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. 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

  14. 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.

  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. 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.

  15. 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

  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. 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.

  1. 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

  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. 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.

  18. 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).

  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. 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.

  7. 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

  8. 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

  9. 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

  10. 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

  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. 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.

  2. 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

  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. 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

  9. 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.

  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. 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.

  15. 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

  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

    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

  2. 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

  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 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

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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

  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

    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.

  2. 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.

  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. 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

  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. 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

  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. 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

  2. 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

  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

    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 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

  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

    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.

  2. 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.

  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. 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

  6. 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

  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. 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.

  9. 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.

  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