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Sample records for large regional domain

  1. Putative Domain-Domain Interactions in the Vesicular Stomatitis Virus L Polymerase Protein Appendage Region

    PubMed Central

    Ruedas, John B.

    2014-01-01

    ABSTRACT The multidomain polymerase protein (L) of nonsegmented negative-strand (NNS) RNA viruses catalyzes transcription and replication of the virus genome. The N-terminal half of the protein forms a ring-like polymerase structure, while the C-terminal half encoding viral mRNA transcript modifications consists of a flexible appendage with three distinct globular domains. To gain insight into putative transient interactions between L domains during viral RNA synthesis, we exchanged each of the four distinct regions encompassing the appendage region of vesicular stomatitis virus (VSV) Indiana serotype L protein with their counterparts from VSV New Jersey and analyzed effects on virus polymerase activity in a minigenome system. The methyltransferase domain exchange yielded a fully active polymerase protein, which functioned as well as wild-type L in the context of a recombinant virus. Exchange of the downstream C-terminal nonconserved region abolished activity, but coexchanging it with the methyltransferase domain generated a polymerase favoring replicase over transcriptase activity, providing strong evidence of interaction between these two regions. Exchange of the capping enzyme domain or the adjacent nonconserved region thought to function as an “unstructured” linker also abrogated polymerase activity even when either domain was coexchanged with other appendage domains. Further probing of the putative linker segment using in-frame enhanced green fluorescent protein (EGFP) insertions similarly abrogated activity. We discuss the implications of these findings with regard to L protein appendage domain structure and putative domain-domain interactions required for polymerase function. IMPORTANCE NNS viruses include many well-known human pathogens (e.g., rabies, measles, and Ebola viruses), as well as emerging viral threats (e.g., Nipah and Hendra viruses). These viruses all encode a large L polymerase protein similarly organized into multiple domains that work in

  2. 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.

  3. 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.

  4. Observation of large nematic domains of discotic liquid crystals

    NASA Astrophysics Data System (ADS)

    Shinde, Abhijeet; Wang, Xuezhen; Cheng, Zhengdong

    2015-03-01

    Discotic liquid crystals are commonly found in nature in the form of clay, nacre. They are technologically important in applications such as conductive polymers, semiconductors and photovoltaics. Size and its distribution play an important role in their self-assemblies. Here we observed large nematic domains of discotic liquid crystals grown on a time scale of months. The development of such domains is observed to be faster for nanodisks that relatively smaller in size. The orientation of nanodisks is affected by gravity and inter-particle interactions which are yet to be fully understood.

  5. 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.

  6. Frequency domain multiplexing for large-scale bolometer arrays

    SciTech Connect

    Spieler, Helmuth

    2002-05-31

    The development of planar fabrication techniques for superconducting transition-edge sensors has brought large-scale arrays of 1000 pixels or more to the realm of practicality. This raises the problem of reading out a large number of sensors with a tractable number of connections. A possible solution is frequency-domain multiplexing. I summarize basic principles, present various circuit topologies, and discuss design trade-offs, noise performance, cross-talk and dynamic range. The design of a practical device and its readout system is described with a discussion of fabrication issues, practical limits and future prospects.

  7. 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.

  8. Visualizing large geospatial datasets with KML Regions

    NASA Astrophysics Data System (ADS)

    Ilyushchenko, S.; Wheeler, D.; Ummel, K.; Hammer, D.; Kraft, R.

    2008-12-01

    Regions are a powerful KML feature that helps viewing very large datasets in Google Earth without sacrificing performance. Data is loaded and drawn only when it falls within the user's view and occupies a certain portion of the screen. Using Regions, it is possible to supply separate levels of detail for the data, so that fine details are loaded only when the data fills a portion of the screen that is large enough for the details to be visible. It becomes easy to create compelling interactive presentations of geospatial datasets that are meaningful at both large and small scale. We present two example datasets: worldwide past, present and future carbon dioxide emissions by power plants provided by Carbon Monitoring for Action, Center for Global Development (http://carma.org), as well as 2007 US bridge safety ratings from Federal Highway Administration (http://www.fhwa.dot.gov/BRIDGE/nbi/ascii.cfm).

  9. 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.

  10. 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.

  11. 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

  12. Large organized surface domains self-assembled from nonpolar amphiphiles.

    PubMed

    Krafft, Marie Pierre

    2012-04-17

    For years, researchers had presumed that Langmuir monolayers of small C(n)F(2n+1)C(m)H(2m+1) (FnHm) diblock molecules (such as F8H16) consisted of continuous, featureless films. Recently we have discovered that they instead form ordered arrays of unusually large (~30-60 nm), discrete self-assembled surface domains or hemimicelles both at the surface of water and on solid substrates. These surface micelles differ in several essential ways from all previously reported or predicted molecular surface aggregates. They self-assemble spontaneously, even at zero surface pressure, depending solely on a critical surface concentration. They are very large (~100 times the length of the diblock) and involve thousands of molecules (orders of magnitude more than classical micelles). At the same time, the surface micelles are highly monodisperse and self-organize in close-packed hexagonal patterns (two-dimensional crystals). Their size is essentially independent from pressure, and they do not coalesce and are unexpectedly sturdy for soft matter (persisting even beyond surface film collapse). We and other researchers have observed large surface micelles for numerous diblocks, using Langmuir-Blodgett (LB) transfer, spin-coating and dip-coating techniques, or expulsion from mixed monolayers, and on diverse supports, establishing that hemimicelle formation and ordering are intrinsic properties of (perfluoroalkyl)alkanes. Notably, they involve "incomplete" surfactants with limited amphiphilic character, which further illustrates the outstanding capacity for perfluoroalkyl chains to promote self-assembly and interfacial film structuring. Using X-ray reflectivity, we determined a perfluoroalkyl-chain-up orientation. Theoretical investigations assigned self-assembly and hemimicelle stability to electrostatic dipole-dipole interactions at the interface between Fn- and Hm-sublayers. Grazing-incidence small-angle X-ray scattering (GISAXS) data collected directly on the surface of water

  13. 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

  14. 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. PMID:27570571

  15. Host cell proteins binding to domain IV of the 5' noncoding region of poliovirus RNA.

    PubMed Central

    Blyn, L B; Chen, R; Semler, B L; Ehrenfeld, E

    1995-01-01

    Translation of poliovirus RNA occurs by the binding of ribosomes to an internal segment of RNA sequence within the 5' untranslated region of the viral RNA. This region is predicted to consist of six domains (I to VI) that possess complex secondary and tertiary structures. Domain IV is a large region in which alterations in the sequence or structure markedly reduce translational efficiency. In this study, we employed RNA mobility shift assays to demonstrate that a protein(s) from uninfected HeLa cell extracts, as well as from neuroblastoma extracts, interacts with the domain IV structure. A mutation in domain IV caused reduced binding of HeLa cell proteins and reduced translation both in vitro and in vivo, suggesting that the binding of at least one of these proteins plays a role in the mechanism of viral translation. UV cross-linking indicated that a protein(s) with a size of approximately 40 kDa interacted directly with the RNA. Using streptavidin beads to capture biotinylated RNA bound to proteins, we were able to visualize a number of HeLa and neuroblastoma cell proteins that interact with domain IV. These proteins have molecular masses of approximately 39, approximately 40, and approximately 42 kDa. PMID:7769700

  16. 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.

  17. 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.

  18. 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.

  19. Unassisted translocation of large polypeptide domains across phospholipid bilayers.

    PubMed

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

    2006-12-01

    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.

  20. 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.

  1. 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.

  2. 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.

  3. Characterization of Arctic Highly Magnetic Domains - the Geophysical Expression of Inferred Large Igneous Province(s)

    NASA Astrophysics Data System (ADS)

    Saltus, R. W.; Oakey, G.; Miller, E. L.; Jackson, R.

    2012-12-01

    The magnetic anomalies of the high arctic are dominated by a large domain (1000 x 1700 km; the High Arctic Magnetic High, HAMH) consisting of numerous high-amplitude magnetic high ridges with a complex set of orientations and by other smaller, but still fundamentally highly magnetic, domains. The magnetic potential anomaly field (also known as pseudogravity) of the HAMH shows a single large intensity high and underscores the crustal-scale thickness of this geophysical feature (which also forms a prominent anomaly on satellite magnetic maps). The seafloor morphology of this region includes the complex linear trends of the Alpha and Mendeleev ridges, but the magnetic expression of this domain extends beyond the complex bathymetry to include areas where Canada Basin sediments have covered the complex basement topography. The calculated magnetic effect of the bathymetric ridges matches some of the observed magnetic anomalies, but not others. We have analyzed and modeled the distinctive HAMH and other smaller magnetic high domains to generate estimates of their volume and to characterize the directionality of their component features. Complimentary processing and modeling of high arctic gravity anomalies allows characterization of the density component of these geophysical features. Spatially, the HAMH encompasses the Alpha and Mendeleev "ridges," that are considered to represent a major mafic igneous province. The term "Alpha-Mendeleev Large Igneous Province" is given to a domain mapped by tracing magnetic anomalies in a recent map published by AAPG (Grantz and others, 2009). On this map the province is described as "alkali basalt with ages between 120 and 90 Ma". New seismic and bathymetric data, collected as part of on-going research efforts for definition of extended continental shelf, are revealing new details about the Alpha ridge. One interesting development is the possible identification of a supervolcano that may represent a major locus of igneous activity. In

  4. 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

  5. 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.

  6. 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

  7. 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.

  8. 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

  9. 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.

  10. Structure of the entire stalk region of the Dynein motor domain.

    PubMed

    Nishikawa, Yosuke; Oyama, Takuji; Kamiya, Narutoshi; Kon, Takahide; Toyoshima, Yoko Y; Nakamura, Haruki; Kurisu, Genji

    2014-09-23

    Dyneins are large microtubule-based motor complexes that power a range of cellular processes including the transport of organelles, as well as the beating of cilia and flagella. The motor domain is located within the dynein heavy chain and comprises an N-terminal mechanical linker element, a central ring of six AAA+ modules of which four bind or hydrolyze ATP, and a long stalk extending from the AAA+ring with a microtubule-binding domain (MTBD) at its tip. A crucial mechanism underlying the motile activity of cytoskeletal motor proteins is precise coupling between the ATPase and track-binding activities. In dynein, a stalk region consisting of a long (~15nm) antiparallel coiled coil separates these two activities, which must facilitate communication between them. This communication is mediated by a small degree of helix sliding in the coiled coil. However, no high-resolution structure is available of the entire stalk region including the MTBD. Here, we have reported the structure of the entire stalk region of mouse cytoplasmic dynein in a weak microtubule-binding state, which was determined using X-ray crystallography, and have compared it with the dynein motor domain from Dictyostelium discoideum in a strong microtubule-binding state and with a mouse MTBD with its distal portion of the coiled coil fused to seryl-tRNA synthetase from Thermus thermophilus. Our results strongly support the helix-sliding model based on the complete structure of the dynein stalk with a different form of coiled-coil packing. We also propose a plausible mechanism of helix sliding together with further analysis using molecular dynamics simulations. Our results present the importance of conserved proline residues for an elastic motion of stalk coiled coil and imply the manner of change between high-affinity state and low-affinity state of MTBD.

  11. 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.

  12. 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.

  13. Investigating the Role of Large-Scale Domain Dynamics in Protein-Protein Interactions

    PubMed Central

    Delaforge, Elise; Milles, Sigrid; Huang, Jie-rong; Bouvier, Denis; Jensen, Malene Ringkjøbing; Sattler, Michael; Hart, Darren J.; Blackledge, Martin

    2016-01-01

    Intrinsically disordered linkers provide multi-domain proteins with degrees of conformational freedom that are often essential for function. These highly dynamic assemblies represent a significant fraction of all proteomes, and deciphering the physical basis of their interactions represents a considerable challenge. Here we describe the difficulties associated with mapping the large-scale domain dynamics and describe two recent examples where solution state methods, in particular NMR spectroscopy, are used to investigate conformational exchange on very different timescales. PMID:27679800

  14. Investigating the Role of Large-Scale Domain Dynamics in Protein-Protein Interactions.

    PubMed

    Delaforge, Elise; Milles, Sigrid; Huang, Jie-Rong; Bouvier, Denis; Jensen, Malene Ringkjøbing; Sattler, Michael; Hart, Darren J; Blackledge, Martin

    2016-01-01

    Intrinsically disordered linkers provide multi-domain proteins with degrees of conformational freedom that are often essential for function. These highly dynamic assemblies represent a significant fraction of all proteomes, and deciphering the physical basis of their interactions represents a considerable challenge. Here we describe the difficulties associated with mapping the large-scale domain dynamics and describe two recent examples where solution state methods, in particular NMR spectroscopy, are used to investigate conformational exchange on very different timescales. PMID:27679800

  15. Investigating the Role of Large-Scale Domain Dynamics in Protein-Protein Interactions

    PubMed Central

    Delaforge, Elise; Milles, Sigrid; Huang, Jie-rong; Bouvier, Denis; Jensen, Malene Ringkjøbing; Sattler, Michael; Hart, Darren J.; Blackledge, Martin

    2016-01-01

    Intrinsically disordered linkers provide multi-domain proteins with degrees of conformational freedom that are often essential for function. These highly dynamic assemblies represent a significant fraction of all proteomes, and deciphering the physical basis of their interactions represents a considerable challenge. Here we describe the difficulties associated with mapping the large-scale domain dynamics and describe two recent examples where solution state methods, in particular NMR spectroscopy, are used to investigate conformational exchange on very different timescales.

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

    PubMed

    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

    2015-05-01

    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.

  17. 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.

  18. Broad domain generality in focal regions of frontal and parietal cortex

    PubMed Central

    Fedorenko, Evelina; Duncan, John; Kanwisher, Nancy

    2013-01-01

    Unlike brain regions that respond selectively to specific kinds of information content, a number of frontal and parietal regions are thought to be domain- and process-general: that is, active during a wide variety of demanding cognitive tasks. However, most previous evidence for this functional generality in humans comes from methods that overestimate activation overlap across tasks. Here we present functional MRI evidence from single-subject analyses for broad functional generality of a specific set of brain regions: the same sets of voxels are engaged across tasks ranging from arithmetic to storing information in working memory, to inhibiting irrelevant information. These regions have a specific topography, often lying directly adjacent to domain-specific regions. Thus, in addition to domain-specific brain regions tailored to solve particular problems of longstanding importance to our species, the human brain also contains a set of functionally general regions that plausibly endow us with the cognitive flexibility necessary to solve novel problems. PMID:24062451

  19. The oncogenic BRD4-NUT chromatin regulator drives aberrant transcription within large topological domains

    PubMed Central

    Alekseyenko, Artyom A.; Walsh, Erica M.; Wang, Xin; Grayson, Adlai R.; Hsi, Peter T.; Kharchenko, Peter V.; Kuroda, Mitzi I.; French, Christopher A.

    2015-01-01

    NUT midline carcinoma (NMC), a subtype of squamous cell cancer, is one of the most aggressive human solid malignancies known. NMC is driven by the creation of a translocation oncoprotein, BRD4-NUT, which blocks differentiation and drives growth of NMC cells. BRD4-NUT forms distinctive nuclear foci in patient tumors, which we found correlate with ∼100 unprecedented, hyperacetylated expanses of chromatin that reach up to 2 Mb in size. These “megadomains” appear to be the result of aberrant, feed-forward loops of acetylation and binding of acetylated histones that drive transcription of underlying DNA in NMC patient cells and naïve cells induced to express BRD4-NUT. Megadomain locations are typically cell lineage-specific; however, the cMYC and TP63 regions are targeted in all NMCs tested and play functional roles in tumor growth. Megadomains appear to originate from select pre-existing enhancers that progressively broaden but are ultimately delimited by topologically associating domain (TAD) boundaries. Therefore, our findings establish a basis for understanding the powerful role played by large-scale chromatin organization in normal and aberrant lineage-specific gene transcription. PMID:26220994

  20. 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

  1. 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...

  2. 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

  3. First Frequency-Domain Interferometry Observations of Large-Scale Vertical Motion in the Atmosphere.

    NASA Astrophysics Data System (ADS)

    Muschinski, Andreas; Chilson, Phillip B.; Kern, Stefan; Nielinger, Jost; Schmidt, Gerhard; Prenosil, Thomas

    1999-05-01

    The spatiotemporal distribution of the vertical velocity at synoptic and subsynoptic scales is key to the patterns of weather and climate on earth. On these scales, the vertical velocity is on the order of one to a few centimeters per second, typically about three orders of magnitude smaller than typical horizontal wind velocities. Because of the smallness of large-scale vertical velocities relative to typical horizontal velocities, a direct observation of the large-scale vertical air velocity is extremely difficult.In a case study on observational material obtained during a 68-h experiment using the SOUSY very high frequency (VHF) radar in the Harz Mountains in Germany, the authors present the first intercomparison between three different sources of physical information that can provide large-scale vertical wind velocities: (i) the Doppler shifts observed with a vertically pointing VHF radar; (ii) the rates of change of the altitudes of refractive-index discontinuities as identified with frequency-domain interferometry (FDI), which is still a relatively unexplored technique in meteorology; and (iii) the output of a regional numerical weather prediction model (NWPM), which has been set up to model the meteorological situation during the observational period.There are several phenomena that have been known to possibly cause significant biases in mean vertical velocities retrieved from the Doppler shifts measured with vertically pointing clear-air VHF radars: (i) stationary or nonstationary gravity waves with vertical-velocity amplitudes up to the order of 1 m s1; (ii) stationary or horizontally advected tilted refractive-index discontinuities that are aspect sensitive in the VHF regime; and (iii) a correlation between the radar-reflectivity fluctuations and the vertical-velocity fluctuations within a vertically propagating gravity wave.On the basis of an intercomparison between the vertical velocities retrieved from (i) `standard Doppler' VHF radar observations, (ii

  4. Free-decay time-domain modal identification for large space structures

    NASA Technical Reports Server (NTRS)

    Kim, Hyoung M.; Vanhorn, David A.; Doiron, Harold H.

    1992-01-01

    Concept definition studies for the Modal Identification Experiment (MIE), a proposed space flight experiment for the Space Station Freedom (SSF), have demonstrated advantages and compatibility of free-decay time-domain modal identification techniques with the on-orbit operational constraints of large space structures. Since practical experience with modal identification using actual free-decay responses of large space structures is very limited, several numerical and test data reduction studies were conducted. Major issues and solutions were addressed, including closely-spaced modes, wide frequency range of interest, data acquisition errors, sampling delay, excitation limitations, nonlinearities, and unknown disturbances during free-decay data acquisition. The data processing strategies developed in these studies were applied to numerical simulations of the MIE, test data from a deployable truss, and launch vehicle flight data. Results of these studies indicate free-decay time-domain modal identification methods can provide accurate modal parameters necessary to characterize the structural dynamics of large space structures.

  5. All Three Variable Regions of the TRIM5α B30.2 Domain Can Contribute to the Specificity of Retrovirus Restriction

    PubMed Central

    Ohkura, Sadayuki; Yap, Melvyn W.; Sheldon, Tom; Stoye, Jonathan P.

    2006-01-01

    Recent studies have revealed the contribution of TRIM5α to retrovirus restriction in cells from a variety of primate species. TRIM5α consists of a tripartite motif (the RBCC domain) followed by a B30.2 domain. The B30.2 domain is thought to be involved in determination of restriction specificity and contains three variable regions. To investigate the relationship between the phylogeny of primate TRIM5α and retrovirus restriction specificity, a series of chimeric TRIM5α consisting of the human RBCC domain followed by the B30.2 domain from various primates was constructed. These constructs showed restriction profiles largely consistent with the origin of the B30.2 domain. Restriction specificity was further investigated with a variety of TRIM5αs containing mixed or mutated B30.2 domains. This study revealed the importance of all three variable regions for determining restriction specificity. Based on the molecular structures of other PRYSPRY domains solved recently, a model for the molecular structure of the B30.2 domain of TRIM5α was developed. The model revealed that the variable regions of the B30.2 domain are present as loops located on one side of the B30.2 core structure. It is hypothesized that these three loops form a binding surface for virus and that evolutionary changes in any one of the loops can alter restriction specificity. PMID:16912305

  6. Crystal structure of a conserved domain in the intermembrane space region of the plastid division protein ARC6.

    PubMed

    Kumar, Nitin; Radhakrishnan, Abhijith; Su, Chih-Chia; Osteryoung, Katherine W; Yu, Edward W

    2016-02-01

    The chloroplast division machinery is composed of numerous proteins that assemble as a large complex to divide double-membraned chloroplasts through binary fission. A key mediator of division-complex formation is ARC6, a chloroplast inner envelope protein and evolutionary descendant of the cyanobacterial cell division protein Ftn2. ARC6 connects stromal and cytosolic contractile rings across the two membranes through interaction with an outer envelope protein within the intermembrane space (IMS). The ARC6 IMS region bears a structurally uncharacterized domain of unknown function, DUF4101, that is highly conserved among ARC6 and Ftn2 proteins. Here we report the crystal structure of this domain from Arabidopsis thaliana ARC6. The domain forms an α/β barrel open towards the outer envelope membrane but closed towards the inner envelope membrane. These findings provide new clues into how ARC6 and its homologs contribute to chloroplast and cyanobacterial cell division.

  7. Crystal structure of a conserved domain in the intermembrane space region of the plastid division protein ARC6.

    PubMed

    Kumar, Nitin; Radhakrishnan, Abhijith; Su, Chih-Chia; Osteryoung, Katherine W; Yu, Edward W

    2016-02-01

    The chloroplast division machinery is composed of numerous proteins that assemble as a large complex to divide double-membraned chloroplasts through binary fission. A key mediator of division-complex formation is ARC6, a chloroplast inner envelope protein and evolutionary descendant of the cyanobacterial cell division protein Ftn2. ARC6 connects stromal and cytosolic contractile rings across the two membranes through interaction with an outer envelope protein within the intermembrane space (IMS). The ARC6 IMS region bears a structurally uncharacterized domain of unknown function, DUF4101, that is highly conserved among ARC6 and Ftn2 proteins. Here we report the crystal structure of this domain from Arabidopsis thaliana ARC6. The domain forms an α/β barrel open towards the outer envelope membrane but closed towards the inner envelope membrane. These findings provide new clues into how ARC6 and its homologs contribute to chloroplast and cyanobacterial cell division. PMID:26452626

  8. INTERACTION REGION LOCAL CORRECTION FOR THE LARGE HADRON COLLIDER.

    SciTech Connect

    WEI,J.; FISCHER,W.; PTITSIN,V.; OSTOJIC,R.; STRAIT,J.

    1999-03-29

    The performance of the Large Hadron Collider (LHC) at collision energy is limited by the field quality of the interaction region (IB) quadrupoles and dipoles. In this paper we study the impact of the expected field errors of these magnets on the dynamic aperture (DA). Since the betatron phase advance is well defined for magnets that are located in regions of large beta functions, local corrections can be very effective and robust. We compare possible compensation schemes and propose a corrector layout to meet the required DA performance.

  9. 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

  10. 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

  11. 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

  12. 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.

  13. 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

  14. 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.

    PubMed

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

    1991-01-29

    The large subunit of Escherichia coli carbamoyl phosphate synthetase (a polypeptide of 117.7 kDa that consists of two homologous halves) is responsible for carbamoyl phosphate synthesis from NH3 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 (demonstrated by NH2-terminal sequencing). UMP, IMP, and ornithine prevent this cleavage and the inactivation. Upon irradiation with ultraviolet light in the presence of [14C]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 irradiation with [14C]UMP. The [14C]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. In the presence of SDS, the labeled large subunit is cleaved by trypsin or by V8 staphylococcal protease at a site located 15 or 25 kDa, respectively, from the COOH terminus (shown by NH2-terminal sequencing), and only the 15- or 25-kDa fragments are labeled. Similarly, upon cleavage of the aspartyl-prolyl bonds of the [14C]UMP-labeled enzyme with 70% formic acid, labeling was found only in the 18.5-kDa fragment that contains the COOH terminus of the subunit. Thus, UMP binds to the COOH-terminal domain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1989678

  15. Local and Regional Impacts of Large Scale Wind Energy Deployment

    NASA Astrophysics Data System (ADS)

    Michalakes, J.; Hammond, S.; Lundquist, J. K.; Moriarty, P.; Robinson, M.

    2010-12-01

    The U.S. is currently on a path to produce 20% of its electricity from wind energy by 2030, almost a 10-fold increase over present levels of electricity generated from wind. Such high-penetration wind energy deployment will entail extracting elevated energy levels from the planetary boundary layer and preliminary studies indicate that this will have significant but uncertain impacts on the local and regional environment. State and federal regulators have raised serious concerns regarding potential agricultural impacts from large farms deployed throughout the Midwest where agriculture is the basis of the local economy. The effects of large wind farms have been proposed to be both beneficial (drying crops to reduce occurrences of fungal diseases, avoiding late spring freezes, enhancing pollen viability, reducing dew duration) and detrimental (accelerating moisture loss during drought) with no conclusive investigations thus far. As both wind and solar technologies are deployed at scales required to replace conventional technologies, there must be reasonable certainty that the potential environmental impacts at the micro, macro, regional and global scale do not exceed those anticipated from carbon emissions. Largely because of computational limits, the role of large wind farms in affecting regional-scale weather patterns has only been investigated in coarse simulations and modeling tools do not yet exist which are capable of assessing the downwind affects of large wind farms may have on microclimatology. In this presentation, we will outline the vision for and discuss technical and scientific challenges in developing a multi-model high-performance simulation capability covering the range of mesoscale to sub-millimeter scales appropriate for assessing local, regional, and ultimately global environmental impacts and quantifying uncertainties of large scale wind energy deployment scenarios. Such a system will allow continuous downscaling of atmospheric processes on wind

  16. 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

  17. 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.

  18. 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.

  19. 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

  20. A conserved hydrophobic surface of the LARG pleckstrin homology domain is critical for RhoA activation in cells

    PubMed Central

    Aittaleb, Mohamed; Gao, Guang; Evelyn, Chris R.; Neubig, Richard R.; Tesmer, John J. G.

    2009-01-01

    Leukemia associated Rho guanine nucleotide exchange factor (LARG) activates RhoA in response to signals received by specific classes of cell surface receptors. The catalytic core of LARG is a Dbl homology (DH) domain whose activity is modulated by an adjacent pleckstrin homology (PH) domain. In this study, we used a transcriptional assay and confocal microscopy to examine the roles of several novel structural features of the LARG DH/PH domains, including a conserved and exposed hydrophobic patch on the PH domain that mediates protein-protein interactions in crystal structures of LARG and its close homolog PDZ-RhoGEF. Mutation of the hydrophobic patch has no effect on nucleotide exchange activity in vitro, but abolished the ability of LARG to activate RhoA and to induce stress fiber formation in cultured cells. The activity of these mutants could be rescued by fusion with exogenous membrane targeting domains. However, because membrane recruitment by activated Gα13 subunits was not sufficient to rescue activity of a hydrophobic patch mutant, the LARG PH domain cannot solely contribute to membrane targeting. Instead, it seems likely the domain is involved in regulatory interactions with other proteins near the membrane surface. We also show that the hydrophobic patch of the PH domain is likely important for the activity of all Lbc family RhoGEFs. PMID:19560536

  1. 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.

  2. 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.

  3. Large area formation of self-aligned crystalline domains of organic semiconductors on transistor channels using CONNECT (Presentation Recording)

    NASA Astrophysics Data System (ADS)

    Park, Steve

    2015-09-01

    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 such as active matrix displays, radio frequency identification tags, and integrated logic circuits. However, practical applications of organic electronics requires patterned and precisely registered OSC film within the transistor channel region with uniform electrical properties over a large area, a task that remains a significant challenge. Here we present a novel technique known as CONNECT (Controlled OSC NucleatioN and Extension for CircuiTs), which utilizes differential surface energy and solution shearing to simultaneously generate self-patterned and self-registered OSC film 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. CONNECT was expanded to use with inkjet printed silver electrodes, showing the versatility of our method to accommodate various solution deposition and fabrication methods.

  4. The membranotropic regions of the endo and ecto domains of HIV gp41 envelope glycoprotein.

    PubMed

    Moreno, Miguel R; Giudici, Marcela; Villalaín, José

    2006-01-01

    We have identified the membranotropic regions of the full sequence of the HIV gp41 envelope glycoprotein by performing an exhaustive study of membrane rupture, phospholipid-mixing and fusion induced by two 15-mer gp41-derived peptide libraries from HIV strains HIV_MN and HIV_consensus_B on model membranes having different phospholipid compositions. The data obtained for the two strains and its comparison have led us to identify different gp41 membranotropic segments in both ecto- and endodomains which might be implicated in viral membrane fusion and/or membrane interaction. The membranotropic segments corresponding to the gp41 ectodomain were the fusion domain, a stretch located on the N-heptad repeat region adjacent to the fusion domain, part of the immunodominant loop, the pre-transmembrane domain and the transmembrane domain. The membranotropic segments corresponding to the gp41 endodomain were mainly located at some specific parts of the previously described lentivirus lytic sequences. Significantly, the C-heptad repeat region and the Kennedy sequence located in the ectodomain and in the endodomain, respectively, presented no membranotropic activity in any model membrane assayed. The identification of these gp41 segments as well as their membranotropic propensity sustain the notion that different segments of gp41 provide the driving force for the merging of the viral and target cell membranes as well as they help us to define those segments as attractive targets for further development of new anti-viral compounds. PMID:16483537

  5. Variable region domain exchange influences the functional properties of IgG.

    PubMed

    Morrison, S L; Porter, S B; Trinh, K R; Wims, L A; Denham, J; Oi, V T

    1998-03-15

    In the present study we have characterized a family of anti-dansyl Abs with the variable region of the heavy chain on human Ckappa and the variable region of the light chain on different human gamma constant regions (creating inside-out molecules). Although fully assembled molecules were secreted, this variable region exchange slowed the kinetics of Ab assembly. Although the variable region exchange does not lead to a detectable change in the microenvironment of the combining site, it did alter the kinetic parameters of binding to immobilized Ag, slowing both the on and off rates. When effector functions were evaluated, inside-out IgG1 and IgG3 were more effective in complement-mediated cytolysis than their wild-type counterparts. Variable region domain exchange may be one approach to obtaining Abs of identical specificity with altered binding characteristics.

  6. Global regularity to the 3D MHD equations with large initial data in bounded domains

    NASA Astrophysics Data System (ADS)

    Yu, Haibo

    2016-08-01

    This paper considers the global regularity to the 3D incompressible MHD equations with large initial data in bounded domains. Let μ, ν, u, and b denote the viscosity coefficient, magnetic diffusivity, velocity field, and magnetic field, respectively. We construct new systems for (u - b) and (u + b) to overcome the difficulties caused by the large initial data. It is shown that ↑" separators=" ( u , b ) ↑ H 1 is globally bounded as long as ↑" separators=" ( u0 - b 0 ) ↑ H 1 + |" separators=" μ - ν | ( μ + ν ) - 1 or ↑" separators=" ( u0 + b 0 ) ↑ H 1 + |" separators=" μ - ν | ( μ + ν ) - 1 is sufficiently small, which indicates that the Navier-Stokes equations can be regularized by the magnetic field.

  7. Runoff estimates across large regions using multiple data sources and regional model calibration schemes

    NASA Astrophysics Data System (ADS)

    Zhang, Y.; Wang, B.; Vaze, J.; Chiew, F. H.; Guerschman, J. P.; McVicar, T.

    2012-12-01

    Estimating runoff in ungauged or poorly gauged catchments is one of the most challenging tasks in surface water hydrology. This study focuses on runoff estimates across large regions using multiple data sources together with different regional model calibration schemes. First, 228 gauged catchments widely located across south-east Australia (~1.4 million km2) are selected. Half of the catchments are randomly selected for regional model calibrations and the remainder used for cross-validations. Four rainfall-runoff and landscape hydrological models (Xinanjiang, AWBM, Sacramento and AWRA-L) are regionally calibrated against multiple data sources, including recorded daily streamflow, gridded monthly remotely-sensed actual evapotranspiration (ETa) and gridded daily remotely-sensed soil moisture (SM) data. The modeling results are assessed against recorded streamflow, remotely sensed ETa and remotely-sensed SM in other half of the catchments. Results indicate that the multi-objective calibrations are better than the traditional model calibration solely against streamflow data, in terms of overall model performance in simulating daily runoff, monthly actual ET and daily SM in the validation catchments. The runoff prediction results using the regional model calibration schemes perform similarly to (or slightly better than) the traditional regionalization approach, i.e., the nearest neighbor (or spatial proximity) approach. However, the regional model calibration approach has an important advantage for runoff estimates across large regions where gauging stations are relatively sparse.

  8. 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.

  9. 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.

  10. 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.

  11. Asymmetric assembly of Merkel cell polyomavirus large T-antigen origin binding domains at the viral origin.

    PubMed

    Harrison, Celia J; Meinke, Gretchen; Kwun, Hyun Jin; Rogalin, Henry; Phelan, Paul J; Bullock, Peter A; Chang, Yuan; Moore, Patrick S; Bohm, Andrew

    2011-06-17

    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 Å 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 ~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.

  12. Synthesis of Large-Sized Single-Crystal Hexagonal Boron Nitride Domains on Nickel Foils by Ion Beam Sputtering Deposition.

    PubMed

    Wang, Haolin; Zhang, Xingwang; Liu, Heng; Yin, Zhigang; Meng, Junhua; Xia, Jing; Meng, Xiang-Min; Wu, Jinliang; You, Jingbi

    2015-12-22

    Large-sized single-crystal h-BN domains with a lateral size up to 100 μm are synthesized on Ni foils by ion-beam sputtering deposition. The nucleation density of h-BN is dramatically decreased by reducing the concentrations of both active sites and species on the Ni surface through a brief in situ pretreatment of the substrate and optimization of the growth parameters, enabling the growth of large-sized domains.

  13. Leveraging Domain Knowledge to Facilitate Visual Exploration of Large Population Datasets

    PubMed Central

    Hsu, William; Bui, Alex A.T.

    2013-01-01

    Observational patient data provides an unprecedented opportunity to gleam new insights into diseases and assess patient quality of care, but a challenge lies in matching our ability to collect data with a comparable ability to understand and apply this information. Visual analytic techniques are promising as they permit the exploration and manipulation of complex datasets through a graphical user interface. Nevertheless, current visualization tools rely on users to manually configure which aspects of the dataset are shown and how they are presented. In this paper, we describe an approach that utilizes characteristics of the data and domain knowledge to assist users with summarizing the information space of a large population. We present a representation that captures contextual information about the data and constructs that operate on this information to tailor the data’s presentation. We describe a use case of this approach in exploring a claims dataset of individuals with spinal dysraphism. PMID:24551363

  14. 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

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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

  20. 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

  1. The ATPase domain but not the acidic region of Cockayne syndrome group B gene product is essential for DNA repair.

    PubMed

    Brosh, R M; Balajee, A S; Selzer, R R; Sunesen, M; Proietti De Santis, L; Bohr, V A

    1999-11-01

    Cockayne syndrome (CS) is a human genetic disorder characterized by UV sensitivity, developmental abnormalities, and premature aging. Two of the genes involved, CSA and CSB, are required for transcription-coupled repair (TCR), a subpathway of nucleotide excision repair that removes certain lesions rapidly and efficiently from the transcribed strand of active genes. CS proteins have also been implicated in the recovery of transcription after certain types of DNA damage such as those lesions induced by UV light. In this study, site-directed mutations have been introduced to the human CSB gene to investigate the functional significance of the conserved ATPase domain and of a highly acidic region of the protein. The CSB mutant alleles were tested for genetic complementation of UV-sensitive phenotypes in the human CS-B homologue of hamster UV61. In addition, the CSB mutant alleles were tested for their ability to complement the sensitivity of UV61 cells to the carcinogen 4-nitroquinoline-1-oxide (4-NQO), which introduces bulky DNA adducts repaired by global genome repair. Point mutation of a highly conserved glutamic acid residue in ATPase motif II abolished the ability of CSB protein to complement the UV-sensitive phenotypes of survival, RNA synthesis recovery, and gene-specific repair. These data indicate that the integrity of the ATPase domain is critical for CSB function in vivo. Likewise, the CSB ATPase point mutant failed to confer cellular resistance to 4-NQO, suggesting that ATP hydrolysis is required for CSB function in a TCR-independent pathway. On the contrary, a large deletion of the acidic region of CSB protein did not impair the genetic function in the processing of either UV- or 4-NQO-induced DNA damage. Thus the acidic region of CSB is likely to be dispensable for DNA repair, whereas the ATPase domain is essential for CSB function in both TCR-dependent and -independent pathways. PMID:10564257

  2. 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

  3. 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

  4. 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).

  5. 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.

  6. 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.

  7. 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

  8. 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).

  9. 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.

  10. Large solar flares and their ionospheric D region enhancements

    NASA Astrophysics Data System (ADS)

    Thomson, Neil R.; Rodger, Craig J.; Clilverd, Mark A.

    2005-06-01

    On 4 November 2003, the largest solar flare ever recorded saturated the GOES satellite X-ray detectors, making an assessment of its size difficult. However, VLF radio phase advances effectively recorded the lowering of the VLF reflection height and hence the lowest edge of the Earth's ionosphere. Previously, these phase advances were used to extrapolate the GOES 0.1-0.8 nm ("XL") fluxes from saturation at X17 to give a peak magnitude of X45 ± 5 for this great flare. Here it is shown that a similar extrapolation, but using the other GOES X-ray band, 0.05-0.4 nm ("XS"), is also consistent with a magnitude of X45. Also reported here are VLF phase measurements from two paths near dawn: "Omega Australia" to Dunedin, New Zealand (only just all sunlit) and NPM, Hawaii, to Ny Alesund, Svalbard (only partly sunlit), which also give remarkably good extrapolations of the flare flux, suggesting that VLF paths monitoring flares do not necessarily need to be in full daylight. D region electron densities are modeled as functions of X-ray flux up to the level of the great X45 flare by using flare-induced VLF amplitudes together with the VLF phase changes. During this great flare, the "Wait" reflection height, H', was found to have been lowered to ˜53 km or ˜17 km below the normal midday value of ˜70 km. Finally, XL/XS ratios are examined during some large flares, including the great flare. Plots of such ratios against XL can give quite good estimates of the great flare's size (X45) but without use of VLF measurements.

  11. 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

  12. 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

  13. 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.

  14. 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

  15. Deletion of the regulatory domain of protein kinase C alpha exposes regions in the hinge and catalytic domains that mediate nuclear targeting.

    PubMed

    James, G; Olson, E

    1992-02-01

    Members of the protein kinase C (PKC) family are characterized by an NH2-terminal regulatory domain containing binding sites for calcium, phosphatidylserine, and diacylglycerol (or tumor-promoting phorbol esters), a small central hinge region and a COOH-terminal catalytic domain. We have constructed fusion proteins in which the regulatory domain of PKC alpha was removed and replaced by a 19-amino acid leader sequence containing a myristoylation consensus or by the same sequence in which the amino-terminal glycine was changed to alanine to prevent myristoylation. The goal was to generate constitutively active mutants of PKC that were either membrane bound, due to their myristoylation, or cytoplasmic. Western blotting of fractions from COS cells transfected with plasmids encoding wild-type and mutant proteins revealed that PKC alpha resided entirely in a Triton X-100 soluble (TS) fraction, whereas both the myristoylated and nonmyristoylated mutants were associated primarily with the nuclear envelope fraction. A similar mutant that lacked the 19 amino acid leader sequence was also found almost entirely in the nuclear envelope, as was a truncation mutant containing only the regulatory domain, hinge region, and a small portion of the catalytic domain. However, an additional truncation mutant consisting of only the regulatory domain plus the first one-third of the hinge region was almost entirely in the TS fraction. A nonmyristoylated fusion protein containing only the catalytic domain was also found in the nuclear envelope. Immunostaining of cells transfected with these constructs revealed that both the myristoylated and nonmyristoylated mutants were localized in nuclei, whereas wild-type PKC alpha was primarily cytoplasmic and perinuclear. Phorbol dibutyrate treatment of PKC alpha-transfected cells resulted in increased perinuclear and nuclear staining. The results are consistent with a model in which activation of PKC, by phorbol esters or by deletion of the

  16. 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

  17. Large-scale phase separation with nano-twin domains in manganite spinel (Co,Fe,Mn)3O4

    NASA Astrophysics Data System (ADS)

    Horibe, Y.; Takeyama, S.; Mori, S.

    2016-08-01

    The effect of Mn concentration on the formation of nano-domain structures in the spinel oxide (Co,Fe,Mn)3O4 was investigated by electron diffraction, bright-, and dark-field imaging technique with transmission electron microscopy. Large scale phase separation with nano-twin domains was observed in Co0.6Fe1.0Mn1.4O4, in contrast to the highly aligned checkerboard nano-domains in Co0.6Fe0.9Mn1.5O4. Diffusion of the Mn3+ ions with the Jahn-Teller distortions is suggested to play an important role in the formation of checkerboard nano-domain structure.

  18. 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.

  19. The SH3 Domain Acts as a Scaffold for the N-Terminal Intrinsically Disordered Regions of c-Src.

    PubMed

    Maffei, Mariano; Arbesú, Miguel; Le Roux, Anabel-Lise; Amata, Irene; Roche, Serge; Pons, Miquel

    2015-05-01

    Regulation of c-Src activity by the intrinsically disordered Unique domain has recently been demonstrated. However, its connection with the classical regulatory mechanisms is still missing. Here we show that the Unique domain is part of a long loop closed by the interaction of the SH4 and SH3 domains. The conformational freedom of the Unique domain is further restricted through direct contacts with SH3 that are allosterically modulated by binding of a poly-proline ligand in the presence and in the absence of lipids. Our results highlight the scaffolding role of the SH3 domain for the c-Src N-terminal intrinsically disordered regions and suggest a connection between the regulatory mechanisms involving the SH3 and Unique domains.

  20. Application of Spectral Filtering scheme for Spherical Limited-Area domain to Regional forecast model

    NASA Astrophysics Data System (ADS)

    Park, J.-R.; Cheong, H.-. B.; Kang, H.-. G.

    2012-04-01

    The spectral filter for spherical limited-area domain was applied to time integration procedure of regional model as a numerical scheme to remove small scale noises, which cannot be properly resolved in numerical models. This filter is designed to provide the sharp filter response, selective scale decomposition, and the isotropy on the limited-area domain by using the filter equation with high-order spherical Laplacian operator. The high-order filter equation is solved by low-order elliptic equations with the first or the second spherical Laplacian operator. It is controlled by the order of the spherical Laplacian operator and wave cutoff scale parameter. For the application to the regional weather forecast model, the filter is reconstructed into the regional map projection, e.g., Mercator map projection. The weather research and forecasting (WRF) model is used and the spectral filter works on the vertical velocity field in which the unresolved kinematic features appear prominently. The filter parameters are set to damp the amplitude of wave component with wavelength of two times the grid interval by half in every time step. The effect of the filter on the removal of small-scale waves was evaluated through the tropical cyclone (TC) track and intensity prediction. For the accurate prediction of typhoon, the TC initialization scheme, named the structure adjustable balanced vortex (SABV) scheme, is used for all test cases. In comparison with the simulated result using the diffusion scheme provided in the model for the same purpose, the model performance was improved, especially in track prediction. The 1-day accumulated precipitation of the test simulation using the spectral filter exhibits the most similar pattern to the observation. The spectra analysis of vertical velocity field showed that the spectral filtering scheme restrains the undesirable small upturned spectral energy usually produced in limited-area models.

  1. 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.

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

    PubMed

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

    2014-10-01

    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

  3. 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

  4. Distinct regions of triadin are required for targeting and retention at the junctional domain of the sarcoplasmic reticulum.

    PubMed

    Rossi, Daniela; Bencini, Cristina; Maritati, Marina; Benini, Francesca; Lorenzini, Stefania; Pierantozzi, Enrico; Scarcella, Angela Maria; Paolini, Cecilia; Protasi, Feliciano; Sorrentino, Vincenzo

    2014-03-01

    Ca2+ release, which is necessary for muscle contraction, occurs at the j-SR (junctional domain of the sarcoplasmic reticulum). It requires the assembly of a large multiprotein complex containing the RyR (ryanodine receptor) and additional proteins, including triadin and calsequestrin. The signals which drive these proteins to the j-SR and how they assemble to form this multiprotein complex are poorly understood. To address aspects of these questions we studied the localization, dynamic properties and molecular interactions of triadin. We identified three regions, named TR1 (targeting region 1), TR2 and TR3, that contribute to the localization of triadin at the j-SR. FRAP experiments showed that triadin is stably associated with the j-SR and that this association is mediated by TR3. Protein pull-down experiments indicated that TR3 contains binding sites for calsequestrin-1 and that triadin clustering can be enhanced by binding to calsequestrin-1. These findings were confirmed by FRET experiments. Interestingly, the stable association of triadin to the j-SR was significantly decreased in myotubes from calsequestrin-1 knockout mice. Taken together, these results identify three regions in triadin that mediate targeting to the j-SR and reveal a role for calsequestrin-1 in promoting the stable association of triadin to the multiprotein complex associated with RyR. PMID:24325401

  5. 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.

  6. 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.

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

    PubMed

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

    2015-04-01

    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 [Formula: see text]for 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 [Formula: see text]at 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.

  8. 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

  9. Sparse reconstruction of breast MRI using homotopic L0 minimization in a regional sparsified domain.

    PubMed

    Wong, Alexander; Mishra, Akshaya; Fieguth, Paul; Clausi, David A

    2013-03-01

    The use of MRI for early breast examination and screening of asymptomatic women has become increasing popular, given its ability to provide detailed tissue characteristics that cannot be obtained using other imaging modalities such as mammography and ultrasound. Recent application-oriented developments in compressed sensing theory have shown that certain types of magnetic resonance images are inherently sparse in particular transform domains, and as such can be reconstructed with a high level of accuracy from highly undersampled k-space data below Nyquist sampling rates using homotopic L0 minimization schemes, which holds great potential for significantly reducing acquisition time. An important consideration in the use of such homotopic L0 minimization schemes is the choice of sparsifying transform. In this paper, a regional differential sparsifying transform is investigated for use within a homotopic L0 minimization framework for reconstructing breast MRI. By taking local regional characteristics into account, the regional differential sparsifying transform can better account for signal variations and fine details that are characteristic of breast MRI than the popular finite differential transform, while still maintaining strong structure fidelity. Experimental results show that good breast MRI reconstruction accuracy can be achieved compared to existing methods.

  10. 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.

  11. 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.

  12. 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.

  13. Photoinduced domain-type collective structural changes with interlayer σ -bonds in the visible region of graphite

    NASA Astrophysics Data System (ADS)

    Ohnishi, Hiromasa; Nasu, Keiichiro

    2009-02-01

    We theoretically study the photoinduced domain-type structural changes in the visible region of graphite. By means of the ab initio total-energy calculation, we clarify the adiabatic path for the nucleation of this domain, wherein the interlayer distance of the original graphite is contracted and new interlayer σ -bonds are induced with a certain periodic buckling pattern. We show that an excitation by few visible photons is energetically enough to trigger the formation of this domain, and this domain is sufficiently stable against the thermal fluctuation at around room temperature. The electronic state of this domain is also shown to have a pseudogap, characteristic to an insulator immersed in the original semimetallic graphite.

  14. 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

  15. 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

  16. 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.

  17. 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

  18. 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.

  19. Physical Environmental Correlates of Domain-Specific Sedentary Behaviours across Five European Regions (the SPOTLIGHT Project)

    PubMed Central

    De Cocker, Katrien; Roda, Célina; Oppert, Jean-Michel; Mackenbach, Joreintje D.; Lakerveld, Jeroen; Glonti, Ketevan; Bardos, Helga; Rutter, Harry; Cardon, Greet; De Bourdeaudhuij, Ilse

    2016-01-01

    Background The relation between neighbourhood environmental factors and domain-specific sedentary behaviours among adults remains unclear. This study firstly aims to examine the association of perceived and objectively measured neighbourhood safety, aesthetics, destinations and functionality with transport-related, work-related and leisure-time sedentary behaviour. Secondly, the study aims to assess whether these associations are moderated by age, gender or educational level. Methods In 60 randomly sampled neighbourhoods from 5 urban regions in Europe (Ghent and suburbs, Paris and inner suburbs, Budapest and suburbs, the Randstad, and Greater London), a virtual audit with Google Street View was performed to assess environmental characteristics. A total of 5,205 adult inhabitants of these neighbourhoods reported socio-demographic characteristics, sedentary behaviours, and neighbourhood perceptions in an online survey. Generalized linear mixed models were conducted to examine associations between physical environmental neighbourhood factors and sedentary behaviours. Interaction terms were added to test the moderating role of individual-level socio-demographic variables. Results Lower levels of leisure-time sedentary behaviour (i.e. all leisure activities except television viewing and computer use) were observed among adults who perceived greater numbers of destinations such as supermarkets, recreational facilities, or restaurants in their neighbourhood, and among adults who lived in a neighbourhood with more objectively measured aesthetic features, such as trees, water areas or public parks. Lower levels of work-related sedentary behaviour were observed among adults who perceived less aesthetic features in their neighbourhood, and among adults who lived in a neighbourhood with less objectively measured destinations. Both age, gender and educational level moderated the associations between neighbourhood environmental factors and sedentary behaviours. Conclusion

  20. 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

  1. Large arteriovenous malformation of the oromaxillofacial region with multiple phleboliths.

    PubMed

    Orhan, Kaan; Icen, Murat; Aksoy, Secil; Avsever, Hakan; Akcicek, Gokcen

    2012-10-01

    Vascular tumors are the most common benign tumors of the head and neck in infancy and childhood. Vascular anomalies of the head and neck were divided into 2 categories including hemangiomas and vascular malformations. Oral and maxillofacial hemangiomas and vascular malformations are congenital lesions with various clinical characteristics, manifestations, indications, and possibilities for treatment. This paper reports a case of large arteriovenous malformations including a description of the features demonstrated by panoramic radiography, cone beam computed tomography, and magnetic resonance imaging. The differential diagnosis and treatment modalities (including embolization with N-butylcyanoacrylate in this case) are also discussed following the case presentation, along with the available literature review.

  2. Modular organization of the PDZ domains in the human discs-large protein suggests a mechanism for coupling PDZ domain-binding proteins to ATP and the membrane cytoskeleton

    PubMed Central

    1996-01-01

    The human homologue (hDIg) of the Drosophila discs-large tumor suppressor (DIg) is a multidomain protein consisting of a carboxyl- terminal guanylate kinase-like domain, an SH3 domain, and three slightly divergent copies of the PDZ (DHR/GLGF) domain. Here have examined the structural organization of the three PDZ domains of hDIg using a combination of protease digestion and in vitro binding measurements. Our results show that the PDZ domains are organized into two conformationally stable modules one (PDZ, consisting of PDZ domains 1 and 2, and the other (PDZ) corresponding to the third PDZ domain. Using amino acid sequencing and mass spectrometry, we determined the boundaries of the PDZ domains after digestion with endoproteinase Asp- N, trypsin, and alpha-chymotrypsin. The purified PDZ1+2, but not the PDZ3 domain, contains a high affinity binding site for the cytoplasmic domain of Shaker-type K+ channels. Similarly, we demonstrate that the PDZ1+2 domain can also specifically bind to ATP. Furthermore, we provide evidence for an in vivo interaction between hDIg and protein 4.1 and show that the hDIg protein contains a single high affinity protein 4.1-binding site that is not located within the PDZ domains. The results suggest a mechanism by which PDZ domain-binding proteins may be coupled to ATP and the membrane cytoskeleton via hDlg. PMID:8909548

  3. Comparison of the applicability domain of a quantitative structure-activity relationship for estrogenicity with a large chemical inventory.

    PubMed

    Netzeva, Tatiana I; Gallegos Saliner, Ana; Worth, Andrew P

    2006-05-01

    The aim of the present study was to illustrate that it is possible and relatively straightforward to compare the domain of applicability of a quantitative structure-activity relationship (QSAR) model in terms of its physicochemical descriptors with a large inventory of chemicals. A training set of 105 chemicals with data for relative estrogenic gene activation, obtained in a recombinant yeast assay, was used to develop the QSAR. A binary classification model for predicting active versus inactive chemicals was developed using classification tree analysis and two descriptors with a clear physicochemical meaning (octanol-water partition coefficient, or log Kow, and the number of hydrogen bond donors, or n(Hdon)). The model demonstrated a high overall accuracy (90.5%), with a sensitivity of 95.9% and a specificity of 78.1%. The robustness of the model was evaluated using the leave-many-out cross-validation technique, whereas the predictivity was assessed using an artificial external test set composed of 12 compounds. The domain of the QSAR training set was compared with the chemical space covered by the European Inventory of Existing Commercial Chemical Substances (EINECS), as incorporated in the CDB-EC software, in the log Kow / n(Hdon) plane. The results showed that the training set and, therefore, the applicability domain of the QSAR model covers a small part of the physicochemical domain of the inventory, even though a simple method for defining the applicability domain (ranges in the descriptor space) was used. However, a large number of compounds are located within the narrow descriptor window.

  4. 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.

  5. 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

  6. The zinc finger region of simian virus 40 large T antigen is needed for hexamer assembly and origin melting.

    PubMed

    Loeber, G; Stenger, J E; Ray, S; Parsons, R E; Anderson, M E; Tegtmeyer, P

    1991-06-01

    Simian virus 40 large T antigen contains a single sequence element with an arrangement of cysteines and histidines that is characteristic of a zinc finger motif. The finger region maps from amino acids 302 through 320 and has the sequence C-302 L K C-305 I K K E Q P S H Y K Y H-317 E K H-320. Previous genetic analysis has shown that the cysteine and histidine sequences and the contiguous S H Y K Y region in the finger are important for DNA replication in vivo. We show here that representative mutations in either of these elements of the finger prevent the assembly of large T antigen into stable hexamers in vitro. These same mutations have a characteristic effect on the interaction of T antigen with the simian virus 40 core origin of replication. The mutant T antigens bind to the central pentanucleotide domain of the core origin but fail to melt the adjacent inverted repeat domain and to untwist the adenine-thymine domain. These defects would prevent the formation of a replication bubble and the initiation of DNA replication. Finger mutations have lesser effects on the helicase function of T antigen and no observable effect on binding of T antigen to the mouse p53 protein. We propose that the zinc finger region contributes to protein-protein interactions essential for the assembly of stable T-antigen hexamers at the origin of replication and that hexamers are needed for subsequent alterations in the structure of origin DNA. We cannot exclude the possibility that the zinc finger region also makes specific contacts with components of origin DNA.

  7. DLC1 Activation Requires Lipid Interaction through a Polybasic Region Preceding the RhoGAP Domain

    PubMed Central

    Erlmann, Patrik; Schmid, Simone; Horenkamp, Florian A.; Geyer, Matthias; Pomorski, Thomas G.

    2009-01-01

    Deleted in Liver Cancer 1 (DLC1) is a GTPase-activating protein (GAP) with specificity for RhoA, RhoB, and RhoC that is frequently deleted in various tumor types. By inactivating these small GTPases, DLC1 controls actin cytoskeletal remodeling and biological processes such as cell migration and proliferation. Here we provide evidence that DLC1 binds to phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) through a previously unrecognized polybasic region (PBR) adjacent to its RhoGAP domain. Importantly, PI(4,5)P2-containing membranes are shown to stimulate DLC1 GAP activity in vitro. In living cells, a DLC1 mutant lacking an intact PBR inactivated Rho signaling less efficiently and was severely compromised in suppressing cell spreading, directed migration, and proliferation. We therefore propose that PI(4,5)P2 is an important cofactor in DLC1 regulation in vivo and that the PBR is essential for the cellular functions of the protein. PMID:19710422

  8. 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.

  9. A New Classifier for Flood Hazard Mapping over Large Regions

    NASA Astrophysics Data System (ADS)

    Samela, C.; Troy, T. J.; Manfreda, S.

    2015-12-01

    The knowledge of the position and the extent of the areas exposed to the flood hazard is essential to any strategy for minimizing the risk. Unfortunately, in ungauged basins the use of traditional floodplain mapping techniques is prevented by the lack of the extensive data required. The main aim of the present work is 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. Their performances in identifying the floodplains have been measured at the change of the topography and the size of the calibration area, and 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 ungauged basins and for large-scale applications, providing good accuracies with low requirements in terms of data and computational costs.

  10. 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.

  11. 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

  12. 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.

  13. 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

  14. 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.

  15. Novel Inhibitors Induce Large Conformational Changes of GAB1 Pleckstrin Homology Domain and Kill Breast Cancer Cells

    PubMed Central

    Chen, Lu; Du-Cuny, Lei; Moses, Sylvestor; Dumas, Sabrina; Song, Zuohe; Rezaeian, Abdol Hossein; Lin, Hui-Kuan; Meuillet, Emmanuelle J.; Zhang, Shuxing

    2015-01-01

    The Grb2-associated binding protein 1 (GAB1) integrates signals from different signaling pathways and is over-expressed in many cancers, therefore representing a new therapeutic target. In the present study, we aim to target the pleckstrin homology (PH) domain of GAB1 for cancer treatment. Using homology models we derived, high-throughput virtual screening of five million compounds resulted in five hits which exhibited strong binding affinities to GAB1 PH domain. Our prediction of ligand binding affinities is also in agreement with the experimental K D values. Furthermore, molecular dynamics studies showed that GAB1 PH domain underwent large conformational changes upon ligand binding. Moreover, these hits inhibited the phosphorylation of GAB1 and demonstrated potent, tumor-specific cytotoxicity against MDA-MB-231 and T47D breast cancer cell lines. This effort represents the discovery of first-in-class GAB1 PH domain inhibitors with potential for targeted breast cancer therapy and provides novel insights into structure-based approaches to targeting this protein. PMID:25569504

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. Large electric-field-induced strain in ferroelectric crystals by point-defect-mediated reversible domain switching

    NASA Astrophysics Data System (ADS)

    Ren, Xiaobing

    2004-02-01

    Ferroelectric crystals are characterized by their asymmetric or polar structures. In an electric field, ions undergo asymmetric displacement and result in a small change in crystal dimension, which is proportional to the applied field. Such electric-field-induced strain (or piezoelectricity) has found extensive applications in actuators and sensors. However, the effect is generally very small and thus limits its usefulness. Here I show that with a different mechanism, an aged BaTiO3 single crystal can generate a large recoverable nonlinear strain of 0.75% at a low field of 200 V mm-1. At the same field this value is about 40 times higher than piezoelectric Pb(Zr, Ti)O3 (PZT) ceramics and more than 10 times higher than the high-strain Pb(Zn1/3Nb2/3)O3-PbTiO3 (PZN-PT) single crystals. This large electro-strain stems from an unusual reversible domain switching (most importantly the switching of non-180° domains) in which the restoring force is provided by a general symmetry-conforming property of point defects. This mechanism provides a general method to achieve large electro-strain effect in a wide range of ferroelectric systems and the effect may lead to novel applications in ultra-large stroke and nonlinear actuators.

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. On the Influence of Grid Resolution and Domain Size on the Structure and Evolution of the Stratocumulus-Topped Boundary Layer: A Large-Eddy Simulation Study

    NASA Astrophysics Data System (ADS)

    Pedersen, J. G.; Malinowski, S. P.

    2015-12-01

    Improved understanding of processes related to the evolution of stratocumulus clouds is needed, e.g. for more accurate prediction of weather and climate. As a supplement to measurements, numerical simulation is a widely used and valuable tool in stratocumulus studies. However, due to limited computational resources, simulations are often run at resolutions too coarse to account for the smallest eddies involved in e.g. the entrainment process, and possibly in computational domains too small to contain the largest relevant flow structures in the boundary layer. Here we investigate how changes in domain size and spatial resolution affect key parameters such as cloud cover and liquid water path in large-eddy simulations of the stratocumulus-topped boundary layer (STBL). Details of the entrainment process and subsequent mixing within the STBL is studied by adding a passive scalar to the flow. We use a modified version of the 3D nonhydrostatic anelastic Eulerian-semi-Lagrangian (EULAG) model, and perform both simulations including an explicit sub-grid scale turbulence model and simulations in which the effect of unresolved turbulence is accounted for implicitly by the applied numerical scheme. The simulations are based on measurements from the second Dynamics and Chemistry of Marine Stratocumulus (DYCOMS-II) and Physics of Stratocumulus Top (POST) field campaigns. We show how refining the horizontal resolution facilitate development of small-scale turbulence in the cloud-top region, which enhance entrainment and tends to dissolve the cloud. Refining the vertical grid spacing, on the other hand, allows for stronger vertical temperature gradients which tend to strengthen the capping inversion and inhibit entrainment. The statistics of the flow and the evolution of the cloud is found to be more sensitive to changes in resolution than to changes in domain size. We do however observe still larger flow structures as the horizontal extent of the computational domain is

  7. An Anomaly in the Domain Chaos State of Rayleigh-B'enard Convection with Large Aspect Ratio

    NASA Astrophysics Data System (ADS)

    Becker, Nathan

    2005-03-01

    Rayleigh-B'enard convection-patterns exhibit a type of spatio-temporal chaos known as domain chaos (DC) at the onset of convection when the sample rotates fast enough about the vertical axis. DC is characterized by domains of straight rolls that chaotically change their orientation and size due to the Küppers-Lortz instability.ootnotetextG. Küppers and D. Lortz, J. Fluid Mech. 35, 609 (1969). However, in a large aspect ratio γ≡r/d=82 cylindrical sample, where r is the radius of the cell and d is the cell thickness, we observed DC in the sample center, surrounded by an annulus of radial rolls populated by occasional defects reminiscent of undulation chaos.ootnotetextK. E. Daniels, B.B. Plapp, and E. Bodenschatz, Phys. Rev. Lett. 84, 5320 (2000). This was unexpected because smaller samples do exhibit domain chaos throughout and the weakly-nonlinear theory that describes the supercritical bifurcation to chaos is expected to be more applicable as γ increases. One possible explanation is that the centrifugal force, which is neglected in the theory, plays an important role.ootnotetextA. Jayaraman and H. Greenside (private communication).

  8. A Frequency-Domain Implementation of a Sliding-Window Traffic Sign Detector for Large Scale Panoramic Datasets

    NASA Astrophysics Data System (ADS)

    Creusen, I. M.; Hazelhoff, L.; De With, P. H. N.

    2013-10-01

    In large-scale automatic traffic sign surveying systems, the primary computational effort is concentrated at the traffic sign detection stage. This paper focuses on reducing the computational load of particularly the sliding window object detection algorithm which is employed for traffic sign detection. Sliding-window object detectors often use a linear SVM to classify the features in a window. In this case, the classification can be seen as a convolution of the feature maps with the SVM kernel. It is well known that convolution can be efficiently implemented in the frequency domain, for kernels larger than a certain size. We show that by careful reordering of sliding-window operations, most of the frequency-domain transformations can be eliminated, leading to a substantial increase in efficiency. Additionally, we suggest to use the overlap-add method to keep the memory use within reasonable bounds. This allows us to keep all the transformed kernels in memory, thereby eliminating even more domain transformations, and allows all scales in a multiscale pyramid to be processed using the same set of transformed kernels. For a typical sliding-window implementation, we have found that the detector execution performance improves with a factor of 5.3. As a bonus, many of the detector improvements from literature, e.g. chi-squared kernel approximations, sub-class splitting algorithms etc., can be more easily applied at a lower performance penalty because of an improved scalability.

  9. Probabilities of large earthquakes in the San Francisco Bay region, California

    SciTech Connect

    Not Available

    1990-01-01

    This book evaluates long-term probabilities of large earthquakes (magnitude 7 or greater) in the San Francisco Bay region by identifying fault segments expected to produce large earthquakes and then estimating the time to the next earthquake on each segment. The probability of one or more large earthquakes in the region in the coming 30 years is estimated at 67 percent. This report contains detailed, technical descriptions of the data and methods used to derive the estimates.

  10. 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

  11. The Replication Domain Model: regulating replicon firing in the context of large-scale chromosome architecture

    PubMed Central

    Pope, Benjamin D.; Gilbert, David M.

    2013-01-01

    The “Replicon Theory” of Jacob, Brenner and Cuzin has reliably served as the paradigm for regulating the sites where individual replicons initiate replication. Concurrent with the replicon model was Taylor’s demonstration that plant and animal chromosomes replicate segmentally in a defined temporal sequence, via cytologically defined units too large to be accounted for by a single replicon. Instead, there seemed to be a program to choreograph when chromosome units replicate during S phase, executed by inititation at clusters of individual replicons within each segment. Here, we summarize recent molecular evidence for the existence of such units, now known as “replication domains”, and discuss how the organization of large chromosomes into structural units has added additional layers of regulation to the original replicon model. PMID:23603017

  12. 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

  13. 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.

  14. 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.

  15. Identification of Regions in the Receiver Domain of the ETHYLENE RESPONSE1 Ethylene Receptor of Arabidopsis Important for Functional Divergence.

    PubMed

    Bakshi, Arkadipta; Wilson, Rebecca L; Lacey, Randy F; Kim, Heejung; Wuppalapati, Sai Keerthana; Binder, Brad M

    2015-09-01

    Ethylene influences the growth and development of Arabidopsis (Arabidopsis thaliana) via five receptor isoforms. However, the ETHYLENE RESPONSE1 (ETR1) ethylene receptor has unique, and sometimes contrasting, roles from the other receptor isoforms. Prior research indicates that the receiver domain of ETR1 is important for some of these noncanonical roles. We determined that the ETR1 receiver domain is not needed for ETR1's predominant role in mediating responses to the ethylene antagonist, silver. To understand the structure-function relationship underlying the unique roles of the ETR1 receiver domain in the control of specific traits, we performed alanine-scanning mutagenesis. We chose amino acids that are poorly conserved and are in regions predicted to have altered tertiary structure compared with the receiver domains of the other two receptors that contain a receiver domain, ETR2 and ETHYLENE INSENSITIVE4. The effects of these mutants on various phenotypes were examined in transgenic, receptor-deficient Arabidopsis plants. Some traits, such as growth in air and growth recovery after the removal of ethylene, were unaffected by these mutations. By contrast, three mutations on one surface of the receiver domain rendered the transgene unable to rescue ethylene-stimulated nutations. Additionally, several mutations on another surface altered germination on salt. Some of these mutations conferred hyperfunctionality to ETR1 in the context of seed germination on salt, but not for other traits, that correlated with increased responsiveness to abscisic acid. Thus, the ETR1 receiver domain has multiple functions where different surfaces are involved in the control of different traits. Models are discussed for these observations.

  16. 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.

  17. 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

  18. Analysis and modeling of the variable region of camelid single-domain antibodies.

    PubMed

    Sircar, Aroop; Sanni, Kayode A; Shi, Jiye; Gray, Jeffrey J

    2011-06-01

    Camelids have a special type of Ab, known as heavy chain Abs, which are devoid of classical Ab light chains. Relative to classical Abs, camelid heavy chain Abs (cAbs) have comparable immunogenicity, Ag recognition diversity and binding affinities, higher stability and solubility, and better manufacturability, making them promising candidates for alternate therapeutic scaffolds. Rational engineering of cAbs to improve therapeutic function requires knowledge of the differences of sequence and structural features between cAbs and classical Abs. In this study, amino acid sequences of 27 cAb variable regions (V(H)H) were aligned with the respective regions of 54 classical Abs to detect amino acid differences, enabling automatic identification of cAb V(H)H CDRs. CDR analysis revealed that the H1 often (and sometimes the H2) adopts diverse conformations not classifiable by established canonical rules. Also, although the cAb H3 is much longer than classical H3 loops, it often contains common structural motifs and sometimes a disulfide bond to the H1. Leveraging these observations, we created a Monte Carlo-based cAb V(H)H structural modeling tool, where the CDR H1 and H2 loops exhibited a median root-mean-square deviation to natives of 3.1 and 1.5 Å, respectively. The protocol generated 8-12, 14-16, and 16-24 residue H3 loops with a median root-mean-square deviation to natives of 5.7, 4.5, and 6.8 Å, respectively. The large deviation of the predicted loops underscores the challenge in modeling such long loops. cAb V(H)H homology models can provide structural insights into interaction mechanisms to enable development of novel Abs for therapeutic and biotechnological use. PMID:21525384

  19. Variable region domain exchange in human IgGs promotes antibody complex formation with accompanying structural changes and altered effector functions.

    PubMed

    Chan, Lisa A; Phillips, Martin L; Wims, Letitia A; Trinh, K Ryan; Denham, Jerrod; Morrison, Sherie L

    2004-07-01

    Variable region domain exchanged IgG, or "inside-out (io)," molecules, were produced to investigate the effects of domain interactions on antibody structure and function. Studies using ultracentrifugation and electron microscopy showed that variable region domain exchange induces non-covalent multimerization through Fab domains. Surprisingly, variable region exchange also affected Fc-associated functions such as serum half-life and binding to protein G and FcgammaRI. These alterations were not merely a consequence of IgG aggregation. Both the extent of multimerization and alterations in Fc-associated properties depended on the IgG isotype.

  20. 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.

  1. 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

  2. Large modal survey testing using the Ibrahim time domain /ITD/ identification technique

    NASA Technical Reports Server (NTRS)

    Ibrahim, S. R.; Pappa, R. S.

    1981-01-01

    The ability of the ITD identification algorithm in identifying a complete set of structural modal parameters using a large number of free-response time histories simultaneously in one analysis, assuming a math model with a high number of degrees-of-freedom, has been studied. Identification results using simulated free responses of a uniform rectangular plate, with 225 measurement stations, and experimental responses from a ground vibration test of the Long Duration Exposure Facility (LDEF) Space Shuttle payload, with 142 measurement stations, are presented. As many as 300 degrees-of-freedom were allowed in analyzing these data. In general, the use of a significantly oversized math model in the identification process was found to maintain or increase identification accuracy and to identify modes of low response level that are not identified with smaller math model sizes. The concept of a Mode Shape Correlation Constant is introduced for use when more than one identification analysis of the same structure are conducted. This constant quantifies the degree of correlation between any two sets of complex mode shapes identified using different excitation conditions, different user-selectable algorithm constants, or overlapping sets of measurements.

  3. Role of the outer pore domain in transient receptor potential vanilloid 1 dynamic permeability to large cations.

    PubMed

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

    2015-02-27

    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.

  4. 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

  5. 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.

  6. Existence domains of large amplitude dust-acoustic solitons in non-thermal plasmas with positive and negative dust

    SciTech Connect

    Maharaj, S. K.; Bharuthram, R.; Singh, S. V.; Lakhina, G. S.; Pillay, S. R.

    2011-11-29

    Using the traditional Sagdeev pseudopotential approach, the existence of large amplitude solitons is investigated for a plasma composed of cold negative dust, adiabatic positive dust, non-thermal ions and Boltzmann electrons. The lower and upper soliton Mach number limitations are determined as a function of various parameters and physical reasons are provided as to why these Mach number limits occur. Some regions in parameter space have been identified where only negative or positive solitons occur, whereas, other regions support the coexistence of both positive and negative potential solitons.

  7. 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...

  8. Nucleation control for large, single crystalline domains of monolayer hexagonal boron nitride via Si-doped Fe catalysts.

    PubMed

    Caneva, Sabina; Weatherup, Robert S; Bayer, Bernhard C; Brennan, Barry; Spencer, Steve J; Mingard, Ken; Cabrero-Vilatela, Andrea; Baehtz, Carsten; Pollard, Andrew J; Hofmann, Stephan

    2015-03-11

    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.

  9. High-precision, large-domain three-dimensional manipulation of nano-materials for fabrication nanodevices

    PubMed Central

    2011-01-01

    Nanoscaled materials are attractive building blocks for hierarchical assembly of functional nanodevices, which exhibit diverse performances and simultaneous functions. We innovatively fabricated semiconductor nano-probes of tapered ZnS nanowires through melting and solidifying by electro-thermal process; and then, as-prepared nano-probes can manipulate nanomaterials including semiconductor/metal nanowires and nanoparticles through sufficiently electrostatic force to the desired location without structurally and functionally damage. With some advantages of high precision and large domain, we can move and position and interconnect individual nanowires for contracting nanodevices. Interestingly, by the manipulating technique, the nanodevice made of three vertically interconnecting nanowires, i.e., diode, was realized and showed an excellent electrical property. This technique may be useful to fabricate electronic devices based on the nanowires' moving, positioning, and interconnecting and may overcome fundamental limitations of conventional mechanical fabrication. PMID:21794151

  10. 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

  11. Time-domain algorithm for single-photon laser-Doppler flowmetry at large interoptode spacing in human bone.

    PubMed

    Binzoni, Tiziano; Van De Ville, Dimitri; Sanguinetti, Bruno

    2014-10-20

    A new laser-Doppler flowmeter at large interoptode spacing, based on single-photon counting (single-photon laser-Doppler flowmetry [SP-LDF]) and allowing assessment of blood flow deep in bone tissue, is proposed and implemented. To exploit the advantages of the new SP-LDF hardware, a dedicated simple and efficient time-domain algorithm has been developed. The new algorithm is based on the zero-order moment of the power density spectrum of the ad hoc prefiltered photoelectric current. The SP-LDF has been validated by Monte Carlo simulations, as well as by experimental measurements on a bone tissue phantom for optical flowmeters and on human. PMID:25402789

  12. Identification of the p53 protein domain involved in formation of the simian virus 40 large T-antigen-p53 protein complex.

    PubMed Central

    Tan, T H; Wallis, J; Levine, A J

    1986-01-01

    An expression vector utilizing the enhancer and promoter region of the simian virus 40 (SV40) DNA regulating a murine p53 cDNA clone was constructed. The vector produced murine p53 protein in monkey cells identified by five different monoclonal antibodies, three of which were specific for the murine form of p53. The murine p53 produced in monkey cells formed an oligomeric protein complex with the SV40 large tumor antigen. A large number of deletion mutations, in-frame linker insertion mutations, and linker insertion mutations resulting in a frameshift mutation were constructed in the cDNA coding portion of the p53 protein expression vector. The wild-type and mutant p53 cDNA vectors were expressed in monkey cells producing the SV40 large T antigen. The conformation and levels of p53 protein and its ability to form protein complexes with the SV40 T antigen were determined by using five different monoclonal antibodies with quite distinct epitope recognition sites. Insertion mutations between amino acid residues 123 and 215 (of a total of 390 amino acids) eliminated the ability of murine p53 to bind to the SV40 large T antigen. Deletion (at amino acids 11 through 33) and insertion mutations (amino acids 222 through 344) located on either side of this T-antigen-binding protein domain produced a murine p53 protein that bound to the SV40 large T antigen. The same five insertion mutations that failed to bind with the SV40 large T antigen also failed to react with a specific monoclonal antibody, PAb246. In contrast, six additional deletion and insertion mutations that produced p53 protein that did bind with T antigen were each recognized by PAb246. The proposed epitope for PAb246 has been mapped adjacent (amino acids 88 through 109) to the T-antigen-binding domain (amino acids 123 through 215) localized by the mutations mapped in this study. Finally, some insertion mutations that produced a protein that failed to bind to the SV40 T antigen appeared to have an enhanced

  13. Hamiltonian Switch Metropolis Monte Carlo Simulations for Improved Conformational Sampling of Intrinsically Disordered Regions Tethered to Ordered Domains of Proteins

    PubMed Central

    2015-01-01

    There is growing interest in the topic of intrinsically disordered proteins (IDPs). Atomistic Metropolis Monte Carlo (MMC) simulations based on novel implicit solvation models have yielded useful insights regarding sequence-ensemble relationships for IDPs modeled as autonomous units. However, a majority of naturally occurring IDPs are tethered to ordered domains. Tethering introduces additional energy scales and this creates the challenge of broken ergodicity for standard MMC sampling or molecular dynamics that cannot be readily alleviated by using generalized tempering methods. We have designed, deployed, and tested our adaptation of the Nested Markov Chain Monte Carlo sampling algorithm. We refer to our adaptation as Hamiltonian Switch Metropolis Monte Carlo (HS-MMC) sampling. In this method, transitions out of energetic traps are enabled by the introduction of an auxiliary Markov chain that draws conformations for the disordered region from a Boltzmann distribution that is governed by an alternative potential function that only includes short-range steric repulsions and conformational restraints on the ordered domain. We show using multiple, independent runs that the HS-MMC method yields conformational distributions that have similar and reproducible statistical properties, which is in direct contrast to standard MMC for equivalent amounts of sampling. The method is efficient and can be deployed for simulations of a range of biologically relevant disordered regions that are tethered to ordered domains. PMID:25136274

  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.

  16. Dynamic triggering potential of large earthquakes recorded by the EarthScope U.S. Transportable Array using a frequency domain detection method

    NASA Astrophysics Data System (ADS)

    Linville, L. M.; Pankow, K. L.; Kilb, D. L.; Velasco, A. A.; Hayward, C.

    2013-12-01

    Because of the abundance of data from the Earthscope U.S. Transportable Array (TA), data paucity and station sampling bias in the US are no longer significant obstacles to understanding some of the physical parameters driving dynamic triggering. Initial efforts to determine locations of dynamic triggering in the US following large earthquakes (M ≥ 8.0) during TA relied on a time domain detection algorithm which used an optimized short-term average to long-term average (STA/LTA) filter and resulted in an unmanageably large number of false positive detections. Specific site sensitivities and characteristic noise when coupled with changes in detection rates often resulted in misleading output. To navigate this problem, we develop a frequency domain detection algorithm that first pre-whitens each seismogram and then computes a broadband frequency stack of the data using a three hour time window beginning at the origin time of the mainshock. This method is successful because of the broadband nature of earthquake signals compared with the more band-limited high frequency picks that clutter results from time domain picking algorithms. Preferential band filtering of the frequency stack for individual events can further increase the accuracy and drive the detection threshold to below magnitude one, but at general cost to detection levels across large scale data sets. Of the 15 mainshocks studied, 12 show evidence of discrete spatial clusters of local earthquake activity occurring within the array during the mainshock coda. Most of this activity is in the Western US with notable sequences in Northwest Wyoming, Western Texas, Southern New Mexico and Western Montana. Repeat stations (associated with 2 or more mainshocks) are generally rare, but when occur do so exclusively in California and Nevada. Notably, two of the most prolific regions of seismicity following a single mainshock occur following the 2009 magnitude 8.1 Samoa (Sep 29, 2009, 17:48:10) event, in areas with few

  17. Enhanced malignant transformation induced by expression of a distinct protein domain of ribonucleotide reductase large subunit from herpes simplex virus type 2.

    PubMed Central

    Ali, M A; McWeeney, D; Milosavljevic, A; Jurka, J; Jariwalla, R J

    1991-01-01

    The 1.3-kilobase (kb) Pst I DNA fragment C (Pst I-C) of herpes simplex virus type 2 (HSV-2) morphological transforming region III (mtrIII; map unit 0.562-0.570) encodes part of the N-terminal half of the large subunit of ribonucleotide reductase (RR1; amino acid residues 71-502) and induces the neoplastic transformation of immortalized cell lines. To assess directly the role of these RR1 protein sequences in cell transformation, the Pst I-C fragment was cloned in an expression vector (p91023) containing an adenovirus-simian virus 40 promoter-enhancer to generate recombinant plasmid p9-C. Expression of a protein domain (approximately 65 kDa) was observed in p9-C-transfected COS-7 and Rat2 cells but not in those transfected with plasmid pHC-14 (Pst I-C in a promoterless vector). In Rat2 cells, p9-C induced highly transformed foci at an elevated frequency compared with that of pHC-14. Introduction of translation termination (TAG) condons within the RR1 coding sequence and within all three reading frames inactivated RR1 protein expression from p9-C and reduced its transforming activity to the level seen with the standard pHC-14 construct. Wild-type p9-C specified a protein kinase capable of autophosphorylation. Computer-assisted analysis further revealed significant similarity between regions of mtrIII-specific RR1 and amino acid patterns conserved within the proinsulin precursor family and DNA transposition proteins. These results identify a distinct domain of the HSV-2 RR1 protein involved in the induction of enhanced malignant transformation. In addition, the data indicate that the mtrIII DNA itself can induce basal-level transformation in the absence of protein expression. Images PMID:1654564

  18. 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.

  19. 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

  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. 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

  2. Process and domain specificity in regions engaged for face processing: an fMRI study of perceptual differentiation.

    PubMed

    Collins, Heather R; Zhu, Xun; Bhatt, Ramesh S; Clark, Jonathan D; Joseph, Jane E

    2012-12-01

    The degree to which face-specific brain regions are specialized for different kinds of perceptual processing is debated. This study parametrically varied demands on featural, first-order configural, or second-order configural processing of faces and houses in a perceptual matching task to determine the extent to which the process of perceptual differentiation was selective for faces regardless of processing type (domain-specific account), specialized for specific types of perceptual processing regardless of category (process-specific account), engaged in category-optimized processing (i.e., configural face processing or featural house processing), or reflected generalized perceptual differentiation (i.e., differentiation that crosses category and processing type boundaries). ROIs were identified in a separate localizer run or with a similarity regressor in the face-matching runs. The predominant principle accounting for fMRI signal modulation in most regions was generalized perceptual differentiation. Nearly all regions showed perceptual differentiation for both faces and houses for more than one processing type, even if the region was identified as face-preferential in the localizer run. Consistent with process specificity, some regions showed perceptual differentiation for first-order processing of faces and houses (right fusiform face area and occipito-temporal cortex and right lateral occipital complex), but not for featural or second-order processing. Somewhat consistent with domain specificity, the right inferior frontal gyrus showed perceptual differentiation only for faces in the featural matching task. The present findings demonstrate that the majority of regions involved in perceptual differentiation of faces are also involved in differentiation of other visually homogenous categories.

  3. 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

  4. 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

  5. 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

  6. 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.

  7. Amplicon structure in multidrug-resistant murine cells: a nonrearranged region of genomic DNA corresponding to large circular DNA.

    PubMed Central

    Ståhl, F; Wettergren, Y; Levan, G

    1992-01-01

    Multidrug resistance (MDR) in tumor cell lines is frequently correlated with amplification of one or more mdr genes. Usually the amplified domain also includes several neighboring genes. Using pulsed-field gel electrophoresis, we have established a restriction map covering approximately 2,200 kb in the drug-sensitive mouse tumor cell line TC13K. The mapped region is located on mouse chromosome 5 and includes the three mdr genes, the gene for the calcium-binding sorcin protein, and a gene with unknown function designated class 5. Long-range maps of the amplified DNA sequences in five of six MDR sublines that had been independently derived from TC13K generally displayed the same pattern as did the parental cell line. All six MDR sublines exhibited numerous double minutes, and one of them displayed a homogeneously staining region in a subpopulation. Large circular molecules, most likely identical to one chromatid of the double minutes, were detected in four of the sublines by linearization with gamma irradiation. The size of the circles was about 2,500 kb, which correlated to a single unit of the amplified domain. We therefore propose that in four independent instances of MDR development, a single unit of about 2,500 kb has been amplified in the form of circular DNA molecules. The restriction enzyme map of the amplified unit is unchanged compared with that of the parental cell line, whereas the joining sites of the circular DNA molecules are not identical but are in the same region. Images PMID:1545798

  8. 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.

  9. Resonance domain surface relief diffractive lens for the visible spectral region.

    PubMed

    Barlev, Omri; Golub, Michael A

    2013-03-01

    Early expectations for a role of diffractive lenses were dramatically lessened by their high order overlapping foci, low optical powers, and competing advances in refractive micro-optics. By bringing the Bragg properties of volume holograms to diffractive lenses we got rid of ghost diffractive orders and the critical trade-off between diffraction efficiency, number of phase levels, and spatial feature-size. Binary off-axis resonance domain diffractive lens with high numerical aperture of 0.16 was designed with analytical effective grating theory, fabricated by direct e-beam writing, etched in fused silica and experimentally investigated. More than 81% measured diffraction efficiency exceeds twice the limits of thin binary optics.

  10. The bridge-region of the Ku superfamily is an atypical zinc ribbon domain

    PubMed Central

    Krishna, S. Sri; Aravind, L.

    2010-01-01

    Members of the Ku superfamily are DNA-end-binding proteins involved in non-homologous end-joining (NHEJ) DNA repair. The published crystal structure of human Ku-DNA complex reveals a heterodimer that forms a ring around dsDNA by means of the Ku core modules. These modules contain a highly conserved seven-stranded β-barrel, which in turn contains an insertion, termed the bridge-region, between its second and third β-strands. The bridge-region adopts an unusual β-strand-rich structure critical for dsDNA-binding and Ku function, but its provenance remains unclear. Here, we demonstrate that the bridge-region of Ku is a novel member of the diverse Zn-ribbon fold group. Sequence analysis reveals that Ku from several Gram-positive bacteria and bacteriophages retain metal-chelating motifs, whereas they have been lost in the versions from most other organisms. Structural comparisons suggest that the Zn-ribbon from Ku bridge-region is the first example of a circularly permuted, segment-swapped Zn-ribbon. This finding helps explain how Ku is likely to bind DNA as an obligate dimer. Further, we hypothesize that retention of the unusual conformation of the turns of the Zn-ribbons, despite loss of the Zn-binding sites, provides clues regarding the mechanism by which the Ku bridge-regions sense the DNA state. PMID:20580930

  11. Escherichia coli methionyl-tRNA formyltransferase: role of amino acids conserved in the linker region and in the C-terminal domain on the specific recognition of the initiator tRNA.

    PubMed

    Gite, S; Li, Y; Ramesh, V; RajBhandary, U L

    2000-03-01

    The formylation of initiator methionyl-tRNA by methionyl-tRNA formyltransferase (MTF) is important for the initiation of protein synthesis in eubacteria. We are studying the molecular mechanisms of recognition of the initiator tRNA by Escherichia coli MTF. MTF from eubacteria contains an approximately 100-amino acid C-terminal extension that is not found in the E. coli glycinamide ribonucleotide formyltransferase, which, like MTF, use N(10)-formyltetrahydrofolate as a formyl group donor. This C-terminal extension, which forms a distinct structural domain, is attached to the N-terminal domain through a linker region. Here, we describe the effect of (i) substitution mutations on some nineteen basic, aromatic and other conserved amino acids in the linker region and in the C-terminal domain of MTF and (ii) deletion mutations from the C-terminus on enzyme activity. We show that the positive charge on two of the lysine residues in the linker region leading to the C-terminal domain are important for enzyme activity. Mutation of some of the basic amino acids in the C-terminal domain to alanine has mostly small effects on the kinetic parameters, whereas mutation to glutamic acid has large effects. However, the deletion of 18, 20, or 80 amino acids from the C-terminus has very large effects on enzyme activity. Overall, our results support the notion that the basic amino acid residues in the C-terminal domain provide a positively charged channel that is used for the nonspecific binding of tRNA, whereas some of the amino acids in the linker region play an important role in activity of MTF.

  12. 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.

  13. 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.

  14. The E-domain region of mechano-growth factor inhibits cellular apoptosis and preserves cardiac function during myocardial infarction.

    PubMed

    Mavrommatis, Evangelos; Shioura, Krystyna M; Los, Tamara; Goldspink, Paul H

    2013-09-01

    Insulin-like growth factor-1 (IGF-1) isoforms are expressed via alternative splicing. Expression of the minor isoform IGF-1Eb [also known as mechano-growth factor (MGF)] is responsive to cell stress. Since IGF-1 isoforms differ in their E-domain regions, we are interested in determining the biological function of the MGF E-domain. To do so, a synthetic peptide analog was used to gain mechanistic insight into the actions of the E-domain. Treatment of H9c2 cells indicated a rapid cellular uptake mechanism that did not involve IGF-1 receptor activation but resulted in a nuclear localization. Peptide treatment inhibited the intrinsic apoptotic pathway in H9c2 cells subjected to cell stress with sorbitol by preventing the collapse of the mitochondrial membrane potential and inhibition of caspase-3 activation. Therefore, we administered the peptide at the time of myocardial infarction (MI) in mice. At 2 weeks post-MI cardiac function, gene expression and cell death were assayed. A significant decline in both systolic and diastolic function was evident in untreated mice based on PV loop analysis. Delivery of the E-peptide ameliorated the decline in function and resulted in significant preservation of cardiac contractility. Associated with these changes were an inhibition of pathologic hypertrophy and significantly fewer apoptotic nuclei in the viable myocardium of E-peptide-treated mice post-MI. We conclude that administration of the MGF E-domain peptide may provide a means of modulating local tissue IGF-1 autocrine/paracrine actions to preserve cardiac function, prevent cell death, and pathologic remodeling in the heart.

  15. 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

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

    PubMed Central

    Chen, Chun-Rong; Salazar, Larry M.; McLachlan, Sandra M.

    2015-01-01

    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

  18. 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.

  19. Wavelength dependence of linear polarization in the visible and near infrared domain for large levitating grains (PROGRA2 instruments)

    NASA Astrophysics Data System (ADS)

    Renard, J.-B.; Hadamcik, E.; Couté, B.; Jeannot, M.; Levasseur-Regourd, A. C.

    2014-10-01

    Remote sensing measurements of light scattered by dust in solar system objects can provide clues on their physical properties. Databases obtained in the laboratory with numerous samples are necessary to interpret these measurements. We present here first studies of the wavelength dependence of the linear polarization between 545 nm and 1.5 μm, using the imaging polarimeters PROGRA2 for large levitating compact grains (PROGRA2-VIS in the visible domain, and the new instrument PROGRA2-IR in the near infrared). The measurements are conducted in microgravity conditions during parabolic flights for glass beads, quartz, sands, silicon carbides, anthracite, and lunar and Martian simulants. Comparison between measurements on glass beads and Mie calculations with glass spheres provides an assessment of the quality of the instruments. The dependence of the polarization on the wavelength is related to the complex refractive index of the particles, i.e. to their composition and to the size of the grains. More laboratory measurements will be necessary, in particular with smaller grains in aggregates, to better reproduce the remote sensing observations of solar system bodies.

  20. 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

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. Transcription elongation factor SII interacts with a domain of the large subunit of human RNA polymerase II

    SciTech Connect

    Rappaport, J.; Cho, K.; Saltzman, A.; Prenger, J.; Golomb, M.; Weinmann, R.

    1988-08-01

    Genomic sequences for the large subunit of human RNA polymerase II corresponding to a part of the fifth exon were inserted into an expression vector at the carboxy-terminal end of the ..beta..-galactosidase gene. The in-frame construct produced a 125-kilodalton fusion protein, containing approximately 10 kilodaltons of the large subunit of RNA polymerase II and 116 kilodaltons of ..beta..-galactosidase. The purified bacterially produced fusion protein inhibited specific transcription from the adenovirus type 2 major late promoter, while ..beta..-galactosidase had no effect. The effect of the fusion protein was during RNA elongation, not at the level of initiation, resembling the faithfully initiated but incomplete transcripts produced with purified factors in the absence of SII. Similarly, monoclonal antibody 2-7B, which reacts with the RNA polymerase II region represented in the fusion protein, inhibited specific transcription at the level of elongation in a whole-cell extract. Both monoclonal antibody 2-7B and the fusion protein, although unable to inhibit purified RNA polymerase II in a nonspecific transcription assay, selectively blocked the stimulation elicited by transcription elongation factor SII on the activity of the purified enzyme in vitro. This suggests that the fusion protein traps the SII in nonstimulatory interactions and that anitibody 2-7B inhibits SII binding to RNA polymerase II. Thus, this suggests that an SII-binding contact required for specific RNA elongation resides within the fifth exon region of the largest RNA polymerase II subunit.

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

    PubMed

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

    2016-06-01

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

  7. 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...

  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. 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

  10. 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

  11. 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.

  12. 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

  13. 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.

  14. 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

  15. 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.

  16. Crystal structure of the functional region of Uro-adherence factor A from Staphylococcus saprophyticus reveals participation of the B domain in ligand binding.

    PubMed

    Matsuoka, Eriko; Tanaka, Yoshikazu; Kuroda, Makoto; Shouji, Yuko; Ohta, Toshiko; Tanaka, Isao; Yao, Min

    2011-02-01

    Staphylococci use cell wall-anchored proteins as adhesins to attach to host tissues. Staphylococcus saprophyticus, a uropathogenic species, has a unique cell wall-anchored protein, uro-adherence factor A (UafA), which shows erythrocyte binding activity. To investigate the mechanism of adhesion by UafA, we determined the crystal structure of the functional region of UafA at 1.5 Å resolution. The structure was composed of three domains, designated as the N2, N3, and B domains, arranged in a triangular relative configuration. Hemagglutination inhibition assay with domain-truncated mutants indicated that both N and B domains were necessary for erythrocyte binding. Based on these results, a novel manner of ligand binding in which the B domain acts as a functional domain was proposed as the adhesion mechanism of S. saprophyticus.

  17. Crystal structure of the functional region of Uro-adherence factor A from Staphylococcus saprophyticus reveals participation of the B domain in ligand binding

    PubMed Central

    Matsuoka, Eriko; Tanaka, Yoshikazu; Kuroda, Makoto; Shouji, Yuko; Ohta, Toshiko; Tanaka, Isao; Yao, Min

    2011-01-01

    Staphylococci use cell wall-anchored proteins as adhesins to attach to host tissues. Staphylococcus saprophyticus, a uropathogenic species, has a unique cell wall-anchored protein, uro-adherence factor A (UafA), which shows erythrocyte binding activity. To investigate the mechanism of adhesion by UafA, we determined the crystal structure of the functional region of UafA at 1.5 Å resolution. The structure was composed of three domains, designated as the N2, N3, and B domains, arranged in a triangular relative configuration. Hemagglutination inhibition assay with domain-truncated mutants indicated that both N and B domains were necessary for erythrocyte binding. Based on these results, a novel manner of ligand binding in which the B domain acts as a functional domain was proposed as the adhesion mechanism of S. saprophyticus. PMID:21280131

  18. Amino Terminal Region of Dengue Virus NS4A Cytosolic Domain Binds to Highly Curved Liposomes

    PubMed Central

    Hung, Yu-Fu; Schwarten, Melanie; Hoffmann, Silke; Willbold, Dieter; Sklan, Ella H.; Koenig, Bernd W.

    2015-01-01

    Dengue virus (DENV) is an important human pathogen causing millions of disease cases and thousands of deaths worldwide. Non-structural protein 4A (NS4A) is a vital component of the viral replication complex (RC) and plays a major role in the formation of host cell membrane-derived structures that provide a scaffold for replication. The N-terminal cytoplasmic region of NS4A(1–48) is known to preferentially interact with highly curved membranes. Here, we provide experimental evidence for the stable binding of NS4A(1–48) to small liposomes using a liposome floatation assay and identify the lipid binding sequence by NMR spectroscopy. Mutations L6E;M10E were previously shown to inhibit DENV replication and to interfere with the binding of NS4A(1–48) to small liposomes. Our results provide new details on the interaction of the N-terminal region of NS4A with membranes and will prompt studies of the functional relevance of the curvature sensitive membrane anchor at the N-terminus of NS4A. PMID:26197333

  19. Use of sequence analysis of the P2 domain for characterization of norovirus strains causing a large multistate outbreak of norovirus gastroenteritis in Germany 2012.

    PubMed

    Höhne, Marina; Niendorf, Sandra; Mas Marques, Andreas; Bock, C-Thomas

    2015-10-01

    Human norovirus is the main cause of non-bacterial gastroenteritis worldwide. It is transmitted from person to person, by fecally contaminated food or water or through virus containing aerosols originating during vomiting of infected persons. In September and October 2012, the largest foodborne norovirus outbreak in Germany so far spread over 5 Federal States (Berlin, Brandenburg, Saxony, Saxony-Anhalt, and Thuringia) affecting nearly 11,000 people mainly in schools and child care facilities. Epidemiological and trace-back investigations supported the assumption that a batch of frozen strawberries imported from China was the likely source of the outbreak. Sequence analysis of the capsid region encoding the P2 domain was used successfully for identification of transmission routes and epidemiologic relationship but was hampered by a lack of universal primers for all known genotypes so far. In the present study, a molecular approach was designed to track outbreak-related samples from the affected states of the large foodborne outbreak in Germany. Therefore, sequence analysis within the highly variable P2 domain of the capsid gene using newly developed universal P2 primers for genogroup I and genogroup II strains in combination with sequencing of the polymerase gene (region A) and the orf1/orf2 junction (region c) was used. The sequence analysis of 138 norovirus positive stool samples suspected to be outbreak-related revealed a considerable genomic diversity. At least 3 strains of genogroup I (I.3, I.4, and I.9) and 5 strains of genogroup II (II.6, II.7, II. 8, and recombinants II.P7_II.6, and II.P16_II.13) as well as 19 samples containing mixtures of these strains were detected. Six samples were considered as not linked to the outbreak. The most prevalent genotype was GI.4 (48/132; 36%). Genotype I.9 and the recombinant strain II.P16_II.13 were detected for the first time in Germany. Notably, the genotype II.P16_II.13 could also be determined in one of the samples of

  20. 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

  1. 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.

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

    PubMed

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

    2016-05-01

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

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

    PubMed

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

    2016-05-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-12-01

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

  5. 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.

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

    PubMed

    Martin, Heather J; Delawska-Elliott, Basia

    2015-01-01

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

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

    PubMed Central

    Martin, Heather J.; Delawska-Elliott, Basia

    2015-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  9. The domain structure of Helicobacter pylori DnaB helicase: the N-terminal domain can be dispensable for helicase activity whereas the extreme C-terminal region is essential for its function

    PubMed Central

    Nitharwal, Ram Gopal; Paul, Subhankar; Dar, Ashraf; Choudhury, Nirupam Roy; Soni, Rajesh K; Prusty, Dhaneswar; Sinha, Sukrat; Kashav, Tara; Mukhopadhyay, Gauranga; Chaudhuri, Tapan Kumar; Gourinath, Samudrala; Dhar, Suman Kumar

    2007-01-01

    Hexameric DnaB type replicative helicases are essential for DNA strand unwinding along with the direction of replication fork movement. These helicases in general contain an amino terminal domain and a carboxy terminal domain separated by a linker region. Due to the lack of crystal structure of a full-length DnaB like helicase, the domain structure and function of these types of helicases are not clear. We have reported recently that Helicobacter pylori DnaB helicase is a replicative helicase in vitro and it can bypass Escherichia coli DnaC activity in vivo. Using biochemical, biophysical and genetic complementation assays, here we show that though the N-terminal region of HpDnaB is required for conformational changes between C6 and C3 rotational symmetry, it is not essential for in vitro helicase activity and in vivo function of the protein. Instead, an extreme carboxy terminal region and an adjacent unique 34 amino acid insertion region were found to be essential for HpDnaB activity suggesting that these regions are important for proper folding and oligomerization of this protein. These results confer great potential in understanding the domain structures of DnaB type helicases and their related function. PMID:17430964

  10. Memory-efficient contour-based region-of-interest coding of arbitrarily large images

    NASA Astrophysics Data System (ADS)

    Sadaka, Nabil G.; Abousleman, Glen P.; Karam, Lina J.

    2007-04-01

    In this paper, we present a memory-efficient, contour-based, region-of-interest (ROI) algorithm designed for ultra-low-bit- rate compression of very large images. The proposed technique is integrated into a user-interactive wavelet-based image coding system in which multiple ROIs of any shape and size can be selected and coded efficiently. The coding technique compresses region-of-interest and background (non-ROI) information independently by allocating more bits to the selected targets and fewer bits to the background data. This allows the user to transmit large images at very low bandwidths with lossy/lossless ROI coding, while preserving the background content to a certain level for contextual purposes. Extremely large images (e.g., 65000 X 65000 pixels) with multiple large ROIs can be coded with minimal memory usage by using intelligent ROI tiling techniques. The foreground information at the encoder/decoder is independently extracted for each tile without adding extra ROI side information to the bit stream. The arbitrary ROI contour is down-sampled and differential chain coded (DCC) for efficient transmission. ROI wavelet masks for each tile are generated and processed independently to handle any size image and any shape/size of overlapping ROIs. The resulting system dramatically reduces the data storage and transmission bandwidth requirements for large digital images with multiple ROIs.

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

    PubMed Central

    Kim, Byoung Sik; Gavin, Hannah E.

    2015-01-01

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

  12. Regional Trends in Large Wildfires and Climate in the Western U.S., 1984-2010

    NASA Astrophysics Data System (ADS)

    Dennison, P. E.; Brewer, S.; Arnold, J.; Moritz, M.

    2013-12-01

    The Monitoring Trends in Burn Severity (MTBS) database provides remote sensing-based maps of fire perimeters for all fires larger than 405 ha (1000 acres) in the Western U.S. The database uniquely permits analysis of large fires on all lands, collected using a uniform methodology, for the 1984-2010 period. We used MTBS data to examine changes in the annual number of large fires, total area burned in large fires, large fire size, and day of year of ignition (DOY) for ten ecoregions across the Western U.S. Fire trends were compared to seasonal trends in maximum temperature, precipitation, and Self-Calibrated Palmer Drought Severity Index (SCPDSI) derived from monthly PRISM data. In a majority of ecoregions, our analysis revealed statistically significant positive trends in the number of large fires and/or total area burned in large fires per year. When all regions were combined, fire occurrence increased at a rate of six large fires per year and total area burned increased at a rate of 274 km2 per year over the 1984-2010 period. Multiple ecoregions demonstrated significant increases in the 90th percentile of large fire size, with trends as high as +3 km2 per year. The 10th percentile of DOY, an indicator of early season large fires, declined in two high elevation ecoregions. This finding agrees with previous research that has observed correlations between earlier snowmelt and increased fire activity at high elevation. Fall maximum temperature trended warmer and SCPDI in all seasons trended drier in the ecoregions with strongest increases in fire activity. At the Western U.S. scale, increases in large fire occurrence and total area burned coincide with increased drought severity over the 1984-2010 period.

  13. Photospheric, Chromospheric and Helioseismic Signatures of a Large Flare in Super-active Region NOAA 10486

    NASA Astrophysics Data System (ADS)

    Ambastha, Ashok

    2006-09-01

    NOAA 10486 produced several powerful flares, including the 4B/X17.2 superflare of October 28, 2003/11:10 UT. This flare was extensively covered by the Hα and GONG instruments operated at the Udaipur Solar Observatory (USO). The central location of the active region on October 28, 2003 was well-suited for the ring diagram analysis to obtain the 3-D power spectra and search for helioseismic response of this large flare on the amplitude, frequency and width of the p-modes. Further, using USO observations, we have identified the sites of new flux emergences, large proper motions and line-of-sight velocity flows in the active region and their relationship with the flare.

  14. A large dispersed chromosomal region required for chromosome segregation in sporulating cells of Bacillus subtilis.

    PubMed

    Wu, Ling Juan; Errington, Jeff

    2002-08-01

    The cis-acting sequences required for chromosome segregation are poorly understood in most organisms, including bacteria. Sporulating cells of Bacillus subtilis undergo an unusual asymmetric cell division during which the origin of DNA replication (oriC) region of the chromosome migrates to an extreme polar position. We have now characterized the sequences required for this migration. We show that the previously characterized soj-spo0J chromosome segregation system is not essential for chromosome movement to the cell pole, so this must be driven by an additional segregation mechanism. Observations on a large set of precisely engineered chromosomal inversions and translocations have identified a polar localization region (PLR), which lies approximately 150-300 kbp to the left of oriC. Surprisingly, oriC itself has no involvement in this chromosome segregation system. Dissection of the PLR showed that it has internal functional redundancy, reminiscent of the large diffuse centromeres of most eukaryotic cells.

  15. A conserved domain of the large subunit of replication factor C binds PCNA and acts like a dominant negative inhibitor of DNA replication in mammalian cells.

    PubMed

    Fotedar, R; Mossi, R; Fitzgerald, P; Rousselle, T; Maga, G; Brickner, H; Messier, H; Kasibhatla, S; Hübscher, U; Fotedar, A

    1996-08-15

    Replication factor C (RF-C), a complex of five polypeptides, is essential for cell-free SV40 origin-dependent DNA replication and viability in yeast. The cDNA encoding the large subunit of human RF-C (RF-Cp145) was cloned in a Southwestern screen. Using deletion mutants of RF-Cp145 we have mapped the DNA binding domain of RF-Cp145 to amino acid residues 369-480. This domain is conserved among both prokaryotic DNA ligases and eukaryotic poly(ADP-ribose) polymerases and is absent in other subunits of RF-C. The PCNA binding domain maps to amino acid residues 481-728 and is conserved in all five subunits of RF-C. The PCNA binding domain of RF-Cp145 inhibits several functions of RF-C, such as: (i) in vitro DNA replication of SV40 origin-containing DNA; (ii) RF-C-dependent loading of PCNA onto DNA; and (iii) RF-C-dependent DNA elongation. The PCNA binding domain of RF-Cp145 localizes to the nucleus and inhibits DNA synthesis in transfected mammalian cells. In contrast, the DNA binding domain of RF-Cp145 does not inhibit DNA synthesis in vitro or in vivo. We therefore conclude that amino acid residues 481-728 of human RF-Cp145 are critical and act as a dominant negative mutant of RF-C function in DNA replication in vivo.

  16. Relationship between structural flexibility and function in the C-terminal region of the heparin-binding domain of VEGF165.

    PubMed

    Jeong, Ki-Woong; Jeong, Min-Cheol; Jin, Bonghwan; Kim, Yangmee

    2013-12-10

    Vascular endothelial growth factor (VEGF) is an angiogenic protein with neurotrophic and neuroprotective effects. Previously, we reported that triamterene (Trm) inhibits VEGF-amyloid β (Aβ) interactions without affecting other biological activities of VEGF or Aβ [Jeong, K.-W., et al. (2011) Biochemistry 50, 4843-4854]. We further showed that molecular motions in the N-terminal disordered loop region of the heparin-binding domain (HBD) are important for interaction with Trm. To investigate the importance of motion at the C-terminal domain of HBD, we constructed a binding model of HBD with heparin octasaccharide (HOS) based on measurements of chemical shift changes and docking studies. Furthermore, the dynamic properties of the HBD-HOS and HBD-Trm-HOS complexes were assessed by measuring spin relaxation rates. The results showed that the HOS-binding site is composed of two basic clusters consisting of side chains of residues R13, R14, and K15 and residues K30, R35, and R49. When HOS binds, values for the heteronuclear nuclear Overhauser effect near HOS-binding sites increased dramatically. CPMG (Carr-Purcell-Meiboom-Gill sequence) experiments as well as an R2 relaxation experiment were undertaken to understand millisecond time-scale motions in HBD. There is large relaxation dispersion of residues at Trm- and HOS-binding sites in free HBD. C-Terminal residues such as S34, C48, and D51 near the HOS-binding sites continued to exhibit slow conformational motions in the HBD-Trm complex, while those slow motions disappeared in the bound conformation of HBD with HOS. Collectively, our results demonstrate that the inherent structural flexibilities of the C-terminal region of the HBD are important in the heparin binding process and that Trm does not inhibit VEGF-heparin interactions necessary for the biological activities of VEGF.

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

    PubMed

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

    2016-07-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-07-01

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

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

    PubMed

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

    2016-01-25

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

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

    SciTech Connect

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

    2012-05-20

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

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

    PubMed

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

    2016-01-25

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-04-01

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

  3. Self-association of isolated large cytoplasmic domain of plasma membrane H+ -ATPase from Saccharomyces cerevisiae: role of the phosphorylation domain in a general dimeric model for P-ATPases.

    PubMed

    Almeida, W I; Martins, O B; Carvalho-Alves, P C

    2006-11-01

    Large cytoplasmic domain (LCD) plasma membrane H+ -ATPase from S. cerevisiae was expressed as two fusion polypeptides in E. coli: a DNA sequence coding for Leu353-Ileu674 (LCDh), comprising both nucleotide (N) and phosphorylation (P) domains, and a DNA sequence coding for Leu353-Thr543 (LCDDeltah, lacking the C-terminus of P domain), were inserted in expression vectors pDEST-17, yielding the respective recombinant plasmids. Overexpressed fusion polypeptides were solubilized with 6 M urea and purified on affinity columns, and urea was removed by dialysis. Their predicted secondary structure contents were confirmed by CD spectra. In addition, both recombinant polypeptides exhibited high-affinity 2',3'-O-(2,4,6-trinitrophenyl)adenosine-5'-triphosphate (TNP-ATP) binding (Kd = 1.9 microM and 2.9 microM for LCDh and LCDDeltah, respectively), suggesting that they have native-like folding. The gel filtration profile (HPLC) of purified LCDh showed two main peaks, with molecular weights of 95 kDa and 39 kDa, compatible with dimeric and monomeric forms, respectively. However, a single elution peak was observed for purified LCDDeltah, with an estimated molecular weight of 29 kDa, as expected for a monomer. Together, these data suggest that LCDh exist in monomer-dimer equilibrium, and that the C-terminus of P domain is necessary for self-association. We propose that such association is due to interaction between vicinal P domains, which may be of functional relevance for H+ -ATPase in native membranes. We discuss a general dimeric model for P-ATPases with interacting P domains, based on published crystallography and cryo-electron microscopy evidence.

  4. The cysteine-rich region and the whey acidic protein domain are essential for anosmin-1 biological functions.

    PubMed

    Esteban, Pedro F; Murcia-Belmonte, Verónica; García-González, Diego; de Castro, Fernando

    2013-03-01

    The protein anosmin-1, coded by the KAL1 gene responsible for the X-linked form of Kallmann syndrome (KS), exerts its biological effects mainly through the interaction with and signal modulation of fibroblast growth factor receptor 1 (FGFR1). We have previously shown the interaction of the third fibronectin-like type 3 (FnIII) domain and the N-terminal region of anosmin-1 with FGFR1. Here, we demonstrate that missense mutations reported in patients with KS, C172R and N267K did not alter or substantially reduce, respectively, the binding to FGFR1. These substitutions annulled the chemoattraction of the full-length protein over subventricular zone (SVZ) neuronal precursors (NPs), but they did not annul it in the N-terminal-truncated protein (A1Nt). We also show that although not essential for binding to FGFR1, the cysteine-rich (CR) region is necessary for anosmin-1 function and that FnIII.3 cannot substitute for FnIII.1 function. Truncated proteins recapitulating nonsense mutations found in KS patients did not show the chemotropic effect on SVZ NPs, suggesting that the presence behind FnIII.1 of any part of anosmin-1 produces an unstable protein incapable of action. We also identify the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway as necessary for the chemotropic effect exerted by FGF2 and anosmin-1 on rat SVZ NPs.

  5. Measured Response of Local, Mid-range and Far-range Discontinuities of Large Metal Groundplanes using Time Domain Techniques

    NASA Astrophysics Data System (ADS)

    Schrader, T.; Münter, K.; Battermann, S.; Garbe, H.

    2005-05-01

    This work describes a method to detect and to quantify any local or mid-range discontinuity on extended flat metal planes. Often these planes are used for antenna calibration (open area test site - OATS) or the plane could be the ground of a semi-anechoic chamber used in Electromagnetic Compatibility (EMC) testing. The measurement uncertainty of antenna calibration or EMC testing depends on the groundplane's quality, which can be accessed using this method. A vector network analyzer with time-domain option is used to determine the complex-valued input scattering parameter S11,F of an aperture antenna in a monostatic setup. S;11,F contains the information desired about the discontinuities and is measured in the frequency domain with high dynamic range. But only after a linear filtering utilizing the Chirp-Z-Transform the obtained time-domain signal S11,T evidence of local and mid-range discontinuities.

  6. Regions outside of conserved PxxPxR motifs drive the high affinity interaction of GRB2 with SH3 domain ligands.

    PubMed

    Bartelt, Rebekah R; Light, Jonathan; Vacaflores, Aldo; Butcher, Alayna; Pandian, Madhana; Nash, Piers; Houtman, Jon C D

    2015-10-01

    SH3 domains are evolutionarily conserved protein interaction domains that control nearly all cellular processes in eukaryotes. The current model is that most SH3 domains bind discreet PxxPxR motifs with weak affinity and relatively low selectivity. However, the interactions of full-length SH3 domain-containing proteins with ligands are highly specific and have much stronger affinity. This suggests that regions outside of PxxPxR motifs drive these interactions. In this study, we observed that PxxPxR motifs were required for the binding of the adaptor protein GRB2 to short peptides from its ligand SOS1. Surprisingly, PxxPxR motifs from the proline rich region of SOS1 or CBL were neither necessary nor sufficient for the in vitro or in vivo interaction with full-length GRB2. Together, our findings show that regions outside of the consensus PxxPxR sites drive the high affinity association of GRB2 with SH3 domain ligands, suggesting that the binding mechanism for this and other SH3 domain interactions may be more complex than originally thought.

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

    PubMed

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

    2015-03-27

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

  8. Key Functional Regions in the Histone Variant H2A.Z C-Terminal Docking Domain

    PubMed Central

    Wang, Alice Y.; Aristizabal, Maria J.; Ryan, Colm; Krogan, Nevan J.; Kobor, Michael S.

    2011-01-01

    The incorporation of histone variants into nucleosomes represents one way of altering the chromatin structure to accommodate diverse functions. Histone variant H2A.Z has specific roles in gene regulation, heterochromatin boundary formation, and genomic integrity. The precise features required for H2A.Z to function and specify an identity different from canonical H2A remain to be fully explored. Analysis of the C-terminal docking domain of H2A.Z in Saccharomyces cerevisiae using epistatic miniarray profile (E-MAP) uncovered nuanced requirements of the H2A.Z C-terminal region for cell growth when additional genes were compromised. Moreover, the H2A.Z(1–114) truncation, lacking the last 20 amino acids of the protein, did not support regular H2A.Z functions, such as resistance to genotoxic stress, restriction of heterochromatin in its native context, GAL1 gene activation, and chromatin anchoring. The corresponding region of H2A could fully rescue the strong defects caused by loss of this functionally essential region in the C terminus of H2A.Z. Despite the dramatic reduction in function, the H2A.Z(1–114) truncation still bound the H2A.Z deposition complex SWR1-C, the histone chaperone Chz1, and histone H2B. These data are consistent with a model in which retaining the variant in chromatin after its deposition by SWR1-C is a crucial determinant of its function. PMID:21791612

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

    NASA Astrophysics Data System (ADS)

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

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

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

    NASA Technical Reports Server (NTRS)

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

    2015-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-06-01

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

  12. LARGE SOLAR ENERGETIC PARTICLE EVENTS ASSOCIATED WITH FILAMENT ERUPTIONS OUTSIDE ACTIVE REGIONS

    SciTech Connect

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

    2015-06-10

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

  13. Optical observations of very low ionization HII regions in the large Magellanic cloud

    NASA Technical Reports Server (NTRS)

    Pena, M.; Ruiz, M. T.; Rubio, M.

    1986-01-01

    Several very low ionization isolated HII regions were detected on a prism-objective plate of the Large Magellanic Cloud. Most of the objects show a very weak (OIII) lambda 5007 emission line and, on the other hand the (OII) lambda 6584 doublets are very intense. This kind of objects seem to be ideal in order to determine accurate N and O abundance, avoiding the use of large ionization correction factors in the N abundance determination. Spectrophotometric observations of these regions were carried out with the 4 m telescope and the 2-D Frutti spectrograph at Cerro Tololo, and with the 1.52 m and the Image Dissector Scanner (IDS) at La Silla, ESO. The wavelength range lambda lambda 3700 to 7000 A was covered. Calibrated fluxes of the emission lines detected were measured, and from these data preliminary results of physical conditions of the gas as well as some ionic abundances were derived. Comparisons of the observations with ionization structure models show that the effective temperatures of the ionizing stars are less than 35,000 K. Possible abundances gradients across the large megallanic cloud are discussed.

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

    NASA Astrophysics Data System (ADS)

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

    2012-04-01

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

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

    SciTech Connect

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

    2011-05-10

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

  16. Radio Emission Toward Regions of Massive Star Formation in the Large Magellanic Cloud

    NASA Astrophysics Data System (ADS)

    Johanson, Adam K.

    2015-01-01

    Four regions of massive star formation in the Large Magellanic Cloud (LMC) were observed for water and methanol maser emission and radio continuum emission. A total of 42 radio detections were made including 27 new radio sources, four water masers, and eight compact H II regions. The lobes of a radio galaxy were resolved for the first time, and the host galaxy identified. Seven sources were associated with known massive young stellar objects (YSOs). A multi-wavelength analysis using both the infrared and radio spectrum was used to characterize the sources. Mid-infrared color-magnitude selection criteria for ultracompact H II (UCHII) regions in the LMC are presented, yielding 136 UCHII region candidates throughout that galaxy. New maser detections identified two previously unknown massive YSOs. No methanol masers were detected, consistent with previous studies and supporting the hypothesis that the LMC may be deficient in these molecules. These discoveries contribute to the history of star formation in the LMC, which will lead to a better understanding of star formation in the Milky Way and throughout the universe.

  17. Large scale photospheric magnetic field: The diffusion of active region fields

    NASA Technical Reports Server (NTRS)

    Schatten, K. H.; Leighton, R. B.; Howard, R.; Wilcox, J. M.

    1972-01-01

    The large-scale phototospheric magnetic field was computed by allowing observed active region fields to diffuse and to be sheared by differential rotation in accordance with the Leighton (1969) magneto-kinematic model of the solar cycle. The differential rotation of the computed field patterns as determined by autocorrelation curves is similar to that of the observed photospheric field, and poleward of 20 deg. latitude both are significantly different from the differential rotation of the long-lived sunspots (Newton and Nunn, 1951) used as an input into the computations.

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

    SciTech Connect

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

    2014-07-20

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

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

    PubMed Central

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

    2003-01-01

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

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

    SciTech Connect

    Wang, Yu U.

    2013-12-06

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

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

    DOEpatents

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

    1998-01-01

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

  2. Solution structure and backbone dynamics of the N-terminal region of the calcium regulatory domain from soybean calcium-dependent protein kinase alpha.

    PubMed

    Weljie, Aalim M; Gagné, Stéphane M; Vogel, Hans J

    2004-12-01

    Ca(2+)-dependent protein kinases (CDPKs) are vital Ca(2+)-signaling proteins in plants and protists which have both a kinase domain and a self-contained calcium regulatory calmodulin-like domain (CLD). Despite being very similar to CaM (>40% identity) and sharing the same fold, recent biochemical and structural evidence suggests that the behavior of CLD is distinct from its namesake, calmodulin. In this study, NMR spectroscopy is employed to examine the structure and backbone dynamics of a 168 amino acid Ca(2+)-saturated construct of the CLD (NtH-CLD) in which almost the entire C-terminal domain is exchange broadened and not visible in the NMR spectra. Structural characterization of the N-terminal domain indicates that the first Ca(2+)-binding loop is significantly more open than in a recently reported structure of the CLD complexed with a putative intramolecular binding region (JD) in the CDPK. Backbone dynamics suggest that parts of the third helix exhibit unusually high mobility, and significant exchange, consistent with previous findings that this helix interacts with the C-terminal domain. Dynamics data also show that the "tether" region, consisting of the first 11 amino acids of CLD, is highly mobile and these residues exhibit distinctive beta-type secondary structure, which may help to position the JD and CLD. Finally, the unusual global dynamic behavior of the protein is rationalized on the basis of possible interdomain rearrangements and the highly variable environments of the C- and N-terminal domains.

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

    NASA Astrophysics Data System (ADS)

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

    2010-03-01

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

  4. Characterization of Two Monoclonal Antibodies That Recognize Linker Region and Carboxyl Terminal Domain of Coronavirus Nucleocapsid Protein

    PubMed Central

    Zhu, Yunnuan; Shi, Hongyan; Chen, Jianfei; Shi, Da; Feng, Li

    2016-01-01

    The transmissible gastroenteritis virus (TGEV) nucleocapsid (N) protein plays important roles in the replication and translation of viral RNA. The present study provides the first description of two monoclonal antibodies (mAbs) (5E8 and 3D7) directed against the TGEV N protein linker region (LKR) and carboxyl terminal domain (CTD). The mAbs 5E8 and 3D7 reacted with native N protein in western blotting and immunofluorescence assay (IFA). Two linear epitopes, 189SVEQAVLAALKKLG202 and 246VTRFYGARSSSA257, located in the LKR and CTD of TGEV N protein, respectively, were identified after truncating the protein and applying a peptide scanning technique. Using mAb 5E8, we observed that the N protein was expressed in the cytoplasm during TGEV replication and that the protein could be immunoprecipitated from TGEV-infected PK-15 cells. The mAb 5E8 can be applied for different approaches to diagnosis of TGEV infection. In addition, the antibodies represent useful tools for investigating the antigenic properties of the N protein. PMID:27689694

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

    NASA Astrophysics Data System (ADS)

    Mohanty, Binayak; Yang, Zhenlei

    2016-04-01

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

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

    ERIC Educational Resources Information Center

    Ryan, Jennifer; Keir, Scott

    2008-01-01

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

  7. Lipid domains in intact fiber-cell plasma membranes isolated from cortical and nuclear regions of human eye lenses of donors from different age groups.

    PubMed

    Raguz, Marija; Mainali, Laxman; O'Brien, William J; Subczynski, Witold K

    2015-03-01

    The results reported here clearly document changes in the properties and the organization of fiber-cell membrane lipids that occur with age, based on electron paramagnetic resonance (EPR) analysis of lens membranes of clear lenses from donors of age groups from 0 to 20, 21 to 40, and 61 to 80 years. The physical properties, including profiles of the alkyl chain order, fluidity, hydrophobicity, and oxygen transport parameter, were investigated using EPR spin-labeling methods, which also provide an opportunity to discriminate coexisting lipid domains and to evaluate the relative amounts of lipids in these domains. Fiber-cell membranes were found to contain three distinct lipid environments: bulk lipid domain, which appears minimally affected by membrane proteins, and two domains that appear due to the presence of membrane proteins, namely boundary and trapped lipid domains. In nuclear membranes the amount of boundary and trapped phospholipids as well as the amount of cholesterol in trapped lipid domains increased with the donors' age and was greater than that in cortical membranes. The difference between the amounts of lipids in domains uniquely formed due to the presence of membrane proteins in nuclear and cortical membranes increased with the donors' age. It was also shown that cholesterol was to a large degree excluded from trapped lipid domains in cortical membranes. It is evident that the rigidity of nuclear membranes was greater than that of cortical membranes for all age groups. The amount of lipids in domains of low oxygen permeability, mainly in trapped lipid domains, were greater in nuclear than cortical membranes and increased with the age of donors. These results indicate that the nuclear fiber cell plasma membranes were less permeable to oxygen than cortical membranes and become less permeable to oxygen with age. In clear lenses, age-related changes in the lens lipid and protein composition and organization appear to occur in ways that increase fiber

  8. Lipid Domains in Intact Fiber-Cell Plasma Membranes Isolated from Cortical and Nuclear Regions of Human Eye Lenses of Donors from Different Age Groups

    PubMed Central

    Raguz, Marija; Mainali, Laxman; O’Brien, William J.; Subczynski, Witold K.

    2015-01-01

    The results reported here clearly document changes in the properties and the organization of fiber-cell membrane lipids that occur with age, based on electron paramagnetic resonance (EPR) analysis of lens membranes of clear lenses from donors of age groups from 0 to 20, 21 to 40, and 61 to 80 years. The physical properties, including profiles of the alkyl chain order, fluidity, hydrophobicity, and oxygen transport parameter, were investigated using EPR spin-labeling methods, which also provide an opportunity to discriminate coexisting lipid domains and to evaluate the relative amounts of lipids in these domains. Fiber-cell membranes were found to contain three distinct lipid environments: bulk lipid domain, which appears minimally affected by membrane proteins, and two domains that appear due to the presence of membrane proteins, namely boundary and trapped lipid domains. In nuclear membranes the amount of boundary and trapped phospholipids as well as the amount of cholesterol in trapped lipid domains increased with the donors’ age and was greater than that in cortical membranes. The difference between the amounts of lipids in domains uniquely formed due to the presence of membrane proteins in nuclear and cortical membranes increased with the donors’ age. It was also shown that cholesterol was to a large degree excluded from trapped lipid domains in cortical membranes. It is evident that the rigidity of nuclear membranes was greater than that of cortical membranes for all age groups. The amount of lipids in domains of low oxygen permeability, mainly in trapped lipid domains, were greater in nuclear than cortical membranes and increased with the age of donors. These results indicate that the nuclear fiber cell plasma membranes were less permeable to oxygen than cortical membranes and become less permeable to oxygen with age. In clear lenses, age-related changes in the lens lipid and protein composition and organization appear to occur in ways that increase fiber

  9. Involvement of the heterodimeric interface region of the nucleotide binding domain-2 (NBD2) in the CFTR quaternary structure and membrane stability.

    PubMed

    Micoud, Julien; Chauvet, Sylvain; Scheckenbach, Klaus Ernst Ludwig; Alfaidy, Nadia; Chanson, Marc; Benharouga, Mohamed

    2015-10-01

    The cystic fibrosis transmembrane conductance regulator (CFTR) is the only member of the ATP-binding cassette (ABC) superfamily that functions as a chloride channel. The predicted structure of CFTR protein contains two membrane-spanning domains (MSDs), each followed by a nucleotide binding domain (NBD1 and NBD2). The opening of the Cl- channel is directly linked to ATP-driven tight dimerization of CFTR's NBD1 and NBD2 domains. The presence of a heterodimeric interfaces (HI) region in NBD1 and NBD2 generated a head to tail orientation necessary for channel activity. This process was also suggested to promote important conformational changes in the associated transmembrane domains of CFTR, which may impact the CFTR plasma membrane stability. To better understand the role of the individual HI region in this process, we generated recombinant CFTR protein with suppressed HI-NBD1 and HI-NBD2. Our results indicate that HI-NBD2 deletion leads to the loss of the dimerization profile of CFTR that affect its plasma membrane stability. We conclude that, in addition to its role in Cl- transport, HI-NBD2 domain confers membrane stability of CFTR by consolidating its quaternary structure through interactions with HI-NBD1 region.

  10. PHYSICAL PROPERTIES OF LARGE AND SMALL GRANULES IN SOLAR QUIET REGIONS

    SciTech Connect

    Yu Daren; Xie Zongxia; Hu Qinghua; Yang Shuhong; Zhang Jun; Wang Jingxiu E-mail: zjun@ourstar.bao.ac.cn

    2011-12-10

    The normal mode observations of seven quiet regions obtained by the Hinode spacecraft are analyzed to study the physical properties of granules. An artificial intelligence technique is introduced to automatically find the spatial distribution of granules in feature spaces. In this work, we investigate the dependence of granular continuum intensity, mean Doppler velocity, and magnetic fields on granular diameter. We recognized 71,538 granules by an automatic segmentation technique and then extracted five properties: diameter, continuum intensity, Doppler velocity, and longitudinal and transverse magnetic flux density to describe the granules. To automatically explore the intrinsic structures of the granules in the five-dimensional parameter space, the X-means clustering algorithm and one-rule classifier are introduced to define the rules for classifying the granules. It is found that diameter is a dominating parameter in classifying the granules and two families of granules are derived: small granules with diameters smaller than 1.''44, and large granules with diameters larger than 1.''44. Based on statistical analysis of the detected granules, the following results are derived: (1) the averages of diameter, continuum intensity, and Doppler velocity in the upward direction of large granules are larger than those of small granules; (2) the averages of absolute longitudinal, transverse, and unsigned flux density of large granules are smaller than those of small granules; (3) for small granules, the average of continuum intensity increases with their diameters, while the averages of Doppler velocity, transverse, absolute longitudinal, and unsigned magnetic flux density decrease with their diameters. However, the mean properties of large granules are stable; (4) the intensity distributions of all granules and small granules do not satisfy Gaussian distribution, while that of large granules almost agrees with normal distribution with a peak at 1.04 I{sub 0}.

  11. Phantoms of the forest: legacy risk effects of a regionally extinct large carnivore.

    PubMed

    Sahlén, Ellinor; Noell, Sonja; DePerno, Christopher S; Kindberg, Jonas; Spong, Göran; Cromsigt, Joris P G M

    2016-02-01

    The increased abundance of large carnivores in Europe is a conservation success, but the impact on the behavior and population dynamics of prey species is generally unknown. In Europe, the recolonization of large carnivores often occurs in areas where humans have greatly modified the landscape through forestry or agriculture. Currently, we poorly understand the effects of recolonizing large carnivores on extant prey species in anthropogenic landscapes. Here, we investigated if ungulate prey species showed innate responses to the scent of a regionally exterminated but native large carnivore, and whether the responses were affected by human-induced habitat openness. We experimentally introduced brown bear Ursus arctos scent to artificial feeding sites and used camera traps to document the responses of three sympatric ungulate species. In addition to controls without scent, reindeer scent Rangifer tarandus was used as a noncarnivore, novel control scent. Fallow deer Dama dama strongly avoided areas with bear scent. In the presence of bear scent, all ungulate species generally used open sites more than closed sites, whereas the opposite was observed at sites with reindeer scent or without scent. The opening of forest habitat by human practices, such as forestry and agriculture, creates a larger gradient in habitat openness than available in relatively unaffected closed forest systems, which may create opportunities for prey to alter their habitat selection and reduce predation risk in human-modified systems that do not exist in more natural forest systems. Increased knowledge about antipredator responses in areas subjected to anthropogenic change is important because these responses may affect prey population dynamics, lower trophic levels, and attitudes toward large carnivores. These aspects may be of particular relevance in the light of the increasing wildlife populations across much of Europe. PMID:26865966

  12. Hydrologic effects of large southwestern USA wildfires significantly increase regional water supply: fact or fiction?

    NASA Astrophysics Data System (ADS)

    Wine, M. L.; Cadol, D.

    2016-08-01

    In recent years climate change and historic fire suppression have increased the frequency of large wildfires in the southwestern USA, motivating study of the hydrological consequences of these wildfires at point and watershed scales, typically over short periods of time. These studies have revealed that reduced soil infiltration capacity and reduced transpiration due to tree canopy combustion increase streamflow at the watershed scale. However, the degree to which these local increases in runoff propagate to larger scales—relevant to urban and agricultural water supply—remains largely unknown, particularly in semi-arid mountainous watersheds co-dominated by winter snowmelt and the North American monsoon. To address this question, we selected three New Mexico watersheds—the Jemez (1223 km2), Mogollon (191 km2), and Gila (4807 km2)—that together have been affected by over 100 wildfires since 1982. We then applied climate-driven linear models to test for effects of fire on streamflow metrics after controlling for climatic variability. Here we show that, after controlling for climatic and snowpack variability, significantly more streamflow discharged from the Gila watershed for three to five years following wildfires, consistent with increased regional water yield due to enhanced infiltration-excess overland flow and groundwater recharge at the large watershed scale. In contrast, we observed no such increase in discharge from the Jemez watershed following wildfires. Fire regimes represent a key difference between the contrasting responses of the Jemez and Gila watersheds with the latter experiencing more frequent wildfires, many caused by lightning strikes. While hydrologic dynamics at the scale of large watersheds were previously thought to be climatically dominated, these results suggest that if one fifth or more of a large watershed has been burned in the previous three to five years, significant increases in water yield can be expected.

  13. Four large-scale field-aligned current systmes in the dayside high-latitude region

    NASA Technical Reports Server (NTRS)

    Ohtani, S.; Potemra, T. A.; Newell, P.T.; Zanetti, L. J.; Iijima, T.; Watanabe, M.; Blomberg, L. G.; Elphinstone, R. D.; Murphree, J. S.; Yamauchi, M.

    1995-01-01

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

  14. Slc26a9 is inhibited by the R-region of the cystic fibrosis transmembrane conductance regulator via the STAS domain.

    PubMed

    Chang, Min-Hwang; Plata, Consuelo; Sindic, Aleksandra; Ranatunga, Wasantha K; Chen, An-Ping; Zandi-Nejad, Kambiz; Chan, Kim W; Thompson, James; Mount, David B; Romero, Michael F

    2009-10-01

    SLC26 proteins function as anion exchangers, channels, and sensors. Previous cellular studies have shown that Slc26a3 and Slc26a6 interact with the R-region of the cystic fibrosis transmembrane conductance regulator (CFTR), (R)CFTR, via the Slc26-STAS (sulfate transporter anti-sigma) domain, resulting in mutual transport activation. We recently showed that Slc26a9 has both nCl(-)-HCO(3)(-) exchanger and Cl(-) channel function. In this study, we show that the purified STAS domain of Slc26a9 (a9STAS) binds purified (R)CFTR. When Slc26a9 and (R)CFTR fragments are co-expressed in Xenopus oocytes, both Slc26a9-mediated nCl(-)-HCO(3)(-) exchange and Cl(-) currents are almost fully inhibited. Deletion of the Slc26a9 STAS domain (a9-DeltaSTAS) virtually eliminated the Cl(-) currents with only a modest affect on nCl(-)-HCO(3)(-) exchange activity. Co-expression of a9-DeltaSTAS and the (R)CFTR fragment did not alter the residual a9-DeltaSTAS function. Replacing the Slc26a9 STAS domain with the Slc26a6 STAS domain (a6-a9-a6) does not change Slc26a9 function and is no longer inhibited by (R)CFTR. These data indicate that the Slc26a9-STAS domain, like other Slc26-STAS domains, binds CFTR in the R-region. However, unlike previously reported data, this binding interaction inhibits Slc26a9 ion transport activity. These results imply that Slc26-STAS domains may all interact with (R)CFTR but that the physiological outcome is specific to differing Slc26 proteins, allowing for dynamic and acute fine tuning of ion transport for various epithelia.

  15. Large methane emission upon spring thaw from natural wetlands in the northern permafrost region

    SciTech Connect

    Song, Changchun; Xu, Xiaofeng; Sun, Xiaoxin; Tian, Hanqin; Sun, Li; Miao, Yuqing; Wang, Xianwei; Guo, Yuedong

    2012-01-01

    The permafrost carbon climate feedback is one of the major mechanisms in controlling the climate ecosystem interactions in northern high latitudes. Of this feedback, methane (CH4) emission from natural wetlands is critically important due to its high warming potential. The freeze thaw transition has been confirmed to play an important role in annual CH4 budget, yet the magnitude of this effect is uncertain. An intensive field campaign was carried out in the Sanjiang Plain, Northeast China to estimate the CH4 emission in the spring freeze thaw transition period. The observation concluded that a large CH4 source was caused by spring thaw; the maximum hourly emission rate was 48.6 g C m 2 h 1, more than three orders of the regularly observed CH4 emission rate in the growing season. In some sporadically observed 'hot spots', the spring thawing effect contributed to a large CH4 source of 31.3 10.1 g C m 2, which is approximately 80% of the previously calculated annual CH4 emission in the same study area. If our results are typical for natural wetlands in the Northern Hemisphere permafrost region, we estimate a global CH4 source strength of 0.5 1.0 Tg C (1 Tg =1012 g) caused by spring thaw in the Northern Hemisphere permafrost region in the year 2011. Combining with available satellite and flask data, a regional extrapolation reaches a temporal pattern of CH4 emission during 2003 2009 which is consistent with recently observed changes in atmospheric CH4 concentration in the high latitudes. This suggests that the CH4 emission upon spring thaw in the high latitudes might be enhanced by the projected climate warming. These findings indicate that the spring thawing effect is an important mechanism in the permafrost carbon climate feedback and needs to be incorporated in Earth system models.

  16. Origin of Strong Lunar Magnetic Anomalies: More Detailed Mapping in Regions Antipodal to Young Large Basins

    NASA Astrophysics Data System (ADS)

    Hood, L. L.; Richmond, N.; Spudis, P.

    2012-12-01

    Previous work has found evidence that the largest concentrations of strong lunar crustal magnetic fields are in regions antipodal to four young large lunar basins: Orientale, Imbrium, Crisium, and Serenitatis (Mitchell et al., Icarus, 2008; and references therein). A preliminary model for the production of lunar basin antipodal magnetic signatures has been developed (Hood and Artemieva, Icarus, 2008; Gattacceca et al., EPSL, 2010). The model involves shock magnetization of crustal materials in the presence of a transient magnetic field amplified by the expanding ionized vapor-melt cloud as it converges in the antipodal region. The model does not exclude a core dynamo; any ambient magnetic field (external solar wind or internal core dynamo) can be amplified in the antipodal zone. In this paper, we report further efforts to map in more detail Lunar Prospector magnetometer data in regions antipodal to young lunar basins. In addition to the four basins identified above, we also consider the polar Schrodinger basin, which is one of the three youngest lunar basins and which has not been previously considered in this context. We apply a direct mapping method (see Hood, Icarus, 2011 for details) to produce more complete maps of lunar magnetic anomalies at low altitudes over the central far side and over the north polar region. We also consider geologic data and spacecraft imagery to identify unusual modified terrain, which may be indicative of shock modification in the same basin antipodal zones. Previous work indicates the existence of such terrain antipodal to Imbrium, Orientale, and Serenitatis, as well as antipodal to the Caloris basin on Mercury. Results first confirm the concentrations of anomalies antipodal to Orientale, Imbrium, Crisium, and Orientale, and the occurrence of modified terrain in three of the four basin antipode zones (see, e.g., Richmond et al., JGR, 2005). In addition, we report here evidence for a large concentration of anomalies that is centered

  17. THE GOULD’S BELT VERY LARGE ARRAY SURVEY. II. THE SERPENS REGION

    SciTech Connect

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

    2015-05-20

    We present deep (∼17 μJy) radio continuum observations of the Serpens molecular cloud, the Serpens south cluster, and the W40 region obtained using the Very Large Array in its A configuration. We detect a total of 146 sources, 29 of which are young stellar objects (YSOs), 2 of which are BV stars, and 5 more of which are associated with phenomena related to YSOs. Based on their radio variability and spectral index, we propose that about 16 of the remaining 110 unclassified sources are also YSOs. For approximately 65% of the known YSOs detected here as radio sources, the emission is most likely non-thermal and related to stellar coronal activity. As also recently observed in Ophiuchus, our sample of YSOs with X-ray counterparts lies below the fiducial Güdel and Benz relation. Finally, we analyze the proper motions of nine sources in the W40 region. This allows us to better constrain the membership of the radio sources in the region.

  18. Representing a Large Region with Few Sites: A New Approach for Studies on Small Streams

    NASA Astrophysics Data System (ADS)

    Rosamond, Madeline; Kaltenecker, Georgina; Mohamed, Mohamed; Taylor, William

    2015-04-01

    Many environmental studies attempt to characterize a large geographical region but financial and logistical constraints limit the number of field sites used. A systematic approach to site selection can ensure that an adequate range in the variables of interest is captured. We present a novel method to select small watersheds for a study examining relationships between agricultural land use, landscape characteristics and stream phosphorus export. This method reduces subjectivity and uses commonly-available geospatial datasets while considering practical constraints on site selections. We selected several variables representing agricultural P inputs or intensity and landscape susceptibility to P loss. We ordinated regional-scale data on cross plots and then superimposed potential field sites, picking those that covered the range shown, and over-representing areas with high P inputs losses. We represent an 110,000 km2 geographic area with 10 sites, with good coverage of four variables, using six sites from a previous study and four new sites. The site selection method can easily be adapted to studies with a variety of goals and settings. Additionally, ordinating watersheds or regions along axes (here, "agricultural" and "landscape") can provide insight into relationships among variables and help identify areas of particular concern, thus guiding stewardship and management programs. The largest challenge is resolution: small study watersheds (20 - 70 km2) may not be well represented by spatially and temporally coarse data.

  19. Crystal Structure of the C-terminal Region of Streptococcus mutans Antigen I/II and Characterization of Salivary Agglutinin Adherence Domains

    SciTech Connect

    Larson, Matthew R.; Rajashankar, Kanagalaghatta R.; Crowley, Paula J.; Kelly, Charles; Mitchell, Tim J.; Brady, L. Jeannine; Deivanayagam, Champion

    2012-05-29

    The Streptococcus mutans antigen I/II (AgI/II) is a cell surface-localized protein that adheres to salivary components and extracellular matrix molecules. Here we report the 2.5 {angstrom} resolution crystal structure of the complete C-terminal region of AgI/II. The C-terminal region is comprised of three major domains: C{sub 1}, C{sub 2}, and C{sub 3}. Each domain adopts a DE-variant IgG fold, with two {beta}-sheets whose A and F strands are linked through an intramolecular isopeptide bond. The adherence of the C-terminal AgI/II fragments to the putative tooth surface receptor salivary agglutinin (SAG), as monitored by surface plasmon resonance, indicated that the minimal region of binding was contained within the first and second DE-variant-IgG domains (C{sub 1} and C{sub 2}) of the C terminus. The minimal C-terminal region that could inhibit S. mutans adherence to SAG was also confirmed to be within the C{sub 1} and C{sub 2} domains. Competition experiments demonstrated that the C- and N-terminal regions of AgI/II adhere to distinct sites on SAG. A cleft formed at the intersection between these C{sub 1} and C{sub 2} domains bound glucose molecules from the cryo-protectant solution, revealing a putative binding site for its highly glycosylated receptor SAG. Finally, electron microscopy images confirmed the elongated structure of AgI/II and enabled building a composite tertiary model that encompasses its two distinct binding regions.

  20. Initiation of mammalian O-mannosylation in vivo is independent of a consensus sequence and controlled by peptide regions within and upstream of the alpha-dystroglycan mucin domain.

    PubMed

    Breloy, Isabelle; Schwientek, Tilo; Gries, Barbara; Razawi, Hanieh; Macht, Marcus; Albers, Christian; Hanisch, Franz-Georg

    2008-07-01

    To reveal insight into the initiation of mammalian O-mannosylation in vivo, recombinant glycosylation probes containing sections of human alpha-dystroglycan (hDG) were expressed in epithelial cell lines. We demonstrate that O-mannosylation within the mucin domain of hDG occurs preferentially at Thr/Ser residues that are flanked by basic amino acids. Protein O-mannosylation is independent of a consensus sequence, but strictly dependent on a peptide region located upstream of the mucin domain. This peptide region cannot be replaced by other N-terminal peptides, however, it is not sufficient to induce O-mannosylation on a structurally distinct mucin domain in hybrid constructs. The presented in vivo evidence for a more complex regulation of mammalian O-mannosylation contrasts with a recent in vitro study of O-mannosylation in human alpha-dystroglycan peptides indicating the existence of an 18-meric consensus sequence. We demonstrate in vivo that the entire region p377-417 is necessary and sufficient for O-mannosylation initiation of hDG, but not of MUC1 tandem repeats. The feature of a doubly controlled initiation process distinguishes mammalian O-mannosylation from other types of O-glycosylation, which are largely controlled by structural properties of the substrate positions and their local peptide environment.

  1. Large structure rearrangement of colicin ia channel domain after membrane binding from 2D 13C spin diffusion NMR.

    PubMed

    Luo, Wenbin; Yao, Xiaolan; Hong, Mei

    2005-05-01

    One of the main mechanisms of membrane protein folding is by spontaneous insertion into the lipid bilayer from the aqueous environment. The bacterial toxin, colicin Ia, is one such protein. To shed light on the conformational changes involved in this dramatic transfer from the polar to the hydrophobic milieu, we carried out 2D magic-angle spinning (13)C NMR experiments on the water-soluble and membrane-bound states of the channel-forming domain of colicin Ia. Proton-driven (13)C spin diffusion spectra of selectively (13)C-labeled protein show unequivocal attenuation of cross-peaks after membrane binding. This attenuation can be assigned to distance increases but not reduction of the diffusion coefficient. Analysis of the statistics of the interhelical and intrahelical (13)C-(13)C distances in the soluble protein structure indicates that the observed cross-peak reduction is well correlated with a high percentage of short interhelical contacts in the soluble protein. This suggests that colicin Ia channel domain becomes open and extended upon membrane binding, thus lengthening interhelical distances. In comparison, cross-peaks with similar intensities between the two states are dominated by intrahelical contacts in the soluble state. This suggests that the membrane-bound structure of colicin Ia channel domain may be described as a "molten globule", in which the helical secondary structure is retained while the tertiary structure is unfolded. This study demonstrates that (13)C spin diffusion NMR is a valuable tool for obtaining qualitative long-range distance constraints on membrane protein folding. PMID:15853348

  2. Activation of G Protein-Coupled Receptor Kinase 1 Involves Interactions between Its N-Terminal Region and Its Kinase Domain

    SciTech Connect

    Huang, Chih-chin; Orban, Tivadar; Jastrzebska, Beata; Palczewski, Krzysztof; Tesmer, John J.G.

    2012-03-16

    G protein-coupled receptor kinases (GRKs) phosphorylate activated G protein-coupled receptors (GPCRs) to initiate receptor desensitization. In addition to the canonical phosphoacceptor site of the kinase domain, activated receptors bind to a distinct docking site that confers higher affinity and activates GRKs allosterically. Recent mutagenesis and structural studies support a model in which receptor docking activates a GRK by stabilizing the interaction of its 20-amino acid N-terminal region with the kinase domain. This interaction in turn stabilizes a closed, more active conformation of the enzyme. To investigate the importance of this interaction for the process of GRK activation, we first validated the functionality of the N-terminal region in rhodopsin kinase (GRK1) by site-directed mutagenesis and then introduced a disulfide bond to cross-link the N-terminal region of GRK1 with its specific binding site on the kinase domain. Characterization of the kinetic and biophysical properties of the cross-linked protein showed that disulfide bond formation greatly enhances the catalytic efficiency of the peptide phosphorylation, but receptor-dependent phosphorylation, Meta II stabilization, and inhibition of transducin activation were unaffected. These data indicate that the interaction of the N-terminal region with the kinase domain is important for GRK activation but does not dictate the affinity of GRKs for activated receptors.

  3. Identifying young stellar objects in nine Large Magellanic Cloud star-forming regions

    NASA Astrophysics Data System (ADS)

    Carlson, L. R.; Sewiło, M.; Meixner, M.; Romita, K. A.; Lawton, B.

    2012-06-01

    We introduce a new set of selection criteria for the identification of infrared bright young stellar object (YSO) candidates and apply them to nine Hii regions in the Large Magellanic Cloud (LMC), focusing particularly on lower mass candidates missed by most surveys. Data are from the Spitzer Space Telescope legacy program SAGE (Surveying the Agents of Galaxy Evolution; Meixner et al. 2006, AJ, 132, 2268), combined with optical photometry from the Magellanic Clouds Photometric Survey (MCPS; Zaritsky et al. 1997, AJ, 114, 1002) and near-infrared photometry from the InfraRed Survey Facility (IRSF; Kato et al. 2007, PASJ, 59, 615). We choose regions of diverse physical size, star formation rates (SFRs), and ages. We also cover a wide range of locations and surrounding environments in the LMC. These active star-forming regions are LHA 120-N 11, N 44, N 51, N 105, N 113, N 120, N 144, N 160, and N 206. Some have been well-studied (e.g., N11, N44, N160) in the past, while others (e.g., N51, N144) have received little attention. We identify 1045 YSO candidates, including 918 never before identified and 127 matching previous candidate lists. We characterize the evolutionary stage and physical properties of each candidate using the spectral energy distribution (SED) fitter of Robitaille et al. (2007, ApJS, 169, 328) and estimate mass functions and SFRs for each region. Full Tables 1-3, 5 are only available at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/542/A66

  4. Carma Large Area Star Formation Survey: Dense Gas in the Young L1451 Region of Perseus

    NASA Astrophysics Data System (ADS)

    Storm, Shaye; Mundy, Lee G.; Lee, Katherine I.; Fernández-López, Manuel; Looney, Leslie W.; Teuben, Peter; Arce, Héctor G.; Rosolowsky, Erik W.; Meisner, Aaron M.; Isella, Andrea; Kauffmann, Jens; Shirley, Yancy L.; Kwon, Woojin; Plunkett, Adele L.; Pound, Marc W.; Segura-Cox, Dominique M.; Tassis, Konstantinos; Tobin, John J.; Volgenau, Nikolaus H.; Crutcher, Richard M.; Testi, Leonardo

    2016-10-01

    We present a 3 mm spectral line and continuum survey of L1451 in the Perseus Molecular Cloud. These observations are from the CARMA Large Area Star Formation Survey (CLASSy), which also imaged Barnard 1, NGC 1333, Serpens Main, and Serpens South. L1451 is the survey region with the lowest level of star formation activity—it contains no confirmed protostars. HCO+, HCN, and N2H+ (J=1\\to 0) are all detected throughout the region, with HCO+ being the most spatially widespread, and molecular emission seen toward 90% of the area above N(H2) column densities of 1.9 × 1021 cm‑2. HCO+ has the broadest velocity dispersion, near 0.3 km s‑1 on average, compared with ∼0.15 km s‑1 for the other molecules, thus representing a range of subsonic to supersonic gas motions. Our non-binary dendrogram analysis reveals that the dense gas traced by each molecule has a similar hierarchical structure, and that gas surrounding the candidate first hydrostatic core (FHSC), L1451-mm, and other previously detected single-dish continuum clumps has similar hierarchical structure; this suggests that different subregions of L1451 are fragmenting on the pathway to forming young stars. We determined that the three-dimensional morphology of the largest detectable dense-gas structures was relatively ellipsoidal compared with other CLASSy regions, which appeared more flattened at the largest scales. A virial analysis shows that the most centrally condensed dust structures are likely unstable against collapse. Additionally, we identify a new spherical, centrally condensed N2H+ feature that could be a new FHSC candidate. The overall results suggest that L1451 is a young region starting to form its generation of stars within turbulent, hierarchical structures.

  5. A Survey of Large Molecules of Biological Interest toward Selected High Mass Star Forming Regions

    NASA Technical Reports Server (NTRS)

    Remijan, A.; Shiao, Y.-S.; Friedel, D. N.; Meier, D. S.; Snyder, L. E.

    2004-01-01

    We have surveyed three high mass Galactic star forming regions for interstellar methanol (CH3OH), formic acid (HCOOH), acetic acid (CH3COOH), methyl formate (HCOOCH3), methyl cyanide (CH3CN), and ethyl cyanide (CH3CH2CN) with the BIMA Array. From our observations, we have detected two new sources of interstellar HCOOH toward the hot core regions G19.61-0.23 and W75N. We have also made the first detections of CH3CH2CN and HCOOCH3 toward G19.61-0.23. The relative HCOOH/HCOOCH3 abundance ratio toward G19.61-0.23 is 0.18 which is comparable to the abundance ratios found by Liu and colleagues toward Sgr B2(N-LMH), Orion and W51(approximately 0.10). We have made the first detection of HCOOCH3 toward W75N. The relative HCOOH/HCOOCH3 abundance ratio toward W75N is 0.26 which is more than twice as large as the abundance ratios found by Liu and colleagues. Furthermore, the hot core regions around W75N show a chemical differentiation between the O and N cores similar to what is seen toward the Orion Hot Core and Compact Ridge and W3(OH) and W3(H2O). It is also apparent from our observations that the high mass star forming region G45.47+0.05 does not contain any compact hot molecular core and as a consequence its chemistry may be similar to cold dark clouds. Finally, the formation of CH3COOH appears to favor HMCs with well mixed N and O, despite the fact that CH3COOH does not contain a N atom. If proved to be true, this is an important constraint on CH3COOH formation and possibly other structurally similar biomolecules.

  6. Regional analgesia for improvement of long-term functional outcome after elective large joint replacement

    PubMed Central

    Atchabahian, Arthur; Schwartz, Gary; Hall, Charles B; Lajam, Claudette M; Andreae, Michael H

    2015-01-01

    Background Regional analgesia is more effective than conventional analgesia for controlling pain and may facilitate rehabilitation after large joint replacement in the short term. It remains unclear if regional anaesthesia improves functional outcomes after joint replacement beyond three months after surgery. Objectives To assess the effects of regional anaesthesia and analgesia on long-term functional outcomes 3, 6 and 12 months after elective major joint (knee, shoulder and hip) replacement surgery. Search methods We performed an electronic search of several databases (CENTRAL, MEDLINE, EMBASE, CINAHL), and handsearched reference lists and conference abstracts. We updated our search in June 2015. Selection criteria We included randomized controlled trials (RCTs) comparing regional analgesia versus conventional analgesia in patients undergoing total shoulder, hip or knee replacement. We included studies that reported a functional outcome with a follow-up of at least three months after surgery. Data collection and analysis We used standard methodological procedures expected by Cochrane. We contacted study authors for additional information. Main results We included six studies with 350 participants followed for at least three months. All of these studies enrolled participants undergoing total knee replacement. Studies were at least partially blinded. Three studies had a high risk of performance bias and one a high risk of attrition bias, but the risk of bias was otherwise unclear or low. Only one study assessed joint function using a global score. Due to heterogeneity in outcome and reporting, we could only pool three out of six RCTs, with range of motion assessed at three months after surgery used as a surrogate for joint function. All studies had a high risk of detection bias. Using the random-effects model, there was no statistically significant difference between the experimental and control groups (mean difference 3.99 degrees, 95% confidence interval (CI)

  7. Polarization Reversal Over Flooded Regions and Applications to Large-Scale Flood Mapping with Spaceborne Scatterometers

    NASA Technical Reports Server (NTRS)

    Nghiem, Son V.; Liu, W. Timothy; Xie, Xiao-Su

    1999-01-01

    We present the polarization reversal in backscatter over flooded land regions, and demonstrate for the first time the utility of spaceborne Ku-band scatterometer for large-scale flood mapping. Scatterometer data were collected over the globe by the NASA Scatterometer (NSCAT) operated at 14 GHz on the Japanese ADEOS spacecraft from September 1996 to June 1997. During this time span, several severe floods occurred. Over most land surface, vertical polarization backscatter (Sigma(sub upsilon(upsilon)) is larger than horizontal polarization backscatter (sigma(sub hh)). Such polarization characteristics is reversed and sigma(sub upsilon(upsilon)) is smaller than sigma(sub hh) over flooded regions, except under a dense forest canopy. The total backscatter from the flooded landscape consists of direct backscatter and boundary-interaction backscatter. The direct term is contributed by direct backscattering from objects protruding above the water surface, and by backscattering from waves on the water surface. The boundary-interaction term is contributed by the forward scattering from the protruding objects and then reflected from the water surface, and also by the forward scattering from these objects after the water-surface reflection. Over flooded regions, the boundary-interaction term is dominant at large incidence angles and the strong water-surface reflection is much larger for horizontal polarization than the vertical one due to the Brewster effect in transverse-magnetic waves. These scattering mechanisms cause the polarization reversal over flooded regions. An example obtained with the Analytic Wave Theory is used to illustrate the scattering mechanisms leading to the polarization reversal. We then demonstrate the utility of spaceborne Ku-band scatterometer for large-scale flood mapping. We process NSCAT data to obtain the polarization ratio sigma(sub hh)/sigma(sub upsilon(upsilon)) with colocated data at incidence angles larger than 40 deg. The results over Asian

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

    DOEpatents

    Todt, V.; Miller, D.J.; Shi, D.; Sengupta, S.

    1998-07-07

    A method of fabricating bulk YBa{sub 2}Cu{sub 3}O{sub x} where compressed powder oxides and/or carbonates of Y and Ba and Cu present in mole ratios to form YBa{sub 2}Cu{sub 3}O{sub x} are heated in the presence of a Nd{sub 1+x}Ba{sub 2{minus}x}Cu{sub 3}O{sub y} seed crystal to a temperature sufficient to form a liquid phase in the YBa{sub 2}Cu{sub 3}O{sub x} while maintaining the seed crystal solid. The materials are slowly cooled to provide a YBa{sub 2}Cu{sub 3}O{sub x} material having a predetermined number of domains between 1 and 5. Crack-free single domain materials can be formed using either plate shaped seed crystals or cube shaped seed crystals with a pedestal of preferential orientation material. 7 figs.

  9. Implementation of a large-scale flow routing scheme in the Canadian Regional Climate Model (CRCM)

    NASA Astrophysics Data System (ADS)

    Lucas-Picher, P.; Arora, V.; Caya, D.; Laprise, R.

    2002-12-01

    Freshwater flux from river acts as an important forcing on the ocean. With lower density than ocean saltwater, freshwater from rivers affects thermohaline circulation and sea-ice formation at high-latitudes. Freshwater flux can be computed in a climate model by using runoff as an input into a flow routing model, which transfers runoff from the land surface to the continental edges. In addition to modeling freshwater flux for oceans, the streamflow obtained by the routing model can be used to assess the performance of atmospheric models on a climatological basis by comparisons with observed streamflow. The variable velocity flow routing algorithm of Arora and Boer (1999, JGR-Atmos., 104, 30965-30979) is used to compute river flow in the Canadian Regional Climate Model (CRCM) (Caya and Laprise, 1999, Mon. Wea. Rev., 127, 341-362). The flow routing scheme consists of surface and groundwater reservoirs, which obtain daily estimates of surface runoff and drainage inputs, respectively simulated by the land surface scheme. The flow routing algorithm uses Manning's equation to estimate flow velocities. A rectangular river cross section is assumed with a fixed width and the variable depth is estimated using the amount of water in the river, slope, and river width. Discretization of major river basins and flow directions for the North America domain are obtained at the polar stereographic resolution of the CRCM using 5 minute global river flow directions (Graham et al., 1999, WRR, 35, 583-587) as a template. Model runoff estimates from a global simulation of Variable Infiltration Capacity (VIC) hydrological model are use to validate the routing scheme. Routing models results show that compared to the unrouted runoff, the inclusion of flow routing improves comparison with observation-based streamflow estimates.

  10. Full domain-decomposition scheme for diffuse optical tomography of large-sized tissues with a combined CPU and GPU parallelization.

    PubMed

    Yi, Xi; Wang, Xin; Chen, Weiting; Wan, Wenbo; Zhao, Huijuan; Gao, Feng

    2014-05-01

    The common approach to diffuse optical tomography is to solve a nonlinear and ill-posed inverse problem using a linearized iteration process that involves repeated use of the forward and inverse solvers on an appropriately discretized domain of interest. This scheme normally brings severe computation and storage burdens to its applications on large-sized tissues, such as breast tumor diagnosis and brain functional imaging, and prevents from using the matrix-fashioned linear inversions for improved image quality. To cope with the difficulties, we propose in this paper a parallelized full domain-decomposition scheme, which divides the whole domain into several overlapped subdomains and solves the corresponding subinversions independently within the framework of the Schwarz-type iterations, with the support of a combined multicore CPU and multithread graphics processing unit (GPU) parallelization strategy. The numerical and phantom experiments both demonstrate that the proposed method can effectively reduce the computation time and memory occupation for the large-sized problem and improve the quantitative performance of the reconstruction.

  11. Large-Scale Structures in the Zone of Avoidance: The Galactic Anticenter Region

    NASA Technical Reports Server (NTRS)

    Lu, Nanyao Y.; Freudling, Wolfram

    1995-01-01

    We have selected a sample of 876 galaxy candidates from the IRAS Point Source Catalog in the region of 2(exp h) < alpha < 10(exp h) and 0 deg < delta < 36 deg, which crosses the Galactic anticenter part of the Zone of Avoidance (ZOA) and includes most of the highly obscured Orion-Taurus complex region. We have identified galaxies among the candidate sources by attempting to detect the 21 cm H I line of those sources which were not known to be galaxies at the beginning of the survey. In this manner, we constructed a galaxy sample which is largely free from Galactic reddening. Of the 272 observed candidates, 89 were detected in the H I line up to a heliocentric velocity of v(sub h) approximately 16,000 km/s. The resulting galaxy sample of 717 galaxies is fairly complete (within about 10%) and uniform (within about 4%) in the part of the survey area 10 deg away from the Galactic plane and for velocities up to at least 9000 km/s. This provides, for the first time, a largely unbiased view on the large-scale structures in much of the survey area. Our main results are the following: (1) Several large voids are identified. In particular, a void between alpha approximately equals 3(sup h) and 4(sup h), up to v(sub h) approximately 6000 km/s, separates the Pisces-Perseus supercluster at alpha < 3(sup h) from structures at alpha > 4(sup h); and a "nearby void" occupies most of our survey area and reaches out to a redshift of nearly 3000 km/s. (2) We found no nearby galaxy concentration that could significantly contribute to the "Local Velocity Anomoly" (LVA), but a general excess of galaxies around v(sub h) approximately 5000 km/s in the survey area. (3) The contrast between the "Great Wall" at v(sub h) approximately 8500 km/s and the void in front of it appears to gradually diffuse out after it enters the Zone of Avoidance from the northern Galactic hemisphere. (4) Our data combined with other galaxy surveys in or near the Galactic anticenter part of the ZOA suggest that the

  12. The linker domain of the Ha-Ras hypervariable region regulates interactions with exchange factors, Raf-1 and phosphoinositide 3-kinase.

    PubMed

    Jaumot, Montserrat; Yan, Jun; Clyde-Smith, Jodi; Sluimer, Judith; Hancock, John F

    2002-01-01

    Ha-Ras and Ki-Ras have different distributions across plasma membrane microdomains. The Ras C-terminal anchors are primarily responsible for membrane micro-localization, but recent work has shown that the interaction of Ha-Ras with lipid rafts is modulated by GTP loading via a mechanism that requires the hypervariable region (HVR). We have now identified two regions in the HVR linker domain that regulate Ha-Ras raft association. Release of activated Ha-Ras from lipid rafts is blocked by deleting amino acids 173-179 or 166-172. Alanine replacement of amino acids 173-179 but not 166-172 restores wild type micro-localization, indicating that specific N-terminal sequences of the linker domain operate in concert with a more C-terminal spacer domain to regulate Ha-Ras raft association. Mutations in the linker domain that confine activated Ha-RasG12V to lipid rafts abrogate Raf-1, phosphoinositide 3-kinase, and Akt activation and inhibit PC12 cell differentiation. N-Myristoylation also prevents the release of activated Ha-Ras from lipid rafts and inhibits Raf-1 activation. These results demonstrate that the correct modulation of Ha-Ras lateral segregation is critical for downstream signaling. Mutations in the linker domain also suppress the dominant negative phenotype of Ha-RasS17N, indicating that HVR sequences are essential for efficient interaction of Ha-Ras with exchange factors in intact cells.

  13. Large velocity shears and associated electrostatic waves and turbulence in the auroral F region

    NASA Technical Reports Server (NTRS)

    Earle, G. D.; Kelley, M. C.; Ganguli, G.

    1989-01-01

    Broadband electrostatic waves at 10-1000 Hz have been observed with very large shears in the plasma flow velocity transverse to the ambient magnetic field in the auroral F region. The shears were detected through their perpendicular electric field signatures, which changed by as much as 200 mV/m over distances of only a few hundred meters. Transverse shears can be uniquely related to field-aligned currents through the current continuity equation, and the resulting field-aligned drift exceeds the threshold for excitation of current-driven electrostatic ion-cyclotron waves. A numerical simulation of this instability has been used to generate electric-field spectra in the rocket frame of reference, and these spectra are similar to the spectra generated form the actual rocket data.

  14. Simultaneous Solar Maximum Mission (SMM) and very large array observations of solar active regions

    NASA Technical Reports Server (NTRS)

    Lang, K. R.

    1986-01-01

    The research deals mainly with Very Large Array and Solar Maximum Mission observations of the ubiquitous coronal loops that dominate the structure of the low corona. As illustrated, the observations of thermal cyclotron lines at microwave wavelengths provide a powerful new method of accurately specifying the coronal magnetic field strength. Processes are delineated that trigger solar eruptions from coronal loops, including preburst heating and the magnetic interaction of coronal loops. Evidence for coherent burst mechanisms is provided for both the Sun and nearby stars, while other observations suggest the presence of currents that may amplify the coronal magnetic field to unexpectedly high levels. The existence is reported of a new class of compact, variable moving sources in regions of apparently weak photospheric field.

  15. Peptide inhibitors of peptidyltransferase alter the conformation of domains IV and V of large subunit rRNA: a model for nascent peptide control of translation.

    PubMed Central

    Harrod, R; Lovett, P S

    1995-01-01

    Peptides of 5 and 8 residues encoded by the leaders of attenuation regulated chloramphenicol-resistance genes inhibit the peptidyltransferase of microorganisms from the three kingdoms. Therefore, the ribosomal target for the peptides is likely to be a conserved structure and/or sequence. The inhibitor peptides "footprint" to nucleotides of domain V in large subunit rRNA when peptide-ribosome complexes are probed with dimethyl sulfate. Accordingly, rRNA was examined as a candidate for the site of peptide binding. Inhibitor peptides MVKTD and MSTSKNAD were mixed with rRNA phenol-extracted from Escherichia coli ribosomes. The conformation of the RNA was then probed by limited digestion with nucleases that cleave at single-stranded (T1 endonuclease) and double-stranded (V1 endonuclease) sites. Both peptides selectively altered the susceptibility of domains IV and V of 23S rRNA to digestion by T1 endonuclease. Peptide effects on cleavage by V1 nuclease were observed only in domain V. The T1 nuclease susceptibility of domain V of in vitro-transcribed 23S rRNA was also altered by the peptides, demonstrating that peptide binding to the rRNA is independent of ribosomal protein. We propose the peptides MVKTD and MSTSKNAD perturb peptidyltransferase center catalytic activities by altering the conformation of domains IV and V of 23S rRNA. These findings provide a general mechanism through which nascent peptides may cis-regulate the catalytic activities of translating ribosomes. Images Fig. 1 Fig. 2 Fig. 4 PMID:7567991

  16. Representation of spatial and temporal variability in large-domain hydrological models: case study for a mesoscale pre-Alpine basin

    NASA Astrophysics Data System (ADS)

    Melsen, Lieke; Teuling, Adriaan; Torfs, Paul; Zappa, Massimiliano; Mizukami, Naoki; Clark, Martyn; Uijlenhoet, Remko

    2016-06-01

    The transfer of parameter sets over different temporal and spatial resolutions is common practice in many large-domain hydrological modelling studies. The degree to which parameters are transferable across temporal and spatial resolutions is an indicator of how well spatial and temporal variability is represented in the models. A large degree of transferability may well indicate a poor representation of such variability in the employed models. To investigate parameter transferability over resolution in time and space we have set up a study in which the Variable Infiltration Capacity (VIC) model for the Thur basin in Switzerland was run with four different spatial resolutions (1 km × 1 km, 5 km × 5 km, 10 km × 10 km, lumped) and evaluated for three relevant temporal resolutions (hour, day, month), both applied with uniform and distributed forcing. The model was run 3150 times using the Hierarchical Latin Hypercube Sample and the best 1 % of the runs was selected as behavioural. The overlap in behavioural sets for different spatial and temporal resolutions was used as an indicator of parameter transferability. A key result from this study is that the overlap in parameter sets for different spatial resolutions was much larger than for different temporal resolutions, also when the forcing was applied in a distributed fashion. This result suggests that it is easier to transfer parameters across different spatial resolutions than across different temporal resolutions. However, the result also indicates a substantial underestimation in the spatial variability represented in the hydrological simulations, suggesting that the high spatial transferability may occur because the current generation of large-domain models has an inadequate representation of spatial variability and hydrologic connectivity. The results presented in this paper provide a strong motivation to further investigate and substantially improve the representation of spatial and temporal variability in

  17. Study of the Seismic Cycle of large Earthquakes in central Peru: Lima Region

    NASA Astrophysics Data System (ADS)

    Norabuena, E. O.; Quiroz, W.; Dixon, T. H.

    2009-12-01

    Since historical times, the Peruvian subduction zone has been source of large and destructive earthquakes. The more damaging one occurred on May 30 1970 offshore Peru’s northern city of Chimbote with a death toll of 70,000 people and several hundred US million dollars in property damage. More recently, three contiguous plate interface segments in southern Peru completed their seismic cycle generating the 1996 Nazca (Mw 7.1), the 2001 Atico-Arequipa (Mw 8.4) and the 2007 Pisco (Mw 7.9) earthquakes. GPS measurements obtained between 1994-2001 by IGP-CIW an University of Miami-RSMAS on the central Andes of Peru and Bolivia were used to estimate their coseismic displacements and late stage of interseismic strain accumulation. However, we focus our interest in central Peru-Lima region, which with its about 9’000,000 inhabitants is located over a locked plate interface that has not broken with magnitude Mw 8 earthquakes since May 1940, September 1966 and October 1974. We use a network of 11 GPS monuments to estimate the interseismic velocity field, infer spatial variations of interplate coupling and its relation with the background seismicity of the region.

  18. Molecular cloning of the white locus region of Drosophila melanogaster using a large transposable element

    PubMed Central

    Goldberg, M.L.; Paro, R.; Gehring, W.J.

    1982-01-01

    We report the molecular cloning of a chromosome segment including the white locus of Drosophila melanogaster. This region was isolated using a deficiency extending from the previously cloned heat-shock puff sequences at 87A7 to a large transposable element containing the loci white and roughest.FB-NOF, a 7.5 kb element with partial homology to a family of inverted repeat sequences (Potter et al., 1980), is found very near the deficiency breakpoint, and is followed by DNA originating from the white locus region. Sequences totalling ˜60 kb surrounding this initial entry point were obtained by the cloning of successively overlapping fragments from a wild-type strain. Several rearrangement breakpoints have been mapped relative to the cloned DNA; these define the limits of the white locus and further differentiate the “white proximal region”, thought to function in gene regulation, from the remainder of the locus. Insertion of the dispersed repetitive element copia into the white locus is observed in strains carrying the white-apricot allele. Analysis of several white-apricot revertants suggests that copia insertion is responsible for the apricot eye color phenotype. ImagesFig. 2.Fig. 4.Fig. 5.Fig. 6. PMID:16453411

  19. SPLASH: the Southern Parkes Large-Area Survey in Hydroxyl - first science from the pilot region

    NASA Astrophysics Data System (ADS)

    Dawson, J. R.; Walsh, A. J.; Jones, P. A.; Breen, S. L.; Cunningham, M. R.; Lowe, V.; Jones, C.; Purcell, C.; Caswell, J. L.; Carretti, E.; McClure-Griffiths, N. M.; Ellingsen, S. P.; Green, J. A.; Gómez, J. F.; Krishnan, V.; Dickey, J. M.; Imai, H.; Gibson, S. J.; Hennebelle, P.; Lo, N.; Hayakawa, T.; Fukui, Y.; Mizuno, A.

    2014-04-01

    The Southern Parkes Large-Area Survey in Hydroxyl (SPLASH) is a sensitive, unbiased, and fully sampled survey of the southern Galactic plane and Galactic Centre in all four ground-state transitions of the hydroxyl (OH) radical. The survey provides a deep census of 1612-, 1665-, 1667-, and 1720-MHz OH absorption and emission from the Galactic interstellar medium, and is also an unbiased search for maser sources in these transitions. We present here first results from the SPLASH pilot region, which covers Galactic longitudes 334° to 344° and latitudes ±2°. Diffuse OH is widely detected in all four transitions, with optical depths that are always small (averaged over the Parkes beam), and with departures from local thermodynamic equilibrium common even in the 1665- and 1667-MHz main lines. To a 3σ sensitivity of ˜30 mK, we find no evidence of OH envelopes extending beyond the CO-bright regions of molecular cloud complexes, and conclude that the similarity of the OH excitation temperature and the level of the continuum background is at least partly responsible for this. We detect masers and maser candidates in all four transitions, approximately 50 per cent of which are new detections. This implies that SPLASH will produce a substantial increase in the known population of ground-state OH masers in the southern Galactic plane.

  20. Regional contraction of brain surface area involves three large-scale networks in schizophrenia.

    PubMed

    Palaniyappan, Lena; Mallikarjun, Pavan; Joseph, Verghese; White, Thomas P; Liddle, Peter F

    2011-07-01

    In schizophrenia, morphological changes in the cerebral cortex have been primarily investigated using volumetric or cortical thickness measurements. In healthy subjects, as the brain size increases, the surface area expands disproportionately when compared to the scaling of cortical thickness. In this structural MRI study, we investigated the changes in brain surface area in schizophrenia by constructing relative areal contraction/expansion maps showing group differences in surface area using Freesurfer software in 57 patients and 41 controls. We observed relative areal contraction affecting Default Mode Network, Central Executive Network and Salience Network, in addition to other regions in schizophrenia. We confirmed the surface area reduction across these three large-scale brain networks by undertaking further region-of-interest analysis of surface area. We also observed a significant hemispheric asymmetry in the surface area changes, with the left hemisphere showing a greater reduction in the areal contraction maps. Our findings suggest that a fundamental disturbance in cortical expansion is likely in individuals who develop schizophrenia. PMID:21497489

  1. Distributed Kalman filtering compared to Fourier domain preconditioned conjugate gradient for laser guide star tomography on extremely large telescopes.

    PubMed

    Gilles, Luc; Massioni, Paolo; Kulcsár, Caroline; Raynaud, Henri-François; Ellerbroek, Brent

    2013-05-01

    This paper discusses the performance and cost of two computationally efficient Fourier-based tomographic wavefront reconstruction algorithms for wide-field laser guide star (LGS) adaptive optics (AO). The first algorithm is the iterative Fourier domain preconditioned conjugate gradient (FDPCG) algorithm developed by Yang et al. [Appl. Opt.45, 5281 (2006)], combined with pseudo-open-loop control (POLC). FDPCG's computational cost is proportional to N log(N), where N denotes the dimensionality of the tomography problem. The second algorithm is the distributed Kalman filter (DKF) developed by Massioni et al. [J. Opt. Soc. Am. A28, 2298 (2011)], which is a noniterative spatially invariant controller. When implemented in the Fourier domain, DKF's cost is also proportional to N log(N). Both algorithms are capable of estimating spatial frequency components of the residual phase beyond the wavefront sensor (WFS) cutoff frequency thanks to regularization, thereby reducing WFS spatial aliasing at the expense of more computations. We present performance and cost analyses for the LGS multiconjugate AO system under design for the Thirty Meter Telescope, as well as DKF's sensitivity to uncertainties in wind profile prior information. We found that, provided the wind profile is known to better than 10% wind speed accuracy and 20 deg wind direction accuracy, DKF, despite its spatial invariance assumptions, delivers a significantly reduced wavefront error compared to the static FDPCG minimum variance estimator combined with POLC. Due to its nonsequential nature and high degree of parallelism, DKF is particularly well suited for real-time implementation on inexpensive off-the-shelf graphics processing units.

  2. VERY LARGE ARRAY OH ZEEMAN OBSERVATIONS OF THE STAR-FORMING REGION S88B

    SciTech Connect

    Sarma, A. P.; Eftimova, M.; Brogan, C. L.; Bourke, T. L.; Troland, T. H.

    2013-04-10

    We present observations of the Zeeman effect in OH thermal absorption main lines at 1665 and 1667 MHz taken with the Very Large Array toward the star-forming region S88B. The OH absorption profiles toward this source are complicated, and contain several blended components toward a number of positions. Almost all of the OH absorbing gas is located in the eastern parts of S88B, toward the compact continuum source S88B-2 and the eastern parts of the extended continuum source S88B-1. The ratio of 1665/1667 MHz OH line intensities indicates the gas is likely highly clumped, in agreement with other molecular emission line observations in the literature. S88-B appears to present a similar geometry to the well-known star-forming region M17, in that there is an edge-on eastward progression from ionized to molecular gas. The detected magnetic fields appear to mirror this eastward transition; we detected line-of-sight magnetic fields ranging from 90 to 400 {mu}G, with the lowest values of the field to the southwest of the S88B-1 continuum peak, and the highest values to its northeast. We used the detected fields to assess the importance of the magnetic field in S88B by a number of methods; we calculated the ratio of thermal to magnetic pressures, we calculated the critical field necessary to completely support the cloud against self-gravity and compared it to the observed field, and we calculated the ratio of mass to magnetic flux in terms of the critical value of this parameter. All these methods indicated that the magnetic field in S88B is dynamically significant, and should provide an important source of support against gravity. Moreover, the magnetic energy density is in approximate equipartition with the turbulent energy density, again pointing to the importance of the magnetic field in this region.

  3. The D1-D2 region of the large subunit ribosomal DNA as barcode for ciliates.

    PubMed

    Stoeck, T; Przybos, E; Dunthorn, M

    2014-05-01

    Ciliates are a major evolutionary lineage within the alveolates, which are distributed in nearly all habitats on our planet and are an essential component for ecosystem function, processes and stability. Accurate identification of these unicellular eukaryotes through, for example, microscopy or mating type reactions is reserved to few specialists. To satisfy the demand for a DNA barcode for ciliates, which meets the standard criteria for DNA barcodes defined by the Consortium for the Barcode of Life (CBOL), we here evaluated the D1-D2 region of the ribosomal DNA large subunit (LSU-rDNA). Primer universality for the phylum Ciliophora was tested in silico with available database sequences as well as in the laboratory with 73 ciliate species, which represented nine of 12 ciliate classes. Primers tested in this study were successful for all tested classes. To test the ability of the D1-D2 region to resolve conspecific and congeneric sequence divergence, 63 Paramecium strains were sampled from 24 mating species. The average conspecific D1-D2 variation was 0.18%, whereas congeneric sequence divergence averaged 4.83%. In pairwise genetic distance analyses, we identified a D1-D2 sequence divergence of <0.6% as an ideal threshold to discriminate Paramecium species. Using this definition, only 3.8% of all conspecific and 3.9% of all congeneric sequence comparisons had the potential of false assignments. Neighbour-joining analyses inferred monophyly for all taxa but for two Paramecium octaurelia strains. Here, we present a protocol for easy DNA amplification of single cells and voucher deposition. In conclusion, the presented data pinpoint the D1-D2 region as an excellent candidate for an official CBOL barcode for ciliated protists.

  4. Delivery of Large Heterologous Polypeptides across the Cytoplasmic Membrane of Antigen-Presenting Cells by the Bordetella RTX Hemolysin Moiety Lacking the Adenylyl Cyclase Domain

    PubMed Central

    Holubova, Jana; Jelinek, Jiri; Tomala, Jakub; Masin, Jiri; Kosova, Martina; Stanek, Ondrej; Bumba, Ladislav; Michalek, Jaroslav; Kovar, Marek; Sebo, Peter

    2012-01-01

    The Bordetella adenylate cyclase toxin-hemolysin (CyaA; also called ACT or AC-Hly) targets CD11b-expressing phagocytes and translocates into their cytosol an adenylyl cyclase (AC) that hijacks cellular signaling by conversion of ATP to cyclic AMP (cAMP). Intriguingly, insertion of large passenger peptides removes the enzymatic activity but not the cell-invasive capacity of the AC domain. This has repeatedly been exploited for delivery of heterologous antigens into the cytosolic pathway of CD11b-expressing dendritic cells by CyaA/AC− toxoids, thus enabling their processing and presentation on major histocompatibility complex (MHC) class I molecules to cytotoxic CD8+ T lymphocytes (CTLs). We produced a set of toxoids with overlapping deletions within the first 371 residues of CyaA and showed that the structure of the AC enzyme does not contain any sequences indispensable for its translocation across target cell membrane. Moreover, replacement of the AC domain (residues 1 to 371) with heterologous polypeptides of 40, 146, or 203 residues yielded CyaAΔAC constructs that delivered passenger CTL epitopes into antigen-presenting cells (APCs) and induced strong antigen-specific CD8+ CTL responses in vivo in mice and ex vivo in human peripheral blood mononuclear cell cultures. This shows that the RTX (repeats in toxin) hemolysin moiety, consisting of residues 374 to 1706 of CyaA, harbors all structural information involved in translocation of the N-terminal AC domain across target cell membranes. These results decipher the extraordinary capacity of the AC domain of CyaA to transport large heterologous cargo polypeptides into the cytosol of CD11b+ target cells and pave the way for the construction of CyaAΔAC-based polyvalent immunotherapeutic T cell vaccines. PMID:22215742

  5. Delineation of a small region within the major transactivation domain of the human glucocorticoid receptor that mediates transactivation of gene expression.

    PubMed Central

    Dahlman-Wright, K; Almlöf, T; McEwan, I J; Gustafsson, J A; Wright, A P

    1994-01-01

    Previous deletion analysis localized the major transactivation function of the human glucocorticoid receptor to a 185-amino acid segment close to the N terminus of the receptor protein. This region was named tau 1 [Hollenberg, S. M. & Evans, R. M. (1988) Cell 55, 899-906]. To delineate the smallest active region within tau 1, we have systematically tested the transactivation capacity of deletion derivatives of the tau 1 domain, fused to the glucocorticoid receptor DNA-binding domain, in yeast cells. Internal scanning deletions suggested that residues near the C terminus of tau 1 are most important for activity. Deletions of N-terminal and C-terminal sequences identified a 41-amino acid "core" region near the C terminus of tau 1 that is crucial for tau 1 function. Small peptide fragments containing the tau 1 core region are competent for transactivation, while regions outside the tau 1 core are not active. We have previously demonstrated that the intact tau 1 domain squelches the activity of a minimal promoter in vivo and in vitro, suggesting involvement of interactions with a component/components of the basal transcription machinery in the mechanism of transactivation. This activity was maintained in the tau 1 core-containing segments. Images PMID:8127854

  6. Near-Infrared Polarization Source Catalog of the Northeastern Regions of the Large Magellanic Cloud

    NASA Astrophysics Data System (ADS)

    Kim, Jaeyeong; Jeong, Woong-Seob; Pak, Soojong; Park, Won-Kee; Tamura, Motohide

    2016-01-01

    We present a near-infrared band-merged photometric and polarimetric catalog for the 39‧ × 69‧ fields in the northeastern part of the Large Magellanic Cloud (LMC), which were observed using SIRPOL, an imaging polarimeter of the InfraRed Survey Facility. This catalog lists 1858 sources brighter than 14 mag in the H band with a polarization signal-to-noise ratio greater than three in the J, H, or Ks bands. Based on the relationship between the extinction and the polarization degree, we argue that the polarization mostly arises from dichroic extinctions caused by local interstellar dust in the LMC. This catalog allows us to map polarization structures to examine the global geometry of the local magnetic field, and to show a statistical analysis of the polarization of each field to understand its polarization properties. In the selected fields with coherent polarization position angles, we estimate magnetic field strengths in the range of 3-25 μG using the Chandrasekhar-Fermi method. This implies the presence of large-scale magnetic fields on a scale of around 100 parsecs. When comparing mid- and far-infrared dust emission maps, we confirmed that the polarization patterns are well aligned with molecular clouds around the star-forming regions.

  7. Occurrences of large-magnitude earthquakes in the Kachchh region, Gujarat, western India: Tectonic implications

    NASA Astrophysics Data System (ADS)

    Khan, Prosanta Kumar; Mohanty, Sarada Prasad; Sinha, Sushmita; Singh, Dhananjay

    2016-06-01

    Moderate-to-large damaging earthquakes in the peninsular part of the Indian plate do not support the long-standing belief of the seismic stability of this region. The historical record shows that about 15 damaging earthquakes with magnitudes from 5.5 to ~ 8.0 occurred in the Indian peninsula. Most of these events were associated with the old rift systems. Our analysis of the 2001 Bhuj earthquake and its 12-year aftershock sequence indicates a seismic zone bound by two linear trends (NNW and NNE) that intersect an E-W-trending graben. The Bouguer gravity values near the epicentre of the Bhuj earthquake are relatively low (~ 2 mgal). The gravity anomaly maps, the distribution of earthquake epicentres, and the crustal strain-rate patterns indicate that the 2001 Bhuj earthquake occurred along a fault within strain-hardened mid-crustal rocks. The collision resistance between the Indian plate and the Eurasian plate along the Himalayas and anticlockwise rotation of the Indian plate provide the far-field stresses that concentrate within a fault-bounded block close to the western margin of the Indian plate and is periodically released during earthquakes, such as the 2001 MW 7.7 Bhuj earthquake. We propose that the moderate-to-large magnitude earthquakes in the deeper crust in this area occur along faults associated with old rift systems that are reactivated in a strain-hardened environment.

  8. Large-scale climate patterns and precipitation in an arid endorheic region: linkage and underlying mechanism

    NASA Astrophysics Data System (ADS)

    Shi, Pengfei; Yang, Tao; Zhang, Ke; Tang, Qiuhong; Yu, Zhongbo; Zhou, Xudong

    2016-04-01

    The interactions between a range of large-scale climate oscillations and their quantitative links with precipitation are basic prerequisites to understand the hydrologic cycle. Restricted by the current limited knowledge on underlying mechanisms, statistical methods (e.g. correlation methods) are often used rather than a physical-based model. However, available correlation methods generally fail to explain the interactions among a wide range of climate oscillations and associated effects on the water cycle. This study presents a new probabilistic analysis approach by means of a state-of-the-art Copula-based joint probability distribution to characterize the aggregated behaviors for large-scale climate patterns and their connections to precipitation. We applied this method to identify the complex connections between climate patterns (westerly circulation (WEC), El Niño-Southern Oscillation (ENSO) and Pacific Decadal Oscillation (PDO)) and seasonal precipitation over a typical endorheic region, the Tarim River Basin in central Asia. Results show that the interactions among multiple climate oscillations are non-uniform in most seasons and phases. Certain joint extreme phases can significantly trigger extremes (flood and drought) owing to the amplification effect among climate oscillations. We further find that the connection is mainly due to the complex effects of climatic and topographical factors.

  9. Interactions of two large antiviral polyamides with the long control region of HPV16.

    PubMed

    Vasilieva, Elena; Niederschulte, Jacquelyn; Song, Yang; Harris, George Davis; Koeller, Kevin J; Liao, Puhong; Bashkin, James K; Dupureur, Cynthia M

    2016-08-01

    PA1 and PA25 are large hairpin polyamides that are effective in nearly eliminating HPV16 episomes (DNA) in cell culture, and PA25 has broad spectrum activity against three cancer-causing forms of HPV (Edwards, T. G., Koeller, K. J., Slomczynska, U., Fok, K., Helmus, M., Bashkin, J. K., Fisher, C., Antiviral Res. 91 (2011) 177-186). Described here are the interactions of these PAs with sequences in the long control region (LCR) of HPV16 (7348-122). Using an FeEDTA conjugate of PA1 (designed to recognize 5'-W2GW7-3'; W = A or T), 34 affinity cleavage (AC) patterns were detected for this fragment. These sites can be rationalized with sequences featuring perfect, single, double, triple and quadruple mismatches. Quantitative DNase I footprinting analysis indicates that perfect sites bind PA1 with Kds between 0.7 and 2.2 nM. Kds for single, double, triple and quadruple mismatch sites range from 1-3 nM-20 nM. Using AC and EDTA conjugates, we report that unlike smaller 8-ring hairpin PAs, introduction of a chiral turn in this large polyamide has no effect on binding orientation (forward vs. reverse). Despite its design to recognize 5'-W2GW5GW4-3' via two Im residues, a motif not represented in this HPV sequence, a PA25-EDTA conjugate yielded 31 affinity cleavage sites on the region. Low nM Kds for PA25 without EDTA indicates a high tolerance for triple and quadruple mismatches. While there is extensive coverage of the sequence examined, AC cleavage patterns for the two PAs show discrete binding events and do not overlap significantly. This indicates that within the context of A/T rich sequences, these PAs do not recognize a simple shared sequence-related feature of the DNA. These insights continue to inform the complex nature of large hairpin PA-DNA interactions and antiviral behavior.

  10. Interactions of two large antiviral polyamides with the long control region of HPV16.

    PubMed

    Vasilieva, Elena; Niederschulte, Jacquelyn; Song, Yang; Harris, George Davis; Koeller, Kevin J; Liao, Puhong; Bashkin, James K; Dupureur, Cynthia M

    2016-08-01

    PA1 and PA25 are large hairpin polyamides that are effective in nearly eliminating HPV16 episomes (DNA) in cell culture, and PA25 has broad spectrum activity against three cancer-causing forms of HPV (Edwards, T. G., Koeller, K. J., Slomczynska, U., Fok, K., Helmus, M., Bashkin, J. K., Fisher, C., Antiviral Res. 91 (2011) 177-186). Described here are the interactions of these PAs with sequences in the long control region (LCR) of HPV16 (7348-122). Using an FeEDTA conjugate of PA1 (designed to recognize 5'-W2GW7-3'; W = A or T), 34 affinity cleavage (AC) patterns were detected for this fragment. These sites can be rationalized with sequences featuring perfect, single, double, triple and quadruple mismatches. Quantitative DNase I footprinting analysis indicates that perfect sites bind PA1 with Kds between 0.7 and 2.2 nM. Kds for single, double, triple and quadruple mismatch sites range from 1-3 nM-20 nM. Using AC and EDTA conjugates, we report that unlike smaller 8-ring hairpin PAs, introduction of a chiral turn in this large polyamide has no effect on binding orientation (forward vs. reverse). Despite its design to recognize 5'-W2GW5GW4-3' via two Im residues, a motif not represented in this HPV sequence, a PA25-EDTA conjugate yielded 31 affinity cleavage sites on the region. Low nM Kds for PA25 without EDTA indicates a high tolerance for triple and quadruple mismatches. While there is extensive coverage of the sequence examined, AC cleavage patterns for the two PAs show discrete binding events and do not overlap significantly. This indicates that within the context of A/T rich sequences, these PAs do not recognize a simple shared sequence-related feature of the DNA. These insights continue to inform the complex nature of large hairpin PA-DNA interactions and antiviral behavior. PMID:27155361

  11. W-phase Source Inversion Using High-rate Regional GPS Data for Large Earthquakes.

    NASA Astrophysics Data System (ADS)

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

    2015-12-01

    W-phase moment tensor inversions have been proven to be a reliable method for rapid characterization for large earthquakes. W-phase is a long period seismic (100s-1000s) wave that arrives between P and S waves and can be synthesized by normal mode summation. For global purposes it has been used at USGS, PTWC and IPGS. These implementations provide moment tensor solutions within 30-60 min after the origin time of moderate and large worldwide earthquakes. W-phase inversion has been successfully implemented at the Chilean National Seismological Center (CSN) for regional distances (5º-12º) obtaining the first solution ~6 minutes after the earthquake. However until now it has been used only with broadband instruments, which saturate in the near field. Therefore, we use near field records from high-rate regional GPS data for some large earthquakes that have occurred in the past five years and with relatively dense azimuthal and station density coverage.Originally the inversion takes the time interval between Tp and Tp + 15 *delta (distance from the epicenter in degrees). In the near field W-phase doesn't develop as well as in the intermediate or far field, therefore we increased the time window for these events. Here we tried different time windows to find the most accurate result for each earthquake and to reduce time response for tsunami early warning purposes. We took near field GPS for the following earthquakes: The 2010 Mw 8.8 Maule Earthquake, the 2011 Mw 9.1 Tohoku Earthquake, The 2014 Mw 8.2 Iquique Earthquake, and The 2014 Mw 7.8 Iquique Aftershock. The solutions for the examples tested here are potentially available 5 min after the origin time. The calculated magnitude for each earthquake is: Mw 8.9 for the Maule earthquake, Mw 9.1 for the Tohoku earthquake, Mw 7.9 for the Iquique earthquake, and Mw 7.8 for the Iquique aftershock. The mechanisms, as expected, are thrust with some variations with respect to the WCMT from National Earthquake Information Center

  12. Biochemical Activities of the Wiskott-Aldrich Syndrome Homology Region 2 Domains of Sarcomere Length Short (SALS) Protein.

    PubMed

    Tóth, Mónika Ágnes; Majoros, Andrea Kinga; Vig, Andrea Teréz; Migh, Ede; Nyitrai, Miklós; Mihály, József; Bugyi, Beáta

    2016-01-01

    Drosophila melanogaster sarcomere length short (SALS) is a recently identified Wiskott-Aldrich syndrome protein homology 2 (WH2) domain protein involved in skeletal muscle thin filament regulation. SALS was shown to be important for the establishment of the proper length and organization of sarcomeric actin filaments. Here, we present the first detailed characterization of the biochemical activities of the tandem WH2 domains of SALS (SALS-WH2). Our results revealed that SALS-WH2 binds both monomeric and filamentous actin and shifts the monomer-filament equilibrium toward the monomeric actin. In addition, SALS-WH2 can bind to but fails to depolymerize phalloidin- or jasplakinolide-bound actin filaments. These interactions endow SALS-WH2 with the following two major activities in the regulation of actin dynamics: SALS-WH2 sequesters actin monomers into non-polymerizable complexes and enhances actin filament disassembly by severing, which is modulated by tropomyosin. We also show that profilin does not influence the activities of the WH2 domains of SALS in actin dynamics. In conclusion, the tandem WH2 domains of SALS are multifunctional regulators of actin dynamics. Our findings suggest that the activities of the WH2 domains do not reconstitute the presumed biological function of the full-length protein. Consequently, the interactions of the WH2 domains of SALS with actin must be tuned in the cellular context by other modules of the protein and/or sarcomeric components for its proper functioning.

  13. Biochemical Large-Scale Interaction Analysis of Murine Olfactory Receptors and Associated Signaling Proteins with Post-Synaptic Density 95, Drosophila Discs Large, Zona-Occludens 1 (PDZ) Domains*

    PubMed Central

    Jansen, Fabian; Kalbe, Benjamin; Scholz, Paul; Fränzel, Benjamin; Osterloh, Markus; Wolters, Dirk; Hatt, Hanns; Neuhaus, Eva Maria; Osterloh, Sabrina

    2015-01-01

    G protein-coupled receptors (GPCRs) constitute the largest family among mammalian membrane proteins and are capable of initiating numerous essential signaling cascades. Various GPCR-mediated pathways are organized into protein microdomains that can be orchestrated and regulated through scaffolding proteins, such as PSD-95/discs-large/ZO1 (PDZ) domain proteins. However, detailed binding characteristics of PDZ–GPCR interactions remain elusive because these interactions seem to be more complex than previously thought. To address this issue, we analyzed binding modalities using our established model system. This system includes the 13 individual PDZ domains of the multiple PDZ domain protein 1 (MUPP1; the largest PDZ protein), a broad range of murine olfactory receptors (a multifaceted gene cluster within the family of GPCRs), and associated olfactory signaling proteins. These proteins were analyzed in a large-scale peptide microarray approach and continuative interaction studies. As a result, we demonstrate that canonical binding motifs were not overrepresented among the interaction partners of MUPP1. Furthermore, C-terminal phosphorylation and distinct amino acid replacements abolished PDZ binding promiscuity. In addition to the described in vitro experiments, we identified new interaction partners within the murine olfactory epithelium using pull-down-based interactomics and could verify the partners through co-immunoprecipitation. In summary, the present study provides important insight into the complexity of the binding characteristics of PDZ–GPCR interactions based on olfactory signaling proteins, which could identify novel clinical targets for GPCR-associated diseases in the future. PMID:25979994

  14. Unique Piezoelectric Properties of the Monoclinic Phase in Pb(Zr,Ti)O_{3} Ceramics: Large Lattice Strain and Negligible Domain Switching.

    PubMed

    Fan, Longlong; Chen, Jun; Ren, Yang; Pan, Zhao; Zhang, Linxing; Xing, Xianran

    2016-01-15

    The origin of the excellent piezoelectric properties at the morphotropic phase boundary is generally attributed to the existence of a monoclinic phase in various piezoelectric systems. However, there exist no experimental studies that reveal the role of the monoclinic phase in the piezoelectric behavior in phase-pure ceramics. In this work, a single monoclinic phase has been identified in Pb(Zr,Ti)O_{3} ceramics at room temperature by in situ high-energy synchrotron x-ray diffraction, and its response to electric field has been characterized for the first time. Unique piezoelectric properties of the monoclinic phase in terms of large intrinsic lattice strain and negligible domain switching have been observed. The extensional strain constant d_{33} and the transverse strain constant d_{31} are calculated to be 520 and -200  pm/V, respectively. These large piezoelectric coefficients are mainly due to the large intrinsic lattice strain, with very little extrinsic contribution from domain switching. The unique properties of the monoclinic phase provide new insights into the mechanisms responsible for the piezoelectric properties at the morphotropic phase boundary. PMID:26824565

  15. Unique Piezoelectric Properties of the Monoclinic Phase in Pb(Zr,Ti)O_{3} Ceramics: Large Lattice Strain and Negligible Domain Switching.

    PubMed

    Fan, Longlong; Chen, Jun; Ren, Yang; Pan, Zhao; Zhang, Linxing; Xing, Xianran

    2016-01-15

    The origin of the excellent piezoelectric properties at the morphotropic phase boundary is generally attributed to the existence of a monoclinic phase in various piezoelectric systems. However, there exist no experimental studies that reveal the role of the monoclinic phase in the piezoelectric behavior in phase-pure ceramics. In this work, a single monoclinic phase has been identified in Pb(Zr,Ti)O_{3} ceramics at room temperature by in situ high-energy synchrotron x-ray diffraction, and its response to electric field has been characterized for the first time. Unique piezoelectric properties of the monoclinic phase in terms of large intrinsic lattice strain and negligible domain switching have been observed. The extensional strain constant d_{33} and the transverse strain constant d_{31} are calculated to be 520 and -200  pm/V, respectively. These large piezoelectric coefficients are mainly due to the large intrinsic lattice strain, with very little extrinsic contribution from domain switching. The unique properties of the monoclinic phase provide new insights into the mechanisms responsible for the piezoelectric properties at the morphotropic phase boundary.

  16. Influence of the valine zipper region on the structure and aggregation of the basic leucine zipper (bZIP) domain of activating transcription factor 5 (ATF5).

    PubMed

    Ciaccio, Natalie A; Reynolds, T Steele; Middaugh, C Russell; Laurence, Jennifer S

    2012-11-01

    Protein aggregation is a major problem for biopharmaceuticals. While the control of aggregation is critically important for the future of protein pharmaceuticals, mechanisms of aggregate assembly, particularly the role that structure plays, are still poorly understood. Increasing evidence indicates that partially folded intermediates critically influence the aggregation pathway. We have previously reported the use of the basic leucine zipper (bZIP) domain of activating transcription factor 5 (ATF5) as a partially folded model system to investigate protein aggregation. This domain contains three regions with differing structural propensity: a N-terminal polybasic region, a central helical leucine zipper region, and a C-terminal extended valine zipper region. Additionally, a centrally positioned cysteine residue readily forms an intermolecular disulfide bond that reduces aggregation. Computational analysis of ATF5 predicts that the valine zipper region facilitates self-association. Here we test this hypothesis using a truncated mutant lacking the C-terminal valine zipper region. We compare the structure and aggregation of this mutant to the wild-type (WT) form under both reducing and nonreducing conditions. Our data indicate that removal of this region results in a loss of α-helical structure in the leucine zipper and a change in the mechanism of self-association. The mutant form displays increased association at low temperature but improved resistance to thermally induced aggregation.

  17. Influence of the valine zipper region on the structure and aggregation of the basic leucine zipper (bZIP) domain of activating transcription factor 5 (ATF5).

    PubMed

    Ciaccio, Natalie A; Reynolds, T Steele; Middaugh, C Russell; Laurence, Jennifer S

    2012-11-01

    Protein aggregation is a major problem for biopharmaceuticals. While the control of aggregation is critically important for the future of protein pharmaceuticals, mechanisms of aggregate assembly, particularly the role that structure plays, are still poorly understood. Increasing evidence indicates that partially folded intermediates critically influence the aggregation pathway. We have previously reported the use of the basic leucine zipper (bZIP) domain of activating transcription factor 5 (ATF5) as a partially folded model system to investigate protein aggregation. This domain contains three regions with differing structural propensity: a N-terminal polybasic region, a central helical leucine zipper region, and a C-terminal extended valine zipper region. Additionally, a centrally positioned cysteine residue readily forms an intermolecular disulfide bond that reduces aggregation. Computational analysis of ATF5 predicts that the valine zipper region facilitates self-association. Here we test this hypothesis using a truncated mutant lacking the C-terminal valine zipper region. We compare the structure and aggregation of this mutant to the wild-type (WT) form under both reducing and nonreducing conditions. Our data indicate that removal of this region results in a loss of α-helical structure in the leucine zipper and a change in the mechanism of self-association. The mutant form displays increased association at low temperature but improved resistance to thermally induced aggregation. PMID:23067245

  18. Influence of the Valine Zipper Region on the Structure and Aggregation of the Basic Leucine Zipper (bZIP) Domain of Activating Transcription Factor 5 (ATF5)

    PubMed Central

    Ciaccio, Natalie A.; Reynolds, T. Steele; Middaugh, C. Russell; Laurence, Jennifer S.

    2012-01-01

    Protein aggregation is a major problem for biopharmaceuticals. While the control of aggregation is critically important for the future of protein pharmaceuticals, mechanisms of aggregate assembly, particularly the role that structure plays, are still poorly understood. Increasing evidence indicates that partially folded intermediates critically influence the aggregation pathway. We have previously reported the use of the basic leucine zipper (bZIP) domain of Activating Transcription Factor 5 (ATF5) as a partially folded model system to investigate protein aggregation. This domain contains three regions with differing structural propensity: a N-terminal polybasic region, a central helical leucine zipper region, and a C-terminal extended valine zipper region. Additionally, a centrally positioned cysteine residue readily forms an intermolecular disulfide bond that reduces aggregation. Computational analysis of ATF5 predicts that the valine zipper region facilitates self-association. Here we test this hypothesis using a truncated mutant lacking the C-terminal valine zipper region. We compare the structure and aggregation of this mutant to the wild-type (WT) form under both reducing and non-reducing conditions. Our data indicate that removal of this region results in a loss of alpha-helical structure in the leucine zipper and a change in the mechanism of self-association. The mutant form displays increased association at low temperature but improved resistance to thermally induced aggregation. PMID:23067245

  19. Potential effects of large linear pipeline construction on soil and vegetation in ecologically fragile regions.

    PubMed

    Xiao, Jun; Wang, Ya-Feng; Shi, Peng; Yang, Lei; Chen, Li-Ding

    2014-11-01

    Long-distance pipeline construction results in marked human disturbance of the regional ecosystem and brings into question the safety of pipeline construction with respect to the environment. Thus, the direct environmental impact and proper handling of such large projects have received much attention. The potential environmental effects, however, have not been fully addressed, particularly for large linear pipeline projects, and the threshold of such effects is unclear. In this study, two typical eco-fragile areas in western China, where large linear construction projects have been conducted, were chosen as the case study areas. Soil quality indices (SQI) and vegetation indices (VI), representing the most important potential effects, were used to analyze the scope of the effect of large pipeline construction on the surrounding environment. These two indices in different buffer zones along the pipeline were compared against the background values. The analysis resulted in three main findings. First, pipeline construction continues to influence the nearby eco-environment even after a 4-year recovery period. During this period, the effect on vegetation due to pipeline construction reaches 300 m beyond the working area, and is much larger in distance than the effect on soil, which is mainly confined to within 30 m either side of the pipeline, indicating that vegetation is more sensitive than soil to this type of human disturbance. However, the effect may not reach beyond 500 m from the pipeline. Second, the scope of the effect in terms of distance on vegetation may also be determined by the frequency of disturbance and the intensity of the pipeline construction. The greater the number of pipelines in an area, the higher the construction intensity and the more frequent the disturbance. Frequent disturbance may expand the effect on vegetation on both sides of the pipeline, but not on soil quality. Third, the construction may eliminate the stable, resident plant

  20. Potential effects of large linear pipeline construction on soil and vegetation in ecologically fragile regions.

    PubMed

    Xiao, Jun; Wang, Ya-Feng; Shi, Peng; Yang, Lei; Chen, Li-Ding

    2014-11-01

    Long-distance pipeline construction results in marked human disturbance of the regional ecosystem and brings into question the safety of pipeline construction with respect to the environment. Thus, the direct environmental impact and proper handling of such large projects have received much attention. The potential environmental effects, however, have not been fully addressed, particularly for large linear pipeline projects, and the threshold of such effects is unclear. In this study, two typical eco-fragile areas in western China, where large linear construction projects have been conducted, were chosen as the case study areas. Soil quality indices (SQI) and vegetation indices (VI), representing the most important potential effects, were used to analyze the scope of the effect of large pipeline construction on the surrounding environment. These two indices in different buffer zones along the pipeline were compared against the background values. The analysis resulted in three main findings. First, pipeline construction continues to influence the nearby eco-environment even after a 4-year recovery period. During this period, the effect on vegetation due to pipeline construction reaches 300 m beyond the working area, and is much larger in distance than the effect on soil, which is mainly confined to within 30 m either side of the pipeline, indicating that vegetation is more sensitive than soil to this type of human disturbance. However, the effect may not reach beyond 500 m from the pipeline. Second, the scope of the effect in terms of distance on vegetation may also be determined by the frequency of disturbance and the intensity of the pipeline construction. The greater the number of pipelines in an area, the higher the construction intensity and the more frequent the disturbance. Frequent disturbance may expand the effect on vegetation on both sides of the pipeline, but not on soil quality. Third, the construction may eliminate the stable, resident plant

  1. The Relationship between Intelligence and Multiple Domains of Religious Belief: Evidence from a Large Adult US Sample

    ERIC Educational Resources Information Center

    Lewis, Gary J.; Ritchie, Stuart J.; Bates, Timothy C.

    2011-01-01

    High levels of religiosity have been linked to lower levels of intelligence in a number of recent studies. These results have generated both controversy and theoretical interest. Here in a large sample of US adults we address several issues that restricted the generalizability of these previous results. We measured six dimensions of religiosity…

  2. Comparison between method of lines and time domain method in evaluating the large signal responses of Fabry-Perot semiconductor lasers

    NASA Astrophysics Data System (ADS)

    Braverman, Ada L.

    1998-07-01

    An extensive comparison between two modeling methods: Method of Lines and Time Domain Method in analyzing the large signal responses of Fabry-Perot semiconductor lasers is presented. The methods are implemented in two numerical codes written in FORTRAN and using DIGITAL ALPHA workstations under VAX/VMS and UNIX operating systems. The comparison shows good agreement between the simulation results under specific conditions. A special accent is placed on the advantages and drawbacks of both methods by taking into account their numerical problems and the computational effort implied by simulations.

  3. Normal cardiac contraction in mice lacking the proline-alanine rich region and C1 domain of cardiac myosin binding protein C.

    PubMed

    van Dijk, Sabine J; Witt, Christian C; Harris, Samantha P

    2015-11-01

    Cardiac myosin binding protein C (cMyBP-C) is an essential regulator of cross bridge cycling. Through mechanisms that are incompletely understood the N-terminal domains (NTDs) of cMyBP-C can activate contraction even in the absence of calcium and can also inhibit cross bridge kinetics in the presence of calcium. In vitro studies indicated that the proline-alanine rich (p/a) region and C1 domain are involved in these processes, although effects were greater using human proteins compared to murine proteins (Shaffer et al. J Biomed Biotechnol 2010, 2010: 789798). We hypothesized that the p/a and C1 region are critical for the timing of contraction. In this study we tested this hypothesis using a mouse model lacking the p/a and C1 region (p/a-C1(-/-) mice) to investigate the in vivo relevance of these regions on cardiac performance. Surprisingly, hearts of adult p/a-C1(-/-) mice functioned normally both on a cellular and whole organ level. Force measurements in permeabilized cardiomyocytes from adult p/a-C1(-/-) mice and wild type (Wt) littermate controls demonstrated similar rates of force redevelopment both at submaximal and maximal activation. Maximal and passive force and calcium sensitivity of force were comparable between groups as well. Echocardiograms showed normal isovolumetric contraction times, fractional shortening and ejection fraction, indicating proper systolic function in p/a-C1(-/-) mouse hearts. p/a-C1(-/-) mice showed a slight but significant reduction in isovolumetric relaxation time compared to Wt littermates, yet this difference disappeared in older mice (7-8months of age). Moreover, stroke volume was preserved in p/a-C1(-/-) mice, corroborating sufficient time for normal filling of the heart. Overall, the hearts of p/a-C1(-/-) mice showed no signs of dysfunction even after chronic stress with an adrenergic agonist. Together, these results indicate that the p/a region and the C1 domain of cMyBP-C are not critical for normal cardiac contraction in

  4. Peculiarities of mantle lithosphere beneath the large kimberlite pipes in different regions for Siberian craton

    NASA Astrophysics Data System (ADS)

    Ashchepkov, Igor; Logvinova, Alla; Ntaflos, Theodoros; Vladykin, Nikolai; Spetsius, Zdislav; Kostrovitsky, Sergey; Stegnitsky, Yuri; Prokopyev, Sergey

    2016-04-01

    Comparison of the structure of the mantle columns and mineralogy of the large kimberlite pipes in Yakutia from the different regions, kimberlite fields and mantle terranes in Yakutia allowed several assumptions. 1. The large kimberlite pipes possibly trace the ancient magma feeders occurred in the time of the continent growth. Commonly kimberlites and large pipes are tracing the deep faults and lineaments tracing the ancient sutures, rift zones, trans -lithospheric faults and other permeable structures, which may be parallel to the ancient continental margins. Large pipes locate at the periodic distance like volcanoes in arc settings tracing the "volcanic fronts". 2. Large pipes commonly contain the higher amounts of the sub-calcic garnets representing the dunitic associations (Stachel et al., 2008). In ophiolites dunites veins are representing the channels for the melt transfer (Kelemen et al., 2002). It is likely that ancient large magmatic arc system could have also deep seated roots represented by the (sub calcic) garnet - bearing dunitic systems. 3. Many large pipes including Udachnaya (Pokhilenko et al., 1999) and Mir (Roden et al., 2006) contain in mantle roots high amount of various pyroxenites. The most ancient pyroxenites are supplementary to the dunitic associations. But mostly they represent the materials from the re-melted eclogites and partial and hybrid melts (plume and subduction -related). They are concentrating in the traps in the lithosphere base, in the middle part of mantle section and in the basaltic trap 2.0-3.0 GPa. Pyroxenites in the lithosphere base in some cases are vary abundant but mostly they are protokimberlitic cumulates from of the latest stages of plume activity. Products of the melts crystallization from the earlier stages represent easy melting material at the lithosphere base could be the traps for the later plume melts. 5. Large pipes as a rule reveal contrast layering which is favorite for the capturing of the material from

  5. Peculiarities of mantle lithosphere beneath the large kimberlite pipes in different regions for Siberian craton

    NASA Astrophysics Data System (ADS)

    Ashchepkov, Igor; Logvinova, Alla; Ntaflos, Theodoros; Vladykin, Nikolai; Spetsius, Zdislav; Kostrovitsky, Sergey; Stegnitsky, Yuri; Prokopyev, Sergey

    2016-04-01

    Comparison of the structure of the mantle columns and mineralogy of the large kimberlite pipes in Yakutia from the different regions, kimberlite fields and mantle terranes in Yakutia allowed several assumptions. 1. The large kimberlite pipes possibly trace the ancient magma feeders occurred in the time of the continent growth. Commonly kimberlites and large pipes are tracing the deep faults and lineaments tracing the ancient sutures, rift zones, trans -lithospheric faults and other permeable structures, which may be parallel to the ancient continental margins. Large pipes locate at the periodic distance like volcanoes in arc settings tracing the "volcanic fronts". 2. Large pipes commonly contain the higher amounts of the sub-calcic garnets representing the dunitic associations (Stachel et al., 2008). In ophiolites dunites veins are representing the channels for the melt transfer (Kelemen et al., 2002). It is likely that ancient large magmatic arc system could have also deep seated roots represented by the (sub calcic) garnet - bearing dunitic systems. 3. Many large pipes including Udachnaya (Pokhilenko et al., 1999) and Mir (Roden et al., 2006) contain in mantle roots high amount of various pyroxenites. The most ancient pyroxenites are supplementary to the dunitic associations. But mostly they represent the materials from the re-melted eclogites and partial and hybrid melts (plume and subduction -related). They are concentrating in the traps in the lithosphere base, in the middle part of mantle section and in the basaltic trap 2.0-3.0 GPa. Pyroxenites in the lithosphere base in some cases are vary abundant but mostly they are protokimberlitic cumulates from of the latest stages of plume activity. Products of the melts crystallization from the earlier stages represent easy melting material at the lithosphere base could be the traps for the later plume melts. 5. Large pipes as a rule reveal contrast layering which is favorite for the capturing of the material from

  6. Recent Regional Climate State and Change - Derived through Downscaling Homogeneous Large-scale Components of Re-analyses

    NASA Astrophysics Data System (ADS)

    Von Storch, H.; Klehmet, K.; Geyer, B.; Li, D.; Schubert-Frisius, M.; Tim, N.; Zorita, E.

    2015-12-01

    Global re-analyses suffer from inhomogeneities, as they process data from networks under development. However, the large-scale component of such re-analyses is mostly homogeneous; additional observational data add in most cases to a better description of regional details and less so on large-scale states. Therefore, the concept of downscaling may be applied to homogeneously complementing the large-scale state of the re-analyses with regional detail - wherever the condition of homogeneity of the large-scales is fulfilled. Technically this can be done by using a regional climate model, or a global climate model, which is constrained on the large scale by spectral nudging. This approach has been developed and tested for the region of Europe, and a skillful representation of regional risks - in particular marine risks - was identified. While the data density in Europe is considerably better than in most other regions of the world, even here insufficient spatial and temporal coverage is limiting risk assessments. Therefore, downscaled data-sets are frequently used by off-shore industries. We have run this system also in regions with reduced or absent data coverage, such as the Lena catchment in Siberia, in the Yellow Sea/Bo Hai region in East Asia, in Namibia and the adjacent Atlantic Ocean. Also a global (large scale constrained) simulation has been. It turns out that spatially detailed reconstruction of the state and change of climate in the three to six decades is doable for any region of the world.The different data sets are archived and may freely by used for scientific purposes. Of course, before application, a careful analysis of the quality for the intended application is needed, as sometimes unexpected changes in the quality of the description of large-scale driving states prevail.

  7. Large stresses in the lithosphere in regions of strong Neotectonic uplift

    NASA Astrophysics Data System (ADS)

    Artyushkov, Eugene; Chekhovich, Peter

    2014-05-01

    Several mechanisms have been proposed to explain the drift of lithospheric plates: subduction pull, basal drag, ridge push and some other ones. Among them only ridge push can be quantified reliably enough as (1.5-2)×1012 Nm (Artyushkov, JGR, 1973, 78, 7675-7708; Geodynamics, Elsevier, 1983, 312 p.). Due to uncertainty of another mechanisms, estimates of the forces acting along the lithospheric layer still differ by one order of magnitude. Ridge push is only a special case of the forces produced in the gravity field by density heterogeneities in the crust and subcrustal lithosphere. These forces generally increase with the potential energy stored in the relief. This allows us to estimate what force is necessary to shorten the crust with its surface reaching a certain altitude. As follows from a large volume of data, strong shortening of the crust in folds belts usually produced a ragged topography. However, after its erosion in a few million years the crustal surface remained near to sea level and mountain building occurred after the termination of crustal shortening. Thus the present Alps were formed during the past 5 Ma after 99% of shortening in them were already over. In the Urals high mountains were formed in the late Early Permian while intense preceding shortening of the crust terminated in the middle of the Carboniferous. Using this constraint the mean force acting in the lithosphere in areas which are located near to sea level can be estimated as 3×1012 Nm. The forces produced by the above mechanism increase with the altitude of the topography. In such regions as the Tibetan Plateau, Pamir and Southern Tien-Shan they can be as large as (5-7)×1012 N/m. Depending on the boundary conditions, the forces can be compressive or tensile. Most of the present mountain ranges and high plateaus were formed due to a rapid crustal uplift during the past several million years. The main cause was infiltration of mantle fluids into the lithosphere (Artyushkov, Russian

  8. Structural features of T cell receptor variable regions that enhance domain stability and enable expression as single-chain VαVβ fragments

    PubMed Central

    Richman, Sarah A.; Aggen, David H.; Dossett, Michelle L.; Donermeyer, David L.; Allen, Paul M.; Greenberg, Philip D.; Kranz, David M.

    2009-01-01

    The variable (V) domains of antibodies and T cell receptors (TCRs) share sequence homology and striking structural similarity. Single-chain antibody V domain constructs (scFv) are routinely expressed in a variety of heterologous systems, both for production of soluble protein as well as for in vitro engineering. In contrast, single-chain T cell receptor V domain constructs (scTCR) are prone to aggregation and misfolding and are refractory to display on phage or yeast in their wild-type form. However, through random mutagenesis and yeast display engineering, it has been possible to isolate scTCR mutants that are properly folded and displayed on the yeast surface. These displayed mutants can serve not only as a scaffold for further engineering but also as scTCR variants that exhibit favorable biophysical properties in E. coli expression. Thus, a more comprehensive understanding of the V domain mutations that allowed display would be beneficial. Our goal here was to identify generalizable patterns of important mutations that can be applied to different TCRs. We compared five different scTCRs, four from mice and one from a human, for yeast surface display. Analysis of a collection of mutants revealed four distinct regions of TCR V domains that were most important for enabling surface expression: the Vα-Vβ interface, the HV4 of Vβ, and the region of the Vα and Vβ domains normally apposed against the constant (C) domains. Consistent with the role of the V-C interface in surface display, reconstitution of this interface, by including the constant domains of each chain, allowed V domain display and αβ chain association on the yeast surface, thus providing an alternative TCR scaffold. However, the surface levels of TCR achieved with engineered scTCR mutants were superior to that of the VαCα/VβCβ constructs. Therefore, we describe further optimization of the current strategy for surface display of the single-chain format in order to facilitate yeast display

  9. SagE induces highly effective protective immunity against Streptococcus iniae mainly through an immunogenic domain in the extracellular region

    PubMed Central

    2013-01-01

    Background Streptococcus iniae is a Gram-positive bacterium and a severe pathogen of a wide range of farmed fish. S. iniae possesses a virulence-associated streptolysin S cluster composed of several components, one of which is SagE. SagE a transmembrane protein with one major extracellular region named ECR. This study aimed to develop a SagE-based DNA candidate vaccine against streptococcosis and examine the immunoprotective mechanism of the vaccine. Results We constructed a DNA vaccine, pSagE, based on the sagE gene and examined its immunological property in a Japanese flounder (Paralichthys olivaceus) model. The results showed that at 7 days post-vaccination, expression of SagE at transcription and translation levels was detected in the tissues of the vaccinated fish. After challenge with S. iniae at one and two months post-vaccination, pSagE-vaccinated fish exhibited relative percent survival (RPS) of 95% and 88% respectively. Immunological analysis showed that (i) pSagE significantly upregulated the expression of a wide range of immune genes, (ii) pSagE induced the production of specific serum antibodies that bound whole-cell S. iniae, and (iii) treatment of S. iniae with pSagE-induced antibodies blocked bacterial invasion of host cells. To localize the immunoprotective domain of SagE, the ECR-expressing DNA vaccine pSagEECR was constructed. Immunization analysis showed that flounder vaccinated with pSagEECR exhibited a RPS of 68%, and that pSagEECR induced serum antibody production and immune gene expression in a manner similar to, though to lower magnitudes than, those induced by pSagE. Conclusions We in this study developed a DNA vaccine, pSagE, which induces highly protective immunity against S. iniae. The protective effect of pSagE is probably due to its ability to elicit systemic immune response, in particular that of the humoral branch, which leads to production of specific serum antibodies that impair bacterial infection. These results add insights to

  10. Entry of Duck Hepatitis B Virus into Primary Duck Liver and Kidney Cells after Discovery of a Fusogenic Region within the Large Surface Protein▿

    PubMed Central

    Maenz, Claudia; Chang, Shau-Feng; Iwanski, Alicja; Bruns, Michael

    2007-01-01

    Hepatitis B viruses exhibit a narrow host range specificity that is believed to be mediated by a domain of the large surface protein, designated L. For duck hepatitis B virus, it has been shown that the pre-S domain of L binds to carboxypeptidase D, a cellular receptor present in many species on a wide variety of cell types. Nonetheless, only hepatocytes become infected. It has remained vague which viral features determine host range specificity and organotropicity. By using chymotrypsin to treat duck hepatitis B virus, we addressed the question of whether a putative fusogenic region within the amino-terminal end of the small surface protein may participate in viral entry and possibly constitute one of the determinants of the host range of the virus. Addition of the enzyme to virions resulted in increased infectivity. Remarkably, even remnants of enzyme-treated subviral particles proved to be inhibitory to infection. A noninfectious deletion mutant devoid of the binding region for carboxypeptidase D could be rendered infectious for primary duck hepatocytes by treatment with chymotrypsin. Although because of the protease treatment mutant and wild-type viruses may have become infectious in an unspecific and receptor-independent manner, their host range specificity was not affected, as shown by the inability of the virus to replicate in different hepatoma cell lines, as well as primary chicken hepatocytes. Instead, the organotropicity of the virus could be reduced, which was demonstrated by infection of primary duck kidney cells. PMID:17360753

  11. Large Scale Evapotranspiration Estimates: An Important Component in Regional Water Balances to Assess Water Availability

    NASA Astrophysics Data System (ADS)

    Garatuza-Payan, J.; Yepez, E. A.; Watts, C.; Rodriguez, J. C.; Valdez-Torres, L. C.; Robles-Morua, A.

    2013-05-01

    Water security, can be defined as the reliable supply in quantity and quality of water to help sustain future populations and maintaining ecosystem health and productivity. Water security is rapidly declining in many parts of the world due to population growth, drought, climate change, salinity, pollution, land use change, over-allocation and over-utilization, among other issues. Governmental offices (such as the Comision Nacional del Agua in Mexico, CONAGUA) require and conduct studies to estimate reliable water balances at regional or continental scales in order to provide reasonable assessments of the amount of water that can be provided (from surface or ground water sources) to supply all the human needs while maintaining natural vegetation, on an operational basis and, more important, under disturbances, such as droughts. Large scale estimates of evapotranspiration (ET), a critical component of the water cycle, are needed for a better comprehension of the hydrological cycle at large scales, which, in most water balances is left as the residual. For operational purposes, such water balance estimates can not rely on ET measurements since they do not exist, should be simple and require the least ground information possible, information that is often scarce or does not exist at all. Given this limitation, the use of remotely sensed data to estimate ET could supplement the lack of ground information, particularly in remote regions In this study, a simple method, based on the Makkink equation is used to estimate ET for large areas at high spatial resolutions (1 km). The Makkink model used here is forced using three remotely sensed datasets. First, the model uses solar radiation estimates obtained from the Geostationary Operational Environmental Satellite (GOES); Second, the model uses an Enhanced Vegetation Index (EVI) obtained from the Moderate-resolution Imaging Spectroradiometer (MODIS) normalized to get an estimate for vegetation amount and land use which was

  12. Merged interaction regions and large-scale magnetic field fluctuations during 1991: Voyager 2 observations

    NASA Technical Reports Server (NTRS)

    Burlaga, L. F.; Ness, N. F.

    1994-01-01

    This paper analyzes Voyager 2 observations of the magnetic field between 33.6 AU and 36.2 AU during 1991 when extraordinary events were observed on the Sun and in the heliosphere. The magnetic field strength signal B(t) has the unusual form of two large transient merged interaction regions (MIRs) on a fluctuating background. The two MIRs moved past the spacecraft in 32 days and 18 days, respectively. The mean field strength in each transient MIR was approx. equals 2.6 times the mean field during the remaining part of the year (0.11 nT). Each of the MIRs is related to a fast stream. The magnetic field is strong throughout each stream, suggesting that the strong fields are carried by the streams as well as produced by shock and stream compression. The fluctuations in B(t) during 1991 are not multifractal, and the MIRs cannot be approximated as multifractal clusters of intense magnetic fields. The distribution of the hour-averaged magnetic field strengths is approximately lognormal over 90% of its intermediate range, and it has an exponential tail for B greater than the average magnetic field strength. The elevation angles of B have a normal distribution with a standard deviation of 16 deg +/- 4 deg. The distributions of the azimuthal angles of B in the ranges 1 deg - 180 deg and 180 deg - 360 deg are approximately normal over a more limited range, and non-Gaussian tails associated with nearly radial magnetic fields; the standard deviations are approx. equal to 40 deg. Individual sectors are present throughout most of the interval, even in the MIRs, but there is no recurrent sector pattern. A model of the large-scale fluctuations in 1991 will have to include both determinaistic and statistical factors.

  13. Daily air temperature interpolated at high spatial resolution over a large mountainous region

    USGS Publications Warehouse

    Dodson, R.; Marks, D.

    1997-01-01

    Two methods are investigated for interpolating daily minimum and maximum air temperatures (Tmin and Tmax) at a 1 km spatial resolution over a large mountainous region (830 000 km2) in the U.S. Pacific Northwest. The methods were selected because of their ability to (1) account for the effect of elevation on temperature and (2) efficiently handle large volumes of data. The first method, the neutral stability algorithm (NSA), used the hydrostatic and potential temperature equations to convert measured temperatures and elevations to sea-level potential temperatures. The potential temperatures were spatially interpolated using an inverse-squared-distance algorithm and then mapped to the elevation surface of a digital elevation model (DEM). The second method, linear lapse rate adjustment (LLRA), involved the same basic procedure as the NSA, but used a constant linear lapse rate instead of the potential temperature equation. Cross-validation analyses were performed using the NSA and LLRA methods to interpolate Tmin and Tmax each day for the 1990 water year, and the methods were evaluated based on mean annual interpolation error (IE). The NSA method showed considerable bias for sites associated with vertical extrapolation. A correction based on climate station/grid cell elevation differences was developed and found to successfully remove the bias. The LLRA method was tested using 3 lapse rates, none of which produced a serious extrapolation bias. The bias-adjusted NSA and the 3 LLRA methods produced almost identical levels of accuracy (mean absolute errors between 1.2 and 1.3??C), and produced very similar temperature surfaces based on image difference statistics. In terms of accuracy, speed, and ease of implementation, LLRA was chosen as the best of the methods tested.

  14. Large-scale regionalization of water table depth in peatlands optimized for greenhouse gas emission upscaling

    NASA Astrophysics Data System (ADS)

    Bechtold, M.; Tiemeyer, B.; Laggner, A.; Leppelt, T.; Frahm, E.; Belting, S.

    2014-04-01

    Fluxes of the three main greenhouse gases (GHG) CO2, CH4 and N2O from peat and other organic soils are strongly controlled by water table depth. Information about the spatial distribution of water level is thus a crucial input parameter when upscaling GHG emissions to large scales. Here, we investigate the potential of statistical modeling for the regionalization of water levels in organic soils when data covers only a small fraction of the peatlands of the final map. Our study area is Germany. Phreatic water level data from 53 peatlands in Germany were compiled in a new dataset comprising 1094 dip wells and 7155 years of data. For each dip well, numerous possible predictor variables were determined using nationally available data sources, which included information about land cover, ditch network, protected areas, topography, peatland characteristics and climatic boundary conditions. We applied boosted regression trees to identify dependencies between predictor variables and dip well specific long-term annual mean water level (WL) as well as a transformed form of it (WLt). The latter was obtained by assuming a hypothetical GHG transfer function and is linearly related to GHG emissions. Our results demonstrate that model calibration on WLt is superior. It increases the explained variance of the water level in the sensitive range for GHG emissions and avoids model bias in subsequent GHG upscaling. The final model explained 45% of WLt variance and was built on nine predictor variables that are based on information about land cover, peatland characteristics, drainage network, topography and climatic boundary conditions. Their individual effects on WLt and the observed parameter interactions provide insights into natural and anthropogenic boundary conditions that control water levels in organic soils. Our study also demonstrates that a large fraction of the observed WLt variance cannot be explained by nationally available predictor variables and that predictors with

  15. Large Amplitude IMF Fluctuations in Corotating Interaction Regions: Ulysses at Midlatitudes

    NASA Technical Reports Server (NTRS)

    Tsurutani, Bruce T.; Ho, Christian M.; Arballo, John K.; Goldstein, Bruce E.; Balogh, Andre

    1995-01-01

    Corotating Interaction Regions (CIRs), formed by high-speed corotating streams interacting with slow speed streams, have been examined from -20 deg to -36 deg heliolatitudes. The high-speed streams emanate from a polar coronal hole that Ulysses eventually becomes fully embedded in as it travels towards the south pole. We find that the trailing portion of the CIR, from the interface surface (IF) to the reverse shock (RS), contains both large amplitude transverse fluctuations and magnitude fluctuations. Similar fluctuations have been previously noted to exist within CIRs detected in the ecliptic plane, but their existence has not been explained. The normalized magnetic field component variances within this portion of the CIR and in the trailing high-speed stream are approximately the same, indicating that the fluctuations in the CIR are compressed Alfven waves. Mirror mode structures with lower intensities are also observed in the trailing portion of the CIR, presumably generated from a local instability driven by free energy associated with compression of the high-speed solar wind plasma. The mixture of these two modes (compressed Alfven waves and mirror modes) plus other modes generated by three wave processes (wave-shock interactions) lead to a lower Alfvenicity within the trailing portion of the CfR than in the high-speed stream proper. The results presented in this paper suggest a mechanism for generation of large amplitude B(sub z) fluctuations within CIRS. Such phenomena have been noted to be responsible for the generation of moderate geomagnetic storms during the declining phase of the solar cycle.

  16. Identification of Regions in the Receiver Domain of the ETHYLENE RESPONSE1 Ethylene Receptor of Arabidopsis Important for Functional Divergence1[OPEN

    PubMed Central

    Bakshi, Arkadipta; Wilson, Rebecca L.; Lacey, Randy F.; Kim, Heejung; Wuppalapati, Sai Keerthana; Binder, Brad M.

    2015-01-01

    Ethylene influences the growth and development of Arabidopsis (Arabidopsis thaliana) via five receptor isoforms. However, the ETHYLENE RESPONSE1 (ETR1) ethylene receptor has unique, and sometimes contrasting, roles from the other receptor isoforms. Prior research indicates that the receiver domain of ETR1 is important for some of these noncanonical roles. We determined that the ETR1 receiver domain is not needed for ETR1’s predominant role in mediating responses to the ethylene antagonist, silver. To understand the structure-function relationship underlying the unique roles of the ETR1 receiver domain in the control of specific traits, we performed alanine-scanning mutagenesis. We chose amino acids that are poorly conserved and are in regions predicted to have altered tertiary structure compared with the receiver domains of the other two receptors that contain a receiver domain, ETR2 and ETHYLENE INSENSITIVE4. The effects of these mutants on various phenotypes were examined in transgenic, receptor-deficient Arabidopsis plants. Some traits, such as growth in air and growth recovery after the removal of ethylene, were unaffected by these mutations. By contrast, three mutations on one surface of the receiver domain rendered the transgene unable to rescue ethylene-stimulated nutations. Additionally, several mutations on another surface altered germination on salt. Some of these mutations conferred hyperfunctionality to ETR1 in the context of seed germination on salt, but not for other traits, that correlated with increased responsiveness to abscisic acid. Thus, the ETR1 receiver domain has multiple functions where different surfaces are involved in the control of different traits. Models are discussed for these observations. PMID:26160962

  17. A refined regional modeling approach for the Corn Belt - experiences and recommendations for large-scale integrated modeling

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Nonpoint source pollution from agriculture is the main source of nitrogen and phosphorus in the stream systems of the Corn Belt region in the Midwestern U.S. This region is comprised of two large river basins, the intensely row-cropped Upper Mississippi River Basin (UMRB) and Ohio-Tennessee River B...

  18. Structural Study of the HD-PTP Bro1 Domain in a Complex with the Core Region of STAM2, a Subunit of ESCRT-0.

    PubMed

    Lee, Juhyeon; Oh, Kyoung-Jin; Lee, Dasom; Kim, Bo Yeon; Choi, Joon Sig; Ku, Bonsu; Kim, Seung Jun

    2016-01-01

    EGFR is a key player in cell proliferation and survival signaling, and its sorting into MVBs for eventual lysosomal degradation is controlled by the coordination of multiple ESCRT complexes on the endosomal membrane. HD-PTP is a cytosolic protein tyrosine phosphatase, and is associated with EGFR trafficking by interacting with the ESCRT-0 protein STAM2 and the ESCRT-III protein CHMP4B via its N-terminal Bro1 domain. Intriguingly, the homologous domain of two other human Bro1 domain-containing proteins, Alix and Brox, binds CHMP4B but not STAM2, despite their high structural similarity. To elucidate this binding specificity, we determined the complex structure of the HD-PTP Bro1 domain bound to the STAM2 core region. STAM2 binds to the hydrophobic concave pocket of the HD-PTP Bro1 domain, as CHMP4B does to the pocket of Alix, Brox, or HD-PTP but in the opposite direction. Critically, Thr145 of HD-PTP, corresponding to Lys151 of Alix and Arg145 of Brox, is revealed to be a determinant residue enabling this protein to bind STAM2, as the Alix- or Brox-mimicking mutations of this residue blocks the intermolecular interaction. This work therefore provides the structural basis for how HD-PTP recognizes the ESCRT-0 component to control EGFR sorting. PMID:26866605

  19. Structure of the iSH2 domain of Human phosphatidylinositol 3-kinase p85 beta Subunit Reveals Conformational Plasticity in the Interhelical Turn Region

    SciTech Connect

    C Schauder; L Ma; R Krug; G Montelione; R Guan

    2011-12-31

    Phosphatidylinositol 3-kinase (PI3K) proteins actively trigger signaling pathways leading to cell growth, proliferation and survival. These proteins have multiple isoforms and consist of a catalytic p110 subunit and a regulatory p85 subunit. The iSH2 domain of the p85 {beta} isoform has been implicated in the binding of nonstructural protein 1 (NS1) of influenza A viruses. Here, the crystal structure of human p85 {beta} iSH2 determined to 3.3 {angstrom} resolution is reported. The structure reveals that this domain mainly consists of a coiled-coil motif. Comparison with the published structure of the bovine p85 {beta} iSH2 domain bound to the influenza A virus nonstructural protein 1 indicates that little or no structural change occurs upon complex formation. By comparing this human p85 {beta} iSH2 structure with the bovine p85 {beta} iSH2 domain, which shares 99% sequence identity, and by comparing the multiple conformations observed within the asymmetric unit of the bovine iSH2 structure, it was found that this coiled-coil domain exhibits a certain degree of conformational variability or 'plasticity' in the interhelical turn region. It is speculated that this plasticity of p85 {beta} iSH2 may play a role in regulating its functional and molecular-recognition properties.

  20. A unique GCN5-related glucosamine N-acetyltransferase region exist in the fungal multi-domain glycoside hydrolase family 3 β-N-acetylglucosaminidase

    PubMed Central

    Qin, Zhen; Xiao, Yibei; Yang, Xinbin; Mesters, Jeroen R.; Yang, Shaoqing; Jiang, Zhengqiang

    2015-01-01

    Glycoside hydrolase (GH) family 3 β-N-acetylglucosaminidases widely exist in the filamentous fungi, which may play a key role in chitin metabolism of fungi. A multi-domain GH family 3 β-N-acetylglucosaminidase from Rhizomucor miehei (RmNag), exhibiting a potential N-acetyltransferase region, has been recently reported to show great potential in industrial applications. In this study, the crystal structure of RmNag was determined at 2.80 Å resolution. The three-dimensional structure of RmNag showed four distinctive domains, which belong to two distinguishable functional regions — a GH family 3 β-N-acetylglucosaminidase region (N-terminal) and a N-acetyltransferase region (C-terminal). From structural and functional analysis, the C-terminal region of RmNag was identified as a unique tandem array linking general control non-derepressible 5 (GCN5)-related N-acetyltransferase (GNAT), which displayed glucosamine N-acetyltransferase activity. Structural analysis of this glucosamine N-acetyltransferase region revealed that a unique glucosamine binding pocket is located in the pantetheine arm binding terminal region of the conserved CoA binding pocket, which is different from all known GNAT members. This is the first structural report of a glucosamine N-acetyltransferase, which provides novel structural information about substrate specificity of GNATs. The structural and functional features of this multi-domain β-N-acetylglucosaminidase could be useful in studying the catalytic mechanism of GH family 3 proteins. PMID:26669854

  1. ALK kinase domain mutations in primary anaplastic large cell lymphoma: consequences on NPM-ALK activity and sensitivity to tyrosine kinase inhibitors.

    PubMed

    Lovisa, Federica; Cozza, Giorgio; Cristiani, Andrea; Cuzzolin, Alberto; Albiero, Alessandro; Mussolin, Lara; Pillon, Marta; Moro, Stefano; Basso, Giuseppe; Rosolen, Angelo; Bonvini, Paolo

    2015-01-01

    ALK inhibitor crizotinib has shown potent antitumor activity in children with refractory Anaplastic Large Cell Lymphoma (ALCL) and the opportunity to include ALK inhibitors in first-line therapies is oncoming. However, recent studies suggest that crizotinib-resistance mutations may emerge in ALCL patients. In the present study, we analyzed ALK kinase domain mutational status of 36 paediatric ALCL patients at diagnosis to identify point mutations and gene aberrations that could impact on NPM-ALK gene expression, activity and sensitivity to small-molecule inhibitors. Amplicon ultra-deep sequencing of ALK kinase domain detected 2 single point mutations, R335Q and R291Q, in 2 cases, 2 common deletions of exon 23 and 25 in all the patients, and 7 splicing-related INDELs in a variable number of them. The functional impact of missense mutations and INDELs was evaluated. Point mutations were shown to affect protein kinase activity, signalling output and drug sensitivity. INDELs, instead, generated kinase-dead variants with dominant negative effect on NPM-ALK kinase, in virtue of their capacity of forming non-functional heterocomplexes. Consistently, when co-expressed, INDELs increased crizotinib inhibitory activity on NPM-ALK signal processing, as demonstrated by the significant reduction of STAT3 phosphorylation. Functional changes in ALK kinase activity induced by both point mutations and structural rearrangements were resolved by molecular modelling and dynamic simulation analysis, providing novel insights into ALK kinase domain folding and regulation. Therefore, these data suggest that NPM-ALK pre-therapeutic mutations may be found at low frequency in ALCL patients. These mutations occur randomly within the ALK kinase domain and affect protein activity, while preserving responsiveness to crizotinib.

  2. YOUNG STELLAR OBJECTS IN THE LARGE MAGELLANIC CLOUD STAR-FORMING REGION N206

    SciTech Connect

    Romita, Krista Alexandra; Meixner, M.; Sewilo, M.; Shiao, B.; Carlson, Lynn Redding; Whitney, B.; Babler, B.; Meade, M.; Indebetouw, R.; Hora, J. L. E-mail: carlson@stsci.ed E-mail: brian@sal.wisc.ed E-mail: jhora@cfa.harvard.ed

    2010-09-20

    We present analysis of the energetic star-forming region Henize 206 (N206) located near the southern edge of the Large Magellanic Cloud (LMC) based on photometric data from the Spitzer Surveying the Agents of Galaxy Evolution (SAGE-LMC; IRAC 3.6, 4.5, 5.8, 8.0 {mu}m and MIPS 24 {mu}m), Infrared Survey Facility near-infrared survey (J, H, K{sub s}), and the Magellanic Clouds Photometric Survey (MCPS UBVI) covering a wavelength range of 0.36-24 {mu}m. Young stellar object (YSO) candidates are identified based upon their location in infrared color-magnitude space and classified by the shapes of their spectral energy distributions in comparison with a pre-computed grid of YSO models. We identify 116 YSO candidates: 102 are well characterized by the YSO models, predominately Stage I, and 14 may be multiple sources or young sources with transition disks. Careful examination of the individual sources and their surrounding environment allows us to identify a factor of {approx}14.5 more YSO candidates than have already been identified. The total mass of these well-fit YSO candidates is {approx}520 M{sub sun}. We calculate a current star formation rate of 0.27 x 10{sup -1} M{sub sun} yr{sup -1} kpc{sup -2}. The distribution of YSO candidates appears to follow shells of neutral material in the interstellar medium.

  3. Particle precipitation prior to large earthquakes of both the Sumatra and Philippine Regions: A statistical analysis

    NASA Astrophysics Data System (ADS)

    Fidani, Cristiano

    2015-12-01

    A study of statistical correlation between low L-shell electrons precipitating into the atmosphere and strong earthquakes is presented. More than 11 years of the Medium Energy Protons Electrons Detector data from the NOAA-15 Sun-synchronous polar orbiting satellite were analysed. Electron fluxes were analysed using a set of adiabatic coordinates. From this, significant electron counting rate fluctuations were evidenced during geomagnetic quiet periods. Electron counting rates were compared to earthquakes by defining a seismic event L-shell obtained radially projecting the epicentre geographical positions to a given altitude towards the zenith. Counting rates were grouped in every satellite semi-orbit together with strong seismic events and these were chosen with the L-shell coordinates close to each other. NOAA-15 electron data from July 1998 to December 2011 were compared for nearly 1800 earthquakes with magnitudes larger than or equal to 6, occurring worldwide. When considering 30-100 keV precipitating electrons detected by the vertical NOAA-15 telescope and earthquake epicentre projections at altitudes greater that 1300 km, a significant correlation appeared where a 2-3 h electron precipitation was detected prior to large events in the Sumatra and Philippine Regions. This was in physical agreement with different correlation times obtained from past studies that considered particles with greater energies. The Discussion below of satellite orbits and detectors is useful for future satellite missions for earthquake mitigation.

  4. Seismicity trends and potential for large earthquakes in the Alaska-Aleutian region

    USGS Publications Warehouse

    Bufe, C.G.; Nishenko, S.P.; Varnes, D.J.

    1994-01-01

    The high likelihood of a gap-filling thrust earthquake in the Alaska subduction zone within this decade is indicated by two independent methods: analysis of historic earthquake recurrence data and time-to-failure analysis applied to recent decades of instrumental data. Recent (May 1993) earthquake activity in the Shumagin Islands gap is consistent with previous projections of increases in seismic release, indicating that this segment, along with the Alaska Peninsula segment, is approaching failure. Based on this pattern of accelerating seismic release, we project the occurrence of one or more M???7.3 earthquakes in the Shumagin-Alaska Peninsula region during 1994-1996. Different segments of the Alaska-Aleutian seismic zone behave differently in the decade or two preceding great earthquakes, some showing acceleration of seismic release (type "A" zones), while others show deceleration (type "D" zones). The largest Alaska-Aleutian earthquakes-in 1957, 1964, and 1965-originated in zones that exhibit type D behavior. Type A zones currently showing accelerating release are the Shumagin, Alaska Peninsula, Delarof, and Kommandorski segments. Time-to-failure analysis suggests that the large earthquakes could occur in these latter zones within the next few years. ?? 1994 Birkha??user Verlag.

  5. Improved confinement region without large magnetohydrodynamic activity in TPE-RX reversed-field pinch plasma

    SciTech Connect

    Yambe, Kiyoyuki; Hirano, Yoichi; Sakakita, Hajime; Koguchi, Haruhisa

    2014-11-15

    We found that spontaneous improved confinement was brought about depending on the operating region in the Toroidal Pinch Experiment-Reversed eXperiment (TPE-RX) reversed-field pinch plasma [Y. Yagi et al., Fusion Eng. Des. 45, 421 (1999)]. Gradual decay of the toroidal magnetic field at plasma surface B{sub tw} reversal makes it possible to realize a prolonged discharge, and the poloidal beta value and energy confinement time increase in the latter half of the discharge, where reversal and pinch parameters become shallow and low, respectively. In the latter half of the discharge, the plasma current and volume-averaged toroidal magnetic field 〈B{sub t}〉 increase again, the electron density slowly decays, the electron temperature and soft X-ray radiation intensity increase, and the magnetic fluctuations are markedly reduced. In this period of improved confinement, the value of (〈B{sub t}〉-B{sub tw})/B{sub pw}, where B{sub pw} is the poloidal magnetic field at the plasma surface, stays almost constant, which indicates that the dynamo action occurs without large magnetohydrodynamic activities.

  6. Ganymede - Mixture of Terrains and Large Impact Crater in Uruk Sulcus Region

    NASA Technical Reports Server (NTRS)

    1996-01-01

    A mixture of terrains studded with a large impact crater is shown in this view of the Uruk Sulcus region of Jupiter's moon Ganymede taken by NASA's Galileo spacecraft during its first flyby of the planet-sized moon on June 27, 1996. The image shows fine details of bright areas that make up about half of the surface of Ganymede. Pock-marked, ancient, heavily cratered terrain is seen at the top; it is cut by younger, line-like structures in the lower left of the image. The bright, circular feature in the lower middle is an impact crater with some dark ejecta superimposed on the linear ridges. These types of relationships revealed by Galileo allow scientists to work out the complex geologic history of Ganymede. In this view, north is to the top and the sun illuminates the surface from the lower left nearly overhead. The area shown, at latitude 10 degrees north, longitude 168 degrees west, is about 59 by 40 kilometers (36 by 25 miles), and the resolution is 74 meters (80 yards) per picture element. The image was taken on June 27 at a range of 7,448 kilometers (4.628 miles). The Jet Propulsion Laboratory manages the Galileo mission for NASA's Office of Space Science.

  7. The C-terminal region of the transcriptional regulator THAP11 forms a parallel coiled-coil domain involved in protein dimerization.

    PubMed

    Cukier, Cyprian D; Maveyraud, Laurent; Saurel, Olivier; Guillet, Valérie; Milon, Alain; Gervais, Virginie

    2016-06-01

    Thanatos associated protein 11 (THAP11) is a cell cycle and cell growth regulator differentially expressed in cancer cells. THAP11 belongs to a distinct family of transcription factors recognizing specific DNA sequences via an atypical zinc finger motif and regulating diverse cellular processes. Outside the extensively characterized DNA-binding domain, THAP proteins vary in size and predicted domains, for which structural data are still lacking. We report here the crystal structure of the C-terminal region of human THAP11 protein, providing the first 3D structure of a coiled-coil motif from a THAP family member. We further investigate the stability, dynamics and oligomeric properties of the determined structure combining molecular dynamics simulations and biophysical experiments. Our results show that the C-ter region of THAP11 forms a left-handed parallel homo-dimeric coiled-coil structure possessing several unusual features. PMID:26975212

  8. Use of the myosin motor domain as large-affinity tag for the expression and purification of proteins in Dictyostelium discoideum.

    PubMed

    Kollmar, Martin

    2006-08-15

    The cellular slime mold Dictyostelium discoideum is increasingly be used for the overexpression of proteins. Dictyostelium is amenable to classical and molecular genetic approaches and can easily be grown in large quantities. It contains a variety of chaperones and folding enzymes, and is able to perform all kinds of post-translational protein modifications. Here, new expression vectors are presented that have been designed for the production of proteins in large quantities for biochemical and structural studies. The expression cassettes of the most successful vectors are based on a tandem affinity purification tag consisting of an octahistidine tag followed by the myosin motor domain tag. The myosin motor domain not only strongly enhances the production of fused proteins but is also used for a fast affinity purification step through its ATP-dependent binding to actin. The applicability of the new system has been demonstrated for the expression and purification of subunits of the dynein-dynactin motor protein complex from different species. PMID:16516959

  9. Mapping of the mouse homolog of the human runt domain gene, AML2, to the distal region of mouse chromosome 4

    SciTech Connect

    Avraham, K.B.; Copeland, N.G.; Jenkins, N.A.

    1995-01-20

    AML2 is a runt domain belonging to a group of transcription factors that appear to play a role in Drosophila embryogenesis and mammalian oncogenic transformation. AML2 maps to human chromosome 1p36, a region involved in the t(1;3)(p36;q21) translocation found in association with myelodysplastic syndrome (MDS), myeloproliferative disease (MPD), and acute nonlymphocytic leukemia. 9 refs., 1 fig.

  10. Improvement of lateral resolution of spectral domain optical coherence tomography images in out-of-focus regions with holographic data processing techniques

    SciTech Connect

    Moiseev, A A; Gelikonov, G V; Terpelov, D A; Shilyagin, P A; Gelikonov, V M

    2014-08-31

    An analogy between spectral-domain optical coherence tomography (SD OCT) data and broadband digital holography data is considered. Based on this analogy, a method for processing SD OCT data, which makes it possible to construct images with a lateral resolution in the whole investigated volume equal to the resolution in the in-focus region, is developed. Several issues concerning practical application of the proposed method are discussed. (laser biophotonics)

  11. Evaluation of the Diurnal Evolution of the Size of Tropical Convective Systems in Large Domain, High Resolution Simulations using Observations of Outgoing Longwave Radiation

    NASA Astrophysics Data System (ADS)

    Pearson, K.; Hogan, R.; Allan, R.; Holloway, C. E.; Lister, G.

    2010-12-01

    A long-standing problem in climate models is the failure to capture either the correct diurnal cycle in convective clouds or the growth of individual cells into larger scale complexes. Cascade is a multi-institution project to study the formation and development of tropical convective systems using high-resolution numerical modeling (down to 1.5~km) run over large domains ( ˜2000×2000~km) and observations. As one element of this, we have developed a technique for visualizing and testing the diurnal cycle in the size of convective cloud systems using observations of outgoing longwave radiation. This has been applied to a 2006 test case over Africa using GERB observations and models run with differing configurations and resolutions. We are now applying this to a large domain simulation of the Maritime continent covering several weeks during April 2009 comparing with TRMM observations. The image shows a comparison of the Met Office Unified Model run at 4~km and 12~km resolution, with and without convective parametrization respectively, for the West Africa test case. The grayscale represents the anomaly in the number of systems falling into each lengthscale bin against time. The middle panel is derived from observations by the Geostationary Earth Radiation Budget (GERB) instrument. It shows a broad upward stripe reflecting growth from smaller to larger systems beginning in the late afternoon. The 12~km model shows the effect of the parametrization scheme with systems of all sizes peaking at similar times much earlier than the observations. The 4~km model bears much closer comparison to the observations with growth in the middle to large size range occurring at a similar time to the observations. The small scale behavior, however, is affected by an unrealistic "shattering" of the large systems into many fragments in the early morning rather than a gradual decay.

  12. Future summer precipitation changes over CORDEX-East Asia domain downscaled by a regional ocean-atmosphere coupled model: A comparison to the stand-alone RCM

    NASA Astrophysics Data System (ADS)

    Zou, Liwei; Zhou, Tianjun

    2016-03-01

    Climate changes under the RCP8.5 scenario over the Coordinated Regional Downscaling Experiment (CORDEX)-East Asia domain downscaled by a regional ocean-atmosphere coupled model Flexible Regional Ocean-Atmosphere Land System (FROALS) are compared to those downscaled by the corresponding atmosphere-only regional climate model driven by a global climate system model. Changes in the mean and interannual variability of summer rainfall were discussed for the period of 2051-2070 with respect to the present-day period of 1986-2005. Followed by an enhanced western North Pacific subtropical high and an intensified East Asian summer monsoon, an increase in total rainfall over north China, the Korean Peninsula, and Japan but a decrease in total rainfall over southern China are observed in the FROALS projection. Homogeneous increases of extreme rainfall amounts were found over the CORDEX-East Asia domain. A predominant increase in the interannual variability was evident for both total rainfall and the extreme rainfall amount. The spatial patterns of the projected rainfall changes by FROALS were generally consistent with those from the driving global model at a broad scale due to similar projected circulation changes. In both models, the enhanced southerlies over east China increased the moisture divergences over southern China and enhanced the moisture advection over north China. However, the atmosphere-only regional climate model (RCM) exhibited responses to the underlying sea surface temperature (SST) warming anomalies that were too strong, which induced an anomalous cyclone over the north South China Sea, followed by increases (decreases) of total and extreme rainfall over southern China (central China). The differences of the projected changes in both rainfall and circulation between FROALS and the atmosphere-only RCM were partly affected by the differences in the projected SST changes. The results recommend the employment of a regional ocean-atmosphere coupled model in the

  13. Tethered domains and flexible regions in tRNase Z(L), the long form of tRNase Z.

    PubMed

    Wilson, Christopher; Ramai, Daryl; Serjanov, Dmitri; Lama, Neema; Levinger, Louis; Chang, Emmanuel J

    2013-01-01

    tRNase Z, a member of the metallo-β-lactamase family, endonucleolytically removes the pre-tRNA 3' trailer in a step central to tRNA maturation. The short form (tRNase Z(S)) is the only one found in bacteria and archaebacteria and is also present in some eukaryotes. The homologous long form (tRNase Z(L)), exclusively found in eukaryotes, consists of related amino- and carboxy-domains, suggesting that tRNase Z(L) arose from a tandem duplication of tRNase Z(S) followed by interdependent divergence of the domains. X-ray crystallographic structures of tRNase Z(S) reveal a flexible arm (FA) extruded from the body of tRNase Z remote from the active site that binds tRNA far from the scissile bond. No tRNase Z(L) structures have been solved; alternative biophysical studies are therefore needed to illuminate its functional characteristics. Structural analyses of tRNase Z(L) performed by limited proteolysis, two dimensional gel electrophoresis and mass spectrometry establish stability of the amino and carboxy domains and flexibility of the FA and inter-domain tether, with implications for tRNase Z(L) function.

  14. A numerical approach for simulating fluid structure interaction of flexible thin shells undergoing arbitrarily large deformations in complex domains

    NASA Astrophysics Data System (ADS)

    Gilmanov, Anvar; Le, Trung Bao; Sotiropoulos, Fotis

    2015-11-01

    We present a new numerical methodology for simulating fluid-structure interaction (FSI) problems involving thin flexible bodies in an incompressible fluid. The FSI algorithm uses the Dirichlet-Neumann partitioning technique. The curvilinear immersed boundary method (CURVIB) is coupled with a rotation-free finite element (FE) model for thin shells enabling the efficient simulation of FSI problems with arbitrarily large deformation. Turbulent flow problems are handled using large-eddy simulation with the dynamic Smagorinsky model in conjunction with a wall model to reconstruct boundary conditions near immersed boundaries. The CURVIB and FE solvers are coupled together on the flexible solid-fluid interfaces where the structural nodal positions, displacements, velocities and loads are calculated and exchanged between the two solvers. Loose and strong coupling FSI schemes are employed enhanced by the Aitken acceleration technique to ensure robust coupling and fast convergence especially for low mass ratio problems. The coupled CURVIB-FE-FSI method is validated by applying it to simulate two FSI problems involving thin flexible structures: 1) vortex-induced vibrations of a cantilever mounted in the wake of a square cylinder at different mass ratios and at low Reynolds number; and 2) the more challenging high Reynolds number problem involving the oscillation of an inverted elastic flag. For both cases the computed results are in excellent agreement with previous numerical simulations and/or experiential measurements. Grid convergence tests/studies are carried out for both the cantilever and inverted flag problems, which show that the CURVIB-FE-FSI method provides their convergence. Finally, the capability of the new methodology in simulations of complex cardiovascular flows is demonstrated by applying it to simulate the FSI of a tri-leaflet, prosthetic heart valve in an anatomic aorta and under physiologic pulsatile conditions.

  15. Protein domain architectures.

    PubMed

    Mulder, Nicola J

    2010-01-01

    Proteins are composed of functional units, or domains, that can be found alone or in combination with other domains. Analysis of protein domain architectures and the movement of protein domains within and across different genomes provide clues about the evolution of protein function. The classification of proteins into families and domains is provided through publicly available tools and databases that use known protein domains to predict other members in new proteins sequences. Currently at least 80% of the main protein sequence databases can be classified using these tools, thus providing a large data set to work from for analyzing protein domain architectures. Each of the protein domain databases provide intuitive web interfaces for viewing and analyzing their domain classifications and provide their data freely for downloading. Some of the main protein family and domain databases are described here, along with their Web-based tools for analyzing domain architectures.

  16. The catalytic region and PEST domain of PTPN18 distinctly regulate the HER2 phosphorylation and ubiquitination barcodes.

    PubMed

    Wang, Hong-Mei; Xu, Yun-Fei; Ning, Shang-Lei; Yang, Du-Xiao; Li, Yi; Du, Yu-Jie; Yang, Fan; Zhang, Ya; Liang, Nan; Yao, Wei; Zhang, Ling-Li; Gu, Li-Chuan; Gao, Cheng-Jiang; Pang, Qi; Chen, Yu-Xin; Xiao, Kun-Hong; Ma, Rong; Yu, Xiao; Sun, Jin-Peng

    2014-09-01

    The tyrosine phosphorylation barcode encoded in C-terminus of HER2 and its ubiquitination regulate diverse HER2 functions. PTPN18 was reported as a HER2 phosphatase; however, the exact mechanism by which it defines HER2 signaling is not fully understood. Here, we demonstrate that PTPN18 regulates HER2-mediated cellular functions through defining both its phosphorylation and ubiquitination barcodes. Enzymologic characterization and three crystal structures of PTPN18 in complex with HER2 phospho-peptides revealed the molecular basis for the recognition between PTPN18 and specific HER2 phosphorylation sites, which assumes two distinct conformations. Unique structural properties of PTPN18 contribute to the regulation of sub-cellular phosphorylation networks downstream of HER2, which are required for inhibition of HER2-mediated cell growth and migration. Whereas the catalytic domain of PTPN18 blocks lysosomal routing and delays the degradation of HER2 by dephosphorylation of HER2 on pY(1112), the PEST domain of PTPN18 promotes K48-linked HER2 ubiquitination and its rapid destruction via the proteasome pathway and an HER2 negative feedback loop. In agreement with the negative regulatory role of PTPN18 in HER2 signaling, the HER2/PTPN18 ratio was correlated with breast cancer stage. Taken together, our study presents a structural basis for selective HER2 dephosphorylation, a previously uncharacterized mechanism for HER2 degradation and a novel function for the PTPN18 PEST domain. The new regulatory role of the PEST domain in the ubiquitination pathway will broaden our understanding of the functions of other important PEST domain-containing phosphatases, such as LYP and PTPN12. PMID:25081058

  17. Large-scale regionalization of water table depth in peatlands optimized for greenhouse gas emission upscaling

    NASA Astrophysics Data System (ADS)

    Bechtold, M.; Tiemeyer, B.; Laggner, A.; Leppelt, T.; Frahm, E.; Belting, S.

    2014-09-01

    Fluxes of the three main greenhouse gases (GHG) CO2, CH4 and N2O from peat and other soils with high organic carbon contents are strongly controlled by water table depth. Information about the spatial distribution of water level is thus a crucial input parameter when upscaling GHG emissions to large scales. Here, we investigate the potential of statistical modeling for the regionalization of water levels in organic soils when data covers only a small fraction of the peatlands of the final map. Our study area is Germany. Phreatic water level data from 53 peatlands in Germany were compiled in a new data set comprising 1094 dip wells and 7155 years of data. For each dip well, numerous possible predictor variables were determined using nationally available data sources, which included information about land cover, ditch network, protected areas, topography, peatland characteristics and climatic boundary conditions. We applied boosted regression trees to identify dependencies between predictor variables and dip-well-specific long-term annual mean water level (WL) as well as a transformed form (WLt). The latter was obtained by assuming a hypothetical GHG transfer function and is linearly related to GHG emissions. Our results demonstrate that model calibration on WLt is superior. It increases the explained variance of the water level in the sensitive range for GHG emissions and avoids model bias in subsequent GHG upscaling. The final model explained 45% of WLt variance and was built on nine predictor variables that are based on information about land cover, peatland characteristics, drainage network, topography and climatic boundary conditions. Their individual effects on WLt and the observed parameter interactions provide insight into natural and anthropogenic boundary conditions that control water levels in organic soils. Our study also demonstrates that a large fraction of the observed WLt variance cannot be explained by nationally available predictor variables and

  18. Exon organization of the mouse entactin gene corresponds to the structural domains of the polypeptide and has regional homology to the low-density lipoprotein receptor gene

    SciTech Connect

    Durkin, M.E.; Chung, A.E.; Wewer, U.M.

    1995-03-20

    Entactin is a widespread basement membrane protein of 150 kDa that binds to type IV collagen and laminin. The complete exon-intron structure of the mouse entactin gene has been determined from {lambda} genomic DNA clones. The gene spans at least 65 kb and contains 20 exons. The exon organization of the mouse entactin gene closely corresponds to the organization of the polypeptide into distinct structural and functional domains. The two amino-terminal globular domains are encoded by three exons each. Single exons encode the two protease-sensitive, O-glycosylated linking regions. The six EGF-like repeats and the single thyroglobulin-type repeat are each encoded by separate exons. The carboxyl-terminal half of entactin displays sequence homology to the growth factor-like region of the low-density lipoprotein receptor, and in both genes this region is encoded by eight exons. The positions of four introns are also conserved in the homologous region of the two genes. These observations suggest that the entactin gene has evolved via exon shuffling. Finally, several sequence polymorphisms useful for gene linkage analysis were found in the 3{prime} noncoding region of the last exon. 52 refs., 8 figs.

  19. Multi-Scale Associations between Vegetation Cover and Woodland Bird Communities across a Large Agricultural Region

    PubMed Central

    Ikin, Karen; Barton, Philip S.; Stirnemann, Ingrid A.; Stein, John R.; Michael, Damian; Crane, Mason; Okada, Sachiko; Lindenmayer, David B.

    2014-01-01

    Improving biodiversity conservation in fragmented agricultural landscapes has become an important global issue. Vegetation at the patch and landscape-scale is important for species occupancy and diversity, yet few previous studies have explored multi-scale associations between vegetation and community assemblages. Here, we investigated how patch and landscape-scale vegetation cover structure woodland bird communities. We asked: (1) How is the bird community associated with the vegetation structure of woodland patches and the amount of vegetation cover in the surrounding landscape? (2) Do species of conservation concern respond to woodland vegetation structure and surrounding vegetation cover differently to other species in the community? And (3) Can the relationships between the bird community and the woodland vegetation structure and surrounding vegetation cover be explained by the ecological traits of the species comprising the bird community? We studied 103 woodland patches (0.5 - 53.8 ha) over two time periods across a large (6,800 km2) agricultural region in southeastern Australia. We found that both patch vegetation and surrounding woody vegetation cover were important for structuring the bird community, and that these relationships were consistent over time. In particular, the occurrence of mistletoe within the patches and high values of woody vegetation cover within 1,000 ha and 10,000 ha were important, especially for bird species of conservation concern. We found that the majority of these species displayed similar, positive responses to patch and landscape vegetation attributes. We also found that these relationships were related to the foraging and nesting traits of the bird community. Our findings suggest that management strategies to increase both remnant vegetation quality and the cover of surrounding woody vegetation in fragmented agricultural landscapes may lead to improved conservation of bird communities. PMID:24830684

  20. Multi-scale associations between vegetation cover and woodland bird communities across a large agricultural region.

    PubMed

    Ikin, Karen; Barton, Philip S; Stirnemann, Ingrid A; Stein, John R; Michael, Damian; Crane, Mason; Okada, Sachiko; Lindenmayer, David B

    2014-01-01

    Improving biodiversity conservation in fragmented agricultural landscapes has become an important global issue. Vegetation at the patch and landscape-scale is important for species occupancy and diversity, yet few previous studies have explored multi-scale associations between vegetation and community assemblages. Here, we investigated how patch and landscape-scale vegetation cover structure woodland bird communities. We asked: (1) How is the bird community associated with the vegetation structure of woodland patches and the amount of vegetation cover in the surrounding landscape? (2) Do species of conservation concern respond to woodland vegetation structure and surrounding vegetation cover differently to other species in the community? And (3) Can the relationships between the bird community and the woodland vegetation structure and surrounding vegetation cover be explained by the ecological traits of the species comprising the bird community? We studied 103 woodland patches (0.5 - 53.8 ha) over two time periods across a large (6,800 km(2)) agricultural region in southeastern Australia. We found that both patch vegetation and surrounding woody vegetation cover were important for structuring the bird community, and that these relationships were consistent over time. In particular, the occurrence of mistletoe within the patches and high values of woody vegetation cover within 1,000 ha and 10,000 ha were important, especially for bird species of conservation concern. We found that the majority of these species displayed similar, positive responses to patch and landscape vegetation attributes. We also found that these relationships were related to the foraging and nesting traits of the bird community. Our findings suggest that management strategies to increase both remnant vegetation quality and the cover of surrounding woody vegetation in fragmented agricultural landscapes may lead to improved conservation of bird communities.

  1. The experimental folding landscape of monomeric lactose repressor, a large two-domain protein, involves two kinetic intermediates.

    PubMed

    Wilson, Corey J; Das, Payel; Clementi, Cecilia; Matthews, Kathleen S; Wittung-Stafshede, Pernilla

    2005-10-11

    To probe the experimental folding behavior of a large protein with complex topology, we created a monomeric variant of the lactose repressor protein (MLAc), a well characterized tetrameric protein that regulates transcription of the lac operon. Purified MLAc is folded, fully functional, and binds the inducer isopropyl beta-d-thiogalactoside with the same affinity as wild-type LacI. Equilibrium unfolding of MLAc induced by the chemical denaturant urea is a reversible, apparent two-state process (pH 7.5, 20 degrees C). However, time-resolved experiments demonstrate that unfolding is single-exponential, whereas refolding data indicate two transient intermediates. The data reveal the initial formation of a burst-phase (tau < ms) intermediate that corresponds to approximately 50% of the total secondary-structure content. This step is followed by a rearrangement reaction that is rate-limited by an unfolding process (tau approximately 3 s; pH 7.5, 20 degrees C) and results in a second intermediate. This MLAc intermediate converts to the native structure (tau approximately 30 s; pH 7.5, 20 degrees C). Remarkably, the experimental folding-energy landscape for MLAc is in excellent agreement with theoretical predictions using a simple topology-based C(alpha)-model as presented in a companion article in this issue. PMID:16203983

  2. Effect of Glycosylation on an Immunodominant Region in the V1V2 Variable Domain of the HIV-1 Envelope gp120 Protein

    PubMed Central

    Derdeyn, Cynthia A.; Jones, Morris S.; Pinter, Abraham; Korber, Bette; Gnanakaran, S.

    2016-01-01

    Heavy glycosylation of the envelope (Env) surface subunit, gp120, is a key adaptation of HIV-1; however, the precise effects of glycosylation on the folding, conformation and dynamics of this protein are poorly understood. Here we explore the patterns of HIV-1 Env gp120 glycosylation, and particularly the enrichment in glycosylation sites proximal to the disulfide linkages at the base of the surface-exposed variable domains. To dissect the influence of glycans on the conformation these regions, we focused on an antigenic peptide fragment from a disulfide bridge-bounded region spanning the V1 and V2 hyper-variable domains of HIV-1 gp120. We used replica exchange molecular dynamics (MD) simulations to investigate how glycosylation influences its conformation and stability. Simulations were performed with and without N-linked glycosylation at two sites that are highly conserved across HIV-1 isolates (N156 and N160); both are contacts for recognition by V1V2-targeted broadly neutralizing antibodies against HIV-1. Glycosylation stabilized the pre-existing conformations of this peptide construct, reduced its propensity to adopt other secondary structures, and provided resistance against thermal unfolding. Simulations performed in the context of the Env trimer also indicated that glycosylation reduces flexibility of the V1V2 region, and provided insight into glycan-glycan interactions in this region. These stabilizing effects were influenced by a combination of factors, including the presence of a disulfide bond between the Cysteines at 131 and 157, which increased the formation of beta-strands. Together, these results provide a mechanism for conservation of disulfide linkage proximal glycosylation adjacent to the variable domains of gp120 and begin to explain how this could be exploited to enhance the immunogenicity of those regions. These studies suggest that glycopeptide immunogens can be designed to stabilize the most relevant Env conformations to focus the immune

  3. The heparin binding domain of vitronectin is the region that is required to enhance insulin-like growth factor-I signaling.

    PubMed

    Maile, Laura A; Busby, Walker H; Sitko, Kevin; Capps, Byron E; Sergent, Tiffany; Badley-Clarke, Jane; Ling, Yan; Clemmons, David R

    2006-04-01

    We have shown that vitronectin (Vn) binding to a cysteine loop sequence within the extracellular domain of the beta3-subunit (amino acids 177-184) of alphaVbeta3 is required for the positive effects of Vn on IGF-I signaling. When Vn binding to this sequence is blocked, IGF-I signaling in smooth muscle cells is impaired. Because this binding site is distinct from the site on beta3 to which the Arg-Gly-Asp sequence of extracellular matrix ligands bind (amino acids 107-171), we hypothesized that the region of Vn that binds to the cysteine loop on beta3 is distinct from the region that contains the Arg-Gly-Asp sequence. The results presented in this study demonstrate that this heparin binding domain (HBD) is the region of Vn that binds to the cysteine loop region of beta3 and that this region is sufficient to mediate the positive effects of Vn on IGF-I signaling. We provide evidence that binding of the HBD of Vn to alphaVbeta3 has direct effects on the activation state of beta3 as measured by beta3 phosphorylation. The increase in beta3 phosphorylation associated with exposure of cells to this HBD is associated with enhanced phosphorylation of the adaptor protein Src homology 2 domain-containing transforming protein C and enhanced activation MAPK, a downstream mediator of IGF-I signaling. We conclude that the interaction of the HBD of Vn binding to the cysteine loop sequence of beta3 is necessary and sufficient for the positive effects of Vn on IGF-I-mediated effects in smooth muscle cells.

  4. CBF mediates adenovirus Ela trans-activation by interaction at the C-terminal promoter targeting domain of conserved region 3.

    PubMed

    Agoff, S N; Wu, B

    1994-12-01

    Genetic and biochemical evidence suggest that conserved region 3 (CR3) of the adenovirus Ela polypeptide can provide two distinct and separable functions: an N-terminal transcriptional activation region and a C-terminal promoter targeting region. It is thought that the promoter targeting region of Ela CR3 interacts with promoter-specific transcription factors, thereby bringing the activation region of Ela CR3 in proximity of the promoter. Here we report that CBF, a CCAAT-box-binding factor that regulates hsp70 gene expression and mediates Ela trans-activation in vivo, interacts with the promoter targeting region of Ela CR3 in vitro. Point mutations in Ela CR3 that are defective in stimulating transcription from the hsp70 promoter are also defective in stimulating transcription directed by a synthetic activator, GAL-CBF, composed of the DNA-binding domain of yeast GAL4 fused to CBF. These mutations fall into two classes with respect to their abilities to interact with CBF in vitro. Mutations in the transcriptional activation region of Ela CR3 do not affect binding to CBF, but mutation of the promoter targeting region of Ela CR3 prevents association with CBF in vitro.

  5. Evaluation of regional fracture properties for groundwater development using hydrolithostructural domain approach in variably fractured hard rocks of Purulia district, West Bengal, India

    NASA Astrophysics Data System (ADS)

    Acharya, Tapas; Prasad, Rajesh; Chakrabarti, S.

    2014-04-01

    Estimation of geohydrologic properties of fractured aquifers in hard crystalline and/or metamorphosed country rocks is a challenge due to the complex nature of secondary porosity that is caused by differential fracturing. Hydrologic potentiality of such aquifers may be assessed if the geological controls governing the spatial distribution of these fracture systems are computed using a software-based model. As an exemplar, the Precambrian metamorphics exposed in and around the Balarampur town of Purulia district, West Bengal (India) were studied to find out the spatial pattern and consistency of such fracture systems. Surfer and Statistica softwares were used to characterize these rock masses in terms of hydrological, structural and lithological domains. The technique is based on the use of hydraulically significant fracture properties to generate representative modal and coefficient of variance ( Cν) of fracture datasets of each domain. The Cν is interpreted to obtain the spatial variability of hydraulically significant fracture properties that, in turn, define and identify the corresponding hydrolithostructural domains. The groundwater flow estimated from such a technique is verified with the routine hydrological studies to validate the procedure. It is suggested that the hydrolithostructural domain approach is a useful alternative for evaluation of fracture properties and aquifer potentiality, and development of a regional groundwater model thereof.

  6. A missense mutation in the PISA domain of HsSAS-6 causes autosomal recessive primary microcephaly in a large consanguineous Pakistani family.

    PubMed

    Khan, Muzammil A; Rupp, Verena M; Orpinell, Meritxell; Hussain, Muhammad S; Altmüller, Janine; Steinmetz, Michel O; Enzinger, Christian; Thiele, Holger; Höhne, Wolfgang; Nürnberg, Gudrun; Baig, Shahid M; Ansar, Muhammad; Nürnberg, Peter; Vincent, John B; Speicher, Michael R; Gönczy, Pierre; Windpassinger, Christian

    2014-11-15

    Asymmetric cell division is essential for normal human brain development. Mutations in several genes encoding centrosomal proteins that participate in accurate cell division have been reported to cause autosomal recessive primary microcephaly (MCPH). By homozygosity mapping including three affected individuals from a consanguineous MCPH family from Pakistan, we delineated a critical region of 18.53 Mb on Chromosome 1p21.3-1p13.1. This region contains the gene encoding HsSAS-6, a centrosomal protein primordial for seeding the formation of new centrioles during the cell cycle. Both next-generation and Sanger sequencing revealed a homozygous c.185T>C missense mutation in the HsSAS-6 gene, resulting in a p.Ile62Thr substitution within a highly conserved region of the PISA domain of HsSAS-6. This variant is neither present in any single-nucleotide polymorphism or exome sequencing databases nor in a Pakistani control cohort. Experiments in tissue culture cells revealed that the Ile62Thr mutant of HsSAS-6 is substantially less efficient than the wild-type protein in sustaining centriole formation. Together, our findings demonstrate a dramatic impact of the mutation p.Ile62Thr on HsSAS-6 function and add this component to the list of genes mutated in primary microcephaly.

  7. A Ras-like domain in the light intermediate chain bridges the dynein motor to a cargo-binding region

    PubMed Central

    Schroeder, Courtney M; Ostrem, Jonathan ML; Hertz, Nicholas T; Vale, Ronald D

    2014-01-01

    Cytoplasmic dynein, a microtubule-based motor protein, transports many intracellular cargos by means of its light intermediate chain (LIC). In this study, we have determined the crystal structure of the conserved LIC domain, which binds the motor heavy chain, from a thermophilic fungus. We show that the LIC has a Ras-like fold with insertions that distinguish it from Ras and other previously described G proteins. Despite having a G protein fold, the fungal LIC has lost its ability to bind nucleotide, while the human LIC1 binds GDP preferentially over GTP. We show that the LIC G domain binds the dynein heavy chain using a conserved patch of aromatic residues, whereas the less conserved C-terminal domain binds several Rab effectors involved in membrane transport. These studies provide the first structural information and insight into the evolutionary origin of the LIC as well as revealing how this critical subunit connects the dynein motor to cargo. DOI: http://dx.doi.org/10.7554/eLife.03351.001 PMID:25272277

  8. Large decrease of characteristic frequency of dielectric relaxation associated with domain-wall motion in Sb5+-modified (K,Na)NbO3-based ceramics

    NASA Astrophysics Data System (ADS)

    Zhang, Jialiang; Hao, Wentao; Gao, Yong; Qin, Yalin; Tan, Yongqiang; Wang, Chunlei

    2012-12-01

    The (K,Na)NbO3-based ceramics have drawn considerable attention as a type of promising lead-free piezoelectric materials in recent years. However, investigations on the dielectric dispersion spectra in the microwave range have rarely been conducted so far. Dielectric dispersion spectra of several representative (K,Na)NbO3-based ceramics were measured and compared in this study. An interesting physical phenomenon that the Sb5+-modified (K,Na)NbO3-based ceramics differ distinctly from those without Sb5+-modification in the aspect of characteristic frequency fp of dielectric relaxation associated with the domain-wall motion has been found. The former group shows the fp values in several tens of MHz at room temperature, whereas the latter group has generally the fp values of several GHz at least. For the Sb5+-modified (K,Na)NbO3-based ceramics, the change of fp with temperature follows roughly a thermally activated character. In contrast, the ones without Sb5+-modification exhibit a temperature-insensitive character in fp. Analysis showed that the results could be understood from the viewpoint of domain-wall vibration. It is speculated that a large change occurring in the damping constant due to the incorporation of Sb5+ is possibly the origin.

  9. Cache domains that are homologous to, but different from PAS domains comprise the largest superfamily of extracellular sensors in prokaryotes

    DOE PAGES

    Upadhyay, Amit A.; Fleetwood, Aaron D.; Adebali, Ogun; Finn, Robert D.; Zhulin, Igor B.; Schlessinger, Avner

    2016-04-06

    Cellular receptors usually contain a designated sensory domain that recognizes the signal. Per/Arnt/Sim (PAS) domains are ubiquitous sensors in thousands of species ranging from bacteria to humans. Although PAS domains were described as intracellular sensors, recent structural studies revealed PAS-like domains in extracytoplasmic regions in several transmembrane receptors. However, these structurally defined extracellular PAS-like domains do not match sequence-derived PAS domain models, and thus their distribution across the genomic landscape remains largely unknown. Here we show that structurally defined extracellular PAS-like domains belong to the Cache superfamily, which is homologous to, but distinct from the PAS superfamily. Our newly builtmore » computational models enabled identification of Cache domains in tens of thousands of signal transduction proteins including those from important pathogens and model organisms.Moreover, we show that Cache domains comprise the dominant mode of extracellular sensing in prokaryotes.« less

  10. Cache Domains That are Homologous to, but Different from PAS Domains Comprise the Largest Superfamily of Extracellular Sensors in Prokaryotes.

    PubMed

    Upadhyay, Amit A; Fleetwood, Aaron D; Adebali, Ogun; Finn, Robert D; Zhulin, Igor B

    2016-04-01

    Cellular receptors usually contain a designated sensory domain that recognizes the signal. Per/Arnt/Sim (PAS) domains are ubiquitous sensors in thousands of species ranging from bacteria to humans. Although PAS domains were described as intracellular sensors, recent structural studies revealed PAS-like domains in extracytoplasmic regions in several transmembrane receptors. However, these structurally defined extracellular PAS-like domains do not match sequence-derived PAS domain models, and thus their distribution across the genomic landscape remains largely unknown. Here we show that structurally defined extracellular PAS-like domains belong to the Cache superfamily, which is homologous to, but distinct from the PAS superfamily. Our newly built computational models enabled identification of Cache domains in tens of thousands of signal transduction proteins including those from important pathogens and model organisms. Furthermore, we show that Cache domains comprise the dominant mode of extracellular sensing in prokaryotes.

  11. Cache Domains That are Homologous to, but Different from PAS Domains Comprise the Largest Superfamily of Extracellular Sensors in Prokaryotes.

    PubMed

    Upadhyay, Amit A; Fleetwood, Aaron D; Adebali, Ogun; Finn, Robert D; Zhulin, Igor B

    2016-04-01

    Cellular receptors usually contain a designated sensory domain that recognizes the signal. Per/Arnt/Sim (PAS) domains are ubiquitous sensors in thousands of species ranging from bacteria to humans. Although PAS domains were described as intracellular sensors, recent structural studies revealed PAS-like domains in extracytoplasmic regions in several transmembrane receptors. However, these structurally defined extracellular PAS-like domains do not match sequence-derived PAS domain models, and thus their distribution across the genomic landscape remains largely unknown. Here we show that structurally defined extracellular PAS-like domains belong to the Cache superfamily, which is homologous to, but distinct from the PAS superfamily. Our newly built computational models enabled identification of Cache domains in tens of thousands of signal transduction proteins including those from important pathogens and model organisms. Furthermore, we show that Cache domains comprise the dominant mode of extracellular sensing in prokaryotes. PMID:27049771

  12. Cache Domains That are Homologous to, but Different from PAS Domains Comprise the Largest Superfamily of Extracellular Sensors in Prokaryotes

    PubMed Central

    Upadhyay, Amit A.; Fleetwood, Aaron D.; Adebali, Ogun; Finn, Robert D.; Zhulin, Igor B.

    2016-01-01

    Cellular receptors usually contain a designated sensory domain that recognizes the signal. Per/Arnt/Sim (PAS) domains are ubiquitous sensors in thousands of species ranging from bacteria to humans. Although PAS domains were described as intracellular sensors, recent structural studies revealed PAS-like domains in extracytoplasmic regions in several transmembrane receptors. However, these structurally defined extracellular PAS-like domains do not match sequence-derived PAS domain models, and thus their distribution across the genomic landscape remains largely unknown. Here we show that structurally defined extracellular PAS-like domains belong to the Cache superfamily, which is homologous to, but distinct from the PAS superfamily. Our newly built computational models enabled identification of Cache domains in tens of thousands of signal transduction proteins including those from important pathogens and model organisms. Furthermore, we show that Cache domains comprise the dominant mode of extracellular sensing in prokaryotes. PMID:27049771

  13. Ligand- and coactivator-mediated transactivation function (AF2) of the androgen receptor ligand-binding domain is inhibited by the cognate hinge region.

    PubMed

    Wang, Q; Lu, J; Yong, E L

    2001-03-01

    Transactivation functions (AF2) in the ligand-binding domains (LBD) of many steroid receptors are well characterized, but there is little evidence to support such a function for the LBD of the androgen receptor (AR). We report a mutant AR, with residues 628-646 in the hinge region deleted, which exhibited transactivation activity that was more than double that of the wild type (WT) AR. Although no androgen-dependent AF2 activity could be observed for the WT ARLBD fused to a heterologous DNA-binding domain, the mutant ARLBD(Delta628-646) was 30-40 times more active than the WT ARLBD. In the presence of the p160 coactivator TIF2, AR(Delta628-646) was significantly more active than similarly treated WT AR. Deletion of residues 628-646 also enhanced TIF2-ARLBD activity 8-fold, an effect not present when the LBD-interacting LXXLL motifs of TIF2 were mutated, suggesting that the negative modulatory activity of residues 628-646 were exerted via coactivator pathways. Although the AP-1 (c-Jun/c-Fos) system and NcoR have been reported to interact with and repress the activity of some steroid receptors, c-Jun, c-Fos, c-Jun/c-Fos, nor NcoR function was consistently affected by the absence or presence of residues 628-646, implying that the AR hinge region exerts its silencing effects in a manner independent of these corepressors. Our data provide evidence for the novel finding that strong androgen-dependent AF2 exists in the ARLBD and is the first report of a negative regulatory domain in the AR. Because mutations in this region are commonly associated with prostate cancer, it is important to characterize the mechanisms by which the hinge region exerts its repressor effect on ligand-activated and coactivator-mediated AF2 activity of the ARLBD.

  14. Spatial Structure of Large-Scale Plasma Density Perturbations HF-Induced in the Ionospheric F 2 Region

    NASA Astrophysics Data System (ADS)

    Frolov, V. L.; Komrakov, G. P.; Glukhov, Ya. V.; Andreeva, E. S.; Kunitsyn, V. E.; Kurbatov, G. A.

    2016-07-01

    We consider the experimental results obtained by studying the large-scale structure of the HF-disturbed ionospheric region. The experiments were performed using the SURA heating facility. The disturbed ionospheric region was sounded by signals radiated by GPS navigation satellite beacons as well as by signals of low-orbit satellites (radio tomography). The results of the experiments show that large-scale plasma density perturbations induced at altitudes higher than the F2 layer maximum can contribute significantly to the measured variations of the total electron density and can, with a certain arrangement of the reception points, be measured by the GPS sounding method.

  15. Statistical searches for microlensing events in large, non-uniformly sampled time-domain surveys: A test using palomar transient factory data

    SciTech Connect

    Price-Whelan, Adrian M.; Agüeros, Marcel A.; Fournier, Amanda P.; Street, Rachel; Ofek, Eran O.; Covey, Kevin R.; Levitan, David; Sesar, Branimir; Laher, Russ R.; Surace, Jason

    2014-01-20

    Many photometric time-domain surveys are driven by specific goals, such as searches for supernovae or transiting exoplanets, which set the cadence with which fields are re-imaged. In the case of the Palomar Transient Factory (PTF), several sub-surveys are conducted in parallel, leading to non-uniform sampling over its ∼20,000 deg{sup 2} footprint. While the median 7.26 deg{sup 2} PTF field has been imaged ∼40 times in the R band, ∼2300 deg{sup 2} have been observed >100 times. We use PTF data to study the trade off between searching for microlensing events in a survey whose footprint is much larger than that of typical microlensing searches, but with far-from-optimal time sampling. To examine the probability that microlensing events can be recovered in these data, we test statistics used on uniformly sampled data to identify variables and transients. We find that the von Neumann ratio performs best for identifying simulated microlensing events in our data. We develop a selection method using this statistic and apply it to data from fields with >10 R-band observations, 1.1 × 10{sup 9} light curves, uncovering three candidate microlensing events. We lack simultaneous, multi-color photometry to confirm these as microlensing events. However, their number is consistent with predictions for the event rate in the PTF footprint over the survey's three years of operations, as estimated from near-field microlensing models. This work can help constrain all-sky event rate predictions and tests microlensing signal recovery in large data sets, which will be useful to future time-domain surveys, such as that planned with the Large Synoptic Survey Telescope.

  16. Statistical Searches for Microlensing Events in Large, Non-uniformly Sampled Time-Domain Surveys: A Test Using Palomar Transient Factory Data

    NASA Astrophysics Data System (ADS)

    Price-Whelan, Adrian M.; Agüeros, Marcel A.; Fournier, Amanda P.; Street, Rachel; Ofek, Eran O.; Covey, Kevin R.; Levitan, David; Laher, Russ R.; Sesar, Branimir; Surace, Jason

    2014-01-01

    Many photometric time-domain surveys are driven by specific goals, such as searches for supernovae or transiting exoplanets, which set the cadence with which fields are re-imaged. In the case of the Palomar Transient Factory (PTF), several sub-surveys are conducted in parallel, leading to non-uniform sampling over its ~20,000 deg2 footprint. While the median 7.26 deg2 PTF field has been imaged ~40 times in the R band, ~2300 deg2 have been observed >100 times. We use PTF data to study the trade off between searching for microlensing events in a survey whose footprint is much larger than that of typical microlensing searches, but with far-from-optimal time sampling. To examine the probability that microlensing events can be recovered in these data, we test statistics used on uniformly sampled data to identify variables and transients. We find that the von Neumann ratio performs best for identifying simulated microlensing events in our data. We develop a selection method using this statistic and apply it to data from fields with >10 R-band observations, 1.1 × 109 light curves, uncovering three candidate microlensing events. We lack simultaneous, multi-color photometry to confirm these as microlensing events. However, their number is consistent with predictions for the event rate in the PTF footprint over the survey's three years of operations, as estimated from near-field microlensing models. This work can help constrain all-sky event rate predictions and tests microlensing signal recovery in large data sets, which will be useful to future time-domain surveys, such as that planned with the Large Synoptic Survey Telescope.

  17. A technique for extrapolating and validating forest cover across large regions - Calibrating AVHRR data with TM data

    NASA Technical Reports Server (NTRS)

    Iverson, L. R.; Cook, E. A.; Graham, R. L.

    1989-01-01

    A method is presented for extending high-resolution forest cover information across large regions. Using Landsat TM data with AVHRR data, an empirical relationship beween AVHRR spectral signatures and forest cover is developed. The resulting regression equation is applied to an AVHRR scene covering a large area centered around southern Illinois. The map is used to estimate forest cover within a geographical information system. The results are compared with U.S. Forest Service estimates, showing good agreement.

  18. Large Higgs energy region in Higgs associated top pair production at the Linear Collider

    SciTech Connect

    Farrell, Cailin; Hoang, Andre H.

    2005-07-01

    The process e{sup +}e{sup -}{yields}ttH is considered in the kinematic end point region where the Higgs energy is close to its maximal energy. In perturbative QCD, using the loop expansion, the amplitudes are plagued by Coulomb singularities that need to be resummed. We show that the QCD dynamics in this end point region is governed by nonrelativistic heavy quarkonium dynamics, and we use a nonrelativistic effective theory to compute the Higgs energy distribution at leading and next-to-leading-logarithmic approximation in the nonrelativistic expansion. Updated numbers for the total cross section including the summations in the Higgs energy end point region are presented.

  19. Paring Down HIV Env: Design and Crystal Structure of a Stabilized Inner Domain of HIV-1 gp120 Displaying a Major ADCC Target of the A32 Region.

    PubMed

    Tolbert, William D; Gohain, Neelakshi; Veillette, Maxime; Chapleau, Jean-Philippe; Orlandi, Chiara; Visciano, Maria L; Ebadi, Maryam; DeVico, Anthony L; Fouts, Timothy R; Finzi, Andrés; Lewis, George K; Pazgier, Marzena

    2016-05-01

    Evidence supports a role of antibody-dependent cellular cytotoxicity (ADCC) toward transitional epitopes in the first and second constant (C1-C2) regions of gp120 (A32-like epitopes) in preventing HIV-1 infection and in vaccine-induced protection. Here, we describe the first successful attempt at isolating the inner domain (ID) of gp120 as an independent molecule that encapsulates the A32-like region within a minimal structural unit of the HIV-1 Env. Through structure-based design, we developed ID2, which consists of the ID expressed independently of the outer domain and stabilized in the CD4-bound conformation by an inter-layer disulfide bond. ID2 expresses C1-C2 epitopes in the context of CD4-triggered full-length gp120 but without any known neutralizing epitope present. Thus, ID2 represents a novel probe for the analysis and/or selective induction of antibody responses to the A32 epitope region. We also present the crystal structure of ID2 complexed with mAb A32, which defines its epitope.

  20. Indirect evidence for lipid-domain formation in the transition region of phospholipid bilayers by two-probe fluorescence energy transfer.

    PubMed Central

    Pedersen, S; Jørgensen, K; Baekmark, T R; Mouritsen, O G

    1996-01-01

    The fluorescence energy transfer between two lipid probes, N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-1, 2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine (donor) and N-(Lissamine rhodamine B sulfonyl)-1, 2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine (acceptor), incorporated into 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine unilamellar and multilamellar lipid bilayers, is studied in the temperature region of the main phase transition. The two probes display different relative solubilities in the gel and fluid lipid-bilayer phases. A distinct maximum in the fluorescence intensity of the donor is observed in the transition region, indicating that the two probes are demixing and hence increasing their average separation. The observation is interpreted in terms of dynamic segregation of the two probes into coexisting gel and fluid lipid domains that are formed dynamically in the transition region due to strong density fluctuations. The interpretation of the experimental observations is supported by a detailed theoretical calculation using computer simulation of a microscopic model that takes full account of diffusion of the two probes and the fluctuations of gel and fluid lipid domains characteristic of the main phase transition. Images FIGURE 4 PMID:8842195

  1. Paring Down HIV Env: Design and Crystal Structure of a Stabilized Inner Domain of HIV-1 gp120 Displaying a Major ADCC Target of the A32 Region.

    PubMed

    Tolbert, William D; Gohain, Neelakshi; Veillette, Maxime; Chapleau, Jean-Philippe; Orlandi, Chiara; Visciano, Maria L; Ebadi, Maryam; DeVico, Anthony L; Fouts, Timothy R; Finzi, Andrés; Lewis, George K; Pazgier, Marzena

    2016-05-01

    Evidence supports a role of antibody-dependent cellular cytotoxicity (ADCC) toward transitional epitopes in the first and second constant (C1-C2) regions of gp120 (A32-like epitopes) in preventing HIV-1 infection and in vaccine-induced protection. Here, we describe the first successful attempt at isolating the inner domain (ID) of gp120 as an independent molecule that encapsulates the A32-like region within a minimal structural unit of the HIV-1 Env. Through structure-based design, we developed ID2, which consists of the ID expressed independently of the outer domain and stabilized in the CD4-bound conformation by an inter-layer disulfide bond. ID2 expresses C1-C2 epitopes in the context of CD4-triggered full-length gp120 but without any known neutralizing epitope present. Thus, ID2 represents a novel probe for the analysis and/or selective induction of antibody responses to the A32 epitope region. We also present the crystal structure of ID2 complexed with mAb A32, which defines its epitope. PMID:27041594

  2. Mapping composition in dust-producing regions: Extending geochemical measurements over large scales with remote sensing

    NASA Astrophysics Data System (ADS)

    Tollerud, H. J.; Elmore, A. J.; Fantle, M. S.

    2009-12-01

    Dust is a critical, yet understudied, component of geochemical cycles. Dust inputs to the ocean have been deemed especially significant in the iron cycle, for instance, since dust stimulates natural iron fertilization and thus potentially affects climate. Dust may also be important to the cycles of other elements, such as calcium (Ca). To determine the importance of dust relative to other geochemical inputs, some estimate must be made of the mass flux of Ca from dust-producing regions. However, understanding the spatial distribution of Ca within terrain known to generate dust has been problematic. Remote sensing may offer a critical perspective with measurement at landscape scales instead of extrapolation from a few point measurements, allowing for investigation closer to the scale at which dust is produced. This study investigates the elemental geochemistry of surface sediments and the distribution of non-silicate bound Ca in a large playa system (Black Rock Desert) in northwestern Nevada (USA). We used satellite-derived hyperspectral data, field-collected ground spectra, surface sediment samples, and Synthetic Aperture Radar (SAR) in our analysis. We collected approximately 50 samples and their spectra from the Black Rock Desert in July/August 2007. We measured the bulk and soluble Ca by ICP-OES and mineralogy by x-ray diffraction (XRD). Assuming all Ca in weak HCl (0.5 N) leaches is derived from calcite, we found that calcite concentrations in a subset of collected samples range from 5 to 15 wt. %. Acid-soluble calcite, which was generally 90 to 100 mol % of the total Ca in sediments (determined by lithium metaborate fusion), correlates well with the relative abundance of calcite determined by XRD analyses. Using hyperspectral measurements of surface reflectance, we found that acid soluble Ca concentration is correlated with the depth of a calcite absorption feature at 2335 nm. We then mapped this depth in satellite hyperspectral data from the Hyperion

  3. Toward a Solution of the Edwards Equation for the Vertex Function of Quantum Electrodynamics in the Region of Large Momenta

    NASA Astrophysics Data System (ADS)

    Agamalieva, L. A.; Gadjiev, S. A.; Jafarov, R. G.

    2016-03-01

    An asymptotic expression for the vertex function in the region of large momenta in quantum electrodynamics is investigated in the ladder approximation. To formulate a calculational model in the ladder approximation, an iterative scheme has been used to solve the Schwinger-Dyson equation in the formalism of a bilocal source of fields. For the chirally symmetric leading approximation, the Edwards equation for the electron-positron-photon vertex has been obtained in the case of arbitrary values of the photon momentum. Our primary task is to develop a method to solve the vertex equation in the region of large momenta. Nontrivial behavior of the vertex function in the deeply inelastic region of momenta has been revealed.

  4. Large mammals from the Upper Neopleistocene reference sections in the Tunka rift valley, southwestern Baikal Region

    NASA Astrophysics Data System (ADS)

    Shchetnikov, A. A.; Klementiev, A. M.; Filinov, I. A.; Semeney, E. Yu.

    2015-03-01

    This work presents the data on new finds of fossil macrotheriofauna in the reference sections of the Upper Neopleistocene sediments in the Tunka rift valley (southwestern Baikal Region). The osteological material of a number of Late Neopleistocene mammals including extinct species rare for the Baikal region such as Crocuta spelaea, Panthera spelaea, and Spirocerus kiakhtensis (?) was directly dated with a radiocarbon (AMS) method. The obtained 14C data (18000-35000 years) allow one to rejuvenate significantly the upper limit of the common age interval of habitat of these animals in southern part of Eastern Siberia. Cave hyena and spiral-horned antelope lived in the Tunka rift valley in the Baikal region in Late Kargino time (37-24 ka), and cave lion survived the maximum in the Sartan cryochron in the region (21-20 ka). The study of collected paleontological collections provides a basis for selection of independent Kargino (MIS 3) faunal assemblages to use them for regional biostratigraphic analysis of Pleistocene deposits. Radiocarbon age dating of samples allows one to attribute confidently all paleofaunal remains available to the second half of the Late Pleistocene.

  5. Inclusive electron scattering from nuclei in the quasielastic region at large momentum transfer

    NASA Astrophysics Data System (ADS)

    Fomin, Nadia

    2008-12-01

    Experiment E02-019, performed in Hall C at the Thomas Jefferson National Accelerator Facility (TJNAF), was a measurement of inclusive electron cross sections for several nuclei (^{2}H,^{3}He, ^{4}He, ^{9}Be,^{12}C, ^{63}Cu, and ^{197}Au) in the quasielastic region at high momentum transfer. In the region of low energy transfer, the cross sections were analyzed in terms of the reduced response, F(y), by examining its y-scaling behavior. The data were also examined in terms of the nuclear structure function ν W_2^A and its behavior in x and the Nachtmann variable ξ. The data show approximate scaling of ν W_2^A in ξ for all targets at all kinematics, unlike scaling in x, which is confined to the DIS regime. However, y-scaling observations are limited to the kinematic region dominated by the quasielastic response ({y<0}), where some scaling violations arising from FSIs are observed.

  6. Role of multifractal analysis in understanding the preparation zone for large size earthquake in the North-Western Himalaya region

    NASA Astrophysics Data System (ADS)

    Teotia, S. S.; Kumar, D.

    2011-02-01

    Seismicity has power law in space, time and magnitude distributions and same is expressed by the fractal dimension D, Omori's exponent p and b-value. The spatio-temporal patterns of epicenters have heterogeneous characteristics. As the crust gets self-organised into critical state, the spatio-temporal clustering of epicenters emerges to heterogeneous nature of seismicity. To understand the heterogeneous characteristics of seismicity in a region, multifractal studies hold promise to characterise the dynamics of region. Multifractal study is done on seismicity data of the North-Western Himalaya region which mainly involve seismogenic region of 1905 Kangra great earthquake in the North-Western Himalaya region. The seismicity data obtained from USGS catalogue for time period 1973-2009 has been analysed for the region which includes the October 2005 Muzafrabad-Kashmir earthquake (Mw =7.6). Significant changes have been observed in generalised dimension Dq, Dq spectra and b-value. The significant temporal changes in generalised dimension Dq, b-value and Dq-q spectra prior to occurrence of Muzaffrabad-Kashmir earthquake relates to distribution of epicenters in the region. The decrease in generalised dimension and b-value observed in our study show the relationship with the clustering of seismicity as is expected in self-organised criticality behaviour of earthquake occurrences. Such study may become important in understanding the preparation zone of large and great size earthquake in various tectonic regions.

  7. A tripartite paternally methylated region within the Gpr1-Zdbf2 imprinted domain on mouse chromosome 1 identified by meDIP-on-chip

    PubMed Central

    Hiura, Hitoshi; Sugawara, Atsushi; Ogawa, Hidehiko; John, Rosalind M.; Miyauchi, Naoko; Miyanari, Yusuke; Horiike, Tokumasa; Li, Yufeng; Yaegashi, Nobuo; Sasaki, Hiroyuki; Kono, Tomohiro; Arima, Takahiro

    2010-01-01

    The parent-of-origin specific expression of imprinted genes relies on DNA methylation of CpG-dinucleotides at differentially methylated regions (DMRs) during gametogenesis. To date, four paternally methylated DMRs have been identified in screens based on conventional approaches. These DMRs are linked to the imprinted genes H19, Gtl2 (IG-DMR), Rasgrf1 and, most recently, Zdbf2 which encodes zinc finger, DBF-type containing 2. In this study, we applied a novel methylated-DNA immunoprecipitation-on-chip (meDIP-on-chip) method to genomic DNA from mouse parthenogenetic- and androgenetic-derived stem cells and sperm and identified 458 putative DMRs. This included the majority of known DMRs. We further characterized the paternally methylated Zdbf2/ZDBF2 DMR. In mice, this extensive germ line DMR spanned 16 kb and possessed an unusual tripartite structure. Methylation was dependent on DNA methyltransferase 3a (Dnmt3a), similar to H19 DMR and IG-DMR. In both humans and mice, the adjacent gene, Gpr1/GPR1, which encodes a G-protein-coupled receptor 1 protein with transmembrane domain, was also imprinted and paternally expressed. The Gpr1-Zdbf2 domain was most similar to the Rasgrf1 domain as both DNA methylation and the actively expressed allele were in cis on the paternal chromosome. This work demonstrates the effectiveness of meDIP-on-chip as a technique for identifying DMRs. PMID:20385583

  8. The TAF9 C-terminal conserved region domain is required for SAGA and TFIID promoter occupancy to promote transcriptional activation.

    PubMed

    Saint, Malika; Sawhney, Sonal; Sinha, Ishani; Singh, Rana Pratap; Dahiya, Rashmi; Thakur, Anushikha; Siddharthan, Rahul; Natarajan, Krishnamurthy

    2014-05-01

    A common function of the TFIID and SAGA complexes, which are recruited by transcriptional activators, is to deliver TBP to promoters to stimulate transcription. Neither the relative contributions of the five shared TBP-associated factor (TAF) subunits in TFIID and SAGA nor the requirement for different domains in shared TAFs for transcriptional activation is well understood. In this study, we uncovered the essential requirement for the highly conserved C-terminal region (CRD) of Taf9, a shared TAF, for transcriptional activation in yeast. Transcriptome profiling performed under Gcn4-activating conditions showed that the Taf9 CRD is required for induced expression of ∼9% of the yeast genome. The CRD was not essential for the Taf9-Taf6 interaction, TFIID or SAGA integrity, or Gcn4 interaction with SAGA in cell extracts. Microarray profiling of a SAGA mutant (spt20Δ) yielded a common set of genes induced by Spt20 and the Taf9 CRD. Chromatin immunoprecipitation (ChIP) assays showed that, although the Taf9 CRD mutation did not impair Gcn4 occupancy, the occupancies of TFIID, SAGA, and the preinitiation complex were severely impaired at several promoters. These results suggest a crucial role for the Taf9 CRD in genome-wide transcription and highlight the importance of conserved domains, other than histone fold domains, as a common determinant for TFIID and SAGA functions.

  9. Complex active regions as the main source of extreme and large solar proton events

    NASA Astrophysics Data System (ADS)

    Ishkov, V. N.

    2013-12-01

    A study of solar proton sources indicated that solar flare events responsible for ≥2000 pfu proton fluxes mostly occur in complex active regions (CARs), i.e., in transition structures between active regions and activity complexes. Different classes of similar structures and their relation to solar proton events (SPEs) and evolution, depending on the origination conditions, are considered. Arguments in favor of the fact that sunspot groups with extreme dimensions are CARs are presented. An analysis of the flare activity in a CAR resulted in the detection of "physical" boundaries, which separate magnetic structures of the same polarity and are responsible for the independent development of each structure.

  10. Nonhemolytic Streptococcus pyogenes Isolates That Lack Large Regions of the sag Operon Mediating Streptolysin S Production▿

    PubMed Central

    Yoshino, Miho; Murayama, Somay Y.; Sunaoshi, Katsuhiko; Wajima, Takeaki; Takahashi, Miki; Masaki, Junko; Kurokawa, Iku; Ubukata, Kimiko

    2010-01-01

    Among nonhemolytic Streptococcus pyogenes (group A streptococcus) strains (n = 9) isolated from patients with pharyngitis or acute otitis media, we identified three deletions in the region from the epf gene, encoding the extracellular matrix binding protein, to the sag operon, mediating streptolysin S production. PMID:20018818

  11. Identification of Important Regions for Ethylene Binding and Signaling in the Transmembrane Domain of the ETR1 Ethylene Receptor of Arabidopsis[W][OA

    PubMed Central

    Wang, Wuyi; Esch, Jeff J.; Shiu, Shin-Han; Agula, Hasi; Binder, Brad M.; Chang, Caren; Patterson, Sara E.; Bleecker, Anthony B.

    2006-01-01

    The ethylene binding domain (EBD) of the Arabidopsis thaliana ETR1 receptor is modeled as three membrane-spanning helices. We surveyed ethylene binding activity in different kingdoms and performed a bioinformatic analysis of the EBD. Ethylene binding is confined to land plants, Chara, and a group of cyanobacteria but is largely absent in other organisms, consistent with our finding that EBD-like sequences are overrepresented among plant and cyanobacterial species. We made amino acid substitutions in 37 partially or completely conserved residues of the EBD and assayed their effects on ethylene binding and signaling. Mutations primarily in residues in Helices I and II midregions eliminated ethylene binding and conferred constitutive signaling, consistent with the inverse-agonist model of ethylene receptor signaling and indicating that these residues define the ethylene binding pocket. The largest class of mutations, clustered near the cytoplasmic ends of Helices I and III, gave normal ethylene binding activity yet still conferred constitutive signaling. Therefore, these residues may play a role in turning off the signal transmitter domain of the receptor. By contrast, only two mutations were loss of function with respect to signaling. These findings yield insight into the structure and function of the EBD and suggest a conserved role of the EBD as a negative regulator of the signal transmitter domain. PMID:17189345

  12. Quantitative analysis of spin exchange interactions to identify β strand and turn regions in Ure2 prion domain fibrils with site-directed spin labeling.

    PubMed

    Ngo, Sam; Chiang, Vicky; Guo, Zhefeng

    2012-11-01

    Amyloid formation is associated with a range of debilitating human disorders including Alzheimer's and prion diseases. The amyloid structure is essential for understanding the role of amyloids in these diseases. Amyloid formation of Ure2 protein underlies the yeast prion [URE3]. Here we use site-directed spin labeling and electron paramagnetic resonance (EPR) spectroscopy to investigate the structure of amyloid fibrils formed by the Ure2 prion domain. The Ure2 prion domain under study contains a Sup35M domain at C-terminus as a solubilization element. We introduced spin labels at every residue from positions 2-15, and every 5th residue from positions 20-80 in Ure2 prion domain. EPR spectra at most labeling sites show strong spin exchange interactions, suggesting a parallel in-register β structure. With quantitative analysis of spin exchange interactions, we show that residues 8-12 form the first β strand, followed by a turn at residues 13-14, and then the second β strand from residue 15 to at least residue 20. Comparison of the spin exchange frequency for the fibrils formed under quiescent and agitated conditions also revealed differences in the fibril structures. Currently there is a lack of techniques for in-depth structural studies of amyloid fibrils. Detailed structural information is obtained almost exclusively from solid-state NMR. The identification of β-strand and turn regions in this work suggests that quantitative analysis of spin exchange interactions in spin-labeled amyloid fibrils is a powerful approach for identifying the β-strand and turn/loop residues and for studying structural differences of different fibril polymorphs.

  13. Factor VIII C1 domain spikes 2092-2093 and 2158-2159 comprise regions that modulate cofactor function and cellular uptake.

    PubMed

    Bloem, Esther; van den Biggelaar, Maartje; Wroblewska, Aleksandra; Voorberg, Jan; Faber, Johan H; Kjalke, Marianne; Stennicke, Henning R; Mertens, Koen; Meijer, Alexander B

    2013-10-11

    The C1 domain of factor VIII (FVIII) has been implicated in binding to multiple constituents, including phospholipids, von Willebrand factor, and low-density lipoprotein receptor-related protein (LRP). We have previously described a human monoclonal antibody called KM33 that blocks these interactions as well as cellular uptake by LRP-expressing cells. To unambiguously identify the apparent "hot spot" on FVIII to which this antibody binds, we have employed hydrogen-deuterium exchange mass spectrometry. The results showed that KM33 protects FVIII regions 2091-2104 and 2157-2162 from hydrogen-deuterium exchange. These comprise the two C1 domain spikes 2092-2093 and 2158-2159. Spike 2092-2093 has been demonstrated recently to contribute to assembly with lipid membranes with low phosphatidylserine (PS) content. Therefore, spike 2158-2159 might serve a similar role. This was assessed by replacement of Arg-2159 for Asn, which introduces a motif for N-linked glycosylation. Binding studies revealed that the purified, glycosylated R2159N variant had lost its interaction with antibody KM33 but retained substantial binding to von Willebrand factor and LRP. Cellular uptake of the R2159N variant was reduced both by LRP-expressing U87-MG cells and by human monocyte-derived dendritic cells. FVIII activity was virtually normal on membranes containing 15% PS but reduced at low PS content. These findings suggest that the C1 domain spikes 2092-2093 and 2158-2159 together modulate FVIII membrane assembly by a subtle, PS-dependent mechanism. These findings contribute evidence in favor of an increasingly important role of the C1 domain in FVIII biology. PMID:24009077

  14. Factor VIII C1 Domain Spikes 2092–2093 and 2158–2159 Comprise Regions That Modulate Cofactor Function and Cellular Uptake

    PubMed Central

    Bloem, Esther; van den Biggelaar, Maartje; Wroblewska, Aleksandra; Voorberg, Jan; Faber, Johan H.; Kjalke, Marianne; Stennicke, Henning R.; Mertens, Koen; Meijer, Alexander B.

    2013-01-01

    The C1 domain of factor VIII (FVIII) has been implicated in binding to multiple constituents, including phospholipids, von Willebrand factor, and low-density lipoprotein receptor-related protein (LRP). We have previously described a human monoclonal antibody called KM33 that blocks these interactions as well as cellular uptake by LRP-expressing cells. To unambiguously identify the apparent “hot spot” on FVIII to which this antibody binds, we have employed hydrogen-deuterium exchange mass spectrometry. The results showed that KM33 protects FVIII regions 2091–2104 and 2157–2162 from hydrogen-deuterium exchange. These comprise the two C1 domain spikes 2092–2093 and 2158–2159. Spike 2092–2093 has been demonstrated recently to contribute to assembly with lipid membranes with low phosphatidylserine (PS) content. Therefore, spike 2158–2159 might serve a similar role. This was assessed by replacement of Arg-2159 for Asn, which introduces a motif for N-linked glycosylation. Binding studies revealed that the purified, glycosylated R2159N variant had lost its interaction with antibody KM33 but retained substantial binding to von Willebrand factor and LRP. Cellular uptake of the R2159N variant was reduced both by LRP-expressing U87-MG cells and by human monocyte-derived dendritic cells. FVIII activity was virtually normal on membranes containing 15% PS but reduced at low PS content. These findings suggest that the C1 domain spikes 2092–2093 and 2158–2159 together modulate FVIII membrane assembly by a subtle, PS-dependent mechanism. These findings contribute evidence in favor of an increasingly important role of the C1 domain in FVIII biology. PMID:24009077

  15. Performance of the lake model FLake in the Canadian Regional Climate Model, version 5 simulations over two CORDEX domains - North America and Africa.

    NASA Astrophysics Data System (ADS)

    Martynov, A.; Sushama, L.; Laprise, R.; Winger, K.; Dugas, B.

    2012-04-01

    The Canadian Regional Climate Model, version 5 (CRCM5), has been used for simulating the climate over two CORDEX domains for the 1989-2008 period, using the ERA-Interim reanalysis boundary forcing. The interactively-coupled lake model FLake was used for simulating the thermal regime of lakes in these experiments. Both simulations were performed with identical lake model settings and initialization conditions. The performance of the coupled FLake model for different climatic regions, going from arctic to equatorial conditions, was assessed by comparing with observations, where available. It was shown that for a wide range of lakes and climate zones the FLake model is capable of reproducing satisfactorily the water surface conditions. Limitations of the model and possible application of the coupled FLake model to inland seas in different climate zones will also be discussed.

  16. Bidirectional Modulation of Thermal and Chemical Sensitivity of TRPM8 Channels by the Initial Region of the N-terminal Domain*

    PubMed Central

    Pertusa, María; González, Alejandro; Hardy, Paulina; Madrid, Rodolfo; Viana, Félix

    2014-01-01

    TRPM8, a nonselective cation channel activated by cold, voltage, and cooling compounds such as menthol, is the principal molecular detector of cold temperatures in primary sensory neurons of the somatosensory system. The N-terminal domain of TRPM8 consists of 693 amino acids, but little is known about its contribution to channel function. Here, we identified two distinct regions within the initial N terminus of TRPM8 that contribute differentially to channel activity and proper folding and assembly. Deletion or substitution of the first 40 residues yielded channels with augmented responses to cold and menthol. The thermal threshold of activation of these mutants was shifted 2 °C to higher temperatures, and the menthol dose-response curve was displaced to lower concentrations. Site-directed mutagenesis screening revealed that single point mutations at positions Ser-26 or Ser-27 by proline caused a comparable increase in the responses to cold and menthol. Electrophysiological analysis of the S27P mutant revealed that the enhanced sensitivity to agonists is related to a leftward shift in the voltage dependence of activation, increasing the probability of channel openings at physiological membrane potentials. In addition, we found that the region encompassing positions 40–60 is a key element in the proper folding and assembly of TRPM8. Different deletions and mutations within this region rendered channels with an impaired function that are retained within the endoplasmic reticulum. Our results suggest a critical contribution of the initial region of the N-terminal domain of TRPM8 to thermal and chemical sensitivity and the proper biogenesis of this polymodal ion channel. PMID:24917670

  17. Bidirectional modulation of thermal and chemical sensitivity of TRPM8 channels by the initial region of the N-terminal domain.

    PubMed

    Pertusa, María; González, Alejandro; Hardy, Paulina; Madrid, Rodolfo; Viana, Félix

    2014-08-01

    TRPM8, a nonselective cation channel activated by cold, voltage, and cooling compounds such as menthol, is the principal molecular detector of cold temperatures in primary sensory neurons of the somatosensory system. The N-terminal domain of TRPM8 consists of 693 amino acids, but little is known about its contribution to channel function. Here, we identified two distinct regions within the initial N terminus of TRPM8 that contribute differentially to channel activity and proper folding and assembly. Deletion or substitution of the first 40 residues yielded channels with augmented responses to cold and menthol. The thermal threshold of activation of these mutants was shifted 2 °C to higher temperatures, and the menthol dose-response curve was displaced to lower concentrations. Site-directed mutagenesis screening revealed that single point mutations at positions Ser-26 or Ser-27 by proline caused a comparable increase in the responses to cold and menthol. Electrophysiological analysis of the S27P mutant revealed that the enhanced sensitivity to agonists is related to a leftward shift in the voltage dependence of activation, increasing the probability of channel openings at physiological membrane potentials. In addition, we found that the region encompassing positions 40-60 is a key element in the proper folding and assembly of TRPM8. Different deletions and mutations within this region rendered channels with an impaired function that are retained within the endoplasmic reticulum. Our results suggest a critical contribution of the initial region of the N-terminal domain of TRPM8 to thermal and chemical sensitivity and the proper biogenesis of this polymodal ion channel.

  18. Large Eddy Simulations of the Effects of EMBr and SEN Submergence Depth on Turbulent Flow in the Mold Region of a Steel Caster

    NASA Astrophysics Data System (ADS)

    Jin, Kai; Vanka, Surya P.; Thomas, Brian G.

    2016-09-01

    Transient turbulent flow in the mold region during continuous casting of steel is related to many quality problems, such as surface defects and slag entrainment. This work applies an efficient multi-GPU based code, CUFlow, to perform large eddy simulations (LES) of the turbulent flow in a domain that includes the slide gate, SEN, and mold region. The computations were first validated by comparing the predicted surface velocity with plant measurements. Then, seven LES simulations were conducted to study the effects of casting speed, electromagnetic braking (EMBr) field strength, and submerged entry nozzle (SEN) depth on the transient flow. The results show that EMBr has an important influence on flow inside the SEN, in addition to flow in the mold. With EMBr, an "M-shaped" flow profile is seen inside the SEN. The swirling flow behavior in the SEN and ports is more symmetrical at high casting speed and with higher EMBr strength. The position of the SEN ports relative to the peak magnetic field affects the EMBr performance. The results confirm and quantify how applying EMBr greatly lowers both the magnitude and turbulent variations of the surface velocity and level profile.

  19. A Helioseismic Survey to Investigate Relationships between Subsurface Flows beneath Large Active Regions and Solar Flares

    NASA Astrophysics Data System (ADS)

    Braun, Douglas; Leka, K D.; Barnes, Graham

    2014-06-01

    A survey of the subsurface flow properties of about 120 of the largest active regions, determined from the application of helioseismic holography to Dopplergrams obtained with the HMI instrument onboard the Solar Dynamics Observatory, is being carried out. The overriding goal is to characterize differences in the subsurface flows between active regions associated with eruptive flares and the flows observed in relatively quiescent regions. Applications to flare forecasting comprise only one part of this investigation, since the potential response of the subsurface environment to eruptive events during and after their occurrence is also of scientific interest. Other priorities include understanding the limitations of the helioseismic methods, identifying and correcting systematic effects, and validating the reliability of the measurements using artificial data. While inversions to determine the variation with depth of subsurface flows are planned, preliminary results will be discussed which make use of proxies for near-surface depth-integrated properties, including the horizontal component of the flow divergence and the vertical component of the flow vorticity.This work is supported by the Solar Terrestrial Program of the National Science Foundation, through grant AGS-1127327, and by the National Oceanic and Atmospheric Administration SBIR program.

  20. Inclusive electron scattering from nuclei in the quasielastic region at large momentum transfer

    SciTech Connect

    Fomin, Nadia

    2008-12-01

    Experiment E02-019, performed in Hall C at the Thomas Jefferson National Accelerator Facility (TJNAF), was a measurement of inclusive electron cross sections for several nuclei (2H,3He, 4He, 9Be,12C, 63Cu, and 197Au) in the quasielastic region at high momentum transfer. In the region of low energy transfer, the cross sections were analyzed in terms of the reduced response, F(y), by examining its y-scaling behavior. The data were also examined in terms of the nuclear structure function νWA 2 and its behavior in x and the Nachtmann variable ξ. The data show approximate scaling of νWA 2 in ξ for all targets at all kinematics, unlike scaling in x, which is confined to the DIS regime. However, y-scaling observations are limited to the kinematic region dominated by the quasielastic response (y <0), where some scaling violations arising from FSIs are observed.

  1. Structural dynamics and ssDNA binding activity of the three N-terminal domains of the large subunit of Replication Protein A from small angle X-ray scattering

    SciTech Connect

    Pretto, Dalyir I.; Tsutakawa, Susan; Brosey, Chris A.; Castillo, Amalchi; Chagot, Marie-Eve; Smith, Jarrod A.; Tainer, John A.; Chazin, Walter J.

    2010-03-11

    Replication Protein A (RPA) is the primary eukaryotic ssDNA binding protein utilized in diverse DNA transactions in the cell. RPA is a heterotrimeric protein with seven globular domains connected by flexible linkers, which enable substantial inter-domain motion that is essential to its function. Small angle X-ray scattering (SAXS) experiments on two multi-domain constructs from the N-terminus of the large subunit (RPA70) were used to examine the structural dynamics of these domains and their response to the binding of ssDNA. The SAXS data combined with molecular dynamics simulations reveal substantial interdomain flexibility for both RPA70AB (the tandem high affinity ssDNA binding domains A and B connected by a 10-residue linker) and RPA70NAB (RPA70AB extended by a 70-residue linker to the RPA70N protein interaction domain). Binding of ssDNA to RPA70NAB reduces the interdomain flexibility between the A and B domains, but has no effect on RPA70N. These studies provide the first direct measurements of changes in orientation of these three RPA domains upon binding ssDNA. The results support a model in which RPA70N remains structurally independent of RPA70AB in the DNA bound state and therefore freely available to serve as a protein recruitment module.

  2. Dynamical downscaling of historical climate over CORDEX East Asia domain: A comparison of regional ocean-atmosphere coupled model to stand-alone RCM simulations

    NASA Astrophysics Data System (ADS)

    Zou, Liwei; Zhou, Tianjun; Peng, Dongdong

    2016-02-01

    The FROALS (flexible regional ocean-atmosphere-land system) model, a regional ocean-atmosphere coupled model, has been applied to the Coordinated Regional Downscaling Experiment (CORDEX) East Asia domain. Driven by historical simulations from a global climate system model, dynamical downscaling for the period from 1980 to 2005 has been conducted at a uniform horizontal resolution of 50 km. The impacts of regional air-sea couplings on the simulations of East Asian summer monsoon rainfall have been investigated, and comparisons have been made to corresponding simulations performed using a stand-alone regional climate model (RCM). The added value of the FROALS model with respect to the driving global climate model was evident in terms of both climatology and the interannual variability of summer rainfall over East China by the contributions of both the high horizontal resolution and the reasonably simulated convergence of the moisture fluxes. Compared with the stand-alone RCM simulations, the spatial pattern of the simulated low-level monsoon flow over East Asia and the western North Pacific was improved in the FROALS model due to its inclusion of regional air-sea coupling. The results indicated that the simulated sea surface temperature (SSTs) resulting from the regional air-sea coupling were lower than those derived directly from the driving global model over the western North Pacific north of 15°N. These colder SSTs had both positive and negative effects. On the one hand, they strengthened the western Pacific subtropical high, which improved the simulation of the summer monsoon circulation over East Asia. On the other hand, the colder SSTs suppressed surface evaporation and favored weaker local interannual variability in the SST, which led to less summer rainfall and weaker interannual rainfall variability over the Korean Peninsula and Japan. Overall, the reference simulation performed using the FROALS model is reasonable in terms of rainfall over the land area of

  3. Improving a regional outreach program in a large health system using geographic information systems.

    PubMed

    Gabbert, John P; Trine, Robert M; Bintz, Marilu

    2012-06-01

    As government-insured populations grow, commercially insured populations decrease, and declining insurance reimbursements pressure cost and revenue. Health systems must strive to improve quality while lowering costs. Large medical centers with rural sites must understand their geography and how distances impede access to services, thereby affecting patient health. Without relevant data, which can be provided through the use of geographic information systems (GIS) technology, improvement is often delayed. Gundersen Lutheran Health System, a large multi-specialty system with urban and rural sites in 3 states, is developing an evaluative outreach GIS to facilitate understanding of, and response to, rural health needs. Investing in GIS technology furthers the health system's ability to deliver superior, affordable care.

  4. Isolation of a monoclonal antibody that recognizes the origin binding domain of JCV, but not SV40, large T-antigen.

    PubMed

    Grubman, Shelley A; Shin, Jong; Phelan, Paul J; Gong, Aaron; Can, Hande; Dilworth, Ryan; Kini, Sandeep Kuntadi; Gagnon, David; Archambault, Jacques; Meinke, Gretchen; Bohm, Andrew; Jefferson, Douglas M; Bullock, Peter A

    2016-10-01

    Within immunocompromised populations, the JC polyomavirus is the cause of the often-fatal disease Progressive Multifocal Leukoencephalopathy (PML). JC virus encodes a protein, termed T-antigen (T-ag), which is essential for its replication and pathogenicity. Previous studies of JCV T-ag have, in general, used antibodies raised against SV40 T-ag. Unfortunately, SV40 T-ag is also detected in humans and therefore there have been concerns about cross-reactivity. To address this issue, we have isolated a monoclonal antibody that binds to the JCV, but not the SV40, T-ag origin-binding domain (OBD). Furthermore, the region on the surface of the JCV T-ag OBD that is recognized by the "anti-JCV OBD mAb" has been mapped. We also demonstrate that the "anti-JCV OBD mAb" will be a useful reagent for standard techniques (e.g., Westerns blots and ELISAs). Finally, we note that additional monoclonal Abs that are specific for the T-ags encoded by the other human polyomaviruses could be generated by adopting the approach described herein. PMID:27433780

  5. A New Module for Large Scale Bayesian Evaluation in the Fast Neutron Energy Region

    SciTech Connect

    Schnabel, G. Leeb, H.

    2015-01-15

    We present an improved update scheme for the Linearized Bayesian Update procedure (LBUP). The revised procedure extends the application of the LBUP to a large number of observables. The consistent update of dozens of millions of observables becomes manageable by circumventing the costly calculation of the prior covariance matrix. Nuclear data evaluations based on the revised scheme may exhaustively enclose all differential and angle-integrated channels, treating all correlations between them exactly in the update procedure.

  6. Complete primary structure of the triple-helical region and the carboxyl-terminal domain of a new type IV collagen chain, alpha 5(IV).

    PubMed

    Pihlajaniemi, T; Pohjolainen, E R; Myers, J C

    1990-08-15

    We have isolated and characterized overlapping cDNA clones which code for a previously unidentified human collagen chain. Although the cDNA-derived primary structure of this new polypeptide is very similar to the basement membrane collagen alpha 1(IV) and alpha 2(IV) chains, the carboxyl-terminal collagenous/non-collagenous junction sequence does not correspond to the junction sequence in either of the newly described alpha 3(IV) or alpha 4(IV) chains (Butkowski, R.J., Langeveld, J.P.M., Wieslander, J., Hamilton, J., and Hudson, B. G. (1987) J. Biol. Chem. 262, 7874-7877). Thus the protein presented here has been designated the alpha 5 chain of type IV collagen. Four clones encode an open reading frame of 1602 amino acids that cover about 95% of the entire chain including half of the amino-terminal 7S domain and all of the central triple-helical region and carboxyl-terminal NC1 domain. The collagenous region of the alpha 5(IV) chain contains 22 interruptions which are in most cases identical in distribution to those in both the alpha 1(IV) and alpha 2(IV) chains. Despite the relatively low degree of conservation among the amino acids in the triple-helical region of the three type IV collagen chains, analysis of the sequences clearly showed that alpha 5(IV) is more related to alpha 1(IV) than to alpha 2(IV). This similarity between the alpha 5(IV) and alpha 1(IV) chains is particularly evident in the NC1 domains where the two polypeptides are 83% identical in contrast to the alpha 5(IV) and alpha 2(IV) identity of 63%. In addition to greatly increasing the complexity of basement membranes, the alpha 5 chain of type IV collagen may be responsible for specialized functions of some of these extracellular matrices. In this regard, it is important to note that we have recently assigned the alpha 5(IV) gene to the region of the X chromosome containing the locus for a familial type of hereditary nephritis known as Alport syndrome (Myers, J.C., Jones, T.A., Pohjalainen, E

  7. Purification and Structural Analysis of LEM-Domain Proteins.

    PubMed

    Herrada, Isaline; Bourgeois, Benjamin; Samson, Camille; Buendia, Brigitte; Worman, Howard J; Zinn-Justin, Sophie

    2016-01-01

    LAP2-emerin-MAN1 (LEM)-domain proteins are modular proteins characterized by the presence of a conserved motif of about 50 residues. Most LEM-domain proteins localize at the inner nuclear membrane, but some are also found in the endoplasmic reticulum or nuclear interior. Their architecture has been analyzed by predicting the limits of their globular domains, determining the 3D structure of these domains and in a few cases calculating the 3D structure of specific domains bound to biological targets. The LEM domain adopts an α-helical fold also found in SAP and HeH domains of prokaryotes and unicellular eukaryotes. The LEM domain binds to BAF (barrier-to-autointegration factor; BANF1), which interacts with DNA and tethers chromatin to the nuclear envelope. LAP2 isoforms also share an N-terminal LEM-like domain, which binds DNA. The structure and function of other globular domains that distinguish LEM-domain proteins from each other have been characterized, including the C-terminal dimerization domain of LAP2α and C-terminal WH and UHM domains of MAN1. LEM-domain proteins also have large intrinsically disordered regions that are involved in intra- and intermolecular interactions and are highly regulated by posttranslational modifications in vivo.

  8. Blockade of oncogenic IκB kinase activity in diffuse large B-cell lymphoma by bromodomain and extraterminal domain protein inhibitors.

    PubMed

    Ceribelli, Michele; Kelly, Priscilla N; Shaffer, Arthur L; Wright, George W; Xiao, Wenming; Yang, Yibin; Mathews Griner, Lesley A; Guha, Rajarshi; Shinn, Paul; Keller, Jonathan M; Liu, Dongbo; Patel, Paresma R; Ferrer, Marc; Joshi, Shivangi; Nerle, Sujata; Sandy, Peter; Normant, Emmanuel; Thomas, Craig J; Staudt, Louis M

    2014-08-01

    In the activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL), NF-κB activity is essential for viability of the malignant cells and is sustained by constitutive activity of IκB kinase (IKK) in the cytoplasm. Here, we report an unexpected role for the bromodomain and extraterminal domain (BET) proteins BRD2 and BRD4 in maintaining oncogenic IKK activity in ABC DLBCL. IKK activity was reduced by small molecules targeting BET proteins as well as by genetic knockdown of BRD2 and BRD4 expression, thereby inhibiting downstream NF-κB-driven transcriptional programs and killing ABC DLBCL cells. Using a high-throughput platform to screen for drug-drug synergy, we observed that the BET inhibitor JQ1 combined favorably with multiple drugs targeting B-cell receptor signaling, one pathway that activates IKK in ABC DLBCL. The BTK kinase inhibitor ibrutinib, which is in clinical development for the treatment of ABC DLBCL, synergized strongly with BET inhibitors in killing ABC DLBCL cells in vitro and in a xenograft mouse model. These findings provide a mechanistic basis for the clinical development of BET protein inhibitors in ABC DLBCL, particularly in combination with other modulators of oncogenic IKK signaling.

  9. NEMO Binding Domain peptide inhibits constitutive NF-κB activity and reduces tumor burden in a canine model of relapsed, refractory Diffuse Large B-Cell Lymphoma

    PubMed Central

    Gaurnier-Hausser, Anita; Patel, Reema; Baldwin, Albert S.; May, Michael J.; Mason, Nicola J.

    2011-01-01

    Purpose Activated B-Cell Diffuse Large B-Cell Lymphoma (ABC-DLBCL) is an aggressive, poorly chemoresponsive lymphoid malignancy characterized by constitutive canonical NF-κB activity that promotes lymphomagenesis and chemotherapy resistance via over-expression of anti-apoptotic NF-κB target genes. Inhibition of the canonical NF-κB pathway may therefore have therapeutic relevance in ABC-DLBCL. Here we set out to determine whether dogs with spontaneous DLBCL have comparative aberrant constitutive NF-κB activity and to determine the therapeutic relevance of NF-κB inhibition in dogs with relapsed, resistant DLBCL. Experimental Design Canonical NF-κB activity was evaluated by electrophoretic mobility shift assays and immunoblot analyses, and NF-κB target gene expression was measured by qRT-PCR. Primary malignant canine B lymphocytes were treated with the selective IKK complex inhibitor Nemo Binding Domain (NBD) peptide, and evaluated for NF-κB activity and apoptosis. NBD peptide was administered intra-nodally to dogs with relapsed B-cell lymphoma and NF-κB target gene expression and tumor burden were evaluated pre and post treatment. Results Constitutive canonical NF-κB activity and increased NF-κB target gene expression was detected in primary DLBCL tissue. NBD peptide inhibited this activity and induced apoptosis of primary malignant B cells in vitro. Intra-tumoral injections of NBD peptide to dogs with relapsed DLBCL inhibited NF-κB target gene expression and reduced tumor burden. Conclusions This work shows that dogs with spontaneous DLBCL represent a clinically relevant, spontaneous, large animal model for human ABC-DLBCL and demonstrates the therapeutic relevance of NF-κB inhibition in the treatment of ABC-DLBCL. These results have important translational relevance for ABC-DLBCL treatment in human patients. PMID:21610150

  10. VERY LARGE ARRAY H I ZEEMAN OBSERVATIONS OF THE CYGNUS X REGION: DR 22 AND ON 2

    SciTech Connect

    Mayo, E. A.; Troland, T. H. E-mail: troland@pa.uky.edu

    2012-02-15

    We have used the Very Large Array to study the Zeeman effect in 21 cm H I absorption lines from two star-forming regions in the Cygnus X complex, DR 22 and ON 2. We measure the line-of-sight magnetic field toward these regions, finding B{sub los} = -84 {+-} 11 {mu}G toward the DR 22 H II region and B{sub los} < 50 {mu}G toward each of the two H II regions in ON 2. We interpret these results in terms of two different models. In one model, we assume that the H I Zeeman effect is a measure of magnetic fields in the associated molecular clouds. If so, then the DR 22 molecular cloud is magnetically subcritical, that is, magnetically dominated. The ON 2 molecular clouds are magnetically supercritical. In a second model, we assume that the H I Zeeman effect is a measure of magnetic fields in photon-dominated regions where the gas has been compressed (and the field amplified) by absorption of stellar radiation. We find that this second model, where the measured field strength has been affected by star formation, accounts well for the DR 22 H I Zeeman effect. This same model, however, overpredicts the magnetic field in ON 2. ON 2 may be a region where the magnetic field is energetically insignificant or where the field happens to lie nearly in the plane of the sky.

  11. Impact of initial and boundary conditions on regional winter climate over the Western Himalayas: A fixed domain size experiment

    NASA Astrophysics Data System (ADS)

    Maharana, P.; Dimri, A. P.

    2014-03-01

    The Western Himalayas during winter receives precipitation due to the eastward moving low pressure synoptic weather systems, called Western Disturbances (WDs) in Indian meteorological parlance. The complex Himalayan topography, sparse observational data, less understanding of physical processes, etc. form many interesting research questions over this region. One of the important research goals is to study the change in the winter (Dec., Jan. and Feb. - DJF) climate over the Himalayas. In the presented study with modelling efforts having varying initial and boundary conditions (ICBC) with same model physics option is attempted to provide a comment on important physical processes pertaining to precipitation and temperature fields. A 22 year (1980-2001) simulation with Regional Climate Model version 3 (RegCM3) forced with National Centre for Environmental Prediction/National Centre for Atmospheric Research (NCEP/NCAR) reanalysis 1 (NNRP1), NCEP/NCAR reanalysis 2 (NNRP2) and European Centre for Medium Range Weather Forecast 40 Year reanalysis (ERA40) as three different ICBC is carried out. The present study focuses on the winter climatology of the main meteorological parameters viz., temperature, precipitation and snow depth and interannual variability of winter seasonal precipitation. The model shows overestimation of seasonal average precipitation and underestimation of seasonal average temperature fields over the Western Himalayas in all the three model simulations. The interannual variability of precipitation and temperature over this region is nicely captured by the model. The model simulation with NNRP2 as the ICBC shows more realistic results. In addition the ensemble mean of the three simulations has shown improved results and is closer to the abovementioned simulation. Precipitation bias explained in terms of the higher vertical integrated moisture flux and transport shows strong convergence zone over and along the southern rim of the Indian Himalayas. The

  12. Small beetle, large-scale drivers: how regional and landscape factors affect outbreaks of the European spruce bark beetle

    PubMed Central

    Seidl, Rupert; Müller, Jörg; Hothorn, Torsten; Bässler, Claus; Heurich, Marco; Kautz, Markus

    2016-01-01

    Summary 1. Unprecedented bark beetle outbreaks have been observed for a variety of forest ecosystems recently, and damage is expected to further intensify as a consequence of climate change. In Central Europe, the response of ecosystem management to increasing infestation risk has hitherto focused largely on the stand level, while the contingency of outbreak dynamics on large-scale drivers remains poorly understood. 2. To investigate how factors beyond the local scale contribute to the infestation risk from Ips typographus (Col., Scol.), we analysed drivers across seven orders of magnitude in scale (from 103 to 1010 m2) over a 23-year period, focusing on the Bavarian Forest National Park. Time-discrete hazard modelling was used to account for local factors and temporal dependencies. Subsequently, beta regression was applied to determine the influence of regional and landscape factors, the latter characterized by means of graph theory. 3. We found that in addition to stand variables, large-scale drivers also strongly influenced bark beetle infestation risk. Outbreak waves were closely related to landscape-scale connectedness of both host and beetle populations as well as to regional bark beetle infestation levels. Furthermore, regional summer drought was identified as an important trigger for infestation pulses. Large-scale synchrony and connectivity are thus key drivers of the recently observed bark beetle outbreak in the area. 4. Synthesis and applications. Our multiscale analysis provides evidence that the risk for biotic disturbances is highly dependent on drivers beyond the control of traditional stand-scale management. This finding highlights the importance of fostering the ability to cope with and recover from disturbance. It furthermore suggests that a stronger consideration of landscape and regional processes is needed to address changing disturbance regimes in ecosystem management. PMID:27041769

  13. A method for computation of inviscid three-dimensional flow over blunt bodies having large embedded subsonic regions

    NASA Technical Reports Server (NTRS)

    Weilmuenster, K. J.; Hamilton, H. H., II

    1981-01-01

    A computational technique for computing the three-dimensional inviscid flow over blunt bodies having large regions of embedded subsonic flow is detailed. Results, which were obtained using the CDC Cyber 203 vector processing computer, are presented for several analytic shapes with some comparison to experimental data. Finally, windward surface pressure computations over the first third of the Space Shuttle vehicle are compared with experimental data for angles of attack between 25 and 45 degrees.

  14. Acquisition of electroencephalographic data in a large regional hospital - Bringing the brain waves to the computer.

    NASA Technical Reports Server (NTRS)

    Low, M. D.; Baker, M.; Ferguson, R.; Frost, J. D., Jr.

    1972-01-01

    This paper describes a complete electroencephalographic acquisition and transmission system, designed to meet the needs of a large hospital with multiple critical care patient monitoring units. The system provides rapid and prolonged access to a centralized recording and computing area from remote locations within the hospital complex, and from locations in other hospitals and other cities. The system includes quick-on electrode caps, amplifier units and cable transmission for access from within the hospital, and EEG digitization and telephone transmission for access from other hospitals or cities.

  15. Large-scale nitrogen oxide plumes in the tropopause region and implications for ozone

    PubMed

    Brunner; Staehelin; Jeker

    1998-11-13

    Continuous measurements of nitrogen oxide and ozone were performed from a commercial airliner during 1 year at cruising altitudes below and above the tropopause. The upper tropospheric nitrogen oxides distribution was found to be strongly influenced by large-scale plumes extending about 100 to 1300 kilometers along the flight track. The plumes were frequently observed downwind of thunderstorms and frontal systems, which most probably caused upward transport of polluted air from the continental boundary layer or nitrogen oxide production in lightning strokes, or both. Particularly in summer, average ozone concentrations in the plumes were enhanced compared to the tropospheric background levels.

  16. A3 domain region 1803-1818 contributes to the stability of activated factor VIII and includes a binding site for activated factor IX.

    PubMed

    Bloem, Esther; Meems, Henriet; van den Biggelaar, Maartje; Mertens, Koen; Meijer, Alexander B

    2013-09-01

    A recent chemical footprinting study in our laboratory suggested that region 1803-1818 might contribute to A2 domain retention in activated factor VIII (FVIIIa). This site has also been implicated to interact with activated factor IX (FIXa). Asn-1810 further comprises an N-linked glycan, which seems incompatible with a role of the amino acids 1803-1818 for FIXa or A2 domain binding. In the present study, FVIIIa stability and FIXa binding were evaluated in a FVIII-N1810C variant, and two FVIII variants in which residues 1803-1810 and 1811-1818 are replaced by the corresponding residues of factor V (FV). Enzyme kinetic studies showed that only FVIII/FV 1811-1818 has a decreased apparent binding affinity for FIXa. Flow cytometry analysis indicated that fluorescent FIXa exhibits impaired complex formation with only FVIII/FV 1811-1818 on lipospheres. Site-directed mutagenesis revealed that Phe-1816 contributes to the interaction with FIXa. To evaluate FVIIIa stability, the FVIII/FV chimeras were activated by thrombin, and the decline in cofactor function was followed over time. FVIII/FV 1803-1810 and FVIII/FV 1811-1818 but not FVIII-N1810C showed a decreased FVIIIa half-life. However, when the FVIII variants were activated in presence of FIXa, only FVIII/FV 1811-1818 demonstrated an enhanced decline in cofactor function. Surface plasmon resonance analysis revealed that the FVIII variants K1813A/K1818A, E1811A, and F1816A exhibit enhanced dissociation after activation. The results together demonstrate that the glycan at 1810 is not involved in FVIII cofactor function, and that Phe-1816 of region 1811-1818 contributes to FIXa binding. Both regions 1803-1810 and 1811-1818 contribute to FVIIIa stability.

  17. A3 domain region 1803-1818 contributes to the stability of activated factor VIII and includes a binding site for activated factor IX.

    PubMed

    Bloem, Esther; Meems, Henriet; van den Biggelaar, Maartje; Mertens, Koen; Meijer, Alexander B

    2013-09-01

    A recent chemical footprinting study in our laboratory suggested that region 1803-1818 might contribute to A2 domain retention in activated factor VIII (FVIIIa). This site has also been implicated to interact with activated factor IX (FIXa). Asn-1810 further comprises an N-linked glycan, which seems incompatible with a role of the amino acids 1803-1818 for FIXa or A2 domain binding. In the present study, FVIIIa stability and FIXa binding were evaluated in a FVIII-N1810C variant, and two FVIII variants in which residues 1803-1810 and 1811-1818 are replaced by the corresponding residues of factor V (FV). Enzyme kinetic studies showed that only FVIII/FV 1811-1818 has a decreased apparent binding affinity for FIXa. Flow cytometry analysis indicated that fluorescent FIXa exhibits impaired complex formation with only FVIII/FV 1811-1818 on lipospheres. Site-directed mutagenesis revealed that Phe-1816 contributes to the interaction with FIXa. To evaluate FVIIIa stability, the FVIII/FV chimeras were activated by thrombin, and the decline in cofactor function was followed over time. FVIII/FV 1803-1810 and FVIII/FV 1811-1818 but not FVIII-N1810C showed a decreased FVIIIa half-life. However, when the FVIII variants were activated in presence of FIXa, only FVIII/FV 1811-1818 demonstrated an enhanced decline in cofactor function. Surface plasmon resonance analysis revealed that the FVIII variants K1813A/K1818A, E1811A, and F1816A exhibit enhanced dissociation after activation. The results together demonstrate that the glycan at 1810 is not involved in FVIII cofactor function, and that Phe-1816 of region 1811-1818 contributes to FIXa binding. Both regions 1803-1810 and 1811-1818 contribute to FVIIIa stability. PMID:23884417

  18. A3 Domain Region 1803–1818 Contributes to the Stability of Activated Factor VIII and Includes a Binding Site for Activated Factor IX

    PubMed Central

    Bloem, Esther; Meems, Henriet; van den Biggelaar, Maartje; Mertens, Koen; Meijer, Alexander B.

    2013-01-01

    A recent chemical footprinting study in our laboratory suggested that region 1803–1818 might contribute to A2 domain retention in activated factor VIII (FVIIIa). This site has also been implicated to interact with activated factor IX (FIXa). Asn-1810 further comprises an N-linked glycan, which seems incompatible with a role of the amino acids 1803–1818 for FIXa or A2 domain binding. In the present study, FVIIIa stability and FIXa binding were evaluated in a FVIII-N1810C variant, and two FVIII variants in which residues 1803–1810 and 1811–1818 are replaced by the corresponding residues of factor V (FV). Enzyme kinetic studies showed that only FVIII/FV 1811–1818 has a decreased apparent binding affinity for FIXa. Flow cytometry analysis indicated that fluorescent FIXa exhibits impaired complex formation with only FVIII/FV 1811–1818 on lipospheres. Site-directed mutagenesis revealed that Phe-1816 contributes to the interaction with FIXa. To evaluate FVIIIa stability, the FVIII/FV chimeras were activated by thrombin, and the decline in cofactor function was followed over time. FVIII/FV 1803–1810 and FVIII/FV 1811–1818 but not FVIII-N1810C showed a decreased FVIIIa half-life. However, when the FVIII variants were activated in presence of FIXa, only FVIII/FV 1811–1818 demonstrated an enhanced decline in cofactor function. Surface plasmon resonance analysis revealed that the FVIII variants K1813A/K1818A, E1811A, and F1816A exhibit enhanced dissociation after activation. The results together demonstrate that the glycan at 1810 is not involved in FVIII cofactor function, and that Phe-1816 of region 1811–1818 contributes to FIXa binding. Both regions 1803–1810 and 1811–1818 contribute to FVIIIa stability. PMID:23884417

  19. The 5'-untranslated regions of picornavirus RNAs contain independent functional domains essential for RNA replication and translation.

    PubMed Central

    Rohll, J B; Percy, N; Ley, R; Evans, D J; Almond, J W; Barclay, W S

    1994-01-01

    The role of the 5'-untranslated region (5'UTR) in the replication of enteroviruses has been studied by using a series of poliovirus type 3 (PV3) replicons containing the chloramphenicol acetyltransferase reporter gene in which the 5'UTR was replaced by the 5'UTR of either coxsackievirus B4 or human rhinovirus 14 or composite 5'UTRs derived from sequences of PV3, human rhinovirus 14, coxsackievirus B4, or encephalomyocarditis virus. The results indicate that efficient replication of an enterovirus genome requires a compatible interaction between the 5'-terminal cloverleaf structure and the coding and/or 3'-noncoding regions of the genome. A crucial determinant of this interaction is the stem-loop formed by nucleotides 46 to 81 (stem-loop d). The independence of the cloverleaf structure formed by the 5'-terminal 88 nucleotides and the ribosome landing pad or internal ribosome entry site (IRES) was investigated by constructing a 5'UTR composed of the PV3 cloverleaf and the IRES from encephalomyocarditis virus. Chloramphenicol acetyltransferase gene-containing replicons and viruses containing this recombinant 5'UTR showed levels of replication similar to those of the corresponding genomes containing the complete PV3 5'UTR, indicating that the cloverleaf and the IRES may be regarded as functionally independent and nonoverlapping elements. Images PMID:8207812

  20. Large systematic trend difference between national and regional homogenized datasets and global collections

    NASA Astrophysics Data System (ADS)

    Venema, Victor

    2016-04-01

    The global land temperature trend may be biased due to remaining inhomogeneities. Well-homogenized national datasets on average clearly show more warming than global collections when averaged over the region of common coverage. For this study we have collected a dataset with more than 40 national and regional average monthly temperature series (called "national" from now on). National datasets can be better homogenized than global ones. More data is available at national weather services to serve as a reference in the detection and correction of breaks. More stations and knowledge of the local climatology can help in selecting better references that are expected to have the same climate signal. More metadata is available nationally on network-wide breaks and to determine the right date of the statistically detected breaks. Furthermore, better homogenization methods are available for regional networks. Here we compare these national datasets to the global collections BEST, CRUCY, CRUTEM4, GHCNv3 and GISS. For all datasets the country average series have been computed. A subset of 10 well-homogenized national datasets shows a clearly stronger temperature trend, which is several tenths of a degree Celsius per century larger and mostly statistically significant. These differences are seen for the entire period between 1800 and now. The differences are smallest for CRUTEM4 and CRUCY, which include homogenized data from many of our national datasets. The differences are largest for BEST and GISS. GHCN represents a middle case. We are working on better understanding these differences by comparing all datasets, which range from raw data to data homogenized by various methods and which use a range of different methods to compute the national average. We look for relationships between the methods used for homogenization and averaging and the trend differences. In an accompanying poster, we i) review the literature on trend uncertainties due to remaining inhomogeneities, ii

  1. Seismological Segmentation of Halmahera Thrust, Molucca Sea Region, based on Large Earthquake Sequences

    NASA Astrophysics Data System (ADS)

    Shiddiqi, H. A.; Widiyantoro, S.; Nugraha, A. D.; Ramdhan, M.; Wiyono, S. H.; Wandono, W.

    2015-12-01

    The Molucca Sea region in eastern Indonesia is a complex tectonic region, where the arc-arc collision between the Sangihe and Halmahera arcs takes place. Two recent largest earthquakes occurred in this area are Mw 7.5, January 2007, and Mw 7.2, November 2014, that occurred 90 km to the north from the 2007 earthquake site. Both earthquakes occurred along the Halmahera thrust, however, the aftershock of the two events occurred in separated parts of the same fault. In this study, we aim to investigate the segmentation of the seismogenic zone in Molucca Sea by using seismological analysis. We employed teleseismic double-difference relocation using P- and S-wave arrival times from the Meteorological, Climatological, and Geophysical Agency of Indonesia (BMKG) and the International Seismological Centre (ISC) catalog. We used a 3D velocity model for the Indonesian region. Our relocation result revealed that aftershocks of the two events did not overlap each other. Although they have similar focal mechanisms with NNE-SSW direction, the aftershock patterns were different. While the 2014 event aftershock distribution is consistent with the strike direction inferred from the focal mechanism, the 2007 event aftershocks occurred in NEE-SWW direction. Furthermore we analyzed the spatial variation in b-value for different time ranges. The b-value analysis also showed two separated segments of low b-value anomaly around both events for each time range. We envisage that stress regime directions and geometries of the fault are different for both aftershock clusters. For this reason we analyzed focal mechanism data and found that fault segment around the 2014 event is steeper than that related to the 2007 event. We applied focal mechanism inversion to obtain the direction of stress and fault orientation, and found different stress directions for the two segments. While the northern part segment has maximum stress with SSE direction, the stress in the southern part is rotated in SE

  2. The Pliny-Strabo trench region: A large shear zone resulting from slab tearing

    NASA Astrophysics Data System (ADS)

    Özbakır, Ali D.; Şengör, A. M. C.; Wortel, M. J. R.; Govers, R.

    2013-08-01

    The eastern part of the Hellenic subduction zone is composed of the Pliny and Strabo "trenches" that have been regarded as a zone of convergence between the subducting African lithosphere and the overriding Anatolian-Aegean plate. In the Pliny and Strabo "trenches", the oblique relative plate motion is generally thought to be accommodated by a typical strain partitioning consisting of strike-slip and convergence components. Notwithstanding the occurrence of strike-slip motion parallel with the Pliny-Strabo "trenches", trench-normal thrusting is not observed so far. Therefore, we conducted a detailed analysis to investigate the deformation mechanisms of the eastern part of the Hellenic Trench system. Our analyses of offshore faulting and mechanisms of earthquakes in the overriding Aegean lithosphere show that the region of the Pliny and Strabo "trenches" obeys the mechanics of the sinistral shear zone model of Tchalenko (1970). We propose that the trench perpendicular convergence is taken up by the Rhodes fold and thrust belt, which has been postulated off the southeast coast of Rhodes. Several regional P-wave tomography results give indications of a slow seismic anomaly under this zone, which is interpreted as a tear between the Hellenic and Cyprus subduction zones. The primary reason for such tear and its propagation is the ongoing rollback of the subducted part of the African lithosphere, also referred to as "the Aegean slab". Our work elucidates the surface expression of this tearing process in the form of the development of a shear zone between the Aegean lithosphere in the NW and the African lithosphere in the SE, the Pliny-Strabo Shear Zone.

  3. Binding of heparin by type III domains and peptides from the carboxy terminal hep-2 region of fibronectin.

    PubMed

    Ingham, K C; Brew, S A; Migliorini, M M; Busby, T F

    1993-11-23

    The major sites of heparin binding by fibronectin are located in fragments of 30 or 40 kDa that contain type III modules 12 through 14 or 15. Various proteolytic or recombinant subfragments and several synthetic peptides derived from this region have been compared with respect to their binding to fluorescein-labeled heparin in solution. Binding was monitored by the change in fluorescence anisotropy at 25 degrees C and pH 7.4 in 0.02 M Tris buffer, alone (TB) or with 0.15M NaCl (TBS). A 23-kDa fragment containing III13 and III14 but lacking III12 had Kd values of 0.3 and 1.8 microM in TB, and TBS, respectively, indistinguishable from the 30-kDa parent. Fragments containing only module III13 bound 2-3-fold weaker than the parent while those containing only III14 bound 6-50-fold weaker depending on the ionic strength. Fragments containing only III12 or III15 failed to bind at all in TBS. A cationic peptide derived from the amino terminus of III13 and containing the Arg-Arg-Ala-Arg consensus sequence, whose integrity was shown by Barkalow and Schwarzbauer [Barkalow, F. J., & Schwarzbauer, J. E. (1991) J. Biol. Chem. 266, 7812-7818] to be critical, failed to bind in TBS but bound weakly in TB. Two additional cationic peptides derived from the middle and C-terminal regions of III14 showed similar behavior. Thus while the major determinant(s) of heparin binding are located in III13, those determinants are only active when part of a properly folded structure. Furthermore, module III13 when isolated had a slightly lower affinity than fragments containing both III13 and III14.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8241146

  4. A Third-Order Item Response Theory Model for Modeling the Effects of Domains and Subdomains in Large-Scale Educational Assessment Surveys

    ERIC Educational Resources Information Center

    Rijmen, Frank; Jeon, Minjeong; von Davier, Matthias; Rabe-Hesketh, Sophia

    2014-01-01

    Second-order item response theory models have been used for assessments consisting of several domains, such as content areas. We extend the second-order model to a third-order model for assessments that include subdomains nested in domains. Using a graphical model framework, it is shown how the model does not suffer from the curse of…

  5. A refined regional modeling approach for the Corn Belt - Experiences and recommendations for large-scale integrated modeling

    NASA Astrophysics Data System (ADS)

    Panagopoulos, Yiannis; Gassman, Philip W.; Jha, Manoj K.; Kling, Catherine L.; Campbell, Todd; Srinivasan, Raghavan; White, Michael; Arnold, Jeffrey G.

    2015-05-01

    Nonpoint source pollution from agriculture is the main source of nitrogen and phosphorus in the stream systems of the Corn Belt region in the Midwestern US. This region is comprised of two large river basins, the intensely row-cropped Upper Mississippi River Basin (UMRB) and Ohio-Tennessee River Basin (OTRB), which are considered the key contributing areas for the Northern Gulf of Mexico hypoxic zone according to the US Environmental Protection Agency. Thus, in this area it is of utmost importance to ensure that intensive agriculture for food, feed and biofuel production can coexist with a healthy water environment. To address these objectives within a river basin management context, an integrated modeling system has been constructed with the hydrologic Soil and Water Assessment Tool (SWAT) model, capable of estimating river basin responses to alternative cropping and/or management strategies. To improve modeling performance compared to previous studies and provide a spatially detailed basis for scenario development, this SWAT Corn Belt application incorporates a greatly refined subwatershed structure based on 12-digit hydrologic units or 'subwatersheds' as defined by the US Geological Service. The model setup, calibration and validation are time-demanding and challenging tasks for these large systems, given the scale intensive data requirements, and the need to ensure the reliability of flow and pollutant load predictions at multiple locations. Thus, the objectives of this study are both to comprehensively describe this large-scale modeling approach, providing estimates of pollution and crop production in the region as well as to present strengths and weaknesses of integrated modeling at such a large scale along with how it can be improved on the basis of the current modeling structure and results. The predictions were based on a semi-automatic hydrologic calibration approach for large-scale and spatially detailed modeling studies, with the use of the Sequential

  6. Systematic Analysis of Bacterial Effector-Postsynaptic Density 95/Disc Large/Zonula Occludens-1 (PDZ) Domain Interactions Demonstrates Shigella OspE Protein Promotes Protein Kinase C Activation via PDLIM Proteins*

    PubMed Central

    Yi, Chae-ryun; Allen, John E.; Russo, Brian; Lee, Soo Young; Heindl, Jason E.; Baxt, Leigh A.; Herrera, Bobby Brooke; Kahoud, Emily; MacBeath, Gavin; Goldberg, Marcia B.

    2014-01-01

    Diseases caused by many Gram-negative bacterial pathogens depend on the activities of bacterial effector proteins that are delivered into eukaryotic cells via specialized secretion systems. Effector protein function largely depends on specific subcellular targeting and specific interactions with cellular ligands. PDZ domains are common domains that serve to provide specificity in protein-protein interactions in eukaryotic systems. We show that putative PDZ-binding motifs are significantly enriched among effector proteins delivered into mammalian cells by certain bacterial pathogens. We use PDZ domain microarrays to identify candidate interaction partners of the Shigella flexneri effector proteins OspE1 and OspE2, which contain putative PDZ-binding motifs. We demonstrate in vitro and in cells that OspE proteins interact with PDLIM7, a member of the PDLIM family of proteins, which contain a PDZ domain and one or more LIM domains, protein interaction domains that participate in a wide variety of functions, including activation of isoforms of protein kinase C (PKC). We demonstrate that activation of PKC during S. flexneri infection is attenuated in the absence of PDLIM7 or OspE proteins and that the OspE PDZ-binding motif is required for wild-type levels of PKC activation. These results are consistent with a model in which binding of OspE to PDLIM7 during infection regulates the activity of PKC isoforms that bind to the PDLIM7 LIM domain. PMID:25124035

  7. Systematic analysis of bacterial effector-postsynaptic density 95/disc large/zonula occludens-1 (PDZ) domain interactions demonstrates Shigella OspE protein promotes protein kinase C activation via PDLIM proteins.

    PubMed

    Yi, Chae-ryun; Allen, John E; Russo, Brian; Lee, Soo Young; Heindl, Jason E; Baxt, Leigh A; Herrera, Bobby Brooke; Kahoud, Emily; MacBeath, Gavin; Goldberg, Marcia B

    2014-10-24

    Diseases caused by many Gram-negative bacterial pathogens depend on the activities of bacterial effector proteins that are delivered into eukaryotic cells via specialized secretion systems. Effector protein function largely depends on specific subcellular targeting and specific interactions with cellular ligands. PDZ domains are common domains that serve to provide specificity in protein-protein interactions in eukaryotic systems. We show that putative PDZ-binding motifs are significantly enriched among effector proteins delivered into mammalian cells by certain bacterial pathogens. We use PDZ domain microarrays to identify candidate interaction partners of the Shigella flexneri effector proteins OspE1 and OspE2, which contain putative PDZ-binding motifs. We demonstrate in vitro and in cells that OspE proteins interact with PDLIM7, a member of the PDLIM family of proteins, which contain a PDZ domain and one or more LIM domains, protein interaction domains that participate in a wide variety of functions, including activation of isoforms of protein kinase C (PKC). We demonstrate that activation of PKC during S. flexneri infection is attenuated in the absence of PDLIM7 or OspE proteins and that the OspE PDZ-binding motif is required for wild-type levels of PKC activation. These results are consistent with a model in which binding of OspE to PDLIM7 during infection regulates the activity of PKC isoforms that bind to the PDLIM7 LIM domain.

  8. Isothermal internal friction behaviour of a Zr based bulk metallic glass with large supercooled liquid region

    NASA Astrophysics Data System (ADS)

    Wang, Q.; Lu, J.; Gu, F. J.; Xu, H.; Dong, Y. D.

    2006-07-01

    In this paper, the internal friction behaviour of Zr-Ti-Cu-Ni-Be bulk metallic glass (BMG) containing 2 at% Fe at elevated temperatures has been studied in isothermal dynamic mechanical analysis experiments. The experiments lead to the determination of metastable equilibrium internal friction Q_{\\rme}^{-1} , as a function of temperature, which can be well described by the Maxwell model with viscosity, η(T), following a Vogel-Fulcher-Tammann (VFT) relation or Arrehnius law. Comparison with the Zr-Ti-Cu-Ni-Be glass-forming liquid shows that a small addition of Fe results in a stronger liquid behaviour of the alloy, exhibiting a higher strength parameter as well as lower VFT temperature and therefore correlates better glass forming ability and thermal stability. From the isothermal internal friction data, the activation energies for viscous flow and primary crystallization of the Zr based supercooled metallic liquid are also derived. It is found that the former is comparable to the activation energy controlling the diffusion process of atoms, e.g. the Ni element of medium size and higher mobility among the components of this alloy, while the latter to that of atoms, e.g. the Ti element of larger size and lower mobility. Thus, it is proposed that both isothermal viscous flow and primary crystallization of the alloy in the supercooleld liquid region are atom diffusion-controlled processes. However, the dominating atomic species are different from each other in the multicomponent Zr based BMG.

  9. Large-scale traveling ionospheric disturbances observed using GPS receivers over high-latitude and equatorial regions

    NASA Astrophysics Data System (ADS)

    Idrus, Intan Izafina; Abdullah, Mardina; Hasbi, Alina Marie; Husin, Asnawi; Yatim, Baharuddin

    2013-09-01

    This paper presents the first results of large-scale traveling ionospheric disturbances (LSTIDs) observation during two moderate magnetic storm events on 28 May 2011 (SYM-H∼ -94 nT and Dst∼-80 nT) and 6 August 2011 (SYM-H∼-126 nT and Dst∼-113 nT) over the high-latitude region in Russia, Sweden, Norway, Iceland and Greenland and equatorial region in the Peninsular Malaysia using vertical total electron content (VTEC) from the Global Positioning System (GPS) observations measurement. The propagation of the LSTID signatures in the GPS TEC measurements over Peninsular Malaysia was also investigated using VTEC map. The LSTIDs were found to propagate both equatorward and poleward directions during these two events. The results showed that the LSTIDs propagated faster at high-latitude region with an average phase velocity of 1074.91 m/s than Peninsular Malaysia with an average phase velocity of 604.84 m/s. The LSTIDs at the high-latitude region have average periods of 150 min whereas the ones observed over Peninsular Malaysia have average periods of 115 min. The occurrences of these LSTIDs were also found to be the subsequent effects of substorm activities in the auroral region. To our knowledge, this is the first result of observation of LSTIDs over Peninsular Malaysia during the 24th solar cycle.

  10. (1)H, (15)N and (13)C resonance assignments of the conserved region in the middle domain of S. pombe Sin1 protein.

    PubMed

    Kataoka, Saori; Furuita, Kyoko; Hattori, Yoshikazu; Kobayashi, Naohiro; Ikegami, Takahisa; Shiozaki, Kazuhiro; Fujiwara, Toshimichi; Kojima, Chojiro

    2015-04-01

    SAPK-interacting protein 1 (Sin1) is an important component of the target of rapamycin (TOR) complex 2 (TORC2). TOR is a serine/threonine-specific protein kinase and forms functionally distinct protein complexes referred to as TORC1 and TORC2. TORC2, conserved from yeast to humans, phosphorylates AGC-family protein kinases and has many cellular functions including the regulation of actin cytoskeleton. The Sin1 subunit of TORC2 is required for the binding of TORC2 to substrates, and the conserved region in the middle (CRIM) domain of Sin1 is important in the substrate recognition of TORC2. Here, we report on the (1)H, (13)C and (15)N resonance assignments of fission yeast Schizosaccharomyces pombe Sin1 (amino acids 247-400) (Sin1CRIM), which possesses the CRIM domain. These data contribute toward the structure determination of Sin1CRIM and an understanding of the interactions of Sin1CRIM with substrates of TORC2.

  11. The Atomic Structure of the HIV-1 gp41 Transmembrane Domain and Its Connection to the Immunogenic Membrane-proximal External Region.

    PubMed

    Apellániz, Beatriz; Rujas, Edurne; Serrano, Soraya; Morante, Koldo; Tsumoto, Kouhei; Caaveiro, Jose M M; Jiménez, M Ángeles; Nieva, José L

    2015-05-22

    The membrane-proximal external region (MPER) C-terminal segment and the transmembrane domain (TMD) of gp41 are involved in HIV-1 envelope glycoprotein-mediated fusion and modulation of immune responses during viral infection. However, the atomic structure of this functional region remains unsolved. Here, based on the high resolution NMR data obtained for peptides spanning the C-terminal segment of MPER and the TMD, we report two main findings: (i) the conformational variability of the TMD helix at a membrane-buried position; and (ii) the existence of an uninterrupted α-helix spanning MPER and the N-terminal region of the TMD. Thus, our structural data provide evidence for the bipartite organization of TMD predicted by previous molecular dynamics simulations and functional studies, but they do not support the breaking of the helix at Lys-683, as was suggested by some models to mark the initiation of the TMD anchor. Antibody binding energetics examined with isothermal titration calorimetry and humoral responses elicited in rabbits by peptide-based vaccines further support the relevance of a continuous MPER-TMD helix for immune recognition. We conclude that the transmembrane anchor of HIV-1 envelope is composed of two distinct subdomains: 1) an immunogenic helix at the N terminus also involved in promoting membrane fusion; and 2) an immunosuppressive helix at the C terminus, which might also contribute to the late stages of the fusion process. The unprecedented high resolution structural data reported here may guide future vaccine and inhibitor developments.

  12. Local Condensation Curve from Dropwise to Glacial Region on Large Vertical Surface

    NASA Astrophysics Data System (ADS)

    Haraguchi, Tadao; Shimada, Ryohachi; Takeyama, Toshiro

    The existence of several regimes of condensation heat transfer is well known. Regimes are given academic names as dropwise, transition, film and glacial condensation along the condensation curve showing the relationship between heat flux and surface subcooling. In case of comparatively large vertical surface, the lower part on the gravitational direction is affected by condensate from the upper part, and will be covered by water stream like a rivulet. It has no longer an existence as dropwise condition, and it is absolutely impossible that heat transfer problems under constant temperature or constant heat flux take place. The reason is why as follows, heat transfer of film condensation is some orders of magnitude less than dropwise condensation, and various regimes exist together simultaneously. In the present paper we shall try to observe the coexisting appearance of regimes in steam condensation at atmospheric pressure and make researches in the local condensation curve from top to bottom on the same surface, that is divided into eight parts in the rear side. The main results are shown as follows (1) Enhancement of heat transfer by wiping of drops appears toward somewhat lower position from top. (2) Frazil ice is observed in the supercooled liquid film flowing down on glacial condensation. (3) The regime of glacial condensation describes a thermal hysteresis loop.

  13. Anti-NMDA Receptor Encephalitis Antibody Binding Is Dependent on Amino Acid Identity of a Small Region Within the GluN1 Amino Terminal Domain

    PubMed Central

    Gleichman, Amy J.; Spruce, Lynn A.; Dalmau, Josep; Seeholzer, Steven H.; Lynch, David R.

    2012-01-01

    Anti-NMDA receptor (NMDAR) encephalitis is a newly identified autoimmune disorder that targets NMDARs, causing severe neurological symptoms including hallucinations, psychosis, and seizures, and may result in death (Dalmau et al., 2008). However, the exact epitope to which these antibodies bind is unknown. A clearly defined antigenic region could provide more precise testing, allow for comparison of immunogenicity between patients to explore potential clinically relevant variations, elucidate the functional effects of antibodies, and make patients’ antibodies a more effective tool with which to study NMDAR function. Here, we use human cerebrospinal fluid to explore the antigenic region of the NMDAR. We created a series of mutants within the amino terminal domain of GluN1 that change patient antibody binding in transfected cells in stereotyped ways. These mutants demonstrate that the N368/G369 region of GluN1 is crucial for the creation of immunoreactivity. Mass spectrometry experiments show that N368 is glycosylated in transfected cells and rat brain regions; however, this glycosylation is not directly required for epitope formation. Mutations of residues N368/G369 change the closed time of the receptor in single channel recordings; more frequent channel openings correlates with the degree of antibody staining, and acute antibody exposure prolongs open time of the receptor. The staining pattern of mutant receptors is similar across subgroups of patients, indicating consistent immunogenicity, although we have identified one region that has a variable role in epitope formation. These findings provide tools for detailed comparison of antibodies across patients and suggest an interaction between antibody binding and channel function. PMID:22875940

  14. Dataset for the NMR structure of the intrinsically disordered acidic region of XPC bound to the PH domain of TFIIH p62

    PubMed Central

    Okuda, Masahiko; Nishimura, Yoshifumi

    2016-01-01

    The global genome nucleotide excision repair factor XPC firstly detects DNA lesions and then recruits a ten-subunit complex TFIIH through binding to the subunit p62 to unwind the damaged DNA for excision repair. This data article contains detailed nuclear magnetic resonance (NMR) restraints (nuclear Overhauser enhancement (NOE)-derived distance restraints, dihedral angle restraints, and hydrogen bond restraints) used for the structure determination of the complex formed between the intrinsically disordered acidic region of XPC and the pleckstrin homology (PH) domain of TFIIH p62, related to the recent work entitled “Structural insight into the mechanism of TFIIH recognition by the acidic string of the nucleotide excision repair factor XPC.” [1]. PMID:26909369

  15. Cold region river discharge uncertainty—estimates from large Russian rivers

    NASA Astrophysics Data System (ADS)

    Shiklomanov, Alexander I.; Yakovleva, Tatyana I.; Lammers, Richard B.; Karasev, Iosiph Ph.; Vörösmarty, Charles. J.; Linder, Ernst

    2006-07-01

    We develop an error model to understand the reliability and accuracy of river discharge datasets that are now being used for a variety of important global change questions. The developed error model for cold region river discharge uses standard hydrometric data along with information on the frequency and precision of measurements, characteristics of river channel capacity, and method of discharge computation. The uncertainties of daily, monthly and annual discharge data for the downstream gauges of the six largest Eurasian rivers (Severnaya Dvina, Pechora, Ob', Yenisei, Lena and Kolyma) in the pan-Arctic drainage along with uncertainty of aggregated annual time series are evaluated using the suggested methodology. The study shows that uncertainties associated with discharge determination significantly change from year to year and strongly depend on the computational methods used and frequency of discharge measurements. Recent work by Peterson et al. (2002) has shown increases in river discharge to the Arctic Ocean of the six largest Eurasian rivers of 7% from 1936 to 1999. This paper focuses on determination of reliability in the discharge data which provided such conclusion. The obtained results further confirm the findings of Peterson et al. (2002) concerning the rise in river discharge. We found that errors of the total annual discharge for the six rivers over the period 1950-2000 are in the range 1.5-3.5%. The long-term trend of the observed discharge from these six rivers into the Arctic Ocean for 1936-2000, along with uncertainty associated with discharge data, is 2.0±0.4 km 3/year.

  16. Complex regional pain syndrome: evidence for warm and cold subtypes in a large prospective clinical sample.

    PubMed

    Bruehl, Stephen; Maihöfner, Christian; Stanton-Hicks, Michael; Perez, Roberto S G M; Vatine, Jean-Jacques; Brunner, Florian; Birklein, Frank; Schlereth, Tanja; Mackey, Sean; Mailis-Gagnon, Angela; Livshitz, Anatoly; Harden, R Norman

    2016-08-01

    Limited research suggests that there may be Warm complex regional pain syndrome (CRPS) and Cold CRPS subtypes, with inflammatory mechanisms contributing most strongly to the former. This study for the first time used an unbiased statistical pattern recognition technique to evaluate whether distinct Warm vs Cold CRPS subtypes can be discerned in the clinical population. An international, multisite study was conducted using standardized procedures to evaluate signs and symptoms in 152 patients with clinical CRPS at baseline, with 3-month follow-up evaluations in 112 of these patients. Two-step cluster analysis using automated cluster selection identified a 2-cluster solution as optimal. Results revealed a Warm CRPS patient cluster characterized by a warm, red, edematous, and sweaty extremity and a Cold CRPS patient cluster characterized by a cold, blue, and less edematous extremity. Median pain duration was significantly (P < 0.001) shorter in the Warm CRPS (4.7 months) than in the Cold CRPS subtype (20 months), with pain intensity comparable. A derived total inflammatory score was significantly (P < 0.001) elevated in the Warm CRPS group (compared with Cold CRPS) at baseline but diminished significantly (P < 0.001) over the follow-up period, whereas this score did not diminish in the Cold CRPS group (time × subtype interaction: P < 0.001). Results support the existence of a Warm CRPS subtype common in patients with acute (<6 months) CRPS and a relatively distinct Cold CRPS subtype most common in chronic CRPS. The pattern of clinical features suggests that inflammatory mechanisms contribute most prominently to the Warm CRPS subtype but that these mechanisms diminish substantially during the first year postinjury. PMID:27023422

  17. Regional uplift associated with continental large igneous provinces: The roles of mantle plumes and the lithosphere

    USGS Publications Warehouse

    Saunders, A.D.; Jones, S.M.; Morgan, L.A.; Pierce, K.L.; Widdowson, M.; Xu, Y.G.

    2007-01-01

    The timing and duration of surface uplift associated with large igneous provinces provide important constraints on mantle convection processes. Here we review geological indicators of surface uplift associated with five continent-based magmatic provinces: Emeishan Traps (260??million years ago: Ma), Siberian Traps (251??Ma), Deccan Traps (65??Ma), North Atlantic (Phase 1, 61??Ma and Phase 2, 55??Ma), and Yellowstone (16??Ma to recent). All five magmatic provinces were associated with surface uplift. Surface uplift can be measured directly from sedimentary indicators of sea-level in the North Atlantic and from geomorpholocial indicators of relative uplift and tilting in Yellowstone. In the other provinces, surface uplift is inferred from the record of erosion. In the Deccan, North Atlantic and Emeishan provinces, transient uplift that results from variations in thermal structure of the lithosphere and underlying mantle can be distinguished from permanent uplift that results from the extraction and emplacement of magma. Transient surface uplift is more useful in constraining mantle convection since models of melt generation and emplacement are not required for its interpretation. Observations of the spatial and temporal relationships between surface uplift, rifting and magmatism are also important in constraining models of LIP formation. Onset of surface uplift preceded magmatism in all five of the provinces. Biostratigraphic constraints on timing of uplift and erosion are best for the North Atlantic and Emeishan Provinces, where the time interval between significant uplift and first magmatism is less than 1??million years and 2.5??million years respectively. Rifting post-dates the earliest magmatism in the case of the North Atlantic Phase 1 and possibly in the case of Siberia. The relative age of onset of offshore rifting is not well constrained for the Deccan and the importance of rifting in controlling magmatism is disputed in the Emeishan and Yellowstone

  18. Regional differences in rat large intestinal crypt function in relation to dehydrating capacity in vivo

    PubMed Central

    Naftalin, R J; Zammit, P S; Pedley, K C

    1999-01-01

    Rat descending colon absorbed fluid against a large hydraulic resistance, imposed by 10% agarose (w/v) gel plugs inserted in the lumen, by raising the tonicity of the absorbate from the gel to 880 ± 54 mosmol kg−1; the tonicity of the absorbate from 2.5% gels was 352 ± 38 mosmol kg−1. The hypertonic absorbate generated an osmotic pressure which created a fluid tension in the crypt lumen. This was monitored as a suction tension in colonic luminal gels of 45.3 ± 3 cmH2O with 2.5% gels and 725 ± 145 cmH2O with 10% gels. The caecum was unable to absorb fluid against a significant hydraulic resistance.Fluorescein isothiocyanate-labelled dextran (FITC dextran; molecular mass 10000 Da) accumulated within descending colonic crypt lumens by concentration polarization. Maximal accumulation at a depth of 20–40 μm below the mucosal surface was 5.68 ± 0.2-fold above control levels. Caecal crypts accumulated dextran to a maximum of 1.8 ± 0.17-fold above control levels.The relationship between crypt luminal tension and suction tension of the distal colon was also demonstrated using paraffin, which occluded the crypt lumens with microscopic droplets and completely inhibited fluid absorption from high resistance luminal gels.Reduction in dietary Na+ intake raised plasma aldosterone and the capacity of the distal colon to dehydrate against a high luminal hydraulic resistance. The caecum did not respond in this way to varied Na+ intake. PMID:9831727

  19. Influence of Large-scale Climate Modes on Atmospheric Rivers That Drive Regional Precipitation Extremes

    NASA Astrophysics Data System (ADS)

    Guan, B.; Molotch, N. P.; Waliser, D. E.; Fetzer, E. J.; Neiman, P. J.

    2014-12-01

    Atmospheric rivers (ARs) are narrow channels of enhanced meridional water vapor transport between the tropics and extratropics that drive precipitation extremes in the west coast areas of North America and other continents. The influence of large-scale climate modes on ARs is analyzed in terms of modulation on AR frequency and AR-related snow water equivalent (SWE) anomalies, with a focus on understanding the causes of the anomalously snowy winter season of 2010/2011 in California's Sierra Nevada. Mean SWE on 1 April 2011 was ~70% above normal averaged over 100 snow sensors. AR occurrence was anomalously high during the season, with 20 AR dates from November to March and 14 dates in the month of December 2010, compared to the mean occurrence of 9 dates per season. Most of the season's ARs occurred during negative phases of the Arctic Oscillation (AO) and the Pacific-North American (PNA) teleconnection pattern. Analysis of all winter ARs in California during water years 1998-2011 indicates more ARs occur during the negative phase of AO and PNA, with the increase between positive and negative phases being ~90% for AO, and ~50% for PNA. The circulation pattern associated with concurrent negative phases of AO and PNA, characterized by cyclonic anomalies centered northwest of California, provides a favorable dynamical condition for ARs. The analysis suggests that the massive Sierra Nevada snowpack during the 2010/2011 winter season is primarily related to anomalously high frequency of ARs favored by the joint phasing of -AO and -PNA, and that a secondary contribution is from increased snow accumulation during these ARs favored by colder air temperatures associated with -AO, -PNA and La Niña. The results have implications for subseasonal-to-seasonal predictability of AR activities and related weather and water extremes.

  20. Selection for Unequal Densities of Sigma70 Promoter-like Signalsin Different Regions of Large Bacterial Genomes

    SciTech Connect

    Huerta, Araceli M.; Francino, M. Pilar; Morett, Enrique; Collado-Vides, Julio

    2006-03-01

    distribution of promoter-like signals between regulatory and nonregulatory regions detected in large bacterial genomes confers a significant, although small, fitness advantage. This study paves the way for further identification of the specific types of selective constraints that affect the organization of regulatory regions and the overall distribution of promoter-like signals through more detailed comparative analyses among closely-related bacterial genomes.

  1. Eradication of large tumors expressing human papillomavirus E7 protein by therapeutic vaccination with E7 fused to the extra domain a from fibronectin.

    PubMed

    Mansilla, Cristina; Berraondo, Pedro; Durantez, Maika; Martínez, Marta; Casares, Noelia; Arribillaga, Laura; Rudilla, Francesc; Fioravanti, Jessica; Lozano, Teresa; Villanueva, Lorea; Sarobe, Pablo; Borrás, Francisco; Leclerc, Claude; Prieto, Jesús; Lasarte, Juan José

    2012-08-01

    Cervical carcinoma is one of the most common cancers in women worldwide. It is well established that chronic infection of the genital tract by various mucosatropic human papillomavirus (HPV) types causes cervical cancer. Cellular immunity to E7 protein from HPV (HPVE7) has been associated with clinical and cytologic resolution of HPV-induced lesions. Thus, we decided to test if targeting of HPVE7 to dendritic cells using a fusion protein containing the extra domain A (EDA) from fibronectin, a natural ligand for TLR4, and HPVE7 (EDA-HPVE7) might be an efficient vaccine for the treatment of cervical carcinoma. We found that EDA-HPVE7 fusion protein was efficiently captured by bone marrow derived dendritic cells in vitro and induced their maturation, with the upregulation of maturation markers and the production of IL-12. Immunization of mice with EDA-HPVE7 fusion protein induced antitumor CD8(+) T cell responses in the absence of additional adjuvants. Repeated intratumoral administration of EDA-HPVE7 in saline was able to cure established TC-1 tumors of 5-7 mm in diameter. More importantly, intravenous injection with EDA-HPVE7 in combination with the TLR ligand polyinosinic-polycytidylic acid (pIC), or with low doses of cyclophosphamide and the TLR9 ligand CpG-B complexed in cationic lipids, were able to eradicate large established TC-1 tumors (1.2 cm in diameter). Thus, therapeutic vaccination with EDA-HPVE7 fusion protein may be effective in the treatment of human cervical carcinoma. PMID:21898393

  2. Mapping asbestos-cement roofing with hyperspectral remote sensing over a large mountain region of the Italian Western Alps.

    PubMed

    Frassy, Federico; Candiani, Gabriele; Rusmini, Marco; Maianti, Pieralberto; Marchesi, Andrea; Rota Nodari, Francesco; Dalla Via, Giorgio; Albonico, Carlo; Gianinetto, Marco

    2014-01-01

    The World Health Organization estimates that 100 thousand people in the world die every year from asbestos-related cancers and more than 300 thousand European citizens are expected to die from asbestos-related mesothelioma by 2030. Both the European and the Italian legislations have banned the manufacture, importation, processing and distribution in commerce of asbestos-containing products and have recommended action plans for the safe removal of asbestos from public and private buildings. This paper describes the quantitative mapping of asbestos-cement covers over a large mountainous region of Italian Western Alps using the Multispectral Infrared and Visible Imaging Spectrometer sensor. A very large data set made up of 61 airborne transect strips covering 3263 km2 were processed to support the identification of buildings with asbestos-cement roofing, promoted by the Valle d'Aosta Autonomous Region with the support of the Regional Environmental Protection Agency. Results showed an overall mapping accuracy of 80%, in terms of asbestos-cement surface detected. The influence of topography on the classification's accuracy suggested that even in high relief landscapes, the spatial resolution of data is the major source of errors and the smaller asbestos-cement covers were not detected or misclassified.

  3. The Large-Scale Oscillations Influence Over the Interdecadal Climate Variability in Mexico's Central Region

    NASA Astrophysics Data System (ADS)

    Jofre, R.; Brito-Castillo, L.; Tereshchenko, I.; Atmospheric Sciences Climatology Climate Variability

    2013-05-01

    Climate in the highlands of Mexico displays high variability due to its complex terrain and elevation. The knowledge to elucidate the principal forcings of these variations can be useful for forecasting annual and seasonal temperature and precipitation over this area. Due to its complexity a small area in the highlands was delimited with defined physical boundaries, encompassing several states of Mexico. The study area was defined as Mexico's Central Region (MCR), which is located between 19.5 ° - 22.5 ° N and 98.5 ° - 104 ° W. Most of this area overlies the plateau of Anahuac, whose physical boundaries extend to the north from the "Sierras Transversales" (composed by the "Sierra de Zacatecas", the "Sierra de la "Breña" and the "Sierra de San Luis") to the "Eje Neovolcánico" to the south; east and west boundaries are confined by the "Sierra Madre Oriental" and the "Sierra Madre Occidental", respectively. Daily data of maximum and minimum temperature and precipitation series from a total of 112 weather stations were obtained from CLICOM and ERICIII databases. Several climatic indices with average periods of phase oscillations greater than five years, such as the Pacific Decadal Oscillation (PDOI), the Atlantic Multidecadal Oscillation (AMOI), The Arctic Oscillation (AOI), the North Atlantic Oscillation (NAOI), and Aleutian Low Pressure (ALPI) on a monthly basis for all series, except the ALPI series which is on annual rate, were also used in this study. Indices data were obtained from the web site http://www.cicimar.ipn.mx/oacis/Indices_Climaticos.php/. The common period of all series was 1961-2000. We applied Principal Component Analysis to precipitation and temperature series to identify the principal modes of variation of the series. The first mode explained more than 68% of the variance in the original series and corresponds to annual variations. Contour maps were useful to elucidate that temperature variations are highly correlated with the terrain

  4. Large-scale analysis reveals a functional single-nucleotide polymorphism in the 5′-flanking region of PRDM16 gene associated with lean body mass

    PubMed Central

    Urano, Tomohiko; Shiraki, Masataka; Sasaki, Noriko; Ouchi, Yasuyoshi; Inoue, Satoshi

    2014-01-01

    Genetic factors are important for the development of sarcopenia, a geriatric disorder characterized by low lean body mass. The aim of this study was to search for novel genes that regulate lean body mass in humans. We performed a large-scale search for 250K single-nucleotide polymorphisms (SNPs) associated with bone mineral density (BMD) using SNP arrays in 1081 Japanese postmenopausal women. We focused on an SNP (rs12409277) located in the 5′-flanking region of the PRDM16 (PRD1-BF-1-RIZ1 homologous domain containing protein 16) gene that showed a significant P value in our screening. We demonstrated that PRDM16 gene polymorphisms were significantly associated with total body BMD in 1081 postmenopausal Japanese women. The rs12409277 SNP affected the transcriptional activity of PRDM16. The subjects with one or two minor allele(s) had a higher lean body mass than the subjects with two major alleles. Genetic analyses uncovered the importance of the PRDM16 gene in the regulation of lean body mass. PMID:24863034

  5. MAGNETIC FIELDS IN LARGE-DIAMETER H II REGIONS REVEALED BY THE FARADAY ROTATION OF COMPACT EXTRAGALACTIC RADIO SOURCES

    SciTech Connect

    Harvey-Smith, L.; Madsen, G. J.; Gaensler, B. M.

    2011-08-01

    We present a study of the line-of-sight magnetic fields in five large-diameter Galactic H II regions. Using the Faraday rotation of background polarized radio sources, as well as dust-corrected H{alpha} surface brightness as a probe of electron density, we estimated the strength and orientation of the magnetic field along 93 individual sight lines through the H II regions. Each of the H II regions displayed a coherent magnetic field. The magnetic field strength (line-of-sight component) in the regions ranges from 2 to 6 {mu}G, which is similar to the typical magnetic field strength in the diffuse interstellar medium. We investigated the relationship between magnetic field strength and electron density in the five H II regions. The slope of magnetic field versus density in the low-density regime (0.8 cm{sup -3} < n{sub e} <30 cm{sup -3}) is very slightly above zero. We also calculated the ratio of thermal to magnetic pressure, {beta}{sub th}, for each data point, which fell in the range 1.01 < {beta}{sub th} < 25. Finally, we studied the orientation of the magnetic field in the solar neighborhood (d < 1.1 kpc) using our data from five H II regions along with existing measurements of the line-of-sight magnetic field strength from polarized pulsars whose distances have been determined from their annual parallax. We identify a net direction for the magnetic field in the solar neighborhood, but find no evidence for a preferred vertical direction of the magnetic field above or below the Galactic plane.

  6. A see-saw of pre-Columbian boom regions in southern Peru, determined by large-scale circulation changes

    NASA Astrophysics Data System (ADS)

    Mächtle, B.; Schittek, K.; Forbriger, M.; Schäbitz, F.; Eitel, B.

    2012-04-01

    Environmental changes and cultural transitions during several periods of Peruvian history show a strong coincidence between humid and dry climatic oscillations and the rise and decline of cultures. It is noteworthy, that alternating periods of geo-ecological fragility and stability occurred in time and space between the coastal Nasca region (14.5° S) and the high Andean northern Titicaca basin, just a few hundred kilometers to the east. Based on a multi-proxy palynological and sedimentological approach to reconstruct palaeoenvironmental changes, we found that the Nasca region received a maximum of precipitation during the archaeological boom times of the Early Horizon and the Early Intermediate Period (800 BC - 650 AD, Paracas and Nasca cultures) as well as during the late intermediate period (1150-1450 AD), whereas, in contrast, the Titicaca region further to the south-east experienced drought and cultural depression during that times. During the Middle Horizon (650 - 1150 AD), the Tiwanaku agronomy and culture boomed in the Titicaca region and expanded to the west, contemporaneous with a raised lake level and more humid conditions. In the Nasca region, runoff for irrigation purposes was reduced and less reliable due to drought. Considering a coincidence between environmental and cultural changes, we state that success and decline of civilizations were controlled by hydrological oscillations, triggering fertility as well as a critical loss of natural resources. In response to spatial changing resources, cultural foci were shifted. Therefore, the success of pre-Columbian civilizations was closely coupled to areas of geo-ecological favorability, which were directly controlled by distinct regional impacts of large-scale circulation mechanisms, including El Niño - Southern Oscillation (ENSO). Changes in the position of the intertropical convergence zone (ITCZ) and the Bolivian anticyclone determined meridional shifts in moisture transport across the Andes, which

  7. Method for identification of rigid domains and hinge residues in proteins based on exhaustive enumeration.

    PubMed

    Sim, Jaehyun; Sim, Jun; Park, Eunsung; Lee, Julian

    2015-06-01

    Many proteins undergo large-scale motions where relatively rigid domains move against each other. The identification of rigid domains, as well as the hinge residues important for their relative movements, is important for various applications including flexible docking simulations. In this work, we develop a method for protein rigid domain identification based on an exhaustive enumeration of maximal rigid domains, the rigid domains not fully contained within other domains. The computation is performed by mapping the problem to that of finding maximal cliques in a graph. A minimal set of rigid domains are then selected, which cover most of the protein with minimal overlap. In contrast to the results of existing methods that partition a protein into non-overlapping domains using approximate algorithms, the rigid domains obtained from exact enumeration naturally contain overlapping regions, which correspond to the hinges of the inter-domain bending motion. The performance of the algorithm is demonstrated on several proteins.

  8. Daily precipitation analysis using the CLARIS-LPB models over hydrological basins and climate regions within the CORDEX South America domain

    NASA Astrophysics Data System (ADS)

    Remedio, A. C.; Carril, A. F.; Jacob, D.; Menendez, C.; Pfeifer, S.; Cavalcanti, I. F.; Solman, S.; Da Rocha, R.; Mourao, C. F.; Samuelsson, P.; Sanchez, E.; Li, L.; Berbery, E.; Marengo, J.

    2013-05-01

    Multiyear simulations of the South America daily precipitation are derived by six regional models and a stretched-grid general circulation model within the framework of the EU FP7 CLARIS-LPB Project. The different institution and models which participated in the coordinated project are SMHI RCA, MPI-M REMO, UCLM PROMES, USP RegCM3, CIMA MM5, IPSL LMDZ and INPE ETA. The setup of the different models attempts to follow the WCRP CORDEX protocol closely such as the horizontal resolution of about 50 km and size of the domain, which covers the whole continent of South America. These models have been integrated for the period of 1989-2008 using the ECMWF ERA-Interim reanalysis as initial and lateral boundary conditions. The daily precipitation observational dataset used is from the NOAA Climate Prediction Center (CPC) with a resolution of 0.5 degree. The precipitation estimates from the high resolution TRMM are also used to ascertain observational uncertainties. The skill of the models and ensemble are evaluated using the probabilistic distribution function over twelve regions with different hydrological and climate characteristics. The seven regions representing hydrological basins are South Amazon, Northeast Brazil, South Atlantic Convergence Zone, Paraguay, Upper Parana, Lower Parana and Uruguay. The other five regions have tropical humid, tropical wet-dry, dry semi-arid, subtropical humid and temperate oceanic climate based on the Koeppen-Trewartha classification. The regions are established to evaluate the simulated daily precipitation at areas of similar characteristics. The seasonal means and extreme indices based on percentile approach are also calculated The models have a relatively high skill in simulating the wintertime precipitation at the different regions. During summer, when the precipitation is mainly driven by convective activity, most of the models have relatively low skill. Attempts are made to explain the different biases among each region due to the

  9. An Approach to Automatic Detection and Hazard Risk Assessment of Large Protruding Rocks in Densely Forested Hilly Region

    NASA Astrophysics Data System (ADS)

    Chhatkuli, S.; Kawamura, K.; Manno, K.; Satoh, T.; Tachibana, K.

    2016-06-01

    Rock-fall along highways or railways presents one of the major threats to transportation and human safety. So far, the only feasible way to detect the locations of such protruding rocks located in the densely forested hilly region is by physically visiting the site and assessing the situation. Highways or railways are stretched to hundreds of kilometres; hence, this traditional approach of determining rock-fall risk zones is not practical to assess the safety throughout the highways or railways. In this research, we have utilized a state-of-the-art airborne LiDAR technology and derived a workflow to automatically detect protruding rocks in densely forested hilly regions and analysed the level of hazard risks they pose. Moreover, we also performed a 3D dynamic simulation of rock-fall to envisage the event. We validated that our proposed technique could automatically detect most of the large protruding rocks in the densely forested hilly region. Automatic extraction of protruding rocks and proper risk zoning could be used to identify the most crucial place that needs the proper protection measures. Hence, the proposed technique would provide an invaluable support for the management and planning of highways and railways safety, especially in the forested hilly region.

  10. A large, dominant pedigree of atrioventricular septal defect (AVSD): Exclusion from the Down syndrome critical region on chromosome 21

    SciTech Connect

    Wilson, L.; Curtis, A.; Stephenson, A.; Goodship, J.; Burn, J. ); Korenberg, J.R.; Schipper, R.D. ); Allan, L. ); Chenevix-Trench, G. )

    1993-12-01

    The authors describe a large pedigree of individuals with autosomal dominant atrioventricular septal defect (AVSD). The pedigree includes affected individuals and individuals who have transmitted the defect but are not clinically affected. AVSDs are a rare congenital heart malformation that occurs as only 2.8% of isolated cardiac lesions. They are the predominant heart defect in children with Down syndrome, making chromosome 21 a candidate for genes involved in atrioventricular septal development. The authors have carried out a linkage study in the pedigree by using 10 simple-sequence polymorphisms from chromosome 21. Multipoint linkage analysis gives lod scores of less than [minus]2 for the region of trisomy 21 associated with heart defects, which excludes a locus within this region as the cause of the defect in this family. 34 refs., 5 figs.

  11. Lateral supracerebellar infratentorial approach for microsurgical resection of large midline pineal region tumors: techniques to expand the operative corridor.

    PubMed

    Kulwin, Charles; Matsushima, Ken; Malekpour, Mahdi; Cohen-Gadol, Aaron A

    2016-01-01

    Pineal region tumors pose certain challenges in regard to their resection: a deep surgical field, associated critical surrounding neurovascular structures, and narrow operative working corridor due to obstruction by the apex of the culmen. The authors describe a lateral supracerebellar infratentorial approach that was successfully used in the treatment of 10 large (> 3 cm) midline pineal region tumors. The patients were placed in a modified lateral decubitus position. A small lateral suboccipital craniotomy exposed the transverse sinus. Tentorial retraction sutures were used to gently rotate and elevate the transverse sinus to expand the lateral supracerebellar operative corridor. This approach placed only unilateral normal structures at risk and minimized vermian venous sacrifice. The surgeon achieved generous exposure of the caudal midline mesencephalon through a "cross-court" oblique trajectory, while avoiding excessive retraction on the culmen. All patients underwent the lateral approach with no approach-related complication. The final pathological diagnoses were consistent with meningioma in 3 cases, pilocytic astrocytoma in 3 cases, intermediate grade pineal region tumor in 2 cases, and pineoblastoma in 2 cases. The entire extent of these tumors was readily reachable through the lateral supracerebellar route. Gross-total resection was achieved in 8 (80%) of the 10 cases; in 2 cases (20%) near-total resection was performed due to adherence of these tumors to deep diencephalic veins. Large midline pineal region tumors can be removed through a unilateral paramedian suboccipital craniotomy. This approach is simple, may spare some of the midline vermian bridging veins, and may be potentially less invasive and more efficient. PMID:26275000

  12. Nonhomologous recombination between the large unassigned region of the male and female mitochondrial genomes in the mussel, Mytilus trossulus.

    PubMed

    Rawson, Paul D

    2005-12-01

    Doubly uniparental inheritance of mtDNA (DUI) is commonly observed in several genera of bivalves. Under DUI, female offspring inherit mtDNA from their mothers, while male offspring inherit mtDNA from both parents but preferentially transmit the paternally inherited mtDNA to their sons. Several studies have shown that the female- and male-specific mtDNA lineages in blue mussels, Mytilus spp., vary by upward of 20% at the nucleotide level. In addition to high levels of nucleotide substitution, the present study observed substantial gender-based length polymorphism in the presumptive mitochondrial control region (=large unassigned region; LUR) of North American M. trossulus. In this species, female lineage LUR haplotypes are over 2 kb larger than male lineage LUR haplotypes. Analysis of sequence data for these length variants indicates that the F LUR haplotypes of North American M. trossulus contain sequences similar to the F lineage control region in the congeners M. edulis and M. galloprovincialis. Relative to the F LUR in the latter two species, however, the F lineage LUR haplotypes in M. trossulus contain two large sequence insertions, each nearly 1 kb in size. One of these insertions has high sequence similarity to the male lineage LUR of M. trossulus. The tandem arrangement of F and M control region sequences in the F lineage LUR of M. trossulus is most likely the result of nonhomologous recombination between the male and the female mitochondrial genomes in M. trossulus, a finding that has important implications regarding the transmission and evolution of blue mussel mitochondrial genomes.

  13. Lateral supracerebellar infratentorial approach for microsurgical resection of large midline pineal region tumors: techniques to expand the operative corridor.

    PubMed

    Kulwin, Charles; Matsushima, Ken; Malekpour, Mahdi; Cohen-Gadol, Aaron A

    2016-01-01

    Pineal region tumors pose certain challenges in regard to their resection: a deep surgical field, associated critical surrounding neurovascular structures, and narrow operative working corridor due to obstruction by the apex of the culmen. The authors describe a lateral supracerebellar infratentorial approach that was successfully used in the treatment of 10 large (> 3 cm) midline pineal region tumors. The patients were placed in a modified lateral decubitus position. A small lateral suboccipital craniotomy exposed the transverse sinus. Tentorial retraction sutures were used to gently rotate and elevate the transverse sinus to expand the lateral supracerebellar operative corridor. This approach placed only unilateral normal structures at risk and minimized vermian venous sacrifice. The surgeon achieved generous exposure of the caudal midline mesencephalon through a "cross-court" oblique trajectory, while avoiding excessive retraction on the culmen. All patients underwent the lateral approach with no approach-related complication. The final pathological diagnoses were consistent with meningioma in 3 cases, pilocytic astrocytoma in 3 cases, intermediate grade pineal region tumor in 2 cases, and pineoblastoma in 2 cases. The entire extent of these tumors was readily reachable through the lateral supracerebellar route. Gross-total resection was achieved in 8 (80%) of the 10 cases; in 2 cases (20%) near-total resection was performed due to adherence of these tumors to deep diencephalic veins. Large midline pineal region tumors can be removed through a unilateral paramedian suboccipital craniotomy. This approach is simple, may spare some of the midline vermian bridging veins, and may be potentially less invasive and more efficient.

  14. Validation and sensitivity study for the MedCORDEX domain and the Carpathian Region using RegCM4.3

    NASA Astrophysics Data System (ADS)

    Pongracz, Rita; Pieczka, Ildiko; Andre, Karolina; Bartholy, Judit

    2015-04-01

    In the framework of the Med-CORDEX international initiative our research group is participating with the specific aim of contributing to the complex regional climate modelling database with RegCM4.3 experiments at 50 km horizontal resolution using the mosaic-type subgridding option in order to take into account subgrid processes. For this purpose, we used ERA-Interim data (1981-2010) and HadGEM2 global model outputs (1951-2005) as initial and lateral boundary conditions (ICBC) for the entire MED-44 CORDEX area covering the extended Mediterranean region of Europe. The 50-km resolution RegCM-outputs serve as an ICBC input for further downscaling using 10 km as a horizontal resolution for a smaller domain covering Central Europe with special focus on the Carpathian Region. In order to quantify the impact of the use of different parameterization schemes on regional climate model outputs, hindcast experiments are completed applying the RegCM4.3 model to the Carpathian Region and its surroundings at 10 km horizontal resolution with three different cumulus convection schemes (i.e., Kuo, Emanuel, and Grell schemes with different closure methods). Besides, sensitivity of outputs for subgrid-scale processes is also studied by activating the subgrid Biosphere-Atmosphere Transfer Scheme (BATS) model within other RegCM experiments. RegCM simulation results are sensitive to the driving data since the completed experiments with ERA-Interim and HadGEM2-driven 50-km outputs as ICBC result in different bias patterns. However, when the same driving data are used with different specific set-ups, the simulation results look quite similar. To some extent RegCM is able to reduce the errors inherited from the global datasets. Our validation results for temperature and precipitation suggest that for the Carpathian Region the overall best performance is achieved when using the mixed Grell-Emanuel scheme together with Fritsch & Chappell closure. Moreover, turning the subgrid model on

  15. Transvection in the Drosophila Abd-B domain: extensive upstream sequences are involved in anchoring distant cis-regulatory regions to the promoter.

    PubMed Central

    Sipos, L; Mihály, J; Karch, F; Schedl, P; Gausz, J; Gyurkovics, H

    1998-01-01

    The Abd-B gene, one of the three homeotic genes in the Drosophila bithorax complex (BX-C), is required for the proper identity of the fifth through the eighth abdominal segments (corresponding to parasegments 10-14) of the fruitfly. The morphological difference between these four segments is due to the differential expression of Abd-B, which is achieved by the action of the parasegment-specific cis-regulatory regions infra-abdominal-5 (iab-5), -6, -7 and -8. The dominant gain-of-function mutation Frontabdominal-7 (Fab-7) removes a boundary separating two of these cis-regulatory regions, iab-6 and iab-7. As a consequence of the Fab-7 deletion, the parasegment 12- (PS12-) specific iab-7 is ectopically activated in PS11. This results in the transformation of the sixth abdominal segment (A6) into the seventh (A7) in Fab-7 flies. Here we report that point mutations of the Abd-B gene in trans suppress the Fab-7 phenotype in a pairing-dependent manner and thus represent a type of transvection. We show that the observed suppression is the result of trans-regulation of the defective Abd-B gene by the ectopically activated iab-7. Unlike previously demonstrated cases of trans-regulation in the Abd-B locus, trans-suppression of Fab-7 is sensitive to heterozygosity for chromosomal rearrangements that disturb homologous pairing at the nearby Ubx locus. However, in contrast to Ubx, the transvection we observed in the Abd-B locus is insensitive to the allelic status of zeste. Analysis of different deletion alleles of Abd-B that enhance trans-regulation suggests that an extensive upstream region, different from the sequences required for transcription initiation, mediates interactions between the iab cis-regulatory regions and the proximal Abd-B promoter. Moreover, we find that the amount of DNA deleted in the upstream region is roughly proportional to the strength of trans-interaction, suggesting that this region consists of numerous discrete elements that cooperate in tethering

  16. From gas to stars in energetic environments: dense gas clumps in the 30 Doradus region within the Large Magellanic Cloud

    SciTech Connect

    Anderson, Crystal N.; Meier, David S.; Ott, Jürgen; Hughes, Annie; Wong, Tony; Looney, Leslie; Henkel, Christian; Chen, Rosie; Indebetouw, Remy; Muller, Erik; Pineda, Jorge L.; Seale, Jonathan

    2014-09-20

    We present parsec-scale interferometric maps of HCN(1-0) and HCO{sup +}(1-0) emission from dense gas in the star-forming region 30 Doradus, obtained using the Australia Telescope Compact Array. This extreme star-forming region, located in the Large Magellanic Cloud (LMC), is characterized by a very intense ultraviolet ionizing radiation field and sub-solar metallicity, both of which are expected to impact molecular cloud structure. We detect 13 bright, dense clumps within the 30 Doradus-10 giant molecular cloud. Some of the clumps are aligned along a filamentary structure with a characteristic spacing that is consistent with formation via varicose fluid instability. Our analysis shows that the filament is gravitationally unstable and collapsing to form stars. There is a good correlation between HCO{sup +} emission in the filament and signatures of recent star formation activity including H{sub 2}O masers and young stellar objects (YSOs). YSOs seem to continue along the same direction of the filament toward the massive compact star cluster R136 in the southwest. We present detailed comparisons of clump properties (masses, linewidths, and sizes) in 30Dor-10 to those in other star forming regions of the LMC (N159, N113, N105, and N44). Our analysis shows that the 30Dor-10 clumps have similar masses but wider linewidths and similar HCN/HCO{sup +} (1-0) line ratios as clumps detected in other LMC star-forming regions. Our results suggest that the dense molecular gas clumps in the interior of 30Dor-10 are well shielded against the intense ionizing field that is present in the 30 Doradus region.

  17. Inhalational anesthetics disrupt postsynaptic density protein-95, Drosophila disc large tumor suppressor, and zonula occludens-1 domain protein interactions critical to action of several excitatory receptor channels related to anesthesia

    PubMed Central

    Tao, Feng; Chen, Qiang; Sato, Yuko; Skinner, John; Tang, Pei; Johns, Roger A.

    2015-01-01

    Background We have shown previously that inhaled anesthetics disrupt the interaction between the second postsynaptic density protein-95, Drosophila disc large tumor suppressor, and zonula occludens-1 (PDZ) domain of postsynaptic density protein-95 (PSD-95) and the C-terminus of N-methyl-D-aspartate receptor subunits NR2A and NR2B. Our data indicate that PDZ domains may serve as a molecular target for inhaled anesthetics. However, the underlying molecular mechanisms remain to be illustrated. Methods Glutathione S-transferase pull-down assay, co-immunoprecipitation and yeast two-hybrid analysis were used to assess PDZ domain-mediated protein-protein interactions in different conditions. Nuclear magnetic resonance spectroscopy was used to investigate isoflurane-induced chemical shift changes in the PDZ1–3 domains of PSD-95. A surface plasmon resonance-based BIAcore assay was used to examine the ability of isoflurane to inhibit the PDZ domain-mediated protein-protein interactions in real time. Results Halothane and isoflurane dose dependently inhibited PDZ domain-mediated interactions between PSD-95 and Shaker-type potassium channel Kv1.4 and between α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor subunit GluA2 and its interacting proteins— glutamate receptor interacting protein or protein interacting with c kinase 1. However, halothane and isoflurane had no effect on PDZ domain-mediated interactions between γ-aminobutyric acid, type B receptor and its interacting proteins. The inhaled anesthetic isoflurane mostly affected the residues close to or in the peptide binding groove of PSD-95 PDZ1 and PDZ2 (especially PDZ2), while barely affecting the peptide binding groove of PSD-95 PDZ3. Conclusion These results suggest that inhaled anesthetics interfere with PDZ domain-mediated protein-protein interactions at several receptors important to neuronal excitation, anesthesia and pain processing. PMID:25654436

  18. Immunoglobulin Heavy Chain Variable Region and Major Histocompatibility Region Genes Are Linked to Induced Graves' Disease in Females From Two Very Large Families of Recombinant Inbred Mice

    PubMed Central

    Aliesky, Holly; Banuelos, Bianca; Magana, Jessica; Williams, Robert W.; Rapoport, Basil

    2014-01-01

    Graves' hyperthyroidism is caused by antibodies to the TSH receptor (TSHR) that mimic thyroid stimulation by TSH. Stimulating TSHR antibodies and hyperthyroidism can be induced by immunizing mice with adenovirus expressing the human TSHR A-subunit. Prior analysis of induced Graves' disease in small families of recombinant inbred (RI) female mice demonstrated strong genetic control but did not resolve trait loci for TSHR antibodies or elevated serum T4. We investigated the genetic basis for induced Graves' disease in female mice of two large RI families and combined data with earlier findings to provide phenotypes for 178 genotypes. TSHR antibodies measured by inhibition of TSH binding to its receptor were highly significantly linked in the BXD set to the major histocompatibility region (chromosome 17), consistent with observations in 3 other RI families. In the LXS family, we detected linkage between T4 levels after TSHR-adenovirus immunization and the Ig heavy chain variable region (Igvh, chromosome 12). This observation is a key finding because components of the antigen binding region of Igs determine antibody specificity and have been previously linked to induced thyroid-stimulating antibodies. Data from the LXS family provide the first evidence in mice of a direct link between induced hyperthyroidism and Igvh genes. A role for major histocompatibility genes has now been established for genetic susceptibility to Graves' disease in both humans and mice. Future studies using arrays incorporating variation in the complex human Ig gene locus will be necessary to determine whether Igvh genes are also linked to Graves' disease in humans. PMID:25051451

  19. A region of the N-terminal domain of meningococcal factor H-binding protein that elicits bactericidal antibody across antigenic variant groups.

    PubMed

    Beernink, Peter T; LoPasso, Carla; Angiolillo, Antonella; Felici, Franco; Granoff, Dan

    2009-05-01

    Meningococcal factor H-binding protein (fHbp) is a promising vaccine antigen. Previous studies described three fHbp antigenic variant groups and identified amino acid residues between 100 and 255 as important targets of variant-specific bactericidal antibodies. We investigated residues affecting expression of an epitope recognized by a murine IgG2a anti-fHbp mAb, designated JAR 4, which cross-reacted with fHbps in variant group 1 or 2 (95% of strains), and elicited human complement-mediated, cooperative bactericidal activity with other non-bactericidal anti-fHbp mAbs with epitopes involving residues between 121 and 216. From filamentous bacteriophage libraries containing random peptides that were recognized by JAR 4, we identified a consensus tripeptide, DHK that matched residues 25-27 in the N-terminal domain of fHbp. Since DHK was present in both JAR 4-reactive and non-reactive fHbps, the tripeptide was necessary but not sufficient for reactivity. Based on site-directed mutagenesis studies, the JAR 4 epitope could either be knocked out of a reactive variant 1 fHbp, or introduced into a non-reactive variant 3 protein. Collectively, the data indicated that the JAR 4 epitope was discontinuous and involved DHK residues beginning at position 25; YGN residues beginning at position 57; and a KDN tripeptide that was present in variant 3 proteins beginning at position 67 that negatively affected expression of the epitope. Thus, the region of fHbp encompassing residues 25-59 in the N-terminal domain is important for eliciting antibodies that can cooperate with other anti-fHbp antibodies for cross-reactive bactericidal activity against strains expressing fHbp from different antigenic variant groups.

  20. The Atomic Structure of the HIV-1 gp41 Transmembrane Domain and Its Connection to the Immunogenic Membrane-proximal External Region*♦

    PubMed Central

    Apellániz, Beatriz; Rujas, Edurne; Serrano, Soraya; Morante, Koldo; Tsumoto, Kouhei; Caaveiro, Jose M. M.; Jiménez, M. Ángeles; Nieva, José L.

    2015-01-01

    The membrane-proximal external region (MPER) C-terminal segment and the transmembrane domain (TMD) of gp41 are involved in HIV-1 envelope glycoprotein-mediated fusion and modulation of immune responses during viral infection. However, the atomic structure of this functional region remains unsolved. Here, based on the high resolution NMR data obtained for peptides spanning the C-terminal segment of MPER and the TMD, we report two main findings: (i) the conformational variability of the TMD helix at a membrane-buried position; and (ii) the existence of an uninterrupted α-helix spanning MPER and the N-terminal region of the TMD. Thus, our structural data provide evidence for the bipartite organization of TMD predicted by previous molecular dynamics simulations and functional studies, but they do not support the breaking of the helix at Lys-683, as was suggested by some models to mark the initiation of the TMD anchor. Antibody binding energetics examined with isothermal titration calorimetry and humoral responses elicited in rabbits by peptide-based vaccines further support the relevance of a continuous MPER-TMD helix for immune recognition. We conclude that the transmembrane anchor of HIV-1 envelope is composed of two distinct subdomains: 1) an immunogenic helix at the N terminus also involved in promoting membrane fusion; and 2) an immunosuppressive helix at the C terminus, which might also contribute to the late stages of the fusion process. The unprecedented high resolution structural data reported here may guide future vaccine and inhibitor developments. PMID:25787074