubMed Central

    Fisher, Robert C.; Olson, Marilyn C.; Pongubala, Jagan M. R.; Perkel, Jeffrey M.; Atchison, Michael L.; Scott, Edward W.; Simon, M. Celeste

    1998-01-01

    Gene targeting of transcription factor PU.1 results in an early block to fetal hematopoiesis, with no detectable lymphoid or myeloid cells produced in mouse embryos. Furthermore, PU.1−/− embryonic stem (ES) cells fail to differentiate into Mac-1+ and F4/80+ macrophages in vitro. We have previously shown that a PU.1 transgene under the control of its own promoter restores the ability of PU.1−/− ES cells to differentiate into macrophages. In this study, we take advantage of our PU.1−/− ES cell rescue system to genetically test which previously identified PU.1 functional domains are necessary for the development of mature macrophages. PU.1 functional domains include multiple N-terminal acidic and glutamine-rich transactivation domains, a PEST domain, several serine phosphorylation sites, and a C-terminal Ets DNA binding domain, all delineated and characterized by using standard biochemical and transactivational assays. By using the production of mature macrophages as a functional readout in our assay system, we have established that the glutamine-rich transactivation domain, a portion of the PEST domain, and the DNA binding domain are required for myelopoiesis. Deletion of three acidic domains, which exhibit potent transactivation potential in vitro, had no effect on the ability of PU.1 to promote macrophage development. Furthermore, mutagenesis of four independent sites of serine phosphorylation also had no effect on myelopoiesis. Collectively, our results indicate that PU.1 interacts with important regulatory proteins during macrophage development via the glutamine-rich and PEST domains. The PU.1−/− ES cell rescue system represents a powerful, in vitro strategy to functionally map domains of PU.1 essential for normal hematopoiesis and the generation of mature macrophages. PMID:9632818

  13. The flagellin hypervariable region is a potential flagella display domain in probiotic Escherichia coli strain Nissle 1917.

    PubMed

    Yang, Ying; Yang, Yi; Ou, Bingming; Xia, Pengpeng; Zhou, Mingxu; Li, Luan; Zhu, Guoqiang

    2016-09-01

    The most studied probiotic, Escherichia coli strain Nissle 1917 (EcN) possesses flagella of serotype H1. To explore the potential to use EcN flagellin in flagella display applications, we investigated the effect of deleting amino acids in the hypervariable region of flagellin on EcNc (EcN cured of its two cryptic plasmids pMUT1 and pMUT2). Two EcNc flagellin isogenic mutants with deletions of amino acid residual from 277 to 286 and from 287 to 296 in the hypervariable domain were constructed. Both mutants were flagellated, adherent to IPEC-J2 cells, and colonized BALB/c mice. These hypervariable regions may have future utility in the display of heterologous epitopes. PMID:27071621

  14. Large-scale regional comparisons of ecosystem processes: Methods and approaches

    NASA Astrophysics Data System (ADS)

    Legendre, Louis; Niquil, Nathalie

    2013-01-01

    Large-scale regional marine ecosystems can be compared for various processes that include their structure and biodiversity, functioning, services, and effects on biogeochemical processes. The comparisons can proceed from data up, or from conceptual models down, or from a combination of models and data. This study proposes a typology of methods and approaches that are currently used, or could possibly be used for making large-scale ecosystem comparisons. The various methods and approaches are illustrated with examples drawn from the literature.

  15. Deleting the Redundant TSH Receptor C-Peptide Region Permits Generation of the Conformationally Intact Extracellular Domain by Insect Cells.

    PubMed

    Chen, Chun-Rong; Salazar, Larry M; McLachlan, Sandra M; Rapoport, Basil

    2015-07-01

    The TSH receptor (TSHR) extracellular domain (ECD) comprises a N-terminal leucine-rich repeat domain and an hinge region (HR), the latter contributing to ligand binding and critical for receptor activation. The crystal structure of the leucine-rich repeat domain component has been solved, but previous attempts to generate conformationally intact complete ECD or the isolated HR component for structural analysis have failed. The TSHR HR contains a C-peptide segment that is removed during spontaneous TSHR intramolecular cleavage into disulfide linked A- and B-subunits. We hypothesized that deletion of the redundant C-peptide would overcome the obstacle to generating conformationally intact TSHR ECD protein. Indeed, lacking the C-peptide region, the TSHR ECD (termed ECD-D1) and the isolated HR (termed HR-D1) were secreted into medium of insect cells infected with baculoviruses coding for these modified proteins. The identities of TSHR ECD-D1 and HR-D1 were confirmed by ELISA and immunoblotting using TSHR-specific monoclonal antibodies. The TSHR-ECD-D1 in conditioned medium was folded correctly, as demonstrated by its ability to inhibit radiolabeled TSH binding to the TSH holoreceptor. The TSHR ECD-D1 purification was accomplished in a single step using a TSHR monoclonal antibody affinity column, whereas the HR-D1 required a multistep protocol with a low yield. In conclusion, we report a novel approach to generate the TSHR ECD, as well as the isolated HR in insect cells, the former in sufficient amounts for structural studies. However, such studies will require previous complexing of the ECD with a ligand such as TSH or a thyroid-stimulating antibody. PMID:25860033

  16. New Features of Time Domain Electric-Field Structures in the Auroral Acceleration Region

    SciTech Connect

    Mozer, F.S.; Ergun, R.; Temerin, M.; Cattell, C.; Dombeck, J.; Wygant, J.

    1997-08-01

    The Polar Satellite carries the first three-axis electric field detector flown in the magnetosphere. Its direct measurement of electric field components perpendicular and parallel to the local magnetic field has revealed new classes and features of electric field structures associated with the plasma acceleration that produces discrete auroras and that populates the magnetosphere with plasma of ionospheric origin. These structures, associated with the hydrogen ion cyclotron mode, include very large solitary waves, spiky field structures, wave envelopes of parallel electric fields, and very large amplitude, nonlinear, coherent ion cyclotron waves. {copyright} {ital 1997} {ital The American Physical Society}

  17. Identification of a Major Dimorphic Region in the Functionally Critical N-Terminal ID1 Domain of VAR2CSA.

    PubMed

    Doritchamou, Justin; Sabbagh, Audrey; Jespersen, Jakob S; Renard, Emmanuelle; Salanti, Ali; Nielsen, Morten A; Deloron, Philippe; Tuikue Ndam, Nicaise

    2015-01-01

    The VAR2CSA protein of Plasmodium falciparum is transported to and expressed on the infected erythrocyte surface where it plays a key role in placental malaria (PM). It is the current leading candidate for a vaccine to prevent PM. However, the antigenic polymorphism integral to VAR2CSA poses a challenge for vaccine development. Based on detailed analysis of polymorphisms in the sequence of its ligand-binding N-terminal region, currently the main focus for vaccine development, we assessed var2csa from parasite isolates infecting pregnant women. The results reveal for the first time the presence of a major dimorphic region in the functionally critical N-terminal ID1 domain. Parasite isolates expressing VAR2CSA with particular motifs present within this domain are associated with gravidity- and parasite density-related effects. These observations are of particular interest in guiding efforts with respect to optimization of the VAR2CSA-based vaccines currently under development. PMID:26393516

  18. Identification of a Major Dimorphic Region in the Functionally Critical N-Terminal ID1 Domain of VAR2CSA

    PubMed Central

    Doritchamou, Justin; Sabbagh, Audrey; Jespersen, Jakob S.; Renard, Emmanuelle; Salanti, Ali; Nielsen, Morten A.; Deloron, Philippe; Tuikue Ndam, Nicaise

    2015-01-01

    The VAR2CSA protein of Plasmodium falciparum is transported to and expressed on the infected erythrocyte surface where it plays a key role in placental malaria (PM). It is the current leading candidate for a vaccine to prevent PM. However, the antigenic polymorphism integral to VAR2CSA poses a challenge for vaccine development. Based on detailed analysis of polymorphisms in the sequence of its ligand-binding N-terminal region, currently the main focus for vaccine development, we assessed var2csa from parasite isolates infecting pregnant women. The results reveal for the first time the presence of a major dimorphic region in the functionally critical N-terminal ID1 domain. Parasite isolates expressing VAR2CSA with particular motifs present within this domain are associated with gravidity- and parasite density-related effects. These observations are of particular interest in guiding efforts with respect to optimization of the VAR2CSA-based vaccines currently under development. PMID:26393516

  19. An improved method for oriT-directed cloning and functionalization of large bacterial genomic regions.

    PubMed

    Kvitko, Brian H; McMillan, Ian A; Schweizer, Herbert P

    2013-08-01

    We have made significant improvements to a broad-host-range system for the cloning and manipulation of large bacterial genomic regions based on site-specific recombination between directly repeated oriT sites during conjugation. Using two suicide capture vectors carrying flanking homology regions, oriT sites are recombined on either side of the target region. Using a broad-host-range conjugation helper plasmid, the region between the oriT sites is conjugated into an Escherichia coli recipient strain, where it is circularized and maintained as a chimeric mini-F vector. The cloned target region is functionalized in multiple ways to accommodate downstream manipulation. The target region is flanked with Gateway attB sites for recombination into other vectors and by rare 18-bp I-SceI restriction sites for subcloning. The Tn7-functionalized target can also be inserted at a naturally occurring chromosomal attTn7 site(s) or maintained as a broad-host-range plasmid for complementation or heterologous expression studies. We have used the oriTn7 capture technique to clone and complement Burkholderia pseudomallei genomic regions up to 140 kb in size and have created isogenic Burkholderia strains with various combinations of genomic islands. We believe this system will greatly aid the cloning and genetic analysis of genomic islands, biosynthetic gene clusters, and large open reading frames. PMID:23747708

  20. An Improved Method for oriT-Directed Cloning and Functionalization of Large Bacterial Genomic Regions

    PubMed Central

    Kvitko, Brian H.; McMillan, Ian A.

    2013-01-01

    We have made significant improvements to a broad-host-range system for the cloning and manipulation of large bacterial genomic regions based on site-specific recombination between directly repeated oriT sites during conjugation. Using two suicide capture vectors carrying flanking homology regions, oriT sites are recombined on either side of the target region. Using a broad-host-range conjugation helper plasmid, the region between the oriT sites is conjugated into an Escherichia coli recipient strain, where it is circularized and maintained as a chimeric mini-F vector. The cloned target region is functionalized in multiple ways to accommodate downstream manipulation. The target region is flanked with Gateway attB sites for recombination into other vectors and by rare 18-bp I-SceI restriction sites for subcloning. The Tn7-functionalized target can also be inserted at a naturally occurring chromosomal attTn7 site(s) or maintained as a broad-host-range plasmid for complementation or heterologous expression studies. We have used the oriTn7 capture technique to clone and complement Burkholderia pseudomallei genomic regions up to 140 kb in size and have created isogenic Burkholderia strains with various combinations of genomic islands. We believe this system will greatly aid the cloning and genetic analysis of genomic islands, biosynthetic gene clusters, and large open reading frames. PMID:23747708

  1. An Analytical Model of the Large Neutral Regions during the Late Stage of Reionization

    NASA Astrophysics Data System (ADS)

    Xu, Yidong; Yue, Bin; Su, Meng; Fan, Zuhui; Chen, Xuelei

    2014-02-01

    In this paper, we investigate the nature and distribution of large neutral regions during the late epoch of reionization. In the "bubble model" of reionization, the mass distribution of large ionized regions ("bubbles") during the early stage of reionization is obtained by using the excursion set model, where the ionization of a region corresponds to the first up-crossing of a barrier by random trajectories. We generalize this idea and develop a method to predict the distribution of large-scale neutral regions during the late stage of reionization, taking into account the ionizing background after the percolation of H II regions. The large-scale neutral regions, which we call "neutral islands," are not individual galaxies or minihalos, but larger regions where fewer galaxies formed and hence ionized later and they are identified in the excursion set model with the first down-crossings of the island barrier. Assuming that the consumption rate of ionizing background photons is proportional to the surface area of the neutral islands, we obtained the size distribution of the neutral islands. We also take the "bubbles-in-island" effect into account by considering the conditional probability of up-crossing a bubble barrier after down-crossing the island barrier. We find that this effect is very important. An additional barrier is set to avoid islands being percolated through. We find that there is a characteristic scale for the neutral islands, while the small islands are rapidly swallowed up by the ionizing background; this characteristic scale does not change much as the reionization proceeds.

  2. An analytical model of the large neutral regions during the late stage of reionization

    SciTech Connect

    Xu, Yidong; Yue, Bin; Chen, Xuelei; Su, Meng; Fan, Zuhui

    2014-02-01

    In this paper, we investigate the nature and distribution of large neutral regions during the late epoch of reionization. In the 'bubble model' of reionization, the mass distribution of large ionized regions ('bubbles') during the early stage of reionization is obtained by using the excursion set model, where the ionization of a region corresponds to the first up-crossing of a barrier by random trajectories. We generalize this idea and develop a method to predict the distribution of large-scale neutral regions during the late stage of reionization, taking into account the ionizing background after the percolation of H II regions. The large-scale neutral regions, which we call 'neutral islands', are not individual galaxies or minihalos, but larger regions where fewer galaxies formed and hence ionized later and they are identified in the excursion set model with the first down-crossings of the island barrier. Assuming that the consumption rate of ionizing background photons is proportional to the surface area of the neutral islands, we obtained the size distribution of the neutral islands. We also take the 'bubbles-in-island' effect into account by considering the conditional probability of up-crossing a bubble barrier after down-crossing the island barrier. We find that this effect is very important. An additional barrier is set to avoid islands being percolated through. We find that there is a characteristic scale for the neutral islands, while the small islands are rapidly swallowed up by the ionizing background; this characteristic scale does not change much as the reionization proceeds.

  3. Synthesis of Polystyrene-Polylactide Bottlebrush Block Copolymers and Their Melt Self-Assembly into Large Domain Nanostructures

    SciTech Connect

    Rzayev, J.

    2009-04-07

    High molecular weight polystyrene-polylactide (PS-PLA) bottlebrush block copolymers have been shown to self-assemble into highly ordered lamellae structures with domain spacings as large as 163 nm, as identified by ultrasmall-angle X-ray scattering. Bottlebrush block copolymers were synthesized by a combination of living radical and ring-opening polymerizations. The backbone was prepared by RAFT block copolymerization of solketal methacrylate (SM) and 2-(bromoisobutyryl)ethyl methacrylate (BIEM). Polystyrene branches were grafted by ATRP from poly(BIEM) block, and PLA branches were grafted from the poly(SM) block after the removal of ketal groups. The investigation into the self-assembly of PS-PLA bottlebrush block copolymers with varying lengths of branches and backbones revealed a number of unusual trends, which were attributed to their dynamic, three-dimensional structure. The results suggest that in phase-separated melts the bottlebrush block copolymer backbone, while extended, still possesses a certain degree of flexibility to accommodate for different interfacial areas necessary to pack into lamellae microstructures.

  4. Large irreversible non-180° domain switching after poling treatment in Pb(Zr, Ti)O3 films

    NASA Astrophysics Data System (ADS)

    Ehara, Yoshitaka; Yasui, Shintaro; Oikawa, Takahiro; Shiraishi, Takahisa; Oshima, Naoya; Yamada, Tomoaki; Imai, Yasuhiko; Sakata, Osami; Funakubo, Hiroshi

    2016-05-01

    (11 1 ¯ )/(111)-oriented rhombohedral Pb(Zr0.65Ti0.35)O3 films with different domain fractions were epitaxially grown on various single crystals. The volume fraction of (111)-polar-axis oriented domains in as-deposited films, Vpol.(as-depo.), was controlled by selecting a single crystal substrate with a different thermal expansion coefficient. Applying an electric field, referred to as "poling treatment", resulted in irreversible non-180° domain switching from the (11 1 ¯ )-oriented domain (non-polar-axis) to the (111)-oriented domain (polar-axis), which was observed by synchrotron X-ray diffraction. Remanent polarization (Pr) values were higher than those estimated using the proportional relationship with Vpol.(as-depo.). However, the experimental Pr values were in good agreement with the values estimated using the volume fraction of (111)-oriented domains after applying the poling treatment. In rhombohedral Pb(Zr0.65Ti0.35)O3 films, 30%-50% of the (11 1 ¯ )-oriented domains switched irreversibly to (111)-oriented domains as a result of the poling treatment. The present results show that the domain structures of films may change dramatically after the poling process, and both before and after the poling state should be characterized in order to interpret polarization and piezoelectric behaviors. This study helps to clarify the ferroelectric and piezoelectric properties of Pb(Zr, Ti)O3 films after poling treatment.

  5. Characterization of the {alpha}-helix region in domain 3 of the haemolytic lectin CEL-III: implications for self-oligomerization and haemolytic processes.

    PubMed

    Hisamatsu, Keigo; Tsuda, Nobuaki; Goda, Shuichiro; Hatakeyama, Tomomitsu

    2008-01-01

    CEL-III is a haemolytic lectin, which has two beta-trefoil domains (domains 1 and 2) and a beta-sheet-rich domain (domain 3). In domain 3 (residues 284-432), there is a hydrophobic region containing two alpha-helices (H8 and H9, residues 317-357) and a loop between them, in which alternate hydrophobic residues, especially Val residues, are present. To elucidate the role of the alpha-helix region in the haemolytic process, peptides corresponding to different parts of this region were synthesized and characterized. The peptides containing the sequence that corresponded to the loop and second alpha-helix (H9) showed the strongest antibacterial activity for Staphylococcus aureus and Bacillus subtilis through a marked permeabilization of the bacterial cell membrane. The recombinant glutathione S-transferase (GST)-fusion proteins containing domain 3 or the alpha-helix region peptide formed self-oligomers, whereas mutations in the alternate Val residues in the alpha-helix region lead to decreased oligomerization ability of the fusion proteins. These results suggest that the alpha-helix region, particularly its alternate Val residues are important for oligomerization of CEL-III in target cell membranes, which is also required for a subsequent haemolytic action. PMID:17965430

  6. Carbohydrate-binding module 74 is a novel starch-binding domain associated with large and multidomain α-amylase enzymes.

    PubMed

    Valk, Vincent; Lammerts van Bueren, Alicia; van der Kaaij, Rachel M; Dijkhuizen, Lubbert

    2016-06-01

    Microbacterium aurum B8.A is a bacterium that originates from a potato starch-processing plant and employs a GH13 α-amylase (MaAmyA) enzyme that forms pores in potato starch granules. MaAmyA is a large and multi-modular protein that contains a novel domain at its C terminus (Domain 2). Deletion of Domain 2 from MaAmyA did not affect its ability to degrade starch granules but resulted in a strong reduction in granular pore size. Here, we separately expressed and purified this Domain 2 in Escherichia coli and determined its likely function in starch pore formation. Domain 2 independently binds amylose, amylopectin, and granular starch but does not have any detectable catalytic (hydrolytic or oxidizing) activity on α-glucan substrates. Therefore, we propose that this novel starch-binding domain is a new carbohydrate-binding module (CBM), the first representative of family CBM74 that assists MaAmyA in efficient pore formation in starch granules. Protein sequence-based BLAST searches revealed that CBM74 occurs widespread, but in bacteria only, and is often associated with large and multi-domain α-amylases containing family CBM25 or CBM26 domains. CBM74 may specifically function in binding to granular starches to enhance the capability of α-amylase enzymes to degrade resistant starches (RSs). Interestingly, the majority of family CBM74 representatives are found in α-amylases originating from human gut-associated Bifidobacteria, where they may assist in resistant starch degradation. The CBM74 domain thus may have a strong impact on the efficiency of RS digestion in the mammalian gastrointestinal tract. PMID:27101946

  7. Process Domains in Synthetic Landscapes: Slope-Area Relationships in the Mountaintop Mining Region of Central Appalachia.

    NASA Astrophysics Data System (ADS)

    Jaeger, K. L.; Ross, M. R.

    2014-12-01

    Landscapes and the governing geomorphic processes that shape them have been described in a conceptual framework of process domains. At a coarse scale, process domains are segregated between hillslope, colluvial, and alluvial processes, which can be distinguished by governing erosional processes and partitioned by local slope-drainage area relationships. In landscapes that have experienced dramatic topographic alteration such as the mountaintop coal-mining (MTM) region of central Appalachia, the resulting modified environment may be considered a synthetic landscape. Such a landscape has process domains that are decoupled from prior landscape evolution trajectories. In particular, landslide and debris flow processes, which are a predominant geomorphic agent in these steep mountain systems and a primary sediment delivery mechanism to the downstream fluvial network, may be eliminated from this landscape and detectable through changes in slope-area relationships. We evaluate differences in slope-area relationships using 10-m DEMs between two time periods, pre-mined and post-mined. At five study site located within the MTM region in the central Appalachian Mountains, US, we compare slope-area changes to adjacent unmined landscapes over the same time periods. Distinct differences exist in the character of slope-area relationships between unmined and MTM sites and local slopes are systematically and considerably reduced in all process zones of mined sites. In particular, there is an expansion of the unchanneled valley zone through either an individual or simultaneous upslope shift into the hillslope region and downslope shift into the debris flow region. In addition, local slopes are markedly reduced (33% to 44%) in the post-mined period relative to the pre-mined period at all sites and are generally below the threshold required to trigger landslides and debris flows. The consequence of altered erosion processes in this upper portion of the catchment, particularly the

  8. Bayesian WLS/GLS regression for regional skewness analysis for regions with large crest stage gage networks

    USGS Publications Warehouse

    Veilleux, Andrea G.; Stedinger, Jery R.; Eash, David A.

    2012-01-01

    This paper summarizes methodological advances in regional log-space skewness analyses that support flood-frequency analysis with the log Pearson Type III (LP3) distribution. A Bayesian Weighted Least Squares/Generalized Least Squares (B-WLS/B-GLS) methodology that relates observed skewness coefficient estimators to basin characteristics in conjunction with diagnostic statistics represents an extension of the previously developed B-GLS methodology. B-WLS/B-GLS has been shown to be effective in two California studies. B-WLS/B-GLS uses B-WLS to generate stable estimators of model parameters and B-GLS to estimate the precision of those B-WLS regression parameters, as well as the precision of the model. The study described here employs this methodology to develop a regional skewness model for the State of Iowa. To provide cost effective peak-flow data for smaller drainage basins in Iowa, the U.S. Geological Survey operates a large network of crest stage gages (CSGs) that only record flow values above an identified recording threshold (thus producing a censored data record). CSGs are different from continuous-record gages, which record almost all flow values and have been used in previous B-GLS and B-WLS/B-GLS regional skewness studies. The complexity of analyzing a large CSG network is addressed by using the B-WLS/B-GLS framework along with the Expected Moments Algorithm (EMA). Because EMA allows for the censoring of low outliers, as well as the use of estimated interval discharges for missing, censored, and historic data, it complicates the calculations of effective record length (and effective concurrent record length) used to describe the precision of sample estimators because the peak discharges are no longer solely represented by single values. Thus new record length calculations were developed. The regional skewness analysis for the State of Iowa illustrates the value of the new B-WLS/BGLS methodology with these new extensions.

  9. 77 FR 35357 - Atlantic Highly Migratory Species; Commercial Atlantic Region Non-Sandbar Large Coastal Shark...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-13

    ...-Stevens Fishery Conservation and Management Act (16 U.S.C. 1801 et seq.). On January 24, 2012 (77 FR 3393... rule implementing the Atlantic HMS electronic dealer ] reporting system (76 FR 37750; June 28, 2011) or...; Commercial Atlantic Region Non-Sandbar Large Coastal Shark Fishery Opening Date AGENCY: National...

  10. Regional modeling of large wildfires under current and potential future climates in Colorado and Wyoming, USA

    USGS Publications Warehouse

    West, Amanda; Kumar, Sunil; Jarnevich, Catherine S.

    2016-01-01

    Regional analysis of large wildfire potential given climate change scenarios is crucial to understanding areas most at risk in the future, yet wildfire models are not often developed and tested at this spatial scale. We fit three historical climate suitability models for large wildfires (i.e. ≥ 400 ha) in Colorado andWyoming using topography and decadal climate averages corresponding to wildfire occurrence at the same temporal scale. The historical models classified points of known large wildfire occurrence with high accuracies. Using a novel approach in wildfire modeling, we applied the historical models to independent climate and wildfire datasets, and the resulting sensitivities were 0.75, 0.81, and 0.83 for Maxent, Generalized Linear, and Multivariate Adaptive Regression Splines, respectively. We projected the historic models into future climate space using data from 15 global circulation models and two representative concentration pathway scenarios. Maps from these geospatial analyses can be used to evaluate the changing spatial distribution of climate suitability of large wildfires in these states. April relative humidity was the most important covariate in all models, providing insight to the climate space of large wildfires in this region. These methods incorporate monthly and seasonal climate averages at a spatial resolution relevant to land management (i.e. 1 km2) and provide a tool that can be modified for other regions of North America, or adapted for other parts of the world.

  11. MPAS-CICE: A new Los Alamos sea-ice model for regionally refined model domains

    NASA Astrophysics Data System (ADS)

    Turner, A. K.

    2015-12-01

    We present MPAS-CICE, the new Los Alamos National Laboratory sea-ice model. MPAS-CICE uses the Modeling for Prediction Across Scales (MPAS) modeling framework and has been developed to use variable resolution spherical Voronoi tessellation meshes, which allow regional refinement, as well as regular quadrilateral grids. In the later case the model physics reduces to that of the current Los Alamos model, CICE. While the velocity solver and incremental remapping advection have been written specifically for meshes composed of arbitrary shaped polygons, the model uses the column physics directly from CICE. MPAS-CICE is a component of ACME, the new Department of Energy global coupled climate model.

  12. The large N-terminal region of the Brr2 RNA helicase guides productive spliceosome activation.

    PubMed

    Absmeier, Eva; Wollenhaupt, Jan; Mozaffari-Jovin, Sina; Becke, Christian; Lee, Chung-Tien; Preussner, Marco; Heyd, Florian; Urlaub, Henning; Lührmann, Reinhard; Santos, Karine F; Wahl, Markus C

    2015-12-15

    The Brr2 helicase provides the key remodeling activity for spliceosome catalytic activation, during which it disrupts the U4/U6 di-snRNP (small nuclear RNA protein), and its activity has to be tightly regulated. Brr2 exhibits an unusual architecture, including an ∼ 500-residue N-terminal region, whose functions and molecular mechanisms are presently unknown, followed by a tandem array of structurally similar helicase units (cassettes), only the first of which is catalytically active. Here, we show by crystal structure analysis of full-length Brr2 in complex with a regulatory Jab1/MPN domain of the Prp8 protein and by cross-linking/mass spectrometry of isolated Brr2 that the Brr2 N-terminal region encompasses two folded domains and adjacent linear elements that clamp and interconnect the helicase cassettes. Stepwise N-terminal truncations led to yeast growth and splicing defects, reduced Brr2 association with U4/U6•U5 tri-snRNPs, and increased ATP-dependent disruption of the tri-snRNP, yielding U4/U6 di-snRNP and U5 snRNP. Trends in the RNA-binding, ATPase, and helicase activities of the Brr2 truncation variants are fully rationalized by the crystal structure, demonstrating that the N-terminal region autoinhibits Brr2 via substrate competition and conformational clamping. Our results reveal molecular mechanisms that prevent premature and unproductive tri-snRNP disruption and suggest novel principles of Brr2-dependent splicing regulation. PMID:26637280

  13. The large N-terminal region of the Brr2 RNA helicase guides productive spliceosome activation

    PubMed Central

    Absmeier, Eva; Wollenhaupt, Jan; Mozaffari-Jovin, Sina; Becke, Christian; Lee, Chung-Tien; Preussner, Marco; Heyd, Florian; Urlaub, Henning; Lührmann, Reinhard; Santos, Karine F.; Wahl, Markus C.

    2015-01-01

    The Brr2 helicase provides the key remodeling activity for spliceosome catalytic activation, during which it disrupts the U4/U6 di-snRNP (small nuclear RNA protein), and its activity has to be tightly regulated. Brr2 exhibits an unusual architecture, including an ∼500-residue N-terminal region, whose functions and molecular mechanisms are presently unknown, followed by a tandem array of structurally similar helicase units (cassettes), only the first of which is catalytically active. Here, we show by crystal structure analysis of full-length Brr2 in complex with a regulatory Jab1/MPN domain of the Prp8 protein and by cross-linking/mass spectrometry of isolated Brr2 that the Brr2 N-terminal region encompasses two folded domains and adjacent linear elements that clamp and interconnect the helicase cassettes. Stepwise N-terminal truncations led to yeast growth and splicing defects, reduced Brr2 association with U4/U6•U5 tri-snRNPs, and increased ATP-dependent disruption of the tri-snRNP, yielding U4/U6 di-snRNP and U5 snRNP. Trends in the RNA-binding, ATPase, and helicase activities of the Brr2 truncation variants are fully rationalized by the crystal structure, demonstrating that the N-terminal region autoinhibits Brr2 via substrate competition and conformational clamping. Our results reveal molecular mechanisms that prevent premature and unproductive tri-snRNP disruption and suggest novel principles of Brr2-dependent splicing regulation. PMID:26637280

  14. The application of ICOM, a non-hydrostatic, fully unstructured mesh model in large scale ocean domains

    NASA Astrophysics Data System (ADS)

    Kramer, Stephan C.; Piggott, Matthew D.; Cotter, Colin J.; Pain, Chris C.; Nelson, Rhodri B.

    2010-05-01

    given of some of the difficulties that were encountered in the application of ICOM in large scale, high aspect ratio ocean domains and how they have been overcome. A large scale application in the form of a baroclinic, wind-driven double gyre will be presented and the results are compared to two other models, the MIT general circulation model (MITgcm, [3]) and NEMO (Nucleus for European Modelling of the Ocean, [4]). Also a comparison of the performance and parallel scaling of the models on a supercomputing platform will be made. References [1] M.D. Piggott, G.J. Gorman, C.C. Pain, P.A. Allison, A.S. Candy, B.T. Martin and W.R. Wells, "A new computational framework for multi-scale ocean modelling based on adapting unstructured meshes", International Journal for Numerical Methods in Fluids 56, pp 1003 - 1015, 2008 [2] S.C. Kramer, C.J. Cotter and C.C. Pain, "Solving the Poisson equation on small aspect ratio domains using unstructured meshes", submitted to Ocean Modelling [3] J. Marshall, C. Hill, L. Perelman, and A. Adcroft, "Hydrostatic, quasi-hydrostatic, and nonhydrostatic ocean modeling", J. Geophysical Res., 102(C3), pp 5733-5752, 1997 [4] G. Madec, "NEMO ocean engine", Note du Pole de modélisation, Institut Pierre-Simon Laplace (IPSL), France, No 27 ISSN No 1288-1619

  15. High-altitude cusp: The tremendous large and extremely dynamic region in geospace

    NASA Astrophysics Data System (ADS)

    Chen, J.; Fritz, T. A.

    2003-04-01

    High-altitude dayside cusps (both northern and southern) are the tremendous large and extremely dynamic regions in geospace. They have a size of as large as 6 Re and are always there day after day. Turbulent diamagnetic cavities have been observed there. Associated with these cavities are charged particles with energies from 20 keV up to 10 MeV. The intensities of the cusp energetic ions are observed to increase by as large as four orders of the magnitude when compared to regions adjacent to the cusp which includes the magnetosheath. Their seed populations is a mixture of ionospheric and solar wind particles. Some of the diamagnetic cavities were independent of the IMF directions, suggesting that the cusp diamagnetic cavities are different from the magnetospheric sash predicted by MHD simulations. Turbulent electrical field with an amplitude of about 10 mV/m also presents in the cusp, and a cusp resonant acceleration mechanism is suggested.

  16. Large-Scale Covariability Between Aerosol and Precipitation Over the 7-SEAS Region: Observations and Simulations

    NASA Technical Reports Server (NTRS)

    Huang, Jingfeng; Hsu, N. Christina; Tsay, Si-Chee; Zhang, Chidong; Jeong, Myeong Jae; Gautam, Ritesh; Bettenhausen, Corey; Sayer, Andrew M.; Hansell, Richard A.; Liu, Xiaohong; Jiang, Jonathan H.

    2012-01-01

    One of the seven scientific areas of interests of the 7-SEAS field campaign is to evaluate the impact of aerosol on cloud and precipitation (http://7-seas.gsfc.nasa.gov). However, large-scale covariability between aerosol, cloud and precipitation is complicated not only by ambient environment and a variety of aerosol effects, but also by effects from rain washout and climate factors. This study characterizes large-scale aerosol-cloud-precipitation covariability through synergy of long-term multi ]sensor satellite observations with model simulations over the 7-SEAS region [10S-30N, 95E-130E]. Results show that climate factors such as ENSO significantly modulate aerosol and precipitation over the region simultaneously. After removal of climate factor effects, aerosol and precipitation are significantly anti-correlated over the southern part of the region, where high aerosols loading is associated with overall reduced total precipitation with intensified rain rates and decreased rain frequency, decreased tropospheric latent heating, suppressed cloud top height and increased outgoing longwave radiation, enhanced clear-sky shortwave TOA flux but reduced all-sky shortwave TOA flux in deep convective regimes; but such covariability becomes less notable over the northern counterpart of the region where low ]level stratus are found. Using CO as a proxy of biomass burning aerosols to minimize the washout effect, large-scale covariability between CO and precipitation was also investigated and similar large-scale covariability observed. Model simulations with NCAR CAM5 were found to show similar effects to observations in the spatio-temporal patterns. Results from both observations and simulations are valuable for improving our understanding of this region's meteorological system and the roles of aerosol within it. Key words: aerosol; precipitation; large-scale covariability; aerosol effects; washout; climate factors; 7- SEAS; CO; CAM5

  17. THEMIS Observations of the Magnetopause Electron Diffusion Region: Large Amplitude Waves and Heated Electrons

    NASA Technical Reports Server (NTRS)

    Tang, Xiangwei; Cattell, Cynthia; Dombeck, John; Dai, Lei; Wilson, Lynn B. III; Breneman, Aaron; Hupack, Adam

    2013-01-01

    We present the first observations of large amplitude waves in a well-defined electron diffusion region based on the criteria described by Scudder et al at the subsolar magnetopause using data from one Time History of Events and Macroscale Interactions during Substorms (THEMIS) satellite. These waves identified as whistler mode waves, electrostatic solitary waves, lower hybrid waves, and electrostatic electron cyclotron waves, are observed in the same 12 s waveform capture and in association with signatures of active magnetic reconnection. The large amplitude waves in the electron diffusion region are coincident with abrupt increases in electron parallel temperature suggesting strong wave heating. The whistler mode waves, which are at the electron scale and which enable us to probe electron dynamics in the diffusion region were analyzed in detail. The energetic electrons (approx. 30 keV) within the electron diffusion region have anisotropic distributions with T(sub e(right angle))/T(sub e(parallel)) > 1 that may provide the free energy for the whistler mode waves. The energetic anisotropic electrons may be produced during the reconnection process. The whistler mode waves propagate away from the center of the "X-line" along magnetic field lines, suggesting that the electron diffusion region is a possible source region of the whistler mode waves.

  18. Syncytium-inducing mutations localize to two discrete regions within the cytoplasmic domain of herpes simplex virus type 1 glycoprotein B.

    PubMed Central

    Gage, P J; Levine, M; Glorioso, J C

    1993-01-01

    Herpes simplex virus type 1 glycoprotein B (gB) is essential for virus entry, an event involving fusion of the virus envelope with the cell surface membrane, and virus-induced cell-cell fusion, resulting in polykaryocyte, or syncytium, formation. The experiments described in this report employed a random mutagenesis strategy to develop a more complete genetic map of mutations resulting in the syn mutant phenotype. The results indicate that syn mutations occur within two essential and highly conserved hydrophilic, alpha-helical regions of the gB cytoplasmic domain. Region I is immediately proximal to the transmembrane domain and includes residues R796 to E816/817. Region II is localized centrally in the cytoplasmic domain and includes residues A855 and R858. Positively charged residues were particularly affected in both regions, suggesting that charge interactions may be required to suppress the syn mutant phenotype. No syn mutations were identified within the transmembrane domain. A virus containing a rate of entry (roe) mutation at residue A851, either within or immediately proximal to syn region II, was isolated. Since roe mutations have also been discovered in the external domain of gB, it appears likely that the external and cytoplasmic domains cooperate in virus penetration. Moreover, the observation that both roe and syn mutations occur in the cytoplasmic domain further suggests that gB functions in an analogous manner in both membrane fusion events. It might be predicted from these observations that membrane fusion involves transduction of a fusion signal along the gB molecule through the transmembrane domain. Communication between the external and cytoplasmic domain may thus be required for gB-mediated membrane fusion events. Images PMID:8383236

  19. Functional Anthology of Intrinsic Disorder. II. Cellular Components, Domains, Technical Terms, Developmental Processes and Coding Sequence Diversities Correlated with Long Disordered Regions

    PubMed Central

    Vucetic, Slobodan; Xie, Hongbo; Iakoucheva, Lilia M.; Oldfield, Christopher J.; Dunker, A. Keith; Obradovic, Zoran; Uversky, Vladimir N.

    2008-01-01

    Biologically active proteins without stable ordered structure (i.e., intrinsically disordered proteins) are attracting increased attention. Functional repertoires of ordered and disordered proteins are very different, and the ability to differentiate whether a given function is associated with intrinsic disorder or with a well-folded protein is crucial for modern protein science. However, there is a large gap between the number of proteins experimentally confirmed to be disordered and their actual number in nature. As a result, studies of functional properties of confirmed disordered proteins, while helpful in revealing the functional diversity of protein disorder, provide only a limited view. To overcome this problem, a bioinformatics approach for comprehensive study of functional roles of protein disorder was proposed in the first paper of this series (Xie H., Vucetic S., Iakoucheva L.M., Oldfield C.J., Dunker A.K., Obradovic Z., Uversky V.N. (2006) Functional anthology of intrinsic disorder. I. Biological processes and functions of proteins with long disordered regions. J. Proteome Res.). Applying this novel approach to Swiss-Prot sequences and functional keywords, we found over 238 and 302 keywords to be strongly positively or negatively correlated, respectively, with long intrinsically disordered regions. This paper describes ~90 Swiss-Prot keywords attributed to the cellular components, domains, technical terms, developmental processes and coding sequence diversities possessing strong positive and negative correlation with long disordered regions. PMID:17391015

  20. The intrinsically disordered amino-terminal region of human RecQL4: multiple DNA-binding domains confer annealing, strand exchange and G4 DNA binding

    PubMed Central

    Keller, Heidi; Kiosze, Kristin; Sachsenweger, Juliane; Haumann, Sebastian; Ohlenschläger, Oliver; Nuutinen, Tarmo; Syväoja, Juhani E.; Görlach, Matthias; Grosse, Frank; Pospiech, Helmut

    2014-01-01

    Human RecQL4 belongs to the ubiquitous RecQ helicase family. Its N-terminal region represents the only homologue of the essential DNA replication initiation factor Sld2 of Saccharomyces cerevisiae, and also participates in the vertebrate initiation of DNA replication. Here, we utilized a random screen to identify N-terminal fragments of human RecQL4 that could be stably expressed in and purified from Escherichia coli. Biophysical characterization of these fragments revealed that the Sld2 homologous RecQL4 N-terminal domain carries large intrinsically disordered regions. The N-terminal fragments were sufficient for the strong annealing activity of RecQL4. Moreover, this activity appeared to be the basis for an ATP-independent strand exchange activity. Both activities relied on multiple DNA-binding sites with affinities to single-stranded, double-stranded and Y-structured DNA. Finally, we found a remarkable affinity of the N-terminus for guanine quadruplex (G4) DNA, exceeding the affinities for other DNA structures by at least 60-fold. Together, these findings suggest that the DNA interactions mediated by the N-terminal region of human RecQL4 represent a central function at the replication fork. The presented data may also provide a mechanistic explanation for the role of elements with a G4-forming propensity identified in the vicinity of vertebrate origins of DNA replication. PMID:25336622

  1. A novel simian virus 40 early-region domain mediates transactivation of the cyclin A promoter by small-t antigen and is required for transformation in small-t antigen-dependent assays.

    PubMed Central

    Porrás, A; Bennett, J; Howe, A; Tokos, K; Bouck, N; Henglein, B; Sathyamangalam, S; Thimmapaya, B; Rundell, K

    1996-01-01

    At least three regions of the simian virus 40 small-t antigen (small-t) contribute to the protein's ability to enhance cellular transformation. As we showed previously for rat F111 cells, one region includes sequences from residues 97 to 103 that are involved in the binding and inhibition of protein phosphatase 2A. In the present study, the role of the protein phosphatase 2A binding region was confirmed in two additional small-t-dependent transformation systems. Second, small-t was found to provide a function previously identified as a large-T transformation domain. Mutations in residues 19 to 28 of large-T affected its transforming ability, but these mutations were complemented by a wild-type small-t. A third region of small-t was also required for efficient transformation. This region, the 42-47 region, is shared by large-T and small-t and contains a conserved HPDKGG hexapeptide. The 42-47 region function could be provided by either small-t or large-T in small-t-dependent systems. Mutations in the 42-47 region reduced the ability of small-t to transactivate the cyclin A promoter, of interest because small-t increased endogenous cyclin A mRNA levels in both human and monkey cells, as well as transactivating the promoter in transient assays. PMID:8794333

  2. Multiple Functional Domains of AML1: PU.1 and C/EBPα Synergize with Different Regions of AML1

    PubMed Central

    Petrovick, Martha S.; Hiebert, Scott W.; Friedman, Alan D.; Hetherington, Christopher J.; Tenen, Daniel G.; Zhang, Dong-Er

    1998-01-01

    Control elements of many genes are regulated by multiple activators working in concert to confer the maximal level of expression, but the mechanism of such synergy is not completely understood. The promoter of the human macrophage colony-stimulating factor (M-CSF) receptor presents an excellent model with which we can study synergistic, tissue-specific activation for two reasons. First, myeloid-specific expression of the M-CSF receptor is regulated transcriptionally by three factors which are crucial for normal hematopoiesis: PU.1, AML1, and C/EBPα. Second, these proteins interact in such a way as to demonstrate at least two examples of synergistic activation. We have shown that AML1 and C/EBPα activate the M-CSF receptor promoter in a synergistic manner. As we report here, AML1 also synergizes, and interacts physically, with PU.1. Detailed analysis of the physical and functional interaction of AML1 with PU.1 and C/EBPα has revealed that the proteins contact one another through their DNA-binding domains and that AML1 exhibits cooperative DNA binding with C/EBPα but not with PU.1. This difference in DNA-binding abilities may explain, in part, the differences observed in synergistic activation. Furthermore, the activation domains of all three factors are required for synergistic activation, and the region of AML1 required for synergy with PU.1 is distinct from that required for synergy with C/EBPα. These observations present the possibility that synergistic activation is mediated by secondary proteins contacted through the activation domains of AML1, C/EBPα, and PU.1. PMID:9632776

  3. Evaluation of regional climate simulations over the CORDEX-EA-II domain using the COSMO-CLM model

    NASA Astrophysics Data System (ADS)

    Zhou, Weidan; Tang, Jianping; Wang, Xueyuan; Wang, Shuyu; Niu, Xiaorui; Wang, Yuan

    2016-05-01

    The COSMO-CLM (CCLM) model is applied to perform regional climate simulation over the second phase of CORDEX-East Asia (CORDEX-EA-II) domain in this study. Driven by the ERAInterim reanalysis data, the model was integrated from 1988 to 2010 with a high resolution of 0.22°. The model's ability to reproduce mean climatology and climatic extremes is evaluated based on various aspects. The CCLM model is capable of capturing the basic features of the East Asia climate, including the seasonal mean patterns, interannual variations, annual cycles and climate extreme indices for both surface air temperature and precipitation. Some biases are evident in certain areas and seasons. Warm and wet biases appear in the arid and semi-arid areas over the northwestern and northern parts of the domain. The simulated climate over the Tibetan Plateau is colder and wetter than the observations, while South China, East China, and India are drier. The model biases may be caused by the simulated anticyclonic and cyclonic biases in low-level circulations, the simulated water vapor content biases, and the inadequate physical parameterizations in the CCLM model. A parallel 0.44° simulation is conducted and the comparison results show some added value introduced by the higher resolution 0.22° simulation. As a result, the CCLM model could be an adequate member for the next stage of the CORDEX-EA project, while further studies should be encouraged.

  4. Statistical and Scaling Properties of Remotely-Sensed Soil Moisture in Two Contrasting Domains in the North American Monsoon Region

    NASA Technical Reports Server (NTRS)

    Mascaro, Giuseppe; Vivoni, Enrique

    2009-01-01

    Characterizing soil moisture (theta) variability is important for inferring high-resolution information from coarse estimates provided by remote sensors. In this study, we analyze the spatial variability and scale invariance of high-resolution theta estimates collected in two contrasting semiarid areas, Arizona (AZ) and Sonora (SON), during the Soil Moisture Experiment - North American Monsoon in 2004 (SMEX04- NAME). Results reveal that as the mean theta condition () becomes drier, the spatial standard deviation becomes smaller in both domains. The coefficient of variation of theta decreases with in SON, but does not display a clear tendency with in AZ. We also found the presence of scale invariance and multifractality in the range of support scales from 51.2 km to 0.8 km for all soil moisture fields in the two regions. The multifractal properties of theta are clearly linked to in SON, while the relation is affected by more dispersion in AZ. We argue this is due to differences in the dynamic (rainfall) and static (vegetation) controls on theta in the two domains.

  5. N-Terminal Region of the Catalytic Domain of Human N-Myristoyltransferase 1 Acts as an Inhibitory Module

    PubMed Central

    Kumar, Sujeet; Sharma, Rajendra K.

    2015-01-01

    N-myristoyltransferase (NMT) plays critical roles in the modulation of various signaling molecules, however, the regulation of this enzyme in diverse cellular states remains poorly understood. We provide experimental evidence to show for the first time that for the isoform 1 of human NMT (hNMT1), the regulatory roles extend into the catalytic core. In our present study, we expressed, purified, and characterized a truncation mutant devoid of 28 N-terminal amino acids from the catalytic module (Δ28-hNMT1s) and compared its properties to the full-length catalytic domain of hNMT1. The deletion of the N-terminal peptide had no effect on the enzyme stability. Our findings suggest that the N-terminal region in the catalytic module of hNMT1 functions serves as a regulatory control element. The observations of an ~3 fold increase in enzymatic efficiency following removal of the N-terminal peptide of hNMT1s indicates that N-terminal amino acids acts as an inhibitory segment and negatively regulate the enzyme activity. Our findings that the N-terminal region confers control over activity, taken together with the earlier observations that the N-terminal of hNMT1 is differentially processed in diverse cellular states, suggests that the proteolytic processing of the peptide segment containing the inhibitory region provides a molecular mechanism for physiological up-regulation of myristoyltransferase activity. PMID:26000639

  6. Large homogeneous genome regions (isochores) in soybean [glycine max (L.) merr].

    PubMed

    Woody, J L; Beavis, W; Shoemaker, R C

    2012-01-01

    The landscape of plant genomes, while slowly being characterized and defined, is still composed primarily of regions of undefined function. Many eukaryotic genomes contain isochore regions, mosaics of homogeneous GC content that can abruptly change from one neighboring isochore to the next. Isochores are broken into families that are characterized by their GC levels. We identified 4,339 compositionally distinct domains and 331 of these were identified as long homogeneous genome regions (LHGRs). We assigned these to four families based on finite mixture models of GC content. We then characterized each family with respect to exon length, gene content, and transposable elements. The LHGR pattern of soybeans is unique in that while the majority of the genes within LHGRs are found within a single LHGR family with a narrow GC range (Family B), that family is not the highest in GC content as seen in vertebrates and invertebrates. Instead Family B has a mean GC content of 35%. The range of GC content for all LHGRs is 16-59% GC which is a larger range than what is typical of vertebrates. This is the first study in which LHGRs have been identified in soybeans and the functions of the genes within the LHGRs have been analyzed. PMID:22934101

  7. Large-scale data analysis of power grid resilience across multiple US service regions

    NASA Astrophysics Data System (ADS)

    Ji, Chuanyi; Wei, Yun; Mei, Henry; Calzada, Jorge; Carey, Matthew; Church, Steve; Hayes, Timothy; Nugent, Brian; Stella, Gregory; Wallace, Matthew; White, Joe; Wilcox, Robert

    2016-05-01

    Severe weather events frequently result in large-scale power failures, affecting millions of people for extended durations. However, the lack of comprehensive, detailed failure and recovery data has impeded large-scale resilience studies. Here, we analyse data from four major service regions representing Upstate New York during Super Storm Sandy and daily operations. Using non-stationary spatiotemporal random processes that relate infrastructural failures to recoveries and cost, our data analysis shows that local power failures have a disproportionally large non-local impact on people (that is, the top 20% of failures interrupted 84% of services to customers). A large number (89%) of small failures, represented by the bottom 34% of customers and commonplace devices, resulted in 56% of the total cost of 28 million customer interruption hours. Our study shows that extreme weather does not cause, but rather exacerbates, existing vulnerabilities, which are obscured in daily operations.

  8. Large Earthquakes at the Ibero-Maghrebian Region: Basis for an EEWS

    NASA Astrophysics Data System (ADS)

    Buforn, Elisa; Udías, Agustín; Pro, Carmen

    2015-09-01

    Large earthquakes (Mw > 6, Imax > VIII) occur at the Ibero-Maghrebian region, extending from a point (12ºW) southwest of Cape St. Vincent to Tunisia, with different characteristics depending on their location, which cause considerable damage and casualties. Seismic activity at this region is associated with the boundary between the lithospheric plates of Eurasia and Africa, which extends from the Azores Islands to Tunisia. The boundary at Cape St. Vincent, which has a clear oceanic nature in the westernmost part, experiences a transition from an oceanic to a continental boundary, with the interaction of the southern border of the Iberian Peninsula, the northern border of Africa, and the Alboran basin between them, corresponding to a wide area of deformation. Further to the east, the plate boundary recovers its oceanic nature following the northern coast of Algeria and Tunisia. The region has been divided into four zones with different seismic characteristics. From west to east, large earthquake occurrence, focal depth, total seismic moment tensor, and average seismic slip velocities for each zone along the region show the differences in seismic release of deformation. This must be taken into account in developing an EEWS for the region.

  9. Simulated binding of transcription factors to active and inactive regions folds human chromosomes into loops, rosettes and topological domains

    PubMed Central

    Brackley, Chris A.; Johnson, James; Kelly, Steven; Cook, Peter R.; Marenduzzo, Davide

    2016-01-01

    Biophysicists are modeling conformations of interphase chromosomes, often basing the strengths of interactions between segments distant on the genetic map on contact frequencies determined experimentally. Here, instead, we develop a fitting-free, minimal model: bivalent or multivalent red and green ‘transcription factors’ bind to cognate sites in strings of beads (‘chromatin’) to form molecular bridges stabilizing loops. In the absence of additional explicit forces, molecular dynamic simulations reveal that bound factors spontaneously cluster—red with red, green with green, but rarely red with green—to give structures reminiscent of transcription factories. Binding of just two transcription factors (or proteins) to active and inactive regions of human chromosomes yields rosettes, topological domains and contact maps much like those seen experimentally. This emergent ‘bridging-induced attraction’ proves to be a robust, simple and generic force able to organize interphase chromosomes at all scales. PMID:27060145

  10. Simulated binding of transcription factors to active and inactive regions folds human chromosomes into loops, rosettes and topological domains.

    PubMed

    Brackley, Chris A; Johnson, James; Kelly, Steven; Cook, Peter R; Marenduzzo, Davide

    2016-05-01

    Biophysicists are modeling conformations of interphase chromosomes, often basing the strengths of interactions between segments distant on the genetic map on contact frequencies determined experimentally. Here, instead, we develop a fitting-free, minimal model: bivalent or multivalent red and green 'transcription factors' bind to cognate sites in strings of beads ('chromatin') to form molecular bridges stabilizing loops. In the absence of additional explicit forces, molecular dynamic simulations reveal that bound factors spontaneously cluster-red with red, green with green, but rarely red with green-to give structures reminiscent of transcription factories. Binding of just two transcription factors (or proteins) to active and inactive regions of human chromosomes yields rosettes, topological domains and contact maps much like those seen experimentally. This emergent 'bridging-induced attraction' proves to be a robust, simple and generic force able to organize interphase chromosomes at all scales. PMID:27060145

  11. Oscillons and domain walls

    SciTech Connect

    Hindmarsh, Mark; Salmi, Petja

    2008-05-15

    Oscillons, extremely long-lived localized oscillations of a scalar field, are shown to be produced by evolving domain wall networks in {phi}{sup 4} theory in two spatial dimensions. We study the oscillons in frequency space using the classical spectral function at zero momentum, and obtain that the velocity distribution is suppressed as {gamma}{sup -2} at large Lorentz factor {gamma}, with oscillons produced up to at least {gamma}{approx}10. This leads us to speculate that oscillons are produced at cusps, regions of the domain wall travelling near the speed of light. In order to gain some insight onto the dilute oscillon 'gas' produced by the domain walls, we prepare a denser gas by filling the simulation volume with oscillons boosted in random directions. We finish the study by revisiting collisions between oscillons and between an oscillon and a domain wall, showing that in the latter case they can pass straight through with minimal distortion.

  12. Effects of large scale deforestation on precipitation in the monsoon regions: Remote versus local effects

    NASA Astrophysics Data System (ADS)

    Bala, G.; N, D.; Modak, A.

    2015-12-01

    In this study, we investigate the bio-geophysical effects of large-scale deforestation on monsoon regions using idealized deforestation simulations. The simulations are performed using the NCAR CAM5 atmospheric model coupled to a mixed layer ocean model. The four deforestation experiments are named Global, Boreal, Temperate and Tropical, respectively. In these deforestation experiments, trees are replaced by grasses around the globe, between 20oS and 20oN, between 20oN and 50oN and poleward of 50oN, respectively. We find that the remote forcing from large-scale deforestation in the Temperate and Boreal cases shift the Inter-tropical Convergence Zone (ITCZ) southward. This results in a significant decrease in precipitation in the Northern Hemisphere monsoon regions (East Asia, North America, North Africa, South Asia) and moderate precipitation increases in the Southern Hemisphere monsoon regions (South Africa, South America and Australia). The magnitude of the monsoonal precipitation changes depend on the location of deforestation with remote effects showing a larger influence than local effects. The South Asian Monsoon region is affected the most with 18% decline in precipitation over India in the Global deforestation case. Our results indicate that any comprehensive assessment of afforestation/reforestation as climate change mitigation strategies should carefully evaluate the remote effects on monsoonal precipitation besides the large local impacts on temperatures and carbon sequestration benefits. Our results also demonstrate the linkages between any large scale forcing that causes large warming/cooling in the high latitudes and rainfall changes in tropical monsoonal regions via ITCZ shifts. Figure Caption: Changes in annual mean precipitation (mm/day) between the deforestation experiments and the control simulation. Hatched areas are regions where changes are statistically significant at the 95% confidence level. Shading in line plots represents the ±1 standard

  13. Mapping regional patterns of large forest fires in Wildland-Urban Interface areas in Europe.

    PubMed

    Modugno, Sirio; Balzter, Heiko; Cole, Beth; Borrelli, Pasquale

    2016-05-01

    Over recent decades, Land Use and Cover Change (LUCC) trends in many regions of Europe have reconfigured the landscape structures around many urban areas. In these areas, the proximity to landscape elements with high forest fuels has increased the fire risk to people and property. These Wildland-Urban Interface areas (WUI) can be defined as landscapes where anthropogenic urban land use and forest fuel mass come into contact. Mapping their extent is needed to prioritize fire risk control and inform local forest fire risk management strategies. This study proposes a method to map the extent and spatial patterns of the European WUI areas at continental scale. Using the European map of WUI areas, the hypothesis is tested that the distance from the nearest WUI area is related to the forest fire probability. Statistical relationships between the distance from the nearest WUI area, and large forest fire incidents from satellite remote sensing were subsequently modelled by logistic regression analysis. The first European scale map of the WUI extent and locations is presented. Country-specific positive and negative relationships of large fires and the proximity to the nearest WUI area are found. A regional-scale analysis shows a strong influence of the WUI zones on large fires in parts of the Mediterranean regions. Results indicate that the probability of large burned surfaces increases with diminishing WUI distance in touristic regions like Sardinia, Provence-Alpes-Côte d'Azur, or in regions with a strong peri-urban component as Catalunya, Comunidad de Madrid, Comunidad Valenciana. For the above regions, probability curves of large burned surfaces show statistical relationships (ROC value > 0.5) inside a 5000 m buffer of the nearest WUI. Wise land management can provide a valuable ecosystem service of fire risk reduction that is currently not explicitly included in ecosystem service valuations. The results re-emphasise the importance of including this ecosystem service

  14. Distinct Roles of the Repeat-Containing Regions and Effector Domains of the Vibrio vulnificus Multifunctional-Autoprocessing Repeats-in-Toxin (MARTX) Toxin

    PubMed Central

    Kim, Byoung Sik; Gavin, Hannah E.

    2015-01-01

    ABSTRACT Vibrio vulnificus is a seafood-borne pathogen that destroys the intestinal epithelium, leading to rapid bacterial dissemination and death. The most important virulence factor is the multifunctional-autoprocessing repeats-in-toxin (MARTX) toxin comprised of effector domains in the center region flanked by long repeat-containing regions which are well conserved among MARTX toxins and predicted to translocate effector domains. Here, we examined the role of the repeat-containing regions using a modified V. vulnificus MARTX (MARTXVv) toxin generated by replacing all the internal effector domains with β-lactamase (Bla). Bla activity was detected in secretions from the bacterium and also in the cytosol of intoxicated epithelial cells. The modified MARTXVv toxin without effector domains retained its necrotic activity but lost its cell-rounding activity. Further, deletion of the carboxyl-terminal repeat-containing region blocked toxin secretion from the bacterium. Deletion of the amino-terminal repeat-containing region had no effect on secretion but completely abolished translocation and necrosis. Neither secretion nor translocation was affected by enzymatically inactivating the cysteine protease domain of the toxin. These data demonstrate that the amino-terminal and carboxyl-terminal repeat-containing regions of the MARTXVv toxin are necessary and sufficient for the delivery of effector domains and epithelial cell lysis in vitro but that effector domains are required for other cytopathic functions. Furthermore, Ca2+-dependent secretion of the modified MARTXVv toxin suggests that nonclassical RTX-like repeats found in the carboxyl-terminal repeat-containing region are functionally similar to classical RTX repeats found in other RTX proteins. PMID:25827415

  15. Combining resources, combining forces: regionalizing hospital library services in a large statewide health system*

    PubMed Central

    Martin, Heather J.; Delawska-Elliott, Basia

    2015-01-01

    After a reduction in full-time equivalents, 2 libraries in large teaching hospitals and 2 libraries in small community hospitals in a western US statewide health system saw opportunity for expansion through a regional reorganization. Despite a loss of 2/3 of the professional staff and a budgetary decrease of 27% over the previous 3 years, the libraries were able to grow business, usage, awareness, and collections through organizational innovation and improved efficiency. This paper describes the experience—including process, challenges, and lessons learned—of an organizational shift to regionalized services, collections, and staffing. Insights from this process may help similar organizations going through restructuring. PMID:25552945

  16. Combining resources, combining forces: regionalizing hospital library services in a large statewide health system.

    PubMed

    Martin, Heather J; Delawska-Elliott, Basia

    2015-01-01

    After a reduction in full-time equivalents, 2 libraries in large teaching hospitals and 2 libraries in small community hospitals in a western US statewide health system saw opportunity for expansion through a regional reorganization. Despite a loss of 2/3 of the professional staff and a budgetary decrease of 27% over the previous 3 years, the libraries were able to grow business, usage, awareness, and collections through organizational innovation and improved efficiency. This paper describes the experience--including process, challenges, and lessons learned--of an organizational shift to regionalized services, collections, and staffing. Insights from this process may help similar organizations going through restructuring. PMID:25552945

  17. Past, present and future of Tropical Cyclone climatology over CORDEX South-Asia domain: A coupled regional climate model study

    NASA Astrophysics Data System (ADS)

    Kumar, P.; Sein, D.; Koldunov, N.; Hodges, K.; Haensler, A.; Daniela, J.

    2015-12-01

    Tropical cyclones (TC) in the Indian Ocean arise from cyclonic disturbances that naturally form in the inter-tropical convergence zone between 5N and 20N latitudes when sea surface temperatures (SST) are at 27C or above. This relationship between SST and TC formation and intensification implies that rising SST in the climate change era will increase the probability of tropical cyclone formation and that therefore as global temperatures rise so will the frequency and intensity of tropical cyclones. However horizontal resolution of the global general circulation models used in IPCC simulations are usually too coarse to reproduce many smaller scale processes like TC. We present a novel approach to downscale climate change scenarios, which could be also used to investigate the generation and propagation of tropical cyclones over the northern Indian Ocean. The REgional atmosphere MOdel REMO is coupled to the global ocean - sea ice model MPIOM with increased resolution over the Indian Ocean (~20km). The resulting coupled system called ROM. The coupled domain is standard CORDEX south Asia domain (0.44 deg). The models are coupled via the OASIS coupler. Exchange between ocean and atmosphere was made every three hours. Lateral atmospheric and upper oceanic boundary conditions outside the coupled domain were prescribed using ERA40, MPIESM-LR historical and MPIESM-LR RCP85 data. Here we present the results of the dynamical downscaling approach both coupled (ROM) and uncoupled (REMO) simulations for the same period. The validation period (ERA40 and Historical) is 1958-2001. While comparing with observations mean (1958-2001) annual frequency of 8 TC/year, ROM simulated with ERA40 (Historical) TCs are 12 (10), whereas with REMO they are 21 (18). Therefore ROM simulated TC frequency is much more realistic than REMO. REMO has simulated two times more TCs than ROM, hence leading to strong overestimation of TC tracks densities over the region. Scenario simulations (RCP85) showed

  18. Mapping of the amino-terminal half of polyomavirus middle-T antigen indicates that this region is the binding domain for pp60c-src.

    PubMed Central

    Markland, W; Smith, A E

    1987-01-01

    The majority of the carboxy-terminal half of polyomavirus middle-T antigen has been variously mutated and, with the exception of the putative membrane-binding domain (amino acids 394 to 415), was found to be largely dispensible for the transforming activity of the protein. A comparison of the small-T antigen amino acid sequences (equivalent to the region of middle-T encoded by exon 1) of simian virus 40, BK virus, polyomavirus, and a recently described hamster papovavirus highlighted regions of potential interest in mapping functions to the amino-terminal half of polyomavirus middle-T antigen. The regions of interest include amino acids 168 to 191 (previously investigated by this group [S. H. Cheng, W. Markland, A. F. Markham, and A. E. Smith, EMBO J. 5:325-334, 1986]), two cysteine-rich clusters (amino acids 120 to 125 and 148 to 153), and amino acids 92 to 117 (within the limits of the previously described hr-t mutant, SD15). Point mutations, multiple point mutations, and deletions were made by site-specific and site-directed mutagenesis within the cysteine-rich clusters and residues 92 to 117. Studies of the transforming ability of the altered middle-T species demonstrated that this activity is highly sensitive to amino acid changes. All four regions (as defined above) within the amino-terminal half of middle-T have now been studied in detail. The phenotype of the mutants is predominantly transformation defective, and the corresponding variant middle-T species are characterized by being either totally or severely handicapped in the ability to associate actively with pp60c-src. Whether the mutations affect the regions of interaction between middle-T and pp60c-src or simply interfere with the overall conformation of this domain is not known. However, there would appear to be a conformational constraint on this portion of the molecule with regard to its interaction with pp60c-src and by extension to the ability of the middle-T species to transform. Images PMID

  19. Inter-point procrustes: identifying regional and large differences in 3D anatomical shapes.

    PubMed

    Lekadir, Karim; Frangi, Alejandro F; Yang, Guang-Zhong

    2012-01-01

    This paper presents a new approach for the robust alignment and interpretation of 3D anatomical structures with large and localized shape differences. In such situations, existing techniques based on the well-known Procrustes analysis can be significantly affected due to the introduced non-Gaussian distribution of the residuals. In the proposed technique, influential points that induce large dissimilarities are identified and displaced with the aim to obtain an intermediate template with an improved distribution of the residuals. The key element of the algorithm is the use of pose invariant shape variables to robustly guide both the influential point detection and displacement steps. The intermediate template is then used as the basis for the estimation of the final pose parameters between the source and destination shapes, enabling to effectively highlight the regional differences of interest. The validation using synthetic and real datasets of different morphologies demonstrates robustness up-to 50% regional differences and potential for shape classification. PMID:23286119

  20. Precise predictions for B -> Xs l+ l- in the large q2 region

    SciTech Connect

    Ligeti, Zoltan; Ligeti, Zoltan; Tackmann, Frank J.

    2007-07-12

    The inclusive B -> Xs l+ l- decay rate in the large q2 region (q2> m_psi'2) receives significant nonperturbative corrections. The resulting uncertainties can be drastically reduced by normalizing the rate to the B -> Xu l nu rate with the same q2 cut, which allows for much improved tests of short distance physics. We calculate this ratio, including the order 1/m_b3 nonperturbative corrections and the analytically known NNLO perturbative corrections. Since in the large q2 region an inclusive measurement may be feasible via a sum over exclusive states, our results could be useful for measurements at LHCb and possibly for studies of B -> Xd l+ l-.

  1. Spitzer observations of dust emission from H II regions in the Large Magellanic Cloud

    SciTech Connect

    Stephens, Ian W.; Evans, Jessica Marie; Xue, Rui; Chu, You-Hua; Gruendl, Robert A.; Segura-Cox, Dominique M.

    2014-04-01

    Massive stars can alter physical conditions and properties of their ambient interstellar dust grains via radiative heating and shocks. The H II regions in the Large Magellanic Cloud (LMC) offer ideal sites to study the stellar energy feedback effects on dust because stars can be resolved, and the galaxy's nearly face-on orientation allows us to unambiguously associate H II regions with their ionizing massive stars. The Spitzer Space Telescope survey of the LMC provides multi-wavelength (3.6-160 μm) photometric data of all H II regions. To investigate the evolution of dust properties around massive stars, we have analyzed spatially resolved IR dust emission from two classical H II regions (N63 and N180) and two simple superbubbles (N70 and N144) in the LMC. We produce photometric spectral energy distributions (SEDs) of numerous small subregions for each region based on its stellar distributions and nebular morphologies. We use DustEM dust emission model fits to characterize the dust properties. Color-color diagrams and model fits are compared with the radiation field (estimated from photometric and spectroscopic surveys). Strong radial variations of SEDs can be seen throughout the regions, reflecting the available radiative heating. Emission from very small grains drastically increases at locations where the radiation field is the highest, while polycyclic aromatic hydrocarbons (PAHs) appear to be destroyed. PAH emission is the strongest in the presence of molecular clouds, provided that the radiation field is low.

  2. Magnetospheric Multiscale Observations of the Electron Diffusion Region of Large Guide Field Magnetic Reconnection.

    PubMed

    Eriksson, S; Wilder, F D; Ergun, R E; Schwartz, S J; Cassak, P A; Burch, J L; Chen, L-J; Torbert, R B; Phan, T D; Lavraud, B; Goodrich, K A; Holmes, J C; Stawarz, J E; Sturner, A P; Malaspina, D M; Usanova, M E; Trattner, K J; Strangeway, R J; Russell, C T; Pollock, C J; Giles, B L; Hesse, M; Lindqvist, P-A; Drake, J F; Shay, M A; Nakamura, R; Marklund, G T

    2016-07-01

    We report observations from the Magnetospheric Multiscale (MMS) satellites of a large guide field magnetic reconnection event. The observations suggest that two of the four MMS spacecraft sampled the electron diffusion region, whereas the other two spacecraft detected the exhaust jet from the event. The guide magnetic field amplitude is approximately 4 times that of the reconnecting field. The event is accompanied by a significant parallel electric field (E_{∥}) that is larger than predicted by simulations. The high-speed (∼300  km/s) crossing of the electron diffusion region limited the data set to one complete electron distribution inside of the electron diffusion region, which shows significant parallel heating. The data suggest that E_{∥} is balanced by a combination of electron inertia and a parallel gradient of the gyrotropic electron pressure. PMID:27419573

  3. Magnetospheric Multiscale Observations of the Electron Diffusion Region of Large Guide Field Magnetic Reconnection

    NASA Astrophysics Data System (ADS)

    Eriksson, S.; Wilder, F. D.; Ergun, R. E.; Schwartz, S. J.; Cassak, P. A.; Burch, J. L.; Chen, L.-J.; Torbert, R. B.; Phan, T. D.; Lavraud, B.; Goodrich, K. A.; Holmes, J. C.; Stawarz, J. E.; Sturner, A. P.; Malaspina, D. M.; Usanova, M. E.; Trattner, K. J.; Strangeway, R. J.; Russell, C. T.; Pollock, C. J.; Giles, B. L.; Hesse, M.; Lindqvist, P.-A.; Drake, J. F.; Shay, M. A.; Nakamura, R.; Marklund, G. T.

    2016-07-01

    We report observations from the Magnetospheric Multiscale (MMS) satellites of a large guide field magnetic reconnection event. The observations suggest that two of the four MMS spacecraft sampled the electron diffusion region, whereas the other two spacecraft detected the exhaust jet from the event. The guide magnetic field amplitude is approximately 4 times that of the reconnecting field. The event is accompanied by a significant parallel electric field (E∥ ) that is larger than predicted by simulations. The high-speed (˜300 km /s ) crossing of the electron diffusion region limited the data set to one complete electron distribution inside of the electron diffusion region, which shows significant parallel heating. The data suggest that E∥ is balanced by a combination of electron inertia and a parallel gradient of the gyrotropic electron pressure.

  4. Unexpectedly large number of conserved noncoding regions within the ancestral chordate Hox cluster.

    PubMed

    Pascual-Anaya, Juan; D'Aniello, Salvatore; Garcia-Fernàndez, Jordi

    2008-12-01

    The single amphioxus Hox cluster contains 15 genes and may well resemble the ancestral chordate Hox cluster. We have sequenced the Hox genomic complement of the European amphioxus Branchiostoma lanceolatum and compared it to the American species, Branchiostoma floridae, by phylogenetic footprinting to gain insights into the evolution of Hox gene regulation in chordates. We found that Hox intergenic regions are largely conserved between the two amphioxus species, especially in the case of genes located at the 3' of the cluster, a trend previously observed in vertebrates. We further compared the amphioxus Hox cluster with the human HoxA, HoxB, HoxC, and HoxD clusters, finding several conserved noncoding regions, both in intergenic and intronic regions. This suggests that the regulation of Hox genes is highly conserved across chordates, consistent with the similar Hox expression patterns in vertebrates and amphioxus. PMID:18791732

  5. The Compact Body Plan of Tardigrades Evolved by the Loss of a Large Body Region.

    PubMed

    Smith, Frank W; Boothby, Thomas C; Giovannini, Ilaria; Rebecchi, Lorena; Jockusch, Elizabeth L; Goldstein, Bob

    2016-01-25

    The superphylum Panarthropoda (Arthropoda, Onychophora, and Tardigrada) exhibits a remarkable diversity of segment morphologies, enabling these animals to occupy diverse ecological niches. The molecular identities of these segments are specified by Hox genes and other axis patterning genes during development [1, 2]. Comparisons of molecular segment identities between arthropod and onychophoran species have yielded important insights into the origins and diversification of their body plans [3-9]. However, the relationship of the segments of tardigrades to those of arthropods and onychophorans has remained enigmatic [10, 11], limiting our understanding of early panarthropod body plan diversification. Here, we reveal molecular identities for all of the segments of a tardigrade. Based on our analysis, we conclude that tardigrades have lost a large intermediate region of the body axis-a region corresponding to the entire thorax and most of the abdomen of insects-and that they have lost the Hox genes that originally specified this region. Our data suggest that nearly the entire tardigrade body axis is homologous to just the head region of arthropods. Based on our results, we reconstruct a last common ancestor of Panarthropoda that had a relatively elongate body plan like most arthropods and onychophorans, rather than a compact, tardigrade-like body plan. These results demonstrate that the body plan of an animal phylum can originate by the loss of a large part of the body. PMID:26776737

  6. CURRENT HELICITY OF ACTIVE REGIONS AS A TRACER OF LARGE-SCALE SOLAR MAGNETIC HELICITY

    SciTech Connect

    Zhang, H.; Gao, Y.; Xu, H.; Moss, D.; Kleeorin, N.; Rogachevskii, I.; Kuzanyan, K.; Sokoloff, D.

    2012-05-20

    We demonstrate that the current helicity observed in solar active regions traces the magnetic helicity of the large-scale dynamo generated field. We use an advanced two-dimensional mean-field dynamo model with dynamo saturation based on the evolution of the magnetic helicity and algebraic quenching. For comparison, we also studied a more basic two-dimensional mean-field dynamo model with simple algebraic alpha-quenching only. Using these numerical models we obtained butterfly diagrams both for the small-scale current helicity and also for the large-scale magnetic helicity, and compared them with the butterfly diagram for the current helicity in active regions obtained from observations. This comparison shows that the current helicity of active regions, as estimated by -A {center_dot} B evaluated at the depth from which the active region arises, resembles the observational data much better than the small-scale current helicity calculated directly from the helicity evolution equation. Here B and A are, respectively, the dynamo generated mean magnetic field and its vector potential. A theoretical interpretation of these results is given.

  7. W phase source inversion using high-rate regional GPS data for large earthquakes

    NASA Astrophysics Data System (ADS)

    Riquelme, S.; Bravo, F.; Melgar, D.; Benavente, R.; Geng, J.; Barrientos, S.; Campos, J.

    2016-04-01

    W phase moment tensor inversion has proven to be a reliable method for rapid characterization of large earthquakes. For global purposes it is used at the United States Geological Survey, Pacific Tsunami Warning Center, and Institut de Physique du Globe de Strasbourg. These implementations provide moment tensors within 30-60 min after the origin time of moderate and large worldwide earthquakes. Currently, the method relies on broadband seismometers, which clip in the near field. To ameliorate this, we extend the algorithm to regional records from high-rate GPS data and retrospectively apply it to six large earthquakes that occurred in the past 5 years in areas with relatively dense station coverage. These events show that the solutions could potentially be available 4-5 min from origin time. Continuously improving GPS station availability and real-time positioning solutions will provide significant enhancements to the algorithm.

  8. Computational analysis of the extracellular domain of the Ca²⁺-sensing receptor: an alternate model for the Ca²⁺ sensing region.

    PubMed

    Morrill, Gene A; Kostellow, Adele B; Gupta, Raj K

    2015-03-27

    The extracellular Ca(2+) sensing receptor (CaSR) belongs to Class C G-protein-coupled receptors (GPCRs) which include receptors for amino acids, γ-aminobutyric acid and glutamate neurotransmitters. CaSR has been described as having an extended sequence containing a Ca(2+) binding pocket within an extracellular amino (N)-terminal domain, called a Venus Fly Trap (VFT) module. CaSR is thought to consist of three domains: 1) a Ca(2+-)sensory domain, 2) a region containing 7 transmembrane (TM) helices, and 3) a carboxy (C)-terminal tail. We find that SPOCTOPUS (a combination of hidden Markov models and artificial neural networks) predicts that Homo sapiens CaSR contains two additional TM helices ((190)D - G(210); (262)S-E(282)), with the second TM helix containing a pore-lining region ((265)K - I(280)). This predicts that the putative Ca(2+) sensory domain is within an extracellular loop, N-terminal to the highly conserved heptahelical bundle. This loop contains both the cysteine-rich domain ((537)V - C(598)) and a 14 residue "linker" sequence ((599)I - F(612)) thought to support signal transmission to the heptahelical bundle. Thus domain 1 may contain a 189 residue N-terminal extracellular region followed successively by TM-1, a short intracellular loop, TM-2 and a 329 residue extracellular loop; rather than the proposed 620 residue VFT module based on crystallography of the N-terminal region of mGluR1. Since the topologies of the two proteins differ, the published CaSR VFT model is questionable. CaSR also contains multiple caveolin-binding motifs and cholesterol-binding (CRAC/CARC) domains, facilitating localization to plasma membrane lipid rafts. Ion sensing may involve combination of pore-lining regions from CaSR dimers and CaSR-bound caveolins to form ion channels capable of monitoring ionized Ca(2+) levels. PMID:25701780

  9. Four large-scale field-aligned current systems in the dayside high-latitude region

    SciTech Connect

    Ohtani, S.; Potemra, T.A.; Newell, P.T.

    1995-01-01

    A system of four current sheets of large-scale field-aligned currents (FACs) was discovered in the data set of simultaneous Viking and DMSP-F7 crossings of the dayside high-latitude region. This paper reports four examples of this system that were observed in the prenoon sector. The flow polarities of FACs are upward, downward, upward, and downward, from equatorward to poleward. The lowest-latitude upward current is flowing mostly in the CPS precipitation region, often overlapping with the BPS at its poleward edge, and is interpreted as a region 2 current. The pair of downward and upward FACs in the middle of the structure are collocated with structured electron precipitation. The precipitation of high-energy (>1 keV) electrons is more intense in the lower-latitude downward current sheet. The highest-latitude downward flowing current sheet is located in a weak, low-energy particle precipitation region, suggesting that this current is flowing on open field lines. Simultaneous observations in the postnoon local time sector reveal the standard three-sheet structure of FACs, sometimes described as region 2, region 1, and mantle (referred to the midday region 0) currents. A high correlation was found between the occurrence of the four FAC sheet structure and negative interplanetary magnetic field (IMF) B{sub Y}. The authors discuss the FAC structure in terms of three types of convection cells: the merging, viscous, and lobe cells. During strongly negative IMF B{sub Y}, two convection reversals exist in the prenoon sector; one is inside the viscous cell, and the other is between the viscous cell and the lobe cell. This structure of convection flow is supported by the Viking electric field and auroral UV image data. Based on the convection pattern, the four FAC sheet structure is interpreted as the latitudinal overlap of midday and morning FAC systems. 47 refs., 12 figs., 1 tab.

  10. Severe deep convection events in the Andes region (Mendoza, Argentina) and their relation with large amplitude mountain waves

    NASA Astrophysics Data System (ADS)

    de la Torre, Alejandro; Hierro, Lic. R.; Llamedo, Lic. P.; Rolla, Lic. A.; Alexander, Peter

    In addition to an environmental lapse rate conditionally unstable and sufficient available mois-ture, some process by which a parcel is lifted to its LFC is required for the occurrence of deep convection. Since rising motions associated with synoptic scale processes are too weak to lift a moist parcel to its LFC, some strong sub-synoptic mechanism such us upward motion over a frontal zone, anabatic/katabatic winds or mountain waves are required to supply the necessary energy to trigger deep convection. We analyze here, two selected recent severe storms developed in the absence of fronts and registered at the south of Mendoza, Argentina, a semiarid region situated at midlatitudes (roughly between 32S and 36S) at the east of the highest Andes tops. The storms were initiated at the same local time. In both cases, large amplitude stationary mountain waves with similar wavelengths were generated through the forcing of the NW wind by the Andes Range, just before the first cell was detected in the S-band radar. Mesoscale model simulatons (WRF3V, three domains, inner at 4 km) were conducted. The wave pat-tern was analyzed at several constant pressure levels with a Morlet wavelet. This wavelet has proven to be a useful technique for this purpose, as propagating mountain waves are well local-ized within a horizontal domain of some hundred kilometers. The simulated evolution in space and time of vertical wind oscillations (even better than reflectivity) reveal their influence in the genesis zone of both storms. The synoptic conditions observed (low-pressure system over the NW of Argentina, slow displacement of anticyclones in Pacific and Atlantic oceans, a low level jet carrying warm and moist air from the N and geopotential distribution at 1000, 500 and 300 hPa) are consistent with earlier works. We describe and discuss, in both cases, i) the vertical and horizontal wavelengths, ii) the direction of propagation of the main wave modes, iii) their lineal polarization and phase

  11. Large Solar Energetic Particle Events Associated With Filament Eruptions Outside Active Regions

    NASA Technical Reports Server (NTRS)

    Gopalswamy, N.; Makela, P.; Akiyama, S.; Yashiro, S.; Xie, H.; Thakur, N.; Kahler, S. W.

    2015-01-01

    We report on four large filament eruptions (FEs) from solar cycles 23 and 24 that were associated with large solar energetic particle (SEP) events and interplanetary type II radio bursts. The post-eruption arcades corresponded mostly to C-class soft X-ray enhancements, but an M1.0 flare was associated with one event. However, the associated coronal mass ejections (CMEs) were fast (speeds approx. 1000 km/s) and appeared as halo CMEs in the coronagraph field of view. The interplanetary type II radio bursts occurred over a wide wavelength range, indicating the existence of strong shocks throughout the inner heliosphere. No metric type II bursts were present in three events, indicating that the shocks formed beyond 2-3 Rs. In one case, there was a metric type II burst with low starting frequency, indicating a shock formation height of approx.2 Rs. The FE-associated SEP events did have softer spectra (spectral index >4) in the 10-100 MeV range, but there were other low-intensity SEP events with spectral indices ?4. Some of these events are likely FE-SEP events, but were not classified as such in the literature because they occurred close to active regions. Some were definitely associated with large active region flares, but the shock formation height was large. We definitely find a diminished role for flares and complex type III burst durations in these large SEP events. Fast CMEs and shock formation at larger distances from the Sun seem to be the primary characteristics of the FE-associated SEP events.

  12. Large Solar Energetic Particle Events Associated with Filament Eruptions Outside of Active Regions

    NASA Astrophysics Data System (ADS)

    Gopalswamy, N.; Mäkelä, P.; Akiyama, S.; Yashiro, S.; Xie, H.; Thakur, N.; Kahler, S. W.

    2015-06-01

    We report on four large filament eruptions (FEs) from solar cycles 23 and 24 that were associated with large solar energetic particle (SEP) events and interplanetary type II radio bursts. The post-eruption arcades corresponded mostly to C-class soft X-ray enhancements, but an M1.0 flare was associated with one event. However, the associated coronal mass ejections (CMEs) were fast (speeds ˜ 1000 km s-1) and appeared as halo CMEs in the coronagraph field of view. The interplanetary type II radio bursts occurred over a wide wavelength range, indicating the existence of strong shocks throughout the inner heliosphere. No metric type II bursts were present in three events, indicating that the shocks formed beyond 2-3 Rs. In one case, there was a metric type II burst with low starting frequency, indicating a shock formation height of ˜2 Rs. The FE-associated SEP events did have softer spectra (spectral index >4) in the 10-100 MeV range, but there were other low-intensity SEP events with spectral indices ≥4. Some of these events are likely FE-SEP events, but were not classified as such in the literature because they occurred close to active regions. Some were definitely associated with large active region flares, but the shock formation height was large. We definitely find a diminished role for flares and complex type III burst durations in these large SEP events. Fast CMEs and shock formation at larger distances from the Sun seem to be the primary characteristics of the FE-associated SEP events.

  13. Regional Climate Implications of Large-scale Cultivation of Biofuel Crops

    NASA Astrophysics Data System (ADS)

    Rowe, C. M.; Oglesby, R. J.; Hays, C. J.; van Etten, A. R.

    2008-12-01

    Conversion from corn-based ethanol to cellulosic ethanol has the potential to dramatically alter the production of biofuels in the United States and could result in large-scale changes in the agricultural landscape of vast areas of the country. Regions currently dominated by corn production could see widespread planting of switchgrass and other fast-growing, water-efficient sources of cellulose biomass. An often overlooked side effect of these land-cover changes could be a significant alteration of the energy fluxes between the land surface and the atmosphere with profound local, regional, and continental impacts on the climate system. Changes in the surface energy balance result primarily from differences in the seasonality of transpiration from corn versus switchgrass and could be enhanced as a result of a reduced need for irrigation of switchgrass in areas where corn can be produced only under irrigation. Preliminary modeling results using a simple "bucket" land surface model coupled to the WRF mesoscale model have demonstrated increases in summertime average daily maximum temperature of up to 4° C, smaller increases of up to 2° C in nighttime minimum temperatures and reductions in precipitation by up to 25% when corn was changed to switchgrass over the central United States. Improved parameterization of biofuel crops in more sophisticated land surface models will allow us to refine these preliminary estimates and assess the impacts of large-scale conversion to cellulosic biofuel crops, relative to greenhouse gas induced regional climate change.

  14. pRB-Dependent, J Domain-Independent Function of Simian Virus 40 Large T Antigen in Override of p53 Growth Suppression

    PubMed Central

    Gjoerup, Ole; Chao, Herta; DeCaprio, James A.; Roberts, Thomas M.

    2000-01-01

    Simian virus 40 (SV40) large T antigen (LT) can immortalize and transform many cell types. These activities are attributed in large part to the binding and functional inactivation by LT of two major tumor suppressors: p53 and the retinoblastoma protein, pRB. Most effects of LT on pRB have been shown to additionally require an intact J domain, which mediates binding to Hsc70. We show here that the J domain is not required for p53 override in full-length LT. Although LT binds p53, it was shown previously that overcoming a p53-induced cell cycle arrest requires binding to pRB family members (R. S. Quartin et al., J. Virol. 68:1334–1341). We demonstrate that an LT mutant defective for pRB family member binding (K1) can be complemented for efficient override of p53 arrest by a construct encoding the first 135 amino acids of LT with a J domain-inactivating mutation, H42Q. Hence, complementation does not require the J domain, and pRB binding by LT is important for more than dissociating pRB-E2F complexes, which is J dependent. In accordance with this notion, LT alleviates pRB small-pocket-mediated transcriptional repression independently of the J domain. The LT K1 mutant can also be complemented for p53 override by small t antigen (st) in a manner independent of its J domain. Our observations underscore the importance of multiple SV40 functions, two in LT and one in st, that act cooperatively to counteract p53 growth suppression. PMID:10623749

  15. Crystal Structures of the Pilus Retraction Motor PilT Suggest Large Domain Movements and Subunit Cooperation Drive Motility

    PubMed Central

    Satyshur, Kenneth A.; Worzalla, Gregory A.; Meyer, Lorraine S.; Heiniger, Erin K.; Aukema, Kelly G.; Misic, Ana M.; Forest, Katrina T.

    2007-01-01

    Summary PilT is a hexameric ATPase required for bacterial Type IV pilus retraction and surface motility. Crystal structures of ADP and ATP-bound Aquifex aeolicus PilT at 2.8 and 3.2 Å resolution show N-terminal PAS-like and C-terminal RecA-like ATPase domains followed by a set of short C-terminal helices. The hexamer is formed by extensive polar subunit interactions between the ATPase core of one monomer and the N-terminal domain of the next. An additional structure captures a non-symmetric PilT hexamer in which approach of invariant arginines from two subunits to the bound nucleotide forms an enzymatically competent active site. A panel of pilT mutations highlights the importance of the arginines, the PAS-like domain, the polar subunit interface, and the C-terminal helices for retraction. We present a model for ATP binding leading to dramatic PilT domain motions, engagement of the arginine wire, and subunit communication in this hexameric motor. Our conclusions apply to the entire Type II/IV secretion ATPase family. PMID:17355871

  16. Feasibility of large-scale water monitoring and forecasting in the Asia-Pacific region

    NASA Astrophysics Data System (ADS)

    van Dijk, A. I. J. M.; Peña-Arancibia, J. L.; Sardella, C. S. E.

    2012-04-01

    The Asian-Pacific region (including China, India and Pakistan) is home to 51% of the global population. It accounts for 53% of agricultural and 32% of domestic water use world wide. Due to the influence of Pacific Ocean and Indian Ocean circulation patterns, the region experiences strong inter-annual variations in water availability and occurrence of drought, flood and severe weather. Some of the countries in the region have national water monitoring or forecasting systems, but they are typically of fairly narrow scope. We investigated the feasibility and utility of an integrated regional water monitoring and forecasting system for water resources, floods and drought. In particular, we assessed the quality of information that can be achieved by relying on internationally available data sources, including numerical weather prediction (NWP) and satellite observations of precipitation, soil moisture and vegetation. Combining these data sources with a large scale hydrological model, we produced monitoring and forecast information for selected retrospective case studies. The information was compared to that from national systems, both in terms of information content and system characteristics (e.g. scope, data sources, and information latency). While national systems typically have better access to national observation systems, they do not always make effective use of the available data, science and technology. The relatively slow changing nature of important Pacific and Indian Ocean circulation patterns adds meaningful seasonal forecast skill for some regions. Satellite and NWP precipitation estimates can add considerable value to the national gauge networks: as forecasts, as near-real time observations and as historic reference data. Satellite observations of soil moisture and vegetation are valuable for drought monitoring and underutilised. Overall, we identify several important opportunities for better water monitoring and forecasting in the Asia-Pacific region.

  17. The evolutionarily conserved region of the U snRNA export mediator PHAX is a novel RNA-binding domain that is essential for U snRNA export.

    PubMed Central

    Segref, A; Mattaj, I W; Ohno, M

    2001-01-01

    In metazoa, a subset of spliceosomal U snRNAs are exported from the nucleus after transcription. This export occurs in a large complex containing a U snRNA, the nuclear cap binding complex (CBC), the leucine-rich nuclear export signal receptor CRM1/Xpo1, RanGTP, and the recently identified phosphoprotein PHAX (phosphorylated adaptor for RNA export). Previous results indicated that PHAX made direct contact with RNA, CBC, and Xpo1 in the U snRNA export complex. We have now performed a systematic characterization of the functional domains of PHAX. The most evolutionarily conserved region of PHAX is shown to be a novel RNA-binding domain that is essential for U snRNA export. In addition, PHAX contains two major nuclear localization signals (NLSs) that are required for its recycling to the nucleus after export. The interaction domain of PHAX with CBC is at least partly distinct from the RNA-binding domain and the NLSs. Thus, the different interaction domains of PHAX allow it to act as a scaffold for the assembly of U snRNA export complexes. PMID:11333016

  18. DUST EMISSION FROM EVOLVED AND UNEVOLVED H II REGIONS IN THE LARGE MAGELLANIC CLOUD

    SciTech Connect

    Slater, C. T.; Oey, M. S.; Li, A.; Bernard, J.-Ph.; Paradis, D.; Churchwell, E.; Gordon, K. D.; Lawton, B.; Meixner, M.; Indebetouw, R.; Reach, W.T.

    2011-05-10

    We present a study of the dust properties of 12 classical and superbubble H II regions in the Large Magellanic Cloud. We use infrared photometry from Spitzer (8, 24, 70, and 160 {mu} m bands), obtained as part of the Surveying the Agents of a Galaxy's Evolution (SAGE) program, along with archival spectroscopic classifications of the ionizing stars to examine the role of stellar sources on dust heating and processing. Our infrared observations show surprisingly little correlation between the emission properties of the dust and the effective temperatures or bolometric magnitudes of stars in the H II regions, suggesting that the H II region evolutionary timescale is not on the order of the dust processing timescale. We find that the infrared emission of superbubbles and classical H II regions shows little differentiation between the two classes, despite the significant differences in age and morphology. We do detect a correlation of the 24 {mu} m emission from hot dust with the ratio of 70-160 {mu} m flux. This correlation can be modeled as a trend in the temperature of a minority hot dust component, while a majority of the dust remains significantly cooler.

  19. Inhibition of protein kinase C catalytic activity by additional regions within the human protein kinase Calpha-regulatory domain lying outside of the pseudosubstrate sequence.

    PubMed

    Kirwan, Angie F; Bibby, Ashley C; Mvilongo, Thierry; Riedel, Heimo; Burke, Thomas; Millis, Sherri Z; Parissenti, Amadeo M

    2003-07-15

    The N-terminal pseudosubstrate site within the protein kinase Calpha (PKCalpha)-regulatory domain has long been regarded as the major determinant for autoinhibition of catalytic domain activity. Previously, we observed that the PKC-inhibitory capacity of the human PKCalpha-regulatory domain was only reduced partially on removal of the pseudosubstrate sequence [Parissenti, Kirwan, Kim, Colantonio and Schimmer (1998) J. Biol. Chem. 273, 8940-8945]. This finding suggested that one or more additional region(s) contributes to the inhibition of catalytic domain activity. To assess this hypothesis, we first examined the PKC-inhibitory capacity of a smaller fragment of the PKCalpha-regulatory domain consisting of the C1a, C1b and V2 regions [GST-Ralpha(39-177): this protein contained the full regulatory domain of human PKCalpha fused to glutathione S-transferase (GST), but lacked amino acids 1-38 (including the pseudosubstrate sequence) and amino acids 178-270 (including the C2 region)]. GST-Ralpha(39-177) significantly inhibited PKC in a phorbol-independent manner and could not bind the peptide substrate used in our assays. These results suggested that a region within C1/V2 directly inhibits catalytic domain activity. Providing further in vivo support for this hypothesis, we found that expression of N-terminally truncated pseudosubstrate-less bovine PKCalpha holoenzymes in yeast was capable of inhibiting cell growth in a phorbol-dependent manner. This suggested that additional autoinhibitory force(s) remained within the truncated holoenzymes that could be relieved by phorbol ester. Using tandem PCR-mediated mutagenesis, we observed that mutation of amino acids 33-86 within GST-Ralpha(39-177) dramatically reduced its PKC-inhibitory capacity when protamine was used as substrate. Mutagenesis of a broad range of sequences within C2 (amino acids 159-242) also significantly reduced PKC-inhibitory capacity. Taken together, these observations support strongly the existence of

  20. Bulk glassy Cu-based alloys with a large supercooled liquid region of 110 K

    NASA Astrophysics Data System (ADS)

    Inoue, Akihisa; Zhang, Wei

    2003-09-01

    The replacement of Cu by 5%Ag for Cu50Hf45Al5 glassy alloy was found to increase significantly the stability of supercooled liquid against crystallization. The supercooled liquid region reached as large as 110 K for Cu45Hf45Al5Ag5. The extension of the supercooled liquid region is due to an increase in the crystallization temperature, accompanying the change in the primary crystalline phases. The effectiveness of Ag addition was interpreted to result from the retardation of long-range atomic rearrangements for the progress of crystallization reaction. The selection of the quaternary composition enabled us to form bulk glassy alloys with diameters up to 3 mm. The Young's modulus and compressive fracture strength of the 5%Ag-containing alloy are 119 GPa and 2220 MPa, respectively.

  1. The Gould's Belt very large array survey. III. The Orion region

    SciTech Connect

    Kounkel, Marina; Hartmann, Lee; Loinard, Laurent; Ortiz-León, Gisela N.; Rodríguez, Luis F.; Pech, Gerardo; Rivera, Juana L.; Mioduszewski, Amy J.; Dzib, Sergio A.; Torres, Rosa M.; Boden, Andrew F.; Evans, Neal J. II; Briceño, Cesar; Tobin, John

    2014-07-20

    We present results from a high-sensitivity (60 μJy), large-scale (2.26 deg{sup 2}) survey obtained with the Karl G. Jansky Very Large Array as part of the Gould's Belt Survey program. We detected 374 and 354 sources at 4.5 and 7.5 GHz, respectively. Of these, 148 are associated with previously known young stellar objects (YSOs). Another 86 sources previously unclassified at either optical or infrared wavelengths exhibit radio properties that are consistent with those of young stars. The overall properties of our sources at radio wavelengths such as their variability and radio to X-ray luminosity relation are consistent with previous results from the Gould's Belt Survey. Our detections provide target lists for follow-up Very Long Baseline Array radio observations to determine their distances as YSOs are located in regions of high nebulosity and extinction, making it difficult to measure optical parallaxes.

  2. Large optical nonlinearity of indium tin oxide in its epsilon-near-zero region.

    PubMed

    Alam, M Zahirul; De Leon, Israel; Boyd, Robert W

    2016-05-13

    Nonlinear optical phenomena are crucial for a broad range of applications, such as microscopy, all-optical data processing, and quantum information. However, materials usually exhibit a weak optical nonlinearity even under intense coherent illumination. We report that indium tin oxide can acquire an ultrafast and large intensity-dependent refractive index in the region of the spectrum where the real part of its permittivity vanishes. We observe a change in the real part of the refractive index of 0.72 ± 0.025, corresponding to 170% of the linear refractive index. This change in refractive index is reversible with a recovery time of about 360 femtoseconds. Our results offer the possibility of designing material structures with large ultrafast nonlinearity for applications in nanophotonics. PMID:27127238

  3. The biogeophysical effect of large-scale afforestation in semi-arid regions

    NASA Astrophysics Data System (ADS)

    Yosef, Gil; Avissar, Roni; Walko, Robert; Medvigy, David; Yakir, Dan

    2015-04-01

    Forestation in the semi-arid region can significantly influence the surface energy budget and, in turn, the local atmospheric circulations. Such effects could be particularly important in regions under the influence of monsoon regimes, such as the Sahel and North Australia. In these regions, summer solar heating leads first to migration of the equatorial through and the tropical convergence zones (ITCZ) and to the monsoon rain. And second, to a meridional surface temperature gradient that generates low-level easterly jet that acts as a barrier to the penetration of the precipitation into the semi arid areas. In this study we tested the hypothesis that large-scale afforestation in these semi-regions can result in changes in local and regional atmospheric circulation and, consequently, in the precipitation and potential changes in land cover and land use. The GCM OLAM was used to performing high-resolution simulations (50km horizontal grid scale and 50 vertical layers) of afforestation scenarios in the Sahel and North Australia. These areas (Sahel 2.6 E6 km2 and North Australia 2.1 E6 km2) were afforested with a mature pine forest, using the extensive data form the long-term semi-arid Yatir forest in Israel as a reference forest for surface parameterization. The regional effect of the afforestation was analyzed for the following parameters; Surface energy budget, temperature, Easterly jet stream location and intensity, above forest atmospheric instability, water recycling and precipitation. Afforestation in the Sahel resulted in large increase of the surface net radiation (45 W m-2), mainly as a result of decrease in albedo (43 W m-2), decrease of incoming short wave radiation (21 W m-2) and increase of downward long wave radiation (13 W m-2) due to higher clouds cover, and decrease in long wave upward radiation (10 W m-2), as a result of the lower surface temperature. Increasing soil moisture because of the new forest is expressed into higher evapotranspiration, i

  4. Gain-of-function mutations cluster in distinct regions associated with the signalling pathway in the PAS domain of the aerotaxis receptor, Aer.

    PubMed

    Campbell, Asharie J; Watts, Kylie J; Johnson, Mark S; Taylor, Barry L

    2010-08-01

    The Aer receptor monitors internal energy (redox) levels in Escherichia coli with an FAD-containing PAS domain. Here, we randomly mutagenized the region encoding residues 14-119 of the PAS domain and found 72 aerotaxis-defective mutants, 24 of which were gain-of-function, signal-on mutants. The mutations were mapped onto an Aer homology model based on the structure of the PAS-FAD domain in NifL from Azotobacter vinlandii. Signal-on lesions clustered in the FAD binding pocket, the beta-scaffolding and in the N-cap loop. We suggest that the signal-on lesions mimic the 'signal-on' state of the PAS domain, and therefore may be markers for the signal-in and signal-out regions of this domain. We propose that the reduction of FAD rearranges the FAD binding pocket in a way that repositions the beta-scaffolding and the N-cap loop. The resulting conformational changes are likely to be conveyed directly to the HAMP domain, and on to the kinase control module. In support of this hypothesis, we demonstrated disulphide band formation between cysteines substituted at residues N98C or I114C in the PAS beta-scaffold and residue Q248C in the HAMP AS-2 helix. PMID:20545849

  5. A highly conserved region of the Sendai virus nucleocapsid protein contributes to the NP-NP binding domain.

    PubMed

    Myers, T M; Pieters, A; Moyer, S A

    1997-03-17

    The nucleocapsid protein (NP) of Sendai virus is an essential component of both the nucleocapsid template and the NP-NP and NP0-P protein complexes required for viral RNA replication. When expressed alone in mammalian cells NP self-assembles into nucleocapsid-like particles which appear to contain cellular RNA. To identify putative NP-NP binding domains, fusions between the monomeric maltose-binding protein (MBP) and portions of NP were constructed. The fusion proteins which contain the central conserved region (CCR) (amino acids 258-357, MBP-NP1) and the N-terminal 255 amino acids (MBP-NP2) of NP both oligomerized, suggesting that these regions contain sequences important for NP-NP self-assembly. In addition, the MBP-NP1 fusion protein can function as an inhibitor of viral RNA replication. Complementary studies involving site-directed mutagenesis of the full-length NP protein have identified specific residues in the CCR which are essential for viral RNA replication in vitro. Two such replication-negative mutants, F324V and F324I, were defective in self-assembly, suggesting that the Phe residue at amino acid 324 is essential for the NP-NP interaction. A third mutant, NP260-1 (Y260D), self-assembled to form aberrant oligomers which exhibit an unusual helical structure and appear to lack any associated RNA. The mutants NP299-5 (L299I and I300V) and NP313-2 (I313F), in contrast, appear to form all the required protein complexes, but were inactive in viral RNA replication, suggesting that interactions specifically with Sendai RNA were disrupted. These data have thus identified specific residues in the CCR of the native NP protein which appear to be important for NP-NP or NP-RNA interactions and for genome replication. PMID:9126246

  6. Both the Charged Linker Region and ATPase Domain of Hsp90 Are Essential for Rad51-Dependent DNA Repair

    PubMed Central

    Suhane, Tanvi; Laskar, Shyamasree; Advani, Siddheshwari; Roy, Nabamita; Varunan, Shalu; Bhattacharyya, Dibyendu

    2014-01-01

    The inhibition of Hsp90 in cancerous cells has been correlated with the reduction in double-strand break (DSB repair) activity. However, the precise effect of Hsp90 on the DSB repair pathway in normal cells has remained enigmatic. Our results show that the Hsp82 chaperone, the ortholog of mammalian Hsp90, is indispensable for homologous-recombination (HR)-mediated DNA repair in the budding yeast Saccharomyces cerevisiae. A considerable reduction in cell viability is observed in an Hsp82-inactivated mutant upon methyl methanesulfonate (MMS) treatment as well as upon UV treatment. The loss of Hsp82 function results in a dramatic decrease in gene-targeting efficiency and a marked decrease in the endogenous levels of the key recombination proteins Rad51 and Rad52 without any notable change in the levels of RAD51 or RAD52 transcripts. Our results establish Rad51 as a client of Hsp82, since they interact physically in vivo, and also show that when Hsp82 is inhibited by 17-AAG, Rad51 undergoes proteasomal degradation. By analyzing a number of point mutants with mutations in different domains of Hsp82, we observe a strong association between the sensitivity of an ATPase mutant of Hsp82 to DNA damage and the decreases in the amounts of Rad51 and Rad52 proteins. The most significant observations include the dramatic abrogation of HR activity and the marked decrease in Rad51 focus formation in the charged linker deletion mutant of Hsp82 upon MMS treatment. The charged linker region of Hsp82 is evolutionarily conserved in all eukaryotes, but until now, no biological significance has been assigned to it. Our findings elucidate the importance of this region in DNA repair for the first time. PMID:25380755

  7. Coupled Soil Water and Heat Transport Near the Land Surface in Arid and Semiarid Regions - Multi-Domain Modeling

    NASA Astrophysics Data System (ADS)

    Mohanty, Binayak; Yang, Zhenlei

    2016-04-01

    Understanding and simulating coupled water and heat transfer appropriately in the shallow subsurface is of vital significance for accurate prediction of soil evaporation that would improve the coupling between land surface and atmosphere, which consequently could enhance the reliability of weather as well as climate forecast. The theory of Philip and de Vries (1957), accounting for water vapor diffusion only, was considered physically incomplete and consequently extended and improved by several researchers by explicitly taking water vapor convection, dispersion or air flow into account. It is generally believed that the soil moisture is usually low in the near surface layer under highly transient field conditions, particularly in arid and semiarid regions, and that accurate characterization of water vapor transport is critical when modeling simultaneous water and heat transport in the shallow field soils. The first objective of this study is thus mainly to test existing coupled water and heat transport theories and to develop reasonable and simplified numerical models using field experimental data collected under semi-arid and arid hydro-climatic conditions. In addition, more complex multi-domain models are developed for ubiquitous heterogeneous terrestrial surfaces such as horizontal textural contrasts or structured heterogeneity including macropores (fractures, cracks, root channels, etc.). This would make coupled water and heat transfer models applicable in such non-homogeneous soils more meaningful and enhance the skill of land-atmosphere interaction models at a larger context.

  8. Characterization of lipid domains in erythrocyte membranes.

    PubMed Central

    Rodgers, W; Glaser, M

    1991-01-01

    Fluorescence digital imaging microscopy was used to study the lateral distribution of the lipid components in erythrocyte membranes. Intact erythrocytes labeled with phospholipids containing a fluorophore attached to one fatty acid chain showed an uneven distribution of the phospholipids in the membrane thereby demonstrating the presence of membrane domains. The enrichment of the lipotropic compound chlor-promazine in domains in intact erythrocytes also suggested that the domains are lipid-enriched regions. Similar membrane domains were present in erythrocyte ghosts. The phospholipid enrichment was increased in the domains by inducing membrane protein aggregation. Double-labeling experiments were done to determine the relative distributions of different phospholipids in the membrane. Vesicles made from extracted lipids did not show the presence of domains consistent with the conclusion that membrane proteins were responsible for creating the domains. Overall, it was found that large domains exist in the red blood cell membrane with unequal enrichment of the different phospholipid species. Images PMID:1996337

  9. Src Homology 2 Domain Containing Protein 5 (SH2D5) Binds the Breakpoint Cluster Region Protein, BCR, and Regulates Levels of Rac1-GTP*

    PubMed Central

    Gray, Elizabeth J.; Petsalaki, Evangelia; James, D. Andrew; Bagshaw, Richard D.; Stacey, Melissa M.; Rocks, Oliver; Gingras, Anne-Claude; Pawson, Tony

    2014-01-01

    SH2D5 is a mammalian-specific, uncharacterized adaptor-like protein that contains an N-terminal phosphotyrosine-binding domain and a C-terminal Src homology 2 (SH2) domain. We show that SH2D5 is highly enriched in adult mouse brain, particularly in Purkinjie cells in the cerebellum and the cornu ammonis of the hippocampus. Despite harboring two potential phosphotyrosine (Tyr(P)) recognition domains, SH2D5 binds minimally to Tyr(P) ligands, consistent with the absence of a conserved Tyr(P)-binding arginine residue in the SH2 domain. Immunoprecipitation coupled to mass spectrometry (IP-MS) from cultured cells revealed a prominent association of SH2D5 with breakpoint cluster region protein, a RacGAP that is also highly expressed in brain. This interaction occurred between the phosphotyrosine-binding domain of SH2D5 and an NxxF motif located within the N-terminal region of the breakpoint cluster region. siRNA-mediated depletion of SH2D5 in a neuroblastoma cell line, B35, induced a cell rounding phenotype correlated with low levels of activated Rac1-GTP, suggesting that SH2D5 affects Rac1-GTP levels. Taken together, our data provide the first characterization of the SH2D5 signaling protein. PMID:25331951

  10. The Status of Large-Scale Assessment in the Pacific Region. REL Technical Brief. REL 2008-No. 003

    ERIC Educational Resources Information Center

    Ryan, Jennifer; Keir, Scott

    2008-01-01

    This technical brief describes the large-scale assessment measures and practices used in the jurisdictions served by the Pacific Regional Educational Laboratory. The need for effective large-scale assessment was identified as a major priority for improving student achievement in the Pacific Region jurisdictions: American Samoa, Guam, Hawaii, the…

  11. SISGR -- Domain Microstructures and Mechanisms for Large, Reversible and Anhysteretic Strain Behaviors in Phase Transforming Ferroelectric Materials

    SciTech Connect

    Wang, Yu U.

    2013-12-06

    This four-year project (including one-year no-cost extension) aimed to advance fundamental understanding of field-induced strain behaviors of phase transforming ferroelectrics. We performed meso-scale phase field modeling and computer simulation to study domain evolutions, mechanisms and engineering techniques, and developed computational techniques for nanodomain diffraction analysis; to further support above originally planned tasks, we also carried out preliminary first-principles density functional theory calculations of point defects and domain walls to complement meso-scale computations as well as performed in-situ high-energy synchrotron X-ray single crystal diffraction experiments to guide theoretical development (both without extra cost to the project thanks to XSEDE supercomputers and DOE user facility Advanced Photon Source).

  12. Large single domain 123 material produced by seeding with single crystal rare earth barium copper oxide single crystals

    DOEpatents

    Todt, Volker; Miller, Dean J.; Shi, Donglu; Sengupta, Suvankar

    1998-01-01

    A method of fabricating bulk YBa.sub.2 Cu.sub.3 O.sub.x where compressed powder oxides and/or carbonates of Y and Ba and Cu present in mole ratios to form YBa.sub.2 Cu.sub.3 O.sub.x are heated in the presence of a Nd.sub.1+x Ba.sub.2-x Cu.sub.3 O.sub.y seed crystal to a temperature sufficient to form a liquid phase in the YBa.sub.2 Cu.sub.3 O.sub.x while maintaining the seed crystal solid. The materials are slowly cooled to provide a YBa.sub.2 Cu.sub.3 O.sub.x material having a predetermined number of domains between 1 and 5. Crack-free single domain materials can be formed using either plate shaped seed crystals or cube shaped seed crystals with a pedestal of preferential orientation material.

  13. Observing Large Ionospheric Spatial Decorrelation for Ground-Based Augmentation System in the Brazilian Region

    NASA Astrophysics Data System (ADS)

    Kim, D.; Yoon, M.; Choi, P.; Lee, J.

    2014-12-01

    Ground-Based Augmentation Systems (GBAS) support aircraft precision approach and landing by broadcasting differential Global Positioning System (GPS) corrections and integrity information to aviation users. Under anomalous ionospheric condition, unacceptably large residual errors can occur due to anomalously large ionospheric spatial decorrelation, and this can pose integrity threats to GBAS users. Thus, the development of an ionospheric anomaly threat model is required to simulate worst-case ionospheric errors and develop mitigation strategies. Ionosphere in low latitudes is known to be much more intense than that in mid latitudes due to active geomagnetic effect, and investigation of low latitude ionospheric anomalies must take precedence before operation of GBAS. In this paper, ionospheric spatial decorrelation is investigated for GBAS operation in the Brazilian region. Dual-frequency observation data are collected from Brazilian GPS reference stations. This analysis is performed using data sets collected on scintillating days, less-scintillating days, and storm days from 2012 to 2014. Precise ionospheric spatial gradient on the L1 signal is automatically estimated from dual-frequency observation data using simple truth method and station pair method. In the Brazilian region, however, intense ionospheric scintillations cause a large numbers of cycle slips in carrier-phase data. The simple truth process removes a considerably large number of those data through short-arc and outlier removals, and thus potential ionospheric gradients may not be detected. This motivates a data recovery process which skips short-arc and outlier removals if there appears a large ionospheric spatial gradient in the removed data. We also use a series of methods to validate anomalous ionospheric spatial gradients using manual validation with L1 single frequency measurement, station-wide check, satellite-wide check, and time-step check. In particular, the time-step check validates

  14. Large reduction of the depinning field for a transverse domain wall under application of rf and dc currents

    NASA Astrophysics Data System (ADS)

    Metaxas, P. J.; Anane, A.; Cros, V.; Grollier, J.; Deranlot, C.; Petroff, F.; Fert, A.; Ulysse, C.; Faini, G.

    2010-03-01

    A new generation of proposed spintronic devices are based on domain wall (DW) motion (DW-MRAM, DW logic, racetrack memory...). However, reliable depinning of domain walls remains elusive, especially in zero field. Here, we have studied the combined effect of rf and dc currents on the depinning of transverse walls in the soft NiFe layer of a 100 nm wide Co/Cu/NiFe spin valve wire. Using the GMR effect, we ensure that the domain wall is always prepared at the same intrinsic defect and then measure the depinning field for different applied dc and rf currents. Notably, for a narrow range of rf frequencies at around 3GHz, we evidence a strong reduction in the depinning field (from ˜80 Oe to ˜30 Oe). Our results are suggestive of a very efficient resonant depinning effect in our spin valve wire which depends not only on the rf power but also on the polarity and amplitude of the accompanying dc current.

  15. Design and implementation of an efficient finite-difference, time-domain computer code for large problems

    SciTech Connect

    White, W.T. III; Taflove, A.; Stringer, J.C.; Kluge, R.F.

    1986-12-01

    As computers get larger and faster, demands upon electromagnetics codes increase. Ever larger volumes of space must be represented with increasingly more accuracy and detail. This requires continually more efficient EM codes. To meet present and future needs in DOE and DOD, we are developing FDTD3D, a three-dimensional finite-difference, time-domain EM solver. When complete, the code will efficiently solve problems with tens of millions of unknowns. It already operates faster than any other 3D, time-domain EM code, and we are using it to model linear coupling to a generic missile section. At Lawrence Livermore National Laboratory (LLNL), we anticipate the ultimate need for such a code if we are to model EM threats to objects such as airplanes or missiles. This article describes the design and implementation of FDTD3D. The first section, ''Design of FDTD3D,'' contains a brief summary of other 3D time-domain EM codes at LLNL followed by a description of the efficiency of FDTD3D. The second section, ''Implementation of FDTD3D,'' discusses recent work and future plans.

  16. Crystal Structure of the C-terminal Region of Streptococcus mutans Antigen I/II and Characterization of Salivary Agglutinin Adherence Domains

    SciTech Connect

    Larson, Matthew R.; Rajashankar, Kanagalaghatta R.; Crowley, Paula J.; Kelly, Charles; Mitchell, Tim J.; Brady, L. Jeannine; Deivanayagam, Champion

    2012-05-29

    The Streptococcus mutans antigen I/II (AgI/II) is a cell surface-localized protein that adheres to salivary components and extracellular matrix molecules. Here we report the 2.5 {angstrom} resolution crystal structure of the complete C-terminal region of AgI/II. The C-terminal region is comprised of three major domains: C{sub 1}, C{sub 2}, and C{sub 3}. Each domain adopts a DE-variant IgG fold, with two {beta}-sheets whose A and F strands are linked through an intramolecular isopeptide bond. The adherence of the C-terminal AgI/II fragments to the putative tooth surface receptor salivary agglutinin (SAG), as monitored by surface plasmon resonance, indicated that the minimal region of binding was contained within the first and second DE-variant-IgG domains (C{sub 1} and C{sub 2}) of the C terminus. The minimal C-terminal region that could inhibit S. mutans adherence to SAG was also confirmed to be within the C{sub 1} and C{sub 2} domains. Competition experiments demonstrated that the C- and N-terminal regions of AgI/II adhere to distinct sites on SAG. A cleft formed at the intersection between these C{sub 1} and C{sub 2} domains bound glucose molecules from the cryo-protectant solution, revealing a putative binding site for its highly glycosylated receptor SAG. Finally, electron microscopy images confirmed the elongated structure of AgI/II and enabled building a composite tertiary model that encompasses its two distinct binding regions.

  17. Extraordinary boundary morphologies of large-scale ordered domains of spheres in thin films of a narrowly dispersed diblock copolymer via thermodynamic control.

    PubMed

    Shi, Ling-Ying; Li, Hang; Lei, Wei-Wei; Ni, Wei; Ran, Rong; Pan, Yu; Fan, Xing-He; Shen, Zhihao

    2015-11-14

    Long-range ordering of body centered cubic (BCC) spheres and various extraordinary morphologies at the boundaries of the adjacent orderly oriented domains are observed in thermally annealed thin films of a series of specific narrowly dispersed diblock copolymers, poly(dimethylsiloxane)-b-poly{2,5-bis[(4-butoxyphenyl)oxycarbonylstyrene} (PDMS-b-PBPCS, DB). The series of asymmetrical DB block copolymers (BCPs) with volume fractions of PDMS (f(PDMS)'s) from 10% to 23% self-assemble into thermodynamically stable body centered cubic (BCC) nanostructures in bulk at ambient temperature after thermal annealing. The thin films of these BCPs with a relatively large film thickness on a carbon-film coated substrate are annealed in a vacuum at 180 °C for 3 days and are characterized by transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS). For all thin films of these BCPs, micrometer-scale domains with a rectangular unit cell similar to the projection of the BCC lattice along the [110] direction to the substrate are observed. And the XPS results indicate that the surface layers of the thin films are composed of both PDMS and PBPCS blocks. For the thin films of the BCPs with f(PDMS) values of 10% and 13%, the neighboring [110]-oriented BCC domains match well with each other, and the boundaries are defect-free. For the thin film of the BCP with a f(PDMS) value of 23%, the PDMS spheres in the [110]-oriented BCC domains in the TEM micrograph are overlapped with each other, and interesting morphologies including defect-free interfaces, interfaces with line defects, and domains with defects and local ordering are observed at the boundaries of the neighboring [110]-oriented domains. PMID:26456491

  18. Four large-scale field-aligned current systmes in the dayside high-latitude region

    NASA Technical Reports Server (NTRS)

    Ohtani, S.; Potemra, T. A.; Newell, P.T.; Zanetti, L. J.; Iijima, T.; Watanabe, M.; Blomberg, L. G.; Elphinstone, R. D.; Murphree, J. S.; Yamauchi, M.

    1995-01-01

    A system of four current sheets of large-scale field-aligned currents (FACs) was discovered in the data set of simultaneous Viking and Defense Meteorological Satellire Program-F7 (DMSP-F7) crossing of the dayside high-latitude region. This paper reports four examples of this system that were observed in the prenoon sector. The flow polarities of FACs are upward, downward, upward, and downward, from equatorward to poleward. The lowest-latitude upward current is flowing mostly in the central plasma sheet (CPS) precipitation region, often overlapping with the boundary plasma sheet (BPS) at its poleward edge, andis interpreted as a region 2 current. The pair of downward and upward FACs in the middle of te structure are collocated with structured electron precipitation. The precipitation of high-energy (greater than 1 keV) electrons is more intense in the lower-latitude downward current sheet. The highest-latitude downward flowing current sheet is located in a weak, low-energy particle precipitation region, suggesting that this current is flowing on open field lines. Simulaneous observations in the postnoon local time sector reveal the standard three-sheet structure of FACs, sometimes described as region 2, region 1, and mantle (referred to the midday region O) currents. A high correlation was found between the occurrence of the four FAC sheet structure and negative interplanetary magnetic field (IMF) B(sub Y). We discuss the FAC structurein terms of three types of convection cells: the merging, viscous, andlobe cells. During strongly negative IMF B(sub Y), two convection reversals exist in the prenoon sector; one is inside the viscous cell, and the other is between the viscous cell and the lobe cell. This structure of convection flow is supported by the Viking electric field and auroral UV image data. Based on the convection pattern, the four FAC sheet structure is interpreted as the latitude overlap of midday and morning FAC systems. We suggest that the for

  19. Phantoms of the forest: legacy risk effects of a regionally extinct large carnivore.

    PubMed

    Sahlén, Ellinor; Noell, Sonja; DePerno, Christopher S; Kindberg, Jonas; Spong, Göran; Cromsigt, Joris P G M

    2016-02-01

    The increased abundance of large carnivores in Europe is a conservation success, but the impact on the behavior and population dynamics of prey species is generally unknown. In Europe, the recolonization of large carnivores often occurs in areas where humans have greatly modified the landscape through forestry or agriculture. Currently, we poorly understand the effects of recolonizing large carnivores on extant prey species in anthropogenic landscapes. Here, we investigated if ungulate prey species showed innate responses to the scent of a regionally exterminated but native large carnivore, and whether the responses were affected by human-induced habitat openness. We experimentally introduced brown bear Ursus arctos scent to artificial feeding sites and used camera traps to document the responses of three sympatric ungulate species. In addition to controls without scent, reindeer scent Rangifer tarandus was used as a noncarnivore, novel control scent. Fallow deer Dama dama strongly avoided areas with bear scent. In the presence of bear scent, all ungulate species generally used open sites more than closed sites, whereas the opposite was observed at sites with reindeer scent or without scent. The opening of forest habitat by human practices, such as forestry and agriculture, creates a larger gradient in habitat openness than available in relatively unaffected closed forest systems, which may create opportunities for prey to alter their habitat selection and reduce predation risk in human-modified systems that do not exist in more natural forest systems. Increased knowledge about antipredator responses in areas subjected to anthropogenic change is important because these responses may affect prey population dynamics, lower trophic levels, and attitudes toward large carnivores. These aspects may be of particular relevance in the light of the increasing wildlife populations across much of Europe. PMID:26865966

  20. PHYSICAL PROPERTIES OF LARGE AND SMALL GRANULES IN SOLAR QUIET REGIONS

    SciTech Connect

    Yu Daren; Xie Zongxia; Hu Qinghua; Yang Shuhong; Zhang Jun; Wang Jingxiu E-mail: zjun@ourstar.bao.ac.cn

    2011-12-10

    The normal mode observations of seven quiet regions obtained by the Hinode spacecraft are analyzed to study the physical properties of granules. An artificial intelligence technique is introduced to automatically find the spatial distribution of granules in feature spaces. In this work, we investigate the dependence of granular continuum intensity, mean Doppler velocity, and magnetic fields on granular diameter. We recognized 71,538 granules by an automatic segmentation technique and then extracted five properties: diameter, continuum intensity, Doppler velocity, and longitudinal and transverse magnetic flux density to describe the granules. To automatically explore the intrinsic structures of the granules in the five-dimensional parameter space, the X-means clustering algorithm and one-rule classifier are introduced to define the rules for classifying the granules. It is found that diameter is a dominating parameter in classifying the granules and two families of granules are derived: small granules with diameters smaller than 1.''44, and large granules with diameters larger than 1.''44. Based on statistical analysis of the detected granules, the following results are derived: (1) the averages of diameter, continuum intensity, and Doppler velocity in the upward direction of large granules are larger than those of small granules; (2) the averages of absolute longitudinal, transverse, and unsigned flux density of large granules are smaller than those of small granules; (3) for small granules, the average of continuum intensity increases with their diameters, while the averages of Doppler velocity, transverse, absolute longitudinal, and unsigned magnetic flux density decrease with their diameters. However, the mean properties of large granules are stable; (4) the intensity distributions of all granules and small granules do not satisfy Gaussian distribution, while that of large granules almost agrees with normal distribution with a peak at 1.04 I{sub 0}.

  1. Large methane emission upon spring thaw from natural wetlands in the northern permafrost region

    SciTech Connect

    Song, Changchun; Xu, Xiaofeng; Sun, Xiaoxin; Tian, Hanqin; Sun, Li; Miao, Yuqing; Wang, Xianwei; Guo, Yuedong

    2012-01-01

    The permafrost carbon climate feedback is one of the major mechanisms in controlling the climate ecosystem interactions in northern high latitudes. Of this feedback, methane (CH4) emission from natural wetlands is critically important due to its high warming potential. The freeze thaw transition has been confirmed to play an important role in annual CH4 budget, yet the magnitude of this effect is uncertain. An intensive field campaign was carried out in the Sanjiang Plain, Northeast China to estimate the CH4 emission in the spring freeze thaw transition period. The observation concluded that a large CH4 source was caused by spring thaw; the maximum hourly emission rate was 48.6 g C m 2 h 1, more than three orders of the regularly observed CH4 emission rate in the growing season. In some sporadically observed 'hot spots', the spring thawing effect contributed to a large CH4 source of 31.3 10.1 g C m 2, which is approximately 80% of the previously calculated annual CH4 emission in the same study area. If our results are typical for natural wetlands in the Northern Hemisphere permafrost region, we estimate a global CH4 source strength of 0.5 1.0 Tg C (1 Tg =1012 g) caused by spring thaw in the Northern Hemisphere permafrost region in the year 2011. Combining with available satellite and flask data, a regional extrapolation reaches a temporal pattern of CH4 emission during 2003 2009 which is consistent with recently observed changes in atmospheric CH4 concentration in the high latitudes. This suggests that the CH4 emission upon spring thaw in the high latitudes might be enhanced by the projected climate warming. These findings indicate that the spring thawing effect is an important mechanism in the permafrost carbon climate feedback and needs to be incorporated in Earth system models.

  2. Representing a Large Region with Few Sites: A New Approach for Studies on Small Streams

    NASA Astrophysics Data System (ADS)

    Rosamond, Madeline; Kaltenecker, Georgina; Mohamed, Mohamed; Taylor, William

    2015-04-01

    Many environmental studies attempt to characterize a large geographical region but financial and logistical constraints limit the number of field sites used. A systematic approach to site selection can ensure that an adequate range in the variables of interest is captured. We present a novel method to select small watersheds for a study examining relationships between agricultural land use, landscape characteristics and stream phosphorus export. This method reduces subjectivity and uses commonly-available geospatial datasets while considering practical constraints on site selections. We selected several variables representing agricultural P inputs or intensity and landscape susceptibility to P loss. We ordinated regional-scale data on cross plots and then superimposed potential field sites, picking those that covered the range shown, and over-representing areas with high P inputs losses. We represent an 110,000 km2 geographic area with 10 sites, with good coverage of four variables, using six sites from a previous study and four new sites. The site selection method can easily be adapted to studies with a variety of goals and settings. Additionally, ordinating watersheds or regions along axes (here, "agricultural" and "landscape") can provide insight into relationships among variables and help identify areas of particular concern, thus guiding stewardship and management programs. The largest challenge is resolution: small study watersheds (20 - 70 km2) may not be well represented by spatially and temporally coarse data.

  3. The Gould's Belt Very Large Array Survey. II. The Serpens Region

    NASA Astrophysics Data System (ADS)

    Ortiz-León, Gisela N.; Loinard, Laurent; Mioduszewski, Amy J.; Dzib, Sergio A.; Rodríguez, Luis F.; Pech, Gerardo; Rivera, Juana L.; Torres, Rosa M.; Boden, Andrew F.; Hartmann, Lee; Evans, Neal J., II; Briceño, Cesar; Tobin, John; Kounkel, Marina A.; González-Lópezlira, Rosa A.

    2015-05-01

    We present deep (∼17 μJy) radio continuum observations of the Serpens molecular cloud, the Serpens south cluster, and the W40 region obtained using the Very Large Array in its A configuration. We detect a total of 146 sources, 29 of which are young stellar objects (YSOs), 2 of which are BV stars, and 5 more of which are associated with phenomena related to YSOs. Based on their radio variability and spectral index, we propose that about 16 of the remaining 110 unclassified sources are also YSOs. For approximately 65% of the known YSOs detected here as radio sources, the emission is most likely non-thermal and related to stellar coronal activity. As also recently observed in Ophiuchus, our sample of YSOs with X-ray counterparts lies below the fiducial Güdel & Benz relation. Finally, we analyze the proper motions of nine sources in the W40 region. This allows us to better constrain the membership of the radio sources in the region.

  4. Large Eddy Simulations of Volume Restriction Effects on Canopy-Induced Increased-Uplift Regions

    NASA Astrophysics Data System (ADS)

    Chatziefstratiou, E.; Bohrer, G.; Velissariou, V.

    2012-12-01

    ABSTRACT Previous modeling and empirical work have shown the development of important areas of increased uplift past forward-facing steps, and recirculation zones past backward-facing steps. Forests edges represent a special kind of step - a semi-porous one. Current models of the effects of forest edges on the flow represent the forest with a prescribed drag term and does not account for the effects of the solid volume in the forest that restrict the airflow. The RAMS-based Forest Large Eddy Simulation (RAFLES) resolves flows inside and above forested canopies. RAFLES is spatially explicit, and uses the finite volume method to solve a descretized set of Navier-Stokes equations. It accounts for vegetation drag effects on the flow and on the flux exchange between the canopy and the canopy air, proportional to the local leaf density. For a better representation of the vegetation structure in the numerical grid within the canopy sub-domain, the model uses a modified version of the cut cell coordinate system. The hard volume of vegetation elements, in forests, or buildings, in urban environments, within each numerical grid cell is represented via a sub-grid-scale process that shrinks the open apertures between grid cells and reduces the open cell volume. We used RAFLES to simulate the effects of a canopy of varying foliage and stem densities on flow over virtual qube-shaped barriers under neutrally buoyant conditions. We explicitly tested the effects of the numerical representation of volume restriction, independent of the effects of the leaf drag by comparing drag-only simulations, where we prescribed no volume or aperture restriction to the flow, restriction-only simulations, where we prescribed no drag, and control simulations, where both drag and volume plus aperture restriction were included. Our simulations show that representation of the effects of the volume and aperture restriction due to obstacles to flow is important (figure 1) and leads to differences in the

  5. Activation of G Protein-Coupled Receptor Kinase 1 Involves Interactions between Its N-Terminal Region and Its Kinase Domain

    SciTech Connect

    Huang, Chih-chin; Orban, Tivadar; Jastrzebska, Beata; Palczewski, Krzysztof; Tesmer, John J.G.

    2012-03-16

    G protein-coupled receptor kinases (GRKs) phosphorylate activated G protein-coupled receptors (GPCRs) to initiate receptor desensitization. In addition to the canonical phosphoacceptor site of the kinase domain, activated receptors bind to a distinct docking site that confers higher affinity and activates GRKs allosterically. Recent mutagenesis and structural studies support a model in which receptor docking activates a GRK by stabilizing the interaction of its 20-amino acid N-terminal region with the kinase domain. This interaction in turn stabilizes a closed, more active conformation of the enzyme. To investigate the importance of this interaction for the process of GRK activation, we first validated the functionality of the N-terminal region in rhodopsin kinase (GRK1) by site-directed mutagenesis and then introduced a disulfide bond to cross-link the N-terminal region of GRK1 with its specific binding site on the kinase domain. Characterization of the kinetic and biophysical properties of the cross-linked protein showed that disulfide bond formation greatly enhances the catalytic efficiency of the peptide phosphorylation, but receptor-dependent phosphorylation, Meta II stabilization, and inhibition of transducin activation were unaffected. These data indicate that the interaction of the N-terminal region with the kinase domain is important for GRK activation but does not dictate the affinity of GRKs for activated receptors.

  6. A Survey of Large Molecules of Biological Interest toward Selected High Mass Star Forming Regions

    NASA Technical Reports Server (NTRS)

    Remijan, A.; Shiao, Y.-S.; Friedel, D. N.; Meier, D. S.; Snyder, L. E.

    2004-01-01

    We have surveyed three high mass Galactic star forming regions for interstellar methanol (CH3OH), formic acid (HCOOH), acetic acid (CH3COOH), methyl formate (HCOOCH3), methyl cyanide (CH3CN), and ethyl cyanide (CH3CH2CN) with the BIMA Array. From our observations, we have detected two new sources of interstellar HCOOH toward the hot core regions G19.61-0.23 and W75N. We have also made the first detections of CH3CH2CN and HCOOCH3 toward G19.61-0.23. The relative HCOOH/HCOOCH3 abundance ratio toward G19.61-0.23 is 0.18 which is comparable to the abundance ratios found by Liu and colleagues toward Sgr B2(N-LMH), Orion and W51(approximately 0.10). We have made the first detection of HCOOCH3 toward W75N. The relative HCOOH/HCOOCH3 abundance ratio toward W75N is 0.26 which is more than twice as large as the abundance ratios found by Liu and colleagues. Furthermore, the hot core regions around W75N show a chemical differentiation between the O and N cores similar to what is seen toward the Orion Hot Core and Compact Ridge and W3(OH) and W3(H2O). It is also apparent from our observations that the high mass star forming region G45.47+0.05 does not contain any compact hot molecular core and as a consequence its chemistry may be similar to cold dark clouds. Finally, the formation of CH3COOH appears to favor HMCs with well mixed N and O, despite the fact that CH3COOH does not contain a N atom. If proved to be true, this is an important constraint on CH3COOH formation and possibly other structurally similar biomolecules.

  7. Regional frequency analysis conditioned on large-scale atmospheric or oceanic fields

    NASA Astrophysics Data System (ADS)

    Renard, Benjamin; Lall, Upmanu

    2014-12-01

    Many studies report that hydrologic regimes are modulated by large-scale modes of climate variability such as the El Niño Southern Oscillation (ENSO) or the North Atlantic Oscillation (NAO). Climate-informed frequency analysis models have therefore been proposed to condition the distribution of hydrologic variables on climate indices. However, standard climate indices may be poor predictors in some regions. This paper therefore describes a regional frequency analysis framework that conditions the distribution of hydrologic variables directly on atmospheric or oceanic fields, as opposed to predefined climate indices. This framework is based on a two-level probabilistic model describing both climate and hydrologic data. The climate data set (predictor) is typically a time series of atmospheric of oceanic fields defined on a grid over some area, while the hydrologic data set (predictand) is typically a regional data set of station data (e.g., annual average flow at several gauging stations). A Bayesian estimation framework is used, so that a natural quantification of uncertainties affecting hydrologic predictions is available. A case study aimed at predicting the number of autumn flood events in 16 catchments located in Mediterranean France using geopotential heights at 500 hPa over the North-Atlantic region is presented. The temporal variability of hydrologic data is shown to be associated with a particular spatial pattern in the geopotential heights. A cross-validation experiment indicates that the resulting probabilistic climate-informed predictions are skillful: their reliability is acceptable and they are much sharper than predictions based on standard climate indices and baseline predictions that ignore climate information.

  8. Regional frequency analysis conditioned on large-scale atmospheric or oceanic fields

    NASA Astrophysics Data System (ADS)

    Renard, Benjamin; Lall, Upmanu

    2015-04-01

    Many studies report that hydrologic regimes are modulated by large-scale modes of climate variability such as the El Niño Southern Oscillation (ENSO) or the North Atlantic Oscillation (NAO). Climate-informed frequency analysis models have therefore been proposed to condition the distribution of hydrologic variables on climate indices. However, standard climate indices may be poor predictors in some regions. This paper therefore describes a regional frequency analysis framework that conditions the distribution of hydrologic variables directly on atmospheric or oceanic fields, as opposed to predefined climate indices. This framework is based on a 2-level probabilistic model describing both climate and hydrologic data. The climate dataset (predictor) is typically a time series of atmospheric of oceanic fields defined on a grid over some area, while the hydrologic dataset (predictand) is typically a regional dataset of station data (e.g. annual peak flow at several gauging stations). A Bayesian estimation framework is used, so that a natural quantification of uncertainties affecting hydrologic predictions is available. A case study aimed at predicting the number of autumn flood events in 16 catchments located in Mediterranean France using geopotential heights at 500 hPa over the North-Atlantic region is presented. The temporal variability of hydrologic data is shown to be associated with a particular spatial pattern in the geopotential heights. A cross-validation experiment indicates that the resulting probabilistic climate-informed predictions are skillful: their reliability is acceptable and they are much sharper than predictions based on standard climate indices and baseline predictions that ignore climate information.

  9. Large structure rearrangement of colicin ia channel domain after membrane binding from 2D 13C spin diffusion NMR.

    PubMed

    Luo, Wenbin; Yao, Xiaolan; Hong, Mei

    2005-05-01

    One of the main mechanisms of membrane protein folding is by spontaneous insertion into the lipid bilayer from the aqueous environment. The bacterial toxin, colicin Ia, is one such protein. To shed light on the conformational changes involved in this dramatic transfer from the polar to the hydrophobic milieu, we carried out 2D magic-angle spinning (13)C NMR experiments on the water-soluble and membrane-bound states of the channel-forming domain of colicin Ia. Proton-driven (13)C spin diffusion spectra of selectively (13)C-labeled protein show unequivocal attenuation of cross-peaks after membrane binding. This attenuation can be assigned to distance increases but not reduction of the diffusion coefficient. Analysis of the statistics of the interhelical and intrahelical (13)C-(13)C distances in the soluble protein structure indicates that the observed cross-peak reduction is well correlated with a high percentage of short interhelical contacts in the soluble protein. This suggests that colicin Ia channel domain becomes open and extended upon membrane binding, thus lengthening interhelical distances. In comparison, cross-peaks with similar intensities between the two states are dominated by intrahelical contacts in the soluble state. This suggests that the membrane-bound structure of colicin Ia channel domain may be described as a "molten globule", in which the helical secondary structure is retained while the tertiary structure is unfolded. This study demonstrates that (13)C spin diffusion NMR is a valuable tool for obtaining qualitative long-range distance constraints on membrane protein folding. PMID:15853348

  10. Magnetic signature of large exhumed mantle domains of the Southwest Indian Ridge: results from a deep-tow geophysical survey over 0 to 11 Ma old seafloor

    NASA Astrophysics Data System (ADS)

    Bronner, A.; Sauter, D.; Munschy, M.; Carlut, J.; Searle, R.; Cannat, M.; Manatschal, G.

    2013-12-01

    We investigate the magnetic signature of an ultramafic seafloor in the eastern part of the Southwest Indian Ridge (SWIR). There, detachment faulting, continuous over 11 Myrs, exhumed large areas of mantle derived rocks. These exhumed mantle domains occur in the form of a smooth rounded topography with broad ridges locally covered by a thin highly discontinuous volcanic carapace. We present high-resolution data combining deep-tow magnetics, side-scan sonar images and dredged samples collected within two exhumed mantle domains between 62° E and 65° E. We show that, despite an ultraslow spreading rate, volcanic areas within robust magmatic segments are characterized by well defined seafloor spreading anomalies. By contrast, the exhumed mantle domains, including a few thin volcanic patches, reveal a weak and highly variable magnetic pattern. The analysis of the magnetic properties of the dredged samples and careful comparison between the nature of the seafloor, the deep-tow magnetic anomalies and the seafloor equivalent magnetization suggest that the serpentinized peridotites do not carry a sufficiently stable remanent magnetization to produce seafloor spreading magnetic anomalies in exhumed mantle domains.

  11. Magnetic signature of large exhumed mantle domains of the Southwest Indian Ridge - results from a deep-tow geophysical survey over 0 to 11 Ma old seafloor

    NASA Astrophysics Data System (ADS)

    Bronner, A.; Sauter, D.; Munschy, M.; Carlut, J.; Searle, R.; Cannat, M.; Manatschal, G.

    2014-05-01

    We investigate the magnetic signature of ultramafic seafloor in the eastern part of the Southwest Indian Ridge (SWIR). There, detachment faulting, continuous over 11 Myr, exhumed large areas of mantle-derived rocks. These exhumed mantle domains occur in the form of a smooth rounded topography with broad ridges locally covered by a thin highly discontinuous volcanic carapace. We present high-resolution data combining deep-tow magnetics, side-scan sonar images and dredged samples collected within two exhumed mantle domains between 62° E and 65° E. We show that, despite an ultra-slow spreading rate, volcanic areas within robust magmatic segments are characterized by well-defined seafloor spreading anomalies. By contrast, the exhumed mantle domains, including a few thin volcanic patches, reveal a weak and highly variable magnetic pattern. The analysis of the magnetic properties of the dredged samples and careful comparison between the nature of the seafloor, the deep-tow magnetic anomalies and the seafloor equivalent magnetization suggest that the serpentinized peridotites do not carry a sufficiently stable remanent magnetization to produce seafloor spreading magnetic anomalies in exhumed mantle domains.

  12. Regional analgesia for improvement of long-term functional outcome after elective large joint replacement

    PubMed Central

    Atchabahian, Arthur; Schwartz, Gary; Hall, Charles B; Lajam, Claudette M; Andreae, Michael H

    2015-01-01

    Background Regional analgesia is more effective than conventional analgesia for controlling pain and may facilitate rehabilitation after large joint replacement in the short term. It remains unclear if regional anaesthesia improves functional outcomes after joint replacement beyond three months after surgery. Objectives To assess the effects of regional anaesthesia and analgesia on long-term functional outcomes 3, 6 and 12 months after elective major joint (knee, shoulder and hip) replacement surgery. Search methods We performed an electronic search of several databases (CENTRAL, MEDLINE, EMBASE, CINAHL), and handsearched reference lists and conference abstracts. We updated our search in June 2015. Selection criteria We included randomized controlled trials (RCTs) comparing regional analgesia versus conventional analgesia in patients undergoing total shoulder, hip or knee replacement. We included studies that reported a functional outcome with a follow-up of at least three months after surgery. Data collection and analysis We used standard methodological procedures expected by Cochrane. We contacted study authors for additional information. Main results We included six studies with 350 participants followed for at least three months. All of these studies enrolled participants undergoing total knee replacement. Studies were at least partially blinded. Three studies had a high risk of performance bias and one a high risk of attrition bias, but the risk of bias was otherwise unclear or low. Only one study assessed joint function using a global score. Due to heterogeneity in outcome and reporting, we could only pool three out of six RCTs, with range of motion assessed at three months after surgery used as a surrogate for joint function. All studies had a high risk of detection bias. Using the random-effects model, there was no statistically significant difference between the experimental and control groups (mean difference 3.99 degrees, 95% confidence interval (CI)

  13. Polarization Reversal Over Flooded Regions and Applications to Large-Scale Flood Mapping with Spaceborne Scatterometers

    NASA Technical Reports Server (NTRS)

    Nghiem, Son V.; Liu, W. Timothy; Xie, Xiao-Su

    1999-01-01

    We present the polarization reversal in backscatter over flooded land regions, and demonstrate for the first time the utility of spaceborne Ku-band scatterometer for large-scale flood mapping. Scatterometer data were collected over the globe by the NASA Scatterometer (NSCAT) operated at 14 GHz on the Japanese ADEOS spacecraft from September 1996 to June 1997. During this time span, several severe floods occurred. Over most land surface, vertical polarization backscatter (Sigma(sub upsilon(upsilon)) is larger than horizontal polarization backscatter (sigma(sub hh)). Such polarization characteristics is reversed and sigma(sub upsilon(upsilon)) is smaller than sigma(sub hh) over flooded regions, except under a dense forest canopy. The total backscatter from the flooded landscape consists of direct backscatter and boundary-interaction backscatter. The direct term is contributed by direct backscattering from objects protruding above the water surface, and by backscattering from waves on the water surface. The boundary-interaction term is contributed by the forward scattering from the protruding objects and then reflected from the water surface, and also by the forward scattering from these objects after the water-surface reflection. Over flooded regions, the boundary-interaction term is dominant at large incidence angles and the strong water-surface reflection is much larger for horizontal polarization than the vertical one due to the Brewster effect in transverse-magnetic waves. These scattering mechanisms cause the polarization reversal over flooded regions. An example obtained with the Analytic Wave Theory is used to illustrate the scattering mechanisms leading to the polarization reversal. We then demonstrate the utility of spaceborne Ku-band scatterometer for large-scale flood mapping. We process NSCAT data to obtain the polarization ratio sigma(sub hh)/sigma(sub upsilon(upsilon)) with colocated data at incidence angles larger than 40 deg. The results over Asian

  14. Implementation of a large-scale flow routing scheme in the Canadian Regional Climate Model (CRCM)

    NASA Astrophysics Data System (ADS)

    Lucas-Picher, P.; Arora, V.; Caya, D.; Laprise, R.

    2002-12-01

    Freshwater flux from river acts as an important forcing on the ocean. With lower density than ocean saltwater, freshwater from rivers affects thermohaline circulation and sea-ice formation at high-latitudes. Freshwater flux can be computed in a climate model by using runoff as an input into a flow routing model, which transfers runoff from the land surface to the continental edges. In addition to modeling freshwater flux for oceans, the streamflow obtained by the routing model can be used to assess the performance of atmospheric models on a climatological basis by comparisons with observed streamflow. The variable velocity flow routing algorithm of Arora and Boer (1999, JGR-Atmos., 104, 30965-30979) is used to compute river flow in the Canadian Regional Climate Model (CRCM) (Caya and Laprise, 1999, Mon. Wea. Rev., 127, 341-362). The flow routing scheme consists of surface and groundwater reservoirs, which obtain daily estimates of surface runoff and drainage inputs, respectively simulated by the land surface scheme. The flow routing algorithm uses Manning's equation to estimate flow velocities. A rectangular river cross section is assumed with a fixed width and the variable depth is estimated using the amount of water in the river, slope, and river width. Discretization of major river basins and flow directions for the North America domain are obtained at the polar stereographic resolution of the CRCM using 5 minute global river flow directions (Graham et al., 1999, WRR, 35, 583-587) as a template. Model runoff estimates from a global simulation of Variable Infiltration Capacity (VIC) hydrological model are use to validate the routing scheme. Routing models results show that compared to the unrouted runoff, the inclusion of flow routing improves comparison with observation-based streamflow estimates.

  15. Large single domain 123 material produced by seeding with single crystal rare earth barium copper oxide single crystals

    DOEpatents

    Todt, V.; Miller, D.J.; Shi, D.; Sengupta, S.

    1998-07-07

    A method of fabricating bulk YBa{sub 2}Cu{sub 3}O{sub x} where compressed powder oxides and/or carbonates of Y and Ba and Cu present in mole ratios to form YBa{sub 2}Cu{sub 3}O{sub x} are heated in the presence of a Nd{sub 1+x}Ba{sub 2{minus}x}Cu{sub 3}O{sub y} seed crystal to a temperature sufficient to form a liquid phase in the YBa{sub 2}Cu{sub 3}O{sub x} while maintaining the seed crystal solid. The materials are slowly cooled to provide a YBa{sub 2}Cu{sub 3}O{sub x} material having a predetermined number of domains between 1 and 5. Crack-free single domain materials can be formed using either plate shaped seed crystals or cube shaped seed crystals with a pedestal of preferential orientation material. 7 figs.

  16. Large-Scale Structures in the Zone of Avoidance: The Galactic Anticenter Region

    NASA Technical Reports Server (NTRS)

    Lu, Nanyao Y.; Freudling, Wolfram

    1995-01-01

    We have selected a sample of 876 galaxy candidates from the IRAS Point Source Catalog in the region of 2(exp h) < alpha < 10(exp h) and 0 deg < delta < 36 deg, which crosses the Galactic anticenter part of the Zone of Avoidance (ZOA) and includes most of the highly obscured Orion-Taurus complex region. We have identified galaxies among the candidate sources by attempting to detect the 21 cm H I line of those sources which were not known to be galaxies at the beginning of the survey. In this manner, we constructed a galaxy sample which is largely free from Galactic reddening. Of the 272 observed candidates, 89 were detected in the H I line up to a heliocentric velocity of v(sub h) approximately 16,000 km/s. The resulting galaxy sample of 717 galaxies is fairly complete (within about 10%) and uniform (within about 4%) in the part of the survey area 10 deg away from the Galactic plane and for velocities up to at least 9000 km/s. This provides, for the first time, a largely unbiased view on the large-scale structures in much of the survey area. Our main results are the following: (1) Several large voids are identified. In particular, a void between alpha approximately equals 3(sup h) and 4(sup h), up to v(sub h) approximately 6000 km/s, separates the Pisces-Perseus supercluster at alpha < 3(sup h) from structures at alpha > 4(sup h); and a "nearby void" occupies most of our survey area and reaches out to a redshift of nearly 3000 km/s. (2) We found no nearby galaxy concentration that could significantly contribute to the "Local Velocity Anomoly" (LVA), but a general excess of galaxies around v(sub h) approximately 5000 km/s in the survey area. (3) The contrast between the "Great Wall" at v(sub h) approximately 8500 km/s and the void in front of it appears to gradually diffuse out after it enters the Zone of Avoidance from the northern Galactic hemisphere. (4) Our data combined with other galaxy surveys in or near the Galactic anticenter part of the ZOA suggest that the

  17. Simultaneous Solar Maximum Mission (SMM) and very large array observations of solar active regions

    NASA Technical Reports Server (NTRS)

    Lang, K. R.

    1986-01-01

    The research deals mainly with Very Large Array and Solar Maximum Mission observations of the ubiquitous coronal loops that dominate the structure of the low corona. As illustrated, the observations of thermal cyclotron lines at microwave wavelengths provide a powerful new method of accurately specifying the coronal magnetic field strength. Processes are delineated that trigger solar eruptions from coronal loops, including preburst heating and the magnetic interaction of coronal loops. Evidence for coherent burst mechanisms is provided for both the Sun and nearby stars, while other observations suggest the presence of currents that may amplify the coronal magnetic field to unexpectedly high levels. The existence is reported of a new class of compact, variable moving sources in regions of apparently weak photospheric field.

  18. Representation of spatial and temporal variability in large-domain hydrological models: case study for a mesoscale pre-Alpine basin

    NASA Astrophysics Data System (ADS)

    Melsen, Lieke; Teuling, Adriaan; Torfs, Paul; Zappa, Massimiliano; Mizukami, Naoki; Clark, Martyn; Uijlenhoet, Remko

    2016-06-01

    The transfer of parameter sets over different temporal and spatial resolutions is common practice in many large-domain hydrological modelling studies. The degree to which parameters are transferable across temporal and spatial resolutions is an indicator of how well spatial and temporal variability is represented in the models. A large degree of transferability may well indicate a poor representation of such variability in the employed models. To investigate parameter transferability over resolution in time and space we have set up a study in which the Variable Infiltration Capacity (VIC) model for the Thur basin in Switzerland was run with four different spatial resolutions (1 km × 1 km, 5 km × 5 km, 10 km × 10 km, lumped) and evaluated for three relevant temporal resolutions (hour, day, month), both applied with uniform and distributed forcing. The model was run 3150 times using the Hierarchical Latin Hypercube Sample and the best 1 % of the runs was selected as behavioural. The overlap in behavioural sets for different spatial and temporal resolutions was used as an indicator of parameter transferability. A key result from this study is that the overlap in parameter sets for different spatial resolutions was much larger than for different temporal resolutions, also when the forcing was applied in a distributed fashion. This result suggests that it is easier to transfer parameters across different spatial resolutions than across different temporal resolutions. However, the result also indicates a substantial underestimation in the spatial variability represented in the hydrological simulations, suggesting that the high spatial transferability may occur because the current generation of large-domain models has an inadequate representation of spatial variability and hydrologic connectivity. The results presented in this paper provide a strong motivation to further investigate and substantially improve the representation of spatial and temporal variability in

  19. The large-scale biosphere-atmosphere experiment in Amazonia: Analyzing regional land use change effects

    NASA Astrophysics Data System (ADS)

    Keller, Michael; Silva-Dias, Maria Assunção; Nepstad, Daniel C.; Silva-Andreae, Meinrat O.

    The Large-Scale Biosphere-Atmosphere Experiment in Amazonia (LBA) is a multi-disciplinary, multinational scientific project led by Brazil. LBA researchers seek to understand Amazonia in its global context especially with regard to regional and global climate. Current development activities in Amazonia including deforestation, logging, cattle ranching, and agriculture significantly perturb regional and global carbon budgets and the atmospheric radiation budget through both greenhouse gas inputs and the increase in atmospheric particulates generated by fires. The Brazilian Amazon currently releases about 0.2 Pg-C to the atmosphere each year as a result of net deforestation. Logging and forest fire activity are poorly quantified but certainly increase this amount by more than 10%. Fires associated with land management activities generate smoke that leads to heating of the lower atmosphere, decreases in overall cloudiness, increases in cloud lifetimes, and the suppression of rainfall. There are considerable uncertainties associated with our understanding of smoke effects. Present development trends point to agricultural intensification in the Brazilian Amazon. This intensification and the associated generation of wealth present an opportunity to enhance governance on the frontier and to minimize the damaging effects of fires.

  20. Study of the Seismic Cycle of large Earthquakes in central Peru: Lima Region

    NASA Astrophysics Data System (ADS)

    Norabuena, E. O.; Quiroz, W.; Dixon, T. H.

    2009-12-01

    Since historical times, the Peruvian subduction zone has been source of large and destructive earthquakes. The more damaging one occurred on May 30 1970 offshore Peru’s northern city of Chimbote with a death toll of 70,000 people and several hundred US million dollars in property damage. More recently, three contiguous plate interface segments in southern Peru completed their seismic cycle generating the 1996 Nazca (Mw 7.1), the 2001 Atico-Arequipa (Mw 8.4) and the 2007 Pisco (Mw 7.9) earthquakes. GPS measurements obtained between 1994-2001 by IGP-CIW an University of Miami-RSMAS on the central Andes of Peru and Bolivia were used to estimate their coseismic displacements and late stage of interseismic strain accumulation. However, we focus our interest in central Peru-Lima region, which with its about 9’000,000 inhabitants is located over a locked plate interface that has not broken with magnitude Mw 8 earthquakes since May 1940, September 1966 and October 1974. We use a network of 11 GPS monuments to estimate the interseismic velocity field, infer spatial variations of interplate coupling and its relation with the background seismicity of the region.

  1. Regional contraction of brain surface area involves three large-scale networks in schizophrenia.

    PubMed

    Palaniyappan, Lena; Mallikarjun, Pavan; Joseph, Verghese; White, Thomas P; Liddle, Peter F

    2011-07-01

    In schizophrenia, morphological changes in the cerebral cortex have been primarily investigated using volumetric or cortical thickness measurements. In healthy subjects, as the brain size increases, the surface area expands disproportionately when compared to the scaling of cortical thickness. In this structural MRI study, we investigated the changes in brain surface area in schizophrenia by constructing relative areal contraction/expansion maps showing group differences in surface area using Freesurfer software in 57 patients and 41 controls. We observed relative areal contraction affecting Default Mode Network, Central Executive Network and Salience Network, in addition to other regions in schizophrenia. We confirmed the surface area reduction across these three large-scale brain networks by undertaking further region-of-interest analysis of surface area. We also observed a significant hemispheric asymmetry in the surface area changes, with the left hemisphere showing a greater reduction in the areal contraction maps. Our findings suggest that a fundamental disturbance in cortical expansion is likely in individuals who develop schizophrenia. PMID:21497489

  2. SPLASH: the Southern Parkes Large-Area Survey in Hydroxyl - first science from the pilot region

    NASA Astrophysics Data System (ADS)

    Dawson, J. R.; Walsh, A. J.; Jones, P. A.; Breen, S. L.; Cunningham, M. R.; Lowe, V.; Jones, C.; Purcell, C.; Caswell, J. L.; Carretti, E.; McClure-Griffiths, N. M.; Ellingsen, S. P.; Green, J. A.; Gómez, J. F.; Krishnan, V.; Dickey, J. M.; Imai, H.; Gibson, S. J.; Hennebelle, P.; Lo, N.; Hayakawa, T.; Fukui, Y.; Mizuno, A.

    2014-04-01

    The Southern Parkes Large-Area Survey in Hydroxyl (SPLASH) is a sensitive, unbiased, and fully sampled survey of the southern Galactic plane and Galactic Centre in all four ground-state transitions of the hydroxyl (OH) radical. The survey provides a deep census of 1612-, 1665-, 1667-, and 1720-MHz OH absorption and emission from the Galactic interstellar medium, and is also an unbiased search for maser sources in these transitions. We present here first results from the SPLASH pilot region, which covers Galactic longitudes 334° to 344° and latitudes ±2°. Diffuse OH is widely detected in all four transitions, with optical depths that are always small (averaged over the Parkes beam), and with departures from local thermodynamic equilibrium common even in the 1665- and 1667-MHz main lines. To a 3σ sensitivity of ˜30 mK, we find no evidence of OH envelopes extending beyond the CO-bright regions of molecular cloud complexes, and conclude that the similarity of the OH excitation temperature and the level of the continuum background is at least partly responsible for this. We detect masers and maser candidates in all four transitions, approximately 50 per cent of which are new detections. This implies that SPLASH will produce a substantial increase in the known population of ground-state OH masers in the southern Galactic plane.

  3. Characterizing moisture delivery mechanisms for extreme precipitation in large geographic regions

    NASA Astrophysics Data System (ADS)

    Bracken, C.; Rajagopalan, B.; Gangopadhyay, S.

    2014-12-01

    Understanding dominant moisture delivery sources for extreme precipitation events is extremely important for characterizing their statistical behavior and behavior under specific climate regimes. Typically, for a given region, the largest extreme events occur in specific seasons but events occurring in off seasons can be just as socio-economically devastating. A complete picture of how and where events originate in all seasons paves the way for statistical forecasting and simulation of extreme precipitation. We present a data driven methodology applicable to large geographic regions that can partition heterogeneous areas into subregions and then characterize the moisture delivery mechanisms for each subregion under specific climate regimes (e.g., ENSO phases, PDO, etc.) and in each season. Extreme subregions are defined using a new nonparametric extreme value clustering method and moisture delivery characterization is done using the HYSPLIT storm backtracking algorithm. We apply this methodology to the Western United States where the nature of extreme events varies widely due to complex terrain, teleconnections and climate interactions.

  4. VERY LARGE ARRAY OH ZEEMAN OBSERVATIONS OF THE STAR-FORMING REGION S88B

    SciTech Connect

    Sarma, A. P.; Eftimova, M.; Brogan, C. L.; Bourke, T. L.; Troland, T. H.

    2013-04-10

    We present observations of the Zeeman effect in OH thermal absorption main lines at 1665 and 1667 MHz taken with the Very Large Array toward the star-forming region S88B. The OH absorption profiles toward this source are complicated, and contain several blended components toward a number of positions. Almost all of the OH absorbing gas is located in the eastern parts of S88B, toward the compact continuum source S88B-2 and the eastern parts of the extended continuum source S88B-1. The ratio of 1665/1667 MHz OH line intensities indicates the gas is likely highly clumped, in agreement with other molecular emission line observations in the literature. S88-B appears to present a similar geometry to the well-known star-forming region M17, in that there is an edge-on eastward progression from ionized to molecular gas. The detected magnetic fields appear to mirror this eastward transition; we detected line-of-sight magnetic fields ranging from 90 to 400 {mu}G, with the lowest values of the field to the southwest of the S88B-1 continuum peak, and the highest values to its northeast. We used the detected fields to assess the importance of the magnetic field in S88B by a number of methods; we calculated the ratio of thermal to magnetic pressures, we calculated the critical field necessary to completely support the cloud against self-gravity and compared it to the observed field, and we calculated the ratio of mass to magnetic flux in terms of the critical value of this parameter. All these methods indicated that the magnetic field in S88B is dynamically significant, and should provide an important source of support against gravity. Moreover, the magnetic energy density is in approximate equipartition with the turbulent energy density, again pointing to the importance of the magnetic field in this region.

  5. Large-scale interaction of the H II region and the quiescent gas in Orion A

    NASA Astrophysics Data System (ADS)

    Rodriguez-Franco, A.; Martin-Pintado, J.; Gomez-Gonzalez, J.; Planesas, P.

    1992-10-01

    Large-scale high-angular-resolution mapping of the Orion A molecular cloud in the J = 12-11, J = 16-15, and J = 24-23 lines of HC3N is reported. Besides the molecular ridge, the large-scale maps show new long and thin molecular filaments (MFs) and 'complex' condensations (CCs). All MFs emerge from the molecular ridge and extend to the west. Their typical H2 densities, kinetic temperatures, and masses are about 100,000/cu cm, about 40 K, and 10-30 solar masses, respectively. Most of the MFs exhibit a velocity gradient of 1-2 km/s pc along their length. Though the HC3N abundance is fairly constant (about 10 exp -9) for the molecular ridge, MFs, and CCs, the data suggest a one order of magnitude decrease toward the ionization front at the optical bar. The highest angular resolution (12 arcsec) map in the J = 24-23 line shows this emission to be strongly concentrated around the BN/KL region. Its spatial distribution exhibits an incomplete ringlike structure with IRc2 at the inner edge. It is suggested that the HC3N ring constitutes the wall of the cavity where the slow-wind from IRc2 is plunging.

  6. Occurrences of large-magnitude earthquakes in the Kachchh region, Gujarat, western India: Tectonic implications

    NASA Astrophysics Data System (ADS)

    Khan, Prosanta Kumar; Mohanty, Sarada Prasad; Sinha, Sushmita; Singh, Dhananjay

    2016-06-01

    Moderate-to-large damaging earthquakes in the peninsular part of the Indian plate do not support the long-standing belief of the seismic stability of this region. The historical record shows that about 15 damaging earthquakes with magnitudes from 5.5 to ~ 8.0 occurred in the Indian peninsula. Most of these events were associated with the old rift systems. Our analysis of the 2001 Bhuj earthquake and its 12-year aftershock sequence indicates a seismic zone bound by two linear trends (NNW and NNE) that intersect an E-W-trending graben. The Bouguer gravity values near the epicentre of the Bhuj earthquake are relatively low (~ 2 mgal). The gravity anomaly maps, the distribution of earthquake epicentres, and the crustal strain-rate patterns indicate that the 2001 Bhuj earthquake occurred along a fault within strain-hardened mid-crustal rocks. The collision resistance between the Indian plate and the Eurasian plate along the Himalayas and anticlockwise rotation of the Indian plate provide the far-field stresses that concentrate within a fault-bounded block close to the western margin of the Indian plate and is periodically released during earthquakes, such as the 2001 MW 7.7 Bhuj earthquake. We propose that the moderate-to-large magnitude earthquakes in the deeper crust in this area occur along faults associated with old rift systems that are reactivated in a strain-hardened environment.

  7. Large-scale climate patterns and precipitation in an arid endorheic region: linkage and underlying mechanism

    NASA Astrophysics Data System (ADS)

    Shi, Pengfei; Yang, Tao; Zhang, Ke; Tang, Qiuhong; Yu, Zhongbo; Zhou, Xudong

    2016-04-01

    The interactions between a range of large-scale climate oscillations and their quantitative links with precipitation are basic prerequisites to understand the hydrologic cycle. Restricted by the current limited knowledge on underlying mechanisms, statistical methods (e.g. correlation methods) are often used rather than a physical-based model. However, available correlation methods generally fail to explain the interactions among a wide range of climate oscillations and associated effects on the water cycle. This study presents a new probabilistic analysis approach by means of a state-of-the-art Copula-based joint probability distribution to characterize the aggregated behaviors for large-scale climate patterns and their connections to precipitation. We applied this method to identify the complex connections between climate patterns (westerly circulation (WEC), El Niño-Southern Oscillation (ENSO) and Pacific Decadal Oscillation (PDO)) and seasonal precipitation over a typical endorheic region, the Tarim River Basin in central Asia. Results show that the interactions among multiple climate oscillations are non-uniform in most seasons and phases. Certain joint extreme phases can significantly trigger extremes (flood and drought) owing to the amplification effect among climate oscillations. We further find that the connection is mainly due to the complex effects of climatic and topographical factors.

  8. The Gould’s Belt Very Large Array Survey. V. The Perseus Region

    NASA Astrophysics Data System (ADS)

    Pech, Gerardo; Loinard, Laurent; Dzib, Sergio A.; Mioduszewski, Amy J.; Rodríguez, Luis F.; Ortiz-León, Gisela N.; Rivera, Juana L.; Torres, Rosa M.; Boden, Andrew F.; Hartman, Lee; Kounkel, Marina A.; Evans, Neal J., II; Briceño, Cesar; Tobin, John; Zapata, Luis A.

    2016-02-01

    We present multiepoch, large-scale (˜2000 arcmin2), fairly deep (˜16 μJy), high-resolution (˜1″) radio observations of the Perseus star-forming complex obtained with the Karl G. Jansky Very Large Array at frequencies of 4.5 and 7.5 GHz. These observations were mainly focused on the clouds NGC 1333 and IC 348, although we also observed several fields in other parts of the Perseus complex. We detect a total of 206 sources, 42 of which are associated with young stellar objects (YSOs). The radio properties of about 60% of the YSOs are compatible with a nonthermal radio emission origin. Based on our sample, we find a fairly clear relation between the prevalence of nonthermal radio emission and evolutionary status of the YSOs. By comparing our results with previously reported X-ray observations, we show that YSOs in Perseus follow a Güdel-Benz relation with κ = 0.03, consistent with other regions of star formation. We argue that most of the sources detected in our observations but not associated with known YSOs are extragalactic, but provide a list of 20 unidentified radio sources whose radio properties are consistent with being YSO candidates. Finally, we also detect five sources with extended emission features that can clearly be associated with radio galaxies.

  9. Near-Infrared Polarization Source Catalog of the Northeastern Regions of the Large Magellanic Cloud

    NASA Astrophysics Data System (ADS)

    Kim, Jaeyeong; Jeong, Woong-Seob; Pak, Soojong; Park, Won-Kee; Tamura, Motohide

    2016-01-01

    We present a near-infrared band-merged photometric and polarimetric catalog for the 39‧ × 69‧ fields in the northeastern part of the Large Magellanic Cloud (LMC), which were observed using SIRPOL, an imaging polarimeter of the InfraRed Survey Facility. This catalog lists 1858 sources brighter than 14 mag in the H band with a polarization signal-to-noise ratio greater than three in the J, H, or Ks bands. Based on the relationship between the extinction and the polarization degree, we argue that the polarization mostly arises from dichroic extinctions caused by local interstellar dust in the LMC. This catalog allows us to map polarization structures to examine the global geometry of the local magnetic field, and to show a statistical analysis of the polarization of each field to understand its polarization properties. In the selected fields with coherent polarization position angles, we estimate magnetic field strengths in the range of 3-25 μG using the Chandrasekhar-Fermi method. This implies the presence of large-scale magnetic fields on a scale of around 100 parsecs. When comparing mid- and far-infrared dust emission maps, we confirmed that the polarization patterns are well aligned with molecular clouds around the star-forming regions.

  10. Evidence against extracellular exposure of a highly immunogenic region in the C-terminal domain of the simian immunodeficiency virus gp41 transmembrane protein.

    PubMed

    Postler, Thomas S; Martinez-Navio, José M; Yuste, Eloísa; Desrosiers, Ronald C

    2012-01-01

    The generally accepted model for human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein topology includes a single membrane-spanning domain. An alternate model has been proposed which features multiple membrane-spanning domains. Consistent with the alternate model, a high percentage of HIV-1-infected individuals produce unusually robust antibody responses to a region of envelope, the so-called "Kennedy epitope," that in the conventional model should be in the cytoplasm. Here we show analogous, robust antibody responses in simian immunodeficiency virus SIVmac239-infected rhesus macaques to a region of SIVmac239 envelope located in the C-terminal domain, which in the conventional model should be inside the cell. Sera from SIV-infected rhesus macaques consistently reacted with overlapping oligopeptides corresponding to a region located within the cytoplasmic domain of gp41 by the generally accepted model, at intensities comparable to those observed for immunodominant areas of the surface component gp120. Rabbit serum raised against this highly immunogenic region (HIR) reacted with SIV envelope in cell surface-staining experiments, as did monoclonal anti-HIR antibodies isolated from an SIVmac239-infected rhesus macaque. However, control experiments demonstrated that this surface staining could be explained in whole or in part by the release of envelope protein from expressing cells into the supernatant and the subsequent attachment to the surfaces of cells in the culture. Serum and monoclonal antibodies directed against the HIR failed to neutralize even the highly neutralization-sensitive strain SIVmac316. Furthermore, a potential N-linked glycosylation site located close to the HIR and postulated to be outside the cell in the alternate model was not glycosylated. An artificially introduced glycosylation site within the HIR was also not utilized for glycosylation. Together, these data support the conventional model of SIV envelope as a type Ia transmembrane

  11. Delivery of Large Heterologous Polypeptides across the Cytoplasmic Membrane of Antigen-Presenting Cells by the Bordetella RTX Hemolysin Moiety Lacking the Adenylyl Cyclase Domain

    PubMed Central

    Holubova, Jana; Jelinek, Jiri; Tomala, Jakub; Masin, Jiri; Kosova, Martina; Stanek, Ondrej; Bumba, Ladislav; Michalek, Jaroslav; Kovar, Marek; Sebo, Peter

    2012-01-01

    The Bordetella adenylate cyclase toxin-hemolysin (CyaA; also called ACT or AC-Hly) targets CD11b-expressing phagocytes and translocates into their cytosol an adenylyl cyclase (AC) that hijacks cellular signaling by conversion of ATP to cyclic AMP (cAMP). Intriguingly, insertion of large passenger peptides removes the enzymatic activity but not the cell-invasive capacity of the AC domain. This has repeatedly been exploited for delivery of heterologous antigens into the cytosolic pathway of CD11b-expressing dendritic cells by CyaA/AC− toxoids, thus enabling their processing and presentation on major histocompatibility complex (MHC) class I molecules to cytotoxic CD8+ T lymphocytes (CTLs). We produced a set of toxoids with overlapping deletions within the first 371 residues of CyaA and showed that the structure of the AC enzyme does not contain any sequences indispensable for its translocation across target cell membrane. Moreover, replacement of the AC domain (residues 1 to 371) with heterologous polypeptides of 40, 146, or 203 residues yielded CyaAΔAC constructs that delivered passenger CTL epitopes into antigen-presenting cells (APCs) and induced strong antigen-specific CD8+ CTL responses in vivo in mice and ex vivo in human peripheral blood mononuclear cell cultures. This shows that the RTX (repeats in toxin) hemolysin moiety, consisting of residues 374 to 1706 of CyaA, harbors all structural information involved in translocation of the N-terminal AC domain across target cell membranes. These results decipher the extraordinary capacity of the AC domain of CyaA to transport large heterologous cargo polypeptides into the cytosol of CD11b+ target cells and pave the way for the construction of CyaAΔAC-based polyvalent immunotherapeutic T cell vaccines. PMID:22215742

  12. Distributed Kalman filtering compared to Fourier domain preconditioned conjugate gradient for laser guide star tomography on extremely large telescopes.

    PubMed

    Gilles, Luc; Massioni, Paolo; Kulcsár, Caroline; Raynaud, Henri-François; Ellerbroek, Brent

    2013-05-01

    This paper discusses the performance and cost of two computationally efficient Fourier-based tomographic wavefront reconstruction algorithms for wide-field laser guide star (LGS) adaptive optics (AO). The first algorithm is the iterative Fourier domain preconditioned conjugate gradient (FDPCG) algorithm developed by Yang et al. [Appl. Opt.45, 5281 (2006)], combined with pseudo-open-loop control (POLC). FDPCG's computational cost is proportional to N log(N), where N denotes the dimensionality of the tomography problem. The second algorithm is the distributed Kalman filter (DKF) developed by Massioni et al. [J. Opt. Soc. Am. A28, 2298 (2011)], which is a noniterative spatially invariant controller. When implemented in the Fourier domain, DKF's cost is also proportional to N log(N). Both algorithms are capable of estimating spatial frequency components of the residual phase beyond the wavefront sensor (WFS) cutoff frequency thanks to regularization, thereby reducing WFS spatial aliasing at the expense of more computations. We present performance and cost analyses for the LGS multiconjugate AO system under design for the Thirty Meter Telescope, as well as DKF's sensitivity to uncertainties in wind profile prior information. We found that, provided the wind profile is known to better than 10% wind speed accuracy and 20 deg wind direction accuracy, DKF, despite its spatial invariance assumptions, delivers a significantly reduced wavefront error compared to the static FDPCG minimum variance estimator combined with POLC. Due to its nonsequential nature and high degree of parallelism, DKF is particularly well suited for real-time implementation on inexpensive off-the-shelf graphics processing units. PMID:23695321

  13. Interactions of two large antiviral polyamides with the long control region of HPV16.

    PubMed

    Vasilieva, Elena; Niederschulte, Jacquelyn; Song, Yang; Harris, George Davis; Koeller, Kevin J; Liao, Puhong; Bashkin, James K; Dupureur, Cynthia M

    2016-08-01

    PA1 and PA25 are large hairpin polyamides that are effective in nearly eliminating HPV16 episomes (DNA) in cell culture, and PA25 has broad spectrum activity against three cancer-causing forms of HPV (Edwards, T. G., Koeller, K. J., Slomczynska, U., Fok, K., Helmus, M., Bashkin, J. K., Fisher, C., Antiviral Res. 91 (2011) 177-186). Described here are the interactions of these PAs with sequences in the long control region (LCR) of HPV16 (7348-122). Using an FeEDTA conjugate of PA1 (designed to recognize 5'-W2GW7-3'; W = A or T), 34 affinity cleavage (AC) patterns were detected for this fragment. These sites can be rationalized with sequences featuring perfect, single, double, triple and quadruple mismatches. Quantitative DNase I footprinting analysis indicates that perfect sites bind PA1 with Kds between 0.7 and 2.2 nM. Kds for single, double, triple and quadruple mismatch sites range from 1-3 nM-20 nM. Using AC and EDTA conjugates, we report that unlike smaller 8-ring hairpin PAs, introduction of a chiral turn in this large polyamide has no effect on binding orientation (forward vs. reverse). Despite its design to recognize 5'-W2GW5GW4-3' via two Im residues, a motif not represented in this HPV sequence, a PA25-EDTA conjugate yielded 31 affinity cleavage sites on the region. Low nM Kds for PA25 without EDTA indicates a high tolerance for triple and quadruple mismatches. While there is extensive coverage of the sequence examined, AC cleavage patterns for the two PAs show discrete binding events and do not overlap significantly. This indicates that within the context of A/T rich sequences, these PAs do not recognize a simple shared sequence-related feature of the DNA. These insights continue to inform the complex nature of large hairpin PA-DNA interactions and antiviral behavior. PMID:27155361

  14. Influence of the Valine Zipper Region on the Structure and Aggregation of the Basic Leucine Zipper (bZIP) Domain of Activating Transcription Factor 5 (ATF5)

    PubMed Central

    Ciaccio, Natalie A.; Reynolds, T. Steele; Middaugh, C. Russell; Laurence, Jennifer S.

    2012-01-01

    Protein aggregation is a major problem for biopharmaceuticals. While the control of aggregation is critically important for the future of protein pharmaceuticals, mechanisms of aggregate assembly, particularly the role that structure plays, are still poorly understood. Increasing evidence indicates that partially folded intermediates critically influence the aggregation pathway. We have previously reported the use of the basic leucine zipper (bZIP) domain of Activating Transcription Factor 5 (ATF5) as a partially folded model system to investigate protein aggregation. This domain contains three regions with differing structural propensity: a N-terminal polybasic region, a central helical leucine zipper region, and a C-terminal extended valine zipper region. Additionally, a centrally positioned cysteine residue readily forms an intermolecular disulfide bond that reduces aggregation. Computational analysis of ATF5 predicts that the valine zipper region facilitates self-association. Here we test this hypothesis using a truncated mutant lacking the C-terminal valine zipper region. We compare the structure and aggregation of this mutant to the wild-type (WT) form under both reducing and non-reducing conditions. Our data indicate that removal of this region results in a loss of alpha-helical structure in the leucine zipper and a change in the mechanism of self-association. The mutant form displays increased association at low temperature but improved resistance to thermally induced aggregation. PMID:23067245

  15. Large-scale changes in the cloud radiative forcing over the Indian region

    NASA Astrophysics Data System (ADS)

    Patil, S. D.; Yadav, R. K.

    Based on earth radiation budget experiment (ERBE) data, earlier studies have shown that in tropical deep-convective regions there is a near cancellation between shortwave and longwave cloud radiative forcing and El Nino event affects the cloud radiative forcing in the Pacific Ocean. The present study investigates these features over the Indian region (0-30°N, 60-120°E) in the peak monsoon month July, (being a representative month of the southwest monsoon season) using satellite measurements of ERBE and International Satellite Cloud Climatology Project (ISCCP) cloud data during the period 1985-1989. It has been observed from the study that a unique imbalance is seen between shortwave cloud radiative forcing (SWCRF) and longwave cloud radiative forcing (LWCRF). It is found to be prominent when the magnitude of LWCRF is higher than 50 W m -2. Net cloud radiative forcing (NCRF) is highly negative in the Indian region from Arabian sea to Indochina and near zero in the equatorial Indian Ocean. The ratio N, i.e., N=-SWCRF/LWCRF, is showing significantly higher values for all the years, the variation of observed N against SWCRF also shows higher values with SWCRF during average of 1985-1989, 1987 and 1988 because it is more than (N=˜1) that mentioned by Kiehl and Ramanathan (1990, Comparison of cloud forcing derived from the earth radiation budget experiment with that simulated by NCAR community climate model. Journal of Geophysical Research 95, 11679-11698) suggesting more imbalance between SWCRF and LWCRF and the lowering of the cloud top pressure particularly in 1987. Cloud radiative forcing (CRF) components are undergoing year-to-year variability with maximum magnitude in 1988 and minimum in 1987 similar to rainfall variation over the region, indicating an association between monsoon rainfall activity and CRF. Large-scale reduction occurred in the magnitudes of CRF and cloud physical properties in the Arabian Sea and south Bay of Bengal especially in 1987, and NCEP

  16. Biochemical Large-Scale Interaction Analysis of Murine Olfactory Receptors and Associated Signaling Proteins with Post-Synaptic Density 95, Drosophila Discs Large, Zona-Occludens 1 (PDZ) Domains*

    PubMed Central

    Jansen, Fabian; Kalbe, Benjamin; Scholz, Paul; Fränzel, Benjamin; Osterloh, Markus; Wolters, Dirk; Hatt, Hanns; Neuhaus, Eva Maria; Osterloh, Sabrina

    2015-01-01

    G protein-coupled receptors (GPCRs) constitute the largest family among mammalian membrane proteins and are capable of initiating numerous essential signaling cascades. Various GPCR-mediated pathways are organized into protein microdomains that can be orchestrated and regulated through scaffolding proteins, such as PSD-95/discs-large/ZO1 (PDZ) domain proteins. However, detailed binding characteristics of PDZ–GPCR interactions remain elusive because these interactions seem to be more complex than previously thought. To address this issue, we analyzed binding modalities using our established model system. This system includes the 13 individual PDZ domains of the multiple PDZ domain protein 1 (MUPP1; the largest PDZ protein), a broad range of murine olfactory receptors (a multifaceted gene cluster within the family of GPCRs), and associated olfactory signaling proteins. These proteins were analyzed in a large-scale peptide microarray approach and continuative interaction studies. As a result, we demonstrate that canonical binding motifs were not overrepresented among the interaction partners of MUPP1. Furthermore, C-terminal phosphorylation and distinct amino acid replacements abolished PDZ binding promiscuity. In addition to the described in vitro experiments, we identified new interaction partners within the murine olfactory epithelium using pull-down-based interactomics and could verify the partners through co-immunoprecipitation. In summary, the present study provides important insight into the complexity of the binding characteristics of PDZ–GPCR interactions based on olfactory signaling proteins, which could identify novel clinical targets for GPCR-associated diseases in the future. PMID:25979994

  17. Unique Piezoelectric Properties of the Monoclinic Phase in Pb (Zr ,Ti )O3 Ceramics: Large Lattice Strain and Negligible Domain Switching

    NASA Astrophysics Data System (ADS)

    Fan, Longlong; Chen, Jun; Ren, Yang; Pan, Zhao; Zhang, Linxing; Xing, Xianran

    2016-01-01

    The origin of the excellent piezoelectric properties at the morphotropic phase boundary is generally attributed to the existence of a monoclinic phase in various piezoelectric systems. However, there exist no experimental studies that reveal the role of the monoclinic phase in the piezoelectric behavior in phase-pure ceramics. In this work, a single monoclinic phase has been identified in Pb (Zr ,Ti )O3 ceramics at room temperature by in situ high-energy synchrotron x-ray diffraction, and its response to electric field has been characterized for the first time. Unique piezoelectric properties of the monoclinic phase in terms of large intrinsic lattice strain and negligible domain switching have been observed. The extensional strain constant d33 and the transverse strain constant d31 are calculated to be 520 and -200 pm /V , respectively. These large piezoelectric coefficients are mainly due to the large intrinsic lattice strain, with very little extrinsic contribution from domain switching. The unique properties of the monoclinic phase provide new insights into the mechanisms responsible for the piezoelectric properties at the morphotropic phase boundary.

  18. Potential effects of large linear pipeline construction on soil and vegetation in ecologically fragile regions.

    PubMed

    Xiao, Jun; Wang, Ya-Feng; Shi, Peng; Yang, Lei; Chen, Li-Ding

    2014-11-01

    Long-distance pipeline construction results in marked human disturbance of the regional ecosystem and brings into question the safety of pipeline construction with respect to the environment. Thus, the direct environmental impact and proper handling of such large projects have received much attention. The potential environmental effects, however, have not been fully addressed, particularly for large linear pipeline projects, and the threshold of such effects is unclear. In this study, two typical eco-fragile areas in western China, where large linear construction projects have been conducted, were chosen as the case study areas. Soil quality indices (SQI) and vegetation indices (VI), representing the most important potential effects, were used to analyze the scope of the effect of large pipeline construction on the surrounding environment. These two indices in different buffer zones along the pipeline were compared against the background values. The analysis resulted in three main findings. First, pipeline construction continues to influence the nearby eco-environment even after a 4-year recovery period. During this period, the effect on vegetation due to pipeline construction reaches 300 m beyond the working area, and is much larger in distance than the effect on soil, which is mainly confined to within 30 m either side of the pipeline, indicating that vegetation is more sensitive than soil to this type of human disturbance. However, the effect may not reach beyond 500 m from the pipeline. Second, the scope of the effect in terms of distance on vegetation may also be determined by the frequency of disturbance and the intensity of the pipeline construction. The greater the number of pipelines in an area, the higher the construction intensity and the more frequent the disturbance. Frequent disturbance may expand the effect on vegetation on both sides of the pipeline, but not on soil quality. Third, the construction may eliminate the stable, resident plant

  19. SagE induces highly effective protective immunity against Streptococcus iniae mainly through an immunogenic domain in the extracellular region

    PubMed Central

    2013-01-01

    Background Streptococcus iniae is a Gram-positive bacterium and a severe pathogen of a wide range of farmed fish. S. iniae possesses a virulence-associated streptolysin S cluster composed of several components, one of which is SagE. SagE a transmembrane protein with one major extracellular region named ECR. This study aimed to develop a SagE-based DNA candidate vaccine against streptococcosis and examine the immunoprotective mechanism of the vaccine. Results We constructed a DNA vaccine, pSagE, based on the sagE gene and examined its immunological property in a Japanese flounder (Paralichthys olivaceus) model. The results showed that at 7 days post-vaccination, expression of SagE at transcription and translation levels was detected in the tissues of the vaccinated fish. After challenge with S. iniae at one and two months post-vaccination, pSagE-vaccinated fish exhibited relative percent survival (RPS) of 95% and 88% respectively. Immunological analysis showed that (i) pSagE significantly upregulated the expression of a wide range of immune genes, (ii) pSagE induced the production of specific serum antibodies that bound whole-cell S. iniae, and (iii) treatment of S. iniae with pSagE-induced antibodies blocked bacterial invasion of host cells. To localize the immunoprotective domain of SagE, the ECR-expressing DNA vaccine pSagEECR was constructed. Immunization analysis showed that flounder vaccinated with pSagEECR exhibited a RPS of 68%, and that pSagEECR induced serum antibody production and immune gene expression in a manner similar to, though to lower magnitudes than, those induced by pSagE. Conclusions We in this study developed a DNA vaccine, pSagE, which induces highly protective immunity against S. iniae. The protective effect of pSagE is probably due to its ability to elicit systemic immune response, in particular that of the humoral branch, which leads to production of specific serum antibodies that impair bacterial infection. These results add insights to

  20. Recent Regional Climate State and Change - Derived through Downscaling Homogeneous Large-scale Components of Re-analyses

    NASA Astrophysics Data System (ADS)

    Von Storch, H.; Klehmet, K.; Geyer, B.; Li, D.; Schubert-Frisius, M.; Tim, N.; Zorita, E.

    2015-12-01

    Global re-analyses suffer from inhomogeneities, as they process data from networks under development. However, the large-scale component of such re-analyses is mostly homogeneous; additional observational data add in most cases to a better description of regional details and less so on large-scale states. Therefore, the concept of downscaling may be applied to homogeneously complementing the large-scale state of the re-analyses with regional detail - wherever the condition of homogeneity of the large-scales is fulfilled. Technically this can be done by using a regional climate model, or a global climate model, which is constrained on the large scale by spectral nudging. This approach has been developed and tested for the region of Europe, and a skillful representation of regional risks - in particular marine risks - was identified. While the data density in Europe is considerably better than in most other regions of the world, even here insufficient spatial and temporal coverage is limiting risk assessments. Therefore, downscaled data-sets are frequently used by off-shore industries. We have run this system also in regions with reduced or absent data coverage, such as the Lena catchment in Siberia, in the Yellow Sea/Bo Hai region in East Asia, in Namibia and the adjacent Atlantic Ocean. Also a global (large scale constrained) simulation has been. It turns out that spatially detailed reconstruction of the state and change of climate in the three to six decades is doable for any region of the world.The different data sets are archived and may freely by used for scientific purposes. Of course, before application, a careful analysis of the quality for the intended application is needed, as sometimes unexpected changes in the quality of the description of large-scale driving states prevail.

  1. A Limited-Memory BFGS Algorithm Based on a Trust-Region Quadratic Model for Large-Scale Nonlinear Equations

    PubMed Central

    Li, Yong; Yuan, Gonglin; Wei, Zengxin

    2015-01-01

    In this paper, a trust-region algorithm is proposed for large-scale nonlinear equations, where the limited-memory BFGS (L-M-BFGS) update matrix is used in the trust-region subproblem to improve the effectiveness of the algorithm for large-scale problems. The global convergence of the presented method is established under suitable conditions. The numerical results of the test problems show that the method is competitive with the norm method. PMID:25950725

  2. Peculiarities of mantle lithosphere beneath the large kimberlite pipes in different regions for Siberian craton

    NASA Astrophysics Data System (ADS)

    Ashchepkov, Igor; Logvinova, Alla; Ntaflos, Theodoros; Vladykin, Nikolai; Spetsius, Zdislav; Kostrovitsky, Sergey; Stegnitsky, Yuri; Prokopyev, Sergey

    2016-04-01

    Comparison of the structure of the mantle columns and mineralogy of the large kimberlite pipes in Yakutia from the different regions, kimberlite fields and mantle terranes in Yakutia allowed several assumptions. 1. The large kimberlite pipes possibly trace the ancient magma feeders occurred in the time of the continent growth. Commonly kimberlites and large pipes are tracing the deep faults and lineaments tracing the ancient sutures, rift zones, trans -lithospheric faults and other permeable structures, which may be parallel to the ancient continental margins. Large pipes locate at the periodic distance like volcanoes in arc settings tracing the "volcanic fronts". 2. Large pipes commonly contain the higher amounts of the sub-calcic garnets representing the dunitic associations (Stachel et al., 2008). In ophiolites dunites veins are representing the channels for the melt transfer (Kelemen et al., 2002). It is likely that ancient large magmatic arc system could have also deep seated roots represented by the (sub calcic) garnet - bearing dunitic systems. 3. Many large pipes including Udachnaya (Pokhilenko et al., 1999) and Mir (Roden et al., 2006) contain in mantle roots high amount of various pyroxenites. The most ancient pyroxenites are supplementary to the dunitic associations. But mostly they represent the materials from the re-melted eclogites and partial and hybrid melts (plume and subduction -related). They are concentrating in the traps in the lithosphere base, in the middle part of mantle section and in the basaltic trap 2.0-3.0 GPa. Pyroxenites in the lithosphere base in some cases are vary abundant but mostly they are protokimberlitic cumulates from of the latest stages of plume activity. Products of the melts crystallization from the earlier stages represent easy melting material at the lithosphere base could be the traps for the later plume melts. 5. Large pipes as a rule reveal contrast layering which is favorite for the capturing of the material from

  3. Peculiarities of mantle lithosphere beneath the large kimberlite pipes in different regions for Siberian craton

    NASA Astrophysics Data System (ADS)

    Ashchepkov, Igor; Logvinova, Alla; Ntaflos, Theodoros; Vladykin, Nikolai; Spetsius, Zdislav; Kostrovitsky, Sergey; Stegnitsky, Yuri; Prokopyev, Sergey

    2016-04-01

    Comparison of the structure of the mantle columns and mineralogy of the large kimberlite pipes in Yakutia from the different regions, kimberlite fields and mantle terranes in Yakutia allowed several assumptions. 1. The large kimberlite pipes possibly trace the ancient magma feeders occurred in the time of the continent growth. Commonly kimberlites and large pipes are tracing the deep faults and lineaments tracing the ancient sutures, rift zones, trans -lithospheric faults and other permeable structures, which may be parallel to the ancient continental margins. Large pipes locate at the periodic distance like volcanoes in arc settings tracing the "volcanic fronts". 2. Large pipes commonly contain the higher amounts of the sub-calcic garnets representing the dunitic associations (Stachel et al., 2008). In ophiolites dunites veins are representing the channels for the melt transfer (Kelemen et al., 2002). It is likely that ancient large magmatic arc system could have also deep seated roots represented by the (sub calcic) garnet - bearing dunitic systems. 3. Many large pipes including Udachnaya (Pokhilenko et al., 1999) and Mir (Roden et al., 2006) contain in mantle roots high amount of various pyroxenites. The most ancient pyroxenites are supplementary to the dunitic associations. But mostly they represent the materials from the re-melted eclogites and partial and hybrid melts (plume and subduction -related). They are concentrating in the traps in the lithosphere base, in the middle part of mantle section and in the basaltic trap 2.0-3.0 GPa. Pyroxenites in the lithosphere base in some cases are vary abundant but mostly they are protokimberlitic cumulates from of the latest stages of plume activity. Products of the melts crystallization from the earlier stages represent easy melting material at the lithosphere base could be the traps for the later plume melts. 5. Large pipes as a rule reveal contrast layering which is favorite for the capturing of the material from

  4. Comparison between method of lines and time domain method in evaluating the large signal responses of Fabry-Perot semiconductor lasers

    NASA Astrophysics Data System (ADS)

    Braverman, Ada L.

    1998-07-01

    An extensive comparison between two modeling methods: Method of Lines and Time Domain Method in analyzing the large signal responses of Fabry-Perot semiconductor lasers is presented. The methods are implemented in two numerical codes written in FORTRAN and using DIGITAL ALPHA workstations under VAX/VMS and UNIX operating systems. The comparison shows good agreement between the simulation results under specific conditions. A special accent is placed on the advantages and drawbacks of both methods by taking into account their numerical problems and the computational effort implied by simulations.

  5. Large stresses in the lithosphere in regions of strong Neotectonic uplift

    NASA Astrophysics Data System (ADS)

    Artyushkov, Eugene; Chekhovich, Peter

    2014-05-01

    Several mechanisms have been proposed to explain the drift of lithospheric plates: subduction pull, basal drag, ridge push and some other ones. Among them only ridge push can be quantified reliably enough as (1.5-2)×1012 Nm (Artyushkov, JGR, 1973, 78, 7675-7708; Geodynamics, Elsevier, 1983, 312 p.). Due to uncertainty of another mechanisms, estimates of the forces acting along the lithospheric layer still differ by one order of magnitude. Ridge push is only a special case of the forces produced in the gravity field by density heterogeneities in the crust and subcrustal lithosphere. These forces generally increase with the potential energy stored in the relief. This allows us to estimate what force is necessary to shorten the crust with its surface reaching a certain altitude. As follows from a large volume of data, strong shortening of the crust in folds belts usually produced a ragged topography. However, after its erosion in a few million years the crustal surface remained near to sea level and mountain building occurred after the termination of crustal shortening. Thus the present Alps were formed during the past 5 Ma after 99% of shortening in them were already over. In the Urals high mountains were formed in the late Early Permian while intense preceding shortening of the crust terminated in the middle of the Carboniferous. Using this constraint the mean force acting in the lithosphere in areas which are located near to sea level can be estimated as 3×1012 Nm. The forces produced by the above mechanism increase with the altitude of the topography. In such regions as the Tibetan Plateau, Pamir and Southern Tien-Shan they can be as large as (5-7)×1012 N/m. Depending on the boundary conditions, the forces can be compressive or tensile. Most of the present mountain ranges and high plateaus were formed due to a rapid crustal uplift during the past several million years. The main cause was infiltration of mantle fluids into the lithosphere (Artyushkov, Russian

  6. The Relationship between Intelligence and Multiple Domains of Religious Belief: Evidence from a Large Adult US Sample

    ERIC Educational Resources Information Center

    Lewis, Gary J.; Ritchie, Stuart J.; Bates, Timothy C.

    2011-01-01

    High levels of religiosity have been linked to lower levels of intelligence in a number of recent studies. These results have generated both controversy and theoretical interest. Here in a large sample of US adults we address several issues that restricted the generalizability of these previous results. We measured six dimensions of religiosity…

  7. Entry of Duck Hepatitis B Virus into Primary Duck Liver and Kidney Cells after Discovery of a Fusogenic Region within the Large Surface Protein▿

    PubMed Central

    Maenz, Claudia; Chang, Shau-Feng; Iwanski, Alicja; Bruns, Michael

    2007-01-01

    Hepatitis B viruses exhibit a narrow host range specificity that is believed to be mediated by a domain of the large surface protein, designated L. For duck hepatitis B virus, it has been shown that the pre-S domain of L binds to carboxypeptidase D, a cellular receptor present in many species on a wide variety of cell types. Nonetheless, only hepatocytes become infected. It has remained vague which viral features determine host range specificity and organotropicity. By using chymotrypsin to treat duck hepatitis B virus, we addressed the question of whether a putative fusogenic region within the amino-terminal end of the small surface protein may participate in viral entry and possibly constitute one of the determinants of the host range of the virus. Addition of the enzyme to virions resulted in increased infectivity. Remarkably, even remnants of enzyme-treated subviral particles proved to be inhibitory to infection. A noninfectious deletion mutant devoid of the binding region for carboxypeptidase D could be rendered infectious for primary duck hepatocytes by treatment with chymotrypsin. Although because of the protease treatment mutant and wild-type viruses may have become infectious in an unspecific and receptor-independent manner, their host range specificity was not affected, as shown by the inability of the virus to replicate in different hepatoma cell lines, as well as primary chicken hepatocytes. Instead, the organotropicity of the virus could be reduced, which was demonstrated by infection of primary duck kidney cells. PMID:17360753

  8. A unique GCN5-related glucosamine N-acetyltransferase region exist in the fungal multi-domain glycoside hydrolase family 3 β-N-acetylglucosaminidase

    PubMed Central

    Qin, Zhen; Xiao, Yibei; Yang, Xinbin; Mesters, Jeroen R.; Yang, Shaoqing; Jiang, Zhengqiang

    2015-01-01

    Glycoside hydrolase (GH) family 3 β-N-acetylglucosaminidases widely exist in the filamentous fungi, which may play a key role in chitin metabolism of fungi. A multi-domain GH family 3 β-N-acetylglucosaminidase from Rhizomucor miehei (RmNag), exhibiting a potential N-acetyltransferase region, has been recently reported to show great potential in industrial applications. In this study, the crystal structure of RmNag was determined at 2.80 Å resolution. The three-dimensional structure of RmNag showed four distinctive domains, which belong to two distinguishable functional regions — a GH family 3 β-N-acetylglucosaminidase region (N-terminal) and a N-acetyltransferase region (C-terminal). From structural and functional analysis, the C-terminal region of RmNag was identified as a unique tandem array linking general control non-derepressible 5 (GCN5)-related N-acetyltransferase (GNAT), which displayed glucosamine N-acetyltransferase activity. Structural analysis of this glucosamine N-acetyltransferase region revealed that a unique glucosamine binding pocket is located in the pantetheine arm binding terminal region of the conserved CoA binding pocket, which is different from all known GNAT members. This is the first structural report of a glucosamine N-acetyltransferase, which provides novel structural information about substrate specificity of GNATs. The structural and functional features of this multi-domain β-N-acetylglucosaminidase could be useful in studying the catalytic mechanism of GH family 3 proteins. PMID:26669854

  9. A unique GCN5-related glucosamine N-acetyltransferase region exist in the fungal multi-domain glycoside hydrolase family 3 β-N-acetylglucosaminidase.

    PubMed

    Qin, Zhen; Xiao, Yibei; Yang, Xinbin; Mesters, Jeroen R; Yang, Shaoqing; Jiang, Zhengqiang

    2015-01-01

    Glycoside hydrolase (GH) family 3 β-N-acetylglucosaminidases widely exist in the filamentous fungi, which may play a key role in chitin metabolism of fungi. A multi-domain GH family 3 β-N-acetylglucosaminidase from Rhizomucor miehei (RmNag), exhibiting a potential N-acetyltransferase region, has been recently reported to show great potential in industrial applications. In this study, the crystal structure of RmNag was determined at 2.80 Å resolution. The three-dimensional structure of RmNag showed four distinctive domains, which belong to two distinguishable functional regions--a GH family 3 β-N-acetylglucosaminidase region (N-terminal) and a N-acetyltransferase region (C-terminal). From structural and functional analysis, the C-terminal region of RmNag was identified as a unique tandem array linking general control non-derepressible 5 (GCN5)-related N-acetyltransferase (GNAT), which displayed glucosamine N-acetyltransferase activity. Structural analysis of this glucosamine N-acetyltransferase region revealed that a unique glucosamine binding pocket is located in the pantetheine arm binding terminal region of the conserved CoA binding pocket, which is different from all known GNAT members. This is the first structural report of a glucosamine N-acetyltransferase, which provides novel structural information about substrate specificity of GNATs. The structural and functional features of this multi-domain β-N-acetylglucosaminidase could be useful in studying the catalytic mechanism of GH family 3 proteins. PMID:26669854

  10. Structural Study of the HD-PTP Bro1 Domain in a Complex with the Core Region of STAM2, a Subunit of ESCRT-0

    PubMed Central

    Lee, Juhyeon; Oh, Kyoung-Jin; Lee, Dasom; Kim, Bo Yeon; Choi, Joon Sig; Ku, Bonsu; Kim, Seung Jun

    2016-01-01

    EGFR is a key player in cell proliferation and survival signaling, and its sorting into MVBs for eventual lysosomal degradation is controlled by the coordination of multiple ESCRT complexes on the endosomal membrane. HD-PTP is a cytosolic protein tyrosine phosphatase, and is associated with EGFR trafficking by interacting with the ESCRT-0 protein STAM2 and the ESCRT-III protein CHMP4B via its N-terminal Bro1 domain. Intriguingly, the homologous domain of two other human Bro1 domain-containing proteins, Alix and Brox, binds CHMP4B but not STAM2, despite their high structural similarity. To elucidate this binding specificity, we determined the complex structure of the HD-PTP Bro1 domain bound to the STAM2 core region. STAM2 binds to the hydrophobic concave pocket of the HD-PTP Bro1 domain, as CHMP4B does to the pocket of Alix, Brox, or HD-PTP but in the opposite direction. Critically, Thr145 of HD-PTP, corresponding to Lys151 of Alix and Arg145 of Brox, is revealed to be a determinant residue enabling this protein to bind STAM2, as the Alix- or Brox-mimicking mutations of this residue blocks the intermolecular interaction. This work therefore provides the structural basis for how HD-PTP recognizes the ESCRT-0 component to control EGFR sorting. PMID:26866605

  11. Structure of the iSH2 domain of Human phosphatidylinositol 3-kinase p85 beta Subunit Reveals Conformational Plasticity in the Interhelical Turn Region

    SciTech Connect

    C Schauder; L Ma; R Krug; G Montelione; R Guan

    2011-12-31

    Phosphatidylinositol 3-kinase (PI3K) proteins actively trigger signaling pathways leading to cell growth, proliferation and survival. These proteins have multiple isoforms and consist of a catalytic p110 subunit and a regulatory p85 subunit. The iSH2 domain of the p85 {beta} isoform has been implicated in the binding of nonstructural protein 1 (NS1) of influenza A viruses. Here, the crystal structure of human p85 {beta} iSH2 determined to 3.3 {angstrom} resolution is reported. The structure reveals that this domain mainly consists of a coiled-coil motif. Comparison with the published structure of the bovine p85 {beta} iSH2 domain bound to the influenza A virus nonstructural protein 1 indicates that little or no structural change occurs upon complex formation. By comparing this human p85 {beta} iSH2 structure with the bovine p85 {beta} iSH2 domain, which shares 99% sequence identity, and by comparing the multiple conformations observed within the asymmetric unit of the bovine iSH2 structure, it was found that this coiled-coil domain exhibits a certain degree of conformational variability or 'plasticity' in the interhelical turn region. It is speculated that this plasticity of p85 {beta} iSH2 may play a role in regulating its functional and molecular-recognition properties.

  12. Large Scale Evapotranspiration Estimates: An Important Component in Regional Water Balances to Assess Water Availability

    NASA Astrophysics Data System (ADS)

    Garatuza-Payan, J.; Yepez, E. A.; Watts, C.; Rodriguez, J. C.; Valdez-Torres, L. C.; Robles-Morua, A.

    2013-05-01

    Water security, can be defined as the reliable supply in quantity and quality of water to help sustain future populations and maintaining ecosystem health and productivity. Water security is rapidly declining in many parts of the world due to population growth, drought, climate change, salinity, pollution, land use change, over-allocation and over-utilization, among other issues. Governmental offices (such as the Comision Nacional del Agua in Mexico, CONAGUA) require and conduct studies to estimate reliable water balances at regional or continental scales in order to provide reasonable assessments of the amount of water that can be provided (from surface or ground water sources) to supply all the human needs while maintaining natural vegetation, on an operational basis and, more important, under disturbances, such as droughts. Large scale estimates of evapotranspiration (ET), a critical component of the water cycle, are needed for a better comprehension of the hydrological cycle at large scales, which, in most water balances is left as the residual. For operational purposes, such water balance estimates can not rely on ET measurements since they do not exist, should be simple and require the least ground information possible, information that is often scarce or does not exist at all. Given this limitation, the use of remotely sensed data to estimate ET could supplement the lack of ground information, particularly in remote regions In this study, a simple method, based on the Makkink equation is used to estimate ET for large areas at high spatial resolutions (1 km). The Makkink model used here is forced using three remotely sensed datasets. First, the model uses solar radiation estimates obtained from the Geostationary Operational Environmental Satellite (GOES); Second, the model uses an Enhanced Vegetation Index (EVI) obtained from the Moderate-resolution Imaging Spectroradiometer (MODIS) normalized to get an estimate for vegetation amount and land use which was

  13. A refined regional modeling approach for the Corn Belt - experiences and recommendations for large-scale integrated modeling

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Nonpoint source pollution from agriculture is the main source of nitrogen and phosphorus in the stream systems of the Corn Belt region in the Midwestern U.S. This region is comprised of two large river basins, the intensely row-cropped Upper Mississippi River Basin (UMRB) and Ohio-Tennessee River B...

  14. Large-scale regionalization of water table depth in peatlands optimized for greenhouse gas emission upscaling

    NASA Astrophysics Data System (ADS)

    Bechtold, M.; Tiemeyer, B.; Laggner, A.; Leppelt, T.; Frahm, E.; Belting, S.

    2014-04-01

    Fluxes of the three main greenhouse gases (GHG) CO2, CH4 and N2O from peat and other organic soils are strongly controlled by water table depth. Information about the spatial distribution of water level is thus a crucial input parameter when upscaling GHG emissions to large scales. Here, we investigate the potential of statistical modeling for the regionalization of water levels in organic soils when data covers only a small fraction of the peatlands of the final map. Our study area is Germany. Phreatic water level data from 53 peatlands in Germany were compiled in a new dataset comprising 1094 dip wells and 7155 years of data. For each dip well, numerous possible predictor variables were determined using nationally available data sources, which included information about land cover, ditch network, protected areas, topography, peatland characteristics and climatic boundary conditions. We applied boosted regression trees to identify dependencies between predictor variables and dip well specific long-term annual mean water level (WL) as well as a transformed form of it (WLt). The latter was obtained by assuming a hypothetical GHG transfer function and is linearly related to GHG emissions. Our results demonstrate that model calibration on WLt is superior. It increases the explained variance of the water level in the sensitive range for GHG emissions and avoids model bias in subsequent GHG upscaling. The final model explained 45% of WLt variance and was built on nine predictor variables that are based on information about land cover, peatland characteristics, drainage network, topography and climatic boundary conditions. Their individual effects on WLt and the observed parameter interactions provide insights into natural and anthropogenic boundary conditions that control water levels in organic soils. Our study also demonstrates that a large fraction of the observed WLt variance cannot be explained by nationally available predictor variables and that predictors with

  15. Merged interaction regions and large-scale magnetic field fluctuations during 1991: Voyager 2 observations

    NASA Technical Reports Server (NTRS)

    Burlaga, L. F.; Ness, N. F.

    1994-01-01

    This paper analyzes Voyager 2 observations of the magnetic field between 33.6 AU and 36.2 AU during 1991 when extraordinary events were observed on the Sun and in the heliosphere. The magnetic field strength signal B(t) has the unusual form of two large transient merged interaction regions (MIRs) on a fluctuating background. The two MIRs moved past the spacecraft in 32 days and 18 days, respectively. The mean field strength in each transient MIR was approx. equals 2.6 times the mean field during the remaining part of the year (0.11 nT). Each of the MIRs is related to a fast stream. The magnetic field is strong throughout each stream, suggesting that the strong fields are carried by the streams as well as produced by shock and stream compression. The fluctuations in B(t) during 1991 are not multifractal, and the MIRs cannot be approximated as multifractal clusters of intense magnetic fields. The distribution of the hour-averaged magnetic field strengths is approximately lognormal over 90% of its intermediate range, and it has an exponential tail for B greater than the average magnetic field strength. The elevation angles of B have a normal distribution with a standard deviation of 16 deg +/- 4 deg. The distributions of the azimuthal angles of B in the ranges 1 deg - 180 deg and 180 deg - 360 deg are approximately normal over a more limited range, and non-Gaussian tails associated with nearly radial magnetic fields; the standard deviations are approx. equal to 40 deg. Individual sectors are present throughout most of the interval, even in the MIRs, but there is no recurrent sector pattern. A model of the large-scale fluctuations in 1991 will have to include both determinaistic and statistical factors.

  16. Daily air temperature interpolated at high spatial resolution over a large mountainous region

    USGS Publications Warehouse

    Dodson, R.; Marks, D.

    1997-01-01

    Two methods are investigated for interpolating daily minimum and maximum air temperatures (Tmin and Tmax) at a 1 km spatial resolution over a large mountainous region (830 000 km2) in the U.S. Pacific Northwest. The methods were selected because of their ability to (1) account for the effect of elevation on temperature and (2) efficiently handle large volumes of data. The first method, the neutral stability algorithm (NSA), used the hydrostatic and potential temperature equations to convert measured temperatures and elevations to sea-level potential temperatures. The potential temperatures were spatially interpolated using an inverse-squared-distance algorithm and then mapped to the elevation surface of a digital elevation model (DEM). The second method, linear lapse rate adjustment (LLRA), involved the same basic procedure as the NSA, but used a constant linear lapse rate instead of the potential temperature equation. Cross-validation analyses were performed using the NSA and LLRA methods to interpolate Tmin and Tmax each day for the 1990 water year, and the methods were evaluated based on mean annual interpolation error (IE). The NSA method showed considerable bias for sites associated with vertical extrapolation. A correction based on climate station/grid cell elevation differences was developed and found to successfully remove the bias. The LLRA method was tested using 3 lapse rates, none of which produced a serious extrapolation bias. The bias-adjusted NSA and the 3 LLRA methods produced almost identical levels of accuracy (mean absolute errors between 1.2 and 1.3??C), and produced very similar temperature surfaces based on image difference statistics. In terms of accuracy, speed, and ease of implementation, LLRA was chosen as the best of the methods tested.

  17. The C-terminal region of the transcriptional regulator THAP11 forms a parallel coiled-coil domain involved in protein dimerization.

    PubMed

    Cukier, Cyprian D; Maveyraud, Laurent; Saurel, Olivier; Guillet, Valérie; Milon, Alain; Gervais, Virginie

    2016-06-01

    Thanatos associated protein 11 (THAP11) is a cell cycle and cell growth regulator differentially expressed in cancer cells. THAP11 belongs to a distinct family of transcription factors recognizing specific DNA sequences via an atypical zinc finger motif and regulating diverse cellular processes. Outside the extensively characterized DNA-binding domain, THAP proteins vary in size and predicted domains, for which structural data are still lacking. We report here the crystal structure of the C-terminal region of human THAP11 protein, providing the first 3D structure of a coiled-coil motif from a THAP family member. We further investigate the stability, dynamics and oligomeric properties of the determined structure combining molecular dynamics simulations and biophysical experiments. Our results show that the C-ter region of THAP11 forms a left-handed parallel homo-dimeric coiled-coil structure possessing several unusual features. PMID:26975212

  18. Gravity Wave Disturbances in the F-Region Ionosphere Above Large Earthquakes

    NASA Astrophysics Data System (ADS)

    Bruff, Margie

    The direction of propagation, duration and wavelength of gravity waves in the ionosphere above large earthquakes were studied using data from the Super Dual Auroral Radar Network. Ground scatter data were plotted versus range and time to identify gravity waves as alternating focused and de-focused regions of radar power in wave-like patterns. The wave patterns before and after earthquakes were analyzed to determine the directions of propagation and wavelengths. Conditions were considered 48 hours before and after each identified disturbances to exclude waves from geomagnetic activity. Gravity waves were found travelling away from the epicenter before all six earthquakes for which data were available and after four of the six earthquakes. Gravity waves travelled in at least two directions away from the epicenter in all cases, and even stronger patterns were found for two earthquakes. Waves appeared, on average, 4 days before, persisting 2-3 hours, and 1-2 days after earthquakes, persisting 4-6 hours. Most wavelengths were between 200-300 km. We show a possible correlation between magnitude and depth of earthquakes and gravity wave patterns, but study of more earthquakes is required. This study provides a better understanding of the causes of ionospheric gravity wave disturbances and has potential applications for predicting earthquakes.

  19. Ganymede - Mixture of Terrains and Large Impact Crater in Uruk Sulcus Region

    NASA Technical Reports Server (NTRS)

    1996-01-01

    A mixture of terrains studded with a large impact crater is shown in this view of the Uruk Sulcus region of Jupiter's moon Ganymede taken by NASA's Galileo spacecraft during its first flyby of the planet-sized moon on June 27, 1996. The image shows fine details of bright areas that make up about half of the surface of Ganymede. Pock-marked, ancient, heavily cratered terrain is seen at the top; it is cut by younger, line-like structures in the lower left of the image. The bright, circular feature in the lower middle is an impact crater with some dark ejecta superimposed on the linear ridges. These types of relationships revealed by Galileo allow scientists to work out the complex geologic history of Ganymede. In this view, north is to the top and the sun illuminates the surface from the lower left nearly overhead. The area shown, at latitude 10 degrees north, longitude 168 degrees west, is about 59 by 40 kilometers (36 by 25 miles), and the resolution is 74 meters (80 yards) per picture element. The image was taken on June 27 at a range of 7,448 kilometers (4.628 miles). The Jet Propulsion Laboratory manages the Galileo mission for NASA's Office of Space Science.

  20. YOUNG STELLAR OBJECTS IN THE LARGE MAGELLANIC CLOUD STAR-FORMING REGION N206

    SciTech Connect

    Romita, Krista Alexandra; Meixner, M.; Sewilo, M.; Shiao, B.; Carlson, Lynn Redding; Whitney, B.; Babler, B.; Meade, M.; Indebetouw, R.; Hora, J. L. E-mail: carlson@stsci.ed E-mail: brian@sal.wisc.ed E-mail: jhora@cfa.harvard.ed

    2010-09-20

    We present analysis of the energetic star-forming region Henize 206 (N206) located near the southern edge of the Large Magellanic Cloud (LMC) based on photometric data from the Spitzer Surveying the Agents of Galaxy Evolution (SAGE-LMC; IRAC 3.6, 4.5, 5.8, 8.0 {mu}m and MIPS 24 {mu}m), Infrared Survey Facility near-infrared survey (J, H, K{sub s}), and the Magellanic Clouds Photometric Survey (MCPS UBVI) covering a wavelength range of 0.36-24 {mu}m. Young stellar object (YSO) candidates are identified based upon their location in infrared color-magnitude space and classified by the shapes of their spectral energy distributions in comparison with a pre-computed grid of YSO models. We identify 116 YSO candidates: 102 are well characterized by the YSO models, predominately Stage I, and 14 may be multiple sources or young sources with transition disks. Careful examination of the individual sources and their surrounding environment allows us to identify a factor of {approx}14.5 more YSO candidates than have already been identified. The total mass of these well-fit YSO candidates is {approx}520 M{sub sun}. We calculate a current star formation rate of 0.27 x 10{sup -1} M{sub sun} yr{sup -1} kpc{sup -2}. The distribution of YSO candidates appears to follow shells of neutral material in the interstellar medium.

  1. Reconstruction of the solar coronal magnetic field, from active region to large scale

    NASA Astrophysics Data System (ADS)

    Amari, T.; Canou, A.; Delyon, F.; Aly, J. J.; Frey, P.; Alauzet, F.

    2011-12-01

    The low solar corona is dominated by the magnetic field which is created inside the sun by a dynamo process and then emerges into the atmosphere. This magnetic field plays an important role in most structures and phenomena observed at various wavelengths such as prominences, small and large scale eruptive events, and continuous heating of the plasma, and therefore it is important to understand its three-dimensional properties in order to elaborate efficient theoretical models. Unfortunately, the magnetic field is difficult to measure locally in the hot and tenuous corona. But this can be done at the level of the cooler and denser photosphere, and several instruments with high resolution vector magnetographs are currently available (THEMIS, Imaging Vector Magnetograph (IVM), the Advanced Stokes Polarimeter (ASP), SOLIS, HINODE, Solar Dynamics Observatory (SDO), or will be shortly available by future telescopes such as EST and solar missions as SOLAR-ORBITER. This has lead solar physicists to develop an approach which consists in " reconstructing" the coronal magnetic field from boundary data given on the photosphere. We will discuss some of the issues encountered in solving this problem as well our recent progress and results at the scale of active region scales or the larger one such as full sun scale.

  2. The Response Behaviour of Seeding Particles to a Flow Region with a Large Spatial Velocity Gradient

    NASA Astrophysics Data System (ADS)

    Thomas, Peter J.

    1996-11-01

    The motion of small particles, such as those typically used as seeding particles for tracer particle flow velocity measuring techniques, is studied experimentally and numerically for a flow region with a large spatial velocity gradient. A typical flow situation as encountered in similar form in many measuring applications in compressible flow is considered. Experimental LDV data obtained with various types of seeding particles for the flow across an oblique shock are discussed and compared to corresponding numerical simulations. It is found that the degree of agreement between experimental results and numerical simulation depends on the type of particles and on the flow parameters. The biasing of experimental data as a consequence of multi-disperse size distributions of the seeding particles is discussed. The influence of the Basset history integral, which appears in the equation describing the particle motion, is investigated. Its influence on the results of the numerical simulations for single particles as well as its overall effect on the statistics of results based on multi-disperse particle size distributions is studied. It is found that this effect is that the biasing caused by multi-disperse distributions tends to decrease with the density of the particle material.

  3. Improved confinement region without large magnetohydrodynamic activity in TPE-RX reversed-field pinch plasma

    SciTech Connect

    Yambe, Kiyoyuki; Hirano, Yoichi; Sakakita, Hajime; Koguchi, Haruhisa

    2014-11-15

    We found that spontaneous improved confinement was brought about depending on the operating region in the Toroidal Pinch Experiment-Reversed eXperiment (TPE-RX) reversed-field pinch plasma [Y. Yagi et al., Fusion Eng. Des. 45, 421 (1999)]. Gradual decay of the toroidal magnetic field at plasma surface B{sub tw} reversal makes it possible to realize a prolonged discharge, and the poloidal beta value and energy confinement time increase in the latter half of the discharge, where reversal and pinch parameters become shallow and low, respectively. In the latter half of the discharge, the plasma current and volume-averaged toroidal magnetic field 〈B{sub t}〉 increase again, the electron density slowly decays, the electron temperature and soft X-ray radiation intensity increase, and the magnetic fluctuations are markedly reduced. In this period of improved confinement, the value of (〈B{sub t}〉-B{sub tw})/B{sub pw}, where B{sub pw} is the poloidal magnetic field at the plasma surface, stays almost constant, which indicates that the dynamo action occurs without large magnetohydrodynamic activities.

  4. Improved confinement region without large magnetohydrodynamic activity in TPE-RX reversed-field pinch plasma

    NASA Astrophysics Data System (ADS)

    Yambe, Kiyoyuki; Hirano, Yoichi; Sakakita, Hajime; Koguchi, Haruhisa

    2014-11-01

    We found that spontaneous improved confinement was brought about depending on the operating region in the Toroidal Pinch Experiment-Reversed eXperiment (TPE-RX) reversed-field pinch plasma [Y. Yagi et al., Fusion Eng. Des. 45, 421 (1999)]. Gradual decay of the toroidal magnetic field at plasma surface Btw reversal makes it possible to realize a prolonged discharge, and the poloidal beta value and energy confinement time increase in the latter half of the discharge, where reversal and pinch parameters become shallow and low, respectively. In the latter half of the discharge, the plasma current and volume-averaged toroidal magnetic field increase again, the electron density slowly decays, the electron temperature and soft X-ray radiation intensity increase, and the magnetic fluctuations are markedly reduced. In this period of improved confinement, the value of (-Btw)/Bpw, where Bpw is the poloidal magnetic field at the plasma surface, stays almost constant, which indicates that the dynamo action occurs without large magnetohydrodynamic activities.

  5. Particle precipitation prior to large earthquakes of both the Sumatra and Philippine Regions: A statistical analysis

    NASA Astrophysics Data System (ADS)

    Fidani, Cristiano

    2015-12-01

    A study of statistical correlation between low L-shell electrons precipitating into the atmosphere and strong earthquakes is presented. More than 11 years of the Medium Energy Protons Electrons Detector data from the NOAA-15 Sun-synchronous polar orbiting satellite were analysed. Electron fluxes were analysed using a set of adiabatic coordinates. From this, significant electron counting rate fluctuations were evidenced during geomagnetic quiet periods. Electron counting rates were compared to earthquakes by defining a seismic event L-shell obtained radially projecting the epicentre geographical positions to a given altitude towards the zenith. Counting rates were grouped in every satellite semi-orbit together with strong seismic events and these were chosen with the L-shell coordinates close to each other. NOAA-15 electron data from July 1998 to December 2011 were compared for nearly 1800 earthquakes with magnitudes larger than or equal to 6, occurring worldwide. When considering 30-100 keV precipitating electrons detected by the vertical NOAA-15 telescope and earthquake epicentre projections at altitudes greater that 1300 km, a significant correlation appeared where a 2-3 h electron precipitation was detected prior to large events in the Sumatra and Philippine Regions. This was in physical agreement with different correlation times obtained from past studies that considered particles with greater energies. The Discussion below of satellite orbits and detectors is useful for future satellite missions for earthquake mitigation.

  6. Improvement of lateral resolution of spectral domain optical coherence tomography images in out-of-focus regions with holographic data processing techniques

    SciTech Connect

    Moiseev, A A; Gelikonov, G V; Terpelov, D A; Shilyagin, P A; Gelikonov, V M

    2014-08-31

    An analogy between spectral-domain optical coherence tomography (SD OCT) data and broadband digital holography data is considered. Based on this analogy, a method for processing SD OCT data, which makes it possible to construct images with a lateral resolution in the whole investigated volume equal to the resolution in the in-focus region, is developed. Several issues concerning practical application of the proposed method are discussed. (laser biophotonics)

  7. Future summer precipitation changes over CORDEX-East Asia domain downscaled by a regional ocean-atmosphere coupled model: A comparison to the stand-alone RCM

    NASA Astrophysics Data System (ADS)

    Zou, Liwei; Zhou, Tianjun

    2016-03-01

    Climate changes under the RCP8.5 scenario over the Coordinated Regional Downscaling Experiment (CORDEX)-East Asia domain downscaled by a regional ocean-atmosphere coupled model Flexible Regional Ocean-Atmosphere Land System (FROALS) are compared to those downscaled by the corresponding atmosphere-only regional climate model driven by a global climate system model. Changes in the mean and interannual variability of summer rainfall were discussed for the period of 2051-2070 with respect to the present-day period of 1986-2005. Followed by an enhanced western North Pacific subtropical high and an intensified East Asian summer monsoon, an increase in total rainfall over north China, the Korean Peninsula, and Japan but a decrease in total rainfall over southern China are observed in the FROALS projection. Homogeneous increases of extreme rainfall amounts were found over the CORDEX-East Asia domain. A predominant increase in the interannual variability was evident for both total rainfall and the extreme rainfall amount. The spatial patterns of the projected rainfall changes by FROALS were generally consistent with those from the driving global model at a broad scale due to similar projected circulation changes. In both models, the enhanced southerlies over east China increased the moisture divergences over southern China and enhanced the moisture advection over north China. However, the atmosphere-only regional climate model (RCM) exhibited responses to the underlying sea surface temperature (SST) warming anomalies that were too strong, which induced an anomalous cyclone over the north South China Sea, followed by increases (decreases) of total and extreme rainfall over southern China (central China). The differences of the projected changes in both rainfall and circulation between FROALS and the atmosphere-only RCM were partly affected by the differences in the projected SST changes. The results recommend the employment of a regional ocean-atmosphere coupled model in the

  8. Use of the myosin motor domain as large-affinity tag for the expression and purification of proteins in Dictyostelium discoideum.

    PubMed

    Kollmar, Martin

    2006-08-15

    The cellular slime mold Dictyostelium discoideum is increasingly be used for the overexpression of proteins. Dictyostelium is amenable to classical and molecular genetic approaches and can easily be grown in large quantities. It contains a variety of chaperones and folding enzymes, and is able to perform all kinds of post-translational protein modifications. Here, new expression vectors are presented that have been designed for the production of proteins in large quantities for biochemical and structural studies. The expression cassettes of the most successful vectors are based on a tandem affinity purification tag consisting of an octahistidine tag followed by the myosin motor domain tag. The myosin motor domain not only strongly enhances the production of fused proteins but is also used for a fast affinity purification step through its ATP-dependent binding to actin. The applicability of the new system has been demonstrated for the expression and purification of subunits of the dynein-dynactin motor protein complex from different species. PMID:16516959

  9. Evaluation of the Diurnal Evolution of the Size of Tropical Convective Systems in Large Domain, High Resolution Simulations using Observations of Outgoing Longwave Radiation

    NASA Astrophysics Data System (ADS)

    Pearson, K.; Hogan, R.; Allan, R.; Holloway, C. E.; Lister, G.

    2010-12-01

    A long-standing problem in climate models is the failure to capture either the correct diurnal cycle in convective clouds or the growth of individual cells into larger scale complexes. Cascade is a multi-institution project to study the formation and development of tropical convective systems using high-resolution numerical modeling (down to 1.5~km) run over large domains ( ˜2000×2000~km) and observations. As one element of this, we have developed a technique for visualizing and testing the diurnal cycle in the size of convective cloud systems using observations of outgoing longwave radiation. This has been applied to a 2006 test case over Africa using GERB observations and models run with differing configurations and resolutions. We are now applying this to a large domain simulation of the Maritime continent covering several weeks during April 2009 comparing with TRMM observations. The image shows a comparison of the Met Office Unified Model run at 4~km and 12~km resolution, with and without convective parametrization respectively, for the West Africa test case. The grayscale represents the anomaly in the number of systems falling into each lengthscale bin against time. The middle panel is derived from observations by the Geostationary Earth Radiation Budget (GERB) instrument. It shows a broad upward stripe reflecting growth from smaller to larger systems beginning in the late afternoon. The 12~km model shows the effect of the parametrization scheme with systems of all sizes peaking at similar times much earlier than the observations. The 4~km model bears much closer comparison to the observations with growth in the middle to large size range occurring at a similar time to the observations. The small scale behavior, however, is affected by an unrealistic "shattering" of the large systems into many fragments in the early morning rather than a gradual decay.

  10. Lesser Antilles Subduction Zone Investigation by a Cluster of Large Seismic Experiments in the Forearc Region

    NASA Astrophysics Data System (ADS)

    Last, T.

    2007-12-01

    Thales LAST stands for Lesser Antilles Subduction zone Team which gathers the scientific teams of a cluster of surveys and cruises that have been carried out in 2007 and coordinated under the European Union THALES WAS RIGHT project (Coord. A. Hirn). This cluster is composed by the German cruise TRAIL with the vessel F/S Merian (PI E. Flueh and H. Kopp, IFM-GEOMAR), the French cruise SISMANTILLES 2 with the IFREMER vessel N/O Atalante (PI M. Laigle, IPG Paris and JF. Lebrun, Univ. Antilles Guyane), and French cruise OBSANTILLES with the IRD vessel N/O Antea (PI P. Charvis, Geoazur, Nice, France). During these cruises and surveys, 84 Ocean Bottom 3-components Seismometers (OBS) and 20 Hydrophones (OBHs) have been brought together from several pools (Geoazur, INSU, IPGP, IFM-GEOMAR, AWI,), with up to 30 land stations (CSIC Barcelone, IPG Paris, INSU-RLBM and -LITHOSCOPE) in addition to the permanent onshore arrays of IPGP and SRU. The deployment of all these instruments has been supported principally by ANR Catastrophes Telluriques et Tsunamis (SUBSISMANTI), by the EU SALVADOR Programme of IFM-GEOMAR, as well as by the EU project THALES WAS RIGHT on the Antilles and Hellenic active subductions to which contribute IPGP, Geoazur, IFM-GEOMAR (Germany), ETH Zurich (Switzerland), CSIC Barcelona (Spain), Univ. Trieste (Italy) and NOA Athens (Greece). The main goal of this large seismic investigation effort is the understanding of the behaviour of the seismogenic zone and location of potential source regions of mega-thrust earthquakes. Specific goals are the mapping of the subduction interplate in the range where it may be seismogenic along the Lesser Antilles Arc from Antigua to southern Martinique Islands, as a contribution to identification and localisation in advance of main rupture zones of possible future major earthquakes, and to the search for transient signals of the activity. The forearc region, commonly considered as a proxy to the seismogenic portion of the

  11. Exon organization of the mouse entactin gene corresponds to the structural domains of the polypeptide and has regional homology to the low-density lipoprotein receptor gene

    SciTech Connect

    Durkin, M.E.; Chung, A.E.; Wewer, U.M.

    1995-03-20

    Entactin is a widespread basement membrane protein of 150 kDa that binds to type IV collagen and laminin. The complete exon-intron structure of the mouse entactin gene has been determined from {lambda} genomic DNA clones. The gene spans at least 65 kb and contains 20 exons. The exon organization of the mouse entactin gene closely corresponds to the organization of the polypeptide into distinct structural and functional domains. The two amino-terminal globular domains are encoded by three exons each. Single exons encode the two protease-sensitive, O-glycosylated linking regions. The six EGF-like repeats and the single thyroglobulin-type repeat are each encoded by separate exons. The carboxyl-terminal half of entactin displays sequence homology to the growth factor-like region of the low-density lipoprotein receptor, and in both genes this region is encoded by eight exons. The positions of four introns are also conserved in the homologous region of the two genes. These observations suggest that the entactin gene has evolved via exon shuffling. Finally, several sequence polymorphisms useful for gene linkage analysis were found in the 3{prime} noncoding region of the last exon. 52 refs., 8 figs.

  12. The catalytic region and PEST domain of PTPN18 distinctly regulate the HER2 phosphorylation and ubiquitination barcodes.

    PubMed

    Wang, Hong-Mei; Xu, Yun-Fei; Ning, Shang-Lei; Yang, Du-Xiao; Li, Yi; Du, Yu-Jie; Yang, Fan; Zhang, Ya; Liang, Nan; Yao, Wei; Zhang, Ling-Li; Gu, Li-Chuan; Gao, Cheng-Jiang; Pang, Qi; Chen, Yu-Xin; Xiao, Kun-Hong; Ma, Rong; Yu, Xiao; Sun, Jin-Peng

    2014-09-01

    The tyrosine phosphorylation barcode encoded in C-terminus of HER2 and its ubiquitination regulate diverse HER2 functions. PTPN18 was reported as a HER2 phosphatase; however, the exact mechanism by which it defines HER2 signaling is not fully understood. Here, we demonstrate that PTPN18 regulates HER2-mediated cellular functions through defining both its phosphorylation and ubiquitination barcodes. Enzymologic characterization and three crystal structures of PTPN18 in complex with HER2 phospho-peptides revealed the molecular basis for the recognition between PTPN18 and specific HER2 phosphorylation sites, which assumes two distinct conformations. Unique structural properties of PTPN18 contribute to the regulation of sub-cellular phosphorylation networks downstream of HER2, which are required for inhibition of HER2-mediated cell growth and migration. Whereas the catalytic domain of PTPN18 blocks lysosomal routing and delays the degradation of HER2 by dephosphorylation of HER2 on pY(1112), the PEST domain of PTPN18 promotes K48-linked HER2 ubiquitination and its rapid destruction via the proteasome pathway and an HER2 negative feedback loop. In agreement with the negative regulatory role of PTPN18 in HER2 signaling, the HER2/PTPN18 ratio was correlated with breast cancer stage. Taken together, our study presents a structural basis for selective HER2 dephosphorylation, a previously uncharacterized mechanism for HER2 degradation and a novel function for the PTPN18 PEST domain. The new regulatory role of the PEST domain in the ubiquitination pathway will broaden our understanding of the functions of other important PEST domain-containing phosphatases, such as LYP and PTPN12. PMID:25081058

  13. The catalytic region and PEST domain of PTPN18 distinctly regulate the HER2 phosphorylation and ubiquitination barcodes

    PubMed Central

    Wang, Hong-Mei; Xu, Yun-Fei; Ning, Shang-Lei; Yang, Du-Xiao; Li, Yi; Du, Yu-Jie; Yang, Fan; Zhang, Ya; Liang, Nan; Yao, Wei; Zhang, Ling-Li; Gu, Li-Chuan; Gao, Cheng-Jiang; Pang, Qi; Chen, Yu-Xin; Xiao, Kun-Hong; Ma, Rong; Yu, Xiao; Sun, Jin-Peng

    2014-01-01

    The tyrosine phosphorylation barcode encoded in C-terminus of HER2 and its ubiquitination regulate diverse HER2 functions. PTPN18 was reported as a HER2 phosphatase; however, the exact mechanism by which it defines HER2 signaling is not fully understood. Here, we demonstrate that PTPN18 regulates HER2-mediated cellular functions through defining both its phosphorylation and ubiquitination barcodes. Enzymologic characterization and three crystal structures of PTPN18 in complex with HER2 phospho-peptides revealed the molecular basis for the recognition between PTPN18 and specific HER2 phosphorylation sites, which assumes two distinct conformations. Unique structural properties of PTPN18 contribute to the regulation of sub-cellular phosphorylation networks downstream of HER2, which are required for inhibition of HER2-mediated cell growth and migration. Whereas the catalytic domain of PTPN18 blocks lysosomal routing and delays the degradation of HER2 by dephosphorylation of HER2 on pY1112, the PEST domain of PTPN18 promotes K48-linked HER2 ubiquitination and its rapid destruction via the proteasome pathway and an HER2 negative feedback loop. In agreement with the negative regulatory role of PTPN18 in HER2 signaling, the HER2/PTPN18 ratio was correlated with breast cancer stage. Taken together, our study presents a structural basis for selective HER2 dephosphorylation, a previously uncharacterized mechanism for HER2 degradation and a novel function for the PTPN18 PEST domain. The new regulatory role of the PEST domain in the ubiquitination pathway will broaden our understanding of the functions of other important PEST domain-containing phosphatases, such as LYP and PTPN12. PMID:25081058

  14. Large Scale Parameter Estimation Problems in Frequency-Domain Elastodynamics Using an Error in Constitutive Equation Functional

    PubMed Central

    Banerjee, Biswanath; Walsh, Timothy F.; Aquino, Wilkins; Bonnet, Marc

    2012-01-01

    This paper presents the formulation and implementation of an Error in Constitutive Equations (ECE) method suitable for large-scale inverse identification of linear elastic material properties in the context of steady-state elastodynamics. In ECE-based methods, the inverse problem is postulated as an optimization problem in which the cost functional measures the discrepancy in the constitutive equations that connect kinematically admissible strains and dynamically admissible stresses. Furthermore, in a more recent modality of this methodology introduced by Feissel and Allix (2007), referred to as the Modified ECE (MECE), the measured data is incorporated into the formulation as a quadratic penalty term. We show that a simple and efficient continuation scheme for the penalty term, suggested by the theory of quadratic penalty methods, can significantly accelerate the convergence of the MECE algorithm. Furthermore, a (block) successive over-relaxation (SOR) technique is introduced, enabling the use of existing parallel finite element codes with minimal modification to solve the coupled system of equations that arises from the optimality conditions in MECE methods. Our numerical results demonstrate that the proposed methodology can successfully reconstruct the spatial distribution of elastic material parameters from partial and noisy measurements in as few as ten iterations in a 2D example and fifty in a 3D example. We show (through numerical experiments) that the proposed continuation scheme can improve the rate of convergence of MECE methods by at least an order of magnitude versus the alternative of using a fixed penalty parameter. Furthermore, the proposed block SOR strategy coupled with existing parallel solvers produces a computationally efficient MECE method that can be used for large scale materials identification problems, as demonstrated on a 3D example involving about 400,000 unknown moduli. Finally, our numerical results suggest that the proposed MECE

  15. A numerical approach for simulating fluid structure interaction of flexible thin shells undergoing arbitrarily large deformations in complex domains

    NASA Astrophysics Data System (ADS)

    Gilmanov, Anvar; Le, Trung Bao; Sotiropoulos, Fotis

    2015-11-01

    We present a new numerical methodology for simulating fluid-structure interaction (FSI) problems involving thin flexible bodies in an incompressible fluid. The FSI algorithm uses the Dirichlet-Neumann partitioning technique. The curvilinear immersed boundary method (CURVIB) is coupled with a rotation-free finite element (FE) model for thin shells enabling the efficient simulation of FSI problems with arbitrarily large deformation. Turbulent flow problems are handled using large-eddy simulation with the dynamic Smagorinsky model in conjunction with a wall model to reconstruct boundary conditions near immersed boundaries. The CURVIB and FE solvers are coupled together on the flexible solid-fluid interfaces where the structural nodal positions, displacements, velocities and loads are calculated and exchanged between the two solvers. Loose and strong coupling FSI schemes are employed enhanced by the Aitken acceleration technique to ensure robust coupling and fast convergence especially for low mass ratio problems. The coupled CURVIB-FE-FSI method is validated by applying it to simulate two FSI problems involving thin flexible structures: 1) vortex-induced vibrations of a cantilever mounted in the wake of a square cylinder at different mass ratios and at low Reynolds number; and 2) the more challenging high Reynolds number problem involving the oscillation of an inverted elastic flag. For both cases the computed results are in excellent agreement with previous numerical simulations and/or experiential measurements. Grid convergence tests/studies are carried out for both the cantilever and inverted flag problems, which show that the CURVIB-FE-FSI method provides their convergence. Finally, the capability of the new methodology in simulations of complex cardiovascular flows is demonstrated by applying it to simulate the FSI of a tri-leaflet, prosthetic heart valve in an anatomic aorta and under physiologic pulsatile conditions.

  16. Large-scale regionalization of water table depth in peatlands optimized for greenhouse gas emission upscaling

    NASA Astrophysics Data System (ADS)

    Bechtold, M.; Tiemeyer, B.; Laggner, A.; Leppelt, T.; Frahm, E.; Belting, S.

    2014-09-01

    Fluxes of the three main greenhouse gases (GHG) CO2, CH4 and N2O from peat and other soils with high organic carbon contents are strongly controlled by water table depth. Information about the spatial distribution of water level is thus a crucial input parameter when upscaling GHG emissions to large scales. Here, we investigate the potential of statistical modeling for the regionalization of water levels in organic soils when data covers only a small fraction of the peatlands of the final map. Our study area is Germany. Phreatic water level data from 53 peatlands in Germany were compiled in a new data set comprising 1094 dip wells and 7155 years of data. For each dip well, numerous possible predictor variables were determined using nationally available data sources, which included information about land cover, ditch network, protected areas, topography, peatland characteristics and climatic boundary conditions. We applied boosted regression trees to identify dependencies between predictor variables and dip-well-specific long-term annual mean water level (WL) as well as a transformed form (WLt). The latter was obtained by assuming a hypothetical GHG transfer function and is linearly related to GHG emissions. Our results demonstrate that model calibration on WLt is superior. It increases the explained variance of the water level in the sensitive range for GHG emissions and avoids model bias in subsequent GHG upscaling. The final model explained 45% of WLt variance and was built on nine predictor variables that are based on information about land cover, peatland characteristics, drainage network, topography and climatic boundary conditions. Their individual effects on WLt and the observed parameter interactions provide insight into natural and anthropogenic boundary conditions that control water levels in organic soils. Our study also demonstrates that a large fraction of the observed WLt variance cannot be explained by nationally available predictor variables and

  17. The heparin binding domain of vitronectin is the region that is required to enhance insulin-like growth factor-I signaling.

    PubMed

    Maile, Laura A; Busby, Walker H; Sitko, Kevin; Capps, Byron E; Sergent, Tiffany; Badley-Clarke, Jane; Ling, Yan; Clemmons, David R

    2006-04-01

    We have shown that vitronectin (Vn) binding to a cysteine loop sequence within the extracellular domain of the beta3-subunit (amino acids 177-184) of alphaVbeta3 is required for the positive effects of Vn on IGF-I signaling. When Vn binding to this sequence is blocked, IGF-I signaling in smooth muscle cells is impaired. Because this binding site is distinct from the site on beta3 to which the Arg-Gly-Asp sequence of extracellular matrix ligands bind (amino acids 107-171), we hypothesized that the region of Vn that binds to the cysteine loop on beta3 is distinct from the region that contains the Arg-Gly-Asp sequence. The results presented in this study demonstrate that this heparin binding domain (HBD) is the region of Vn that binds to the cysteine loop region of beta3 and that this region is sufficient to mediate the positive effects of Vn on IGF-I signaling. We provide evidence that binding of the HBD of Vn to alphaVbeta3 has direct effects on the activation state of beta3 as measured by beta3 phosphorylation. The increase in beta3 phosphorylation associated with exposure of cells to this HBD is associated with enhanced phosphorylation of the adaptor protein Src homology 2 domain-containing transforming protein C and enhanced activation MAPK, a downstream mediator of IGF-I signaling. We conclude that the interaction of the HBD of Vn binding to the cysteine loop sequence of beta3 is necessary and sufficient for the positive effects of Vn on IGF-I-mediated effects in smooth muscle cells. PMID:16322097

  18. Multi-scale associations between vegetation cover and woodland bird communities across a large agricultural region.

    PubMed

    Ikin, Karen; Barton, Philip S; Stirnemann, Ingrid A; Stein, John R; Michael, Damian; Crane, Mason; Okada, Sachiko; Lindenmayer, David B

    2014-01-01

    Improving biodiversity conservation in fragmented agricultural landscapes has become an important global issue. Vegetation at the patch and landscape-scale is important for species occupancy and diversity, yet few previous studies have explored multi-scale associations between vegetation and community assemblages. Here, we investigated how patch and landscape-scale vegetation cover structure woodland bird communities. We asked: (1) How is the bird community associated with the vegetation structure of woodland patches and the amount of vegetation cover in the surrounding landscape? (2) Do species of conservation concern respond to woodland vegetation structure and surrounding vegetation cover differently to other species in the community? And (3) Can the relationships between the bird community and the woodland vegetation structure and surrounding vegetation cover be explained by the ecological traits of the species comprising the bird community? We studied 103 woodland patches (0.5 - 53.8 ha) over two time periods across a large (6,800 km(2)) agricultural region in southeastern Australia. We found that both patch vegetation and surrounding woody vegetation cover were important for structuring the bird community, and that these relationships were consistent over time. In particular, the occurrence of mistletoe within the patches and high values of woody vegetation cover within 1,000 ha and 10,000 ha were important, especially for bird species of conservation concern. We found that the majority of these species displayed similar, positive responses to patch and landscape vegetation attributes. We also found that these relationships were related to the foraging and nesting traits of the bird community. Our findings suggest that management strategies to increase both remnant vegetation quality and the cover of surrounding woody vegetation in fragmented agricultural landscapes may lead to improved conservation of bird communities. PMID:24830684

  19. Multi-Scale Associations between Vegetation Cover and Woodland Bird Communities across a Large Agricultural Region

    PubMed Central

    Ikin, Karen; Barton, Philip S.; Stirnemann, Ingrid A.; Stein, John R.; Michael, Damian; Crane, Mason; Okada, Sachiko; Lindenmayer, David B.

    2014-01-01

    Improving biodiversity conservation in fragmented agricultural landscapes has become an important global issue. Vegetation at the patch and landscape-scale is important for species occupancy and diversity, yet few previous studies have explored multi-scale associations between vegetation and community assemblages. Here, we investigated how patch and landscape-scale vegetation cover structure woodland bird communities. We asked: (1) How is the bird community associated with the vegetation structure of woodland patches and the amount of vegetation cover in the surrounding landscape? (2) Do species of conservation concern respond to woodland vegetation structure and surrounding vegetation cover differently to other species in the community? And (3) Can the relationships between the bird community and the woodland vegetation structure and surrounding vegetation cover be explained by the ecological traits of the species comprising the bird community? We studied 103 woodland patches (0.5 - 53.8 ha) over two time periods across a large (6,800 km2) agricultural region in southeastern Australia. We found that both patch vegetation and surrounding woody vegetation cover were important for structuring the bird community, and that these relationships were consistent over time. In particular, the occurrence of mistletoe within the patches and high values of woody vegetation cover within 1,000 ha and 10,000 ha were important, especially for bird species of conservation concern. We found that the majority of these species displayed similar, positive responses to patch and landscape vegetation attributes. We also found that these relationships were related to the foraging and nesting traits of the bird community. Our findings suggest that management strategies to increase both remnant vegetation quality and the cover of surrounding woody vegetation in fragmented agricultural landscapes may lead to improved conservation of bird communities. PMID:24830684

  20. Who experiences discrimination in Brazil? Evidence from a large metropolitan region

    PubMed Central

    2012-01-01

    Introduction Perceived discrimination is related to poor health and has been offered as one explanation for the persistence of health inequalities in some societies. In this study, we explore the prevalence and correlates of perceived discrimination in a large, multiracial Brazilian metropolitan area. Methods The study uses secondary analysis of a regionally representative household survey conducted in 2010 (n=12,213). Bivariate analyses and multiple logistic regression assess the magnitude and statistical significance of covariates associated with reports of any discrimination and with discrimination in specific settings, including when seeking healthcare services, in the work environment, in the family, in social occasions among friends or in public places, or in other situations. Results Nearly 9% of the sample reported some type of discrimination. In multivariable models, reports of any discrimination were higher among people who identify as black versus white (OR 1.91), higher (OR 1.21) among women than men, higher (OR 1.33) among people in their 30’s and lower (OR 0.63) among older individuals. People with many health problems (OR 4.97) were more likely to report discrimination than those with few health problems. Subjective social status (OR 1.23) and low social trust (OR 1.27) were additional associated factors. Perceived discrimination experienced while seeking healthcare differed from all other types of discrimination, in that it was not associated with skin color, social status or trust, but was associated with sex, poverty, and poor health. Conclusions There appear to be multiple factors associated with perceived discrimination in this population that may affect health. Policies and programs aimed at reducing discrimination in Brazil will likely need to address this wider set of interrelated risk factors across different populations. PMID:23249451

  1. Large-scale shear velocity structure of the upper mantle beneath Europe and surrounding regions

    NASA Astrophysics Data System (ADS)

    Legendre, C.; Meier, T.; Lebedev, S.; Friederich, W.

    2009-04-01

    The automated multimode waveform inversion technique developed by Lebedev et al., (2005) was applied to available data of broadband stations in Europe and surrounding regions. The Automated Multimode Inversion Method (AMI) foots on an inversion technique originally invented by Nolet (1991) which he called partitioned waveform inversion. It performs a fitting of the complete waveform starting from the S-wave onset to the surface wave. Assuming that the location and focal mechanism of a considered earthquake are known, the first basic step is to consider each available seismogram separately and to to derive from it linear constrains, which are later used to construct the 3D-model. Inversion parameters are variations of shear velocity in the mantle and Moho depth. The theoretical background of AMI is the pure-path approximation which assumes propagation of waves in and around the vertical plane containing source and receiver. AMI extends the partitioned waveform inversion to a completely automated procedure with automated data quality checks and an automated assessment of the quality of fit obtain when determining the linear constrains from the observed seismogram. In this way, large volumes of data can be efficiently inverted for 3D-mantle structure. We collected all available data for the years from 1990 to 2007 from permanent stations in and around Europe via the data centers of ORFEUS, GEOFON and IRIS. In addition, we incorporated data from temporary experiments like ETSE array, SVEKALAPKO, TOR and the Eifel plume project. Just recently we were also able to add the data recorded by the EGELADOS network from the GEOFON data archive. In this way, a huge data set of about 500.000 seismograms came about from which about 65.000 1D-models could be constructed. The reduction of usable seismograms is caused by (1) mislocation or/and errors in the CMT solutions, (2) the rigorous automatic quality checks implemented in AMI, and (3) the elimination of seismograms for which

  2. The experimental folding landscape of monomeric lactose repressor, a large two-domain protein, involves two kinetic intermediates.

    PubMed

    Wilson, Corey J; Das, Payel; Clementi, Cecilia; Matthews, Kathleen S; Wittung-Stafshede, Pernilla

    2005-10-11

    To probe the experimental folding behavior of a large protein with complex topology, we created a monomeric variant of the lactose repressor protein (MLAc), a well characterized tetrameric protein that regulates transcription of the lac operon. Purified MLAc is folded, fully functional, and binds the inducer isopropyl beta-d-thiogalactoside with the same affinity as wild-type LacI. Equilibrium unfolding of MLAc induced by the chemical denaturant urea is a reversible, apparent two-state process (pH 7.5, 20 degrees C). However, time-resolved experiments demonstrate that unfolding is single-exponential, whereas refolding data indicate two transient intermediates. The data reveal the initial formation of a burst-phase (tau < ms) intermediate that corresponds to approximately 50% of the total secondary-structure content. This step is followed by a rearrangement reaction that is rate-limited by an unfolding process (tau approximately 3 s; pH 7.5, 20 degrees C) and results in a second intermediate. This MLAc intermediate converts to the native structure (tau approximately 30 s; pH 7.5, 20 degrees C). Remarkably, the experimental folding-energy landscape for MLAc is in excellent agreement with theoretical predictions using a simple topology-based C(alpha)-model as presented in a companion article in this issue. PMID:16203983

  3. CELLS v1.0: updated and parallelized version of an electrical scheme to simulate multiple electrified clouds and flashes over large domains

    NASA Astrophysics Data System (ADS)

    Barthe, C.; Chong, M.; Pinty, J.-P.; Bovalo, C.; Escobar, J.

    2012-01-01

    The paper describes the fully parallelized electrical scheme CELLS which is suitable to simulate explicitly electrified storm systems on parallel computers. Our motivation here is to show that a cloud electricity scheme can be developed for use on large grids with complex terrain. Large computational domains are needed to perform real case meteorological simulations with many independent convective cells. The scheme computes the bulk electric charge attached to each cloud particle and hydrometeor. Positive and negative ions are also taken into account. Several parametrizations of the dominant non-inductive charging process are included and an inductive charging process as well. The electric field is obtained by inverting the Gauss equation with an extension to terrain-following coordinates. The new feature concerns the lightning flash scheme which is a simplified version of an older detailed sequential scheme. Flashes are composed of a bidirectional leader phase (vertical extension from the triggering point) and a phase obeying a fractal law (with horizontal extension on electrically charged zones). The originality of the scheme lies in the way the branching phase is treated to get a parallel code. The complete electrification scheme is tested for the 10 July 1996 STERAO case and for the 21 July 1998 EULINOX case. Flash characteristics are analysed in detail and additional sensitivity experiments are performed for the STERAO case. Although the simulations were run for flat terrain conditions, they show that the model behaves well on multiprocessor computers. This opens a wide area of application for this electrical scheme with the next objective of running real meterological case on large domains.

  4. CELLS v1.0: updated and parallelized version of an electrical scheme to simulate multiple electrified clouds and flashes over large domains

    NASA Astrophysics Data System (ADS)

    Barthe, C.; Chong, M.; Pinty, J.-P.; Bovalo, C.; Escobar, J.

    2011-10-01

    The paper describes the fully parallelized electrical scheme CELLS which is suitable to simulate explicitly electrified storm systems on parallel computers. Our motivation here is to show that a cloud electricity scheme can be developed for use on large grids with complex terrain. Large computational domains are needed to perform real case meteorological simulations with many independent convective cells. The scheme computes the bulk electric charge attached to each cloud particle. Positive and negative ions are also taken into account. Several parametrizations of the dominant non-inductive charging process are included and an inductive charging process as well. The electric field is obtained by inverting the Gauss equation with an extension to terrain-following coordinates. The new feature concerns the lightning flash scheme which is a simplified version of an older detailed sequential scheme. Flashes are composed of a bidirectional leader phase (vertical extension from the triggering point) and a phase obeying a fractal law (with horizontal extension on electrically charged zones). The originality of the scheme lies in the way the branching phase is treated to get a parallel code. The complete electrification scheme is tested for the 10 July 1996 STERAO case and for the 21 July 1998 EULINOX case. Flash characteristics are analysed in detail and additional sensitivity experiments are performed for the STERAO case. Although the simulations were run for flat terrain conditions, they show that the model behaves well on multiprocessor computers. This opens a wide area of application for this electrical scheme with the next objective of running real meteorological case on large domains.

  5. A Ras-like domain in the light intermediate chain bridges the dynein motor to a cargo-binding region

    PubMed Central

    Schroeder, Courtney M; Ostrem, Jonathan ML; Hertz, Nicholas T; Vale, Ronald D

    2014-01-01

    Cytoplasmic dynein, a microtubule-based motor protein, transports many intracellular cargos by means of its light intermediate chain (LIC). In this study, we have determined the crystal structure of the conserved LIC domain, which binds the motor heavy chain, from a thermophilic fungus. We show that the LIC has a Ras-like fold with insertions that distinguish it from Ras and other previously described G proteins. Despite having a G protein fold, the fungal LIC has lost its ability to bind nucleotide, while the human LIC1 binds GDP preferentially over GTP. We show that the LIC G domain binds the dynein heavy chain using a conserved patch of aromatic residues, whereas the less conserved C-terminal domain binds several Rab effectors involved in membrane transport. These studies provide the first structural information and insight into the evolutionary origin of the LIC as well as revealing how this critical subunit connects the dynein motor to cargo. DOI: http://dx.doi.org/10.7554/eLife.03351.001 PMID:25272277

  6. Presentation of native epitopes in the V1/V2 and V3 regions of human immunodeficiency virus type 1 gp120 by fusion glycoproteins containing isolated gp120 domains.

    PubMed Central

    Kayman, S C; Wu, Z; Revesz, K; Chen, H; Kopelman, R; Pinter, A

    1994-01-01

    The immune response to viral glycoproteins is often directed against conformation- and/or glycosylation-dependent structures; synthetic peptides and bacterially expressed proteins are inadequate probes for the mapping of such epitopes. This report describes a retroviral vector system that presents such native epitopes on chimeric glycoproteins in which protein fragments of interest are fused to the C terminus of the N-terminal domain of the murine leukemia virus surface protein, gp70. The system was used to express two disulfide-bonded domains from gp120, the surface protein of human immunodeficiency virus type 1 (HIV-1), that include potent neutralization epitopes. The resulting fusion glycoproteins were synthesized at high levels and were efficiently transported and secreted. A fusion protein containing the HXB2 V1/V2 domain was recognized by an HIVIIIB-infected patient serum as well as by 17 of 36 HIV-1 seropositive hemophiliac, homosexual male and intravenous drug user patient sera. Many of these HIV+ human sera reacted with V1/V2 domains from several HIV-1 clones expressed in fusion glycoproteins, indicating the presence of cross-reactive antibodies against epitopes in the V1/V2 domain. Recognition of gp(1-263):V1/V2HXB2 by the HIVIIIB-infected human patient serum was largely blocked by synthetic peptides matching V1 but not V2 sequences, while recognition of this construct by a broadly cross-reactive hemophiliac patient serum was not blocked by individual V1 or V2 peptides or by mixtures of these peptides. A construct containing the V3 domain of the IIIB strain of HIV-1, gp(1-263):V3HXB2, was recognized by sera from a human and a chimpanzee that had been infected by HIVIIIB but not by sera from hemophiliac patients who had been infected with HIV-1 of MN-like V3 serotype. The reactive sera had significantly higher titers when assayed against gp(1-263):V3HXB2 than when assayed against matching V3 peptides. Immunoprecipitation of this fusion glycoprotein by the

  7. A missense mutation in the PISA domain of HsSAS-6 causes autosomal recessive primary microcephaly in a large consanguineous Pakistani family.

    PubMed

    Khan, Muzammil A; Rupp, Verena M; Orpinell, Meritxell; Hussain, Muhammad S; Altmüller, Janine; Steinmetz, Michel O; Enzinger, Christian; Thiele, Holger; Höhne, Wolfgang; Nürnberg, Gudrun; Baig, Shahid M; Ansar, Muhammad; Nürnberg, Peter; Vincent, John B; Speicher, Michael R; Gönczy, Pierre; Windpassinger, Christian

    2014-11-15

    Asymmetric cell division is essential for normal human brain development. Mutations in several genes encoding centrosomal proteins that participate in accurate cell division have been reported to cause autosomal recessive primary microcephaly (MCPH). By homozygosity mapping including three affected individuals from a consanguineous MCPH family from Pakistan, we delineated a critical region of 18.53 Mb on Chromosome 1p21.3-1p13.1. This region contains the gene encoding HsSAS-6, a centrosomal protein primordial for seeding the formation of new centrioles during the cell cycle. Both next-generation and Sanger sequencing revealed a homozygous c.185T>C missense mutation in the HsSAS-6 gene, resulting in a p.Ile62Thr substitution within a highly conserved region of the PISA domain of HsSAS-6. This variant is neither present in any single-nucleotide polymorphism or exome sequencing databases nor in a Pakistani control cohort. Experiments in tissue culture cells revealed that the Ile62Thr mutant of HsSAS-6 is substantially less efficient than the wild-type protein in sustaining centriole formation. Together, our findings demonstrate a dramatic impact of the mutation p.Ile62Thr on HsSAS-6 function and add this component to the list of genes mutated in primary microcephaly. PMID:24951542

  8. Cache Domains That are Homologous to, but Different from PAS Domains Comprise the Largest Superfamily of Extracellular Sensors in Prokaryotes

    PubMed Central

    Upadhyay, Amit A.; Fleetwood, Aaron D.; Adebali, Ogun; Finn, Robert D.; Zhulin, Igor B.

    2016-01-01

    Cellular receptors usually contain a designated sensory domain that recognizes the signal. Per/Arnt/Sim (PAS) domains are ubiquitous sensors in thousands of species ranging from bacteria to humans. Although PAS domains were described as intracellular sensors, recent structural studies revealed PAS-like domains in extracytoplasmic regions in several transmembrane receptors. However, these structurally defined extracellular PAS-like domains do not match sequence-derived PAS domain models, and thus their distribution across the genomic landscape remains largely unknown. Here we show that structurally defined extracellular PAS-like domains belong to the Cache superfamily, which is homologous to, but distinct from the PAS superfamily. Our newly built computational models enabled identification of Cache domains in tens of thousands of signal transduction proteins including those from important pathogens and model organisms. Furthermore, we show that Cache domains comprise the dominant mode of extracellular sensing in prokaryotes. PMID:27049771

  9. Nucleocytoplasmic Shuttling of Valosin-Containing Protein (VCP/p97) Regulated by Its N domain and C-terminal Region

    PubMed Central

    Song, Changcheng; Wang, Qing; Song, Changzheng; Lockett, Stephen J.; Colburn, Nancy H.; Li, Chou-Chi H.; Wang, Ji Ming; Rogers, Thomas J.

    2014-01-01

    Valosin-containing protein (VCP or p97), a member of AAA family (ATPases associated with diverse cellular activities), plays a key role in many important cellular activities. A genetic deficiency of VCP can cause inclusion body myopathy associated with Paget’s disease of bone and frontotemporal dementia (IBMPFD). Previous studies showed that the VCP N domain is essential for the regulation of nuclear entry of VCP. Here we report that IBMPFD mutations, which are mainly located in the N domain, suppress the nuclear entry of VCP. Moreover, the peptide sequence G780AGPSQ in the C-terminal region regulates the retention of VCP in the nucleus. A mutant lacking this sequence can increase the nuclear distribution of IBMPFD VCP, suggesting that this sequence is a potential molecular target for correcting the deficient nucleocytoplasmic shuttling of IBMPFD VCP proteins. PMID:25447673

  10. Exploring Large-Scale Cross-Correlation for Teleseismic and Regional Seismic Event Characterization

    NASA Astrophysics Data System (ADS)

    Hauk, T. F.; Dodge, D. A.; Addair, T.; Walter, W. R.; Myers, S. C.; Ford, S. R.; Harris, D. B.; Ruppert, S. D.

    2013-12-01

    The decrease in cost of digital storage space and computation power invites new methods of seismic data processing. At Lawrence Livermore National Laboratory (LLNL), we operate a research database of seismic events and waveforms for nuclear explosion monitoring and other applications. The LLNL database contains several million events associated with more than 330 million waveforms at thousands of stations. We are using this database to explore the power of seismic waveform correlation to quantify signal similarities, to discover new events not in catalogs, and to more accurately locate events and identify source types. The results presented here are preliminary, and apply mostly to a subset of seismicity in Eurasia and North America. Much more remains to be done to understand and make use of these results. We computed the waveform correlation for event pairs in the LLNL database in 15 frequency bands and for 8 phase windows. The correlation coefficient exceeds 0.6 for over 370 million waveform pairs. Overall, about 16% of the events in our waveform database correlate with one or more events on at least one channel. However, at very short distances, this number rises to as high as 55%. At distances > 20 degrees the percent of correlated events ranges from ~1% to 10%. The majority of correlated waveforms are found at relatively small (< 10 degrees) station-event separations in short-period bands. Most correlations at teleseismic distances are in long-period bands. Also, for most events, correlated traces are found at only a few stations. The mean magnitude of correlated events is about 1 unit lower than the mean of the events in our waveform database and the standard deviation of the magnitude difference of correlated events is 0.6. Apparently, large-scale correlation processing is most likely to work well for small events of similar magnitude. We have clustered the correlation results in both short- and long-period bands and have identified 439 long-period and 1333

  11. Characterization of a strong repression domain in the hinge region of orphan nuclear receptor hB1F/hLRH-1.

    PubMed

    Xu, Ping-Long; Shan, Shi-Fang; Kong, Yu-Ying; Xie, You-Hua; Wang, Yuan

    2003-10-01

    Human hepatitis B virus enhancer II B1 binding factor (hB1F also known as NR5A2, LRH-1, FTF or CPF) is an orphan nuclear receptor and belongs to the fushi tarazu factor I (FTZ-F1) subfamily. It plays important roles in the transcriptional regulation of a number of genes involved in bile acid biosynthesis pathway, hepatitis B virus (HBV) replication and liver specific regulatory network. Like other nuclear receptors, hB1F is composed of modular functional domains. We characterized a domain in its hinge region that imposes a strong repression on the transcriptional activity of hB1F, which is important for the function of hB1F on regulating the activity of HBV enhancer II/core promoter. Mutations of the core residues in this domain abrogate the repression. Bioinformatic analysis reveals that the amino acid sequence of this region is highly conserved only among members of the FTZ-F1 subfamily. The repression is observed in five cell lines tested, while the degree of the repression varies greatly, which does not parallel with the expression level of the DEAD box protein of 130 kD (DP103), a potential interacting protein of a homologous domain in the steroidogenic factor 1 (SF-1). Moreover, the repression is not affected by the silencing mediator for retinoic acid receptor and thyroid hormone receptor (SMRT) and steroid receptor coactivator 1 (SRC-1). Collectively, these data suggest a novel regulatory mechanism for the transcriptional activity of hB1F. PMID:14515208

  12. A technique for extrapolating and validating forest cover across large regions - Calibrating AVHRR data with TM data

    NASA Technical Reports Server (NTRS)

    Iverson, L. R.; Cook, E. A.; Graham, R. L.

    1989-01-01

    A method is presented for extending high-resolution forest cover information across large regions. Using Landsat TM data with AVHRR data, an empirical relationship beween AVHRR spectral signatures and forest cover is developed. The resulting regression equation is applied to an AVHRR scene covering a large area centered around southern Illinois. The map is used to estimate forest cover within a geographical information system. The results are compared with U.S. Forest Service estimates, showing good agreement.

  13. Statistical searches for microlensing events in large, non-uniformly sampled time-domain surveys: A test using palomar transient factory data

    SciTech Connect

    Price-Whelan, Adrian M.; Agüeros, Marcel A.; Fournier, Amanda P.; Street, Rachel; Ofek, Eran O.; Covey, Kevin R.; Levitan, David; Sesar, Branimir; Laher, Russ R.; Surace, Jason

    2014-01-20

    Many photometric time-domain surveys are driven by specific goals, such as searches for supernovae or transiting exoplanets, which set the cadence with which fields are re-imaged. In the case of the Palomar Transient Factory (PTF), several sub-surveys are conducted in parallel, leading to non-uniform sampling over its ∼20,000 deg{sup 2} footprint. While the median 7.26 deg{sup 2} PTF field has been imaged ∼40 times in the R band, ∼2300 deg{sup 2} have been observed >100 times. We use PTF data to study the trade off between searching for microlensing events in a survey whose footprint is much larger than that of typical microlensing searches, but with far-from-optimal time sampling. To examine the probability that microlensing events can be recovered in these data, we test statistics used on uniformly sampled data to identify variables and transients. We find that the von Neumann ratio performs best for identifying simulated microlensing events in our data. We develop a selection method using this statistic and apply it to data from fields with >10 R-band observations, 1.1 × 10{sup 9} light curves, uncovering three candidate microlensing events. We lack simultaneous, multi-color photometry to confirm these as microlensing events. However, their number is consistent with predictions for the event rate in the PTF footprint over the survey's three years of operations, as estimated from near-field microlensing models. This work can help constrain all-sky event rate predictions and tests microlensing signal recovery in large data sets, which will be useful to future time-domain surveys, such as that planned with the Large Synoptic Survey Telescope.

  14. Calcium-Dependent Energetics of Calmodulin Domain Interactions with Regulatory Regions of the Ryanodine Receptor Type 1 (RyR1)

    PubMed Central

    Newman, Rhonda A.; Sorensen, Brenda R.; Kilpatrick, Adina M.; Shea, Madeline A.

    2014-01-01

    Calmodulin (CaM) plays a vital role in calcium homeostasis by allosterically modulating intracellular calcium channels including the homo-tetrameric human Ryanodine Receptor Type 1 (hRyR1). Apo (calcium-free) CaM activates hRyR1 while calcium-saturated CaM inhibits it. Two CaM-binding regions (residues 1975–1999 and 3614–3643) identified in each RyR1 monomer were proposed to allow CaM to bridge adjacent RyR1 subunits. We explored the distinct roles of CaM domains by using fluorescence anisotropy to determine the affinity of CaM1–148 (full-length), CaM1–80 (N-domain) and CaM76–148 (C-domain) for peptides encompassing hRyR1 residues 1975–1999 or 3614–3643. Both CaM1–148 and CaM76–148 associated in a calcium-independent manner with similar affinities for hRyR1(3614–3643)p while CaM1–80 required calcium and bound ~250-fold more weakly. Association of CaM1–148, CaM1–80 and CaM76–148 with hRyR1(1975–1999)p was much less favorable than with hRyR1(3614–3643)p; differences between the two CaM domains were smaller. Equilibrium calcium titrations monitored by steady-state fluorescence demonstrated that both hRyR1 peptides increased the calcium-binding affinity of both CaM domains. These thermodynamic properties support a prior model in which the CaM C-domain associates with RyR1(3614–3643) at low levels of calcium, positioning CaM to rapidly respond to calcium efflux. However, the affinity of the N-domain of CaM for hRyR1(1975–1999)p is insufficient to explain a model in which CaM bridges adjacent RyR1 subunits within the tetramer. This indicates that other protein factors or properties of the tertiary or quaternary structure of hRyR1 contribute to the energetics of CaM-mediated regulation. PMID:25145833

  15. Large Higgs energy region in Higgs associated top pair production at the Linear Collider

    SciTech Connect

    Farrell, Cailin; Hoang, Andre H.

    2005-07-01

    The process e{sup +}e{sup -}{yields}ttH is considered in the kinematic end point region where the Higgs energy is close to its maximal energy. In perturbative QCD, using the loop expansion, the amplitudes are plagued by Coulomb singularities that need to be resummed. We show that the QCD dynamics in this end point region is governed by nonrelativistic heavy quarkonium dynamics, and we use a nonrelativistic effective theory to compute the Higgs energy distribution at leading and next-to-leading-logarithmic approximation in the nonrelativistic expansion. Updated numbers for the total cross section including the summations in the Higgs energy end point region are presented.

  16. Probes of large-scale structure in the Corona Borealis region

    NASA Technical Reports Server (NTRS)

    Postman, M.; Huchra, J. P.; Geller, M. J.

    1986-01-01

    The present redshift survey of the Corona Borealis region encompasses redshifts, magnitudes and positions for 83 galaxies covering a 16.4 sq deg region; a complementary survey covers 39.2 sq deg, is complete to m(B)0 of 15.5, and encompasses 37 galaxies. The combined survey furnishes further support for the 'bubble-like' geometry revealed by the shallower CfA survey. The redshift distribution obtained is noted to be very similar to that in the neighboring Bootes region. The structure of voids and surfaces in the galaxy distribution is insensitive to luminosity for M(B)0 of less than about -17.4.

  17. DEVELOPMENT OF LARGE RIVER BIOASSESSMENT PROTOCOLS (LR-BPS) FOR BENTHIC MACROINVERTEBRATES IN EPA REGION 5

    EPA Science Inventory

    Non-wadeable rivers have been largely overlooked by bioassessment programs because of sampling difficulties and a lack of appropriate methods and biological indicators. We are in the process of developing a Large River Bioassessment Protocol (LR-BP) for sampling macroinvertebrat...

  18. Essential regions in the membrane domain of bacterial complex I (NDH-1): the machinery for proton translocation.

    PubMed

    Sato, Motoaki; Torres-Bacete, Jesus; Sinha, Prem Kumar; Matsuno-Yagi, Akemi; Yagi, Takao

    2014-08-01

    The proton-translocating NADH-quinone oxidoreductase (complex I/NDH-1) is the first and largest enzyme of the respiratory chain which has a central role in cellular energy production and is implicated in many human neurodegenerative diseases and aging. It is believed that the peripheral domain of complex I/NDH-1 transfers the electron from NADH to Quinone (Q) and the redox energy couples the proton translocation in the membrane domain. To investigate the mechanism of the proton translocation, in a series of works we have systematically studied all membrane subunits in the Escherichia coli NDH-1 by site-directed mutagenesis. In this mini-review, we have summarized our strategy and results of the mutagenesis by depicting residues essential for proton translocation, along with those for subunit connection. It is suggested that clues to understanding the driving forces of proton translocation lie in the similarities and differences of the membrane subunits, highlighting the communication of essential charged residues among the subunits. A possible proton translocation mechanism with all membrane subunits operating in unison is described. PMID:24973951

  19. Paring Down HIV Env: Design and Crystal Structure of a Stabilized Inner Domain of HIV-1 gp120 Displaying a Major ADCC Target of the A32 Region.

    PubMed

    Tolbert, William D; Gohain, Neelakshi; Veillette, Maxime; Chapleau, Jean-Philippe; Orlandi, Chiara; Visciano, Maria L; Ebadi, Maryam; DeVico, Anthony L; Fouts, Timothy R; Finzi, Andrés; Lewis, George K; Pazgier, Marzena

    2016-05-01

    Evidence supports a role of antibody-dependent cellular cytotoxicity (ADCC) toward transitional epitopes in the first and second constant (C1-C2) regions of gp120 (A32-like epitopes) in preventing HIV-1 infection and in vaccine-induced protection. Here, we describe the first successful attempt at isolating the inner domain (ID) of gp120 as an independent molecule that encapsulates the A32-like region within a minimal structural unit of the HIV-1 Env. Through structure-based design, we developed ID2, which consists of the ID expressed independently of the outer domain and stabilized in the CD4-bound conformation by an inter-layer disulfide bond. ID2 expresses C1-C2 epitopes in the context of CD4-triggered full-length gp120 but without any known neutralizing epitope present. Thus, ID2 represents a novel probe for the analysis and/or selective induction of antibody responses to the A32 epitope region. We also present the crystal structure of ID2 complexed with mAb A32, which defines its epitope. PMID:27041594

  20. Titins in C.elegans with unusual features: coiled-coil domains, novel regulation of kinase activity and two new possible elastic regions.

    PubMed

    Flaherty, Denise B; Gernert, Kim M; Shmeleva, Nataliya; Tang, Xuexin; Mercer, Kristina B; Borodovsky, Mark; Benian, Guy M

    2002-10-25

    We report that there are previously unrecognized proteins in Caenorhabditis elegans that are similar to the giant muscle proteins called titins, and these are encoded by a single approximately 90kb gene. The gene structure was predicted by GeneMark.hmm and then experimentally verified. The Ce titin gene encodes polypeptides of 2.2MDa, 1.2MDa and 301kDa. The 2.2MDa isoform resembles twitchin and UNC-89 in that it contains multiple Ig (56) and FnIII (11) domains, and a single protein kinase domain. In addition, however, the 2.2MDa isoform contains four classes of short, 14-51 residue, repeat motifs arranged mostly in many tandem copies. One of these tandem repeat regions is similar to the PEVK regions of vertebrate and fly titins. As the PEVK region is one of the main elastic elements of the titins and is also composed of short tandem repeats, this suggests that the repeat motifs in the Ce titins may have a similar elastic function. An interesting aspect of the two largest Ce titin isoforms, is that in contrast to other members of the twitchin/titin family, there are multiple regions which are likely to form coiled-coil structure. In transgenic animals, the first approximately 100 residues of the largest isoforms targets to dense bodies, the worm analogs of Z-discs. Anti-Ce titin antibodies show localization to muscle I-bands beginning at the L2-L3 larval stages and this pattern continues into adult muscle. Ce titins may not have a role in early myofibril assembly: (1) Ce titins are too short to span half a sarcomere, and the onset of their expression is well after the initial assembly of thick filaments. (2) Ce titins are not localized to I-bands in embryonic or L1 larval muscle. The Ce titin protein kinase domain is most similar to the kinase domains of the twitchins and projectin. The Ce titin kinase has protein kinase activity in vitro, and this activity is regulated by a novel mechanism. PMID:12381307

  1. Multi-dimension and Comprehensive Assessment on the Utilizing and Sharing of Regional Large-Scale Scientific Equipment

    PubMed Central

    Li, Chen; Yongbo, Lv; Chi, Chen

    2015-01-01

    Based on the data from 30 provincial regions in China, an assessment and empirical analysis was carried out on the utilizing and sharing of the large-scale scientific equipment with a comprehensive assessment model established on the three dimensions, namely, equipment, utilization and sharing. The assessment results were interpreted in light of relevant policies. The results showed that on the whole, the overall development level in the provincial regions in eastern and central China is higher than that in western China. This is mostly because of the large gap among the different provincial regions with respect to the equipped level. But in terms of utilizing and sharing, some of the Western provincial regions, such as Ningxia, perform well, which is worthy of our attention. Policy adjustment targeting at the differentiation, elevation of the capacity of the equipment management personnel, perfection of the sharing and cooperation platform, and the promotion of the establishment of open sharing funds, are all important measures to promote the utilization and sharing of the large-scale scientific equipment and to narrow the gap among different regions. PMID:25937850

  2. Large mammals from the Upper Neopleistocene reference sections in the Tunka rift valley, southwestern Baikal Region

    NASA Astrophysics Data System (ADS)

    Shchetnikov, A. A.; Klementiev, A. M.; Filinov, I. A.; Semeney, E. Yu.

    2015-03-01

    This work presents the data on new finds of fossil macrotheriofauna in the reference sections of the Upper Neopleistocene sediments in the Tunka rift valley (southwestern Baikal Region). The osteological material of a number of Late Neopleistocene mammals including extinct species rare for the Baikal region such as Crocuta spelaea, Panthera spelaea, and Spirocerus kiakhtensis (?) was directly dated with a radiocarbon (AMS) method. The obtained 14C data (18000-35000 years) allow one to rejuvenate significantly the upper limit of the common age interval of habitat of these animals in southern part of Eastern Siberia. Cave hyena and spiral-horned antelope lived in the Tunka rift valley in the Baikal region in Late Kargino time (37-24 ka), and cave lion survived the maximum in the Sartan cryochron in the region (21-20 ka). The study of collected paleontological collections provides a basis for selection of independent Kargino (MIS 3) faunal assemblages to use them for regional biostratigraphic analysis of Pleistocene deposits. Radiocarbon age dating of samples allows one to attribute confidently all paleofaunal remains available to the second half of the Late Pleistocene.

  3. How does large-scale nudging in a regional climate model contribute to improving the simulation of weather regimes and seasonal extremes over North America?

    NASA Astrophysics Data System (ADS)

    Lucas-Picher, Philippe; Cattiaux, Julien; Bougie, Alexandre; Laprise, René

    2016-02-01

    To determine the extent to which regional climate models (RCMs) preserve the large-scale atmospheric circulation of their driving fields, we investigate the ability of two RCM simulations to reproduce weather regimes over North America. Each RCM simulation is driven at its lateral boundaries by the ERA-Interim reanalysis, but one of them uses additional large-scale nudging (LSN) in the domain interior. Four weather regimes describing the variability of the large-scale atmospheric dynamics over North America are identified in winter and in summer. The analysis shows that for both seasons, the mean frequency of occurrence and persistence of the four weather regimes for the two RCM simulations are comparable to those of ERA-Interim. However, the frequency of false daily attributions of a specific regime on day-to-day and seasonal bases is significantly high, especially in summer, for the classic lateral-boundary driven simulation. Those false attributions are largely corrected with LSN. Using composite means for each weather regimes, substantial 2-m air temperature and precipitation anomalies associated to the large-scale atmospheric circulation are found. These anomalies are larger in winter than in summer. The validation of the simulations reveals that the 2-m air temperature bias is dependent on the weather regimes, especially in summer. Conversely, the precipitation bias varies significantly from one regime to another, especially in winter. Overall, the results suggest that a classic RCM simulates the mean statistics of the weather regimes well, but that LSN is necessary to reproduce daily weather regimes and seasonal anomalies that match with the driving field.

  4. Inclusive electron scattering from nuclei in the quasielastic region at large momentum transfer

    NASA Astrophysics Data System (ADS)

    Fomin, Nadia

    2008-12-01

    Experiment E02-019, performed in Hall C at the Thomas Jefferson National Accelerator Facility (TJNAF), was a measurement of inclusive electron cross sections for several nuclei (^{2}H,^{3}He, ^{4}He, ^{9}Be,^{12}C, ^{63}Cu, and ^{197}Au) in the quasielastic region at high momentum transfer. In the region of low energy transfer, the cross sections were analyzed in terms of the reduced response, F(y), by examining its y-scaling behavior. The data were also examined in terms of the nuclear structure function ν W_2^A and its behavior in x and the Nachtmann variable ξ. The data show approximate scaling of ν W_2^A in ξ for all targets at all kinematics, unlike scaling in x, which is confined to the DIS regime. However, y-scaling observations are limited to the kinematic region dominated by the quasielastic response ({y<0}), where some scaling violations arising from FSIs are observed.

  5. Complex active regions as the main source of extreme and large solar proton events

    NASA Astrophysics Data System (ADS)

    Ishkov, V. N.

    2013-12-01

    A study of solar proton sources indicated that solar flare events responsible for ≥2000 pfu proton fluxes mostly occur in complex active regions (CARs), i.e., in transition structures between active regions and activity complexes. Different classes of similar structures and their relation to solar proton events (SPEs) and evolution, depending on the origination conditions, are considered. Arguments in favor of the fact that sunspot groups with extreme dimensions are CARs are presented. An analysis of the flare activity in a CAR resulted in the detection of "physical" boundaries, which separate magnetic structures of the same polarity and are responsible for the independent development of each structure.

  6. Identification of Important Regions for Ethylene Binding and Signaling in the Transmembrane Domain of the ETR1 Ethylene Receptor of Arabidopsis[W][OA

    PubMed Central

    Wang, Wuyi; Esch, Jeff J.; Shiu, Shin-Han; Agula, Hasi; Binder, Brad M.; Chang, Caren; Patterson, Sara E.; Bleecker, Anthony B.

    2006-01-01

    The ethylene binding domain (EBD) of the Arabidopsis thaliana ETR1 receptor is modeled as three membrane-spanning helices. We surveyed ethylene binding activity in different kingdoms and performed a bioinformatic analysis of the EBD. Ethylene binding is confined to land plants, Chara, and a group of cyanobacteria but is largely absent in other organisms, consistent with our finding that EBD-like sequences are overrepresented among plant and cyanobacterial species. We made amino acid substitutions in 37 partially or completely conserved residues of the EBD and assayed their effects on ethylene binding and signaling. Mutations primarily in residues in Helices I and II midregions eliminated ethylene binding and conferred constitutive signaling, consistent with the inverse-agonist model of ethylene receptor signaling and indicating that these residues define the ethylene binding pocket. The largest class of mutations, clustered near the cytoplasmic ends of Helices I and III, gave normal ethylene binding activity yet still conferred constitutive signaling. Therefore, these residues may play a role in turning off the signal transmitter domain of the receptor. By contrast, only two mutations were loss of function with respect to signaling. These findings yield insight into the structure and function of the EBD and suggest a conserved role of the EBD as a negative regulator of the signal transmitter domain. PMID:17189345

  7. Transient stability of the helical pattern of region F19-L22 of the N-terminal domain of p53: a molecular dynamics simulation study.

    PubMed

    Espinoza-Fonseca, L Michel; Trujillo-Ferrara, José G

    2006-04-28

    Two molecular dynamics simulations of the region E17-N29 of p53 (p53(17-29)) at different temperatures were performed for a total time of 0.2 micros, to study the conformational landscape of this region. Previous studies have suggested that this region displays different structural motifs, such as helix of a double beta-turn, and that its secondary structure might be transiently stable. Interestingly, in this study it was found that the region F19-L25, and particularly its fragment F19-L22, display a stable, transient helical pattern at sub-microsecond periods. The region F19-L22, which contains one of the most important residues needed for the interaction of p53 with MDM2, seems to be formed and stabilized by the existence of one hydrophobic and one aromatic cluster. The main function of these clusters is to help their surrounding area to desolvate, to allow the hydrogen bond network, therefore favoring the formation of a stable helix. This preliminary study would be useful for a better understanding of the structure and function of the N-terminal domain of p53 and its implications for the control of different types of cancer. PMID:16530164

  8. Nonhemolytic Streptococcus pyogenes Isolates That Lack Large Regions of the sag Operon Mediating Streptolysin S Production▿

    PubMed Central

    Yoshino, Miho; Murayama, Somay Y.; Sunaoshi, Katsuhiko; Wajima, Takeaki; Takahashi, Miki; Masaki, Junko; Kurokawa, Iku; Ubukata, Kimiko

    2010-01-01

    Among nonhemolytic Streptococcus pyogenes (group A streptococcus) strains (n = 9) isolated from patients with pharyngitis or acute otitis media, we identified three deletions in the region from the epf gene, encoding the extracellular matrix binding protein, to the sag operon, mediating streptolysin S production. PMID:20018818

  9. Bidirectional modulation of thermal and chemical sensitivity of TRPM8 channels by the initial region of the N-terminal domain.

    PubMed

    Pertusa, María; González, Alejandro; Hardy, Paulina; Madrid, Rodolfo; Viana, Félix

    2014-08-01

    TRPM8, a nonselective cation channel activated by cold, voltage, and cooling compounds such as menthol, is the principal molecular detector of cold temperatures in primary sensory neurons of the somatosensory system. The N-terminal domain of TRPM8 consists of 693 amino acids, but little is known about its contribution to channel function. Here, we identified two distinct regions within the initial N terminus of TRPM8 that contribute differentially to channel activity and proper folding and assembly. Deletion or substitution of the first 40 residues yielded channels with augmented responses to cold and menthol. The thermal threshold of activation of these mutants was shifted 2 °C to higher temperatures, and the menthol dose-response curve was displaced to lower concentrations. Site-directed mutagenesis screening revealed that single point mutations at positions Ser-26 or Ser-27 by proline caused a comparable increase in the responses to cold and menthol. Electrophysiological analysis of the S27P mutant revealed that the enhanced sensitivity to agonists is related to a leftward shift in the voltage dependence of activation, increasing the probability of channel openings at physiological membrane potentials. In addition, we found that the region encompassing positions 40-60 is a key element in the proper folding and assembly of TRPM8. Different deletions and mutations within this region rendered channels with an impaired function that are retained within the endoplasmic reticulum. Our results suggest a critical contribution of the initial region of the N-terminal domain of TRPM8 to thermal and chemical sensitivity and the proper biogenesis of this polymodal ion channel. PMID:24917670

  10. Characteristics of regional seismic waves from large explosive events including Korean nuclear explosions

    NASA Astrophysics Data System (ADS)

    Jo, Eunyoung; Lee, Ha-sung

    2015-04-01

    Three North Korean underground nuclear explosion (UNE) tests were conducted in 2006, 2009 and 2013. Discrimination of explosions from natural earthquakes is important in monitoring the seismic activity in the Korean Peninsula. The UNEs were well recorded by dense regional seismic networks in South Korea. The UNEs provide unique regional seismic waveforms with high signal-to-noise ratios. However, the continental crust in the Korean Peninsula changes abruptly into a transitional structure between continental and oceanic crusts across the eastern coast. The complex geological and tectonic structures around the Korean Peninsula cause significant variations in regional waveforms. Outstanding question is whether conventional discrimination techniques can be applicable for explosions including the North Korean UNEs. P/S amplitude ratios are widely used for seismic discrimination. To understand the regional shear-energy composition, we analyze the frequency contents of waveforms. The shear-energy contents for the UNEs are compared with those for natural earthquakes with comparable magnitudes. The result shows that the UNEs are successfully discriminated from earthquakes in the Korean Peninsula. We also analyze the explosive events from North Korean not UNEs to test the applicability of the discrimination technique. The result of high frequency Pn/Sn regional discrimination in the explosions show that as magnitude of event is smaller, available distance of discrimination is decreased particularly in high frequency range. The poor signal to noise ratio of Pn phase in the explosions, and inefficient propagation of Sn phase in the Western part of the peninsula frustrate Pn/Sn discriminant, while the UNEs show good performance using both discriminants because of propagation path effects in the eastern part of the peninsula.

  11. A Topographic Image Map of the Sabrina Valles Region Including Information on Large Martian Impact Craters

    NASA Astrophysics Data System (ADS)

    Gehrke, S.; Köhring, R.; Barlow, N. G.; Gwinner, K.; Scholten, F.; Lehmann, H.; Albertz, J.

    2007-03-01

    The Catalog of Large Martian Impact Craters provides detailed information on 42,283 craters >5 km; it is planned to be integrated in the Topographic Image Map Mars 1:200,000 series. Such an update is shown in a special target map, based on HRSC data.

  12. Dynamical downscaling of historical climate over CORDEX East Asia domain: A comparison of regional ocean-atmosphere coupled model to stand-alone RCM simulations

    NASA Astrophysics Data System (ADS)

    Zou, Liwei; Zhou, Tianjun; Peng, Dongdong

    2016-02-01

    The FROALS (flexible regional ocean-atmosphere-land system) model, a regional ocean-atmosphere coupled model, has been applied to the Coordinated Regional Downscaling Experiment (CORDEX) East Asia domain. Driven by historical simulations from a global climate system model, dynamical downscaling for the period from 1980 to 2005 has been conducted at a uniform horizontal resolution of 50 km. The impacts of regional air-sea couplings on the simulations of East Asian summer monsoon rainfall have been investigated, and comparisons have been made to corresponding simulations performed using a stand-alone regional climate model (RCM). The added value of the FROALS model with respect to the driving global climate model was evident in terms of both climatology and the interannual variability of summer rainfall over East China by the contributions of both the high horizontal resolution and the reasonably simulated convergence of the moisture fluxes. Compared with the stand-alone RCM simulations, the spatial pattern of the simulated low-level monsoon flow over East Asia and the western North Pacific was improved in the FROALS model due to its inclusion of regional air-sea coupling. The results indicated that the simulated sea surface temperature (SSTs) resulting from the regional air-sea coupling were lower than those derived directly from the driving global model over the western North Pacific north of 15°N. These colder SSTs had both positive and negative effects. On the one hand, they strengthened the western Pacific subtropical high, which improved the simulation of the summer monsoon circulation over East Asia. On the other hand, the colder SSTs suppressed surface evaporation and favored weaker local interannual variability in the SST, which led to less summer rainfall and weaker interannual rainfall variability over the Korean Peninsula and Japan. Overall, the reference simulation performed using the FROALS model is reasonable in terms of rainfall over the land area of

  13. Calibration of the Sonseca array with large magnitude regional and teleseismic events

    SciTech Connect

    Dowla, F.U.

    1996-07-01

    In order to calibrate the Sonseca station, a 19-element short-period seismic array with a 9 km diameter circular aperture located in central Spain (39.68N, 3.96W), wavefield measurements made on observed seismic phases are compared with expected values. Thirty-five well-recorded regional and teleseismic events are used to study bearing and phase velocity estimation properties. Preliminary results indicate that in general the Sonseca array performs well for both regional and teleseismic events for frequencies less than 5 Hz using standard array signal processing techniques. Main findings of this study are: (1) A systematic bias is observed in bearing estimates; the bias is a function of the true bearing for events from the easterly directions of the array and can be mitigated with a simple bias correction. Using a least-squares quadratic polynomial fit, the bearing estimation error can be reduced to less than two or three degrees. (2) Measured signal and noise coherence functions and beamforming suggest that for regional events improved SNR is obtained by beamforming in the frequency band of 0.5 to 4 Hz with a resulting array gain as high as 10 dB. (3) Because the element spacing of Sonseca array corresponds to that of a sparse regional array, spatial aliasing can be observed in narrowband f-K analysis at the higher frequencies. We compare performance of narrowband and broadband frequency-wavenumber (f-k) analysis and suggest preliminary recipes for f-k and beamforming analysis.

  14. Stochastic Inverse Modeling of Large-Scale Fractured Domains: Example of the Culebra Dolomite in the Vicinity of the WIPP Site

    NASA Astrophysics Data System (ADS)

    McKenna, S. A.; Hart, D. B.; Kanney, J. D.; Beauheim, R. L.

    2008-12-01

    The challenge described in this work is to create an ensemble of calibrated transmissivity (T) fields for the Culebra Dolomite Member of the Rustler Formation at the Waste Isolation Pilot Plant (WIPP) site in southeastern New Mexico. The T fields must individually represent 20 years of transient pumping tests and a set of steady-state head observations across a nearly 30×30 km area. A recently developed geologic conceptual model provides initial values for the T-field calibrations and provides zonation of the model domain based on classes of fracturing and presence or absence of fracture filling materials. These calibrations are completed using the pilot point method with a large (> 400) number of pilot point locations. For each pumping test, responses from between 2 and 12 observation wells at radial distances of 100s of meters to several km away from the pumping well are available. Over 1200 head and drawdown observations are used in the inverse model. Directionally focused transient responses reflect the fractured nature of the Culebra dolomite and are difficult to represent using the effective porosity conceptual model and the large cell sizes (100×100m) necessary for efficient computations within the model domain. Improved representation of the fractured nature of the Culebra is accomplished by efficient pilot point placement based on the sensitivity of the pumping - observation well pairs to perturbations in transmissivity as well as simultaneous estimation of spatially heterogeneous T, storativity, and hydraulic anisotropy fields. Simultaneous estimation of three spatially heterogeneous fields results in over 900 estimated parameters within the model. Singular value decomposition of the Jacobian matrix and adaptive regularization of the estimated parameters along with parallel computation make these calibrations numerically stable and computationally feasible. By allowing these three parameters to vary, within constraints, accurate matches to the steady

  15. A Helioseismic Survey to Investigate Relationships between Subsurface Flows beneath Large Active Regions and Solar Flares

    NASA Astrophysics Data System (ADS)

    Braun, Douglas; Leka, K D.; Barnes, Graham

    2014-06-01

    A survey of the subsurface flow properties of about 120 of the largest active regions, determined from the application of helioseismic holography to Dopplergrams obtained with the HMI instrument onboard the Solar Dynamics Observatory, is being carried out. The overriding goal is to characterize differences in the subsurface flows between active regions associated with eruptive flares and the flows observed in relatively quiescent regions. Applications to flare forecasting comprise only one part of this investigation, since the potential response of the subsurface environment to eruptive events during and after their occurrence is also of scientific interest. Other priorities include understanding the limitations of the helioseismic methods, identifying and correcting systematic effects, and validating the reliability of the measurements using artificial data. While inversions to determine the variation with depth of subsurface flows are planned, preliminary results will be discussed which make use of proxies for near-surface depth-integrated properties, including the horizontal component of the flow divergence and the vertical component of the flow vorticity.This work is supported by the Solar Terrestrial Program of the National Science Foundation, through grant AGS-1127327, and by the National Oceanic and Atmospheric Administration SBIR program.

  16. Structural dynamics and ssDNA binding activity of the three N-terminal domains of the large subunit of Replication Protein A from small angle X-ray scattering

    SciTech Connect

    Pretto, Dalyir I.; Tsutakawa, Susan; Brosey, Chris A.; Castillo, Amalchi; Chagot, Marie-Eve; Smith, Jarrod A.; Tainer, John A.; Chazin, Walter J.

    2010-03-11

    Replication Protein A (RPA) is the primary eukaryotic ssDNA binding protein utilized in diverse DNA transactions in the cell. RPA is a heterotrimeric protein with seven globular domains connected by flexible linkers, which enable substantial inter-domain motion that is essential to its function. Small angle X-ray scattering (SAXS) experiments on two multi-domain constructs from the N-terminus of the large subunit (RPA70) were used to examine the structural dynamics of these domains and their response to the binding of ssDNA. The SAXS data combined with molecular dynamics simulations reveal substantial interdomain flexibility for both RPA70AB (the tandem high affinity ssDNA binding domains A and B connected by a 10-residue linker) and RPA70NAB (RPA70AB extended by a 70-residue linker to the RPA70N protein interaction domain). Binding of ssDNA to RPA70NAB reduces the interdomain flexibility between the A and B domains, but has no effect on RPA70N. These studies provide the first direct measurements of changes in orientation of these three RPA domains upon binding ssDNA. The results support a model in which RPA70N remains structurally independent of RPA70AB in the DNA bound state and therefore freely available to serve as a protein recruitment module.

  17. Complete primary structure of the triple-helical region and the carboxyl-terminal domain of a new type IV collagen chain, alpha 5(IV).

    PubMed

    Pihlajaniemi, T; Pohjolainen, E R; Myers, J C

    1990-08-15

    We have isolated and characterized overlapping cDNA clones which code for a previously unidentified human collagen chain. Although the cDNA-derived primary structure of this new polypeptide is very similar to the basement membrane collagen alpha 1(IV) and alpha 2(IV) chains, the carboxyl-terminal collagenous/non-collagenous junction sequence does not correspond to the junction sequence in either of the newly described alpha 3(IV) or alpha 4(IV) chains (Butkowski, R.J., Langeveld, J.P.M., Wieslander, J., Hamilton, J., and Hudson, B. G. (1987) J. Biol. Chem. 262, 7874-7877). Thus the protein presented here has been designated the alpha 5 chain of type IV collagen. Four clones encode an open reading frame of 1602 amino acids that cover about 95% of the entire chain including half of the amino-terminal 7S domain and all of the central triple-helical region and carboxyl-terminal NC1 domain. The collagenous region of the alpha 5(IV) chain contains 22 interruptions which are in most cases identical in distribution to those in both the alpha 1(IV) and alpha 2(IV) chains. Despite the relatively low degree of conservation among the amino acids in the triple-helical region of the three type IV collagen chains, analysis of the sequences clearly showed that alpha 5(IV) is more related to alpha 1(IV) than to alpha 2(IV). This similarity between the alpha 5(IV) and alpha 1(IV) chains is particularly evident in the NC1 domains where the two polypeptides are 83% identical in contrast to the alpha 5(IV) and alpha 2(IV) identity of 63%. In addition to greatly increasing the complexity of basement membranes, the alpha 5 chain of type IV collagen may be responsible for specialized functions of some of these extracellular matrices. In this regard, it is important to note that we have recently assigned the alpha 5(IV) gene to the region of the X chromosome containing the locus for a familial type of hereditary nephritis known as Alport syndrome (Myers, J.C., Jones, T.A., Pohjalainen, E

  18. A New Module for Large Scale Bayesian Evaluation in the Fast Neutron Energy Region

    SciTech Connect

    Schnabel, G. Leeb, H.

    2015-01-15

    We present an improved update scheme for the Linearized Bayesian Update procedure (LBUP). The revised procedure extends the application of the LBUP to a large number of observables. The consistent update of dozens of millions of observables becomes manageable by circumventing the costly calculation of the prior covariance matrix. Nuclear data evaluations based on the revised scheme may exhaustively enclose all differential and angle-integrated channels, treating all correlations between them exactly in the update procedure.

  19. An intersubunit contact stimulating transcription initiation by E. coli RNA polymerase: interaction of the α C-terminal domain and σ region 4

    PubMed Central

    Ross, Wilma; Schneider, David A.; Paul, Brian J.; Mertens, Aaron; Gourse, Richard L.

    2003-01-01

    The C-terminal domain of the Escherichia coli RNA polymerase (RNAP) alpha subunit (αCTD) stimulates transcription initiation by interacting with upstream (UP) element DNA and a variety of transcription activators. Here we identify specific substitutions in region 4.2 of sigma 70 (σ70) and in αCTD that decrease transcription initiation from promoters containing some, but not all, UP elements. This decrease in transcription derives from a decrease in the initial equilibrium constant for RNAP binding (KB). The open complexes formed by the mutant and wild-type RNAPs differ in DNAse I sensitivity at the junction of the αCTD and σ DNA binding sites, correlating with the differences in transcription. A model of the DNA–αCTD–σ region 4.2 ternary complex, constructed from the previously determined X-ray structures of the Thermus aquaticus σ region 4.2–DNA complex and the E. coli αCTD–DNA complex, indicates that the residues identified by mutation in σ region 4.2 and in αCTD are in very close proximity. Our results strongly suggest that αCTD, when bound to an UP element proximal subsite, contacts the RNAP σ70 subunit, increasing transcription. Previous data from the literature suggest that this same σ–αCTD interaction also plays a role in transcription factor-mediated activation. PMID:12756230

  20. Impact of initial and boundary conditions on regional winter climate over the Western Himalayas: A fixed domain size experiment

    NASA Astrophysics Data System (ADS)

    Maharana, P.; Dimri, A. P.

    2014-03-01

    The Western Himalayas during winter receives precipitation due to the eastward moving low pressure synoptic weather systems, called Western Disturbances (WDs) in Indian meteorological parlance. The complex Himalayan topography, sparse observational data, less understanding of physical processes, etc. form many interesting research questions over this region. One of the important research goals is to study the change in the winter (Dec., Jan. and Feb. - DJF) climate over the Himalayas. In the presented study with modelling efforts having varying initial and boundary conditions (ICBC) with same model physics option is attempted to provide a comment on important physical processes pertaining to precipitation and temperature fields. A 22 year (1980-2001) simulation with Regional Climate Model version 3 (RegCM3) forced with National Centre for Environmental Prediction/National Centre for Atmospheric Research (NCEP/NCAR) reanalysis 1 (NNRP1), NCEP/NCAR reanalysis 2 (NNRP2) and European Centre for Medium Range Weather Forecast 40 Year reanalysis (ERA40) as three different ICBC is carried out. The present study focuses on the winter climatology of the main meteorological parameters viz., temperature, precipitation and snow depth and interannual variability of winter seasonal precipitation. The model shows overestimation of seasonal average precipitation and underestimation of seasonal average temperature fields over the Western Himalayas in all the three model simulations. The interannual variability of precipitation and temperature over this region is nicely captured by the model. The model simulation with NNRP2 as the ICBC shows more realistic results. In addition the ensemble mean of the three simulations has shown improved results and is closer to the abovementioned simulation. Precipitation bias explained in terms of the higher vertical integrated moisture flux and transport shows strong convergence zone over and along the southern rim of the Indian Himalayas. The

  1. Structural and functional division into two domains of the large (100- to 115-kDa) chains of the clathrin-associated protein complex AP-2.

    PubMed Central

    Kirchhausen, T; Nathanson, K L; Matsui, W; Vaisberg, A; Chow, E P; Burne, C; Keen, J H; Davis, A E

    1989-01-01

    The clathrin-associated protein complex 2 (AP-2 complex) is a group of proteins associated with clathrin-coated vesicles and believed to interact with cytoplasmic domains of receptors found in the plasma membrane. AP-2 was purified as an assembly of several polypeptide chains (alpha, beta, AP50, and AP17), of which only the alpha and beta chains (100-115 kDa) show significant heterogeneity. We have obtained cDNA clones for two distinct rat brain beta chains. We have also studied the domain organization of bovine brain AP-2 complexes by selective proteolysis. Results of these studies show that the alpha and beta chains have a similar two-domain organization. Their amino-terminal domains are relatively invariant whereas their carboxyl-terminal domains are variable in both sequence and length. We propose that the variable domains select receptors for inclusion in coated vesicles. Images PMID:2495531

  2. Large Earthquakes in Low-Strain Regions of Central Asia, Mongolia, and Iran

    NASA Astrophysics Data System (ADS)

    Landgraf, A.

    2014-12-01

    Although often characterized by an apparent low level of seismicity, areas of low-strain accumulation are subjected to considerable seismic and associated natural hazards. However, we are often unaware of these hazards, because in contrast to active plate boundaries, recurrence intervals of ground-rupturing earthquakes are typically on the order of thousands of years. Geodetic or seismicity records may thus not yet reflect full seismic cycles. Low-strain regions may occur in stable continental interiors or tectonically active intracontinental mountain belts, which often comprise areas of spatially disparate reverse and strike-slip faulting, up to thousands of kilometers away from plate boundaries. These regions may be shortened at rates on the order of centimeters per year, with no clear spatiotemporal pattern of seismicity, and single fault-slip rates may attain less than one to a few millimeters per year. The Kyrgyz and Kazakh Tien Shan, the Mongolian Hangay or the Iranian Alborz mountains are prime examples that share these characteristics. These regions are located along the northern rim of the ongoing Indian-Eurasian or Arabian-Eurasian collision, but are hundreds of kilometers away from the corresponding plate boundaries. Historical earthquakes M > 7 are known from the Alborz mountains and several events with M > 8 are known from the northern Tien Shan and Mongolia - all with poorly constrained recurrence rates. We review our ongoing tectonic studies of these areas, which differ in faulting mechanisms, the preservation potential of primary and secondary rupture evidence, and the level of population density and value concentrations. We use paleoseismic trenching, geomorphic and terrestrial LiDAR data analysis, and geochronology to gain insights into the complex deformation processes that govern these areas to better understand how present-day deformation is accommodated in areally extensive deformation zones in continental interiors.

  3. Large-scale sea level, thermocline, and wind variations in the Indonesian throughflow region

    NASA Astrophysics Data System (ADS)

    Bray, Nancy A.; Hautala, Susan; Chong, Jackson; Pariwono, John

    1996-05-01

    The Indonesian throughflow is presumed to be driven by a sea level gradient from the Pacific to the Indian Ocean. Deep throughflow transport may also be driven by a steric gradient between the two basins. The sea level gradient, in turn, is thought to be maintained by the differing wind patterns in the two basins: monsoonal in the Indian Ocean and trades in the western equatorial Pacific. In the interaction between sea level, wind stress, and thermocline depth as identified from historical measurements, we find (1) over the Indian, Indonesian, and equatorial Pacific basins and specifically within the throughflow region, sea level, and thermocline seasonal variations are negatively correlated (sea level rise corresponding to thermocline deepening) and sea level and meridional wind stress are also correlated; (2) the expected strong seasonal gradients in sea level through the eastern throughflow region (near the island of Timor) are found, though without an accompanying thermocline depth gradient; (3) seasonal convergence in baroclinic, upper ocean throughflow transport previously identified [Meyers et al., 1995] in the Timor Sea is associated with changes in sea level as well as upper ocean dynamic height at annual period but not at semiannual; (4) interannual variability explains more of the sea level variance in the eastern throughflow region than is explained by seasonal harmonics; however, there does not appear to be a strong interannual signal in the sea level gradient to drive fluctuations in the upper ocean throughflow. We hypothesize that seasonal variability in the upper layer throughflow and interannual variability in the deep throughflow are the predominant results of the complex interaction of forcing mechanisms.

  4. Large-scale shear velocity structure of the upper mantle beneath Europe and surrounding regions

    NASA Astrophysics Data System (ADS)

    Legendre, C. P.; Meier, T. M.; Lebedev, S.; Friederich, W.

    2009-12-01

    The automated multimode waveform inversion technique developed by Lebedev et al. (2005) was applied to available data of broadband stations in Europe and surrounding regions. It performs a fitting of the complete waveform starting from the S-wave onset to the surface wave. Assuming the location and focal mechanism of a considered earthquake as known, the first basic step is to consider each available seismogram separately and to find the 1D-model that can explain the filtered seismogram best. In a second step, each 1D-model serves as a linear constraint in an inversion for a 3D S-wave velocity model of the upper mantle. We collected data for the years from 1990 to 2006 from all permanent stations for which data were available via the data centers of ORFEUS, GEOFON amd IRIS, and from others that build the Virtual European Seismological Network (VEBSN). In addition, we incorporated data from temporary experiments like SVEKALAPKO, TOR and the Eifel plume project as well as permanent stations in France. Just recently we were also able to add the data recorded by the temporary broadband EGELADOS network in the southern Aegean. In this way, a huge data set of about 500000 seismograms came about from which about 60000 1D-models could be constructed. The resulting models exhibit an overwhelming structural detail in relation to the size of the region considered in the inversion. They are to our knowledge the most detailed models of shear wave velocity currently available for the European upper mantle and surroundings. Most prominent features are an extremely sharp demarcation of the East European platform from Western Europe. Narrow high velocity regions follow the Hellenic arc and the Ionian trench toward the north. Whereas high velocities are found beneath the western Alps between about 100 km to 200 km depth, the eastern Alps show a low velocity anomaly at these depths. Low velocity zones are found at depths around 150 km in the Pannonian basin, the back-arc of the

  5. Observation of artificial spread-F and large region ionization enhancement in an HF heating experiment at HAARP

    NASA Astrophysics Data System (ADS)

    Kuo, Spencer; Snyder, Arnold

    2010-04-01

    A large-scale ionospheric modification by HF heaters was explored via HAARP digisonde operated in a fast mode. The results show that the ionogram virtual heights and the height spread of the ordinary-wave sounding echoes were changed significantly by the O-mode heater; the X-mode heater imposed no noticeable effect on the ionograms. The enhanced virtual height spread exceeds 40 km, more than 15% of sounding echo's average virtual height. The heater downshifted/upshifted the virtual height in the low/high frequency region around the heater frequency by as much as 15 and 7.5 km. The modifications were developing to last more than 10 seconds after the heater was turned off. The perturbed ionosphere took more than 60 seconds to recover. The modified electron density distribution indicates that the electron density and temperature increases exceed 10% and 25% over a large altitude region (>30 Km) from below to above the HF reflection height.

  6. VERY LARGE ARRAY H I ZEEMAN OBSERVATIONS OF THE CYGNUS X REGION: DR 22 AND ON 2

    SciTech Connect

    Mayo, E. A.; Troland, T. H. E-mail: troland@pa.uky.edu

    2012-02-15

    We have used the Very Large Array to study the Zeeman effect in 21 cm H I absorption lines from two star-forming regions in the Cygnus X complex, DR 22 and ON 2. We measure the line-of-sight magnetic field toward these regions, finding B{sub los} = -84 {+-} 11 {mu}G toward the DR 22 H II region and B{sub los} < 50 {mu}G toward each of the two H II regions in ON 2. We interpret these results in terms of two different models. In one model, we assume that the H I Zeeman effect is a measure of magnetic fields in the associated molecular clouds. If so, then the DR 22 molecular cloud is magnetically subcritical, that is, magnetically dominated. The ON 2 molecular clouds are magnetically supercritical. In a second model, we assume that the H I Zeeman effect is a measure of magnetic fields in photon-dominated regions where the gas has been compressed (and the field amplified) by absorption of stellar radiation. We find that this second model, where the measured field strength has been affected by star formation, accounts well for the DR 22 H I Zeeman effect. This same model, however, overpredicts the magnetic field in ON 2. ON 2 may be a region where the magnetic field is energetically insignificant or where the field happens to lie nearly in the plane of the sky.

  7. Large magnitude change of water isotope influence by various factors over the Tibetan Plateau region

    NASA Astrophysics Data System (ADS)

    Tian, L.; Yao, T.; Yu, W.

    2010-12-01

    Paleoclimate and paleoenvironment have been rebuilt from isotopic record of ice cores, tree rings, lacustrine sediments, stalagmite and paleo-soil proxy records etc. This reconstruction method is based upon an established acceptance of relationship between present precipitation stable isotopes with one single climatic parameter, mostly air temperature. However, as hydrogen and oxygen isotopes are in the hydrological cycle, any other changes in atmosphere circulation and hydrological conditions also impact the water isotopic composition. The acknowledgment that parameters besides air temperature, affect water isotope composition is especially crucial when considering a long term geological time scale in which atmospheric circulation may not have been constant. Based on the present monitoring results of oxygen isotopes in precipitation, lake water, and glacial ice on the Tibetan Plateau region, we present here a list of the parameters that can result in significant water isotope variations, including seasonal change of precipitation, altitudinal effect, moisture source changes, long-term change of precipitation isotopes and land surface processes. Conclusions show that all these factors can result in 5-11‰ variations in water δ18O, significant enough to distort the paleo-records. Thus, particularly when considering extended geological timescales, it is crucial to consider all factors that affect stable water isotopes before establishing the true paleo-climate and paleo-environment in the Tibetan Plateau region.

  8. A search for variable white dwarfs in large-area time-domain surveys: a pilot study in SDSS Stripe 82

    NASA Astrophysics Data System (ADS)

    Gentile Fusillo, Nicola Pietro; Hermes, J. J.; Gänsicke, Boris T.

    2016-01-01

    We present a method to reliably select variable white dwarfs from large-area time-domain surveys and apply this method in a pilot study to search for pulsating white dwarfs in the Sloan Digital Sky Survey Stripe 82. From a sample 400 high-confidence white dwarf candidates, we identify 24 which show significant variability in their multi-epoch Stripe 82 data. Using colours, we further selected a sample of pulsating white dwarf (ZZ Ceti) candidates and obtained high-cadence follow-up for six targets. We confirm five of our candidates as cool ZZ Cetis, three of which are new discoveries. Among our 24 candidates we also identify: one eclipsing binary, two magnetic white dwarfs and one pulsating PG1159 star. Finally, we discuss the possible causes for the variability detected in the remaining targets. Even with sparse multi-epoch data over the limited area of Stripe 82, we demonstrate that our selection method can successfully identify various types of variable white dwarfs and efficiently select high-confidence ZZ Ceti candidates.

  9. Functional and topological characteristics of mammalian regulatory domains

    PubMed Central

    Symmons, Orsolya; Uslu, Veli Vural; Tsujimura, Taro; Ruf, Sandra; Nassari, Sonya; Schwarzer, Wibke; Ettwiller, Laurence; Spitz, François

    2014-01-01

    Long-range regulatory interactions play an important role in shaping gene-expression programs. However, the genomic features that organize these activities are still poorly characterized. We conducted a large operational analysis to chart the distribution of gene regulatory activities along the mouse genome, using hundreds of insertions of a regulatory sensor. We found that enhancers distribute their activities along broad regions and not in a gene-centric manner, defining large regulatory domains. Remarkably, these domains correlate strongly with the recently described TADs, which partition the genome into distinct self-interacting blocks. Different features, including specific repeats and CTCF-binding sites, correlate with the transition zones separating regulatory domains, and may help to further organize promiscuously distributed regulatory influences within large domains. These findings support a model of genomic organization where TADs confine regulatory activities to specific but large regulatory domains, contributing to the establishment of specific gene expression profiles. PMID:24398455

  10. Acquisition of electroencephalographic data in a large regional hospital - Bringing the brain waves to the computer.

    NASA Technical Reports Server (NTRS)

    Low, M. D.; Baker, M.; Ferguson, R.; Frost, J. D., Jr.

    1972-01-01

    This paper describes a complete electroencephalographic acquisition and transmission system, designed to meet the needs of a large hospital with multiple critical care patient monitoring units. The system provides rapid and prolonged access to a centralized recording and computing area from remote locations within the hospital complex, and from locations in other hospitals and other cities. The system includes quick-on electrode caps, amplifier units and cable transmission for access from within the hospital, and EEG digitization and telephone transmission for access from other hospitals or cities.

  11. No evidence of unusually large postseismic deformation in Andaman region immediately after 2004 Sumatra-Andaman earthquake

    NASA Astrophysics Data System (ADS)

    Gahalaut, V. K.; Catherine, J. K.; Jade, Sridevi; Gireesh, R.; Gupta, D. C.; Narsaiah, M.; Ambikapathy, A.; Bansal, A.; Chadha, R. K.

    2008-05-01

    Static offsets due to the 26 December 2004 Sumatra-Andaman earthquake have been reported from the campaign mode GPS measurements in the Andaman-Nicobar region. However, these measurements contain contributions from postseismic deformation that must have occurred in the 16-25 days period between the earthquake and the measurements. We analyse these and tide gauge measurements of coseismic deformation, a longer time series of postseismic deformation from GPS measurements at Port Blair in the South Andaman and aftershocks, to suggest that postseismic displacement not larger than 7 cm occurred in the 16-25 days following the earthquake in the South Andaman and probably elsewhere in the Andaman Nicobar region. Earlier, this contribution was estimated to be as large as 1 m in the Andaman region, which implied that the magnitude of the earthquake based on these campaign mode measurements should be decreased. We suggest an Mw for this earthquake as 9.23.

  12. Multiplicity distributions in the forward rapidity region in proton-proton collisions at the Large Hadron Collider

    NASA Astrophysics Data System (ADS)

    Ghosh, Premomoy; Muhuri, Sanjib

    2013-05-01

    Measured multiplicity distributions of primary charged particles produced in the forward rapidity region of the proton-proton (pp) collisions at the center-of-mass energy, s=7TeV, at the LHC have been analyzed in terms of the negative binomial distribution function. Like the multiplicity distributions in the midrapidity region for the pp collisions at s=7TeV, the distributions for the minimum bias events in the forward region are also better described with the superposition of two negative binomail distributions, as proposed by a two-component model of particle production from two processes, the soft and the hard. However, the multiplicity distribution for the “hard-QCD” events in a large pseudorapidity window does not oblige the two-component model.

  13. Prediction of monthly rainfall on homogeneous monsoon regions of India based on large scale circulation patterns using Genetic Programming

    NASA Astrophysics Data System (ADS)

    Kashid, Satishkumar S.; Maity, Rajib

    2012-08-01

    SummaryPrediction of Indian Summer Monsoon Rainfall (ISMR) is of vital importance for Indian economy, and it has been remained a great challenge for hydro-meteorologists due to inherent complexities in the climatic systems. The Large-scale atmospheric circulation patterns from tropical Pacific Ocean (ENSO) and those from tropical Indian Ocean (EQUINOO) are established to influence the Indian Summer Monsoon Rainfall. The information of these two large scale atmospheric circulation patterns in terms of their indices is used to model the complex relationship between Indian Summer Monsoon Rainfall and the ENSO as well as EQUINOO indices. However, extracting the signal from such large-scale indices for modeling such complex systems is significantly difficult. Rainfall predictions have been done for 'All India' as one unit, as well as for five 'homogeneous monsoon regions of India', defined by Indian Institute of Tropical Meteorology. Recent 'Artificial Intelligence' tool 'Genetic Programming' (GP) has been employed for modeling such problem. The Genetic Programming approach is found to capture the complex relationship between the monthly Indian Summer Monsoon Rainfall and large scale atmospheric circulation pattern indices - ENSO and EQUINOO. Research findings of this study indicate that GP-derived monthly rainfall forecasting models, that use large-scale atmospheric circulation information are successful in prediction of All India Summer Monsoon Rainfall with correlation coefficient as good as 0.866, which may appears attractive for such a complex system. A separate analysis is carried out for All India Summer Monsoon rainfall for India as one unit, and five homogeneous monsoon regions, based on ENSO and EQUINOO indices of months of March, April and May only, performed at end of month of May. In this case, All India Summer Monsoon Rainfall could be predicted with 0.70 as correlation coefficient with somewhat lesser Correlation Coefficient (C.C.) values for different

  14. Large systematic trend difference between national and regional homogenized datasets and global collections

    NASA Astrophysics Data System (ADS)

    Venema, Victor

    2016-04-01

    The global land temperature trend may be biased due to remaining inhomogeneities. Well-homogenized national datasets on average clearly show more warming than global collections when averaged over the region of common coverage. For this study we have collected a dataset with more than 40 national and regional average monthly temperature series (called "national" from now on). National datasets can be better homogenized than global ones. More data is available at national weather services to serve as a reference in the detection and correction of breaks. More stations and knowledge of the local climatology can help in selecting better references that are expected to have the same climate signal. More metadata is available nationally on network-wide breaks and to determine the right date of the statistically detected breaks. Furthermore, better homogenization methods are available for regional networks. Here we compare these national datasets to the global collections BEST, CRUCY, CRUTEM4, GHCNv3 and GISS. For all datasets the country average series have been computed. A subset of 10 well-homogenized national datasets shows a clearly stronger temperature trend, which is several tenths of a degree Celsius per century larger and mostly statistically significant. These differences are seen for the entire period between 1800 and now. The differences are smallest for CRUTEM4 and CRUCY, which include homogenized data from many of our national datasets. The differences are largest for BEST and GISS. GHCN represents a middle case. We are working on better understanding these differences by comparing all datasets, which range from raw data to data homogenized by various methods and which use a range of different methods to compute the national average. We look for relationships between the methods used for homogenization and averaging and the trend differences. In an accompanying poster, we i) review the literature on trend uncertainties due to remaining inhomogeneities, ii

  15. Large-scale shear velocity structure of the upper mantle beneath Europe and surrounding regions

    NASA Astrophysics Data System (ADS)

    Legendre, Cédric; Meier, Thomas; Lebedev, Sergei; Friederich, Wolfgang; Egelados Working Group

    2010-05-01

    The automated multimode waveform inversion technique developed by Lebedev et al. (2005) was applied to available data of broadband stations in Europe and surrounding regions. It performs a fitting of the complete waveform starting from the S-wave onset to the surface wave. Assuming the location and focal mechanism of a considered earthquake as known, the first basic step is to consider each available seismogram separately and to find the velocity perturbations that can explain the filtered seismogram best. In a second step, each velocity perturbations serves as a linear constraint in an inversion for a 3D S-wave velocity model of the upper mantle. We collected data for the years from 1990 to 2006 from all permanent stations for which data were available via the data centers of ORFEUS, GEOFON and IRIS, and from others that build the Virtual European Seismological Network (VEBSN). In addition, we incorporated data from temporary experiments like SVEKALAPKO, TOR and the Eifel plume project as well as permanent stations in France. Just recently we were also able to add the data recorded by the temporary broadband EGELADOS network in the southern Aegean. In this way, a huge data set of about 500000 seismograms came about from which about 60000 1D-models could be constructed. The resulting models exhibit an overwhelming structural detail in relation to the size of the region considered in the inversion. They are to our knowledge the most detailed models of shear wave velocity currently available for the European upper mantle and surroundings. Most prominent features are an extremely sharp demarcation of the East European platform from Western Europe. Narrow high velocity regions follow the Hellenic arc and the Ionian trench toward the north. Whereas high velocities are found beneath the western Alps between about 100 km to 200 km depth, the eastern Alps show a low velocity anomaly at these depths. Low velocity zones are found at depths around 150 km in the Pannonian

  16. Seismological Segmentation of Halmahera Thrust, Molucca Sea Region, based on Large Earthquake Sequences

    NASA Astrophysics Data System (ADS)

    Shiddiqi, H. A.; Widiyantoro, S.; Nugraha, A. D.; Ramdhan, M.; Wiyono, S. H.; Wandono, W.

    2015-12-01

    The Molucca Sea region in eastern Indonesia is a complex tectonic region, where the arc-arc collision between the Sangihe and Halmahera arcs takes place. Two recent largest earthquakes occurred in this area are Mw 7.5, January 2007, and Mw 7.2, November 2014, that occurred 90 km to the north from the 2007 earthquake site. Both earthquakes occurred along the Halmahera thrust, however, the aftershock of the two events occurred in separated parts of the same fault. In this study, we aim to investigate the segmentation of the seismogenic zone in Molucca Sea by using seismological analysis. We employed teleseismic double-difference relocation using P- and S-wave arrival times from the Meteorological, Climatological, and Geophysical Agency of Indonesia (BMKG) and the International Seismological Centre (ISC) catalog. We used a 3D velocity model for the Indonesian region. Our relocation result revealed that aftershocks of the two events did not overlap each other. Although they have similar focal mechanisms with NNE-SSW direction, the aftershock patterns were different. While the 2014 event aftershock distribution is consistent with the strike direction inferred from the focal mechanism, the 2007 event aftershocks occurred in NEE-SWW direction. Furthermore we analyzed the spatial variation in b-value for different time ranges. The b-value analysis also showed two separated segments of low b-value anomaly around both events for each time range. We envisage that stress regime directions and geometries of the fault are different for both aftershock clusters. For this reason we analyzed focal mechanism data and found that fault segment around the 2014 event is steeper than that related to the 2007 event. We applied focal mechanism inversion to obtain the direction of stress and fault orientation, and found different stress directions for the two segments. While the northern part segment has maximum stress with SSE direction, the stress in the southern part is rotated in SE

  17. Captured segment exchange: a strategy for custom engineering large genomic regions in Drosophila melanogaster.

    PubMed

    Bateman, Jack R; Palopoli, Michael F; Dale, Sarah T; Stauffer, Jennifer E; Shah, Anita L; Johnson, Justine E; Walsh, Conor W; Flaten, Hanna; Parsons, Christine M

    2013-02-01

    Site-specific recombinases (SSRs) are valuable tools for manipulating genomes. In Drosophila, thousands of transgenic insertions carrying SSR recognition sites have been distributed throughout the genome by several large-scale projects. Here we describe a method with the potential to use these insertions to make custom alterations to the Drosophila genome in vivo. Specifically, by employing recombineering techniques and a dual recombinase-mediated cassette exchange strategy based on the phiC31 integrase and FLP recombinase, we show that a large genomic segment that lies between two SSR recognition-site insertions can be "captured" as a target cassette and exchanged for a sequence that was engineered in bacterial cells. We demonstrate this approach by targeting a 50-kb segment spanning the tsh gene, replacing the existing segment with corresponding recombineered sequences through simple and efficient manipulations. Given the high density of SSR recognition-site insertions in Drosophila, our method affords a straightforward and highly efficient approach to explore gene function in situ for a substantial portion of the Drosophila genome. PMID:23150604

  18. Understanding recharge elasticity through large-scale simulations of Europe's karst regions under varying climatic boundary conditions

    NASA Astrophysics Data System (ADS)

    Hartmann, Andreas; Gleeson, Tom; Wagener, Thorsten

    2014-05-01

    Karst develops through the dissolution of carbonate rock. Karst groundwater in Europe is a major source of fresh water contributing up to half of the total drinking water supply in some countries. Climate model projections suggest that in the next 100 years, European karst regions will experience a strong increase in temperature and a serious decrease of precipitation - especially in the Mediterranean region. To be prepared, policy-makers need quantitative and reliable estimates of potential changes to karst water resources. This study presents an attempt to quantify karst water resources over the whole Mediterranean. This is done by quantifying large-scale karst recharge with a newly developed hydrologic model that considers the strong heterogeneities of recharge processes that evolve from carbonate rock dissolution. The model is driven by long-term gridded data from the European Climate Assessment & Dataset project (ECA&D). Soil moisture and evapotranspiration measurements that are available across Europe's carbonate rock regions are used for model evaluation. To assess the climatic sensitivity of recharge, we define the recharge elasticity as ratio of normalized changes of annual recharge to precipitation between years. Using large-scale simulations of the recharge model we can explore the spatial and temporal variability of the recharge elasticity among the Mediterranean's karst regions and understand the impact climatic change.

  19. Downscaling large-scale climate variability using a regional climate model: the case of ENSO over Southern Africa

    NASA Astrophysics Data System (ADS)

    Boulard, Damien; Pohl, Benjamin; Crétat, Julien; Vigaud, Nicolas; Pham-Xuan, Thanh

    2013-03-01

    This study documents methodological issues arising when downscaling modes of large-scale atmospheric variability with a regional climate model, over a remote region that is yet under their influence. The retained case study is El Niño Southern Oscillation and its impacts on Southern Africa and the South West Indian Ocean. Regional simulations are performed with WRF model, driven laterally by ERA40 reanalyses over the 1971-1998 period. We document the sensitivity of simulated climate variability to the model physics, the constraint of relaxing the model solutions towards reanalyses, the size of the relaxation buffer zone towards the lateral forcings and the forcing fields through ERA-Interim driven simulations. The model's internal variability is quantified using 15-member ensemble simulations for seasons of interest, single 30-year integrations appearing as inappropriate to investigate the simulated interannual variability properly. The incidence of SST prescription is also assessed through additional integrations using a simple ocean mixed-layer model. Results show a limited skill of the model to reproduce the seasonal droughts associated with El Niño conditions. The model deficiencies are found to result from biased atmospheric forcings and/or biased response to these forcings, whatever the physical package retained. In contrast, regional SST forcing over adjacent oceans favor realistic rainfall anomalies over the continent, although their amplitude remains too weak. These results confirm the significant contribution of nearby ocean SST to the regional effects of ENSO, but also illustrate that regionalizing large-scale climate variability can be a demanding exercise.

  20. Large regional differences in incidence of arthroscopic meniscal procedures in the public and private sector in Denmark

    PubMed Central

    Hare, Kristoffer Borbjerg; Vinther, Jesper Høeg; Lohmander, L Stefan; Thorlund, Jonas Bloch

    2015-01-01

    Objectives A recent study reported a large increase in the number of meniscal procedures from 2000 to 2011 in Denmark. We examined the nation-wide distribution of meniscal procedures performed in the private and public sector in Denmark since different incentives may be present and the use of these procedures may differ from region to region. Setting We included data on all patients who underwent an arthroscopic meniscal procedure performed in the public or private sector in Denmark. Participants Data were retrieved from the Danish National Patient Register on patients who underwent arthroscopic meniscus surgery as a primary or secondary procedure in the years 2000 to 2011. Hospital identification codes enabled linkage of performed procedures to specific hospitals. Primary and secondary outcome measures Yearly incidence of meniscal procedures per 100 000 inhabitants was calculated with 95% CIs for public and private procedures for each region. Results Incidence of meniscal procedures increased at private and at public hospitals. The private sector accounted for the largest relative and absolute increase, rising from an incidence of 1 in 2000 to 98 in 2011. In 2011, the incidence of meniscal procedures was three times higher in the Capital Region than in Region Zealand. Conclusions Our study identified a large increase in the use of meniscal procedures in the public and private sector in Denmark. The increase was particularly conspicuous in the private sector as its proportion of procedures performed increased from 1% to 32%. Substantial regional differences were present in the incidence and trend over time of meniscal procedures. PMID:25712820

  1. Binding of heparin by type III domains and peptides from the carboxy terminal hep-2 region of fibronectin.

    PubMed

    Ingham, K C; Brew, S A; Migliorini, M M; Busby, T F

    1993-11-23

    The major sites of heparin binding by fibronectin are located in fragments of 30 or 40 kDa that contain type III modules 12 through 14 or 15. Various proteolytic or recombinant subfragments and several synthetic peptides derived from this region have been compared with respect to their binding to fluorescein-labeled heparin in solution. Binding was monitored by the change in fluorescence anisotropy at 25 degrees C and pH 7.4 in 0.02 M Tris buffer, alone (TB) or with 0.15M NaCl (TBS). A 23-kDa fragment containing III13 and III14 but lacking III12 had Kd values of 0.3 and 1.8 microM in TB, and TBS, respectively, indistinguishable from the 30-kDa parent. Fragments containing only module III13 bound 2-3-fold weaker than the parent while those containing only III14 bound 6-50-fold weaker depending on the ionic strength. Fragments containing only III12 or III15 failed to bind at all in TBS. A cationic peptide derived from the amino terminus of III13 and containing the Arg-Arg-Ala-Arg consensus sequence, whose integrity was shown by Barkalow and Schwarzbauer [Barkalow, F. J., & Schwarzbauer, J. E. (1991) J. Biol. Chem. 266, 7812-7818] to be critical, failed to bind in TBS but bound weakly in TB. Two additional cationic peptides derived from the middle and C-terminal regions of III14 showed similar behavior. Thus while the major determinant(s) of heparin binding are located in III13, those determinants are only active when part of a properly folded structure. Furthermore, module III13 when isolated had a slightly lower affinity than fragments containing both III13 and III14.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8241146

  2. The Pliny-Strabo trench region: A large shear zone resulting from slab tearing

    NASA Astrophysics Data System (ADS)

    Özbakır, Ali D.; Şengör, A. M. C.; Wortel, M. J. R.; Govers, R.

    2013-08-01

    The eastern part of the Hellenic subduction zone is composed of the Pliny and Strabo "trenches" that have been regarded as a zone of convergence between the subducting African lithosphere and the overriding Anatolian-Aegean plate. In the Pliny and Strabo "trenches", the oblique relative plate motion is generally thought to be accommodated by a typical strain partitioning consisting of strike-slip and convergence components. Notwithstanding the occurrence of strike-slip motion parallel with the Pliny-Strabo "trenches", trench-normal thrusting is not observed so far. Therefore, we conducted a detailed analysis to investigate the deformation mechanisms of the eastern part of the Hellenic Trench system. Our analyses of offshore faulting and mechanisms of earthquakes in the overriding Aegean lithosphere show that the region of the Pliny and Strabo "trenches" obeys the mechanics of the sinistral shear zone model of Tchalenko (1970). We propose that the trench perpendicular convergence is taken up by the Rhodes fold and thrust belt, which has been postulated off the southeast coast of Rhodes. Several regional P-wave tomography results give indications of a slow seismic anomaly under this zone, which is interpreted as a tear between the Hellenic and Cyprus subduction zones. The primary reason for such tear and its propagation is the ongoing rollback of the subducted part of the African lithosphere, also referred to as "the Aegean slab". Our work elucidates the surface expression of this tearing process in the form of the development of a shear zone between the Aegean lithosphere in the NW and the African lithosphere in the SE, the Pliny-Strabo Shear Zone.

  3. Identification of the minimal region in lipase ABC transporter recognition domain of Pseudomonas fluorescens for secretion and fluorescence of green fluorescent protein

    PubMed Central

    2012-01-01

    Background TliA is a thermostable lipase secreted by the type 1 secretion system (T1SS) of Pseudomonas fluorescens. The secretion is promoted by its secretion/chaperone domain located near the C-terminus, which is composed mainly of four Repeat-in-Toxin (RTX) repeats. In order to identify the minimal region of TliA responsible for its secretion, five different copies of the secretion/chaperone domain, each involving truncated N-terminal residues and a common C-terminus, were acquired and named as lipase ABC transporter recognition domains (LARDs). Each LARD was fused to epidermal growth factor (EGF) or green fluorescent protein (GFP), and the secretion of EGF-LARD or GFP-LARD fusion proteins was assessed in Escherichia coli with ABC transporter. Results Among the fusion proteins, GFP or EGF with 105-residue LARD3 was most efficiently secreted. In addition, GFP-LARD3 emitted wild type GFP fluorescence. Structurally, LARD3 had the 4 RTX repeats exposed at the N-terminus, while other LARDs had additional residues prior to them or missed some of the RTX repeats. LARD3 was both necessary and sufficient for efficient secretion and maintenance of GFP fluorescence in E. coli, which was also confirmed in P. fluorescens and P. fluorescens ▵tliA, a knock-out mutant of tliA. Conclusion LARD3 was a potent secretion signal in T1SS for its fusion flanking RTX motif, which enhanced secretion and preserved the fluorescence of GFP. LARD3-mediated secretion in E. coli or P. fluorescens will enable the development of enhanced protein manufacturing factory and recombinant microbe secreting protein of interest in situ. PMID:22578275

  4. Engineered CH2 domains (nanoantibodies).

    PubMed

    Dimitrov, Dimiter S

    2009-01-01

    Currently, almost all FDA approved therapeutic antibodies (except ReoPro, Lucentis and Cimzia which are Fabs), and the vast majority of those in clinical trials are full-size antibodies mostly in IgG1 format of about 150 kDa size. A fundamental problem for such large molecules is their poor penetration into tissues (e.g., solid tumors) and poor or absent binding to regions on the surface of some molecules (e.g., on the HIV envelope glycoprotein) which are fully accessible only by molecules of smaller size. Therefore, much work especially during the last decade has been aimed at developing novel scaffolds of much smaller size and high stability. Here I briefly describe a proposition to use the immunoglobulin (Ig) constant CH2 domain (CH3 for IgE and IgM) as a scaffold. CH2 is critical for the Ig effector functions. Isolated CH2 is stable monomer in contrast to all other constant domains and most of the variable domains. CH2 and engineered CH2 domains with improved stability can be used as scaffolds for construction of libraries containing diverse binders to various antigens. Such binders based on a CH2 scaffold could also confer some effector functions. Because the CH2 domains are the smallest independently folded antibody domains that can be engineered to contain simultaneously antigen-binding sites and binding sites mediating effector and stability functions, and to distinguish them from domain antibodies which are used to denote engineered VH or VL domains or nanobodies which are used to denote camelid VHH, I termed them nanoantibodies (nAbs). PMID:20046570

  5. Expression and T cell recognition of hybrid antigens with amino-terminal domains encoded by Qa-2 region of major histocompatibility complex and carboxyl termini of transplantation antigens.

    PubMed

    Stroynowski, I; Forman, J; Goodenow, R S; Schiffer, S G; McMillan, M; Sharrow, S O; Sachs, D H; Hood, L

    1985-05-01

    Coding potential of the Q6 gene from the Qa-2a region of BALB/c Crgl mice was analyzed by a combination of hybrid class I gene construction and DNA-mediated gene transfer. Recombinant genes were created by exon shuffling of the 5' coding region of the Q6 gene and the 3' coding region of a gene encoding a transplantation antigen (Kd, Dd, or Ld), or the inverse. Some of these hybrid class I genes were expressed in the transfected mouse fibroblasts (L cells). The hybrid class I molecules encoded by the 5' end of the Q6 gene and the 3' end of the Ld gene precipitated as 45,000 mol wt molecules associated with beta 2-microglobulin. The expression of the hybrid proteins indicates that 926 basepairs of the 5' flanking region upstream of the structural Q6 gene contain a promoter that functions as a transcription initiation site in L cells. The 3' portion of the Q6 gene appears to be responsible for the lack of cell surface expression of the intact Q6 and the hybrid Ld/Q6 genes in mouse fibroblasts. Accordingly, this portion of the Q6 class I gene may play a regulatory role in tissue-specific expression. Serological analyses of hybrid Q6 proteins suggested that Q6 may be a structural gene for CR (H-2 crossreactive) antigen found normally on subpopulations of lymphocytes. If this identification is correct, Q6 gene will define a new category of class I genes encoding approximately 40,000 mol wt molecules and carrying a characteristic truncated cytoplasmic tail. Analysis of L cells transfected with Q6 hybrid genes demonstrated also that the cytotoxic T cells specific for Qa-2a region-coded antigens recognize the amino-terminal alpha 1-alpha 2 domain of Q6 fusion products. This recognition can be blocked by anti-Qa-2a alloantiserum and monoclonal antibodies reactive with the alpha 3-beta 2-microglobulin portion of the Q6 hybrids. We propose that the structural requirements for the anti-Qa-2a cytotoxic T lymphocyte-specific epitopes on target molecules are the same as for anti

  6. Rotation of the Large-Scale Solar Magnetic Fields in the Equatorial Region

    NASA Astrophysics Data System (ADS)

    Latushko, S.

    1996-07-01

    A study is made of the rotation of large-scale magnetic fields using the synoptic maps from the Kitt Peak National Observatory for the time interval 1976 1985. The auto-correlation method and the mass-centers method of magnetic structures was applied to infer mean differential rotation profiles and rotation profiles separately for each magnetic field polarity. It has been found that in both hemispheres the leading polarity rotates faster than the following polarity at all latitudes by about 0.04° day-1. The maximum rotation rate of the leading polarity is reached at about 6° latitude. In the mean profile for both polarities, this brings about two angular velocity maxima at 6° latitudes in both hemispheres. Such a profile appears as to have a ‘dimple’ on the equator.

  7. Regional Expansion of Minimally Invasive Surgery for Hysterectomy: Implementation and Methodology in a Large Multispecialty Group

    PubMed Central

    Andryjowicz, Esteban; Wray, Teresa

    2011-01-01

    Introduction: Approximately 600,000 hysterectomies are performed in the US each year, making hysterectomy the second most common major operation performed in women. Several methods can be used to perform this procedure. In 2009, a Cochrane Review concluded “that vaginal hysterectomy should be performed in preference to abdominal hysterectomy, where possible. Where vaginal hysterectomy is not possible, a laparoscopic approach may avoid the need for an abdominal hysterectomy. Risks and benefits of different approaches may however be influenced by the surgeon's experience. More research is needed, particularly to examine the long-term effects of the different types of surgery.” This article reviews the steps that a large multispecialty group used to teach non-open hysterectomy methods to improve the quality of care for their patients and to decrease the number of inpatient procedures and therefore costs. The percentages of each type of hysterectomy performed yearly between 2005 and 2010 were calculated, as well as the length of stay (LOS) for each method. Methods: A structured educational intervention with both didactic and hands-on exercises was created and rolled out to 12 medical centers. All patients undergoing hysterectomy for benign conditions through the Southern California Permanente Medical Group (a large multispecialty group that provides medical care to Kaiser Permanente patients in Southern California) between 2005 and 2010 were included. This amounted to 26,055 hysterectomies for benign conditions being performed by more than 350 obstetrician/gynecologists (Ob/Gyns). Results: More than 300 Ob/Gyns took the course across 12 medical centers. On the basis of hospital discharge data, the total number of hysterectomies, types of hysterectomies, and LOS for each type were identified for each year. Between 2005 and 2010, the rate of non-open hysterectomies has increased 120% (from 38% to 78%) and the average LOS has decreased 31%. PMID:22319415

  8. A refined regional modeling approach for the Corn Belt - Experiences and recommendations for large-scale integrated modeling

    NASA Astrophysics Data System (ADS)

    Panagopoulos, Yiannis; Gassman, Philip W.; Jha, Manoj K.; Kling, Catherine L.; Campbell, Todd; Srinivasan, Raghavan; White, Michael; Arnold, Jeffrey G.

    2015-05-01

    Nonpoint source pollution from agriculture is the main source of nitrogen and phosphorus in the stream systems of the Corn Belt region in the Midwestern US. This region is comprised of two large river basins, the intensely row-cropped Upper Mississippi River Basin (UMRB) and Ohio-Tennessee River Basin (OTRB), which are considered the key contributing areas for the Northern Gulf of Mexico hypoxic zone according to the US Environmental Protection Agency. Thus, in this area it is of utmost importance to ensure that intensive agriculture for food, feed and biofuel production can coexist with a healthy water environment. To address these objectives within a river basin management context, an integrated modeling system has been constructed with the hydrologic Soil and Water Assessment Tool (SWAT) model, capable of estimating river basin responses to alternative cropping and/or management strategies. To improve modeling performance compared to previous studies and provide a spatially detailed basis for scenario development, this SWAT Corn Belt application incorporates a greatly refined subwatershed structure based on 12-digit hydrologic units or 'subwatersheds' as defined by the US Geological Service. The model setup, calibration and validation are time-demanding and challenging tasks for these large systems, given the scale intensive data requirements, and the need to ensure the reliability of flow and pollutant load predictions at multiple locations. Thus, the objectives of this study are both to comprehensively describe this large-scale modeling approach, providing estimates of pollution and crop production in the region as well as to present strengths and weaknesses of integrated modeling at such a large scale along with how it can be improved on the basis of the current modeling structure and results. The predictions were based on a semi-automatic hydrologic calibration approach for large-scale and spatially detailed modeling studies, with the use of the Sequential

  9. Mutations in the nucleotide binding domain 1 signature motif region rescue processing and functional defects of cystic fibrosis transmembrane conductance regulator delta f508.

    PubMed

    DeCarvalho, Ana C V; Gansheroff, Lisa J; Teem, John L

    2002-09-27

    The gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR), an ATP binding cassette (ABC) transporter that functions as a phosphorylation- and nucleotide-regulated chloride channel, is mutated in cystic fibrosis (CF) patients. Deletion of a phenylalanine at amino acid position 508 (DeltaF508) in the first nucleotide binding domain (NBD1) is the most prevalent CF-causing mutation and results in defective protein processing and reduced CFTR function, leading to chloride impermeability in CF epithelia and heterologous systems. Using a STE6/CFTRDeltaF508 chimera system in yeast, we isolated two novel DeltaF508 revertant mutations, I539T and G550E, proximal to and within the conserved ABC signature motif of NBD1, respectively. Western blot and functional analysis in mammalian cells indicate that mutations I539T and G550E each partially rescue the CFTRDeltaF508 defect. Furthermore, a combination of both revertant mutations resulted in a 38-fold increase in CFTRDeltaF508-mediated chloride current, representing 29% of wild type channel activity. The G550E mutation increased the sensitivity of CFTRDeltaF508 and wild type CFTR to activation by cAMP agonists and blocked the enhancement of CFTRDeltaF508 channel activity by 2 mm 3-isobutyl-1-methylxanthine. The data show that the DeltaF508 defect can be significantly rescued by second-site mutations in the nucleotide binding domain 1 region, that includes the LSGGQ consensus motif. PMID:12110684

  10. Identification of a region within the ErbB2/HER2 intracellular domain that is necessary for ligand-independent association.

    PubMed

    Penuel, Elicia; Akita, Robert W; Sliwkowski, Mark X

    2002-08-01

    Ligand-independent ErbB2 activation occurs principally by two distinct mechanisms: overexpression and mutation. Overexpression of ErbB2 at the plasma membrane drives receptor self-association in a concentration-dependent manner, which in turn leads to constitutive receptor activation. Subsets of human breast cancers contain a molecular alteration that leads to erbB2 gene amplification and subsequent protein overexpression. Although not recognized to occur in human cancers, mutation can also lead to increased ErbB2 association. A well characterized mutant of the rodent ortholog neu involves substitution of glutamate for valine within the transmembrane domain. In each case, a number of explanations have been proposed to explain the resulting ErbB2 activation. These include stabilization of receptor oligomers, release of negative constraints, and altered receptor conformations. Here we define a short amino acid segment comprising amino acids 966-968 in the intracellular domain that seemingly disrupts receptor-receptor association that is driven either by overexpression or mutation in the transmembrane region. Because of the hydrophobic nature of these amino acids (VVI), we propose that alteration of this segment likely results in a global conformational change in an area that has been proposed previously to be a dimerization motif for ErbB homomeric association. PMID:12000754

  11. A Third-Order Item Response Theory Model for Modeling the Effects of Domains and Subdomains in Large-Scale Educational Assessment Surveys

    ERIC Educational Resources Information Center

    Rijmen, Frank; Jeon, Minjeong; von Davier, Matthias; Rabe-Hesketh, Sophia

    2014-01-01

    Second-order item response theory models have been used for assessments consisting of several domains, such as content areas. We extend the second-order model to a third-order model for assessments that include subdomains nested in domains. Using a graphical model framework, it is shown how the model does not suffer from the curse of…

  12. AHM1, a novel type of nuclear matrix-localized, MAR binding protein with a single AT hook and a J domain-homologous region.

    PubMed

    Morisawa, G; Han-Yama, A; Moda, I; Tamai, A; Iwabuchi, M; Meshi, T

    2000-10-01

    Interactions between the nuclear matrix and special regions of chromosomal DNA called matrix attachment regions (MARs) have been implicated in various nuclear functions. We have identified a novel protein from wheat, AT hook-containing MAR binding protein1 (AHM1), that binds preferentially to MARs. A multidomain protein, AHM1 has the special combination of a J domain-homologous region and a Zn finger-like motif (a J-Z array) and an AT hook. For MAR binding, the AT hook at the C terminus was essential, and an internal portion containing the Zn finger-like motif was additionally required in vivo. AHM1 was found in the nuclear matrix fraction and was localized in the nucleoplasm. AHM1 fused to green fluorescent protein had a speckled distribution pattern inside the nucleus. AHM1 is most likely a nuclear matrix component that functions between intranuclear framework and MARs. J-Z arrays can be found in a group of (hypothetical) proteins in plants, which may share some functions, presumably to recruit specific Hsp70 partners as co-chaperones. PMID:11041885

  13. Anti-NMDA Receptor Encephalitis Antibody Binding Is Dependent on Amino Acid Identity of a Small Region Within the GluN1 Amino Terminal Domain

    PubMed Central

    Gleichman, Amy J.; Spruce, Lynn A.; Dalmau, Josep; Seeholzer, Steven H.; Lynch, David R.

    2012-01-01

    Anti-NMDA receptor (NMDAR) encephalitis is a newly identified autoimmune disorder that targets NMDARs, causing severe neurological symptoms including hallucinations, psychosis, and seizures, and may result in death (Dalmau et al., 2008). However, the exact epitope to which these antibodies bind is unknown. A clearly defined antigenic region could provide more precise testing, allow for comparison of immunogenicity between patients to explore potential clinically relevant variations, elucidate the functional effects of antibodies, and make patients’ antibodies a more effective tool with which to study NMDAR function. Here, we use human cerebrospinal fluid to explore the antigenic region of the NMDAR. We created a series of mutants within the amino terminal domain of GluN1 that change patient antibody binding in transfected cells in stereotyped ways. These mutants demonstrate that the N368/G369 region of GluN1 is crucial for the creation of immunoreactivity. Mass spectrometry experiments show that N368 is glycosylated in transfected cells and rat brain regions; however, this glycosylation is not directly required for epitope formation. Mutations of residues N368/G369 change the closed time of the receptor in single channel recordings; more frequent channel openings correlates with the degree of antibody staining, and acute antibody exposure prolongs open time of the receptor. The staining pattern of mutant receptors is similar across subgroups of patients, indicating consistent immunogenicity, although we have identified one region that has a variable role in epitope formation. These findings provide tools for detailed comparison of antibodies across patients and suggest an interaction between antibody binding and channel function. PMID:22875940

  14. Large-scale traveling ionospheric disturbances observed using GPS receivers over high-latitude and equatorial regions

    NASA Astrophysics Data System (ADS)

    Idrus, Intan Izafina; Abdullah, Mardina; Hasbi, Alina Marie; Husin, Asnawi; Yatim, Baharuddin

    2013-09-01

    This paper presents the first results of large-scale traveling ionospheric disturbances (LSTIDs) observation during two moderate magnetic storm events on 28 May 2011 (SYM-H∼ -94 nT and Dst∼-80 nT) and 6 August 2011 (SYM-H∼-126 nT and Dst∼-113 nT) over the high-latitude region in Russia, Sweden, Norway, Iceland and Greenland and equatorial region in the Peninsular Malaysia using vertical total electron content (VTEC) from the Global Positioning System (GPS) observations measurement. The propagation of the LSTID signatures in the GPS TEC measurements over Peninsular Malaysia was also investigated using VTEC map. The LSTIDs were found to propagate both equatorward and poleward directions during these two events. The results showed that the LSTIDs propagated faster at high-latitude region with an average phase velocity of 1074.91 m/s than Peninsular Malaysia with an average phase velocity of 604.84 m/s. The LSTIDs at the high-latitude region have average periods of 150 min whereas the ones observed over Peninsular Malaysia have average periods of 115 min. The occurrences of these LSTIDs were also found to be the subsequent effects of substorm activities in the auroral region. To our knowledge, this is the first result of observation of LSTIDs over Peninsular Malaysia during the 24th solar cycle.

  15. Complex regional pain syndrome: evidence for warm and cold subtypes in a large prospective clinical sample.

    PubMed

    Bruehl, Stephen; Maihöfner, Christian; Stanton-Hicks, Michael; Perez, Roberto S G M; Vatine, Jean-Jacques; Brunner, Florian; Birklein, Frank; Schlereth, Tanja; Mackey, Sean; Mailis-Gagnon, Angela; Livshitz, Anatoly; Harden, R Norman

    2016-08-01

    Limited research suggests that there may be Warm complex regional pain syndrome (CRPS) and Cold CRPS subtypes, with inflammatory mechanisms contributing most strongly to the former. This study for the first time used an unbiased statistical pattern recognition technique to evaluate whether distinct Warm vs Cold CRPS subtypes can be discerned in the clinical population. An international, multisite study was conducted using standardized procedures to evaluate signs and symptoms in 152 patients with clinical CRPS at baseline, with 3-month follow-up evaluations in 112 of these patients. Two-step cluster analysis using automated cluster selection identified a 2-cluster solution as optimal. Results revealed a Warm CRPS patient cluster characterized by a warm, red, edematous, and sweaty extremity and a Cold CRPS patient cluster characterized by a cold, blue, and less edematous extremity. Median pain duration was significantly (P < 0.001) shorter in the Warm CRPS (4.7 months) than in the Cold CRPS subtype (20 months), with pain intensity comparable. A derived total inflammatory score was significantly (P < 0.001) elevated in the Warm CRPS group (compared with Cold CRPS) at baseline but diminished significantly (P < 0.001) over the follow-up period, whereas this score did not diminish in the Cold CRPS group (time × subtype interaction: P < 0.001). Results support the existence of a Warm CRPS subtype common in patients with acute (<6 months) CRPS and a relatively distinct Cold CRPS subtype most common in chronic CRPS. The pattern of clinical features suggests that inflammatory mechanisms contribute most prominently to the Warm CRPS subtype but that these mechanisms diminish substantially during the first year postinjury. PMID:27023422

  16. Selection for Unequal Densities of Sigma70 Promoter-like Signalsin Different Regions of Large Bacterial Genomes

    SciTech Connect

    Huerta, Araceli M.; Francino, M. Pilar; Morett, Enrique; Collado-Vides, Julio

    2006-03-01

    distribution of promoter-like signals between regulatory and nonregulatory regions detected in large bacterial genomes confers a significant, although small, fitness advantage. This study paves the way for further identification of the specific types of selective constraints that affect the organization of regulatory regions and the overall distribution of promoter-like signals through more detailed comparative analyses among closely-related bacterial genomes.

  17. Regional structure and kinematic history of a large subduction back thrust: Taranaki Fault, New Zealand

    NASA Astrophysics Data System (ADS)

    Stagpoole, V.; Nicol, A.

    2008-01-01

    The Taranaki Fault is a back thrust antithetic to the Hikurangi margin subduction thrust. Subduction back thrusts, like the Taranaki Fault, accrue displacement transferred from the subducting plate, and growth analyses of these structures contribute to an improved understanding of subduction processes. The Taranaki Fault forms the eastern margin of the Taranaki Basin and is part of a system that extends for at least 600 km in continental crust of western New Zealand. The fault is preserved beneath young sedimentary cover and provides a rare opportunity to investigate the geometry and kinematic history of a large subduction back thrust. Two-dimensional seismic reflection lines (2-5 km spacing), tied to recently drilled wells and outcrop, together with magnetotelluric and gravity models are used to examine the fault. These data indicate that the fault is thick skinned with dips of 25-45° to depths of at least 12 km. The fault accommodated at least 12-15 km of dip-slip displacement since the middle Eocene (circa 40-43 Ma). The northern tip of the active section of the fault stepped southward at least three times between the middle Eocene and early Pliocene, producing a total tip retreat of 400-450 km. The history of displacements on the Taranaki Fault is consistent with initiation of Hikurangi margin subduction during the middle Eocene, up to 20 Ma earlier than some previous estimates. Fault tip retreat may have been generated by clockwise rotation of the subduction margin and associated progressive isolation of the fault from the driving downgoing Pacific Plate.

  18. Influence of Large-scale Climate Modes on Atmospheric Rivers That Drive Regional Precipitation Extremes

    NASA Astrophysics Data System (ADS)

    Guan, B.; Molotch, N. P.; Waliser, D. E.; Fetzer, E. J.; Neiman, P. J.

    2014-12-01

    Atmospheric rivers (ARs) are narrow channels of enhanced meridional water vapor transport between the tropics and extratropics that drive precipitation extremes in the west coast areas of North America and other continents. The influence of large-scale climate modes on ARs is analyzed in terms of modulation on AR frequency and AR-related snow water equivalent (SWE) anomalies, with a focus on understanding the causes of the anomalously snowy winter season of 2010/2011 in California's Sierra Nevada. Mean SWE on 1 April 2011 was ~70% above normal averaged over 100 snow sensors. AR occurrence was anomalously high during the season, with 20 AR dates from November to March and 14 dates in the month of December 2010, compared to the mean occurrence of 9 dates per season. Most of the season's ARs occurred during negative phases of the Arctic Oscillation (AO) and the Pacific-North American (PNA) teleconnection pattern. Analysis of all winter ARs in California during water years 1998-2011 indicates more ARs occur during the negative phase of AO and PNA, with the increase between positive and negative phases being ~90% for AO, and ~50% for PNA. The circulation pattern associated with concurrent negative phases of AO and PNA, characterized by cyclonic anomalies centered northwest of California, provides a favorable dynamical condition for ARs. The analysis suggests that the massive Sierra Nevada snowpack during the 2010/2011 winter season is primarily related to anomalously high frequency of ARs favored by the joint phasing of -AO and -PNA, and that a secondary contribution is from increased snow accumulation during these ARs favored by colder air temperatures associated with -AO, -PNA and La Niña. The results have implications for subseasonal-to-seasonal predictability of AR activities and related weather and water extremes.

  19. Large-scale atmospheric response to eastern Mediterranean summer-autumn SST anomalies and the associated regional impact

    NASA Astrophysics Data System (ADS)

    García-Serrano, J.; Polo, I.; Rodríguez-Fonseca, B.; Losada, T.

    2013-11-01

    Since the Mediterranean Sea is halfway between subtropical and middle latitudes, and it represents a marginal oceanic region, research has tended to focus on how large-scale modes of atmospheric variability modulate its surface temperature. Conversely, the present study examines the potential influence of the Mediterranean Sea surface temperature (SST) anomalies on the Northern Hemisphere atmospheric circulation. In particular, this work explores the large-scale changes in the global circulation forced/influenced by the eastern Mediterranean summer-autumn SST pattern. To isolate the atmospheric response, AGCM sensitivity experiments with prescribed SST over the Mediterranean Sea and climatology elsewhere are analysed. Observational diagnostics upon the period used to define the boundary conditions (1979-2002) are also interpreted. Our results support the hypothesis of an atmospheric pattern initiated in the Mediterranean basin, pointing out both a local baroclinic response and a barotropic circumglobal anomaly. This atmospheric teleconnection pattern projects onto a hemispheric wave-like structure, reflecting the waveguide effect of the westerly jets. Results suggest, thereby, that the recurrent summer-autumn circumglobal teleconnection pattern can be excited locally by changes in the atmosphere over the Mediterranean region. A linear behaviour is found upon a regional impact over northeastern Africa. The remote impacts present however a nonlinear signature: anomalous warm conditions influencing on northern Europe and Euro-Asia, whereas anomalous cold conditions impacting more on the North Pacific basin. Limitations in our model setup are also discussed.