Science.gov

Sample records for large regional domain

  1. Regional Climate Model Sensitivity to Domain Size

    NASA Astrophysics Data System (ADS)

    Leduc, M.; Laprise, R.

    2006-05-01

    Regional Climate Models are increasingly used to add small-scale features that are not present in their lateral boundary conditions (LBCs). It is well known that the limited area over which a model integrates must be large enough to allow the full development of small scales features (Jones et al., 1995). On the other hand, integrations on very large domains have shown important departures from the driving data, unless large-scale nudging is applied (e.g., Castro and Pielke, 2005). Here the effects of domain size on the development of small-scales are examined using the "Big-Brother" approach developed by Denis et al. (2002). This method consists of generating a high-resolution simulation over a large domain (the Big-Brother). The next step is to degrade this dataset with a low-pass filter based on discrete cosine transform (DCT; Denis et al., 2002) to emulate coarse-resolution LBCs that are usually taken from GCMs or reanalyses. A second simulation (the Little-Brother) is driven by the coarse-resolution LBCs and generates its own small-scale features inside the new smaller domain. Nested and added scales of the Little- Brother can then be compared with the Big-Brother (unfiltered) ones by using the DCT-filter again. Three February months (1990,1991 and 1992) were integrated over a continental grid (Big-Brother: 196x196 gridpoints) with a spatial resolution of 45 km covering almost the entire North-America. After filtering, this dataset is used to drive five simulations with varying domain size (48x48, 72x72, 96x96, 120x120 and 144x144) centred on the same geographic location; all other parameters are kept constant. Monthly statistics of the five Little-Brothers are compared with the virtual reference (Big-Brother) over the common domain (28x28) corresponding to the smallest Little-Brother but without its sponge zone. Results show that temporal correlation of large-scale events increases when the domain size is reduced from 144x144 to 48x48. For the same domain

  2. Large domain motions in Ago protein controlled by the guide DNA-strand seed region determine the Ago-DNA-mRNA complex recognition process.

    PubMed

    Xia, Zhen; Huynh, Tien; Ren, Pengyu; Zhou, Ruhong

    2013-01-01

    The recognition mechanism and cleavage activity of argonaute (Ago), miRNA, and mRNA complexes are the core processes to the small non-coding RNA world. The 5' nucleation at the 'seed' region (position 2-8) of miRNA was believed to play a significant role in guiding the recognition of target mRNAs to the given miRNA family. In this paper, we have performed all-atom molecular dynamics simulations of the related and recently revealed Ago-DNA:mRNA ternary complexes to study the dynamics of the guide-target recognition and the effect of mutations by introducing "damaging" C·C mismatches at different positions in the seed region of the DNA-RNA duplex. Our simulations show that the A-form-like helix duplex gradually distorts as the number of seed mismatches increases and the complex can survive no more than two such mismatches. Severe distortions of the guide-target heteroduplex are observed in the ruinous 4-sites mismatch mutant, which give rise to a bending motion of the PAZ domain along the L1/L2 "hinge-like" connection segment, resulting in the opening of the nucleic-acid-binding channel. These long-range interactions between the seed region and PAZ domain, moderated by the L1/L2 segments, reveal the central role of the seed region in the guide-target strands recognition: it not only determines the guide-target heteroduplex's nucleation and propagation, but also regulates the dynamic motions of Ago domains around the nucleic-acid-binding channel.

  3. 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.

    PubMed

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

    2012-03-02

    Thaumatin, an intensely sweet-tasting plant protein, elicits a sweet taste at 50 nM. Although the sweetness remains when thaumatin is heated at 80 °C for 4h 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 1.0Å. Comparison to the crystal structure of thaumatin at pH 7.3 and 7.0 revealed the root-mean square deviation value of a Cα 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 β-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. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. 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

  5. Domain regulation of imprinting cluster in Kip2/Lit1 subdomain on mouse chromosome 7F4/F5: large-scale DNA methylation analysis reveals that DMR-Lit1 is a putative imprinting control region.

    PubMed

    Yatsuki, Hitomi; Joh, Keiichiro; Higashimoto, Ken; Soejima, Hidenobu; Arai, Yuji; Wang, Youdong; Hatada, Izuho; Obata, Yayoi; Morisaki, Hiroko; Zhang, Zhongming; Nakagawachi, Tetsuji; Satoh, Yuji; Mukai, Tsunehiro

    2002-12-01

    Mouse chromosome 7F4/F5, where the imprinting domain is located, is syntenic to human 11p15.5, the locus for Beckwith-Wiedemann syndrome. The domain is thought to consist of the two subdomains Kip2 (p57(kip2))/Lit1 and Igf2/H19. Because DNA methylation is believed to be a key factor in genomic imprinting, we performed large-scale DNA methylation analysis to identify the cis-element crucial for the regulation of the Kip2/Lit1 subdomain. Ten CpG islands (CGIs) were found, and these were located at the promoter sites, upstream of genes, and within intergenic regions. Bisulphite sequencing revealed that CGIs 4, 5, 8, and 10 were differentially methylated regions (DMRs). CGIs 4, 5, and 10 were methylated paternally in somatic tissues but not in germ cells. CGI8 was methylated in oocyte and maternally in somatic tissues during development. Parental-specific DNase I hypersensitive sites (HSSs) were found near CGI8. These data indicate that CGI8, called DMR-Lit1, is not only the region for gametic methylation but might also be the imprinting control region (ICR) of the subdomain.

  6. Site-specific mutations in a loop region of the C-terminal domain of the large subunit of ribulose bisphosphate carboxylase/oxygenase that influence substrate partitioning.

    PubMed

    Gutteridge, S; Rhoades, D F; Herrmann, C

    1993-04-15

    Amino acids composing a flexible loop (loop 6) of the eight-stranded barrel domain of the L-subunit of Synechococcus ribulose bisphosphate carboxylase/oxygenase (EC 4.1.1.39) involved in reaction intermediate stabilization have been modified by site-specific mutagenesis. Changes at positions both distant and within the active site affect overall catalysis and substrate partitioning. Most significantly, replacement of the active site Lys (Lys-334) with Arg at the apex of the loop almost completely suppressed the carboxylase activity of the enzyme relative to oxygenation, with only a modest reduction in overall catalysis. Val-331 and Thr-342, more distant from the active site but with interacting side chains, were changed to larger and smaller residues with differential effects on both turnover and substrate partitioning. Substitution of the loop with the sequence found in more efficient carboxylases only increased partitioning marginally when accompanied by alterations in the C-terminal tail of the L-subunit that interacts with the loop. Generally, modifications to the loop composition also affected enediol formation, the first step of catalysis, suggesting that the geometry and hence flexibility of this segment affect more than just stabilization of the intermediates immediately following reaction with CO2 or O2.

  7. 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.

  8. Functional regions of the mouse interleukin-10 receptor cytoplasmic domain.

    PubMed Central

    Ho, A S; Wei, S H; Mui, A L; Miyajima, A; Moore, K W

    1995-01-01

    The functions of wild-type and mutant mouse interleukin-10 receptors (mIL-10R) expressed in murine Ba/F3 cells were studied. As observed previously, IL-10 stimulates proliferation of IL-10R-expressing Ba/F3 cells. Accumulation of viable cells in the proliferation assay is to a significant extent balanced by concomitant cell death. Moreover, growth in IL-10 also induces a previously unrecognized response, differentiation of the cells, as evidenced both by formation of large clusters of cells in cultures with IL-10 and by induction or enhancement of expression of several cell surface antigens, including CD32/16, CD2, LECAM-1 (v-selectin), and heat-stable antigen. Two distinct functional regions near the C terminus of the mIL-10R cytoplasmic domain which mediate proliferation were identified; one of these regions also mediates the differentiation response. A third region proximal to the transmembrane domain was identified; removal of this region renders the cell 10- to 100-fold more sensitive to IL-10 in the proliferation assay. In cells expressing both wild-type and mutant IL-10R, stimulation with IL-10 leads to tyrosine phosphorylation of the kinases JAK1 and TYK2 but not JAK2 or JAK3 under the conditions tested. PMID:7544437

  9. 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.

  10. 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.

  11. Large-scale regions of antimatter

    SciTech Connect

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

    2015-07-15

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

  12. 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.

  13. Multi-Robot FastSLAM for Large Domains

    DTIC Science & Technology

    2007-03-01

    LARGE DOMAINS THESIS Presented to the Faculty Department of Electrical and Computer Engineering Graduate School of Engineering and Management...Air Force Institute of Technology Air University Air Education and Training Command In Partial Fulfillment of the Requirements for the Degree of...in our offices and homes . Like humans, robots rely on sensor measurements to interpret theirs environment and subsequently build maps using the

  14. 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.

  15. Spectral domain of large nonsymmetric correlated Wishart matrices.

    PubMed

    Vinayak; Benet, Luis

    2014-10-01

    We study complex eigenvalues of the Wishart model for nonsymmetric correlation matrices. The model is defined for two statistically equivalent but different Gaussian real matrices, as C=AB(t)/T, where B(t) is the transpose of B and both matrices A and B are of dimensions N×T. If A and B are uncorrelated, or equivalently if C vanishes on average, it is known that at large matrix dimension the domain of the eigenvalues of C is a circle centered-at-origin and the eigenvalue density depends only on the radial distances. We consider actual correlation in A and B and derive a result for the contour describing the domain of the bulk of the eigenvalues of C in the limit of large N and T where the ratio N/T is finite. In particular, we show that the eigenvalue domain is sensitive to the correlations. For example, when C is diagonal on average with the same element c≠0, the contour is no longer a circle centered at origin but a shifted ellipse. In this case we explicitly derive a result for the spectral density which again depends only on the radial distances. For more general cases, we show that the contour depends on the symmetric and antisymmetric parts of the correlation matrix resulting from the ensemble-averaged C. If the correlation matrix is normal, then the contour depends only on its spectrum. We also provide numerics to justify our analytics.

  16. Spectral domain of large nonsymmetric correlated Wishart matrices

    NASA Astrophysics Data System (ADS)

    Vinayak, Benet, Luis

    2014-10-01

    We study complex eigenvalues of the Wishart model for nonsymmetric correlation matrices. The model is defined for two statistically equivalent but different Gaussian real matrices, as C =ABt/T, where Bt is the transpose of B and both matrices A and B are of dimensions N ×T. If A and B are uncorrelated, or equivalently if C vanishes on average, it is known that at large matrix dimension the domain of the eigenvalues of C is a circle centered-at-origin and the eigenvalue density depends only on the radial distances. We consider actual correlation in A and B and derive a result for the contour describing the domain of the bulk of the eigenvalues of C in the limit of large N and T where the ratio N /T is finite. In particular, we show that the eigenvalue domain is sensitive to the correlations. For example, when C is diagonal on average with the same element c ≠0, the contour is no longer a circle centered at origin but a shifted ellipse. In this case we explicitly derive a result for the spectral density which again depends only on the radial distances. For more general cases, we show that the contour depends on the symmetric and antisymmetric parts of the correlation matrix resulting from the ensemble-averaged C. If the correlation matrix is normal, then the contour depends only on its spectrum. We also provide numerics to justify our analytics.

  17. Identification of structural domains within the large subunit of herpes simplex virus ribonucleotide reductase.

    PubMed

    Conner, J; Cross, A; Murray, J; Marsden, H

    1994-12-01

    The large subunit (R1) of herpes simplex virus (HSV) ribonucleotide reductase is a bifunctional protein consisting of a unique N-terminal protein kinase domain and a ribonucleotide reductase domain. Previous studies showed that the two functional domains are linked by a protease sensitive site. Here we provide evidence for two subdomains, of 30K and 53K, within the reductase domain. The two fragments, which were produced by limited proteolysis and were resistant to further degradation, remained tightly associated in a complex containing two molecules of each. They were capable of binding the R2 subunit of HSV ribonucleotide reductase with approximately the same affinity as the intact protein but the complex did not complement the small subunit (R2) to give an active enzyme. At low concentrations (0.4 micrograms/ml) of trypsin or V8 protease, cleavage between the subdomains was prevented by the presence of the N-terminal protein kinase domain. At higher protease concentrations (1 micrograms/ml) the N-terminal domain is extensively proteolysed and the 30K and 53K domains were generated. Identical results were obtained using purified R1 isolated from infected cell extracts or following expression in Escherichia coli. The origin of the two domains was investigated by N-terminal sequencing of the 53K fragment and by examining their reactivity with a panel of R1-specific monoclonal antibodies which we isolated and epitope mapped for that purpose. The trypsin cleavage site was found to lie between arginine 575 and asparagine 576, and proteolysis in this region was not prevented by the presence of R2 or the nonapeptide YAGAVVNDL. We propose that the ribonucleotide reductase region of HSV R1 exists in a two domain structure, and that the interdomain linking region is protected by the unique N terminus.

  18. CORAL: aligning conserved core regions across domain families.

    PubMed

    Fong, Jessica H; Marchler-Bauer, Aron

    2009-08-01

    Homologous protein families share highly conserved sequence and structure regions that are frequent targets for comparative analysis of related proteins and families. Many protein families, such as the curated domain families in the Conserved Domain Database (CDD), exhibit similar structural cores. To improve accuracy in aligning such protein families, we propose a profile-profile method CORAL that aligns individual core regions as gap-free units. CORAL computes optimal local alignment of two profiles with heuristics to preserve continuity within core regions. We benchmarked its performance on curated domains in CDD, which have pre-defined core regions, against COMPASS, HHalign and PSI-BLAST, using structure superpositions and comprehensive curator-optimized alignments as standards of truth. CORAL improves alignment accuracy on core regions over general profile methods, returning a balanced score of 0.57 for over 80% of all domain families in CDD, compared with the highest balanced score of 0.45 from other methods. Further, CORAL provides E-values to aid in detecting homologous protein families and, by respecting block boundaries, produces alignments with improved 'readability' that facilitate manual refinement. CORAL will be included in future versions of the NCBI Cn3D/CDTree software, which can be downloaded at http://www.ncbi.nlm.nih.gov/Structure/cdtree/cdtree.shtml. Supplementary data are available at Bioinformatics online.

  19. CORAL: aligning conserved core regions across domain families

    PubMed Central

    Fong, Jessica H.; Marchler-Bauer, Aron

    2009-01-01

    Motivation: Homologous protein families share highly conserved sequence and structure regions that are frequent targets for comparative analysis of related proteins and families. Many protein families, such as the curated domain families in the Conserved Domain Database (CDD), exhibit similar structural cores. To improve accuracy in aligning such protein families, we propose a profile–profile method CORAL that aligns individual core regions as gap-free units. Results: CORAL computes optimal local alignment of two profiles with heuristics to preserve continuity within core regions. We benchmarked its performance on curated domains in CDD, which have pre-defined core regions, against COMPASS, HHalign and PSI-BLAST, using structure superpositions and comprehensive curator-optimized alignments as standards of truth. CORAL improves alignment accuracy on core regions over general profile methods, returning a balanced score of 0.57 for over 80% of all domain families in CDD, compared with the highest balanced score of 0.45 from other methods. Further, CORAL provides E-values to aid in detecting homologous protein families and, by respecting block boundaries, produces alignments with improved ‘readability’ that facilitate manual refinement. Availability: CORAL will be included in future versions of the NCBI Cn3D/CDTree software, which can be downloaded at http://www.ncbi.nlm.nih.gov/Structure/cdtree/cdtree.shtml. Contact: fongj@ncbi.nlm.nih.gov. Supplementary information: Supplementary data are available at Bioinformatics online. PMID:19470584

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

    PubMed

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

    2005-02-15

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

  1. 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.

  2. A domain decomposition algorithm for solving large elliptic problems

    SciTech Connect

    Nolan, M.P.

    1991-01-01

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

  3. 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.

  4. 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.

  5. Connections between large-domain Newtonian turbulence and minimal-channel exact coherent states

    NASA Astrophysics Data System (ADS)

    Kushwaha, Anubhav; Graham, Michael

    2016-11-01

    Direct numerical simulations (DNS) of plane Poiseuille flow of a Newtonian fluid are performed in a large domain at transitional Reynolds numbers. In this Reynolds number regime, turbulent trajectories in minimal channels move chaotically between lower and upper branch invariant solutions known as exact coherent states (ECS). It is found that while they spend most of the time in a core region of the state space, fluctuating about the upper branch ECS, they occasionally escape the core region and pass through the vicinity of lower branch solutions. One particular set of the lower branch solutions form the lower bound of the turbulent trajectory with regard to flow properties like wall shear stress, energy dissipation rate and turbulent kinetic energy. We compare the evolution of wall shear stress in minimal channels with those in patches the size of minimal channels in a large domain and find that they are not only indistinguishable but also bounded on the lower end by the same set of lower branch ECS. This suggests that localised regions in a large box approach the travelling wave solutions in a way similar to minimal channels. We also show that low and high drag regions occur spatiotemporally when the turbulence trajectory approaches the lower and upper branch ECS, respectively. The work was supported by AFOSR Grant FA9550-15-1-0062.

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

    NASA Astrophysics Data System (ADS)

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

    2015-04-01

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

  7. 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

  8. 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.

  9. Bacterial collagen-binding domain targets undertwisted regions of collagen

    PubMed Central

    Philominathan, Sagaya Theresa Leena; Koide, Takaki; Matsushita, Osamu; Sakon, Joshua

    2012-01-01

    Clostridium histolyticum collagenase causes extensive degradation of collagen in connective tissue that results in gas gangrene. The C-terminal collagen-binding domain (CBD) of these enzymes is the minimal segment required to bind to a collagen fibril. CBD binds unidirectionally to the undertwisted C-terminus of triple helical collagen. Here, we examine whether CBD could also target undertwisted regions even in the middle of the triple helix. Collageneous peptides with an additional undertwisted region were synthesized by introducing a Gly → Ala substitution [(POG)xPOA(POG)y]3, where x + y = 9 and x > 3). 1H–15N heteronuclear single quantum coherence nuclear magnetic resonance (HSQC NMR) titration studies with 15N-labeled CBD demonstrated that the minicollagen binds to a 10 Å wide 25 Å long cleft. Six collagenous peptides each labeled with a nitroxide radical were then titrated with 15N-labeled CBD. CBD binds to either the Gly → Ala substitution site or to the C-terminus of each minicollagen. Small-angle X-ray scattering measurements revealed that CBD prefers to bind the Gly → Ala site to the C-terminus. The HSQC NMR spectra of 15N-labeled minicollagen and minicollagen with undertwisted regions were unaffected by the titration of unlabeled CBD. The results imply that CBD binds to the undertwisted region of the minicollagen but does not actively unwind the triple helix. PMID:22898990

  10. Kininogen domain 3 contains regions recognized by antiphosphatidylethanolamine antibodies.

    PubMed

    Katsunuma, J; Sugi, T; Inomo, A; Matsubayashi, H; Izumi, S-I; Makino, T

    2003-01-01

    Antiphosphatidylethanolamine antibodies (APE) have been described in patients with thrombotic diseases and recurrent pregnancy loss (RPL). It has been reported that certain APE are not specific for phosphatidylethanolamine (PE) per se, but are directed to PE-binding plasma proteins, called kininogens. Our recent in vitro data suggest that APE may recognize the domain 3 (D3) region of kininogens. In this study, we have used synthetic peptides that span the D3 of kininogens in inhibition and direct binding studies to identify epitopes that are sites for binding APE. Our present data demonstrate that among 24 RPL patients who were positive for kininogen-dependent immunoglobulin (IgG) APE, 17 patients (70.8%) recognized the LDC27 peptide. We mapped the APE-binding region on D3 using plasma from a RPL patient (X) who had a high titer of IgG APE that recognized LDC27. APE of patient X recognized a 13-residue segment in LDC27, named CNA13. Leu331-Met357 (LDC27) and Cys333-Lys345 (CNA13) are located on the carboxyl-terminal portion of kininogen D3, which is known as the major kininogen heavy chain cell attachment site where it overlaps its cysteine protease inhibitory region. Because APE interferes with the balance of hemostasis in vitro, APE may therefore induce a similar condition in patients thereby causing thrombosis and RPL.

  11. Simian virus 40 origin DNA-binding domain on large T antigen.

    PubMed Central

    Paucha, E; Kalderon, D; Harvey, R W; Smith, A E

    1986-01-01

    Fifty variant forms of simian virus 40 (SV40) large T antigen bearing point, multiple point, deletion, or termination mutations within a region of the protein thought to be involved in DNA binding were tested for their ability to bind to SV40 origin DNA. A number of the mutant large T species including some with point mutations were unable to bind, whereas many were wild type in this activity. The clustering of the mutations that are defective in origin DNA binding both reported here and by others suggests a DNA-binding domain on large T maps between residues 139 and approximately 220, with a particularly sensitive sequence between amino acids 147 and 166. The results indicate that the domain is involved in binding to both site I and site II on SV40 DNA, but it remains unclear whether it is responsible for binding to cellular DNA. Since all the mutants retain the ability to transform Rat-1 cells, we conclude that the ability of large T to bind to SV40 origin DNA is not a prerequisite for its transforming activity. Images PMID:3001365

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

    PubMed

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

    2012-02-15

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

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

    SciTech Connect

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

    2001-08-20

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

  14. 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.

  15. The large terminase DNA packaging motor grips DNA with its ATPase domain for cleavage by the flexible nuclease domain

    PubMed Central

    Hilbert, Brendan J.; Hayes, Janelle A.; Stone, Nicholas P.; Xu, Rui-Gang

    2017-01-01

    Abstract Many viruses use a powerful terminase motor to pump their genome inside an empty procapsid shell during virus maturation. The large terminase (TerL) protein contains both enzymatic activities necessary for packaging in such viruses: the adenosine triphosphatase (ATPase) that powers DNA translocation and an endonuclease that cleaves the concatemeric genome at both initiation and completion of genome packaging. However, how TerL binds DNA during translocation and cleavage remains mysterious. Here we investigate DNA binding and cleavage using TerL from the thermophilic phage P74-26. We report the structure of the P74-26 TerL nuclease domain, which allows us to model DNA binding in the nuclease active site. We screened a large panel of TerL variants for defects in binding and DNA cleavage, revealing that the ATPase domain is the primary site for DNA binding, and is required for nuclease activity. The nuclease domain is dispensable for DNA binding but residues lining the active site guide DNA for cleavage. Kinetic analysis of DNA cleavage suggests flexible tethering of the nuclease domains during DNA cleavage. We propose that interactions with the procapsid during DNA translocation conformationally restrict the nuclease domain, inhibiting cleavage; TerL release from the capsid upon completion of packaging unlocks the nuclease domains to cleave DNA. PMID:28082398

  16. The large terminase DNA packaging motor grips DNA with its ATPase domain for cleavage by the flexible nuclease domain.

    PubMed

    Hilbert, Brendan J; Hayes, Janelle A; Stone, Nicholas P; Xu, Rui-Gang; Kelch, Brian A

    2017-01-12

    Many viruses use a powerful terminase motor to pump their genome inside an empty procapsid shell during virus maturation. The large terminase (TerL) protein contains both enzymatic activities necessary for packaging in such viruses: the adenosine triphosphatase (ATPase) that powers DNA translocation and an endonuclease that cleaves the concatemeric genome at both initiation and completion of genome packaging. However, how TerL binds DNA during translocation and cleavage remains mysterious. Here we investigate DNA binding and cleavage using TerL from the thermophilic phage P74-26. We report the structure of the P74-26 TerL nuclease domain, which allows us to model DNA binding in the nuclease active site. We screened a large panel of TerL variants for defects in binding and DNA cleavage, revealing that the ATPase domain is the primary site for DNA binding, and is required for nuclease activity. The nuclease domain is dispensable for DNA binding but residues lining the active site guide DNA for cleavage. Kinetic analysis of DNA cleavage suggests flexible tethering of the nuclease domains during DNA cleavage. We propose that interactions with the procapsid during DNA translocation conformationally restrict the nuclease domain, inhibiting cleavage; TerL release from the capsid upon completion of packaging unlocks the nuclease domains to cleave DNA.

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. Definition of a DNA repair domain in the genomic region containing the human p53 gene.

    PubMed

    Tolbert, D M; Kantor, G J

    1996-07-15

    The human p53 gene is repaired in UV (254 nm)-irradiated xeroderma pigmentosum group C (XP-C) cells as part of a large genomic region that is about twice the size of the gene. Surrounding genomic regions are not repaired. Through DNA cloning and measurements of DNA repair, we mapped the location of the repair domain, including the terminal regions, relative to the topological features of the gene. The domain includes only the DNA strand that is transcribed and extends in both 3' and 5' directions beyond the promoter and transcription termination sites. No transcriptional activity other than that associated with the p53 gene was detected. The results suggest that nontranscribed regions adjacent to the p53 transcribed regions are efficiently repaired in XP-C cells. This means that factors associated with transcription other than RNA polymerase II and the associated transcription repair coupling factor must also play a role in the selective repair process in XP-C cells. We also found that a DNA fragment that contains the p53 promoters is nearly twice as sensitive to cyclobutane pyrimidine dimer induction by UV irradiation than are the surrounding fragments, which have the expected sensitivity.

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

    PubMed Central

    2012-01-01

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

  4. 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

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

    PubMed

    Mutskov, Vesco; Felsenfeld, Gary

    2009-10-13

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

  6. 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.

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

    PubMed Central

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

    2011-01-01

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

  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.

  9. Insights into interphase large-scale chromatin structure from analysis of engineered chromosome regions.

    PubMed

    Belmont, A S; Hu, Y; Sinclair, P B; Wu, W; Bian, Q; Kireev, I

    2010-01-01

    How chromatin folds into mitotic and interphase chromosomes has remained a difficult question for many years. We have used three generations of engineered chromosome regions as a means of visualizing specific chromosome regions in live cells and cells fixed under conditions that preserve large-scale chromatin structure. Our results confirm the existence of large-scale chromatin domains and fibers formed by the folding of 10-nm and 30-nm chromatin fibers into larger, spatially distinct domains. Transcription at levels within severalfold of the levels measured for endogenous loci occur within these large-scale chromatin structures on a condensed template linearly compacted several hundred fold to 1000-fold relative to B-form DNA. However, transcriptional induction is accompanied by a severalfold decondensation of this large-scale chromatin structure that propagates hundreds of kilobases beyond the induced gene. Examination of engineered chromosome regions in mouse embryonic stem cells (ESCs) and differentiated cells suggests a surprising degree of plasticity in this large-scale chromatin structure, allowing long-range DNA interactions within the context of large-scale chromatin fibers. Recapitulation of gene-specific differences in large-scale chromatin conformation and nuclear positioning using these engineered chromosome regions will facilitate identification of cis and trans determinants of interphase chromosome architecture.

  10. Insights into interphase large-scale chromatin structure from analysis of engineered chromosome regions

    PubMed Central

    Belmont, Andrew S.; Hu, Yan; Sinclair, Paul; Wu, Wei; Bian, Qian; Kireev, Igor

    2012-01-01

    How chromatin folds into mitotic and interphase chromosomes has remained a difficult question for many years. We have used three generations of engineered chromosome regions as a means of visualizing specific chromosome regions in live cells and cells fixed under conditions which preserve large-scale chromatin structure. Our results confirm the existence of large-scale chromatin domains and fibers formed by the folding of 10 and 30 nm chromatin fibers into larger, spatially distinct domains. Transcription at levels within several fold of the levels measured for endogenous loci occur within these large-scale chromatin structures on a condensed template linearly compacted several hundred fold to one thousand fold relative to B-form DNA. However, transcriptional induction is accompanied by a several fold decondensation of this large-scale chromatin structure that propagates hundreds of kb beyond the induced gene. Examination of engineered chromosome regions in mouse ES and differentiated cells suggests a surprising degree of plasticity in this large-scale chromatin structure, allowing long-range DNA interactions within the context of large-scale chromatin fibers. Recapitulation of gene specific differences in large-scale chromatin conformation and nuclear positioning using these engineered chromosome regions will facilitate identification of cis and trans determinants of interphase chromosome architecture. PMID:21467143

  11. The domain architecture of large guanine nucleotide exchange factors for the small GTP-binding protein Arf.

    PubMed

    Mouratou, Barbara; Biou, Valerie; Joubert, Alexandra; Cohen, Jean; Shields, David J; Geldner, Niko; Jürgens, Gerd; Melançon, Paul; Cherfils, Jacqueline

    2005-02-17

    Small G proteins, which are essential regulators of multiple cellular functions, are activated by guanine nucleotide exchange factors (GEFs) that stimulate the exchange of the tightly bound GDP nucleotide by GTP. The catalytic domain responsible for nucleotide exchange is in general associated with non-catalytic domains that define the spatio-temporal conditions of activation. In the case of small G proteins of the Arf subfamily, which are major regulators of membrane trafficking, GEFs form a heterogeneous family whose only common characteristic is the well-characterized Sec7 catalytic domain. In contrast, the function of non-catalytic domains and how they regulate/cooperate with the catalytic domain is essentially unknown. Based on Sec7-containing sequences from fully-annotated eukaryotic genomes, including our annotation of these sequences from Paramecium, we have investigated the domain architecture of large ArfGEFs of the BIG and GBF subfamilies, which are involved in Golgi traffic. Multiple sequence alignments combined with the analysis of predicted secondary structures, non-structured regions and splicing patterns, identifies five novel non-catalytic structural domains which are common to both subfamilies, revealing that they share a conserved modular organization. We also report a novel ArfGEF subfamily with a domain organization so far unique to alveolates, which we name TBS (TBC-Sec7). Our analysis unifies the BIG and GBF subfamilies into a higher order subfamily, which, together with their being the only subfamilies common to all eukaryotes, suggests that they descend from a common ancestor from which species-specific ArfGEFs have subsequently evolved. Our identification of a conserved modular architecture provides a background for future functional investigation of non-catalytic domains.

  12. 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

  13. 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.

  14. 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...

  15. 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...

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

    NASA Astrophysics Data System (ADS)

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

    2015-12-01

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

  17. 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

    2015-05-05

    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.

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

    PubMed Central

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

    2015-01-01

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

  19. Contribution of Large Region Joint Associations to Complex Traits Genetics

    PubMed Central

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

    2015-01-01

    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

  20. 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.

  1. Fine-tuning of protein domain boundary by minimizing potential coiled coil regions.

    PubMed

    Iwaya, Naoko; Goda, Natsuko; Unzai, Satoru; Fujiwara, Kenichiro; Tanaka, Toshiki; Tomii, Kentaro; Tochio, Hidehito; Shirakawa, Masahiro; Hiroaki, Hidekazu

    2007-01-01

    Structural determination of individual protein domains isolated from multidomain proteins is a common approach in the post-genomic era. Novel and thus uncharacterized domains liberated from intact proteins often self-associate due to incorrectly defined domain boundaries. Self-association results in missing signals, poor signal dispersion and a low signal-to-noise ratio in (1)H-(15)N HSQC spectra. We have found that a putative, non-canonical coiled coil region close to a domain boundary can cause transient hydrophobic self-association and monomer-dimer equilibrium in solution. Here we propose a rational method to predict putative coiled coil regions adjacent to the globular core domain using the program COILS. Except for the amino acid sequence, no preexisting knowledge concerning the domain is required. A small number of mutant proteins with a minimized coiled coil region have been rationally designed and tested. The engineered domains exhibit decreased self-association as assessed by (1)H-(15)N HSQC spectra with improved peak dispersion and sharper cross peaks. Two successful examples of isolating novel N-terminal domains from AAA-ATPases are demonstrated. Our method is useful for the experimental determination of domain boundaries suited for structural genomics studies.

  2. Epitaxial Growth and Electronic Properties of Large Hexagonal Graphene Domains on Cu(111) Thin Film

    NASA Astrophysics Data System (ADS)

    Ago, Hiroki; Kawahara, Kenji; Ogawa, Yui; Tanoue, Shota; Bissett, Mark A.; Tsuji, Masaharu; Sakaguchi, Hidetsugu; Koch, Roland J.; Fromm, Felix; Seyller, Thomas; Komatsu, Katsuyoshi; Tsukagoshi, Kazuhito

    2013-07-01

    Large hexagonal single-crystalline domains of single-layer graphene are epitaxially grown by ambient-pressure chemical vapor deposition over a thin Cu(111) film deposited on c-plane sapphire. The hexagonal graphene domains with a maximum size of 100 µm are oriented in the same direction due to the epitaxial growth. Reflecting high crystallinity, a clear band structure with the Dirac cone is observed by angle-resolved photoelectron spectroscopy (ARPES), and a high carrier mobility exceeding 4,000 cm2 V-1 s-1 is obtained on SiO2/Si at room temperature. Our epitaxial approach combined with large domain growth is expected to contribute to future electronic applications.

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

    PubMed

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

    2015-06-01

    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.

  4. 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.

  5. Large- to small-scale dynamo in domains of large aspect ratio: kinematic regime

    NASA Astrophysics Data System (ADS)

    Shumaylova, Valeria; Teed, Robert J.; Proctor, Michael R. E.

    2017-04-01

    The Sun's magnetic field exhibits coherence in space and time on much larger scales than the turbulent convection that ultimately powers the dynamo. In this work, we look for numerical evidence of a large-scale magnetic field as the magnetic Reynolds number, Rm, is increased. The investigation is based on the simulations of the induction equation in elongated periodic boxes. The imposed flows considered are the standard ABC flow (named after Arnold, Beltrami & Childress) with wavenumber ku = 1 (small-scale) and a modulated ABC flow with wavenumbers ku = m, 1, 1 ± m, where m is the wavenumber corresponding to the long-wavelength perturbation on the scale of the box. The critical magnetic Reynolds number R_m^{crit} decreases as the permitted scale separation in the system increases, such that R_m^{crit} ∝ [L_x/L_z]^{-1/2}. The results show that the α-effect derived from the mean-field theory ansatz is valid for a small range of Rm after which small scale dynamo instability occurs and the mean-field approximation is no longer valid. The transition from large- to small-scale dynamo is smooth and takes place in two stages: a fast transition into a predominantly small-scale magnetic energy state and a slower transition into even smaller scales. In the range of Rm considered, the most energetic Fourier component corresponding to the structure in the long x-direction has twice the length-scale of the forcing scale. The long-wavelength perturbation imposed on the ABC flow in the modulated case is not preserved in the eigenmodes of the magnetic field.

  6. Domain wall dynamics in ultrathin Pt/Co/AlOx microstrips under large combined magnetic fields

    NASA Astrophysics Data System (ADS)

    Jué, E.; Thiaville, A.; Pizzini, S.; Miltat, J.; Sampaio, J.; Buda-Prejbeanu, L. D.; Rohart, S.; Vogel, J.; Bonfim, M.; Boulle, O.; Auffret, S.; Miron, I. M.; Gaudin, G.

    2016-01-01

    The dynamics of magnetic domain walls in ultrathin strip-patterned Pt/Co/AlOx samples with perpendicular easy axis has been studied experimentally under an easy-axis field, superposed to a hard-axis field oriented along the strip. The easy-axis field is large so that the domain walls move well beyond the creep regime. A chiral effect is observed where the domain wall velocity shows a monotonous and surprisingly large variation with an in-plane field. A micromagnetic analysis, combining analytic, one-dimensional, and two-dimensional simulations with structural disorder, shows that this behavior can be reproduced with a Dzyaloshinskii-Moriya interaction of the interfacial type, with due consideration of the dynamics of the tilt degree of freedom of the domain wall. The estimated effective value of this interaction (D ≈-2.2 mJ /m2 for a 0.6 nm Co thickness) is consistent with values obtained by other techniques. It is also shown, by micromagnetic analysis, that several modes and characteristic times occur in the dynamics of the tilt of such domain walls.

  7. Probabilistic flood risk assessment over large geographical regions

    NASA Astrophysics Data System (ADS)

    Dyck, Jozef; Willems, Patrick

    2013-06-01

    We develop a probabilistic model to estimate the rate of flood-induced losses for a set of properties distributed over a large geographical region (e.g., a portfolio of insured properties within a country). The use of detailed physically based models over large areas becomes difficult due to the vast amount of data needed and the high implementation cost. The proposed model allows one to incorporate results from such detailed models but can also be used in regions that have not been studied in much detail. Minimal required information includes the rate and spatial extent of severe precipitation, the topography and river network from which regions at risk of flooding can be identified, and information on historical floods with an approximate delineation of the flooded area, and associated aggregate losses for at least a few major events. An application to river flood loss from residential buildings in Belgium is presented.

  8. 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.

  9. Crystal Structure of the Simian Virus 40 Large T-Antigen Origin-Binding Domain

    SciTech Connect

    Meinke,G.; Bullock, P.; Bohm, A.

    2006-01-01

    The origins of replication of DNA tumor viruses have a highly conserved feature, namely, multiple binding sites for their respective initiator proteins arranged as inverted repeats. In the 1.45- Angstroms crystal structure of the simian virus 40 large T-antigen (T-ag) origin-binding domain (obd) reported herein, T-ag obd monomers form a left-handed spiral with an inner channel of 30 Angstroms having six monomers per turn. The inner surface of the spiral is positively charged and includes residues known to bind DNA. Residues implicated in hexamerization of full-length T-ag are located at the interface between adjacent T-ag obd monomers. These data provide a high-resolution model of the hexamer of origin-binding domains observed in electron microscopy studies and allow the obd's to be oriented relative to the hexamer of T-ag helicase domains to which they are connected.

  10. Computational modelling of a large dimension wind farm cluster using domain coupling

    NASA Astrophysics Data System (ADS)

    da Costa Gomes, V. M. M. G.; Palma, J. M. L. M.

    2016-09-01

    The accuracy of Computational Fluid Dynamics (CFD) models for Atmospheric Boundary Layer (ABL) flows relies largely on the placement of the domain boundaries and the quality of the imposed flow conditions, the inlet boundary in particular. Exploiting the parabolic nature of many ABL flows and of CFD modelled ABL flow in particular, a precursor simulation is used as source of flow data to improve the target domain's inlet flow description over the standard synthetic boundary conditions, one-directionally coupling the solutions to the two simulations. Using the approach, a case of flow over a two wind farm offshore cluster is modelled using two small coupled simulations, matching the results of a single simulation including the full cluster at a significant computational time saving, in the order of 70%. Further savings were shown to be possible by reducing the resolution of the precursor simulation, with negligible impact on the results at the target domain.

  11. Crystal structure of the simian virus 40 large T-antigen origin-binding domain.

    PubMed

    Meinke, Gretchen; Bullock, Peter A; Bohm, Andrew

    2006-05-01

    The origins of replication of DNA tumor viruses have a highly conserved feature, namely, multiple binding sites for their respective initiator proteins arranged as inverted repeats. In the 1.45-angstroms crystal structure of the simian virus 40 large T-antigen (T-ag) origin-binding domain (obd) reported herein, T-ag obd monomers form a left-handed spiral with an inner channel of 30 angstroms having six monomers per turn. The inner surface of the spiral is positively charged and includes residues known to bind DNA. Residues implicated in hexamerization of full-length T-ag are located at the interface between adjacent T-ag obd monomers. These data provide a high-resolution model of the hexamer of origin-binding domains observed in electron microscopy studies and allow the obd's to be oriented relative to the hexamer of T-ag helicase domains to which they are connected.

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

    NASA Astrophysics Data System (ADS)

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

    2013-12-01

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

  13. Investigation of multilayer domains in large-scale CVD monolayer graphene by optical imaging

    NASA Astrophysics Data System (ADS)

    Yu, Yuanfang; Li, Zhenzhen; Wang, Wenhui; Guo, Xitao; Jiang, Jie; Nan, Haiyan; Ni, Zhenhua

    2017-03-01

    CVD graphene is a promising candidate for optoelectronic applications due to its high quality and high yield. However, multi-layer domains could inevitably form at the nucleation centers during the growth. Here, we propose an optical imaging technique to precisely identify the multilayer domains and also the ratio of their coverage in large-scale CVD monolayer graphene. We have also shown that the stacking disorder in twisted bilayer graphene as well as the impurities on the graphene surface could be distinguished by optical imaging. Finally, we investigated the effects of bilayer domains on the optical and electrical properties of CVD graphene, and found that the carrier mobility of CVD graphene is seriously limited by scattering from bilayer domains. Our results could be useful for guiding future optoelectronic applications of large-scale CVD graphene. Project supported by the National Natural Science Foundation of China (Nos. 61422503, 61376104), the Open Research Funds of Key Laboratory of MEMS of Ministry of Education (SEU, China), and the Fundamental Research Funds for the Central Universities.

  14. Differences between left- and right-sided neglect revisited: A large cohort study across multiple domains.

    PubMed

    Ten Brink, Antonia F; Verwer, Jurre H; Biesbroek, J Matthijs; Visser-Meily, Johanna M A; Nijboer, Tanja C W

    2017-09-01

    Unilateral spatial neglect (USN) is a syndrome that can occur after right- and left-hemisphere damage. It is generally accepted that left-sided USN is more severe than right-sided USN. Evidence for such a difference in other domains is lacking. Primary aims were to compare frequency, severity, region specificity, cognition, physical functioning, and physical independence between left and right USN. Secondary aims were to compare lesion characteristics. A total of 335 stroke patients admitted for inpatient rehabilitation were included. The severity of the lateralized attentional deficit was measured with a shape cancellation and line bisection test (in peripersonal and extrapersonal space) and the Catherine Bergego scale. The Mini-Mental State Examination, Stichting Afasie Nederland score, search organization (i.e., best R and intersections rate), Motricity Index, balance, mobility, and self-care were assessed. Measures were statistically compared between left, right, and no USN patients. Lesion overlay plots were compared with lesion subtraction analyses. Left USN (15.82%) was more frequent than right USN (9.25%). Demographic and stroke characteristics were comparable between groups. The lateralized attentional deficit was most severe in left USN. USN in both peripersonal and extrapersonal space was more frequently left-sided in nature. Search efficiency was lower in left USN. Balance was poorer in right USN. No differences between left and right USN were found for cognitive ability, communication, motor strength, mobility, and self-care. Most patients with left USN had right-hemispheric lesions, whereas patients with right USN could have lesions in either the left or the right hemisphere. To conclude, left and right USN are both common after stroke. Although the lateralized attention deficit is worse in left than in right USN, consequences at the level of physical functioning and physical independence are largely comparable. From a clinical perspective, it is

  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. Crystal structure of a shark single-domain antibody V region in complex with lysozyme.

    PubMed

    Stanfield, Robyn L; Dooley, Helen; Flajnik, Martin F; Wilson, Ian A

    2004-09-17

    Cartilaginous fish are the phylogenetically oldest living organisms known to possess components of the vertebrate adaptive immune system. Key to their immune response are heavy-chain, homodimeric immunoglobulins called new antigen receptors (IgNARs), in which the variable (V) domains recognize antigens with only a single immunoglobulin domain, akin to camelid heavy-chain V domains. The 1.45 angstrom resolution crystal structure of the type I IgNAR V domain in complex with hen egg-white lysozyme (HEL) reveals a minimal antigen-binding domain that contains only two of the three conventional complementarity-determining regions but still binds HEL with nanomolar affinity by means of a binding interface comparable in size to conventional antibodies.

  17. Linker regions and flexibility around the metalloprotease domain account for conformational activation of ADAMTS13

    PubMed Central

    Deforche, L.; Roose, E.; Vandenbulcke, A.; Vandeputte, N.; Feys, H.B.; Springer, T.A.; Mi, L.Z.; Muia, J.; Sadler, J.E.; Soejima, K.; Rottensteiner, H.; Deckmyn, H.; De Meyer, S.F.; Vanhoorelbeke, K.

    2016-01-01

    Background Recently, conformational activation of ADAMTS13 was identified. This mechanism showed the evolution from a condensed and inhibited conformation, in which the proximal MDTCS and distal T2-CUB2 domains are in close contact with each other, to an activated structure due to ding with the von Willebrand factor (VWF). Objectives Identification of cryptic epitope/exosite exposure after conformational activation and of sites of flexibility in ADAMTS13. Methods The activating effect of 25 anti-T2-CUB2 antibodies was studied in the FRETS-VWF73 and the vortex assay. Cryptic epitope/exosite exposure was determined in ELISA and VWF binding assay. The molecular basis for flexibility was hypothesized through RADAR analysis, tested in ELISA using deletion variants and visualized using electron microscopy. Results Eleven activating anti-ADAMTS13 antibodies, directed against the T5-CUB2 domains, were identified in the FRETS-VWF73 assay. RADAR analysis identified three linker regions in the distal domains. Interestingly, identification of an antibody recognizing a cryptic epitope in the metalloprotease domain confirmed the contribution of these linker regions to conformational activation of the enzyme. The proof of flexibility around both the T2 and metalloprotease domains by electron microscopy furthermore supported this contribution. In addition, cryptic epitope exposure was identified in the distal domains, as activating anti-T2-CUB2 antibodies increased the binding to folded VWF up to ~3-fold. Conclusion Conformational activation of ADAMTS13 leads to cryptic epitope/exosite exposure in both proximal and distal domains, subsequently inducing increased activity. Furthermore, three linker regions in the distal domains are responsible for flexibility and enable the interaction between the proximal and the T8-CUB2 domains. PMID:26391536

  18. Large N: a strategy for improving regional sport performance.

    PubMed

    Cornett, Andrew C; Stager, Joel M

    2015-07-01

    It has been hypothesized that large differences in maximal performance can arise between various geopolitical regions solely on the basis of differing numbers of participants in the target activity. While there is evidence in support of this hypothesis for a measure of intellectual performance, the same relationship has not been examined for a measure of physical performance. To determine whether the number of participants is a predictor of the best athletic performance in a region. The 2005-2010 USA Swimming Age Group Detail reports were used to determine the number of competitive swimmers participating in each age group for the 59 local swimming communities in the United States. The USA Swimming performance database provided 50-yd-freestyle times in each community for boys and girls for each age (6-19 y). Simple linear regression was used to examine the relationship between the outcome variable (fastest time) and the predictor variable (log of the number of swimmers) for each combination of age, sex, and calendar year. The log of the number of swimmers in a region was a significant predictor of the best performance in that region for all 168 combinations of age, sex, and calendar year (P<.05) and explained, on average, 41%, and as much as 62%, of the variance in the fastest time. These findings have important implications for the development of regional sport strategic policy. Increasing the number of participants in the target activity appears a viable strategy for improving regional performance.

  19. Spatial domain-based parallelism in large scale, participating-media, radiative transport applications

    SciTech Connect

    Burns, S.P.; Christon, M.A.

    1996-11-01

    Parallelism for gray participating media radiation heat transfer may be placed in two primary categories: spatial and angular domain-based parallelism. Angular, e.g., ray based, decomposition has received the greatest attention in the open literature for moderate sized applications where the entire geometry may be placed on processor. Angular based decomposition is limited, however, for large scale applications (O(10{sup 6}) to O(10{sup 8}) computational cells) given the memory required to store computational grids of this size on each processor. Therefore, the objective of this work is to examine the application of spatial domain-based parallelism to large scale, three-dimensional, participating-media radiation transport calculations using a massively parallel supercomputer architecture. Both scaled and fixed problem size efficiencies are presented for an application of the Discrete Ordinate method to a three dimensional, non-scattering radiative transport application with nonuniform absorptivity. The data presented shows that the spatial domain-based decomposition paradigm results in some degradation in the parallel efficiency but provides useful speedup for large computational grids.

  20. Regional white matter variation associated with domain-specific metacognitive accuracy.

    PubMed

    Baird, Benjamin; Cieslak, Matthew; Smallwood, Jonathan; Grafton, Scott T; Schooler, Jonathan W

    2015-03-01

    The neural mechanisms that mediate metacognitive ability (the capacity to accurately reflect on one's own cognition and experience) remain poorly understood. An important question is whether metacognitive capacity is a domain-general skill supported by a core neuroanatomical substrate or whether regionally specific neural structures underlie accurate reflection in different cognitive domains. Providing preliminary support for the latter possibility, recent findings have shown that individual differences in metacognitive ability in the domains of memory and perception are related to variation in distinct gray matter volume and resting-state functional connectivity. The current investigation sought to build on these findings by evaluating how metacognitive ability in these domains is related to variation in white matter microstructure. We quantified metacognitive ability across memory and perception domains and used diffusion spectrum imaging to examine the relation between high-resolution measurements of white matter microstructure and individual differences in metacognitive accuracy in each domain. We found that metacognitive accuracy for perceptual decisions and memory were uncorrelated across individuals and that metacognitive accuracy in each domain was related to variation in white matter microstructure in distinct brain areas. Metacognitive accuracy for perceptual decisions was associated with increased diffusion anisotropy in white matter underlying the ACC, whereas metacognitive accuracy for memory retrieval was associated with increased diffusion anisotropy in the white matter extending into the inferior parietal lobule. Together, these results extend previous findings linking metacognitive ability in the domains of perception and memory to variation in distinct brain structures and connections.

  1. The shifting zoom: new possibilities for inverse scattering on electrically large domains

    NASA Astrophysics Data System (ADS)

    Persico, Raffaele; Ludeno, Giovanni; Soldovieri, Francesco; De Coster, Alberic; Lambot, Sebastien

    2017-04-01

    Inverse scattering is a subject of great interest in diagnostic problems, which are in their turn of interest for many applicative problems as investigation of cultural heritage, characterization of foundations or subservices, identification of unexploded ordnances and so on [1-4]. In particular, GPR data are usually focused by means of migration algorithms, essentially based on a linear approximation of the scattering phenomenon. Migration algorithms are popular because they are computationally efficient and do not require the inversion of a matrix, neither the calculation of the elements of a matrix. In fact, they are essentially based on the adjoint of the linearised scattering operator, which allows in the end to write the inversion formula as a suitably weighted integral of the data [5]. In particular, this makes a migration algorithm more suitable than a linear microwave tomography inversion algorithm for the reconstruction of an electrically large investigation domain. However, this computational challenge can be overcome by making use of investigation domains joined side by side, as proposed e.g. in ref. [3]. This allows to apply a microwave tomography algorithm even to large investigation domains. However, the joining side by side of sequential investigation domains introduces a problem of limited (and asymmetric) maximum view angle with regard to the targets occurring close to the edges between two adjacent domains, or possibly crossing these edges. The shifting zoom is a method that allows to overcome this difficulty by means of overlapped investigation and observation domains [6-7]. It requires more sequential inversion with respect to adjacent investigation domains, but the really required extra-time is minimal because the matrix to be inverted is calculated ones and for all, as well as its singular value decomposition: what is repeated more time is only a fast matrix-vector multiplication. References [1] M. Pieraccini, L. Noferini, D. Mecatti, C

  2. 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.

  3. J Domain-Independent Regulation of the Rb Family by Polyomavirus Large T Antigen

    PubMed Central

    Sheng, Qing; Love, Tara M.; Schaffhausen, Brian

    2000-01-01

    The ability of polyomavirus large T antigen (LT) to promote cell cycling, to immortalize primary cells, and to block differentiation has been linked to its effects on tumor suppressors of the retinoblastoma susceptibility (Rb) gene family. Our previous studies have shown that LT requires an intact N-terminal DnaJ domain, in addition to an Rb binding site, for activation of simple E2F-containing promoters and stimulation of cell cycle progression. Here we show that some LT effects dependent on interaction with the Rb family are largely DnaJ independent. In differentiating C2C12 myoblasts, overexpression of LT caused apoptosis. Although this activity of LT completely depended on Rb binding, LTs with mutations in the J domain remained able to kill. Comparisons of Rb− and J− LTs revealed additional differences. Wild-type but not Rb− LT activated the cyclin A promoter under serum starvation conditions. Genetic analysis of the promoter linked the Rb requirement to an E2F site in the promoter. LTs with mutations in the J domain were still able to activate the promoter. Finally, J mutant LTs caused changes in phosphorylation of both pRb and p130. In the case of p130, Thr-986 was shown to be a site that is regulated by J mutant LT. Taken together, these observations reveal that LT regulation of Rb function can be separated into both DnaJ-dependent and DnaJ-independent pathways. PMID:10799605

  4. A fast algorithm based on the domain decomposition method for scattering analysis of electrically large objects

    NASA Astrophysics Data System (ADS)

    Yin, Lei; Hong, Wei

    2002-01-01

    By combining the finite difference (FD) method with the domain decomposition method (DDM), a fast and rigorous algorithm is presented in this paper for the scattering analysis of extremely large objects. Unlike conventional methods, such as the method of moments (MOM) and FD method, etc., the new algorithm decomposes an original large domain into small subdomains and chooses the most efficient method to solve the electromagnetic (EM) equations on each subdomain individually. Therefore the computational complexity and scale are substantially reduced. The iterative procedure of the algorithm and the implementation of virtual boundary conditions are discussed in detail. During scattering analysis of an electrically large cylinder, the conformal band computational domain along the circumference of the cylinder is decomposed into sections, which results in a series of band matrices with very narrow band. Compared with the traditional FD method, it decreases the consumption of computer memory and CPU time from O(N2) to O(N/m) and O(N), respectively, where m is the number of subdomains and Nis the number of nodes or unknowns. Furthermore, this method can be easily applied for the analysis of arbitrary shaped cylinders because the subdomains can be divided into any possible form. On the other hand, increasing the number of subdomains will hardly increase the computing time, which makes it possible to analyze the EM scattering problems of extremely large cylinders only on a PC. The EM scattering by two-dimensional cylinders with maximum perimeter of 100,000 wavelengths is analyzed. Moreover, this method is very suitable for parallel computation, which can further promote the computational efficiency.

  5. 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.

  6. The CHAP domain: a large family of amidases including GSP amidase and peptidoglycan hydrolases.

    PubMed

    Bateman, Alex; Rawlings, Neil D

    2003-05-01

    Cleavage of peptidoglycan plays an important role in bacterial cell division, cell growth and cell lysis. Here, we reveal that several known peptidoglycan amidases fall into a family, which includes many proteins of previously unknown function. The family includes two different peptidoglycan cleavage activities: L-muramoyl-L-alanine amidase and D-alanyl-glycyl endopeptidase activity. The family includes the amidase portion of the bifunctional glutathionylspermidine synthase/amidase enzyme from bacteria and pathogenic trypanosomes. The glutathionylspermidine synthase is thought to be a key component of the alternative pathway in trypanosomes for protection from oxygen-radical damage and has been proposed as a potential drug target. The CHAP (cysteine, histidine-dependent amidohydrolases/peptidases) domain is often found in association with other domains that cleave peptidoglycan. The large number of multifunctional hydrolases suggests that they might act in a cooperative manner to cleave specialized substrates.

  7. 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.

  8. Rayleigh-Bénard convection in large-aspect-ratio domains.

    PubMed

    Paul, M R; Chiam, K-H; Cross, M C; Fischer, P F

    2004-08-06

    The coarsening and wave number selection of striped states growing from random initial conditions are studied in a nonrelaxational, spatially extended, and far-from-equilibrium system by performing large-scale numerical simulations of Rayleigh-Bénard convection in a large-aspect-ratio cylindrical domain with experimentally realistic boundaries. We find evidence that various measures of the coarsening dynamics scale in time with different power-law exponents, indicating that multiple length scales are required in describing the time dependent pattern evolution. The translational correlation length scales with time as t0.12, the orientational correlation length scales as t0.54, and the density of defects scale as t(-0.45). The final pattern evolves toward the wave number where isolated dislocations become motionless, suggesting a possible wave number selection mechanism for large-aspect-ratio convection.

  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. 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.

  11. 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.

  12. Design of the large hadron electron collider interaction region

    NASA Astrophysics Data System (ADS)

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

    2015-11-01

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

  13. Large-Area WS2 Film with Big Single Domains Grown by Chemical Vapor Deposition.

    PubMed

    Liu, Pengyu; Luo, Tao; Xing, Jie; Xu, Hong; Hao, Huiying; Liu, Hao; Dong, Jingjing

    2017-10-03

    High-quality WS2 film with the single domain size up to 400 μm was grown on Si/SiO2 wafer by atmospheric pressure chemical vapor deposition. The effects of some important fabrication parameters on the controlled growth of WS2 film have been investigated in detail, including the choice of precursors, tube pressure, growing temperature, holding time, the amount of sulfur powder, and gas flow rate. By optimizing the growth conditions at one atmospheric pressure, we obtained tungsten disulfide single domains with an average size over 100 μm. Raman spectra, atomic force microscopy, and transmission electron microscopy provided direct evidence that the WS2 film had an atomic layer thickness and a single-domain hexagonal structure with a high crystal quality. And the photoluminescence spectra indicated that the tungsten disulfide films showed an evident layer-number-dependent fluorescence efficiency, depending on their energy band structure. Our study provides an important experimental basis for large-area, controllable preparation of atom-thick tungsten disulfide thin film and can also expedite the development of scalable high-performance optoelectronic devices based on WS2 film.

  14. Time-domain hybrid method for simulating large amplitude motions of ships advancing in waves

    NASA Astrophysics Data System (ADS)

    Liu, Shukui; Papanikolaou, Apostolos D.

    2011-03-01

    Typical results obtained by a newly developed, nonlinear time domain hybrid method for simulating large amplitude motions of ships advancing with constant forward speed in waves are presented. The method is hybrid in the way of combining a time-domain transient Green function method and a Rankine source method. The present approach employs a simple double integration algorithm with respect to time to simulate the free-surface boundary condition. During the simulation, the diffraction and radiation forces are computed by pressure integration over the mean wetted surface, whereas the incident wave and hydrostatic restoring forces/moments are calculated on the instantaneously wetted surface of the hull. Typical numerical results of application of the method to the seakeeping performance of a standard containership, namely the ITTC S175, are herein presented. Comparisons have been made between the results from the present method, the frequency domain 3D panel method (NEWDRIFT) of NTUA-SDL and available experimental data and good agreement has been observed for all studied cases between the results of the present method and comparable other data.

  15. Classical convective energy transport in large gradient regions

    SciTech Connect

    Hinton, F.L.

    1996-12-31

    Large gradients in density and temperature occur near the edge in H-mode plasmas and in the core of tokamak plasmas with negative central shear. Transport in these regions may be comparable to neoclassical. Standard neoclassical theory does not apply when the gradient lengths are comparable to an ion orbit excursion, or banana width. A basic question for neoclassical transport in large gradient regions is: do ion-ion collisions drive particle transport? Near the plasma edge in H-mode, where ion orbit loss requires that the ion energy transport be convective, neoclassical particle transport due to ion-ion collisions may play an important role. In negative central shear plasmas, where transport is inferred to be near neoclassical, it is important to have accurate predictions for the neoclassical rate of energy and particle transport. A simple 2-D slab model has been used, with a momentum-conserving collision operator, to show that ion-ion collisions do drive particle transport. When the gradients are large, the {open_quotes}field particle{close_quotes} contribution to the particle flux is non-local, and does not cancel the {open_quotes}test particle{close_quotes} contribution, which is local. Solutions of the kinetic equation are found which show that the steepness of the density profile, for increasing particle flux, is limited by orbit averaging. The gradient length is limited by the thermal gyroradius, and the convective energy flux is independent of ion temperature. This will allow an ion thermal runaway to occur, if there are no other ion energy loss mechanisms.

  16. Large scale arrays of four-state vortex domains in BiFeO3 thin film

    NASA Astrophysics Data System (ADS)

    Wang, W. Y.; Zhu, Y. L.; Tang, Y. L.; Xu, Y. B.; Liu, Y.; Li, S.; Zhang, S. R.; Wang, Y. J.; Ma, X. L.

    2016-11-01

    Exotic domain states, like vortex, offer the promise of superior properties and the potential disclination strain is a key factor for their formation in ferroelectrics. Here we show that large scale arrays of four-state vortex domains can be obtained in rhombohedral BiFeO3 thin films grown on PrScO3 substrates by pulsed laser deposition. Cs-corrected scanning transmission electron microscopy demonstrates that each vortex domain is comprised of four ferroelectric variants with two 180° domain walls and two 109° domain walls. Atomic mappings of the lattice distortions unit cell by unit cell reveal that the cores of the vortex might be charged. The strains are mainly concentrated on domain walls. The formation mechanism of such large scale vortex-like states was discussed.

  17. Regional climate projections for the MENA-CORDEX domain: analysis of projected temperature and precipitation changes

    NASA Astrophysics Data System (ADS)

    Hänsler, Andreas; Weber, Torsten; Eggert, Bastian; Saeed, Fahad; Jacob, Daniela

    2014-05-01

    Within the CORDEX initiative a multi-model suite of regionalized climate change information will be made available for several regions of the world. The German Climate Service Center (CSC) is taking part in this initiative by applying the regional climate model REMO to downscale global climate projections of different coupled general circulation models (GCMs) for several CORDEX domains. Also for the MENA-CORDEX domain, a set of regional climate change projections has been established at the CSC by downscaling CMIP5 projections of the Max-Planck-Institute Earth System Model (MPI-ESM) for the scenarios RCP4.5 and RCP8.5 with the regional model REMO for the time period from 1950 to 2100 to a horizontal resolution of 0.44 degree. In this study we investigate projected changes in future climate conditions over the domain towards the end of the 21st century. Focus in the analysis is given to projected changes in the temperature and rainfall characteristics and their differences for the two scenarios will be highlighted.

  18. Importance of the Linker Region in Matrix Metalloproteinase-1 Domain Interactions

    PubMed Central

    Singh, Warispreet; Fields, Gregg B.; Christov, Christo Z.; Karabencheva-Christova, Tatyana G.

    2016-01-01

    Collagenolysis is catalyzed by enzymes from the matrix metalloproteinase (MMP) family, where one of the most studied is MMP-1. The X-ray crystallographic structure of MMP-1 complexed with a collagen-model triple-helical peptide (THP) provided important atomistic information, but few details on the effects of the conformational flexibility on catalysis. In addition, the role of the linker region between the catalytic (CAT) and hemopexin-like (HPX) domains was not defined. In order to reveal the dynamics and correlations of MMP-1 comprehensive atomistic molecular dynamics simulations of an MMP-1•THP complex was performed. To examine the role of the linker region for MMP-1 function simulations with linker regions from MT1-MMP/MMP-14 and MMP-13 replacing the MMP-1 linker region were performed. The MD studies were in good agreement with the experimental observation that in the MMP-1•THP X-ray crystallographic structure MMP-1 is in a “closed” conformation. MD revealed that the interactions of the THP with the both the CAT and HPX domains of MMP-1 are dynamic in nature, and the linker region of MMP-1 influences the interactions and dynamics of both the CAT and HPX domains and collagen binding to MMP-1. PMID:26998255

  19. Hypomutable regions of yeast TFIIB in a unigenic evolution test represent structural domains.

    PubMed

    Zeng, Xiao; Zhang, Dongyi; Dorsey, Michael; Ma, Jun

    2003-04-24

    As genome sequences of many organisms - including humans - are being decoded, there is a great need for genetic tools to analyze newly discovered genes/proteins. A 'unigenic evolution' approach has been previously proposed for dissecting protein domains, which is based on the assumption that functionally important regions of a protein may tolerate missense mutations less well than other regions. We describe a unigenic evolution analysis of general transcription factor IIB (TFIIB) - a protein that is well characterized both structurally and functionally - to better understand the molecular basis of this genetic approach. The overall distribution profile of hypomutable regions within yeast TFIIB correlates extremely well with the known compact structural domains, suggesting that the unigenic evolution approach can help reveal structural properties of a protein. We further show that a small region located immediately carboxyl-terminal to the zinc ribbon motif is functionally important despite its strong hypermutability. Our study further demonstrates the usefulness of the unigenic evolution approach in dissecting protein domains, but suggests that the mutability of different regions of a protein in such a test is determined primarily by their structural properties.

  20. Improved precipitation extremes and climatology in a regional coupled model simulation over CORDEX south Asia domain

    NASA Astrophysics Data System (ADS)

    Kumar, P.; Sein, D.; Cabos, W.; Jacob, D.

    2014-12-01

    The South Asian continents are densely populated and their economy is largely dependent on agriculture which primarily depends on the summer monsoon (June-September). The region is highly vulnerable to climate variability and change. It has been well established that the SST anomalies in the Indian and the Pacific Ocean attributes to the monsoon interannual as well as intraseasonal variability. Most of the CMIP3 and CMIP5 climate models have difficulty in simulating the mean climate over South Asia. Regional Climate Models (RCMs) however simulate orographic induced precipitation better, but show limited ability to simulate mean precipitation over land and an overestimation over ocean more generally. These systematic differences between climate models and observation's may be related to poorly represented ocean dynamics and SST.For the first time a regional coupled atmosphere-ocean model is developed to study the monsoon climatology over the CORDEX South Asia domain. The REgional atmosphere MOdel REMO with 50km horizontal resolution is coupled via Oasis coupler to the Max Planck Institute for Meteorology global ocean - sea ice model MPIOM with increased resolution over the Indian Ocean (up to 20 km). Hereafter this coupled system will be called as ROM. For this study, four simulations for the period 1958-2001 are performed (i) REMO forced with ECMWF ERA40 reanalysis (ii) ROM forced with ECMWF ERA40 reanalysis (iii) REMO forced with MPI-ESM-LR CMIP5 historical simulation (iv) ROM forced with MPI-ESM-LR CMIP5 historical simulation. Differences in coupled and un-coupled RCM simulations are analyzed to investigate the effect of coupling on simulated climate, especially precipitation daily annual cycles and monthly spatial patterns. It has been observed that simulated feedback of ocean SST has positive influence on precipitation simulation of ROM both over land and ocean. The intensity of tropical cyclone is well simulated by the model ROM which improves the monsoon

  1. More Than 1,001 Problems with Protein Domain Databases: Transmembrane Regions, Signal Peptides and the Issue of Sequence Homology

    PubMed Central

    Wong, Wing-Cheong; Maurer-Stroh, Sebastian; Eisenhaber, Frank

    2010-01-01

    Large-scale genome sequencing gained general importance for life science because functional annotation of otherwise experimentally uncharacterized sequences is made possible by the theory of biomolecular sequence homology. Historically, the paradigm of similarity of protein sequences implying common structure, function and ancestry was generalized based on studies of globular domains. Having the same fold imposes strict conditions over the packing in the hydrophobic core requiring similarity of hydrophobic patterns. The implications of sequence similarity among non-globular protein segments have not been studied to the same extent; nevertheless, homology considerations are silently extended for them. This appears especially detrimental in the case of transmembrane helices (TMs) and signal peptides (SPs) where sequence similarity is necessarily a consequence of physical requirements rather than common ancestry. Thus, matching of SPs/TMs creates the illusion of matching hydrophobic cores. Therefore, inclusion of SPs/TMs into domain models can give rise to wrong annotations. More than 1001 domains among the 10,340 models of Pfam release 23 and 18 domains of SMART version 6 (out of 809) contain SP/TM regions. As expected, fragment-mode HMM searches generate promiscuous hits limited to solely the SP/TM part among clearly unrelated proteins. More worryingly, we show explicit examples that the scores of clearly false-positive hits, even in global-mode searches, can be elevated into the significance range just by matching the hydrophobic runs. In the PIR iProClass database v3.74 using conservative criteria, we find that at least between 2.1% and 13.6% of its annotated Pfam hits appear unjustified for a set of validated domain models. Thus, false-positive domain hits enforced by SP/TM regions can lead to dramatic annotation errors where the hit has nothing in common with the problematic domain model except the SP/TM region itself. We suggest a workflow of flagging

  2. Solution coating of large-area organic semiconductor thin films with aligned single-crystalline domains.

    PubMed

    Diao, Ying; Tee, Benjamin C-K; Giri, Gaurav; Xu, Jie; Kim, Do Hwan; Becerril, Hector A; Stoltenberg, Randall M; Lee, Tae Hoon; Xue, Gi; Mannsfeld, Stefan C B; Bao, Zhenan

    2013-07-01

    Solution coating of organic semiconductors offers great potential for achieving low-cost manufacturing of large-area and flexible electronics. However, the rapid coating speed needed for industrial-scale production poses challenges to the control of thin-film morphology. Here, we report an approach--termed fluid-enhanced crystal engineering (FLUENCE)--that allows for a high degree of morphological control of solution-printed thin films. We designed a micropillar-patterned printing blade to induce recirculation in the ink for enhancing crystal growth, and engineered the curvature of the ink meniscus to control crystal nucleation. Using FLUENCE, we demonstrate the fast coating and patterning of millimetre-wide, centimetre-long, highly aligned single-crystalline organic semiconductor thin films. In particular, we fabricated thin films of 6,13-bis(triisopropylsilylethynyl) pentacene having non-equilibrium single-crystalline domains and an unprecedented average and maximum mobilities of 8.1±1.2 cm(2) V(-1) s(-1) and 11 cm(2) V(-1) s(-1). FLUENCE of organic semiconductors with non-equilibrium single-crystalline domains may find use in the fabrication of high-performance, large-area printed electronics.

  3. Nucleolus association of chromosomal domains is largely maintained in cellular senescence despite massive nuclear reorganisation

    PubMed Central

    Dillinger, Stefan

    2017-01-01

    Mammalian chromosomes are organized in structural and functional domains of 0.1–10 Mb, which are characterized by high self-association frequencies in the nuclear space and different contact probabilities with nuclear sub-compartments. They exhibit distinct chromatin modification patterns, gene expression levels and replication timing. Recently, nucleolus-associated chromosomal domains (NADs) have been discovered, yet their precise genomic organization and dynamics are still largely unknown. Here, we use nucleolus genomics and single-cell experiments to address these questions in human embryonic fibroblasts during replicative senescence. Genome-wide mapping reveals 1,646 NADs in proliferating cells, which cover about 38% of the annotated human genome. They are mainly heterochromatic and correlate with late replicating loci. Using Hi-C data analysis, we show that interactions of NADs dominate interphase chromosome contacts in the 10–50 Mb distance range. Interestingly, only minute changes in nucleolar association are observed upon senescence. These spatial rearrangements in subdomains smaller than 100 kb are accompanied with local transcriptional changes. In contrast, large centromeric and pericentromeric satellite repeat clusters extensively dissociate from nucleoli in senescent cells. Accordingly, H3K9me3-marked heterochromatin gets remodelled at the perinucleolar space as revealed by immunofluorescence analyses. Collectively, this study identifies connections between the nucleolus, 3D genome structure, and cellular aging at the level of interphase chromosome organization. PMID:28575119

  4. Solution coating of large-area organic semiconductor thin films with aligned single-crystalline domains

    NASA Astrophysics Data System (ADS)

    Diao, Ying; Tee, Benjamin C.-K.; Giri, Gaurav; Xu, Jie; Kim, Do Hwan; Becerril, Hector A.; Stoltenberg, Randall M.; Lee, Tae Hoon; Xue, Gi; Mannsfeld, Stefan C. B.; Bao, Zhenan

    2013-07-01

    Solution coating of organic semiconductors offers great potential for achieving low-cost manufacturing of large-area and flexible electronics. However, the rapid coating speed needed for industrial-scale production poses challenges to the control of thin-film morphology. Here, we report an approach—termed fluid-enhanced crystal engineering (FLUENCE)—that allows for a high degree of morphological control of solution-printed thin films. We designed a micropillar-patterned printing blade to induce recirculation in the ink for enhancing crystal growth, and engineered the curvature of the ink meniscus to control crystal nucleation. Using FLUENCE, we demonstrate the fast coating and patterning of millimetre-wide, centimetre-long, highly aligned single-crystalline organic semiconductor thin films. In particular, we fabricated thin films of 6,13-bis(triisopropylsilylethynyl) pentacene having non-equilibrium single-crystalline domains and an unprecedented average and maximum mobilities of 8.1±1.2 cm2 V-1 s-1 and 11 cm2 V-1 s-1. FLUENCE of organic semiconductors with non-equilibrium single-crystalline domains may find use in the fabrication of high-performance, large-area printed electronics.

  5. Regional Bowen ratio controls on afternoon moist convection: A large eddy simulation study

    NASA Astrophysics Data System (ADS)

    Kang, Song-Lak

    2016-12-01

    This study examines the effect of the regional Bowen ratio β, the ratio of the domain-averaged surface sensible heat flux (SHF) to latent heat flux (LHF), on afternoon moist convection. With a temporally evolving but spatially uniform surface available energy over a mesoscale domain under a weak capping inversion, we run large eddy simulation of the afternoon convective boundary layer (CBL). We first prescribe a small β of 0.56 (a wet surface) and then the reversed large β of 1.80 (a dry surface) by switching the SHF and LHF fields. The perturbation fields of the fluxes are prescribed with the Fourier spectra of κ- 3 (κ is horizontal wave number; strong mesoscale heterogeneity) and κ0 (homogeneity). The large β cases have strong vertical buoyancy fluxes and produce more vigorous updrafts. In the heterogeneous, large β surface case, with the removal of convective inhibition over a mesoscale subdomain of large SHF, deep convection develops. In the heterogeneous, small β surface case, convective clouds develop but do not progress into precipitating convection. In the homogeneous surface cases, randomly distributed shallow clouds develop with significantly more and thicker clouds in the large β case. (Co)spectral analyses confirm the more vigorous turbulent thermals in the large β cases and reveal that the moisture advection by the surface heterogeneity-induced mesoscale flows makes the correlation between mesoscale temperature and moisture perturbations change from negative to positive, which facilitates the mesoscale pool of high relative humidity air just above the CBL top, a necessary condition for deep convection.

  6. 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.

  7. 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.

  8. Can limited area NWP and/or RCM models improve on large scales inside their domain?

    NASA Astrophysics Data System (ADS)

    Mesinger, Fedor; Veljovic, Katarina

    2017-04-01

    In a paper in press in Meteorology and Atmospheric Physics at the time this abstract is being written, Mesinger and Veljovic point out four requirements that need to be fulfilled by a limited area model (LAM), be it in NWP or RCM environment, to improve on large scales inside its domain. First, NWP/RCM model needs to be run on a relatively large domain. Note that domain size in quite inexpensive compared to resolution. Second, NWP/RCM model should not use more forcing at its boundaries than required by the mathematics of the problem. That means prescribing lateral boundary conditions only at its outside boundary, with one less prognostic variable prescribed at the outflow than at the inflow parts of the boundary. Next, nudging towards the large scales of the driver model must not be used, as it would obviously be nudging in the wrong direction if the nested model can improve on large scales inside its domain. And finally, the NWP/RCM model must have features that enable development of large scales improved compared to those of the driver model. This would typically include higher resolution, but obviously does not have to. Integrations showing improvements in large scales by LAM ensemble members are summarized in the mentioned paper in press. Ensemble members referred to are run using the Eta model, and are driven by ECMWF 32-day ensemble members, initialized 0000 UTC 4 October 2012. The Eta model used is the so-called "upgraded Eta," or "sloping steps Eta," which is free of the Gallus-Klemp problem of weak flow in the lee of the bell-shaped topography, seemed to many as suggesting the eta coordinate to be ill suited for high resolution models. The "sloping steps" in fact represent a simple version of the cut cell scheme. Accuracy of forecasting the position of jet stream winds, chosen to be those of speeds greater than 45 m/s at 250 hPa, expressed by Equitable Threat (or Gilbert) skill scores adjusted to unit bias (ETSa) was taken to show the skill at large scales

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. A Regional health care network: eHealth.Braunschweig. Domain fields and architectural challenges.

    PubMed

    Gusew, N; Bartkiewicz, T; Bautsch, W; Gerlach, A; Goldapp, M; Haux, R; Heller, U; Kierdorf, H P; Kleinschmidt, T; Ludwig, W; Markurth, U; Pfingsten-Würzburg, S; Plischke, M; Reilmann, H; Schubert, R; Seidel, C; Warnke, R

    2012-01-01

    Health care network eHealth.Braunschweig has been started in the South-East region of Lower Saxony in Germany in 2009. It composes major health care players, participants from research institutions and important local industry partners. The objective of this paper is firstly to describe the relevant regional characteristics and distinctions of the eHealth.Braunschweig health care network and to inform about the goals and structure of eHealth.Braunschweig; secondly to picture and discuss the main concepts and domain fields which are addressed in the health care network; and finally to discuss the architectural challenges of eHealth.Braunschweig regarding the addressed domain fields and defined requirements. Based on respective literature and former conducted projects we discuss the project structure and goals of eHealth.Braunschweig, depict major domain fields and requirements gained in workshops with participants and discuss the architectural challenges as well as the architectural approach of eHealth.Braunschweig network. The regional healthcare network eHealth.Braunschweig has been established in April 2009. Since then the network has grown constantly and a sufficient progress in network activities has been achieved. The main domain fields have been specified in different workshops with network participants and an architectural realization approach for the transinstitutional information system architecture in the healthcare network has been developed. However, the effects on quality of information processing and quality of patient care have not been proved yet. Systematic evaluation studies have to be done in future in order to investigate the impact of information and communication technology on the quality of information processing and the quality of patient care. In general, the aspects described in this paper are expected to contribute to a systematic approach for the establishment of regional health care networks with lasting and sustainable effects on

  14. Functional regions of the N-terminal domain of the antiterminator RfaH

    PubMed Central

    Belogurov, Georgiy A; Sevostyanova, Anastasia; Svetlov, Vladimir; Artsimovitch, Irina

    2010-01-01

    RfaH is a bacterial elongation factor that increases expression of distal genes in several long, horizontally acquired operons. RfaH is recruited to the transcription complex during RNA chain elongation through specific interactions with a DNA element called ops. Following recruitment, RfaH remains bound to RNA polymerase (RNAP) and acts as an antiterminator by reducing RNAP pausing and termination at some factor-independent and Rho-dependent signals. RfaH consists of two domains connected by a flexible linker. The N-terminal RfaH domain (RfaHN) recognizes the ops element, binds to the RNAP and reduces pausing and termination in vitro. Functional analysis of single substitutions in this domain reported here suggests that three separate RfaHN regions mediate these functions. We propose that a polar patch on one side of RfaHN interacts with the non-template DNA strand during recruitment, whereas a hydrophobic surface on the opposite side of RfaHN remains bound to the β′ subunit clamp helices domain throughout transcription of the entire operon. The third region is apparently dispensable for RfaH binding to the transcription complex but is required for the antitermination modification of RNAP. PMID:20132437

  15. 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.

  16. Sarcocystis neurona: molecular characterization of enolase domain I region and a comparison to other protozoa.

    PubMed

    Bolten, K E; Marsh, A E; Reed, S M; Dubey, J P; Toribio, R E; Saville, W J A

    2008-09-01

    Sarcocystis neurona causes protozoal myeloencephalitis and has the ability to infect a wide host range in contrast to other Sarcocystis species. In the current study, five S. neurona isolates from a variety of sources, three Sarcocystis falcatula, one Sarcocystis dasypi/S. neurona-like isolate, and one Besnoitia darlingi isolate were used to compare the enolase 2 gene segment containing the domain I region to previously sequenced enolase genes from Neospora caninum, Neospora hughesi, Toxoplasma gondii, Plasmodium falciparum, and Trypanosoma cruzi; enolase 2 segment containing domain I region is highly conserved amongst these parasites of veterinary and medical importance. Immunohistochemistry results indicates reactivity of T. gondii enolase 1 and 2 antibodies to S. neurona merozoites and metrocytes, but no reactivity of anti-enolase 1 to the S. neurona bradyzoite stage despite reactivity to T. gondii bradyzoites, suggesting expression differences between organisms.

  17. The methyltransferase SETDB1 regulates a large neuron-specific topological chromatin domain.

    PubMed

    Jiang, Yan; Loh, Yong-Hwee Eddie; Rajarajan, Prashanth; Hirayama, Teruyoshi; Liao, Will; Kassim, Bibi S; Javidfar, Behnam; Hartley, Brigham J; Kleofas, Lisa; Park, Royce B; Labonte, Benoit; Ho, Seok-Man; Chandrasekaran, Sandhya; Do, Catherine; Ramirez, Brianna R; Peter, Cyril J; C W, Julia T; Safaie, Brian M; Morishita, Hirofumi; Roussos, Panos; Nestler, Eric J; Schaefer, Anne; Tycko, Benjamin; Brennand, Kristen J; Yagi, Takeshi; Shen, Li; Akbarian, Schahram

    2017-08-01

    We report locus-specific disintegration of megabase-scale chromosomal conformations in brain after neuronal ablation of Setdb1 (also known as Kmt1e; encodes a histone H3 lysine 9 methyltransferase), including a large topologically associated 1.2-Mb domain conserved in humans and mice that encompasses >70 genes at the clustered protocadherin locus (hereafter referred to as cPcdh). The cPcdh topologically associated domain (TAD(cPcdh)) in neurons from mutant mice showed abnormal accumulation of the transcriptional regulator and three-dimensional (3D) genome organizer CTCF at cryptic binding sites, in conjunction with DNA cytosine hypomethylation, histone hyperacetylation and upregulated expression. Genes encoding stochastically expressed protocadherins were transcribed by increased numbers of cortical neurons, indicating relaxation of single-cell constraint. SETDB1-dependent loop formations bypassed 0.2-1 Mb of linear genome and radiated from the TAD(cPcdh) fringes toward cis-regulatory sequences within the cPcdh locus, counterbalanced shorter-range facilitative promoter-enhancer contacts and carried loop-bound polymorphisms that were associated with genetic risk for schizophrenia. We show that the SETDB1 repressor complex, which involves multiple KRAB zinc finger proteins, shields neuronal genomes from excess CTCF binding and is critically required for structural maintenance of TAD(cPcdh).

  18. Combined domain-decomposition and matrix-decomposition scheme for large-scale diffuse optical tomography.

    PubMed

    Yang, Fang; Gao, Feng; Ruan, Pingqiao; Zhao, Huijuan

    2010-06-01

    Image reconstruction in diffuse optical tomography (DOT) is, in general, posed as a model-based, nonlinear optimization problem, which requires repeated use of the three-dimensional (3D) forward and inverse solvers. To cope with the computation and storage problem for some applications, such as breast tumor diagnosis, it is preferable to develop a subdomain-based parallel computation scheme. In this study, we propose a two-level image reconstruction scheme for 3D DOT, which combines the Schwarz-type domain-decomposition (DD)-based forward calculation and the matrix-decomposition (MD)-based inversion. In the forward calculation, the solution to the diffusion equation is initially obtained using a whole-domain finite difference method at a coarse grid, and then updated with a parallel DD scheme at a fine grid. The inversion procedure starts with the wavelet-decomposition-based reconstruction at a coarse grid, and then follows with a Levenberg-Marquardt least-squares solution at a fine grid, where an MD strategy is adopted for the relevant linear inversion. It is demonstrated that the combination of the DD-based forward solver and MD-based inversion allows for coarse-grain parallel implementation of both the forward and inverse issues and effectively reduces computation and storage loads for the large-scale problem. Also, both numerical simulations and phantom experiments show that MD-based linear inversion is superior to the row-fashioned algebraic reconstruction technique.

  19. A regional paleomagnetic study of lithotectonic domains in the Central Gneiss Belt, Grenville Province, Ontario

    NASA Astrophysics Data System (ADS)

    Constanzo Alvarez, Vincenzo; Dunlop, David J.

    1998-04-01

    We have made a regional paleomagnetic study of lithotectonic domains in the Central Gneiss Belt of the Grenville Province in Ontario along ten N-S and E-W traverses up to 200 km in length. Although originally intended to clarify the tectonic mechanism by which these exotic terranes were assembled and welded to the Archean Superior craton during the ˜1150-Ma Grenvillian orogeny, we actually learned much more about the timing of post-orogenic uplift of the various domains around 1000-900 Ma as they stabilized and became part of the Rodinia supercontinent. The normal (N) and reverse (R) natural remanent magnetizations (NRMs) of all domains, as well as those of reactivated regions flanking the Grenville Front (GF, the Superior-Grenville boundary) to the north and south, have paleomagnetic poles falling on the 980-920-Ma ( 40Ar/ 39Ar calibrated) portion of the Grenville apparent polar wander track for Laurentia. There is a general tendency for paleopoles to young with increasing distance of domains from the GF, implying that more southerly domains were uplifted and magnetized later, but two of the domains do not fit this pattern. Previously reported younging trends away from the GF, based on K/Ar thermochron maps and paleomagnetic 'zone poles', are untrustworthy because of hydrothermal alteration, which causes chemical remagnetization and anomalously old K/Ar ages near the GF. Another trend in our data is a regular increase in the R/N ratio with increasing distance south of the GF. In the reactivated zones flanking the GF, NRMs are overwhelmingly of N polarity, whereas well away from the GF, R/N is close to 50:50. Also, NRM intensities and susceptibility values increase 100-fold away from the GF, peaking ≈10 km south of the front, with a pulse-like pattern similar to that documented in anomalously high 40Ar/ 39Ar dates in the same region. Both the magnetic and Ar/Ar results are likely due to a 'wave' of hydrothermal alteration and remagnetization during which fluids

  20. Leveraging domain knowledge to facilitate visual exploration of large population datasets.

    PubMed

    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.

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

    PubMed

    Rosensteiner, Matthias

    2012-11-01

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

  2. Domain decomposition approach to extract pore-network models from large 3D porous media images

    NASA Astrophysics Data System (ADS)

    Timofey, Sizonenko; Marina, Karsanina; Irina, Bayuk; Kirill, Gerke

    2017-04-01

    Pore-network are very useful and effective method to model porous media structure and properties such as permeability and multi-phase flow. Several methods for pore-network extraction were proposed to date, including median axis, maximal inscribed ball, watershed techniques and their modifications. Input data for pore-network extraction algorithms usually represent 3D binary image. Modern X-ray tomography devices can easily provide scans with dimensions of 4k x 4k x 10k voxels. For such large images extraction algorithms may hit the problem of memory (RAM) consumption or will too time consuming. To overcome such problems or create parallelizable algorithm here we propose to divide the whole volume into sub-volumes with smaller size and extract pore- network sequentially/in parallel manner separately. However, the problem of correct pore-network extraction at the sub-volume connection areas is challenging. In this contribution we address this issue in detail. We propose a method to merge such sub-volumes. Our method explores the slices of porous medium under study at the sub-volumes intersections. Each slice has its own geometric features and associated with a number of pores or throats. Characteristics of pore that associated with slice such as diameter, distance its center to the sub-domain boundary are also taken into account. Based on the pore element properties and also properties of aforementioned slices the algorithm makes decision about how pores from opposite sides of sub-volumes should be connected. There are 3 cases of merging: 1) building a throat between pores, 2) absorption of one pore by the other, 3) breaking connection (no pore or throat are built). We have tested our approach on several different binary 3D images, including soil, sandstones, and carbonates. We also compared this new approach against a conventional one where the extraction is performed using the whole domain without its decomposition into sub-domains. We show that our approach

  3. 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

  4. River Seepage Conductance in Large-Scale Regional Studies.

    PubMed

    Morel-Seytoux, Hubert J; Miller, Calvin D; Miracapillo, Cinzia; Mehl, Steffen

    2016-12-20

    Flow exchange between surface and groundwater is of great importance be it for beneficial allocation and use of water resources or for the proper exercise of water rights. In large-scale regional studies, most numerical models use coarse grid sizes, which make it difficult to provide an accurate depiction of the phenomenon. In particular, a somewhat arbitrary leakance coefficient in a third type (i.e., Cauchy, General Head) boundary condition is used to calculate the seepage discharge as a function of the difference of head in the river and in the aquifer, whose value is often found by calibration. A different approach is presented to analytically estimate that leakance coefficient. It is shown that a simple equivalence can be deduced from the analytical solution for the empirical coefficient, so that it provides the accuracy of the analytical solution while the model maintains a very coarse grid, treating the water-table aquifer as a single calculation layer. Relating the empirical leakance coefficient to the exact conductance, derived from physical principles, provides a physical basis for the leakance coefficient. Factors such as normalized wetted perimeter, degree of penetration of the river, presence of a clogging layer, and anisotropy can be included with little computational demand. In addition the river coefficient in models such as MODFLOW, for example, can be easily modified when grid size is changed without need for recalibration.

  5. Dynamical downscaling of historical climate over CORDEX Central America domain with a regionally coupled ocean-atmosphere model

    NASA Astrophysics Data System (ADS)

    Quintanar, Arturo I.; Sein, Dmitry; Martinez-Lopez, Benjamin; Cabos, William; Ochoa-Moya, Carlos-Abraham

    2017-04-01

    ABSTRACT Recently, there has been a concerted effort by several research groups to model precipitation variability for North America and Central America in the context of the Coordinated Regional Climate Downscaling Experiment (CORDEX). One important objective of CORDEX is to dynamically downscale global output from coupled and non-coupled models and to objectively gauge a measure of added value from higher resolution boundary conditions forcing regional atmospheric and ocean models at their lateral walls. Up to now, a sufficiently large computational domain covering from the southern US to the north of South America including the eastern Pacific Ocean, the southern Atlantic and the Caribbean Seas has been lacking. Such a computational domain permits the analysis of an ample range of inter-annual and intra-seasonal time-scales phenomena and the possibility of exploring sensitivity to horizontal resolution. To date, most simulations performed for the region remain too coarse to be of any use at the regional scale but also, and most importantly, most modeling studies of the region rely on regional atmospheric models forced at their lower boundaries by prescribed sea surface temperature. In this work we explore both, climate sensitivity to coupling and, to the choice of horizontal resolution, using a regional atmospheric model (REMO) coupled to a global ocean model (MPI-OM). External atmospheric forcing is applied to REMO at its lateral walls and over the ocean surface that is not coupled to REMO. In order to gain insight into the sensitivity to the choice of the atmospheric forcing, two sources are used: 1) ERA-Interim and 2) a global free run of the MPI-ESM coupled system. Preliminary results suggest that the original biases between the ERA-Interim and the MPI-ESM forcing data tend to become similar when comparing the downscaled simulations at 50 km and 25 km atmospheric resolutions. Additionally, biases at 25 km tend to become smaller over most of the computational

  6. The Arctic Marine Pulses Model: Linking Contiguous Domains in the Pacific Arctic Region

    NASA Astrophysics Data System (ADS)

    Moore, S. E.; Stabeno, P. J.

    2016-02-01

    The Pacific Arctic marine ecosystem extends from the northern Bering Sea, across the Chukchi and into the East Siberian and Beaufort seas. Food webs in this domain are short, a simplicity that belies the biophysical complexity underlying trophic linkages from primary production to humans. Existing biophysical models, such as pelagic-benthic coupling and advective processes, provide frameworks for connecting certain aspects of the marine food web, but do not offer a full accounting of events that occur seasonally across the Pacific Arctic. In the course of the Synthesis of Arctic Research (SOAR) project, a holistic Arctic Marine Pulses (AMP) model was developed that depicts seasonal biophysical `pulses' across a latitudinal gradient, and linking four previously-described contiguous domains, including the: (i) Pacific-Arctic domain = the focal region; (ii) seasonal ice zone domain; (iii) Pacific marginal domain; and (iv) riverine coastal domain. The AMP model provides a spatial-temporal framework to guide research on dynamic ecosystem processes during this period of rapid biophysical changes in the Pacific Arctic. Some of the processes included in the model, such as pelagic-benthic coupling in the Northern Bering and Chukchi seas, and advection and upwelling along the Beaufort shelf, are already the focus of sampling via the Distributed Biological Observatory (DBO) and other research programs. Other aspects such as biological processes associated with the seasonal ice zone and trophic responses to riverine outflow have received less attention. The AMP model could be enhanced by the application of visualization tools to provide a means to watch a season unfold in space and time. The capability to track sea ice dynamics and water masses and to move nutrients, prey and upper-trophic predators in space and time would provide a strong foundation for the development of predictive human-inclusive ecosystem models for the Pacific Arctic.

  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. Large-scale Meta-analysis Suggests Low Regional Modularity in Lateral Frontal Cortex.

    PubMed

    de la Vega, Alejandro; Yarkoni, Tal; Wager, Tor D; Banich, Marie T

    2017-09-11

    Extensive fMRI study of human lateral frontal cortex (LFC) has yet to yield a consensus mapping between discrete anatomy and psychological states, partly due to the difficulty of inferring mental states from brain activity. Despite this, there have been few large-scale efforts to map the full range of psychological states across the entirety of LFC. Here, we used a data-driven approach to generate a comprehensive functional-anatomical mapping of LFC from 11 406 neuroimaging studies. We identified putatively separable LFC regions on the basis of whole-brain co-activation, revealing 14 clusters organized into 3 whole-brain networks. Next, we generated functional preference profiles by using multivariate classification to identify the psychological states that best predicted activity within each cluster. We observed large functional differences between networks, suggesting brain networks support distinct modes of processing. Within each network, however, we observed relatively low functional specificity, suggesting discrete psychological states are not strongly localized to individual regions; instead, our results are consistent with the view that individual LFC regions work as part of distributed networks to give rise to flexible behavior. Collectively, our results provide a comprehensive synthesis of a diverse neuroimaging literature using relatively unbiased data-driven methods. Published by Oxford University Press 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  9. 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

  10. 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.

  11. Structure of the dimerization domain of DiGeorge Critical Region 8

    PubMed Central

    Senturia, Rachel; Faller, Michael; Yin, Sheng; Loo, Joseph A; Cascio, Duilio; Sawaya, Michael R; Hwang, Daniel; Clubb, Robert T; Guo, Feng

    2010-01-01

    Maturation of microRNAs (miRNAs, ∼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 Å 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. PMID:20506313

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

    PubMed

    Senturia, Rachel; Faller, Michael; Yin, Sheng; Loo, Joseph A; Cascio, Duilio; Sawaya, Michael R; Hwang, Daniel; Clubb, Robert T; Guo, Feng

    2010-07-01

    Maturation of microRNAs (miRNAs, approximately 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 A 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.

  13. 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

  14. Angular dependence of the reflectance from an isotropic polydomain medium: effect of large domain size on total reflection.

    PubMed

    Mayerhöfer, Thomas G; Popp, Jürgen

    2005-03-01

    We investigate the angular dependence of the reflectance from an isotropic medium consisting of optically large and anisotropic, randomly oriented domains, assuming a highly refractive, isotropic, and homogeneous incidence medium, which is presumed to have a higher refractive index than any of the domains' principal indices of refraction. By employing average reflectance and transmittance theory, we are able to show that the onset of total reflection is considerably shifted to higher angles of incidence compared with an isotropic medium with domains that are small compared with the wavelength. The onset of total reflection for a random medium with large domains is found to be dependent only on the largest principal index of refraction of the domains, assuming that all domains have the same optical properties. Therefore the shift of the onset depends on the magnitude of the optical anisotropy of the domains. Even in the case of a small optical anisotropy, large cross-polarization terms are predicted in the vicinity of the onset of total reflection. These terms show a pronounced maximum near that onset and extend beyond it.

  15. Time Domain Science and Fundamental Physics with the Next-generation Very Large Array

    NASA Astrophysics Data System (ADS)

    Demorest, Paul; Bower, Geoffrey C.; ngVLA Time Domain/Physics Science Working Group

    2017-01-01

    The Next-generation Very Large Array (ngVLA) is a design concept for a future large-area radio telescope under development by the NRAO and interested members of the scientific community. The approximate ngVLA specifications call for a frequency range of ~1--116 GHz, ten times the effective collecting area and moderately increased field of view versus the current VLA, and an array configuration consisting of a dense (~km-scale) array core with some baselines extending out to hundreds of km. This instrument will enable new discoveries in many diverse areas of research relevant to modern astronomy; our group has explored the impact the ngVLA will have in time domain astronomy and fundamental physics.Here we present several key science topics considered as part of this work. These include: Searching for and timing radio pulsars at the galactic center -- the frequency coverage and sensitivity of the ngVLA will allow detection of highly-scattered pulsars near Sgr A*. Monitoring these sources will permit unprecedented tests of general relativity. Detecting and characterizing explosive transient sources -- electromagnetic observations of gravitational-wave sources provide complementary information to the GW signals themselves. Observations across the wide frequency range spanned by the ngVLA are critical for energy calorimetry of these events. Finally, with sufficient long-baseline coverage, novel astrometric approaches to cosmology become possible, by watching the expansion of the universe in real time through correlated proper motions of many extragalactic radio sources.

  16. Spatial Bayesian hierarchical modeling of precipitation extremes over a large domain

    NASA Astrophysics Data System (ADS)

    Bracken, C.; Rajagopalan, B.; Cheng, L.; Kleiber, W.; Gangopadhyay, S.

    2016-08-01

    We propose a Bayesian hierarchical model for spatial extremes on a large domain. In the data layer a Gaussian elliptical copula having generalized extreme value (GEV) marginals is applied. Spatial dependence in the GEV parameters is captured with a latent spatial regression with spatially varying coefficients. Using a composite likelihood approach, we are able to efficiently incorporate a large precipitation data set, which includes stations with missing data. The model is demonstrated by application to fall precipitation extremes at approximately 2600 stations covering the western United States, -125°E to -100°E longitude and 30°N-50°N latitude. The hierarchical model provides GEV parameters on a 1/8° grid and, consequently, maps of return levels and associated uncertainty. The model results indicate that return levels and their associated uncertainty have a well-defined spatial structure. Maps of return levels provide information about the spatial variations of the risk of extreme precipitation in the western US and is expected to be useful for infrastructure planning.

  17. Stacking of large interferometric data sets in the image- and uv-domain - a comparative study

    NASA Astrophysics Data System (ADS)

    Lindroos, L.; Knudsen, K. K.; Vlemmings, W.; Conway, J.; Martí-Vidal, I.

    2015-02-01

    We present a new algorithm for stacking radio interferometric data in the uv-domain. The performance of uv-stacking is compared to the stacking of fully imaged data using simulated Atacama Large Millimeter/submillimeter Array and the Karl G. Jansky Very Large Array (VLA) deep extragalactic surveys. We find that image- and uv-stacking produce similar results, however, uv-stacking is typically the more robust method. An advantage of the uv-stacking algorithm is the availability of uv-data post-stacking, which makes it possible to identify and remove problematic baselines. For deep VLA surveys uv-stacking yields a signal-to-noise ratio that is up to 20 per cent higher than image-stacking. Furthermore, we have investigated stacking of resolved sources with a simulated VLA data set where 1.5 arcsec (10-12 kpc at z ˜ 1-4) sources are stacked. We find that uv-stacking, where a model is fitted directly to the visibilities, significantly improves the accuracy and robustness of the size estimates. While scientific motivation for this work is studying faint, high-z galaxies, the algorithm analysed here would also be applicable in other fields of astronomy. Stacking of radio interferometric data is also expected to play a big role for future surveys with telescopes such as Low-Frequency Array and Square Kilometre Array.

  18. Evidences of SNPs in the variable region of hemocyanin Ig-like domain in shrimp Litopenaeus vannamei.

    PubMed

    Guo, Lingling; Zhao, Xianliang; Zhang, Yueling; Wang, Zehuan; Zhong, Mingqi; Li, Shengkang; Lun, Jingsheng

    2013-11-01

    Single nucleotide polymorphisms (SNPs) are the commonest mode of genetic variation in invertebrate immune-related genes. Hemocyanin presents in the hemolymph of both mollusks and arthropods and functions as an important antigen non-specific immune protein. But people know very little about its gene polymorphism so far. In current study, bioinformatics, molecular biology and environmental challenge approaches were used to identify the SNPs within hemocyanin Ig-like domain in shrimp Litopenaeus vannamei. A total of 11 SNPs were found in a variable region of Ig-like domain from L. vannamei hemocyanin large subunit (1258-1460 bp, HcLV1), 5 of which (1272, 1315, 1380, 1410 and 1450) were confirmed present in both genomic DNA and cDNA by clone sequencing. Furthermore, HcLV1 showed 3, 5 and 5 SSCP bands, respectively, in 16, 25 and 30 °C-treated shrimps, suggesting that the SSCP pattern of HcLV1 could be modulated by environmental stress. In addition, HcLV1 displayed two extra bands with different mobility when shrimps treated with Vibrio parahaemolyticus for 6-24 h, which was not observed in the control group. In conclusion, our data suggest that shrimp L. vannamei hemocyanin Ig-like domain possesses SNPs, which may be associated with environmental stress or pathogenic challenge.

  19. Formation of large PEE domains in PEE212-PEO112 diblock copolymer monolayers: shift of the PEO-desorption transition.

    PubMed

    Wesemann, Alexander; Ahrens, Heiko; Förster, Stephan; Helm, Christiane A

    2004-12-21

    PEE212-PEO112 diblock copolymer monolayers are studied at the air/water interface. At large molecular areas, with X-ray reflectivity, PEE domains are observed, which are partly immersed into the water. The domain thickness increases on compression (28 to 40 A). With off-specular X-ray reflectivity, an average domain radius of 750 A is found, but there are also smaller domains. Due to these space constraints, most PEO blocks form a brush beneath the PEE domains. Only a few PEO blocks form a corona surrounding the domains and adsorb flatly onto the air/water interface. The PEO desorption transition is observed at the typical pressure of 9 mN/m, when the flatly adsorbed PEO is compressed at a domain fraction of 95%. It occurs at 6 A2/EO monomer, about half the value found for lipopolymers or diblock copolymers with NPEE approximately NPEO or NPEE < NPEO. Apparently, the thickness of the PEE domains is determined by the forces from the two interfaces, not by the PEO block, for which flat adsorption beneath the domain would be more favorable instead of formation of a PEO brush.

  20. 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

  1. The SV40 large T-antigen origin binding domain directly participates in DNA unwinding.

    PubMed

    Foster, Erin C; Simmons, Daniel T

    2010-03-16

    The origin binding domain (OBD) of SV40 large T-ag serves a critical role during initiation of DNA replication to position T-ag on the origin. After origin recognition, T-ag forms a double hexamer over the origin. Within each hexamer, the OBD adopts a lock washer structure where the origin recognizing A1 and B2 loops face toward the helicase domain and likely become unavailable for binding DNA. In this study, we investigated the role of the central channel of the OBD hexamer in DNA replication by analyzing the effects of mutations of residues lining the channel. All mutants showed binding defects with origin DNA and ssDNA especially at low protein concentrations, but only half were defective at supporting DNA replication in vitro. All mutants were normal in unwinding linear origin DNA fragments. However, replication defective mutants failed to unwind a small origin containing circular DNA whereas replication competent mutants did so normally. The presence of RPA and/or pol/prim restored circular DNA unwinding activity of compromised mutants probably by interacting with the separated DNA strands on the T-ag surface. We interpret these results to indicate a role for the OBD central channel in binding and threading ssDNA during unwinding of circular SV40 DNA. Mixing experiments suggested that only one monomer in an OBD hexamer was necessary for DNA unwinding. We present a model of DNA threading through the T-ag complex illustrating how single-stranded DNA could pass close to a trough generated by key residues in one monomer of the OBD hexamer.

  2. 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

  3. Domain decomposition-based structural condensation of large protein structures for understanding their conformational dynamics.

    PubMed

    Kim, Jae In; Na, Sungsoo; Eom, Kilho

    2011-01-15

    Normal mode analysis (NMA) with coarse-grained model, such as elastic network model (ENM), has allowed the quantitative understanding of protein dynamics. As the protein size is increased, there emerges the expensive computational process to find the dynamically important low-frequency normal modes due to diagonalization of massive Hessian matrix. In this study, we have provided the domain decomposition-based structural condensation method that enables the efficient computations on low-frequency motions. Specifically, our coarse-graining method is established by coupling between model condensation (MC; Eom et al., J Comput Chem 2007, 28, 1400) and component mode synthesis (Kim et al., J Chem Theor Comput 2009, 5, 1931). A protein structure is first decomposed into substructural units, and then each substructural unit is coarse-grained by MC. Once the NMA is implemented to coarse-grained substructural units, normal modes and natural frequencies for each coarse-grained substructural unit are assembled by using geometric constraints to provide the normal modes and natural frequencies for whole protein structure. It is shown that our coarse-graining method enhances the computational efficiency for analysis of large protein complexes. It is clearly suggested that our coarse-graining method provides the B-factors of 100 large proteins, quantitatively comparable with those obtained from original NMA, with computational efficiency. Moreover, the collective behaviors and/or the correlated motions for model proteins are well delineated by our suggested coarse-grained models, quantitatively comparable with those computed from original NMA. It is implied that our coarse-grained method enables the computationally efficient studies on conformational dynamics of large protein complex.

  4. Novel structure of an N-terminal domain that is crucial for the dimeric assembly and DNA-binding of an archaeal DNA polymerase D large subunit from Pyrococcus horikoshii.

    PubMed

    Matsui, Ikuo; Urushibata, Yuji; Shen, Yulong; Matsui, Eriko; Yokoyama, Hideshi

    2011-02-04

    Archaea-specific D-family DNA polymerase forms a heterotetramer consisting of two large polymerase subunits and two small exonuclease subunits. The N-terminal (1-300) domain structure of the large subunit was determined by X-ray crystallography, although ∼50 N-terminal residues were disordered. The determined structure consists of nine alpha helices and three beta strands. We also identified the DNA-binding ability of the domain by SPR measurement. The N-terminal (1-100) region plays crucial roles in the folding of the large subunit dimer by connecting the ∼50 N-terminal residues with their own catalytic region (792-1163).

  5. The basic region of the diaphanous-autoregulatory domain (DAD) is required for autoregulatory interactions with the diaphanous-related formin inhibitory domain.

    PubMed

    Wallar, Bradley J; Stropich, Brittany N; Schoenherr, Jessica A; Holman, Holly A; Kitchen, Susan M; Alberts, Arthur S

    2006-02-17

    Mammalian diaphanous-related (mDia) formins act as Rho GTPase effectors during cytoskeletal remodeling. Rho binding to mDia amino-terminal GTPase-binding domains (GBDs) causes the adjacent Dia-inhibitory domain (DID) to release the carboxyl-terminal Dia-autoregulatory (DAD) domain that flanks the formin homology-2 (FH2) domain. The release of DAD allows the FH2 domain to then nucleate and elongate nonbranched actin filaments. DAD, initially discovered as a region of homology shared between a phylogenetically divergent set of formin proteins, is comprised of a core motif, MDXLLXL, and an adjacent region is comprised of numerous basic residues, typically RRKR in the mDia family. Here, we show that these specific amino acids within the basic region of DAD contribute to the binding of DID and therefore the maintenance of the mDia autoregulatory mechanism. In addition, expression of full-length versions of mDia2 containing amino acid substitutions in either the DAD core or basic regions causes profound changes in the F-actin architecture, including the formation of filopodia-like structures that rapidly elongate from the cell edge. These studies further refine our understanding of the molecular contribution of DAD to mDia control and the role of mDia2 in the assembly of membrane protrusions.

  6. Implementation Strategies for Large-Scale Transport Simulations Using Time Domain Particle Tracking

    NASA Astrophysics Data System (ADS)

    Painter, S.; Cvetkovic, V.; Mancillas, J.; Selroos, J.

    2008-12-01

    Time domain particle tracking is an emerging alternative to the conventional random walk particle tracking algorithm. With time domain particle tracking, particles are moved from node to node on one-dimensional pathways defined by streamlines of the groundwater flow field or by discrete subsurface features. The time to complete each deterministic segment is sampled from residence time distributions that include the effects of advection, longitudinal dispersion, a variety of kinetically controlled retention (sorption) processes, linear transformation, and temporal changes in groundwater velocities and sorption parameters. The simulation results in a set of arrival times at a monitoring location that can be post-processed with a kernel method to construct mass discharge (breakthrough) versus time. Implementation strategies differ for discrete flow (fractured media) systems and continuous porous media systems. The implementation strategy also depends on the scale at which hydraulic property heterogeneity is represented in the supporting flow model. For flow models that explicitly represent discrete features (e.g., discrete fracture networks), the sampling of residence times along segments is conceptually straightforward. For continuous porous media, such sampling needs to be related to the Lagrangian velocity field. Analytical or semi-analytical methods may be used to approximate the Lagrangian segment velocity distributions in aquifers with low-to-moderate variability, thereby capturing transport effects of subgrid velocity variability. If variability in hydraulic properties is large, however, Lagrangian velocity distributions are difficult to characterize and numerical simulations are required; in particular, numerical simulations are likely to be required for estimating the velocity integral scale as a basis for advective segment distributions. Aquifers with evolving heterogeneity scales present additional challenges. Large-scale simulations of radionuclide

  7. 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).

  8. 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.

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

    PubMed Central

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

    2014-01-01

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

  10. 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.

  11. Identification of amino-terminal region of adiponectin as a physiologically functional domain.

    PubMed

    Ujiie, Hidetoshi; Oritani, Kenji; Kato, Hisashi; Yokota, Takafumi; Takahashi, Isao; Maeda, Tetsuo; Masaie, Hiroaki; Ichii, Michiko; Kamada, Yoshihiro; Tamura, Shinji; Kihara, Shinji; Funahashi, Tohru; Tomiyama, Yoshiaki; Kanakura, Yuzuru

    2006-05-01

    Adiponectin is an abundant adipose-specific protein, which acts as an anti-diabetic, anti-atherogenic, and anti-inflammatory adipokine. Although recent advances in the field of adiponectin have been made by the identification of adiponectin receptors and by the understanding about relationship between its multimerization and functions, detailed molecular background remains unclear. Our established anti-human adiponectin antibodies, ANOC 9103 and ANOC 9104, blocked some adiponectin functions such as the growth inhibition of B-lymphocytes on stromal cells and the inhibition of acetylated LDL uptake in macrophages, suggesting that they may recognize important functional regions of adiponectin. As a result of epitope mapping based on the ability to bind to the deleted adiponectin mutants, we identified that these antibodies recognize amino-terminal region of adiponectin before the beginning of the collagen-like domain. Notably, a peptide fragment (DQETTTQGPGVLLPLPKGACTGWMA) corresponding to amino acid residues 17-41 of human adiponectin could bind to restricted types of cells and block adiponectin-induced cyclooxygenase-2 gene expression and prostaglandin E2 production in MS-5 stromal cells. Moreover, the deletion of its amino-terminal region reduced the abilities to inhibit not only collagen-induced platelet aggregation but also diet-induced hepatic steatosis. These data indicate that amino-terminal region of adiponectin is a physiologically functional domain and that a novel receptor, which recognizes amino-terminal region of adiponectin, may exist on some types of cells. Further investigations will contribute to the understanding of molecular mechanisms about adiponectin functions as well as to the designing of novel strategies for the treatment of patients with insulin-resistance, vascular dysfunction, and chronic inflammation.

  12. Zn2+ activates large conductance Ca2+-activated K+ channel via an intracellular domain.

    PubMed

    Hou, Shangwei; Vigeland, Leif E; Zhang, Guangping; Xu, Rong; Li, Min; Heinemann, Stefan H; Hoshi, Toshinori

    2010-02-26

    Zinc is an essential trace element and plays crucial roles in normal development, often as an integral structural component of transcription factors and enzymes. Recent evidence suggests that intracellular Zn(2+) functions as a signaling molecule, mediating a variety of important physiological phenomena. However, the immediate effectors of intracellular Zn(2+) signaling are not well known. We show here that intracellular Zn(2+) potently and reversibly activates large-conductance voltage- and Ca(2+)-activated Slo1 K(+) (BK) channels. The full effect of Zn(2+) requires His(365) in the RCK1 (regulator of conductance for K(+)) domain of the channel. Furthermore, mutation of two nearby acidic residues, Asp(367) and Glu(399), also reduced activation of the channel by Zn(2+), suggesting a possible structural arrangement for Zn(2+) binding by the aforementioned residues. Extracellular Zn(2+) activated Slo1 BK channels when coexpressed with Zn(2+)-permeable TRPM7 (transient receptor potential melastatin 7) channels. The results thus demonstrate that Slo1 BK channels represent a positive and direct effector of Zn(2+) signaling and may participate in sculpting cellular response to an increase in intracellular Zn(2+) concentration.

  13. 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).

  14. Identification of critical regions within the TIR domain of IL-1 receptor type I.

    PubMed

    Radons, Jürgen; Falk, Werner; Dove, Stefan

    2015-11-01

    Interleukin-1 receptor type I (IL-1RI) belongs to a superfamily of proteins characterized by an intracellular Toll/IL-1 receptor (TIR) domain. This domain harbors three conserved regions called boxes 1-3 that play crucial roles in mediating IL-1 responses. Boxes 1 and 2 are considered to be involved in binding of adapter molecules. Amino acids possibly crucial for IL-1RI signaling were predicted via homology models of the IL-1RI TIR domain based on the crystal structure of IL-1RAPL. The role of ten of these residues was investigated by site-directed mutagenesis and a functional luciferase assay reflecting NF-κB activity in transiently transfected Jurkat cells. In particular, the mutants E437K/D438K, E472A/E473A and S465A/S470A/S471A/E472A/E473A showed decreased and the mutant E437A/D438A increased IL-1 responsiveness compared to the mouse IL-1RI wild type. In conclusion, the αC' helix (Q469-E473 in mouse IL-1RI) is probably involved in heterotypic interactions of IL-1RI with IL-1RAcP or MyD88. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. 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.

  16. The generation and selection of single-domain, v region libraries from nurse sharks.

    PubMed

    Flajnik, Martin F; Dooley, Helen

    2009-01-01

    The cartilaginous fish (sharks, skates, and rays) are the oldest phylogenetic group in which a human-type adaptive immune system and immunoglobulins (Igs) have been found. In addition to their conventional (heavy-light chain heterodimeric) isotypes, IgM and IgW, sharks produce the novel isotype, IgNAR, a heavy chain homodimer that does not associate with light chains. Instead, its variable (V) regions act as independent, soluble units in order to bind antigen. In this chapter, we detail our immunization protocol in order to raise a humoral IgNAR response in the nurse shark (Ginglymostoma cirratum) and the subsequent cloning of the single-domain V regions from this isotype in order to select antigen-specific binders by phage display.

  17. 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

  18. 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.

  19. The J-domain proteins of Arabidopsis thaliana: an unexpectedly large and diverse family of chaperones.

    PubMed

    Miernyk, J A

    2001-07-01

    A total of 89 J-domain proteins were identified in the genome of the model flowering plant Arabidopsis thaliana. The deduced amino acid sequences of the J-domain proteins were analyzed for an assortment of structural features and motifs. Based on the results of sequence comparisons and structure and function predictions, 51 distinct families were identified. The families ranged in size from 1 to 6 members. Subcellular localizations of the A thaliana J-domain proteins were predicted; species were found in both the soluble and membrane compartments of all cellular organelles. Based on digital Northern analysis, the J-domain proteins could be separated into groups of low, medium, and moderate expression levels. This genomics-based analysis of the A thaliana J-domain proteins establishes a framework for detailed studies of biological function and specificity. It additionally provides a comprehensive basis for evolutionary comparisons.

  20. 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

  1. A noncanonical PWI domain in the N-terminal helicase-associated region of the spliceosomal Brr2 protein.

    PubMed

    Absmeier, Eva; Rosenberger, Leonie; Apelt, Luise; Becke, Christian; Santos, Karine F; Stelzl, Ulrich; Wahl, Markus C

    2015-04-01

    The spliceosomal RNA helicase Brr2 is required for the assembly of a catalytically active spliceosome on a messenger RNA precursor. Brr2 exhibits an unusual organization with tandem helicase units, each comprising dual RecA-like domains and a Sec63 homology unit, preceded by a more than 400-residue N-terminal helicase-associated region. Whereas recent crystal structures have provided insights into the molecular architecture and regulation of the Brr2 helicase region, little is known about the structural organization and function of its N-terminal part. Here, a near-atomic resolution crystal structure of a PWI-like domain that resides in the N-terminal region of Chaetomium thermophilum Brr2 is presented. CD spectroscopic studies suggested that this domain is conserved in the yeast and human Brr2 orthologues. Although canonical PWI domains act as low-specificity nucleic acid-binding domains, no significant affinity of the unusual PWI domain of Brr2 for a broad spectrum of DNAs and RNAs was detected in band-shift assays. Consistently, the C. thermophilum Brr2 PWI-like domain, in the conformation seen in the present crystal structure, lacks an expanded positively charged surface patch as observed in at least one canonical, nucleic acid-binding PWI domain. Instead, in a comprehensive yeast two-hybrid screen against human spliceosomal proteins, fragments of the N-terminal region of human Brr2 were found to interact with several other spliceosomal proteins. At least one of these interactions, with the Prp19 complex protein SPF27, depended on the presence of the PWI-like domain. The results suggest that the N-terminal region of Brr2 serves as a versatile protein-protein interaction platform in the spliceosome and that some interactions require or are reinforced by the PWI-like domain.

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

    PubMed Central

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

    1999-01-01

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

  3. Extended Big-Brother experiments: the role of lateral boundary data quality and size of integration domain in regional climate modelling

    NASA Astrophysics Data System (ADS)

    Køltzow, Morten; Iversen, Trond; Haugen, Jan Erik

    2008-05-01

    Dynamical downscaling by atmospheric Regional Climate Models (RCMs) forced with low-resolution data should produce fine scale climate details with skill. This is investigated by adopting and extending the Big-Brother approach of Denis et al. (2002). A reference climate is established from a fine resolution RCM simulation in a large domain (the Big-Brother). These Big-Brother (BB) data are degraded by removing small scales, and then used for downscaling by the RCM (the Little Brother) with the same resolution as the BB in three domains of different size. Differences between the Little- and BB are attributed to errors caused by the downscaling. We have furthermore extended the original BB method and investigated the impact of the quality of the driving data. The RCM manage to reproduce the general large scale climate features of the BB when forced with high quality data, but show deficiencies when the driving data differ both in phase and scale from the BB. Forced with data with lower quality on a sufficiently large integration domain and in regions influenced by strong local forcing, the RCM significantly improve the climate statistics for local variables (2 m air-temperature, 10 m wind speed, precipitation). We even found that the improvement increased with domain size.

  4. 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.

  5. 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.

  6. 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.

  7. Keap1 is a forked-stem dimer structure with two large spheres enclosing the intervening, double glycine repeat, and C-terminal domains

    PubMed Central

    Ogura, Toshihiko; Tong, Kit I.; Mio, Kazuhiro; Maruyama, Yuusuke; Kurokawa, Hirofumi; Sato, Chikara; Yamamoto, Masayuki

    2010-01-01

    Keap1 is a substrate adaptor of a Cullin 3-based E3 ubiquitin ligase complex that recognizes Nrf2, and also acts as a cellular sensor for xenobiotics and oxidative stresses. Nrf2 is a transcriptional factor regulating the expression of cytoprotective enzyme genes in response to such stresses. Under unstressed conditions Keap1 binds Nrf2 and results in rapid degradation of Nrf2 through the proteasome pathway. In contrast, upon exposure to oxidative and electrophilic stress, reactive cysteine residues in intervening region (IVR) and Broad complex, Tramtrack, and Bric-à-Brac domains of Keap1 are modified by electrophiles. This modification prevents Nrf2 from rapid degradation and induces Nrf2 activity by repression of Keap1. Here we report the structure of mouse Keap1 homodimer by single particle electron microscopy. Three-dimensional reconstruction at 24-Å resolution revealed two large spheres attached by short linker arms to the sides of a small forked-stem structure, resembling a cherry-bob. Each sphere has a tunnel corresponding to the central hole of the β-propeller domain, as determined by x-ray crystallography. The IVR domain appears to surround the core of the β-propeller domain. The unexpected proximity of IVR to the β-propeller domain suggests that any distortions generated during modification of reactive cysteine residues in the IVR domain may send a derepression signal to the β-propeller domain and thereby stabilize Nrf2. This study thus provides a structural basis for the two-site binding and hinge-latch model of stress sensing by the Nrf2-Keap1 system. PMID:20133743

  8. Layer resolved magnetic domain imaging of epitaxial heterostructures in large applied magnetic fields

    SciTech Connect

    Zohar, S.; Choi, Y.; Love, D. M.; Mansell, R.; Barnes, C. H. W.; Keavney, DJ.; Rosenberg, R. A.

    2015-02-16

    We use X-ray Excited Luminescence Microscopy to investigate the elemental and layer resolved magnetic reversal in an interlayer exchange coupled (IEC) epitaxial Fe/Cr wedge/Co heterostructure. The transition from strongly coupled parallel Co-Fe reversal for Cr thickness t(Cr) < 0.34 nm to weakly coupled layer independent reversal for t(Cr) > 1.5 nm is punctuated at 0.34 < t(Cr) < 1.5 nm by a combination of IEC guided domain wall motion and stationary zig zag domain walls. Domain walls nucleated at switching field minima are guided by IEC spatial gradients and collapse at switching field maxima.

  9. Layer resolved magnetic domain imaging of epitaxial heterostructures in large applied magnetic fields

    NASA Astrophysics Data System (ADS)

    Zohar, S.; Choi, Y.; Love, D. M.; Mansell, R.; Barnes, C. H. W.; Keavney, D. J.; Rosenberg, R. A.

    2015-02-01

    We use X-ray Excited Luminescence Microscopy to investigate the elemental and layer resolved magnetic reversal in an interlayer exchange coupled (IEC) epitaxial Fe/Cr wedge/Co heterostructure. The transition from strongly coupled parallel Co-Fe reversal for Cr thickness tCr < 0.34 nm to weakly coupled layer independent reversal for tCr > 1.5 nm is punctuated at 0.34 < tCr < 1.5 nm by a combination of IEC guided domain wall motion and stationary zig zag domain walls. Domain walls nucleated at switching field minima are guided by IEC spatial gradients and collapse at switching field maxima.

  10. Trichomonas vaginalis initiator binding protein (IBP39) and RNA polymerase II large subunit carboxy terminal domain interaction.

    PubMed

    Lau, Audrey O T; Smith, Alias J; Brown, Mark T; Johnson, Patricia J

    2006-11-01

    The core promoter that directs RNA polymerase to the start of transcription in the protist Trichomonas vaginalis is an initiator (Inr) element recognized by the Inr Binding Protein, IBP39. This nuclear protein is composed of two domains: a 14.5 kDa amino (N-terminal) and a 25 kDa carboxy terminal domain (C-domain). Here we describe the identification of an IBP39-interacting protein by screening a T. vaginalis expression library using a two-hybrid system with the IBP39 C-domain as bait. The CTD of the large subunit of RNAP II was found to specifically interact with the C-domain. The specificity and nature of the interaction between the CTD of RNAP II and the C-domain of IBP39 was validated by three independent biochemical methods: co-immunoprecipitation with epitope-tagged proteins, affinity chromatography and enzyme linked ligand sorbent (ELLSA) assays. Binding was shown to involve hydrophobic bonds and to have a disassociation constant (K(d)) of 690 nM (+/-55). These results confirm and extend our previous binding studies using a peptide composed of the last nine amino acids of RNAP II CTD [Schumacher MA, Lau AOT, Johnson PJ. Structural basis of core promoter recognition in a primitive eukaryote. Cell 2003;115:413-24] that predicted an interaction between the CTD and IBP39. These data further demonstrate that IBP39 minimally possesses two functional domains: a N-terminal DNA binding domain (that recognizes the Inr) [Liston DR, Johnson PJ. Analysis of a ubiquitous promoter element in a primitive eukaryote: early evolution of the initiator element. Mol Cell Biol 1999;19:2380-8] and a C-terminal protein binding domain that recognizes the RNAP II CTD, an interaction that may be critical for recruiting RNAP II for initiation of transcription.

  11. 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.

  12. 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.

  13. Large cholera outbreak in Brong Ahafo Region, Ghana.

    PubMed

    Noora, Charles Lwanga; Issah, Kofi; Kenu, Ernest; Bachan, Emmanuel George; Nuoh, Robert Domo; Nyarko, Kofi Mensah; Appiah, Paulina; Letsa, Timothy

    2017-08-10

    A nationwide outbreak of Vibrio cholerae occurred in Ghana in 2014 with Accra, the nation's capital as the epi-center. The outbreak spread to the Brong Ahafo Region (BAR) which is geographically located in the middle of the country. In this region a review of data collected during the outbreak was carried out and analyzed descriptively to determine the hot spots and make recommendations for effective response to future outbreaks. A review of patient records and line lists of cases of cholera reported in all hospitals during the period of the outbreak (July-December 2014) was conducted. Hospitals used IDSR (Integrated Disease Surveillance and Response system) standard case definitions to detect and report cases for management. The GPS coordinates of all districts and health facilities were collected and utilized in the construction of spot maps. We also obtained populations (denominators) from the BAR Health surveillance unit of the Ghana Health Service. All the data thus collected was analyzed descriptively and expressed as frequencies and rates. A total of 1035 cases were reported, 550 (53.4%) were males and the rest females. Their ages ranged from 1 to 95 years; (mean age of 28.2 ± 19.6 years). The most affected (23.5%) was the 20-29 year old age group. On the 30th July, 2014, a 26 year old male (recorded as the index case of the cholera outbreak in the Brong Ahafo region) with a history of travel from Accra reported to the Nkoranza district hospital with a history of symptoms suggestive of cholera. The reporting of cholera cases reached their peak (17.3%) in week 15 of the outbreak (this lasted 25 weeks). An overall attack rate of 71/100,000 population, and a case fatality rate of 2.4% was recorded in the region. Asutifi South district however recorded a case fatality of 9.1%, the highest amongst all the districts which recorded outbreaks. The majority of the cases reported in the region were from Atebubu-Amanten, Sene West, Pru, and Asunafo North

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

    SciTech Connect

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

    2015-06-28

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

  15. 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

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

    PubMed Central

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

    2014-01-01

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

  17. 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

    2014-10-07

    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.

  18. A new functional motif in Hox domain-containing ceramide synthases: identification of a novel region flanking the Hox and TLC domains essential for activity.

    PubMed

    Mesika, Adi; Ben-Dor, Shifra; Laviad, Elad L; Futerman, Anthony H

    2007-09-14

    Ceramide is synthesized in mammals by a family of ceramide synthases (CerS) each of which uses a relatively restricted set of fatty acyl-CoAs for N-acylation of the sphingoid long chain base (Pewzner-Jung, Y., Ben-Dor, S., and Futerman, A. H. (2006) J. Biol. Chem. 281, 25001-25005). CerS are characterized by two functional domains, the Tram-Lag-CLN8 (TLC) domain and the homeobox (Hox) domain, which is found in all mammalian CerS except CerS1. We now demonstrate that the majority of the Hox domain is not required for CerS activity since its deletion in CerS5 does not affect activity. Subsequently, we define a highly conserved new motif of 12 amino acid residues that flanks the Hox and TLC domains but is not part of the TLC domain, which is essential for CerS5 and CerS6 activity. Two positively charged residues in this domain, one of which is conserved in all putative CerS in all organisms, are essential for activity since site-directed mutagenesis of either (Lys-134 and Lys-140 in CerS5) results in an approximately 50% loss of activity, whereas mutation of both leads to a complete loss of activity. Because this region is conserved across species, we propose that it plays a previously unidentified and essential role in CerS activity and can be used as a new motif to define Hox domain-containing CerS.

  19. Regions of very low H3K27me3 partition the Drosophila genome into topological domains

    PubMed Central

    Flower, Rosalyn; Choo, Siew Woh

    2017-01-01

    It is now well established that eukaryote genomes have a common architectural organization into topologically associated domains (TADs) and evidence is accumulating that this organization plays an important role in gene regulation. However, the mechanisms that partition the genome into TADs and the nature of domain boundaries are still poorly understood. We have investigated boundary regions in the Drosophila genome and find that they can be identified as domains of very low H3K27me3. The genome-wide H3K27me3 profile partitions into two states; very low H3K27me3 identifies Depleted (D) domains that contain housekeeping genes and their regulators such as the histone acetyltransferase-containing NSL complex, whereas domains containing moderate-to-high levels of H3K27me3 (Enriched or E domains) are associated with regulated genes, irrespective of whether they are active or inactive. The D domains correlate with the boundaries of TADs and are enriched in a subset of architectural proteins, particularly Chromator, BEAF-32, and Z4/Putzig. However, rather than being clustered at the borders of these domains, these proteins bind throughout the H3K27me3-depleted regions and are much more strongly associated with the transcription start sites of housekeeping genes than with the H3K27me3 domain boundaries. While we have not demonstrated causality, we suggest that the D domain chromatin state, characterised by very low or absent H3K27me3 and established by housekeeping gene regulators, acts to separate topological domains thereby setting up the domain architecture of the genome. PMID:28282436

  20. Regional climate simulations with COSMO-CLM over MENA-CORDEX domain

    NASA Astrophysics Data System (ADS)

    Galluccio, Salvatore; Bucchignani, Edoardo; Mercogliano, Paola; Montesarchio, Myriam

    2014-05-01

    In the frame of WCRP Coordinated Regional Downscaling Experiment (CORDEX), a set of common Regional Climate Downscaling (RCD) domains has been defined, as a prerequisite for the development of model evaluation and climate projection frameworks. CORDEX domains encompass the majority of land areas of the world. In this work, climate simulations have been performed over MENA-CORDEX domain, which includes North-Africa, southern Europe and the whole Arabian peninsula. The non-hydrostatic regional climate model COSMO-CLM has been used. At CMCC, regional climate modelling is a part of an integrated simulation system and it has been used in different European and African projects to provide qualitative and quantitative evaluation of the hydrogeological and public health risks. A series of simulations has been conducted over the MENA-CORDEX area at spatial resolution of 0.44°. A sensitivity analysis was conducted to adjust the model configuration to better reproduce the observed climate data. The numerical simulations were driven by ERA-Interim reanalysis (horizontal resolution of 0.703°) for the period 1979-1984; the first year, was considered as a spin up period. The validation was performed by using several data sets: CRU data set was used to validate temperature, precipitation and cloud cover; MERRA data set was used to validate temperature and precipitation and GPCP for precipitation. The model sensitivity to the external parameters was tested considering two different configurations for the surface albedo. In the first one, albedo is only function of soil-type whereas in the second configuration it is prescribed by two external fields for dry and saturated soil based on MODIS data. Moreover, we tested two aerosol distributions as well, namely the default Tanre aerosol distribution and aerosol maps according to Tegen (NASA/GISS). We found, as expected, a significant sensitivity, in particular on the African region. We also varied tuning and physical parameters, such

  1. 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.

  2. 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.

  3. 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

  4. Identifying Infection Sources and Regions in Large Networks

    NASA Astrophysics Data System (ADS)

    Luo, Wuqiong; Tay, Wee Peng; Leng, Mei

    2013-06-01

    Identifying the infection sources in a network, including the index cases that introduce a contagious disease into a population network, the servers that inject a computer virus into a computer network, or the individuals who started a rumor in a social network, plays a critical role in limiting the damage caused by the infection through timely quarantine of the sources. We consider the problem of estimating the infection sources and the infection regions (subsets of nodes infected by each source) in a network, based only on knowledge of which nodes are infected and their connections, and when the number of sources is unknown a priori. We derive estimators for the infection sources and their infection regions based on approximations of the infection sequences count. We prove that if there are at most two infection sources in a geometric tree, our estimator identifies the true source or sources with probability going to one as the number of infected nodes increases. When there are more than two infection sources, and when the maximum possible number of infection sources is known, we propose an algorithm with quadratic complexity to estimate the actual number and identities of the infection sources. Simulations on various kinds of networks, including tree networks, small-world networks and real world power grid networks, and tests on two real data sets are provided to verify the performance of our estimators.

  5. 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

    ...; Commercial Atlantic Region Non-Sandbar Large Coastal Shark Fishery Opening Date AGENCY: National Marine...-sandbar large coastal shark fishery. This action is necessary to inform fishermen and dealers about the fishery opening date. DATES: The commercial Atlantic region non-sandbar large coastal shark fishery will...

  6. Application of a Regional Thermohaline Inverse Method to observational reanalyses in an Arctic domain

    NASA Astrophysics Data System (ADS)

    Mackay, Neill; Wilson, Chris; Zika, Jan

    2017-04-01

    The Overturning in the Subpolar North Atlantic Program (OSNAP) aims to quantify the subpolar AMOC and its variability, including associated fluxes of heat and freshwater, using a combination of observations and models. In contribution OSNAP, we have developed a novel inverse method that diagnoses the interior mixing and advective flux at the boundary of an enclosed volume in the ocean. This Regional Thermohaline Inverse Method (RTHIM) operates in salinity-temperature (S-T) coordinates, a framework which allows us to gain insights into water mass transformation within the control volume and boundary fluxes of heat and freshwater. RTHIM will use multiple long-term observational datasets and reanalyses, including Argo, to provide a set of inverse estimates to be used to understand the sub-annual transport timescales sampled by the OSNAP array. Having validated the method using the NEMO model, we apply RTHIM to an Arctic domain using temperature and salinity and surface flux data from reanalyses. We also use AVISO surface absolute geostrophic velocities which, combined with thermal wind balance, provide an initial estimate for the inflow and outflow through the boundary. We diagnose the interior mixing in S-T coordinates and the boundary flow, calculating the transformation rates of well-known water masses and the individual contributions to these rates from surface flux processes, boundary flow and interior mixing. Outputs from RTHIM are compared with similar metrics from previous literature on the region. The inverse solution reproduces an observed pattern of warm, saline Atlantic waters entering the Arctic volume and cooler, fresher waters leaving. Meanwhile, surface fluxes act to create waters at the extremes of the S-T distribution and interior mixing acts in opposition, creating water masses at intermediate S-T and destroying them at the extremes. RTHIM has the potential to be compared directly with the OSNAP array observations by defining a domain boundary which

  7. Age-associated hyper-methylated regions in the human brain overlap with bivalent chromatin domains.

    PubMed

    Watson, Corey T; Disanto, Giulio; Sandve, Geir Kjetil; Breden, Felix; Giovannoni, Gavin; Ramagopalan, Sreeram V

    2012-01-01

    Recent associations between age-related differentially methylated sites and bivalently marked chromatin domains have implicated a role for these genomic regions in aging and age-related diseases. However, the overlap between such epigenetic modifications has so far only been identified with respect to age-associated hyper-methylated sites in blood. In this study, we observed that age-associated differentially methylated sites characterized in the human brain were also highly enriched in bivalent domains. Analysis of hyper- vs. hypo-methylated sites partitioned by age (fetal, child, and adult) revealed that enrichment was significant for hyper-methylated sites identified in children and adults (child, fold difference = 2.28, P = 0.0016; adult, fold difference = 4.73, P = 4.00 × 10(-5)); this trend was markedly more pronounced in adults when only the top 100 most significantly hypo- and hyper-methylated sites were considered (adult, fold difference = 10.7, P = 2.00 × 10(-5)). Interestingly, we found that bivalently marked genes overlapped by age-associated hyper-methylation in the adult brain had strong involvement in biological functions related to developmental processes, including neuronal differentiation. Our findings provide evidence that the accumulation of methylation in bivalent gene regions with age is likely to be a common process that occurs across tissue types. Furthermore, particularly with respect to the aging brain, this accumulation might be targeted to loci with important roles in cell differentiation and development, and the closing off of these developmental pathways. Further study of these genes is warranted to assess their potential impact upon the development of age-related neurological disorders.

  8. LAP2 binds to BAF⋅DNA complexes: requirement for the LEM domain and modulation by variable regions

    PubMed Central

    Shumaker, Dale K.; Lee, Kenneth K.; Tanhehco, Yvette C.; Craigie, Robert; Wilson, Katherine L.

    2001-01-01

    LAP2 belongs to a family of nuclear membrane proteins sharing a 43 residue LEM domain. All LAP2 isoforms have the same N-terminal ‘constant’ region (LAP2-c), which includes the LEM domain, plus a C-terminal ‘variable’ region. LAP2-c polypeptide inhibits nuclear assembly in Xenopus extracts, and binds in vitro to barrier-to-autointegration factor (BAF), a DNA-bridging protein. We tested 17 Xenopus LAP2-c mutants for nuclear assembly inhibition, and binding to BAF and BAF⋅DNA complexes. LEM domain mutations disrupted all activities tested. Some mutations outside the LEM domain had no effect on binding to BAF, but disrupted activity in Xenopus extracts, suggesting that LAP2-c has an additional unknown function required to inhibit nuclear assembly. Mutagenesis results suggest that BAF changes conformation when complexed with DNA. The binding affinity of LAP2 was higher for BAF⋅DNA complexes than for BAF, suggesting that these interactions are physiologically relevant. Nucleoplasmic domains of Xenopus LAP2 isoforms varied 9-fold in their affinities for BAF, but all isoforms supershifted BAF⋅DNA complexes. We propose that the LEM domain is a core BAF-binding domain that can be modulated by the variable regions of LAP2 isoforms. PMID:11285238

  9. LAP2 binds to BAF.DNA complexes: requirement for the LEM domain and modulation by variable regions.

    PubMed

    Shumaker, D K; Lee, K K; Tanhehco, Y C; Craigie, R; Wilson, K L

    2001-04-02

    LAP2 belongs to a family of nuclear membrane proteins sharing a 43 residue LEM domain. All LAP2 isoforms have the same N-terminal 'constant' region (LAP2-c), which includes the LEM domain, plus a C-terminal 'variable' region. LAP2-c polypeptide inhibits nuclear assembly in Xenopus extracts, and binds in vitro to barrier-to-autointegration factor (BAF), a DNA-bridging protein. We tested 17 Xenopus LAP2-c mutants for nuclear assembly inhibition, and binding to BAF and BAF small middle dotDNA complexes. LEM domain mutations disrupted all activities tested. Some mutations outside the LEM domain had no effect on binding to BAF, but disrupted activity in Xenopus extracts, suggesting that LAP2-c has an additional unknown function required to inhibit nuclear assembly. Mutagenesis results suggest that BAF changes conformation when complexed with DNA. The binding affinity of LAP2 was higher for BAF small middle dotDNA complexes than for BAF, suggesting that these interactions are physiologically relevant. Nucleoplasmic domains of Xenopus LAP2 isoforms varied 9-fold in their affinities for BAF, but all isoforms supershifted BAF small middle dotDNA complexes. We propose that the LEM domain is a core BAF-binding domain that can be modulated by the variable regions of LAP2 isoforms.

  10. Interaction of the GTP-binding and GTPase-activating domains of ARD1 involves the effector region of the ADP-ribosylation factor domain.

    PubMed

    Vitale, N; Moss, J; Vaughan, M

    1997-02-14

    ADP-ribosylation factors (ARFs) are a family of approximately 20-kDa guanine nucleotide-binding proteins and members of the Ras superfamily, originally identified and purified by their ability to enhance the ADP-ribosyltransferase activity of cholera toxin and more recently recognized as critical participants in vesicular trafficking pathways and phospholipase D activation. ARD1 is a 64-kDa protein with an 18-kDa carboxyl-terminal ARF domain (p3) and a 46-kDa amino-terminal extension (p5) that is widely expressed in mammalian tissues. Using recombinant proteins, we showed that p5, the amino-terminal domain of ARD1, stimulates the GTPase activity of p3, the ARF domain, and appears to be the GTPase-activating protein (GAP) component of this bifunctional protein, whereas in other members of the Ras superfamily a separate GAP molecule interacts with the effector region of the GTP-binding protein. p5 stimulated the GTPase activity of p3 but not of ARF1, which differs from p3 in several amino acids in the effector domain. After substitution of 7 amino acids from p3 in the appropriate position in ARF1, the chimeric protein ARF1(39-45p3) bound to p5, which increased its GTPase activity. Specifically, after Gly40 and Thr45 in the putative effector domain of ARF1 were replaced with the equivalent Asp and Pro, respectively, from p3, functional interaction of the chimeric ARF1 with p5 was increased. Thus, Asp25 and Pro30 of the ARF domain (p3) of ARD1 are involved in its functional and physical interaction with the GTPase-activating (p5) domain of ARD1. After deletion of the amino-terminal 15 amino acids from ARF1(39-45p3), its interaction with p5 was essentially equivalent to that of p3, suggesting that the amino terminus of ARF1(39-45p3) may interfere with binding to p5. These results are consistent with the conclusion that the GAP domain of ARD1 interacts with the effector region of the ARF domain and thereby stimulates GTP hydrolysis.

  11. Venus - Large Impact Crater in the Eistla Region

    NASA Technical Reports Server (NTRS)

    1991-01-01

    This Magellan image shows an impact crater in the central Eistla Region of the equatorial highlands of Venus. It is centered at 15 degrees north latitude and 5 degrees east longitude. The image is 76.8 kilometers (48 miles) wide. The crater is slightly irregular in planform and approximately 6 kilometers (4 miles) in diameter. The walls appear terraced. Five or six lobes of radar-bright ejecta radiate up to 13.2 kilometers (8 miles) from the crater rim. These lobes are up to 3.5 kilometers (2 miles) in width and form a 'starfish' pattern against the underlying radar-dark plains. The asymmetric pattern of the ejecta suggests the angle of impact was oblique. The alignment of two of the ejecta lobes along fractures in the underlying plains is apparently coincidental.

  12. Venus - Large Impact Crater in the Eistla Region

    NASA Image and Video Library

    1996-09-26

    This image from NASA Magellan spacecraft shows the central Eistla Region of the equatorial highlands of Venus. It is centered at 15 degrees north latitude and 5 degrees east longitude. The image is 76.8 kilometers (48 miles) wide. The crater is slightly irregular in platform and approximately 6 kilometers (4 miles) in diameter. The walls appear terraced. Five or six lobes of radar-bright ejecta radiate up to 13.2 kilometers (8 miles) from the crater rim. These lobes are up to 3.5 kilometers (2 miles) in width and form a "starfish" pattern against the underlying radar-dark plains. The asymmetric pattern of the ejecta suggests the angle of impact was oblique. The alignment of two of the ejecta lobes along fractures in the underlying plains is apparently coincidental. http://photojournal.jpl.nasa.gov/catalog/PIA00466

  13. Estimating cost of large-fire suppression for three Forest Service regions

    Treesearch

    Eric L. Smith; Gonz& aacute; lez-Cab& aacute; n Armando

    1987-01-01

    The annual costs attributable to large fire suppression in three Forest Service Regions (1970-1981) were estimated as a function of fire perimeters using linear regression. Costs calculated on a per chain of perimeterbasis were highest for the Pacific Northwest Region, next highest for the Northern Region, and lowest for the Intermountain Region. Recent costs in real...

  14. 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.

  15. Mouse limb deformity mutations disrupt a global control region within the large regulatory landscape required for Gremlin expression.

    PubMed

    Zuniga, Aimée; Michos, Odyssé; Spitz, François; Haramis, Anna-Pavlina G; Panman, Lia; Galli, Antonella; Vintersten, Kristina; Klasen, Christian; Mansfield, William; Kuc, Sylwia; Duboule, Denis; Dono, Rosanna; Zeller, Rolf

    2004-07-01

    The mouse limb deformity (ld) mutations cause limb malformations by disrupting epithelial-mesenchymal signaling between the polarizing region and the apical ectodermal ridge. Formin was proposed as the relevant gene because three of the five ld alleles disrupt its C-terminal domain. In contrast, our studies establish that the two other ld alleles directly disrupt the neighboring Gremlin gene, corroborating the requirement of this BMP antagonist for limb morphogenesis. Further doubts concerning an involvement of Formin in the ld limb phenotype are cast, as a targeted mutation removing the C-terminal Formin domain by frame shift does not affect embryogenesis. In contrast, the deletion of the corresponding genomic region reproduces the ld limb phenotype and is allelic to mutations in Gremlin. We resolve these conflicting results by identifying a cis-regulatory region within the deletion that is required for Gremlin activation in the limb bud mesenchyme. This distant cis-regulatory region within Formin is also altered by three of the ld mutations. Therefore, the ld limb bud patterning defects are not caused by disruption of Formin, but by alteration of a global control region (GCR) required for Gremlin transcription. Our studies reveal the large genomic landscape harboring this GCR, which is required for tissue-specific coexpression of two structurally and functionally unrelated genes.

  16. 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.

  17. 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.

  18. 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

  19. Sensitivity analysis with the regional climate model COSMO-CLM over the CORDEX-MENA domain

    NASA Astrophysics Data System (ADS)

    Bucchignani, E.; Cattaneo, L.; Panitz, H.-J.; Mercogliano, P.

    2016-02-01

    The results of a sensitivity work based on ERA-Interim driven COSMO-CLM simulations over the Middle East-North Africa (CORDEX-MENA) domain are presented. All simulations were performed at 0.44° spatial resolution. The purpose of this study was to ascertain model performances with respect to changes in physical and tuning parameters which are mainly related to surface, convection, radiation and cloud parameterizations. Evaluation was performed for the whole CORDEX-MENA region and six sub-regions, comparing a set of 26 COSMO-CLM runs against a combination of available ground observations, satellite products and reanalysis data to assess temperature, precipitation, cloud cover and mean sea level pressure. The model proved to be very sensitive to changes in physical parameters. The optimized configuration allows COSMO-CLM to improve the simulated main climate features of this area. Its main characteristics consist in the new parameterization of albedo, based on Moderate Resolution Imaging Spectroradiometer data, and the new parameterization of aerosol, based on NASA-GISS AOD distributions. When applying this configuration, Mean Absolute Error values for the considered variables are as follows: about 1.2 °C for temperature, about 15 mm/month for precipitation, about 9 % for total cloud cover, and about 0.6 hPa for mean sea level pressure.

  20. 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

    2017-08-01

    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.

  1. 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.

  2. A new regional climate simulation using RegCM4 over the CORDEX South Asia domain

    NASA Astrophysics Data System (ADS)

    Mariotti, Laura; Bacer, Sara; Coppola, Erika; Giorgi, Filippo

    2014-05-01

    We present a new high-resolution regional climate simulation over the CORDEX South Asia made with the latest version of the Regional Climate Model RegCM4. The simulation has been performed at 25 km of resolution using the ERA-Interim boundary conditions. The simulated results are compared with the monthly mean surface observations for temperature and precipitation over the entire domain. The rainy season during the June-July-August-September (JJAS) over India shows a bigger improvement using a different parameterization of the MIT-Emanuel convection scheme for land and ocean. Another big improvement has been found with the UW PBL scheme (Bretherton and McCaa, 2004). The model shows in JJAS season a slight cold bias over the mountain compared with CRU dataset, instead in Indian land area the pattern of the temperature is well represented. The monsoon precipitation over the Indian continent is reasonably represented. A good agreement was found from the comparison between RegCM4 with the IMD dataset by studying the area weighted average values time series of monthly accumulated rainfall (cm) in Indian land area.

  3. 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

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

    PubMed

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

    2011-06-01

    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.

  5. 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.

  6. 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

  7. Terahertz-Field-Induced Large Macroscopic Polarization and Domain-Wall Dynamics in an Organic Molecular Dielectric

    NASA Astrophysics Data System (ADS)

    Morimoto, T.; Miyamoto, T.; Yamakawa, H.; Terashige, T.; Ono, T.; Kida, N.; Okamoto, H.

    2017-03-01

    A rapid polarization control in paraelectric materials is important for an ultrafast optical switching useful in the future optical communication. In this study, we applied terahertz-pump second-harmonic-generation-probe and optical-reflectivity-probe spectroscopies to the paraelectric neutral phase of an organic molecular dielectric, tetrathiafulvalene-p -chloranil and revealed that a terahertz pulse with the electric-field amplitude of ˜400 kV /cm produces in the subpicosecond time scale a large macroscopic polarization whose magnitude reaches ˜20 % of that in the ferroelectric ionic phase. Such a large polarization generation is attributed to the intermolecular charge transfers and breathing motions of domain walls between microscopic neutral and ionic domains induced by the terahertz electric field.

  8. Time Domain Analysis and Synthesis of Robust Controllers for Large Scale LQG (Linear Quadratic Gaussian) Regulators.

    DTIC Science & Technology

    1983-08-31

    Time domain analysis of stability 3 robustness. B. Computer software and application 27 .1 examupl es. III. Conclusions & Recommendations for Future...performance requirements may not be met by g that design. Thus, simultaneous consideration of stability and performance -. in the design process is...the design process have been scarce. Towards this direction, research was initiated on these aspects by the author during the Summer IFaculty Research

  9. Sub-terahertz frequency-domain spectroscopy reveals single-grain mobility and scatter influence of large-area graphene.

    PubMed

    Cervetti, Christian; Heintze, Eric; Gorshunov, Boris; Zhukova, Elena; Lobanov, Svyatoslav; Hoyer, Alexander; Burghard, Marko; Kern, Klaus; Dressel, Martin; Bogani, Lapo

    2015-04-24

    The response of individual domains in wafer-sized chemical vapor deposition graphene is measured by contactless sub-terahertz interferometry, observing the intrinsic optical conductance and reaching very high mobility values. It is shown that charged scatterers limit the mobility, validating previous theoretical predictions, and sub-terahertz quality assessment is demonstrated, as necessary for large-scale applications in touchscreens, as well as wearable and optoelectronic devices.

  10. RNA helicase domain of tobamovirus replicase executes cell-to-cell movement possibly through collaboration with its nonconserved region.

    PubMed

    Hirashima, Kyotaro; Watanabe, Yuichiro

    2003-11-01

    UR-hel, a chimeric virus obtained by replacement of the RNA helicase domain of tobacco mosaic virus (TMV)-U1 replicase with that from the TMV-R strain, could replicate similarly to TMV-U1 in protoplasts but could not move from cell to cell (K. Hirashima and Y. Watanabe, J. Virol. 75:8831-8836, 2001). It was suggested that TMV recruited both the movement protein (MP) and replicase for cell-to-cell movement by unknown mechanisms. Here, we found that a recombinant, UR-hel/V, in which the nonconserved region was derived from TMV-R in addition to the RNA helicase domain of replicase, could move from cell to cell. We also analyzed revertants isolated from UR-hel, which recovered cell-to-cell movement by their own abilities. We found amino acid substitutions responsible for phenotypic reversion only in the nonconserved region and/or RNA helicase domain but never in MP. Together, these data show that both the nonconserved region and the RNA helicase domain of replicase are involved in cell-to-cell movement. The RNA helicase domain of tobamovirus replicase possibly does not interact directly with MP but interacts with its nonconserved region to execute cell-to-cell movement.

  11. Large ensemble and large-domain hydrologic modeling: Insights from SUMMA applications in the Columbia River Basin

    NASA Astrophysics Data System (ADS)

    Ou, G.; Nijssen, B.; Nearing, G. S.; Newman, A. J.; Mizukami, N.; Clark, M. P.

    2016-12-01

    The Structure for Unifying Multiple Modeling Alternatives (SUMMA) provides a unifying modeling framework for process-based hydrologic modeling by defining a general set of conservation equations for mass and energy, with the capability to incorporate multiple choices for spatial discretizations and flux parameterizations. In this study, we provide a first demonstration of large-scale hydrologic simulations using SUMMA through an application to the Columbia River Basin (CRB) in the northwestern United States and Canada for a multi-decadal simulation period. The CRB is discretized into 11,723 hydrologic response units (HRUs) according to the United States Geologic Service Geospatial Fabric. The soil parameters are derived from the Natural Resources Conservation Service Soil Survey Geographic (SSURGO) Database. The land cover parameters are based on the National Land Cover Database from the year 2001 created by the Multi-Resolution Land Characteristics (MRLC) Consortium. The forcing data, including hourly air pressure, temperature, specific humidity, wind speed, precipitation, shortwave and longwave radiations, are based on Phase 2 of the North American Land Data Assimilation System (NLDAS-2) and averaged for each HRU. The simulation results are compared to simulations with the Variable Infiltration Capacity (VIC) model and the Precipitation Runoff Modeling System (PRMS). We are particularly interested in SUMMA's capability to mimic model behaviors of the other two models through the selection of appropriate model parameterizations in SUMMA.

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

    PubMed

    Li, Lin; Alper, Joshua; Alexov, Emil

    2016-03-18

    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

    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.

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

    PubMed

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

    2006-12-01

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

  15. Large nuclear spin polarization in gate-defined quantum dots using a single-domain nanomagnet.

    PubMed

    Petersen, Gunnar; Hoffmann, Eric A; Schuh, Dieter; Wegscheider, Werner; Giedke, Geza; Ludwig, Stefan

    2013-04-26

    The electron-nuclei (hyperfine) interaction is central to spin qubits in solid state systems. It can be a severe decoherence source but also allows dynamic access to the nuclear spin states. We study a double quantum dot exposed to an on-chip single-domain nanomagnet and show that its inhomogeneous magnetic field crucially modifies the complex nuclear spin dynamics such that the Overhauser field tends to compensate external magnetic fields. This turns out to be beneficial for polarizing the nuclear spin ensemble. We reach a nuclear spin polarization of ≃50%, unrivaled in lateral dots, and explain our manipulation technique using a comprehensive rate equation model.

  16. 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.

  17. An amphiphilic region in the cytoplasmic domain of KdpD is recognized by the signal recognition particle and targeted to the Escherichia coli membrane

    PubMed Central

    Maier, Katja S; Hubich, Stefanie; Liebhart, Helga; Krauss, Susanne; Kuhn, Andreas; Facey, Sandra J

    2008-01-01

    The sensor protein KdpD of Escherichia coli is composed of a large N-terminal hydrophilic region (aa 1–400), four transmembrane regions (aa 401–498) and a large hydrophilic region (aa 499–894) at the C-terminus. KdpD requires the signal recognition particle (SRP) for its targeting to the membrane. Deletions within KdpD show that the first 50 residues are required for SRP-driven membrane insertion. A fusion protein of the green fluorescent protein (GFP) with KdpD is found localized at the membrane only when SRP is present. The membrane targeting of GFP was not observed when the first 50 KdpD residues were deleted. A truncated mutant of KdpD containing only the first 25 amino acids fused to GFP lost its ability to specifically interact with SRP, whereas a specific interaction between SRP and the first 48 amino acids of KdpD fused to GFP was confirmed by pull-down experiments. Conclusively, a small amphiphilic region of 27 residues within the amino-terminal domain of KdpD (aa 22–48) is recognized by SRP and targets the protein to the membrane. This shows that membrane proteins with a large N-terminal region in the cytoplasm can be membrane-targeted early on to allow co-translational membrane insertion of their distant transmembrane regions. PMID:18433452

  18. 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.

  19. 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.

  20. 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.

  1. [Domain organization of the ORF2 C-terminal region of the German cockroach retroposon R1].

    PubMed

    Kagramanova, A S; Kapelinskaia, T V; Korolev, A L; Mukha, D V

    2010-08-01

    Using cosmid vector, a gene library of German cockroach Blattella germanica was constructed. From this library, clones containing full-length copies of two subfamilies of R1 retroposons were selected. Retroposons R1 of German cockroach belonging to different subfamilies were shown to be different in domain organization of the ORF2 C-terminal region. For the first time, retroposons transmembrane domains were identified in the sequences of R1. It was demonstrated that two retroposon R1 subfamilies of German cockroach arose as a result of intragenomic divergence rather than via horizontal transfer of alien mobile element into cockroach genome. The differences in domain organization appeared not as a result of saltatory recombination processes, but as a consequence of gradual mutation accumulation, which led to either degeneration, or to domain formation.

  2. 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.

  3. Mutations in the ligand-binding domain of the androgen receptor gene cluster in two regions of the gene.

    PubMed

    McPhaul, M J; Marcelli, M; Zoppi, S; Wilson, C M; Griffin, J E; Wilson, J D

    1992-11-01

    We have analyzed the nucleotide sequence of the androgen receptor from 22 unrelated subjects with substitution mutations of the hormone-binding domain. Eleven had the phenotype of complete testicular feminization, four had incomplete testicular feminization, and seven had Reifenstein syndrome. The underlying functional defect in cultured skin fibroblasts included individuals with absent, qualitative, or quantitative defects in ligand binding. 19 of the 21 substitution mutations (90%) cluster in two regions that account for approximately 35% of the hormone-binding domain, namely, between amino acids 726 and 772 and between amino acids 826 and 864. The fact that one of these regions is homologous to a region of the human thyroid hormone receptor (hTR-beta) which is a known cluster site for mutations that cause thyroid hormone resistance implies that this localization of mutations is not a coincidence. These regions of the androgen receptor may be of particular importance for the formation and function of the hormone-receptor complex.

  4. 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.

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

    NASA Astrophysics Data System (ADS)

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

  6. 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.

  7. Mapping of the high affinity Fc epsilon receptor binding site to the third constant region domain of IgE.

    PubMed Central

    Nissim, A; Jouvin, M H; Eshhar, Z

    1991-01-01

    Identification of the precise region(s) on the IgE molecule that take part in the binding of IgE to its high affinity receptor (Fc epsilon RI) may lead to the design of IgE analogues able to block the allergic response. To localize the Fc epsilon RI-binding domain of mouse IgE, we attempted to confer on human IgE, which normally does not bind to the rodent receptor, the ability to bind to the rat Fc epsilon RI. Employing exon shuffling, we have expressed chimeric epsilon-heavy chain genes composed of a mouse (4-hydroxy-3-nitrophenyl)acetic acid (NP)-binding VH domain, and human C epsilon in which various domains were replaced by their murine counterparts. This has enabled us to test the Fc epsilon RI-binding of each mouse IgE domain while maintaining the overall conformation of the molecule. All of the chimeric IgE molecules which contain the murine C epsilon 3, bound equally to both the rodent and human receptor, as well as to monoclonal antibodies recognizing a site on IgE which is identical or very close to the Fc epsilon RI binding site. Deletion of the second constant region domain did not impair either the binding capacity of the mutated IgE or its ability to mediate mast cell degradation. These results assign the third epsilon domain of IgE as the principal region involved in the interaction with the Fc epsilon RI. Images PMID:1824934

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

    PubMed

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

    2016-07-01

    The Z-DNA-binding domain of PKZ from zebrafish (Danio rerio; drZαPKZ ) contains the largest β-wing among known Z-DNA-binding domains. To elucidate the functional implication of the β-wing, we solved the crystal structure of apo-drZαPKZ . Structural comparison with its Z-DNA-bound form revealed a large conformational change within the β-wing during Z-DNA binding. Biochemical studies of protein mutants revealed that two basic residues in the β-wing are responsible for Z-DNA recognition as well as fast B-Z transition. Therefore, the extra basic residues in the β-wing of drZαPKZ are necessary for the fast B-Z transition activity. © 2016 Federation of European Biochemical Societies.

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

    NASA Technical Reports Server (NTRS)

    Horowitz, I. M.; Sidi, M.

    1971-01-01

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

  10. Embedding complex hydrology in the regional climate system - Dynamic coupling across different modelling domains

    NASA Astrophysics Data System (ADS)

    Butts, Michael; Drews, Martin; Larsen, Morten A. D.; Lerer, Sara; Rasmussen, Søren H.; Grooss, Jesper; Overgaard, Jesper; Refsgaard, Jens C.; Christensen, Ole B.; Christensen, Jens H.

    2014-12-01

    To improve our understanding of the impacts of feedback between the atmosphere and the terrestrial water cycle including groundwater and to improve the integration of water resource management modelling for climate adaption we have developed a dynamically coupled climate-hydrological modelling system. The OpenMI modelling interface is used to couple a comprehensive hydrological modelling system, MIKE SHE running on personal computers, and a regional climate modelling system, HIRHAM running on a high performance computing platform. The coupled model enables two-way interaction between the atmosphere and the groundwater via the land surface and can represent the lateral movement of water in both the surface and subsurface and their interactions, not normally accounted for in climate models. Meso-scale processes are important for climate in general and rainfall in particular. Hydrological impacts are assessed at the catchment scale, the most important scale for water management. Feedback between groundwater, the land surface and the atmosphere occurs across a range of scales. Recognising this, the coupling was developed to allow dynamic exchange of water and energy at the catchment scale embedded within a larger meso-scale modelling domain. We present the coupling methodology used and describe the challenges in representing the exchanges between models and across scales. The coupled model is applied to one-way and two-way coupled simulations for a managed groundwater-dominated catchment, the Skjern River, Denmark. These coupled model simulations are evaluated against field observations and then compared with uncoupled climate and hydrological model simulations. Exploratory simulations show significant differences, particularly in the summer for precipitation and evapotranspiration the coupled model including groundwater and the RCM where groundwater is neglected. However, the resulting differences in the net precipitation and the catchment runoff in this groundwater

  11. Hierarchical spatial models for predicting tree species assemblages across large domains

    Treesearch

    Andrew O. Finley; Sudipto Banerjee; Ronald E. McRoberts

    2009-01-01

    Spatially explicit data layers of tree species assemblages, referred to as forest types or forest type groups, are a key component in large-scale assessments of forest sustainability, biodiversity, timber biomass, carbon sinks and forest health monitoring. This paper explores the utility of coupling georeferenced national forest inventory (NFI) data with readily...

  12. Exploring symmetry as an avenue to the computational design of large protein domains.

    PubMed

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

    2011-11-16

    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 (βα)(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.

  13. 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.

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

    PubMed

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

    2016-03-01

    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.

  15. 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

  16. Toward Large Scale Parallelization for Molecular Dynamics of Small Chemical Systems: A Combined Parallel Tempering and Domain Decomposition Approach.

    PubMed

    Slim, Henk A; Wilson, Mark R

    2008-10-14

    A combined parallel tempering (replica exchange) and domain decomposition approach is presented, which allows for the effective use of large numbers of processor cores (>256) on modest sized simulations of chemical systems (∼5000 sites). The approach is implemented in the gbmoldd molecular dynamics program for the simulation of coarse-grained molecular systems composed of combinations of isotropic and/or anisotropic particles. Benchmark results are presented for two test systems: a C24 united atom chain and a coarse-grained system of spherocylinders.

  17. 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.

  18. Gating of the MlotiK1 potassium channel involves large rearrangements of the cyclic nucleotide-binding domains

    PubMed Central

    Mari, Stefania A.; Pessoa, João; Altieri, Stephen; Hensen, Ulf; Thomas, Lise; Morais-Cabral, João H.; Müller, Daniel J.

    2011-01-01

    Cyclic nucleotide-regulated ion channels are present in bacteria, plants, vertebrates, and humans. In higher organisms, they are closely involved in signaling networks of vision and olfaction. Binding of cAMP or cGMP favors the activation of these ion channels. Despite a wealth of structural and studies, there is a lack of structural data describing the gating process in a full-length cyclic nucleotide-regulated channel. We used high-resolution atomic force microscopy (AFM) to directly observe the conformational change of the membrane embedded bacterial cyclic nucleotide-regulated channel MlotiK1. In the nucleotide-bound conformation, the cytoplasmic cyclic nucleotide-binding (CNB) domains of MlotiK1 are disposed in a fourfold symmetric arrangement forming a pore-like vestibule. Upon nucleotide-unbinding, the four CNB domains undergo a large rearrangement, stand up by ∼1.7 nm, and adopt a structurally variable grouped conformation that closes the cytoplasmic vestibule. This fully reversible conformational change provides insight into how CNB domains rearrange when regulating the potassium channel. PMID:22135457

  19. 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).

  20. A non-overlapping domain decomposition method with non-matching grids for modeling large finite antenna arrays

    NASA Astrophysics Data System (ADS)

    Lee, Seung-Cheol; Vouvakis, Marinos N.; Lee, Jin-Fa

    2005-02-01

    A non-overlapping domain decomposition method (DDM) is proposed herein to solve Maxwell equations in R3. In this work, the Maxwell equations are discretized using a vector finite element method with hierarchical H(curl) vector basis functions. There are two major ingredients in the proposed non-overlapping DDM: (a) A proper 1st order transmission condition to enforce field continuity across domain boundaries and (b) A cement technique to allow non-matching grids for neighboring domains. Moreover, a detail Fourier analysis of the transmission condition for a canonical half-space example is presented. The analysis provides significant insights into the convergence behavior of the proposed non-overlapping DDM for solving electromagnetic radiation problems, such as the large finite antenna arrays. Particularly for the antenna arrays, the proposed non-overlapping DDM is extremely efficient since the formulation can easily incorporate geometrical repetitions. Exponentially tapered notch (Vivaldi) antenna arrays with size up to 100 × 100 elements are solved on a common PC to validate the proposed non-overlapping DDM.

  1. The ExbD Periplasmic Domain Contains Distinct Functional Regions for Two Stages in TonB Energization

    PubMed Central

    Ollis, Anne A.; Kumar, Aruna

    2012-01-01

    The TonB system of Gram-negative bacteria energizes the active transport of diverse nutrients through high-affinity TonB-gated outer membrane transporters using energy derived from the cytoplasmic membrane proton motive force. Cytoplasmic membrane proteins ExbB and ExbD harness the proton gradient to energize TonB, which directly contacts and transmits this energy to ligand-loaded transporters. In Escherichia coli, the periplasmic domain of ExbD appears to transition from proton motive force-independent to proton motive force-dependent interactions with TonB, catalyzing the conformational changes of TonB. A 10-residue deletion scanning analysis showed that while all regions except the extreme amino terminus of ExbD were indispensable for function, distinct roles for the amino- and carboxy-terminal regions of the ExbD periplasmic domain were evident. Like residue D25 in the ExbD transmembrane domain, periplasmic residues 42 to 61 facilitated the conformational response of ExbD to proton motive force. This region appears to be important for transmitting signals between the ExbD transmembrane domain and carboxy terminus. The carboxy terminus, encompassing periplasmic residues 62 to 141, was required for initial assembly with the periplasmic domain of TonB, a stage of interaction required for ExbD to transmit its conformational response to proton motive force to TonB. Residues 92 to 121 were important for all three interactions previously observed for formaldehyde-cross-linked ExbD: ExbD homodimers, TonB-ExbD heterodimers, and ExbD-ExbB heterodimers. The distinct requirement of this ExbD region for interaction with ExbB raised the possibility of direct interaction with the few residues of ExbB known to occupy the periplasm. PMID:22493019

  2. The ExbD periplasmic domain contains distinct functional regions for two stages in TonB energization.

    PubMed

    Ollis, Anne A; Kumar, Aruna; Postle, Kathleen

    2012-06-01

    The TonB system of gram-negative bacteria energizes the active transport of diverse nutrients through high-affinity TonB-gated outer membrane transporters using energy derived from the cytoplasmic membrane proton motive force. Cytoplasmic membrane proteins ExbB and ExbD harness the proton gradient to energize TonB, which directly contacts and transmits this energy to ligand-loaded transporters. In Escherichia coli, the periplasmic domain of ExbD appears to transition from proton motive force-independent to proton motive force-dependent interactions with TonB, catalyzing the conformational changes of TonB. A 10-residue deletion scanning analysis showed that while all regions except the extreme amino terminus of ExbD were indispensable for function, distinct roles for the amino- and carboxy-terminal regions of the ExbD periplasmic domain were evident. Like residue D25 in the ExbD transmembrane domain, periplasmic residues 42 to 61 facilitated the conformational response of ExbD to proton motive force. This region appears to be important for transmitting signals between the ExbD transmembrane domain and carboxy terminus. The carboxy terminus, encompassing periplasmic residues 62 to 141, was required for initial assembly with the periplasmic domain of TonB, a stage of interaction required for ExbD to transmit its conformational response to proton motive force to TonB. Residues 92 to 121 were important for all three interactions previously observed for formaldehyde-cross-linked ExbD: ExbD homodimers, TonB-ExbD heterodimers, and ExbD-ExbB heterodimers. The distinct requirement of this ExbD region for interaction with ExbB raised the possibility of direct interaction with the few residues of ExbB known to occupy the periplasm.

  3. A computational approach identifies two regions of Hepatitis C Virus E1 protein as interacting domains involved in viral fusion process.

    PubMed

    Bruni, Roberto; Costantino, Angela; Tritarelli, Elena; Marcantonio, Cinzia; Ciccozzi, Massimo; Rapicetta, Maria; El Sawaf, Gamal; Giuliani, Alessandro; Ciccaglione, Anna Rita

    2009-07-29

    The E1 protein of Hepatitis C Virus (HCV) can be dissected into two distinct hydrophobic regions: a central domain containing an hypothetical fusion peptide (FP), and a C-terminal domain (CT) comprising two segments, a pre-anchor and a trans-membrane (TM) region. In the currently accepted model of the viral fusion process, the FP and the TM regions are considered to be closely juxtaposed in the post-fusion structure and their physical interaction cannot be excluded. In the present study, we took advantage of the natural sequence variability present among HCV strains to test, by purely sequence-based computational tools, the hypothesis that in this virus the fusion process involves the physical interaction of the FP and CT regions of E1. Two computational approaches were applied. The first one is based on the co-evolution paradigm of interacting peptides and consequently on the correlation between the distance matrices generated by the sequence alignment method applied to FP and CT primary structures, respectively. In spite of the relatively low random genetic drift between genotypes, co-evolution analysis of sequences from five HCV genotypes revealed a greater correlation between the FP and CT domains than respect to a control HCV sequence from Core protein, so giving a clear, albeit still inconclusive, support to the physical interaction hypothesis.The second approach relies upon a non-linear signal analysis method widely used in protein science called Recurrence Quantification Analysis (RQA). This method allows for a direct comparison of domains for the presence of common hydrophobicity patterns, on which the physical interaction is based upon. RQA greatly strengthened the reliability of the hypothesis by the scoring of a lot of cross-recurrences between FP and CT peptides hydrophobicity patterning largely outnumbering chance expectations and pointing to putative interaction sites. Intriguingly, mutations in the CT region of E1, reducing the fusion process in

  4. A comparison of different inverse carbon flux estimation approaches for application on a regional domain

    NASA Astrophysics Data System (ADS)

    Tolk, L. F.; Dolman, A. J.; Meesters, A. G. C. A.; Peters, W.

    2011-10-01

    We have implemented six different inverse carbon flux estimation methods in a regional carbon dioxide (CO2) flux modeling system for the Netherlands. The system consists of the Regional Atmospheric Mesoscale Modeling System (RAMS) coupled to a simple carbon flux scheme which is run in a coupled fashion on relatively high resolution (10 km). Using an Ensemble Kalman filter approach we try to estimate spatiotemporal carbon exchange patterns from atmospheric CO2 mole fractions over the Netherlands for a two week period in spring 2008. The focus of this work is the different strategies that can be employed to turn first-guess fluxes into optimal ones, which is known as a fundamental design choice that can affect the outcome of an inversion significantly. Different state-of-the-art approaches with respect to the estimation of net ecosystem exchange (NEE) are compared quantitatively: (1) where NEE is scaled by one linear multiplication factor per land-use type, (2) where the same is done for photosynthesis (GPP) and respiration (R) separately with varying assumptions for the correlation structure, (3) where we solve for those same multiplication factors but now for each grid box, and (4) where we optimize physical parameters of the underlying biosphere model for each land-use type. The pattern to be retrieved in this pseudo-data experiment is different in nearly all aspects from the first-guess fluxes, including the structure of the underlying flux model, reflecting the difference between the modeled fluxes and the fluxes in the real world. This makes our study a stringent test of the performance of these methods, which are currently widely used in carbon cycle inverse studies. Our results show that all methods struggle to retrieve the spatiotemporal NEE distribution, and none of them succeeds in finding accurate domain averaged NEE with correct spatial and temporal behavior. The main cause is the difference between the structures of the first-guess and true CO2 flux

  5. A comparison of different inverse carbon flux estimation approaches for application on a regional domain

    NASA Astrophysics Data System (ADS)

    Tolk, L. F.; Dolman, A. J.; Meesters, A. G. C. A.; Peters, W.

    2011-01-01

    We have implemented six different inverse carbon flux estimation methods in a regional carbon dioxide (CO2) flux modeling system for The Netherlands. The system consists of the Regional Atmospheric Mesoscale Modeling System (RAMS) coupled to a simple carbon flux scheme which is run in a coupled fashion on relatively high resolution (10 km). Using an Ensemble Kalman filter approach we try to estimate spatiotemporal carbon exchange patterns from atmospheric CO2 mole fractions over The Netherlands for a two week period in spring 2008. The focus of this work is the different strategies that can be employed to turn first-guess fluxes into optimal ones, which is known as a fundamental design choice that can affect the outcome of an inversion significantly. Different state-of-the-art approaches with respect to the estimation of net ecosystem exchange (NEE) are compared quantitatively: (1) where NEE is scaled by one linear multiplication factor per land-use type, (2) where the same is done for photosynthesis (GPP) and respiration (R) separately with varying assumptions for the correlation structure, (3) where we solve for those same multiplication factors but now for each grid box, and (4) where we optimize physical parameters of the underlying biosphere model for each land-use type. The pattern to be retrieved in this pseudo-data experiment is different in nearly all aspects from the first-guess fluxes, including the structure of the underlying flux model, reflecting the difference between the modeled fluxes and the fluxes in the real world. This makes our study a stringent test of the performance of these methods, which are currently widely used in carbon cycle inverse studies. Our results show that all methods struggle to retrieve the spatiotemporal NEE distribution, and none of them succeeds in finding accurate domain averaged NEE with correct spatial and temporal behavior. The main cause is the difference between the structures of the first-guess and true CO2 flux

  6. 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

  7. 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.

  8. Nature and distribution of geological domains at the Africa-Eurasia plate boundary off SW Iberia and regional geodynamic implications

    NASA Astrophysics Data System (ADS)

    Martínez-Loriente, Sara; Sallarès, Valentí; Gràcia, Eulàlia; Bartolome, Rafael

    2014-05-01

    We present a new classification of geological domains at the Africa-Eurasia plate boundary off SW Iberia, together with a regional geodynamic reconstruction spanning from the Mesozoic extension to the Neogene-to-present-day convergence. It is based on seismic velocity and density models along two regional wide-angle seismic transects, one running NW-SE from the Horseshoe to the Seine abyssal plains, and the other running N-S from S Portugal to the Seine Abyssal Plain, combined with previously available information. The seismic velocity and density structure at the Seine Abyssal Plain and the internal Gulf of Cadiz indicates the presence of a highly heterogeneous oceanic crust, similar to that described in ultra-slow spreading centers, whereas in the Horseshoe and Tagus abyssal plains, the basement structure resembles that of exhumed mantle sections identified in the Northern Atlantic margin. The integration of all this new information allows defining the presence of three oceanic domains offshore SW Iberia: (1) the Seine Abyssal Plain domain, generated during the first stages of slow seafloor spreading in the NE Central Atlantic (Early Jurassic); (2) the Gulf of Cadiz domain, made of oceanic crust generated in the Alpine-Tethys spreading system between Iberia and Africa, which was coeval with the formation of the Seine Abyssal Plain domain and lasted up to the North Atlantic continental break-up (Late Jurassic); and (3) the Gorringe Bank domain, mainly made of rocks exhumed from the mantle with little synchronous magmatism, which formed during the first stages of North Atlantic opening. Our models suggest that the Seine Abyssal Plain and Gulf of Cadiz domains are separated by the Lineament South strike-slip fault, whereas the Gulf of Cadiz and Gorringe Bank domains appear to be limited by a deep thrust fault located at the center of the Horseshoe Abyssal Plain. The formation and evolution of these three domains during the Mesozoic is key to understand the sequence

  9. Women Workers in Regional Areas and in Large States and Metropolitan Areas, 1971.

    ERIC Educational Resources Information Center

    Employment Standards Administration (DOL), Washington, DC. Women's Bureau.

    Data from the Bureau of Labor Statistics has been summarized on labor force participation and unemployment rates in 1971, of women 16 years of age and over, in the various census regions of the United States and in 10 large States and 20 large Standard Metropolitan Statistical Areas (SMSA's); separate data also have been summarized for women of…

  10. Large single-domain growth of monolayer WS2 by rapid-cooling chemical vapor deposition

    NASA Astrophysics Data System (ADS)

    Li, Chao; Yamaguchi, Yoshiki; Kaneko, Toshiro; Kato, Toshiaki

    2017-07-01

    A novel method for the synthesis of large monolayer and single-crystal tungsten disulfide (WS2) has been developed by introducing a rapid-cooling stage to the conventional chemical vapor deposition (CVD). The maximum size of single-crystal WS2 can be increased up to 320 µm by adjusting the growth parameters during the rapid-cooling CVD. This is one of the largest sizes of single-crystal transition metal dichalcogenides directly grown on an insulating substrate. A theoretical model reveals that the increase in WS2 size can be explained by the enhanced nucleation probability and the growth velocity, caused by the additional precursors supplied during the rapid cooling.

  11. 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.

  12. Molecular insights into the binding of phosphoinositides to the TH domain region of TIPE proteins.

    PubMed

    Antony, Priya; Baby, Bincy; Vijayan, Ranjit

    2016-11-01

    Phosphatidylinositols and their phosphorylated derivatives, phosphoinositides, play a central role in regulating diverse cellular functions. These phospholipids have been shown to interact with the hydrophobic TH domain of the tumor necrosis factor (TNF)-α-induced protein 8 (TIPE) family of proteins. However, the precise mechanism of interaction of these lipids is unclear. Here we report the binding mode and interactions of these phospholipids in the TH domain, as elucidated using molecular docking and simulations. Results indicate that phosphoinositides bind to the TH domain in a similar way by inserting their lipid tails in the hydrophobic cavity. The exposed head group is stabilized by interactions with critical positively charged residues on the surface of these proteins. Further MD simulations confirmed the dynamic stability of these lipids in the TH domain. This computational analysis thus provides insight into the binding mode of phospholipids in the TH domain of the TIPE family of proteins. Graphical abstract A phosphoinositide (phosphatidylinositol 4-phosphate; PtdIns4P) docked to TIPE2.

  13. 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.

  14. 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.

  15. 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

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

    PubMed Central

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

    2014-01-01

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

  17. Domains of importance to the quality of life of older people from two Swiss regions.

    PubMed

    Henchoz, Yves; Meylan, Lionel; Goy, René; Guessous, Idris; Bula, Christophe; Demont, Maurice; Rodondi, Nicolas; Santos-Eggimann, Brigitte

    2015-11-01

    Quality of life (QoL) is a subjective perception whose components may vary in importance between individuals. Little is known about which domains of QoL older people deem most important. This study investigated in community-dwelling older people the relationships between the importance given to domains defining their QoL and socioeconomic, demographic and health status. Data were compiled from older people enrolled in the Lc65+ cohort study and two additional, population-based, stratified random samples (n = 5,300). Principal components analysis (PCA) was used to determine the underlying domains among 28 items that participants defined as important to their QoL. The components extracted were used as dependent variables in multiple linear regression models to explore their associations with socioeconomic, demographic and health status. PCA identified seven domains that older persons considered important to their QoL. In order of importance (highest to lowest): feeling of safety, health and mobility, autonomy, close entourage, material resources, esteem and recognition, and social and cultural life. A total of six and five domains of importance were significantly associated with education and depressive symptoms, respectively. The importance of material resources was significantly associated with a good financial situation (β = 0.16, P = 0.011), as was close entourage with living with others (β = 0.20, P = 0.007) and as was health and mobility with age (β = -0.16, P = 0.014). The importance older people give to domains of their QoL appears strongly related to their actual resources and experienced losses. These findings may help clinicians, researchers and policy makers better adapt strategies to individuals' needs. © The Author 2015. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  18. 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

  19. 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

  20. Different regional climatic drivers of Holocene large wildfires in boreal forests of northeastern America

    NASA Astrophysics Data System (ADS)

    Remy, Cécile C.; Hély, Christelle; Blarquez, Olivier; Magnan, Gabriel; Bergeron, Yves; Lavoie, Martin; Ali, Adam A.

    2017-03-01

    Global warming could increase climatic instability and large wildfire activity in circumboreal regions, potentially impairing both ecosystem functioning and human health. However, links between large wildfire events and climatic and/or meteorological conditions are still poorly understood, partly because few studies have covered a wide range of past climate-fire interactions. We compared palaeofire and simulated climatic data over the last 7000 years to assess causes of large wildfire events in three coniferous boreal forest regions in north-eastern Canada. These regions span an east-west cline, from a hilly region influenced by the Atlantic Ocean currently dominated by Picea mariana and Abies balsamea to a flatter continental region dominated by Picea mariana and Pinus banksiana. The largest wildfires occurred across the entire study zone between 3000 and 1000 cal. BP. In western and central continental regions these events were triggered by increases in both the fire-season length and summer/spring temperatures, while in the eastern region close to the ocean they were likely responses to hydrological (precipitation/evapotranspiration) variability. The impact of climatic drivers on fire size varied spatially across the study zone, confirming that regional climate dynamics could modulate effects of global climate change on wildfire regimes.

  1. 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.

  2. Phage Display Derived IgNAR V Region Binding Domains for Therapeutic Development.

    PubMed

    Ubah, Obinna C; Barelle, Caroline J; Buschhaus, Magdalena J; Porter, Andrew J

    2016-01-01

    Phage display technology has revolutionized the science of drug discovery by transforming the generation and manipulation of ligands, such as antibody fragments, enzymes, and peptides. The basis of this technology is the expression of recombinant proteins or peptides fused to a phage coat protein, and subsequent isolation of ligands based on a variety of catalytic, physicochemical/binding kinetic and/or biological characteristics. An incredible number of diagnostic and therapeutic domains have been successfully isolated using phage display technology. The variable domain of the New Antigen Receptors (VNAR) found in cartilaginous fish, is also amenable to phage display selection. Whilst not an antibody, VNARs are unquestionable the oldest (450 million years), and smallest antigen binding, single-domains so far identified in the vertebrate kingdom. Their role as an integral part of the adaptive immune system of sharks has been well established, enhancing our understanding of the evolutionary origins of humoral immunity and the unusual but divergent ancestry of the VNARs themselves. VNARs exhibit remarkable physicochemical properties, such as small size, stability in extreme conditions, solubility, molecular flexibility, high affinity and selectivity for target. The purpose of this review is to illustrate the important role phage display has played in the isolation and characterization of potent therapeutic and diagnostic VNAR domains.

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

    NASA Astrophysics Data System (ADS)

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

    2012-04-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2011-11-01

    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.

  5. 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.

  6. The c-myc insulator element and matrix attachment regions define the c-myc chromosomal domain.

    PubMed

    Gombert, Wendy M; Farris, Stephen D; Rubio, Eric D; Morey-Rosler, Kristin M; Schubach, William H; Krumm, Anton

    2003-12-01

    Insulator elements and matrix attachment regions are essential for the organization of genetic information within the nucleus. By comparing the pattern of histone modifications at the mouse and human c-myc alleles, we identified an evolutionarily conserved boundary at which the c-myc transcription unit is separated from the flanking condensed chromatin enriched in lysine 9-methylated histone H3. This region harbors the c-myc insulator element (MINE), which contains at least two physically separable, functional activities: enhancer-blocking activity and barrier activity. The enhancer-blocking activity is mediated by CTCF. Chromatin immunoprecipitation assays demonstrate that CTCF is constitutively bound at the insulator and at the promoter region independent of the transcriptional status of c-myc. This result supports an architectural role of CTCF rather than a regulatory role in transcription. An additional higher-order nuclear organization of the c-myc locus is provided by matrix attachment regions (MARs) that define a domain larger than 160 kb. The MARs of the c-myc domain do not act to prevent the association of flanking regions with lysine 9-methylated histones, suggesting that they do not function as barrier elements.

  7. 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

  8. The use of regional coordinating centers in large clinical trials: the DIG trial.

    PubMed

    Collins, Joseph F; Martin, Sylvia; Kent, Eleanor; Liuni, Connie; Garg, Rekha; Egan, Debra

    2003-12-01

    The Digitalis Investigation Group (DIG) trial was a large simple clinical trial that involved 302 participating centers in the United States and Canada. In order to encourage participation by Canadian investigators, to provide additional help to what were expected to be largely research-inexperienced investigators in Canada, and to provide the study's data coordinating center with resources in Canada to deal with potentially different rules, regulations, and cultural differences, regional coordinating centers were established in four regions of Canada: the maritime provinces, Quebec, Ontario, and western Canada. Canadian centers recruited significantly better than their U.S. counterparts and had slightly better retention and follow-up. While it is not possible to declare that the regional coordinating centers were responsible for this improvement, it is believed that these regional centers did play a role. This role included being able to identify investigators who could be expected to do well, providing one-on-one training and instruction to investigators, and being able to solve problems and implement change in the relatively fewer centers in their regions. The regional coordinating center also reduced the intensity of the workload on the data coordinating center by serving as the primary point of contact for Canadian investigators. The use of regional coordinating centers in studies with a large number of participating centers is highly recommended.

  9. Analysis of the large (L) protein gene of the porcine rubulavirus LPMV: identification of possible functional domains.

    PubMed

    Svenda, M; Berg, M; Moreno-López, J; Linné, T

    1997-04-01

    The complete nucleotide sequence of the porcine rubulavirus LPMV (La Piedad Michoacan virus) large (L) protein gene was determined and analysed. The L mRNA was found to span 6,786 nucleotides, containing one single large open reading frame (ORF), putatively encoding a polypeptide of 2,251 amino acids. By aligning the amino acid sequence of the LPMV L-protein with L-protein of a number of viruses belonging to the order mononegavirale, a high degree of similarity between the LPMV L-protein and other rubula virus L-proteins was demonstrated, extending through almost the whole protein. Additionally we could identify several regions as being highly conserved among all studied viruses of the order mononegavirale. The significance of these regions are discussed.

  10. The large groove found in the gH/gL structure is an important functional domain for Epstein-Barr virus fusion.

    PubMed

    Chen, Jia; Jardetzky, Theodore S; Longnecker, Richard

    2013-04-01

    Epstein-Barr virus (EBV) mediates viral entry into cells using four glycoproteins-gB, the gH/gL complex, and gp42-and fusion is cell type specific. gB and gH/gL are required for epithelial cell fusion; B cell fusion also requires gp42. To investigate functional domains within the gH/gL structure, we constructed site-directed EBV gH/gL mutants with alterations of residues located in a large groove that separates domain I (D-I) from domain II (D-II) within the gH/gL structure. We found that substitution of alanine for leucine 207 reduces both epithelial and B cell fusion and is accompanied by reduced gp42 binding. We also observed that substitution of alanine for arginine 152, histidine 154, or threonine 174 reduces fusion with epithelial cells but not with B cells. To test whether flexibility of the region between D-I and D-II of gH/gL could be important for membrane fusion activity and to allow potential interactions across the D-I/D-II groove, we mutated D-I amino acids V47, P48, and G49 to cysteine, allowing novel intersubunit disulfide bonds to form with the free C153 located in D-II. We found that the G49C mutant, predicted to bridge D-I and D-II with C153 of gH/gL, had normal B cell fusion activity but reduced epithelial cell fusion activity, which was partially restored by treatment with dithiothreitol. We conclude that structural rearrangements and/or interactions across the D-I/D-II groove of gH/gL are required for fusion with epithelial cells but not for fusion with B cells.

  11. The Large Groove Found in the gH/gL Structure Is an Important Functional Domain for Epstein-Barr Virus Fusion

    PubMed Central

    Chen, Jia; Jardetzky, Theodore S.

    2013-01-01

    Epstein-Barr virus (EBV) mediates viral entry into cells using four glycoproteins—gB, the gH/gL complex, and gp42—and fusion is cell type specific. gB and gH/gL are required for epithelial cell fusion; B cell fusion also requires gp42. To investigate functional domains within the gH/gL structure, we constructed site-directed EBV gH/gL mutants with alterations of residues located in a large groove that separates domain I (D-I) from domain II (D-II) within the gH/gL structure. We found that substitution of alanine for leucine 207 reduces both epithelial and B cell fusion and is accompanied by reduced gp42 binding. We also observed that substitution of alanine for arginine 152, histidine 154, or threonine 174 reduces fusion with epithelial cells but not with B cells. To test whether flexibility of the region between D-I and D-II of gH/gL could be important for membrane fusion activity and to allow potential interactions across the D-I/D-II groove, we mutated D-I amino acids V47, P48, and G49 to cysteine, allowing novel intersubunit disulfide bonds to form with the free C153 located in D-II. We found that the G49C mutant, predicted to bridge D-I and D-II with C153 of gH/gL, had normal B cell fusion activity but reduced epithelial cell fusion activity, which was partially restored by treatment with dithiothreitol. We conclude that structural rearrangements and/or interactions across the D-I/D-II groove of gH/gL are required for fusion with epithelial cells but not for fusion with B cells. PMID:23325693

  12. Entropy-driven binding of opioid peptides induces a large domain motion in human dipeptidyl peptidase III

    PubMed Central

    Bezerra, Gustavo A.; Dobrovetsky, Elena; Viertlmayr, Roland; Dong, Aiping; Binter, Alexandra; Abramić, Marija; Macheroux, Peter; Dhe-Paganon, Sirano; Gruber, Karl

    2012-01-01

    Opioid peptides are involved in various essential physiological processes, most notably nociception. Dipeptidyl peptidase III (DPP III) is one of the most important enkephalin-degrading enzymes associated with the mammalian pain modulatory system. Here we describe the X-ray structures of human DPP III and its complex with the opioid peptide tynorphin, which rationalize the enzyme's substrate specificity and reveal an exceptionally large domain motion upon ligand binding. Microcalorimetric analyses point at an entropy-dominated process, with the release of water molecules from the binding cleft (“entropy reservoir”) as the major thermodynamic driving force. Our results provide the basis for the design of specific inhibitors that enable the elucidation of the exact role of DPP III and the exploration of its potential as a target of pain intervention strategies. PMID:22493238

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

    PubMed Central

    2015-01-01

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

  14. 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

  15. Entropy-driven binding of opioid peptides induces a large domain motion in human dipeptidyl peptidase III.

    PubMed

    Bezerra, Gustavo A; Dobrovetsky, Elena; Viertlmayr, Roland; Dong, Aiping; Binter, Alexandra; Abramic, Marija; Macheroux, Peter; Dhe-Paganon, Sirano; Gruber, Karl

    2012-04-24

    Opioid peptides are involved in various essential physiological processes, most notably nociception. Dipeptidyl peptidase III (DPP III) is one of the most important enkephalin-degrading enzymes associated with the mammalian pain modulatory system. Here we describe the X-ray structures of human DPP III and its complex with the opioid peptide tynorphin, which rationalize the enzyme's substrate specificity and reveal an exceptionally large domain motion upon ligand binding. Microcalorimetric analyses point at an entropy-dominated process, with the release of water molecules from the binding cleft ("entropy reservoir") as the major thermodynamic driving force. Our results provide the basis for the design of specific inhibitors that enable the elucidation of the exact role of DPP III and the exploration of its potential as a target of pain intervention strategies.

  16. eHealth vision towards cooperative patient care--domain fields and architectural challenges of regional health care networks.

    PubMed

    Gusew, Nathalie; Gerlach, Annekatrin; Bartkiewicz, Thomas; Goldapp, Michael; Haux, Reinhold; Heller, Ulrich; Hellrung, Nils; Kierdorf, Horst-P; Kleinschmidt, Thorsten; Markurth, Ulrich; Marschollek, Michael; Plischke, Maik; Schubert, Rainer; Seidel, Christoph; Wiegmann, Holger

    2010-01-01

    Numerous eHealth projects and efforts to establish inter-organizational communication and to build up regional health care networks could be observed in the last ten years. Nevertheless the success of such efforts is profoundly different. The aim of this paper is to introduce the lately started regional initiative eHealth.Braunschweig compounding of the major health care players (hospitals, physician offices, nursing services and nursing homes) in the region of Braunschweig, participants from research institutions and industry. We propose in this paper the main goals of the regional initiative eHealth.Braunschweig, its constitution and major approaches. Based on respective literature and our former projects as well as experiences in this field we discuss our vision of a patient-oriented cooperative health care by depicting regional distinctions, identifying the major domain fields in this context and discussing the architectural challenges for the regional health care network eHealth.Braunschweig. In our view this work can be considered as a systematical approach to the establishment of regional health care networks with lasting and sustainable effects on patient-centered health care in a region.

  17. Dynamic Triggering of Earthquakes in the Salton Sea Region of Southern California from Large Regional and Teleseismic Earthquakes

    NASA Astrophysics Data System (ADS)

    Doran, A.; Meng, X.; Peng, Z.; Wu, C.; Kilb, D. L.

    2010-12-01

    We perform a systematic survey of dynamically triggered earthquakes in the Salton Sea region of southern California using borehole seismic data recordings (2007 to present). We define triggered events as high-frequency seismic energy during large-amplitude seismic waves of distant earthquakes. Our mainshock database includes 26 teleseismic events (epicentral distances > 1000 km; Mw ≥ 7.5), and 8 regional events (epicentral distances 100 - 1000 km; Mw ≥ 5.5). Of these, 1 teleseismic and 7 regional events produce triggered seismic activity within our study region. The triggering mainshocks are not limited to specific azimuths. For example, triggering is observed following the 2008 Mw 6.0 Nevada earthquake to the north and the 2010 Mw7.2 Northern Baja California earthquake to the south. The peak ground velocities in our study region generated by the triggering mainshocks exceed 0.03 cm/s, which corresponds to a dynamic stress of ~2 kPa. This apparent triggering threshold is consistent with thresholds found in the Long Valley Caldera (Brodsky and Prejean, 2005), the Parkfield section of San Andreas Fault (Peng et al., 2009), and near the San Jacinto Fault (Kane et al., 2007). The triggered events occur almost instantaneously with the arrival of large amplitude seismic waves and appear to be modulated by the passing surface waves, similar to recent observations of triggered deep “non-volcanic” tremor along major plate boundary faults in California, Cascadia, Japan, and Taiwan (Peng and Gomberg, 2010). However, unlike these deep ‘tremor’ events, the triggered signals we find in this study have very short P- to S-arrival times, suggesting that they likely originate from brittle failure in the shallow crust. Confirming this, spectra of the triggered signals mimic spectra of typical shallow events in the region. Extending our observation time window to ~1 month following the mainshock event we find that for the 2010 Mw 7.2 Northern Baja California mainshock

  18. TILT ANGLE AND FOOTPOINT SEPARATION OF SMALL AND LARGE BIPOLAR SUNSPOT REGIONS OBSERVED WITH HMI

    SciTech Connect

    McClintock, B. H.; Norton, A. A. E-mail: aanorton@stanford.edu

    2016-02-10

    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. results that the sunspots appear to be two distinct populations.

  19. 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.

  20. Defining Lipid Interacting Domains in the N-terminal Region of Apolipoprotein B

    PubMed Central

    Jiang, Zhenghui Gordon; Gantz, Donald; Bullitt, Esther; McKnight, C. James

    2008-01-01

    Apolipoprotein B (ApoB) is a nonexchangeable apolipoprotein that dictates the synthesis of chylomicrons and very low density lipoproteins. ApoB is the major protein in low density lipoprotein, also known as the “bad cholesterol” that is directly implicated in atherosclerosis. It has been suggested that the N-terminal domain of apoB plays a critical role in the formation of apoB-containing lipoproteins through the initial recruitment of phospholipids in the endoplasmic reticulum. However, very little is known about the mechanism of lipoprotein nucleation by apoB. Here we demonstrate that a strong phospholipid remodeling function is associated with the predicted α-helical and C-sheet domains in the N-terminal 17% of apoB (B17). Using dimyristoylphosphatidylcholine (DMPC) as a model lipid, these domains can convert multilamellar DMPC vesicles into discoidal-shaped particles. The nascent particles reconstituted from different apoB domains are distinctive and compositionally homogenous. This phospholipid remodeling activity is also observed with egg phosphatidylcholine (egg PC) and is therefore not DMPC dependent. Using kinetic analysis of the DMPC clearance assay, we show that the identified phospholipid binding sequences all map to the surface of the lipid binding pocket in the B17 model based on the homologous protein, lipovitellin. Since both B17 and microsomal triglyceride transfer protein (MTP), a critical chaperone during lipoprotein assembly, are homologous to lipovitellin, the identification of these phospholipid remodeling sequences in B17 provides important insights into the potential mechanism that initiates the assembly of apoB-containing lipoproteins. PMID:17002280

  1. Identification of a positively evolving putative binding region with increased variability in posttranslational motifs in zonadhesin MAM domain 2.

    PubMed

    Herlyn, Holger; Zischler, Hans

    2005-10-01

    Positive selection has been shown to be pervasive in sex-related proteins of many metazoan taxa. However, we are only beginning to understand molecular evolutionary processes on the lineage to humans. To elucidate the evolution of proteins involved in human reproduction, we studied the sequence evolution of MAM domains of the sperm-ligand zonadhesin in respect to single amino acid sites, solvent accessibility, and posttranslational modification. GenBank-data were supplemented by new cDNA-sequences of a representative non-human primate panel. Solvent accessibility predictions identified a probably exposed fragment of 30 amino acids belonging to MAM domain 2 (i.e., MAM domain 3 in mouse). The fragment is characterized by significantly increased rate of positively selected amino acid sites and exhibits high variability in predicted posttranslational modification, and, thus, might represent a binding region in the mature protein. At the same time, there is a significant coincidence of positively selected amino acid sites and non-conserved posttranslational motifs. We conclude that the binding specificity of zonadhesin MAM domains, especially of the presumed epitope, is achieved by positive selection at the level of single amino acid sites and posttranslational modifications, respectively.

  2. 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

  3. Process- and Domain-Specificity in Regions Engaged for Face Processing: An fMRI Study of Perceptual Differentiation

    PubMed Central

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

    2015-01-01

    The degree to which face-specific brain regions are specialized for different kinds of perceptual processing is debated. The present 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). Regions of interest 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. PMID:22849402

  4. Pectin Homogalacturonans: Nanostructural Characterization of Methylesterified Domains

    USDA-ARS?s Scientific Manuscript database

    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...

  5. Regional cerebral abnormalities measured by frequency-domain near-infrared spectroscopy in pediatric patients during extracorporeal membrane oxygenation.

    PubMed

    Tian, Fenghua; Jenks, Christopher; Potter, Donald; Miles, Darryl; Raman, Lakshmi

    2016-12-02

    Extracorporeal membrane oxygenation (ECMO) is a form of advanced cardio-respiratory support provided to critically ill patients with severe respiratory and/or cardiovascular failure. While children undergoing ECMO therapy have significant risk for neurological morbidity, currently there is a lack of reliable bedside tool to detect the neurologic events for patients on ECMO. This study assessed the feasibility of frequency-domain near-infrared spectroscopy (NIRS) for detection of intracranial complications during ECMO therapy. The frequency-domain NIRS device measured the absorption coefficient (µa) and reduced scattering coefficient (µs') at six cranial positions from seven pediatric patients (0-16 years) during ECMO support and five healthy controls (2-14 years). Regional abnormalities in both absorption and scattering were identified among ECMO patients. A main finding in this study is that the abnormalities in scattering appear to be associated with lower-than-normal µs' values in regional areas of the brain. Since light scattering originates from the intracellular structures (such as nuclei and mitochondria), a reduction in scattering primarily reflects loss or decreased density of the brain matter. The results from this study indicate a potential to use the frequency-domain NIRS as a safe and complementary technology for detection of intracranial complications during ECMO therapy.

  6. Structural Rearrangements of the Central Region of the Morbillivirus Attachment Protein Stalk Domain Trigger F Protein Refolding for Membrane Fusion*

    PubMed Central

    Ader, Nadine; Brindley, Melinda A.; Avila, Mislay; Origgi, Francesco C.; Langedijk, Johannes P. M.; Örvell, Claes; Vandevelde, Marc; Zurbriggen, Andreas; Plemper, Richard K.; Plattet, Philippe

    2012-01-01

    It is unknown how receptor binding by the paramyxovirus attachment proteins (HN, H, or G) triggers the fusion (F) protein to fuse with the plasma membrane for cell entry. H-proteins of the morbillivirus genus consist of a stalk ectodomain supporting a cuboidal head; physiological oligomers consist of non-covalent dimer-of-dimers. We report here the successful engineering of intermolecular disulfide bonds within the central region (residues 91–115) of the morbillivirus H-stalk; a sub-domain that also encompasses the putative F-contacting section (residues 111–118). Remarkably, several intersubunit crosslinks abrogated membrane fusion, but bioactivity was restored under reducing conditions. This phenotype extended equally to H proteins derived from virulent and attenuated morbillivirus strains and was independent of the nature of the contacted receptor. Our data reveal that the morbillivirus H-stalk domain is composed of four tightly-packed subunits. Upon receptor binding, these subunits structurally rearrange, possibly inducing conformational changes within the central region of the stalk, which, in turn, promote fusion. Given that the fundamental architecture appears conserved among paramyxovirus attachment protein stalk domains, we predict that these motions may act as a universal paramyxovirus F-triggering mechanism. PMID:22431728

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

    PubMed

    Mittal, Anuradha; Lyle, Nicholas; Harmon, Tyler S; Pappu, Rohit V

    2014-08-12

    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.

  8. Domain structure of antithrombin III. Tentative localization of the heparin binding region using /sup 1/H NMR spectroscopy

    SciTech Connect

    Gettins, P.; Wooten, E.W.

    1987-07-14

    The denaturation of human and bovine antithrombin III by guanidine hydrochloride has been followed by /sup 1/H NMR spectroscopy. The same unfolding transition seen previously from circular dichroism studies at low denaturant concentration was detected here by discontinuous changes in the chemical shifts of the C(2) protons of two of the five histidines in human antithrombin III and of three of the six histidines in bovine antithrombin III. These two histidines in human antithrombin III are assigned to residue 1 and, more tentatively, to residue 65. Two of the three histidines similarly affected in the bovine protein appear to be homologous to residues in the human protein. This supports the proposal of similar structures for the two proteins. In the presence of heparin, the discontinuous titration behavior of these histidine resonances is shifted to higher denaturant concentration, reflecting the stabilization of the easily unfolded first domain of the protein by bound heparin. From the tentative assignment of one of these resonances to histidine-1, it is proposed that the heparin binding site of antithrombin III is located in the N-terminal region and that this region forms a separate domain from the rest of the protein. The pattern of disulfide linkages is such that this domain may well extend from residue 1 to at least residue 128. Thermal denaturation also leads to major perturbation of these two histidine resonances in human antithrombin III, though stable intermediates in the unfolding were not detected.

  9. Multi-ensemble regional simulation of Indian monsoon during contrasting rainfall years: role of convective schemes and nested domain

    NASA Astrophysics Data System (ADS)

    Devanand, Anjana; Ghosh, Subimal; Paul, Supantha; Karmakar, Subhankar; Niyogi, Dev

    2017-08-01

    Regional simulations of the seasonal Indian summer monsoon rainfall (ISMR) require an understanding of the model sensitivities to physics and resolution, and its effect on the model uncertainties. It is also important to quantify the added value in the simulated sub-regional precipitation characteristics by a regional climate model (RCM), when compared to coarse resolution rainfall products. This study presents regional model simulations of ISMR at seasonal scale using the Weather Research and Forecasting (WRF) model with the synoptic scale forcing from ERA-interim reanalysis, for three contrasting monsoon seasons, 1994 (excess), 2002 (deficit) and 2010 (normal). Impact of four cumulus schemes, viz., Kain-Fritsch (KF), Betts-Janjić-Miller, Grell 3D and modified Kain-Fritsch (KFm), and two micro physical parameterization schemes, viz., WRF Single Moment Class 5 scheme and Lin et al. scheme (LIN), with eight different possible combinations are analyzed. The impact of spectral nudging on model sensitivity is also studied. In WRF simulations using spectral nudging, improvement in model rainfall appears to be consistent in regions with topographic variability such as Central Northeast and Konkan Western Ghat sub-regions. However the results are also dependent on choice of cumulus scheme used, with KF and KFm providing relatively good performance and the eight member ensemble mean showing better results for these sub-regions. There is no consistent improvement noted in Northeast and Peninsular Indian monsoon regions. Results indicate that the regional simulations using nested domains can provide some improvements on ISMR simulations. Spectral nudging is found to improve upon the model simulations in terms of reducing the intra ensemble spread and hence the uncertainty in the model simulated precipitation. The results provide important insights regarding the need for further improvements in the regional climate simulations of ISMR for various sub-regions and contribute

  10. 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

  11. 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…

  12. 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…

  13. Evidence that the large noncoding sequence is the main control region of maternally and paternally transmitted mitochondrial genomes of the marine mussel (Mytilus spp.).

    PubMed Central

    Cao, Liqin; Kenchington, Ellen; Zouros, Eleftherios; Rodakis, George C

    2004-01-01

    Both the maternal (F-type) and paternal (M-type) mitochondrial genomes of the Mytilus species complex M. edulis/galloprovincialis contain a noncoding sequence between the l-rRNA and the tRNA(Tyr) genes, here called the large unassigned region (LUR). The LUR, which is shorter in M genomes, is capable of forming secondary structures and contains motifs of significant sequence similarity with elements known to have specific functions in the sea urchin and the mammalian control region. Such features are not present in other noncoding regions of the F or M Mytilus mtDNA. The LUR can be divided on the basis of indels and nucleotide variation in three domains, which is reminiscent of the tripartite structure of the mammalian control region. These features suggest that the LUR is the main control region of the Mytilus mitochondrial genome. The middle domain has diverged by only 1.5% between F and M genomes, while the average divergence over the whole molecule is approximately 20%. In contrast, the first domain is among the most divergent parts of the genome. This suggests that different parts of the LUR are under different selection constraints that are also different from those acting on the coding parts of the molecule. PMID:15238532

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

    PubMed

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

    2014-08-01

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

  15. 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.

  16. Variations of the crustal thickness in the Betic-Rif domain and their foreland regions, by P-Receiver Functions

    NASA Astrophysics Data System (ADS)

    Stich, D.; Mancilla, F.; Morales, J.; Martin, R.; Diaz, J.; Pazos, A.; Cordoba, D.; Pulgar, J. A.; Ibarra, P.; Harnafi, M.; Gonzalez-Lodeiro, F.

    2012-12-01

    To image the crustal structure of the Betic-Rif Range and the surrounding area we perform a P-receiver function study (PRF). We calculate PRFs at 110 broadband stations located in South Iberia Peninsula and North Morocco to obtain thickness and average Vp/Vs ratio for the Crust. The Crustal thickness values show strong lateral variations throughout the region. Crustal thicknesses vary between ~19 km and ~46 km. The Betic and Rif ranges are underlined by a thickened crust with crustal thicknesses between ~35 km and ~46 km, reaching the highest values in the contact between the Alboran Domain and External Zones. Southeast Iberia and Northeast Morocco are affected by significant crustal thinning, with crustal thicknesses ranging from ~19 km to ~30 km, with the shallowest Moho along the Mediterranean coast. The transition from thick to thin crust is coincident with the faults system of the Trans-Alboran Shear Zone. Toward the North, the Iberian Massif is an homogeneous domain of average 30-31 km crustal thickness and flat Moho discontinuity with low average Vp/Vs ratios ~1.72. Further south an extended domain, which includes the Atlas domain and its foreland regions, presents crustal thickness of 27-34km. Vp/Vs ratios in north Morocco show normal values of ~1.75 for most stations except for the Atlas domain, where several stations present low Vp/Vs ratios around 1.71. The obtained PRFs are migrated to depth building cross-section images to delineate the crustal mantle discontinuity (Moho) along the study area. In the migrated images, we include altogether ~11.200 PFRs to follow the Moho discontinuity from the Iberian Massif, in the North, along the Gribraltar arc towards the Moroccan Massif in the South. These images show how, in the North, the Iberian crust underthrust the Alboran domain along their contact with the observation of a slab, from the western limit until the 3°W longitude, reaching the maximum depth of ~70 km under the coast coincide with the

  17. Dipole plasmon resonance induced large third-order optical nonlinearity of Au triangular nanoprism in infrared region.

    PubMed

    Chen, Ziyu; Dai, Hongwei; Liu, Jiaming; Xu, Hui; Li, Zixuan; Zhou, Zhang-Kai; Han, Jun-Bo

    2013-07-29

    Au triangular nanoprisms with strong dipole plasmon absorption peak at 1240 nm were prepared by wet chemical methods. Both numerical calculations and experiments were carried out to investigate the optical properties of the samples. Finite difference time domain (FDTD) and Local Density of States (LDOS) calculations demonstrate that strong electric field enhancement and large LDOS can be obtained at tip areas of the Au triangular nanoprisms. Z scan techniques were used to characterize the nonlinear absorption, nonlinear refraction, as well as one- and two-photon figures of merit (W and T, respectively) of the sample. The results show that maximum nonlinear refractive index can be obtained around the resonance absorption wavelength of 1240 nm, detuning the wavelength from the absorption peak will lead to the decrease of the nonlinear refractive index n(2), while the nonlinear absorption coefficient β doesn't change much with the wavelength. This large wavelength dependence of n(2) and small change of β enable the sample to satisfy the all-optical switching demand of W> 1 and T< 1 easily in a large wavelength range of 1200-1300 nm. These significant nonlinear properties of the sample imply that Au triangular nanoprism is a good candidate for future optical switches in infrared optical communication wavelength region.

  18. Transformation of a continuous rat embryo fibroblast cell line requires three separate domains of simian virus 40 large T antigen.

    PubMed Central

    Zhu, J; Rice, P W; Gorsch, L; Abate, M; Cole, C N

    1992-01-01

    Mouse C3H 10T1/2 cells and the established rat embryo fibroblast cell line REF-52 are two cell lines widely used in studies of viral transformation. Studies have shown that transformation of 10T1/2 cells requires only the amino-terminal 121 amino acids of simian virus 40 (SV40) large T antigen, while transformation of REF-52 cells requires considerably more of large T antigen, extending from near the N terminus to beyond residue 600. The ability of a large set of linker insertion, small deletion, and point mutants of SV40 T antigen to transform these two cell lines and to bind p105Rb was determined. Transformation of 10T1/2 cells was greatly reduced by mutations within the first exon of the gene for large T antigen but was only modestly affected by mutations affecting the p105Rb binding site or the p53 binding region. All mutants defective for transformation of 10T1/2 cells were also defective for transformation of REF-52 cells. In addition, mutants whose T antigens had alterations in the Rb binding site showed a substantial reduction in transformation of REF-52 cells, and the degree of this reduction could be correlated with the ability of the mutant T antigens to bind p105Rb. There was a tight correlation between the ability of mutants to transform REF-52 cells and the ability of their T antigens to bind p53. These results demonstrate that multiple regions of large T antigen are required for full transformation by SV40. Images PMID:1313902

  19. 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

  20. 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.

  1. The Large-Scale Biosphere-Atmosphere Experiment in Amazonia: Analyzing Regional Land Use Change Effects.

    Treesearch

    Michael Keller; Maria Assunção Silva-Dias; Daniel C. Nepstad; Meinrat O. Andreae

    2004-01-01

    The Large-Scale Biosphere-Atmosphere Experiment in Amazonia (LBA) is a multi-disciplinary, multinational scientific project led by Brazil. LBA researchers seek to understand Amazonia in its global context especially with regard to regional and global climate. Current development activities in Amazonia including deforestation, logging, cattle ranching, and agriculture...

  2. 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.

  3. 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

  4. Solution structure of the region 51–160 of human KIN17 reveals an atypical winged helix domain

    PubMed Central

    Carlier, Ludovic; Couprie, Joël; le Maire, Albane; Guilhaudis, Laure; Milazzo-Segalas, Isabelle; Courçon, Marie; Moutiez, Mireille; Gondry, Muriel; Davoust, Daniel; Gilquin, Bernard; Zinn-Justin, Sophie

    2007-01-01

    Human KIN17 is a 45-kDa eukaryotic DNA- and RNA-binding protein that plays an important role in nuclear metabolism and in particular in the general response to genotoxics. Its amino acids sequence contains a zinc finger motif (residues 28–50) within a 30-kDa N-terminal region conserved from yeast to human, and a 15-kDa C-terminal tandem of SH3-like subdomains (residues 268–393) only found in higher eukaryotes. Here we report the solution structure of the region 51–160 of human KIN17. We show that this fragment folds into a three-α-helix bundle packed against a three-stranded β-sheet. It belongs to the winged helix (WH) family. Structural comparison with analogous WH domains reveals that KIN17 WH module presents an additional and highly conserved 310-helix. Moreover, KIN17 WH helix H3 is not positively charged as in classical DNA-binding WH domains. Thus, human KIN17 region 51–160 might rather be involved in protein–protein interaction through its conserved surface centered on the 310-helix. PMID:18029424

  5. Light-controlled one-sided growth of large plasmonic gold domains on quantum rods observed on the single particle level

    NASA Astrophysics Data System (ADS)

    Carbone, Luigi; Jakab, Arpad; Khalavka, Yuriy; Sönnichsen, Carsten

    2010-02-01

    We create large gold domains (up to 15 nm) exclusively on one side of CdS or CdSe/CdS quantum rods by photoreduction of gold ions under anaerobic conditions. Electrons generated in the semiconductor by UV stimulation migrate to one tip where they reduce gold ions. Large gold domains eventually form; these support efficient plasmon oscillations with a light scattering cross section large enough to visualize single hybrid particles in a dark-field microscope during growth in real time.

  6. 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.

  7. Replacement and deletion mutations in the catalytic domain and belt region of Aspergillus awamori glucoamylase to enhance thermostability.

    PubMed

    Liu, H L; Doleyres, Y; Coutinho, P M; Ford, C; Reilly, P J

    2000-09-01

    Three single-residue mutations, Asp71-->Asn, Gln409-->Pro and Gly447-->Ser, two long-to-short loop replacement mutations, Gly23-Ala24-Asp25-Gly26-Ala27-Trp28- Val29-Ser30-->Asn-Pro-Pro (23-30 replacement) and Asp297-Ser298-Glu299-Ala300-Val301-->Ala-G ly-Ala (297-301 replacement) and one deletion mutation removing Glu439, Thr440 and Ser441 (Delta439-441), all based on amino acid sequence alignments, were made to improve Aspergillus awamori glucoamylase thermostability. The first and second single-residue mutations were designed to introduce a potential N:-glycosylation site and to restrict backbone bond rotation, respectively, and therefore to decrease entropy during protein unfolding. The third single-residue mutation was made to decrease flexibility and increase O:-glycosylation in the already highly O:-glycosylated belt region that extends around the globular catalytic domain. The 23-30 replacement mutation was designed to eliminate a very thermolabile extended loop on the catalytic domain surface and to bring the remainder of this region closer to the rest of the catalytic domain, therefore preventing it from unfolding. The 297-301 replacement mutant GA was made to understand the function of the random coil region between alpha-helices 9 and 10. Delta439-441 was constructed to decrease belt flexibility. All six mutations increased glucoamylase thermostability without significantly changing enzyme kinetic properties, with the 23-30 replacement mutation increasing the activation free energy for thermoinactivation by about 4 kJ/mol, which leads to a 4 degrees C increase in operating temperature at constant thermostability.

  8. 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; hide

    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

  9. Identification and analysis of genomic regions with large between-population differentiation in humans.

    PubMed

    Myles, S; Tang, K; Somel, M; Green, R E; Kelso, J; Stoneking, M

    2008-01-01

    The primary aim of genetic association and linkage studies is to identify genetic variants that contribute to phenotypic variation within human populations. Since the overwhelming majority of human genetic variation is found within populations, these methods are expected to be effective and can likely be extrapolated from one human population to another. However, they may lack power in detecting the genetic variants that contribute to phenotypes that differ greatly between human populations. Phenotypes that show large differences between populations are expected to be associated with genomic regions exhibiting large allele frequency differences between populations. Thus, from genome-wide polymorphism data genomic regions with large allele frequency differences between populations can be identified, and evaluated as candidates for large between-population phenotypic differences. Here we use allele frequency data from approximately 1.5 million SNPs from three human populations, and present an algorithm that identifies genomic regions containing SNPs with extreme Fst. We demonstrate that our candidate regions have reduced heterozygosity in Europeans and Chinese relative to African-Americans, and are likely enriched with genes that have experienced positive natural selection. We identify genes that are likely responsible for phenotypes known to differ dramatically between human populations and present several candidates worthy of future investigation. Our list of high Fst genomic regions is a first step in identifying the genetic variants that contribute to large phenotypic differences between populations, many of which have likely experienced positive natural selection. Our approach based on between population differences can compliment traditional within population linkage and association studies to uncover novel genotype-phenotype relationships.

  10. 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.

  11. Blockade of a key region in the extracellular domain inhibits HER2 dimerization and signaling.

    PubMed

    Menendez, Javier A; Schroeder, Barbara; Peirce, Susan K; Vellon, Luciano; Papadimitropoulou, Adriana; Espinoza, Ingrid; Lupu, Ruth

    2015-06-01

    Several treatment strategies target the human epidermal growth factor receptor 2 (HER2) in breast carcinomas, including monoclonal antibodies directed against HER2's extracellular domain (ECD) and small molecule inhibitors of its tyrosine kinase activity. Yet, novel therapies are needed that prevent HER2 dimerization with other HER family members, because current treatments are only partially effective. To test the hypothesis that HER2 activation requires a protein sequence in the HER2-ECD that mediates HER2 homo- and heterodimerization, we introduced a series of deletion mutations in the third subdomain of HER2-ECD. These deletion mutants were retrovirally expressed in breast cancer (BC) cells that naturally overexpress HER2 and in noncancerous, HER2-negative breast epithelial cells. One-factor analysis of variance or Student's t test were used to analyze differences. All statistical tests were two-sided. The smallest deletion in the ECD domain of HER2, which removed only 16 amino acids (HER2-ECDΔ451-466), completely disrupted the oncogenic potential of HER2. In contrast to wild-type HER2, the mutant-inhibited anchorage-independent growth (mean number of colonies: mutant, 70, 95% confidence interval [CI] = 55 to 85; wild-type, 400, 95% CI = 320 to 480, P < .001) increased sensitivity to paclitaxel treatment in both transformed and nontransformed cells. Overexpression of HER2Δ451-466 efficiently inhibited activation of HER1, HER2, and HER3 in all cell lines tested. These findings reveal that an essential "activating" sequence exists in the extracellular domain of HER2. Disruption of this sequence disables the HER2 dimerization loop, blocks subsequent activation of HER2-driven oncogenic signaling, and generates a dominant-negative form of HER2. Reagents specifically against this molecular activation switch may represent a novel targeted approach for the management of HER2-overexpressing carcinomas. © The Author 2015. Published by Oxford University Press. All

  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. 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.

  14. The AtMYB12 activation domain maps to a short C-terminal region of the transcription factor.

    PubMed

    Stracke, Ralf; Turgut-Kara, Neslihan; Weisshaar, Bernd

    2017-03-11

    The Arabidopsis thaliana R2R3-MYB transcription factor MYB12 is a light-inducible, flavonol-specific activator of flavonoid biosynthesis. The transactivation activity of the AtMYB12 protein was analyzed using a C-terminal deletion series in a transient A. thaliana protoplast assay with the goal of mapping the activation domain (AD). Although the deletion of the last 46 C-terminal amino acids did not affect the activation capacity, the deletion of the last 98 amino acids almost totally abolished transactivation of two different target promoters. A domain swap experiment using the yeast GAL4 DNA-binding domain revealed that the region from positions 282 to 328 of AtMYB12 was sufficient for transactivation. In contrast to the R2R3-MYB ADs known thus far, that of AtMYB12 is not located at the rearmost C-terminal end of the protein. The AtMYB12 AD is conserved in other experimentally proven R2R3-MYB flavonol regulators from different species.

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

    NASA Astrophysics Data System (ADS)

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

    2015-05-01

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

  16. Coupling large scale hydrologic-reservoir-hydraulic models for impact studies in data sparse regions

    NASA Astrophysics Data System (ADS)

    O'Loughlin, Fiachra; Neal, Jeff; Wagener, Thorsten; Bates, Paul; Freer, Jim; Woods, Ross; Pianosi, Francesca; Sheffied, Justin

    2017-04-01

    As hydraulic modelling moves to increasingly large spatial domains it has become essential to take reservoirs and their operations into account. Large-scale hydrological models have been including reservoirs for at least the past two decades, yet they cannot explicitly model the variations in spatial extent of reservoirs, and many reservoirs operations in hydrological models are not undertaken during the run-time operation. This requires a hydraulic model, yet to-date no continental scale hydraulic model has directly simulated reservoirs and their operations. In addition to the need to include reservoirs and their operations in hydraulic models as they move to global coverage, there is also a need to link such models to large scale hydrology models or land surface schemes. This is especially true for Africa where the number of river gauges has consistently declined since the middle of the twentieth century. In this study we address these two major issues by developing: 1) a coupling methodology for the VIC large-scale hydrological model and the LISFLOOD-FP hydraulic model, and 2) a reservoir module for the LISFLOOD-FP model, which currently includes four sets of reservoir operating rules taken from the major large-scale hydrological models. The Volta Basin, West Africa, was chosen to demonstrate the capability of the modelling framework as it is a large river basin ( 400,000 km2) and contains the largest man-made lake in terms of area (8,482 km2), Lake Volta, created by the Akosombo dam. Lake Volta also experiences a seasonal variation in water levels of between two and six metres that creates a dynamic shoreline. In this study, we first run our coupled VIC and LISFLOOD-FP model without explicitly modelling Lake Volta and then compare these results with those from model runs where the dam operations and Lake Volta are included. The results show that we are able to obtain variation in the Lake Volta water levels and that including the dam operations and Lake Volta

  17. 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.

  18. 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}

  19. 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.

  20. 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

  1. 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

  2. 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.

  3. Large-scale domain motions and pyridoxal-5'-phosphate assisted radical catalysis in coenzyme B12-dependent aminomutases.

    PubMed

    Maity, Amarendra Nath; Chen, Yung-Han; Ke, Shyue-Chu

    2014-02-20

    Lysine 5,6-aminomutase (5,6-LAM) and ornithine 4,5-aminomutase (4,5-OAM) are two of the rare enzymes that use assistance of two vitamins as cofactors. These enzymes employ radical generating capability of coenzyme B12 (5'-deoxyadenosylcobalamin, dAdoCbl) and ability of pyridoxal-5'-phosphate (PLP, vitamin B6) to stabilize high-energy intermediates for performing challenging 1,2-amino rearrangements between adjacent carbons. A large-scale domain movement is required for interconversion between the catalytically inactive open form and the catalytically active closed form. In spite of all the similarities, these enzymes differ in substrate specificities. 4,5-OAM is highly specific for D-ornithine as a substrate while 5,6-LAM can accept D-lysine and L-β-lysine. This review focuses on recent computational, spectroscopic and structural studies of these enzymes and their implications on the related enzymes. Additionally, we also discuss the potential biosynthetic application of 5,6-LAM.

  4. 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.

  5. Constraint satisfaction techniques for modeling large complexes: Application to the central domain of 16S ribosomal RNA

    SciTech Connect

    Altman, R.B.; Weiser, B.; Noller, H.F.

    1994-12-31

    Standard experimental techniques for determining the structure of small to moderately-sized molecules are difficult to apply to large macromolecular complexes. These complexes, consisting of multiple protein and/or nucleic acid components, can contain many thousands of atoms and the experimental techniques used to study them provide relatively sparse structural information with significant measurement uncertainty. Computational technologies are required to reduce the conformational search space and synthesize the data in order to produce the structures or (more usually) sets of structures compatible with the data. In this paper, we show that a method based on the constraint satisfaction paradigm produces a three-dimensional topology for the central domain of the 16S ribosomal RNA that is generally consistent with interactively built models, although differing in significant ways. The modeling incorporates information about secondary structure of the nucleic acid, neutron diffraction data about the relative positions and uncertainties of the proteins, and protection experiments indicating proximities of segments of RNA to specific protein subunits. Unlike previously proposed models, our model contains explicit information about the range of positions for each subunit that are compatible with the data. The system uses a grid search, checks distances in a direction-dependent manner, uses disjunctive distance constraints, and checks for volume overlap violations.

  6. MASK, a large ankyrin repeat and KH domain-containing protein involved in Drosophila receptor tyrosine kinase signaling.

    PubMed

    Smith, Rachel K; Carroll, Pamela M; Allard, John D; Simon, Michael A

    2002-01-01

    The receptor tyrosine kinases Sevenless (SEV) and the Epidermal growth factor receptor (EGFR) are required for the proper development of the Drosophila eye. The protein tyrosine phosphatase Corkscrew (CSW) is a common component of many RTK signaling pathways, and is required for signaling downstream of SEV and EGFR. In order to identify additional components of these signaling pathways, mutations that enhanced the phenotype of a dominant negative form of Corkscrew were isolated. This genetic screen identified the novel signaling molecule MASK, a large protein that contains two blocks of ankyrin repeats as well as a KH domain. MASK genetically interacts with known components of these RTK signaling pathways. In the developing eye imaginal disc, loss of MASK function generates phenotypes similar to those generated by loss of other components of the SEV and EGFR pathways. These phenotypes include compromised photoreceptor differentiation, cell survival and proliferation. Although MASK is localized predominantly in the cellular cytoplasm, it is not absolutely required for MAPK activation or nuclear translocation. Based on our results, we propose that MASK is a novel mediator of RTK signaling, and may act either downstream of MAPK or transduce signaling through a parallel branch of the RTK pathway.

  7. Structure of the origin-binding domain of simian virus 40 large T antigen bound to DNA.

    PubMed

    Bochkareva, Elena; Martynowski, Dariusz; Seitova, Almagoul; Bochkarev, Alexey

    2006-12-13

    The large T antigen (T-ag) protein binds to and activates DNA replication from the origin of DNA replication (ori) in simian virus 40 (SV40). Here, we determined the crystal structures of the T-ag origin-binding domain (OBD) in apo form, and bound to either a 17 bp palindrome (sites 1 and 3) or a 23 bp ori DNA palindrome comprising all four GAGGC binding sites for OBD. The T-ag OBDs were shown to interact with the DNA through a loop comprising Ser147-Thr155 (A1 loop), a combination of a DNA-binding helix and loop (His203-Asn210), and Asn227. The A1 loop traveled back-and-forth along the major groove and accounted for most of the sequence-determining contacts with the DNA. Unexpectedly, in both T-ag-DNA structures, the T-ag OBDs bound DNA independently and did not make direct protein-protein contacts. The T-ag OBD was also captured bound to a non-consensus site ATGGC even in the presence of its canonical site GAGGC. Our observations taken together with the known biochemical and structural features of the T-ag-origin interaction suggest a model for origin unwinding.

  8. Vibrio type III effector VPA1380 is related to the cysteine protease domain of large bacterial toxins.

    PubMed

    Calder, Thomas; Kinch, Lisa N; Fernandez, Jessie; Salomon, Dor; Grishin, Nick V; Orth, Kim

    2014-01-01

    Vibrio parahaemolyticus is a Gram-negative halophilic bacterium and one of the leading causes of food-borne gastroenteritis. Its genome harbors two Type III Secretion Systems (T3SS1 and T3SS2), but only T3SS2 is required for enterotoxicity seen in animal models. Effector proteins secreted from T3SS2 have been previously shown to promote colonization of the intestinal epithelium, invasion of host cells, and destruction of the epithelial monolayer. In this study, we identify VPA1380, a T3SS2 effector protein that is toxic when expressed in yeast. Bioinformatic analyses revealed that VPA1380 is highly similar to the inositol hexakisphosphate (IP6)-inducible cysteine protease domains of several large bacterial toxins. Mutations in conserved catalytic residues and residues in the putative IP6-binding pocket abolished toxicity in yeast. Furthermore, VPA1380 was not toxic in IP6 deficient yeast cells. Therefore, our findings suggest that VPA1380 is a cysteine protease that requires IP6 as an activator.

  9. Large-Scale Domain Motions and Pyridoxal-5′-Phosphate Assisted Radical Catalysis in Coenzyme B12-Dependent Aminomutases†

    PubMed Central

    Maity, Amarendra Nath; Chen, Yung-Han; Ke, Shyue-Chu

    2014-01-01

    Lysine 5,6-aminomutase (5,6-LAM) and ornithine 4,5-aminomutase (4,5-OAM) are two of the rare enzymes that use assistance of two vitamins as cofactors. These enzymes employ radical generating capability of coenzyme B12 (5′-deoxyadenosylcobalamin, dAdoCbl) and ability of pyridoxal-5′-phosphate (PLP, vitamin B6) to stabilize high-energy intermediates for performing challenging 1,2-amino rearrangements between adjacent carbons. A large-scale domain movement is required for interconversion between the catalytically inactive open form and the catalytically active closed form. In spite of all the similarities, these enzymes differ in substrate specificities. 4,5-OAM is highly specific for d-ornithine as a substrate while 5,6-LAM can accept d-lysine and l-β-lysine. This review focuses on recent computational, spectroscopic and structural studies of these enzymes and their implications on the related enzymes. Additionally, we also discuss the potential biosynthetic application of 5,6-LAM. PMID:24562332

  10. New Evidences for Preserved Segmentation of the Alpine-Tethyan Domain in the Iberia-Africa Plate Boundary Region

    NASA Astrophysics Data System (ADS)

    Fernandez, M.; Torne, M.; Verges, J.; Buffett, G. G.

    2015-12-01

    Based on gravity analysis and previous integrated studies combining potential fields and seismic data, we demonstrate that the Iberia-Africa plate boundary region is characterized by several tectonically inverted transtensional domains inherited from the Jurassic. Gravity data, when filtered for short wavelengths, show conspicuous positive Bouguer anomalies associated with the Gorringe Bank, the Guadalquivir Bank and the Ronda/Beni-Bousera peridotitic massifs. Gravity modelling combined with seismic and geological data shows that the filtered Bouguer anomalies are compatible with relatively high-density and shallow-buried bodies, which correspond to partly serpentinized peridotitic slices with similar densities and geometries as those proved for the Gorringe Bank. The study indicates that the Alpine convergence between Africa and Iberia since Late Cretaceous times reactivated these transtensional domains, which were less deformed westwards and thus preserved their segmentation. The interpretation of these Bouguer anomalies and their distribution substantiates the double-polarity subduction model proposed for the region, and agrees with the present-day seismically diffuse character of the Iberia-Africa plate boundary.

  11. 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

  12. 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.

  13. 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

  14. 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.

  15. 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. © 2016 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

  16. Regionalization of local geomorphometric derivations for geological mapping in the sedimentary domain of central Amazônia

    NASA Astrophysics Data System (ADS)

    Valeriano, Márcio de Morisson; Rossetti, Dilce de Fátima

    2017-03-01

    regionalization process improved the potential of local geomorphometric data for updating and revision of geological maps and for guiding future surveys in the sedimentary domain of Amazônia.

  17. Alternatively spliced C-terminal domains regulate the surface expression of large conductance calcium-activated potassium (BKCa) channels

    PubMed Central

    Kim, Eun Young; Ridgway, Lon D.; Zou, Shengwei; Chiu, Yu-Hsin; Dryer, Stuart E.

    2007-01-01

    The Slo1 gene, also known as KCNMA1, encodes the pore-forming subunits of large-conductance Ca2+-activated K+ (BKCa) channels. Products of this gene are widely expressed in vertebrate tissues, and occur in a large number (≥ 20) of alternatively spliced variants that vary in their gating properties, susceptibility to modulation, and trafficking to the plasma membrane. Motifs in the large cytoplasmic C-terminal are especially important in determining the functional properties of BKCa channels. Here we report that chick ciliary ganglion neurons express transcripts and proteins of two Slo1 splice variants that differ at the extreme C-terminal. We refer to these variants as VEDEC and QEDRL (or QEERL for the orthologous mammalian versions), after the five terminal amino acid residues in each isoform. Individual ciliary ganglion neurons preferentially express these variants in different subcellular compartments. Moreover, QEERL channels show markedly higher levels of constitutive expression on the plasma membrane than VEDEC channels in HEK293T and NG108-15 cells. However, growth factor treatment can stimulate surface expression of VEDEC channels to levels comparable to those seen with QEERL. In addition, we show that co-expression of a soluble protein comprised of VEDEC C-terminal tail residues markedly increases cell surface expression of full-length VEDEC channels, suggesting that this region binds to proteins that cause retention of the these channels in intracellular stores. PMID:17478049

  18. A computational approach identifies two regions of Hepatitis C Virus E1 protein as interacting domains involved in viral fusion process

    PubMed Central

    Bruni, Roberto; Costantino, Angela; Tritarelli, Elena; Marcantonio, Cinzia; Ciccozzi, Massimo; Rapicetta, Maria; El Sawaf, Gamal; Giuliani, Alessandro; Ciccaglione, Anna Rita

    2009-01-01

    Background The E1 protein of Hepatitis C Virus (HCV) can be dissected into two distinct hydrophobic regions: a central domain containing an hypothetical fusion peptide (FP), and a C-terminal domain (CT) comprising two segments, a pre-anchor and a trans-membrane (TM) region. In the currently accepted model of the viral fusion process, the FP and the TM regions are considered to be closely juxtaposed in the post-fusion structure and their physical interaction cannot be excluded. In the present study, we took advantage of the natural sequence variability present among HCV strains to test, by purely sequence-based computational tools, the hypothesis that in this virus the fusion process involves the physical interaction of the FP and CT regions of E1. Results Two computational approaches were applied. The first one is based on the co-evolution paradigm of interacting peptides and consequently on the correlation between the distance matrices generated by the sequence alignment method applied to FP and CT primary structures, respectively. In spite of the relatively low random genetic drift between genotypes, co-evolution analysis of sequences from five HCV genotypes revealed a greater correlation between the FP and CT domains than respect to a control HCV sequence from Core protein, so giving a clear, albeit still inconclusive, support to the physical interaction hypothesis. The second approach relies upon a non-linear signal analysis method widely used in protein science called Recurrence Quantification Analysis (RQA). This method allows for a direct comparison of domains for the presence of common hydrophobicity patterns, on which the physical interaction is based upon. RQA greatly strengthened the reliability of the hypothesis by the scoring of a lot of cross-recurrences between FP and CT peptides hydrophobicity patterning largely outnumbering chance expectations and pointing to putative interaction sites. Intriguingly, mutations in the CT region of E1, reducing the

  19. 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.

  20. 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

  1. 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

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

    PubMed

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

    2008-01-01

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

  3. A Large Pseudoautosomal Region on the Sex Chromosomes of the Frog Silurana tropicalis

    PubMed Central

    Bewick, Adam J.; Chain, Frédéric J.J.; Zimmerman, Lyle B.; Sesay, Abdul; Gilchrist, Michael J.; Owens, Nick D.L.; Seifertova, Eva; Krylov, Vladimir; Macha, Jaroslav; Tlapakova, Tereza; Kubickova, Svatava; Cernohorska, Halina; Zarsky, Vojtech; Evans, Ben J.

    2013-01-01

    Sex chromosome divergence has been documented across phylogenetically diverse species, with amphibians typically having cytologically nondiverged (“homomorphic”) sex chromosomes. With an aim of further characterizing sex chromosome divergence of an amphibian, we used “RAD-tags” and Sanger sequencing to examine sex specificity and heterozygosity in the Western clawed frog Silurana tropicalis (also known as Xenopus tropicalis). Our findings based on approximately 20 million genotype calls and approximately 200 polymerase chain reaction-amplified regions across multiple male and female genomes failed to identify a substantially sized genomic region with genotypic hallmarks of sex chromosome divergence, including in regions known to be tightly linked to the sex-determining region. We also found that expression and molecular evolution of genes linked to the sex-determining region did not differ substantially from genes in other parts of the genome. This suggests that the pseudoautosomal region, where recombination occurs, comprises a large portion of the sex chromosomes of S. tropicalis. These results may in part explain why African clawed frogs have such a high incidence of polyploidization, shed light on why amphibians have a high rate of sex chromosome turnover, and raise questions about why homomorphic sex chromosomes are so prevalent in amphibians. PMID:23666865

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

    SciTech Connect

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

    2014-04-01

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

  5. Preferential binding of the methyl-CpG binding domain protein 2 at methylated transcriptional start site regions.

    PubMed

    Chatagnon, Amandine; Perriaud, Laury; Nazaret, Nicolas; Croze, Séverine; Benhattar, Jean; Lachuer, Joël; Dante, Robert

    2011-11-01

    Methyl-CpG Binding Domain (MBD) proteins are thought to be key molecules in the interpretation of DNA methylation signals leading to gene silencing through recruitment of chromatin remodeling complexes. In cancer, the MBD-family member, MBD2, may be primarily involved in the repression of genes exhibiting methylated CpG at their 5' end. Here we ask whether MBD2 randomly associates methylated sequences, producing chance effects on transcription, or exhibits a more specific recognition of some methylated regions. Using chromatin and DNA immunoprecipitation, we analyzed MBD2 and RNA polymerase II deposition and DNA methylation in HeLa cells on arrays representing 25,500 promoter regions. This first whole-genome mapping revealed the preferential localization of MBD2 near transcription start sites (TSSs), within the region analyzed, 7.5 kb upstream through 2.45 kb downstream of 5' transcription start sites. Probe by probe analysis correlated MBD2 deposition and DNA methylation. Motif analysis did not reveal specific sequence motifs; however, CCG and CGC sequences seem to be overrepresented. Nonrandom association (multiple correspondence analysis, p < 0.0001) between silent genes, DNA methylation and MBD2 binding was observed. The association between MBD2 binding and transcriptional repression weakened as the distance between binding site and TSS increased, suggesting that MBD2 represses transcriptional initiation. This hypothesis may represent a functional explanation for the preferential binding of MBD2 at methyl-CpG in TSS regions.

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

    NASA Technical Reports Server (NTRS)

    Eriksson, S.; Wilder, F. D.; Ergun, R. E.; Schwartz, S. J.; Cassak, P. A.; Burch, J. L.; Chen, Li-Jen; Torbert, R. B.; Phan, T. D.; Lavraud, B.; hide

    2016-01-01

    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(sub parallel lines) that is larger than predicted by simulations. The high-speed (approximately 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(sub parallel lines) is balanced by a combination of electron inertia and a parallel gradient of the gyrotropic electron pressure.

  7. 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.

  8. 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.

  9. Linkage and association of successful aging to the 6q25 region in large Amish kindreds.

    PubMed

    Edwards, Digna R Velez; Gilbert, John R; Hicks, James E; Myers, Jamie L; Jiang, Lan; Cummings, Anna C; Guo, Shengru; Gallins, Paul J; Konidari, Ioanna; Caywood, Laura; Reinhart-Mercer, Lori; Fuzzell, Denise; Knebusch, Claire; Laux, Renee; Jackson, Charles E; Pericak-Vance, Margaret A; Haines, Jonathan L; Scott, William K

    2013-08-01

    Successful aging (SA) is a multidimensional phenotype involving living to older age with high physical function, preserved cognition, and continued social engagement. Several domains underlying SA are heritable, and identifying health-promoting polymorphisms and their interactions with the environment could provide important information regarding the health of older adults. In the present study, we examined 263 cognitively intact Amish individuals age 80 and older (74 SA and 189 "normally aged") all of whom are part of a single 13-generation pedigree. A genome-wide association study of 630,309 autosomal single nucleotide polymorphisms (SNPs) was performed and analyzed for linkage using multipoint analyses and for association using the modified quasi-likelihood score test. There was evidence for linkage on 6q25-27 near the fragile site FRA6E region with a dominant model maximum multipoint heterogeneity LOD score = 3.2. The 1-LOD-down support interval for this linkage contained one SNP for which there was regionally significant evidence of association (rs205990, p = 2.36 × 10(-5)). This marker survived interval-wide Bonferroni correction for multiple testing and was located between the genes QKI and PDE10A. Other areas of chromosome 6q25-q27 (including the FRA6E region) contained several SNPs associated with SA (minimum p = 2.89 × 10(-6)). These findings suggest potentially novel genes in the 6q25-q27 region linked and associated with SA in the Amish; however, these findings should be verified in an independent replication cohort.

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

    PubMed

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

    2015-07-21

    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.

  11. 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

  12. 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.

  13. 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

  14. Molecular genetic analysis of the heterodimeric splicing factor U2AF: the RS domain on either the large or small Drosophila subunit is dispensable in vivo

    PubMed Central

    Rudner, David Z.; Breger, Kevin S.; Rio, Donald C.

    1998-01-01

    The pre-mRNA splicing factor U2AF (U2 snRNP auxiliary factor) has an essential role in 3′ splice site selection. U2AF binds the intron pyrimidine tract between the branchpoint and the 3′ splice site and recruits U2 snRNP to the branch site at an early step in spliceosome assembly. Human U2AF is a heterodimer composed of large (hU2AF65) and small (hU2AF35) subunits. Both subunits contain a domain enriched in arginine–serine dipeptide repeats termed an RS domain. The two U2AF RS domains have been assigned essential and independent roles in spliceosome assembly in vitro—the hU2AF65 RS domain is required to target U2 snRNP to the branch site and the hU2AF35 RS domain is necessary for protein–protein interactions with constitutive and alternative splicing factors. We have investigated the functional requirements for the RS domains on the Drosophila U2AF homolog in vivo. In sharp contrast to its essential role in U2 snRNP recruitment in vitro, the RS domain on the Drosophila large subunit homolog (dU2AF50) was completely dispensable in vivo. Prompted by this unexpected result, we analyzed the RS domain on the Drosophila small subunit homolog (dU2AF38). Despite its requirement for enhancer-dependent splicing activity in vitro, the dU2AF38 RS domain was also inessential in vivo. Finally, we have tested whether the Drosophila U2AF heterodimer requires any RS domain. Flies mutant for both the small and large subunits could not be rescued by dU2AF50ΔRS and dU2AF38ΔRS transgenes. Therefore, in contrast to the separate roles assigned to the U2AF RS domains in vitro, our genetic data suggest that they may have redundant functions in vivo. PMID:9531538

  15. HEp-2 Cell Classification via Combining Multiresolution Co-Occurrence Texture and Large Region Shape Information.

    PubMed

    Qi, Xianbiao; Zhao, Guoying; Li, Chun-Guang; Guo, Jun; Pietikainen, Matti

    2017-03-01

    Indirect immunofluorescence imaging of human epithelial type 2 (HEp-2) cell image is an effective evidence to diagnose autoimmune diseases. Recently, computer-aided diagnosis of autoimmune diseases by the HEp-2 cell classification has attracted great attention. However, the HEp-2 cell classification task is quite challenging due to large intraclass and small interclass variations. In this paper, we propose an effective approach for the automatic HEp-2 cell classification by combining multiresolution co-occurrence texture and large regional shape information. To be more specific, we propose to: 1) capture multiresolution co-occurrence texture information by a novel pairwise rotation-invariant co-occurrence of local Gabor binary pattern descriptor; 2) depict large regional shape information by using an improved Fisher vector model with RootSIFT features, which are sampled from large image patches in multiple scales; and 3) combine both features. We evaluate systematically the proposed approach on the IEEE International Conference on Pattern Recognition (ICPR) 2012, the IEEE International Conference on Image Processing (ICIP) 2013, and the ICPR 2014 contest datasets. The proposed method based on the combination of the introduced two features outperforms the winners of the ICPR 2012 contest using the same experimental protocol. Our method also greatly improves the winner of the ICIP 2013 contest under four different experimental setups. Using the leave-one-specimen-out evaluation strategy, our method achieves comparable performance with the winner of the ICPR 2014 contest that combined four features.

  16. 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.

  17. A conserved proline-rich region of the Saccharomyces cerevisiae cyclase-associated protein binds SH3 domains and modulates cytoskeletal localization.

    PubMed

    Freeman, N L; Lila, T; Mintzer, K A; Chen, Z; Pahk, A J; Ren, R; Drubin, D G; Field, J

    1996-02-01

    Saccharomyces cerevisiae cyclase-associated protein (CAP or Srv2p) is multifunctional. The N-terminal third of CAP binds to adenylyl cyclase and has been implicated in adenylyl cyclase activation in vivo. The widely conserved C-terminal domain of CAP binds to monomeric actin and serves an important cytoskeletal regulatory function in vivo. In addition, all CAP homologs contain a centrally located proline-rich region which has no previously identified function. Recently, SH3 (Src homology 3) domains were shown to bind to proline-rich regions of proteins. Here we report that the proline-rich region of CAP is recognized by the SH3 domains of several proteins, including the yeast actin-associated protein Abp1p. Immunolocalization experiments demonstrate that CAP colocalizes with cortical actin-containing structures in vivo and that a region of CAP containing the SH3 domain binding site is required for this localization. We also demonstrate that the SH3 domain of yeast Abp1p and that of the yeast RAS protein guanine nucleotide exchange factor Cdc25p complex with adenylyl cyclase in vitro. Interestingly, the binding of the Cdc25p SH3 domain is not mediated by CAP and therefore may involve direct binding to adenylyl cyclase or to an unidentified protein which complexes with adenylyl cyclase. We also found that CAP homologous from Schizosaccharomyces pombe and humans bind SH3 domains. The human protein binds most strongly to the SH3 domain from the abl proto-oncogene. These observations identify CAP as an SH3 domain-binding protein and suggest that CAP mediates interactions between SH3 domain proteins and monomeric actin.

  18. A conserved proline-rich region of the Saccharomyces cerevisiae cyclase-associated protein binds SH3 domains and modulates cytoskeletal localization.

    PubMed Central

    Freeman, N L; Lila, T; Mintzer, K A; Chen, Z; Pahk, A J; Ren, R; Drubin, D G; Field, J

    1996-01-01

    Saccharomyces cerevisiae cyclase-associated protein (CAP or Srv2p) is multifunctional. The N-terminal third of CAP binds to adenylyl cyclase and has been implicated in adenylyl cyclase activation in vivo. The widely conserved C-terminal domain of CAP binds to monomeric actin and serves an important cytoskeletal regulatory function in vivo. In addition, all CAP homologs contain a centrally located proline-rich region which has no previously identified function. Recently, SH3 (Src homology 3) domains were shown to bind to proline-rich regions of proteins. Here we report that the proline-rich region of CAP is recognized by the SH3 domains of several proteins, including the yeast actin-associated protein Abp1p. Immunolocalization experiments demonstrate that CAP colocalizes with cortical actin-containing structures in vivo and that a region of CAP containing the SH3 domain binding site is required for this localization. We also demonstrate that the SH3 domain of yeast Abp1p and that of the yeast RAS protein guanine nucleotide exchange factor Cdc25p complex with adenylyl cyclase in vitro. Interestingly, the binding of the Cdc25p SH3 domain is not mediated by CAP and therefore may involve direct binding to adenylyl cyclase or to an unidentified protein which complexes with adenylyl cyclase. We also found that CAP homologous from Schizosaccharomyces pombe and humans bind SH3 domains. The human protein binds most strongly to the SH3 domain from the abl proto-oncogene. These observations identify CAP as an SH3 domain-binding protein and suggest that CAP mediates interactions between SH3 domain proteins and monomeric actin. PMID:8552082

  19. Large-scale phase separation with nano-twin domains in manganite spinel (Co,Fe,Mn){sub 3}O{sub 4}

    SciTech Connect

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

    2016-08-26

    The effect of Mn concentration on the formation of nano-domain structures in the spinel oxide (Co,Fe,Mn){sub 3}O{sub 4} 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 Co{sub 0.6}Fe{sub 1.0}Mn{sub 1.4}O{sub 4}, in contrast to the highly aligned checkerboard nano-domains in Co{sub 0.6}Fe{sub 0.9}Mn{sub 1.5}O{sub 4}. Diffusion of the Mn{sup 3+} ions with the Jahn-Teller distortions is suggested to play an important role in the formation of checkerboard nano-domain structure.

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

    PubMed Central

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

    2008-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  2. The crystal structure of the human nascent polypeptide-associated complex domain reveals a nucleic acid-binding region on the NACA subunit .

    PubMed

    Liu, Yiwei; Hu, Yingxia; Li, Xu; Niu, Liwen; Teng, Maikun

    2010-04-06

    In archaea and eukaryotes, the nascent polypeptide-associated complex (NAC) is one of the cytosolic chaperones that contact the nascent polypeptide chains as they emerge from the ribosome and assist in post-translational processes. The eukaryotic NAC is a heterodimer, and its two subunits form a stable complex through a dimerizing domain called the NAC domain. In addition to acting as a protein translation chaperone, the NAC subunits also function individually in transcriptional regulation. Here we report the crystal structure of the human NAC domain, which reveals the manner of human NAC dimerization. On the basis of the structure, we identified a region in the NAC domain of the human NAC alpha-subunit as a new nucleic acid-binding region, which is blocked from binding nucleic acids in the heterodimeric complex by a helix region in the beta-subunit.

  3. Treatment of large vascular lesions in the orofacial region with the Nd:YAG laser.

    PubMed

    Vesnaver, Ales; Dovsak, David A

    2009-06-01

    Large vascular lesions in the orofacial region are often very difficult to remove. In the 1990s, the neodymium: yttrium-aluminum-garnet (Nd:YAG) laser emerged as a new and effective mode of treatment for vascular lesions. The purpose of this paper was to determine its effectiveness and safety for the treatment of large vascular lesions in the orofacial region. A prospective study was conducted in which 28 patients with large vascular lesions (their surface diameters being more than 3 x 3 cm) in the orofacial region were treated with the Nd:YAG laser by photocoagulation (PhC). Four different modalities of treatment were used: simple transmucosal PhC, transmucosal PhC with the use of compression, simple intralesional PhC, and ultrasound guided intralesional PhC. Follow up was conducted in all of the cases, time until complete healing was recorded, as were postoperative complications. In all of the patients undergoing transmucosal PhC (simple or with the use of compression), tissue sloughing occured within 1-3 days, and the time until complete healing was 3-5 weeks. In patients undergoing intralesional PhC (simple or ultrasound guided), swelling was present for 1 week. There were no cases of inadvertent bleeding. Nine patients required two or more sessions of PhC. Three patients required a corrective surgical procedure as the final step. Two patients required prolonged intubation and one patient a temporary tracheostomy, all due to oedema. Two patients developed a local intraoral infection, which was controlled with broad-spectrum oral antibiotics. If used properly, the Nd:YAG laser is a safe and effective tool for the treatment of large vascular lesions.

  4. The Effector Domain Region of the Vibrio vulnificus MARTX Toxin Confers Biphasic Epithelial Barrier Disruption and Is Essential for Systemic Spread from the Intestine.

    PubMed

    Gavin, Hannah E; Beubier, Nike T; Satchell, Karla J F

    2017-01-01

    Vibrio vulnificus causes highly lethal bacterial infections in which the Multifunctional Autoprocessing Repeats-in-Toxins (MARTX) toxin product of the rtxA1 gene is a key virulence factor. MARTX toxins are secreted proteins up to 5208 amino acids in size. Conserved MARTX N- and C-terminal repeat regions work in concert to form pores in eukaryotic cell membranes, through which the toxin's central region of modular effector domains is translocated. Upon inositol hexakisphosphate-induced activation of the of the MARTX cysteine protease domain (CPD) in the eukaryotic cytosol, effector domains are released from the holotoxin by autoproteolytic activity. We previously reported that the native MARTX toxin effector domain repertoire is dispensable for epithelial cellular necrosis in vitro, but essential for cell rounding and apoptosis prior to necrotic cell death. Here we use an intragastric mouse model to demonstrate that the effector domain region is required for bacterial virulence during intragastric infection. The MARTX effector domain region is essential for bacterial dissemination from the intestine, but dissemination occurs in the absence of overt intestinal tissue pathology. We employ an in vitro model of V. vulnificus interaction with polarized colonic epithelial cells to show that the MARTX effector domain region induces rapid intestinal barrier dysfunction and increased paracellular permeability prior to onset of cell lysis. Together, these results negate the inherent assumption that observations of necrosis in vitro directly predict bacterial virulence, and indicate a paradigm shift in our conceptual understanding of MARTX toxin function during intestinal infection. Results implicate the MARTX effector domain region in mediating early bacterial dissemination from the intestine to distal organs-a key step in V. vulnificus foodborne pathogenesis-even before onset of overt intestinal pathology.

  5. The Effector Domain Region of the Vibrio vulnificus MARTX Toxin Confers Biphasic Epithelial Barrier Disruption and Is Essential for Systemic Spread from the Intestine

    PubMed Central

    Gavin, Hannah E.; Beubier, Nike T.

    2017-01-01

    Vibrio vulnificus causes highly lethal bacterial infections in which the Multifunctional Autoprocessing Repeats-in-Toxins (MARTX) toxin product of the rtxA1 gene is a key virulence factor. MARTX toxins are secreted proteins up to 5208 amino acids in size. Conserved MARTX N- and C-terminal repeat regions work in concert to form pores in eukaryotic cell membranes, through which the toxin’s central region of modular effector domains is translocated. Upon inositol hexakisphosphate-induced activation of the of the MARTX cysteine protease domain (CPD) in the eukaryotic cytosol, effector domains are released from the holotoxin by autoproteolytic activity. We previously reported that the native MARTX toxin effector domain repertoire is dispensable for epithelial cellular necrosis in vitro, but essential for cell rounding and apoptosis prior to necrotic cell death. Here we use an intragastric mouse model to demonstrate that the effector domain region is required for bacterial virulence during intragastric infection. The MARTX effector domain region is essential for bacterial dissemination from the intestine, but dissemination occurs in the absence of overt intestinal tissue pathology. We employ an in vitro model of V. vulnificus interaction with polarized colonic epithelial cells to show that the MARTX effector domain region induces rapid intestinal barrier dysfunction and increased paracellular permeability prior to onset of cell lysis. Together, these results negate the inherent assumption that observations of necrosis in vitro directly predict bacterial virulence, and indicate a paradigm shift in our conceptual understanding of MARTX toxin function during intestinal infection. Results implicate the MARTX effector domain region in mediating early bacterial dissemination from the intestine to distal organs–a key step in V. vulnificus foodborne pathogenesis–even before onset of overt intestinal pathology. PMID:28060924

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

    SciTech Connect

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

    1995-01-01

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

  7. Regionalized PM2.5 Community Multiscale Air Quality model performance evaluation across a continuous spatiotemporal domain

    NASA Astrophysics Data System (ADS)

    Reyes, Jeanette M.; Xu, Yadong; Vizuete, William; Serre, Marc L.

    2017-01-01

    The regulatory Community Multiscale Air Quality (CMAQ) model is a means to understanding the sources, concentrations and regulatory attainment of air pollutants within a model's domain. Substantial resources are allocated to the evaluation of model performance. The Regionalized Air quality Model Performance (RAMP) method introduced here explores novel ways of visualizing and evaluating CMAQ model performance and errors for daily Particulate Matter ≤ 2.5 μm (PM2.5) concentrations across the continental United States. The RAMP method performs a non-homogenous, non-linear, non-homoscedastic model performance evaluation at each CMAQ grid. This work demonstrates that CMAQ model performance, for a well-documented 2001 regulatory episode, is non-homogeneous across space/time. The RAMP correction of systematic errors outperforms other model evaluation methods as demonstrated by a 22.1% reduction in Mean Square Error compared to a constant domain wide correction. The RAMP method is able to accurately reproduce simulated performance with a correlation of r = 76.1%. Most of the error coming from CMAQ is random error with only a minority of error being systematic. Areas of high systematic error are collocated with areas of high random error, implying both error types originate from similar sources. Therefore, addressing underlying causes of systematic error will have the added benefit of also addressing underlying causes of random error.

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

    NASA Technical Reports Server (NTRS)

    Mascaro, Giuseppe; Vivoni, Enrique

    2009-01-01

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

  9. Regionalized PM2.5 Community Multiscale Air Quality model performance evaluation across a continuous spatiotemporal domain.

    PubMed

    Reyes, Jeanette M; Xu, Yadong; Vizuete, William; Serre, Marc L

    2017-01-01

    The regulatory Community Multiscale Air Quality (CMAQ) model is a means to understanding the sources, concentrations and regulatory attainment of air pollutants within a model's domain. Substantial resources are allocated to the evaluation of model performance. The Regionalized Air quality Model Performance (RAMP) method introduced here explores novel ways of visualizing and evaluating CMAQ model performance and errors for daily Particulate Matter ≤ 2.5 micrometers (PM2.5) concentrations across the continental United States. The RAMP method performs a non-homogenous, non-linear, non-homoscedastic model performance evaluation at each CMAQ grid. This work demonstrates that CMAQ model performance, for a well-documented 2001 regulatory episode, is non-homogeneous across space/time. The RAMP correction of systematic errors outperforms other model evaluation methods as demonstrated by a 22.1% reduction in Mean Square Error compared to a constant domain wide correction. The RAMP method is able to accurately reproduce simulated performance with a correlation of r = 76.1%. Most of the error coming from CMAQ is random error with only a minority of error being systematic. Areas of high systematic error are collocated with areas of high random error, implying both error types originate from similar sources. Therefore, addressing underlying causes of systematic error will have the added benefit of also addressing underlying causes of random error.

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

    NASA Technical Reports Server (NTRS)

    Mascaro, Giuseppe; Vivoni, Enrique

    2009-01-01

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

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

    PubMed

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

    2016-05-05

    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.

  12. How Large Is the "Public Domain"? A Comparative Analysis of Ringer's 1961 Copyright Renewal Study and HathiTrust CRMS Data

    ERIC Educational Resources Information Center

    Wilkin, John P.

    2017-01-01

    The 1961 Copyright Office study on renewals, authored by Barbara Ringer, has cast an outsized influence on discussions of the U.S. 1923-1963 public domain. As more concrete data emerge from initiatives such as the large-scale determination process in the Copyright Review Management System (CRMS) project, questions are raised about the reliability…

  13. 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.

  14. 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.

  15. 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.

  16. Saliency region selection in large aerial imagery using multiscale SLIC segmentation

    NASA Astrophysics Data System (ADS)

    Sahli, Samir; Lavigne, Daniel A.; Sheng, Yunlong

    2012-06-01

    Advents in new sensing hardwares like GigE-cameras and fast growing data transmission capability create an imbalance between the amount of large scale aerial imagery and the means at disposal for treating them. Selection of saliency regions can reduce significantly the prospecting time and computation cost for the detection of objects in large scale aerial imagery. We propose a new approach using multiscale Simple Linear Iterative Clustering (SLIC) technique to compute the saliency regions. The SLIC is fast to create compact and uniform superpixels, based on the distances in both color and geometric spaces. When a salient structure of the object is over-segmented by the SLIC, a number of superpixels will follow the edges in the structure and therefore acquires irregular shapes. Thus, the superpixels deformation betrays presence of salient structures. We quantify the non-compactness of the superpixels as a salience measure, which is computed using the distance transform and the shape factor. To treat objects or object details of various sizes in an image, or the multiscale images, we compute the SLIC segmentations and the salient measures at multiple scales with a set of predetermined sizes of the superpixels. The final saliency map is a sum of the salience measures obtained at multiple scales. The proposed approach is fast, requires no input of user-defined parameter, produces well defined salient regions at full resolution and adapted to multi-scale image processing.

  17. Vorticity and large-scale structures in the transition region of a turbulent jet

    NASA Astrophysics Data System (ADS)

    Weisgraber, Todd Heinrich

    Though the existence of large-scale structures in the near and far field of jets has been demonstrated, their exact nature in the self-similar region is still open to debate. Furthermore, the evolution of these structures in the transition region is not well understood. In this thesis, a hybrid experimental-numerical approach is developed to investigate the flow structure of the jet transition region. The spatial-temporal characteristics of these large eddies and their effect on local entrainment are examined. The velocity field in planes normal and parallel to the jet axis are measured using the digital particle image velocimetry (DPIV) technique with a computationally efficient algorithm designed to minimize sub-pixel bias. The numerics employ a second order projection method with adaptive mesh refinement to simulate a natural unforced jet. The link between the experiments and numerics is provided by a temporal sequence of DPIV nozzle velocity data which serves as the inflow boundary condition to the computation. Successful comparisons of the development of near-field primary and secondary structures validate the simulation. The mean jet growth rate is identical to the experiments. Analysis of the experimental data with a proper orthogonal decomposition identifies and reveals the evolution of large-scale structures. After the first pairing the rings develop a tilting instability which is amplified by the interaction of adjacent rings. After the potential core, the inclined rings have a unique time scale and are responsible for a significant fraction of the local turbulent transport and rapid growth of the jet. Further downstream, beginning at nine diameters, the rings evolve into a flow that alternates between ejection and entrainment of fluid. This motion persists through the remainder of the transition region and increases its contribution to lateral mixing with downstream distance. The time scale governing the inward and outward flow oscillations increases

  18. Time and Frequency Domain Synthesis in the Optimal Design of Shock and Vibration Isolation for Large Structural Systems

    DTIC Science & Technology

    1997-06-01

    DOMAIN SYNTHESIS COMPUTER CODE The computer language used for the frequency domain synthesis and all other computer coding in this thesis is MATLAB V.4.2c... method is really not restrictive in its application, but rather in what information it can provide. D. STATIC DISPLACEMENT SYNTHESIS COMPUTER CODE The...synthesis, and perform a comparative analysis of the synthesis versus classical Guyan reduction methods . The programs presented in Appendix B can be

  19. Short forms of the Utrecht-Management of Identity Commitments Scale (U-MICS) with the domains of job, romantic relationship, and region.

    PubMed

    Schubach, Elisabeth; Zimmermann, Julia; Noack, Peter; Neyer, Franz J

    2017-01-01

    The U-MICS is a self-report questionnaire designed to assess the identity dimensions from a domain-specific perspective. The present study reports on the development of a short-form version for the domains of job and romantic relationship in young adults from Germany and extends this scale to include the domain of region (nSample1 = 95, 84% female, mean age 22.45 years; nSample2 = 1,795, 71% female, mean age 24.53 years). We found the short form to possess adequate psychometric properties and to demonstrate a factor structure congruent to the long-form version. Regarding validity, the small correlations across domains within dimensions support a domain-specific approach to identity. The associations between the different identity domains with personality traits are similar, indicating a consistent pattern of convergent validity for all domains. We conclude that "region" provides a valuable complement to the established domains that can all be reliably assessed with the U-MICS-Short Form. Copyright © 2016 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

  20. Large Scale Observatories for Changing Cold Regions - Recent Progress and Future Vision

    NASA Astrophysics Data System (ADS)

    Wheater, H. S.; Pomeroy, J. W.; Carey, S. K.; DeBeer, C. M.

    2016-12-01

    Observatories are at the core of hydrological science and a critical resource for the detection and analysis of environmental change. The combination of multiple pressures on the water environment and new scientific opportunities provides a context where a broader vision is urgently needed. Human activities are increasingly affecting land and water management at multiple scales, so our observatories now need to more fully include the human dimensions of water, including their integration across jurisdictional boundaries and at large basin scales. And large scales are also needed to diagnose and predict impacts of climate change at regional and continental scales, and to address land-water-atmosphere interactions and feedbacks. We argue the need to build on the notable past successes of the World Climate Research Programme and move forward to a new era of globally-distributed large scale observatories. This paper introduces 2 such observatories in rapidly warming western Canada - the 405,000 km2 Saskatchewan and the 1.8 million km2 Mackenzie river basins. We review progress in these multi-scale observatories, including the use of point and small basin-scale observatory sites to observe and diagnose complex regional patterns of hydrological change. And building on new opportunities for observational systems and data assimilation, we present a vision for a pan-Canadian observing system to support the science needed for the management of future societal risk from extreme events and environmental change.

  1. Large-scale image region documentation for fully automated image biomarker algorithm development and evaluation.

    PubMed

    Reeves, Anthony P; Xie, Yiting; Liu, Shuang

    2017-04-01

    With the advent of fully automated image analysis and modern machine learning methods, there is a need for very large image datasets having documented segmentations for both computer algorithm training and evaluation. This paper presents a method and implementation for facilitating such datasets that addresses the critical issue of size scaling for algorithm validation and evaluation; current evaluation methods that are usually used in academic studies do not scale to large datasets. This method includes protocols for the documentation of many regions in very large image datasets; the documentation may be incrementally updated by new image data and by improved algorithm outcomes. This method has been used for 5 years in the context of chest health biomarkers from low-dose chest CT images that are now being used with increasing frequency in lung cancer screening practice. The lung scans are segmented into over 100 different anatomical regions, and the method has been applied to a dataset of over 20,000 chest CT images. Using this framework, the computer algorithms have been developed to achieve over 90% acceptable image segmentation on the complete dataset.

  2. Aspect angle dependence of the E region irregularity velocity at large flow angles

    NASA Astrophysics Data System (ADS)

    Makarevich, R. A.; Koustov, A. V.; Senior, A.; Uspensky, M.; Honary, F.; Dyson, P. L.

    2007-11-01

    We present the Doppler velocity observations of 1-m plasma waves in the auroral E region by the Scandinavian Twin Auroral Radar Experiment (STARE) Norway VHF coherent radar in the context of simultaneous and coincident measurements of electron and ion drift velocities determined by the European Incoherent Scatter (EISCAT) tristatic radar facility. The measurements were performed in the afternoon sector (1500-2000 MLT) at seven locations along the STARE radar beam 2 with different values of the magnetic off-perpendicular (aspect) angle α between 0.48° and 2.63° and at large angles with respect to the electron background drift (θ = 55°-90°). It is demonstrated that the STARE line-of-sight velocity, normalized to the EISCAT-derived electron drift speed at large flow angles, exhibits a decrease with increasing aspect angle, and the rate of decrease is investigated as a function of the flow angle. We also compare the STARE velocity with the electron and ion drift velocity components along the STARE radar beam look direction and show that, at large aspect angles, the E region velocity is correlated (anticorrelated) with the ion (electron) drift velocity component. The results are discussed in the contexts of the linear fluid theory of the modified two-stream plasma instability and the theory of anomalous collisions.

  3. 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

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

    NASA Astrophysics Data System (ADS)

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

    2015-12-01

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

  5. 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.

  6. 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

  7. Architecture of the Nitric-oxide Synthase Holoenzyme Reveals Large Conformational Changes and a Calmodulin-driven Release of the FMN Domain*♦

    PubMed Central

    Yokom, Adam L.; Morishima, Yoshihiro; Lau, Miranda; Su, Min; Glukhova, Alisa; Osawa, Yoichi; Southworth, Daniel R.

    2014-01-01

    Nitric-oxide synthase (NOS) is required in mammals to generate NO for regulating blood pressure, synaptic response, and immune defense. NOS is a large homodimer with well characterized reductase and oxygenase domains that coordinate a multistep, interdomain electron transfer mechanism to oxidize l-arginine and generate NO. Ca2+-calmodulin (CaM) binds between the reductase and oxygenase domains to activate NO synthesis. Although NOS has long been proposed to adopt distinct conformations that alternate between interflavin and FMN-heme electron transfer steps, structures of the holoenzyme have remained elusive and the CaM-bound arrangement is unknown. Here we have applied single particle electron microscopy (EM) methods to characterize the full-length of the neuronal isoform (nNOS) complex and determine the structural mechanism of CaM activation. We have identified that nNOS adopts an ensemble of open and closed conformational states and that CaM binding induces a dramatic rearrangement of the reductase domain. Our three-dimensional reconstruction of the intact nNOS-CaM complex reveals a closed conformation and a cross-monomer arrangement with the FMN domain rotated away from the NADPH-FAD center, toward the oxygenase dimer. This work captures, for the first time, the reductase-oxygenase structural arrangement and the CaM-dependent release of the FMN domain that coordinates to drive electron transfer across the domains during catalysis. PMID:24737326

  8. Aftershock productivity of large megathrust earthquakes: regional variations and influence of mainshock source parameters

    NASA Astrophysics Data System (ADS)

    Wetzler, N.; Brodsky, E. E.; Lay, T.

    2016-12-01

    On average, the number of aftershocks increases with mainshock magnitude following a well-defined relationship for any given region. However, variability around this average relationship provokes important questions. What regional variations exist? How do other mainshock properties such as stress drop affect aftershock productivity? To address these issues we focus on variations of aftershock productivity of large (MW ≥ 7.0) circum-Pacific megathrust earthquakes within the past 25 years. We capitalize on an extant set of finite-fault rupture model inversions to investigate how aftershock productivity varies regionally and with aftershock source parameters. We find aftershock productivity to be higher for islands arcs of the western circum-Pacific than for continental arcs of the eastern circum-Pacific. Surprisingly, events with larger static stress-drops do not produce more aftershocks than those with smaller stress drops. If anything, larger static stress-drops tend to produce fewer aftershocks than comparable magnitude events with lower stress-drop. The regional trend may reflect differences in fault susceptibility between island arcs and continental arcs, and the stress-drop behavior may imply near-total stress release for the largest stress drop events.

  9. 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.

  10. A large outbreak of Japanese encephalitis predominantly among adults in northern region of West Bengal, India.

    PubMed

    Gurav, Yogesh K; Bondre, Vijay P; Tandale, Babasaheb V; Damle, Rekha G; Mallick, Sanjay; Ghosh, Uday S; Nag, Shankha S

    2016-11-01

    Unusual rise of acute encephalitis syndrome cases (AES) were reported in July 2014 in the northern region of West Bengal, India. Investigations were carried out to characterize the outbreak and to identify the associated virus etiology. This observational study is based on 398 line listed AES cases, mostly (70.8%, 282/398) adults, with case fatality ratio of 28.9% (115/398). Japanese encephalitis virus infection was detected in 134 (49.4%) among 271 AES cases tested and most of them (79.1%, 106/134) were adults. The study reports a large outbreak of genotype III Japanese encephalitis among adults in northern region of West Bengal, India. J. Med. Virol. 88:2004-2011, 2016. © 2016 Wiley Periodicals, Inc.

  11. 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.

  12. Ages of calderas, large explosive craters and active volcanoes in the Kuril-Kamchatka region, Russia

    NASA Astrophysics Data System (ADS)

    Braitseva, O. A.; Melekestsev, I. V.; Ponomareva, V. V.; Sulerzhitsky, L. D.

    1995-12-01

    The ages of most of calderas, large explosive craters and active volcanoes in the Kuril-Kamchatka region have been determined by extensive geological, geomorphological, tephrochronological and isotopic geochronological studies, including more than 600 14C dates. Eight ‘Krakatoa-type’ and three ‘Hawaiian-type’ calderas and no less than three large explosive craters formed here during the Holocene. Most of the Late Pleistocene Krakatoa-type calderas were established around 30 000 40 000 years ago. The active volcanoes are geologically very young, with maximum ages of about 40 000 50 000 years. The overwhelming majority of recently active volcanic cones originated at the very end of the Late Pleistocene or in the Holocene. These studies show that all Holocene stratovolcanoes in Kamchatka were emplaced in the Holocene only in the Eastern volcanic belt. Periods of synchronous, intensified Holocene volcanic activity occurred within the time intervals of 7500 7800 and 1300 1800 14C years BP.

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

    NASA Astrophysics Data System (ADS)

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

    2015-04-01

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

  14. Generation of large-scale equatorial F-region plasma depletions during geomagnetic storms: A review

    NASA Astrophysics Data System (ADS)

    Sahai, Y.; Fagundes, P.; Bittencourt, J.; Pimenta, A.

    All-sky imaging observations of the F-region OI 630 nm nightglow emission allow us to visualize large - scale equatorial plasma depletions, generally known as transequatorial plasma bubbles. These quasi north south direction aligned- ionospheric plasma depletions are o tical signatures of strong range type equatorialp spread-F. An extensive data base of the OI 630 nm emission all-sky imaging- observations has been obtained at Cachoeira Paulista (22.7o S, 45.0 o W; dip latitude ~16o S), Brazil, between the years 1987 and 2000. An analysis of these observations revealed that normally large-scale ionospheric plasma depletions do not occur during the months of May to August (southern winter) in the Brazilian sector. However, large-scale ionospheric plasma depletions during thes e months have been observed on several occasions in association with geomagnetic storms. In this paper, a detailed analysis of the events when large - scale ionospheric plasma depletions were initiated and evolved during magnetic disturbances will be present ed and discussed.

  15. 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…

  16. 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.

  17. Regional and stress drop effects on aftershock productivity of large megathrust earthquakes

    NASA Astrophysics Data System (ADS)

    Wetzler, Nadav; Brodsky, Emily E.; Lay, Thorne

    2016-12-01

    The total number of aftershocks increases with main shock magnitude, resulting in an overall well-defined relationship. Observed variations from this trend prompt questions regarding influences of regional environment and individual main shock rupture characteristics. We investigate how aftershock productivity varies regionally and with main shock source parameters for large (Mw ≥ 7.0) circum-Pacific megathrust earthquakes within the past 25 years, drawing on extant finite-fault rupture models. Aftershock productivity is found to be higher for subduction zones of the western circum-Pacific than for subduction zones in the eastern circum-Pacific. This appears to be a manifestation of differences in faulting susceptibility between island arcs and continental arcs. Surprisingly, events with relatively large static stress drop tend to produce fewer aftershocks than comparable magnitude events with lower stress drop; however, for events with similar coseismic rupture area, aftershock productivity increases with stress drop and radiated energy, indicating a significant impact of source rupture process on productivity.

  18. Estrogen-mediated epigenetic repression of large chromosomal regions through DNA looping

    PubMed Central

    Hsu, Pei-Yin; Hsu, Hang-Kai; Singer, Gregory A.C.; Yan, Pearlly S.; Rodriguez, Benjamin A.T.; Liu, Joseph C.; Weng, Yu-I; Deatherage, Daniel E.; Chen, Zhong; Pereira, Julia S.; Lopez, Ricardo; Russo, Jose; Wang, Qianben; Lamartiniere, Coral A.; Nephew, Kenneth P.; Huang, Tim H.-M.

    2010-01-01

    The current concept of epigenetic repression is based on one repressor unit corresponding to one silent gene. This notion, however, cannot adequately explain concurrent silencing of multiple loci observed in large chromosome regions. The long-range epigenetic silencing (LRES) can be a frequent occurrence throughout the human genome. To comprehensively characterize the influence of estrogen signaling on LRES, we analyzed transcriptome, methylome, and estrogen receptor alpha (ESR1)-binding datasets from normal breast epithelia and breast cancer cells. This “omics” approach uncovered 11 large repressive zones (range, 0.35∼5.98 megabases), including a 14-gene cluster located on 16p11.2. In normal cells, estrogen signaling induced transient formation of multiple DNA loops in the 16p11.2 region by bringing 14 distant loci to focal ESR1-docking sites for coordinate repression. However, the plasticity of this free DNA movement was reduced in breast cancer cells. Together with the acquisition of DNA methylation and repressive chromatin modifications at the 16p11.2 loci, an inflexible DNA scaffold may be a novel determinant used by breast cancer cells to reinforce estrogen-mediated repression. PMID:20442245

  19. [Study on large-scale regional laser detection methods for water vapor concentration].

    PubMed

    He, Ying; Zhang, Yu-Jun; Wang, Li-Ming; You, Kun; Zhou, Yi; Sun, Xiao-Min; Liu, Zhen-Min

    2013-03-01

    Water vapor is an important meteorological parameter in the atmosphere, TDLAS direct absorption technology combined with open-path monitoring was used in order to achieve large-scale regional atmospheric water vapor concentration detection with high sensitivity, high accuracy and fast response, and to correct the remote sensing data. The large-scale regional laser detection system for water vapor was designed and the absorption line of water vapor molecules near 1.27 microm was chosen as the goal line. The system performance was verified in conjunction with a multiple reflection cell, that the system limit sensitivity was 14.803 mmol.mol-1 in optical path of 40 m. The continuous field experiment in 1,420 m optical path at the Yucheng Integrated Experimental Station, CAS was completed with this system which worked stably. Then the measured data was compared with the data of a gas analyzer LI-7500 in eddy correlation observation system at the same site, and the data consistency was good. A new method for water vapor concentration monitoring in the complex field of non-uniform underlying surface was provided.

  20. 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.

  1. 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}.

  2. Climate change projections of medicanes with a large multi-model ensemble of regional climate models

    NASA Astrophysics Data System (ADS)

    Romera, Raquel; Gaertner, Miguel Ángel; Sánchez, Enrique; Domínguez, Marta; González-Alemán, Juan Jesús; Miglietta, Mario Marcello

    2017-04-01

    Cyclones with tropical characteristics, usually called medicanes, occasionally develop over the Mediterranean Sea. Possible future changes of medicanes are a matter of concern due to their large damage potential. Here we analyse a large set of climate change projections with regional climate models (RCMs) from the ENSEMBLES project. The aim is to increase our knowledge about the future evolution of medicanes, advancing previous studies along several important lines: use of a large ensemble of RCMs, nested in many different GCMs, and covering a long continuous time period (up to 150 years). The main overall results are a future reduction in the number of medicanes and an increase in the intensity of the strongest medicanes, in agreement with other studies. But the large size of the ensemble reveals some important model-related uncertainties. The frequency decrease is not statistically significant in many of the subset of simulations that extend to 2100, with two simulations even showing no frequency decrease at all. Large decadal changes affect the frequency of medicanes, emphasizing the need for long period simulations. The increase in extreme intensity shows a clear dependence on the GCM driving the simulations. In contrast to the overall results, a few simulations also show changes in the monthly distribution of medicanes, with less winter cases and more autumn and late summer cases. Some environmental variables have been explored in an attempt to offer physical explanations for these results. A plausible reason for the overall decrease of the frequency of medicanes is the projected increase in vertical static stability of the atmosphere. A relevant result is that the general and clear increase in average static stability is unable to stop several simulations projecting higher maximum winds in the future. This could indicate that the increased SST and latent heat fluxes may overcome the limitation of a higher overall static stability, if favourable conditions for

  3. 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.

  4. Physical Properties of Large and Small Granules in Solar Quiet Regions

    NASA Astrophysics Data System (ADS)

    Yu, Daren; Xie, Zongxia; Hu, Qinghua; Yang, Shuhong; Zhang, Jun; Wang, Jingxiu

    2011-12-01

    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 1farcs44, and large granules with diameters larger than 1farcs44. 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 0.

  5. 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

  6. 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

  7. Mutational analysis of the Acropora millepora PaxD paired domain highlights the importance of the linker region for DNA binding.

    PubMed

    Nordström, Karin; Scholten, Ingo; Nordström, Johanna; Larhammar, Dan; Miller, David

    2003-11-27

    Pax transcription factors are found in animals, from simple sponges to insects and vertebrates. The defining feature of Pax proteins is the DNA-binding paired domain (PD), which consists of two helix-turn-helix subdomains, joined with a linker region. Despite high specificity in vivo, the paired domains of different Pax proteins bind similar consensus DNA sequences in vitro. Using bandshift techniques, we show here that the paired domain of the Acropora millepora PaxD protein, which unambiguously belongs to the Pax3/7 group, does not bind to three defined paired domain-binding sites. Domain swapping experiments and site-directed mutagenesis identified two amino acid residues in the linker region of the paired domain as critical to DNA binding; G70 and S71 are highly conserved in Pax proteins, but differ in PaxD (L70 and N71). The PaxD data thus highlight the importance of the linker region, and particularly G70 and S71, in DNA binding by Pax proteins.

  8. 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.

  9. Validation of ICDPIC software injury severity scores using a large regional trauma registry.

    PubMed

    Greene, Nathaniel H; Kernic, Mary A; Vavilala, Monica S; Rivara, Frederick P

    2015-10-01

    Administrative or quality improvement registries may or may not contain the elements needed for investigations by trauma researchers. International Classification of Diseases Program for Injury Categorisation (ICDPIC), a statistical program available through Stata, is a powerful tool that can extract injury severity scores from ICD-9-CM codes. We conducted a validation study for use of the ICDPIC in trauma research. We conducted a retrospective cohort validation study of 40,418 patients with injury using a large regional trauma registry. ICDPIC-generated AIS scores for each body region were compared with trauma registry AIS scores (gold standard) in adult and paediatric populations. A separate analysis was conducted among patients with traumatic brain injury (TBI) comparing the ICDPIC tool with ICD-9-CM embedded severity codes. Performance in characterising overall injury severity, by the ISS, was also assessed. The ICDPIC tool generated substantial correlations in thoracic and abdominal trauma (weighted κ 0.87-0.92), and in head and neck trauma (weighted κ 0.76-0.83). The ICDPIC tool captured TBI severity better than ICD-9-CM code embedded severity and offered the advantage of generating a severity value for every patient (rather than having missing data). Its ability to produce an accurate severity score was consistent within each body region as well as overall. The ICDPIC tool performs well in classifying injury severity and is superior to ICD-9-CM embedded severity for TBI. Use of ICDPIC demonstrates substantial efficiency and may be a preferred tool in determining injury severity for large trauma datasets, provided researchers understand its limitations and take caution when examining smaller trauma datasets. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  10. Triggered star formation in the LMC4/Constellation III region of the Large Magellanic Cloud

    NASA Astrophysics Data System (ADS)

    Efremov, Yuri N.; Elmegreen, Bruce G.

    1998-09-01

    The origin of a regular, 600-pc-long arc of young stars and clusters in the Constellation III region of the Large Magellanic Cloud is considered. The circular form of this arc suggests that the pre-stellar gas was uniformly swept up by a central source of pressure. In the centre of the arc are six ~30-Myr-old A-type supergiant stars and a Cepheid variable of similar age, which may be related to the source of this pressure. We calculate the expansion of a bubble around a cluster of this age, and show that it could have triggered the formation of the arc at the right time and place. Surrounding the central old stars and extending well outside the young arc is the LMC4 superbubble and giant HI shell. We show how this superbubble and shell could have formed by the continued expansion of the 15-Myr-old cavity, following star formation in the arc and the associated new pressures. The age sequence proposed here was not evident in the recent observations by Olsen et al. and Braun et al. because the first generation stars in the centre of the LMC superbubble are relatively faint and scarce compared to the more substantial population of stars less than 15 Myr old that formed throughout the region in a second generation. These considerations lead to an examination of the origin of the LMC4/Constellation III region and other large rings in the LMC and other galaxies. Their size and circularity could be the result of low galactic shear and a thick disc, with several generations of star formation in their interiors now too faint to be seen.

  11. A variably spliced region in the type 1 ryanodine receptor may participate in an inter-domain interaction.

    PubMed

    Kimura, Takashi; Pace, Suzy M; Wei, Lan; Beard, Nicole A; Dirksen, Robert T; Dulhunty, Angela F

    2007-01-01

    The aim of the present study was to examine residues that are variably spliced in the juvenile and adult isoforms of the skeletal-muscle RyR1 (type 1 ryanodine receptor). The juvenile ASI(-) splice variant is less active than the adult ASI(+) variant and is overexpressed in patients with DM (myotonic dystrophy) [Kimura, Nakamori, Lueck, Pouliquin, Aoike, Fujimura, Dirksen, Takahashi, Dulhunty and Sakoda (2005) Hum. Mol. Genet. 14, 2189-2200]. In the present study, we explore the ASI region using synthetic peptides corresponding to rabbit RyR1 residues Thr3471-Gly3500 either containing [PASI(+)] or lacking [PASI(-)] the ASI residues. Both peptides increased [3H]ryanodine binding to rabbit RyR1s, increased Ca2+ release from sarcoplasmic reti-culum vesicles and increased single RyR1 channel activity. The peptide PASI(-) was more active in each case than PASI(+). [3H]Ryanodine binding to recombinant ASI(+)RyR1 or ASI(-)-RyR1 was enhanced more by PASI(-) than PASI(+), with the greatest increase seen when PASI(-) was added to ASI(-)RyR1. The activation of the RyR channels is consistent with the hypo-thesis that the peptides interrupt an inhibitory inter-domain inter-action and that PASI(-) is more effective at interrupting this interaction than PASI(+). We therefore suggest that the ASI(-) sequence interacts more tightly than the ASI(+) sequence with its binding partner, so that the ASI(-)RyR1 is more strongly inhibited (less active) than the ASI(+)RyR1. Thus the affinity of the binding partners in this inter-domain interaction may deter-mine the activities of the mature and juvenile isoforms of RyR1 and the stronger inhibition in the juvenile isoform may contribute to the myopathy in DM.

  12. Regional brain amyloid-β accumulation associates with domain-specific cognitive performance in Parkinson disease without dementia.

    PubMed

    Akhtar, Rizwan S; Xie, Sharon X; Chen, Yin J; Rick, Jacqueline; Gross, Rachel G; Nasrallah, Ilya M; Van Deerlin, Vivianna M; Trojanowski, John Q; Chen-Plotkin, Alice S; Hurtig, Howard I; Siderowf, Andrew D; Dubroff, Jacob G; Weintraub, Daniel

    2017-01-01

    Parkinson disease patients develop clinically significant cognitive impairment at variable times over their disease course, which is often preceded by milder deficits in memory, visuo-spatial, and executive domains. The significance of amyloid-β accumulation to these problems is unclear. We hypothesized that amyloid-β PET imaging by 18F-florbetapir, a radiotracer that detects fibrillar amyloid-β plaque deposits, would identify subjects with global cognitive impairment or poor performance in individual cognitive domains in non-demented Parkinson disease patients. We assessed 61 non-demented Parkinson disease patients with detailed cognitive assessments and 18F-florbetapir PET brain imaging. Scans were interpreted qualitatively (positive or negative) by two independent nuclear medicine physicians blinded to clinical data, and quantitatively by a novel volume-weighted method. The presence of mild cognitive impairment was determined through an expert consensus process using Level 1 criteria from the Movement Disorder Society. Nineteen participants (31.2%) were diagnosed with mild cognitive impairment and the remainder had normal cognition. Qualitative 18F-florbetapir PET imaging was positive in 15 participants (24.6%). Increasing age and presence of an APOE ε4 allele were associated with higher composite 18F-florbetapir binding. In multivariable models, an abnormal 18F-florbetapir scan by expert rating was not associated with a diagnosis of mild cognitive impairment. However, 18F-florbetapir retention values in the posterior cingulate gyrus inversely correlated with verbal memory performance. Retention values in the frontal cortex, precuneus, and anterior cingulate gyrus retention values inversely correlated with naming performance. Regional cortical amyloid-β amyloid, as measured by 18F-florbetapir PET, may be a biomarker of specific cognitive deficits in non-demented Parkinson disease patients.

  13. An integral membrane protein of the pore membrane domain of the nuclear envelope contains a nucleoporin-like region

    PubMed Central

    1993-01-01

    We have identified an integral membrane protein of 145 kD (estimated by SDS-PAGE) of rat liver nuclear envelopes that binds to WGA. We obtained peptide sequence from purified p145 and cloned and sequenced several cDNA clones and one genomic clone. The relative molecular mass of p145 calculated from its complete, cDNA deduced primary structure is 120.7 kD. Antibodies raised against a synthetic peptide represented in p145 reacted monospecifically with p145. In indirect immunofluorescence these antibodies gave punctate staining of the nuclear envelope. Immunogold EM showed specific decoration of the nuclear pores. Thus p145 is an integral membrane protein located specifically in the "pore membrane" domain of the nuclear envelope. To indicate this specific location, and based on its calculated relative molecular mass, the protein is termed POM 121 (pore membrane protein of 121 kD). The 1,199- residue-long primary structure shows a hydrophobic region (residues 29- 72) that is likely to form one (or two adjacent) transmembrane segment(s). The bulk of the protein (residues 73-1199) is predicted to be exposed not on the cisternal side but on the pore side of the pore membrane. It contains 36 consensus sites for various kinases. However, its most striking feature is a repetitive pentapeptide motif XFXFG that has also been shown to occur in several nucleoporins. This nucleoporin- like domain of POM 121 is proposed to function in anchoring components of the nuclear pore complex to the pore membrane. PMID:8335683

  14. 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

  15. 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.

  16. 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.

  17. The Gould's Belt Very Large Array Survey. II. The Serpens Region

    NASA Astrophysics Data System (ADS)

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

    2015-05-01

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

  18. Future changes in daily snowfall intensity projected by large ensemble regional climate experiments

    NASA Astrophysics Data System (ADS)

    Kawase, H.

    2015-12-01

    We investigate the future changes in daily snowfall intensity in Japan analyzing the large ensemble regional climate experiments. Dynamical downscalings are conducted by Non-Hydrostatic Regional Climate Model (NHRCM) with 20 km from the global climate projections using Meteorological Research Institute-Atmospheric General Circulation Model (MRI-AGCM). Fifty ensemble experiments are performed in the present climate. For the future climate projections, 90 ensemble experiments are performed based on the six patterns of SST changes in the periods when 4 K rise in global-mean surface air temperature is projected. The accumulated snowfall in winter decreases in Japan except for the northern parts of Japan. Especially, the inland areas in the Sea of Japan side, which is famous for the heaviest snowfall region in the world, shows the remarkable decrease in snowfall in the future climate. The experiments also show increased number of days without snowfall and decreased number of days with weak snowfall due to significant warming in the most parts of Japan. On the other hand, the extreme daily snowfall, which occurs once ten years, would increase at higher elevations in the Sea of Japan side. This means that extreme daily snowfall in the present climate would occur more frequently in the future climate. The warmer atmosphere can contain more water vapor and warmer ocean can supply more water vapor to the low atmosphere. The surface air temperature at higher elevations is still lower than 0 degree Celsius, which could result in the increased extreme daily snowfall.

  19. 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.

  20. Extraordinary boundary morphologies of large-scale ordered domains of spheres in thin films of a narrowly dispersed diblock copolymer via thermodynamic control

    NASA Astrophysics Data System (ADS)

    Shi, Ling-Ying; Li, Hang; Lei, Wei-Wei; Ni, Wei; Ran, Rong; Pan, Yu; Fan, Xing-He; Shen, Zhihao

    2015-10-01

    Long-range ordering of body centered cubic (BCC) spheres and various extraordinary morphologies at the boundaries of the adjacent orderly oriented domains are observed in thermally annealed thin films of a series of specific narrowly dispersed diblock copolymers, poly(dimethylsiloxane)-b-poly{2,5-bis[(4-butoxyphenyl)oxycarbonylstyrene} (PDMS-b-PBPCS, DB). The series of asymmetrical DB block copolymers (BCPs) with volume fractions of PDMS (fPDMS's) from 10% to 23% self-assemble into thermodynamically stable body centered cubic (BCC) nanostructures in bulk at ambient temperature after thermal annealing. The thin films of these BCPs with a relatively large film thickness on a carbon-film coated substrate are annealed in a vacuum at 180 °C for 3 days and are characterized by transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS). For all thin films of these BCPs, micrometer-scale domains with a rectangular unit cell similar to the projection of the BCC lattice along the [110] direction to the substrate are observed. And the XPS results indicate that the surface layers of the thin films are composed of both PDMS and PBPCS blocks. For the thin films of the BCPs with fPDMS values of 10% and 13%, the neighboring [110]-oriented BCC domains match well with each other, and the boundaries are defect-free. For the thin film of the BCP with a fPDMS value of 23%, the PDMS spheres in the [110]-oriented BCC domains in the TEM micrograph are overlapped with each other, and interesting morphologies including defect-free interfaces, interfaces with line defects, and domains with defects and local ordering are observed at the boundaries of the neighboring [110]-oriented domains.Long-range ordering of body centered cubic (BCC) spheres and various extraordinary morphologies at the boundaries of the adjacent orderly oriented domains are observed in thermally annealed thin films of a series of specific narrowly dispersed diblock copolymers, poly

  1. Large Eddy Simulations of Volume Restriction Effects on Canopy-Induced Increased-Uplift Regions

    NASA Astrophysics Data System (ADS)

    Chatziefstratiou, E.; Bohrer, G.; Velissariou, V.

    2012-12-01

    ABSTRACT Previous modeling and empirical work have shown the development of important areas of increased uplift past forward-facing steps, and recirculation zones past backward-facing steps. Forests edges represent a special kind of step - a semi-porous one. Current models of the effects of forest edges on the flow represent the forest with a prescribed drag term and does not account for the effects of the solid volume in the forest that restrict the airflow. The RAMS-based Forest Large Eddy Simulation (RAFLES) resolves flows inside and above forested canopies. RAFLES is spatially explicit, and uses the finite volume method to solve a descretized set of Navier-Stokes equations. It accounts for vegetation drag effects on the flow and on the flux exchange between the canopy and the canopy air, proportional to the local leaf density. For a better representation of the vegetation structure in the numerical grid within the canopy sub-domain, the model uses a modified version of the cut cell coordinate system. The hard volume of vegetation elements, in forests, or buildings, in urban environments, within each numerical grid cell is represented via a sub-grid-scale process that shrinks the open apertures between grid cells and reduces the open cell volume. We used RAFLES to simulate the effects of a canopy of varying foliage and stem densities on flow over virtual qube-shaped barriers under neutrally buoyant conditions. We explicitly tested the effects of the numerical representation of volume restriction, independent of the effects of the leaf drag by comparing drag-only simulations, where we prescribed no volume or aperture restriction to the flow, restriction-only simulations, where we prescribed no drag, and control simulations, where both drag and volume plus aperture restriction were included. Our simulations show that representation of the effects of the volume and aperture restriction due to obstacles to flow is important (figure 1) and leads to differences in the

  2. Characteristics of very large aspect angle E-region coherent echoes at 933 MHz

    NASA Astrophysics Data System (ADS)

    Jackel, B. J.; Moorcroft, D. R.; Schlegel, K.

    1997-01-01

    The EISCAT UHF radar system was used to study the characteristics of E-region coherent backscatter at very large magnetic aspect angles (5-11°). Data taken using 60 s pulses during elevation scans through horizontally uniform backscatter permitted the use of inversion techniques to determine height profiles of the scattering layer. The layer was always singly peaked, with a mean height of 104 km, and mean thickness (full width at half maximum) of 10 km, both independent of aspect angle. Aspect sensitivities were also estimated, with the Sodankylä-Tromsø link observing 5 dB/degree at aspect angles near 5°, decreasing to 3 dB/degree at 10° aspect angle. Observed coherent phase velocities from all three stations were found to be roughly consistent with LOS measurements of a common E-region phase velocity vector. The E-region phase velocity had the same orientation as the F-region ion drift velocity, but was approximately 50% smaller in magnitude. Spectra were narrow with skewness of about +1 (for negative velocities), increasing slightly with aspect angle. Acknowledgements. The authors are grateful to Prof. D. J. Southwood (Imperial College, London), J. C. Samson (University of Alberta, Edmonton), L. J. Lanzerotti (AT&T Bell Laboratories), A. Wolfe (New York City Technical College) and to Dr. M. Vellante (University of LÁquila) for helpful discussions. They also thank Dr. A. Meloni (Istituto Nazionale di Geofisica, Roma) who made available geomagnetic field observations from LÁquila Geomagnetic Observatory. This research activity at LÁquila is supported by MURST (40% and 60% contracts) and by GIFCO/CNR. Topical Editor K.-H. Glaßmeier thanks C. Waters and S. Fujita for their help in evaluating this paper.-> Correspondence to :P. Francia->

  3. 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.

  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. Nanoparticle migration and delivery of Paclitaxel to regional lymph nodes in a large animal model.

    PubMed

    Khullar, Onkar V; Griset, Aaron P; Gibbs-Strauss, Summer L; Chirieac, Lucian R; Zubris, Kimberly A V; Frangioni, John V; Grinstaff, Mark W; Colson, Yolonda L

    2012-03-01

    The aim of this study was to demonstrate feasibility of migration and in situ chemotherapy delivery to regional lymph nodes (LN) in a large animal model using an expansile polymer nanoparticle (eNP) delivery system. Dual-labeled 50-nm and 100-nm eNP were prepared by encapsulating an IR-813 near-infrared (NIR) fluorescent dye within coumarin-conjugated expansile polymer nanoparticles (NIR-C-eNP). NIR imaging and fluorescent microscopy were used to identify intralymphatic migration of NIR-nanoparticles to draining inguinal or mesenteric LN after injection in swine hind legs or intestine. Nanoparticle-mediated intranodal delivery of chemotherapy was subsequently assessed with Oregon Green paclitaxel-loaded NIR-eNP (NIR-OGpax-eNP). NIR imaging demonstrated direct lymphatic migration of 50-nm, but not 100-nm, NIR-C-eNP and NIR-OGpax-eNP to the draining regional LNs after intradermal injection in the hind leg or subserosal injection in intestine. Fluorescent microscopy demonstrated that IR-813 used for NIR real-time trafficking colocalized with both the coumarin-labeled polymer and paclitaxel chemotherapy and was identified within the subcapsular spaces of the draining LNs. These studies verify nodal migration of both nanoparticle and encapsulated payload, and confirm the feasibility of focusing chemotherapy delivery directly to regional nodes. Regionally-targeted intranodal chemotherapy can be delivered to draining LNs for both skin and solid organs using 50-nm paclitaxel-loaded eNP. Copyright © 2012 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

  6. Amino acids in the COOH-terminal region of the oxytocin receptor third intracellular domain are important for receptor function.

    PubMed

    Zhong, Miao; Parish, Bridgette; Murtazina, Dilyara A; Ku, Chun-Ying; Sanborn, Barbara M

    2007-04-01

    Previously, residue K6.30 in the COOH-terminal region of the third intracellular domain (3iC) of the oxytocin (OT) receptor (OTR) was identified as important for receptor function leading to phospholipase C activation in both OTR and the vasopressin V(2) receptor (V(2)R) chimera V(2)ROTR3iC. Substitution of either A6.28K or V6.30K in wild-type V(2)R did not recapitulate the increase in phosphatidylinositide (PI) turnover observed in V(2)ROTR3iC. Hence, the role of K6.30 may be context-specific. Deletion of two NH(2)-terminal OTR3iC segments in the V(2)ROTR3iC chimera did not diminish vasopressin-stimulated PI turnover, whereas deletion of RVSSVKL (residues 6.19-6.25) reduced receptor expression. Deletion of this sequence in wild-type OTR reduced expression by 50% without affecting affinity for [(3)H]OT. This OTR mutant was unable to activate PI turnover or extracellular signal-regulated kinase 1/2 phosphorylation. The effects of alanine substitution for individual residues in RVSSVKL indicated differential importance for OTR function. The R6.19A substitution lost high-affinity sites for [(3)H]OT and the ability to stimulate PI turnover. Affinity for [(3)H]OT and membrane expression was not affected by any other substitutions. OTR-V6.20A and OTR-K6.24A mutants functioned as well as wild-type OTR, whereas OTR S6.21A, S6.22A, and V6.23A mutants exhibited impaired abilities to activate PI turnover (20-40% of OTR), and the OTR-L6.25A mutant exhibited constitutive activity. In conclusion, specific amino acids in the RVSSVKL segment in the COOH-terminal region of the third intracellular domain of OTR influence the ability of OTR to activate G protein-mediated actions.

  7. 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)

  8. Two-dimensional characterization of 3C-SiC layers using scanning internal photoemission microscopy: Mapping of electrical characteristics and crystal quality in domain boundary regions

    NASA Astrophysics Data System (ADS)

    Shiojima, Kenji; Shingo, Masato; Ichikawa, Naoto; Kato, Masashi

    2017-04-01

    3C-SiC layers epitaxially grown on 4H-SiC substrates have been characterized by forming Ni Schottky contacts by scanning internal photoemission microscopy. The sample surface consists of 3C-SiC domains with a flat top. By focusing and scanning a laser beam over the contacts, the domain pattern was clearly visualized in a photoyield map. By combining photoyield maps measured with red and green lasers, we found that the Schottky barrier height is smaller and larger recombination occurs in the boundary regions than in the flat regions.

  9. 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

  10. Application of tungsten as a carbon sink for synthesis of large-domain uniform monolayer graphene free of bilayers/multilayers.

    PubMed

    Fang, Wenjing; Hsu, Allen; Shin, Yong Cheol; Liao, Albert; Huang, Shengxi; Song, Yi; Ling, Xi; Dresselhaus, Mildred S; Palacios, Tomas; Kong, Jing

    2015-03-21

    We have found that tungsten (W) foils can be used for controlling the carbon diffusion within copper (Cu) enclosures to synthesize large-domain bi-/multi-layer-free monolayer graphene via chemical vapor deposition. We have observed that bi-/multi-layer graphene that nucleate underneath the monolayer graphene can be selectively removed by a W foil placed inside of the Cu enclosure. Both X-ray photoelectron spectroscopy and X-ray diffraction reveal the formation of tungsten sub-carbide (W2C), suggesting the role of the W foil as a carbon sink that alters the carbon concentration inside of the enclosure. Consequently, the bi-/multi-layers appear to dissolve. Utilizing this selective removal process, we were able to demonstrate large-domain (>200 μm) monolayer graphene that is free of any bi-/multi-layers by using Cu double enclosures.

  11. Signaling activity of transforming growth factor beta type II receptors lacking specific domains in the cytoplasmic region.

    PubMed Central

    Wieser, R; Attisano, L; Wrana, J L; Massagué, J

    1993-01-01

    The transforming growth factor beta (TGF-beta) type II receptor (T beta R-II) is a transmembrane serine/threonine kinase that contains two inserts in the kinase region and a serine/threonine-rich C-terminal extension. T beta R-II is required for TGF-beta binding to the type I receptor, with which it forms a heteromeric receptor complex, and its kinase activity is required for signaling by this complex. We investigated the role of various cytoplasmic regions in T beta R-II by altering or deleting these regions and determining the signaling activity of the resulting products in cell lines made resistant to TGF-beta by inactivation of the endogenous T beta R-II. TGF-beta binding to receptor I and responsiveness to TGF-beta in these cells can be restored by transfection of wild-type T beta R-II. Using this system, we show that the kinase insert 1 and the C-terminal tail of T beta R-II, in contrast to the corresponding regions in most tyrosine kinase receptors, are not essential to specify ligand-induced responses. Insert 2 is necessary to support the catalytic activity of the receptor kinase, and its deletion yields a receptor that is unable to mediate any of the responses tested. However, substitution of this insert with insert 2 from the activin receptor, ActR-IIB, does not diminish the ability of T beta R-II to elicit these responses. A truncated T beta R-II lacking the cytoplasmic domain still binds TGF-beta, supports ligand binding to receptor I, and forms a complex with this receptor. However, TGF-beta binding to receptor I facilitated by this truncated T beta R-II fails to inhibit cell proliferation, activate extracellular matrix protein production, or activate transcription from a promoter containing TGF-beta-responsive elements. We conclude that the transcriptional and antiproliferative responses to TGF-beta require both components of a heteromeric receptor complex that differs from tyrosine kinase receptors in its mode of signaling. Images PMID:8246946

  12. Spectral-Domain OCT Analysis of Regional Epithelial Thickness Profiles in Keratoconus, Postoperative Corneal Ectasia, and Normal Eyes

    PubMed Central

    Rocha, Karolinne Maia; Straziota, Claudia Perez; Stulting, R. Doyle; Randleman, J. Bradley

    2014-01-01

    PURPOSE To assess corneal microarchitecture and regional epithelial thickness profile in eyes with keratoconus, postoperative corneal ectasia, and normal unoperated eyes using spectral-domain optical coherence tomography (SD OCT). METHODS Regional corneal epithelial thickness profiles of eyes with keratoconus (KC) and postoperative corneal ectasia (Ectasia) were measured with anterior segment SC OCT (Optovue RTVue-100, Optovue Inc., Fremont, CA) and compared retrospectively to those of normal eyes (Control). Epithelial thickness was assessed at 21 points, 0.5 mm apart, across the central 6-mm of the corneal apex in the horizontal and vertical meridians. RESULTS One hundred twenty eyes were evaluated, including 49 eyes from 29 patients with KC, 32 eyes from 16 patients with Ectasia, and 39 eyes from 21 control patients. Average epithelial thickness at the corneal apex was 41.18±6.47μm (range 30 to 51 μm) in eyes with KC, 46.5±6.72μm in eyes with ectasia (range 34 to 60 μm), and 50.45±3.92 μm in normal eyes (range 42 to 55 μm). Apical epithelial thickness was significantly thinner in eyes with KC (p <.0001) and ectasia (p=.0007) than it was in controls. Epithelial thickness ranges in all other areas varied widely for KC (SD, range 21 to 101 μm) and ectasia (SD, range 30 to 82 μm) compared to controls (SD, range 43 to 64), p = .0063 CONCLUSION Central epithelial thickness was, on average, significantly thinner in ectatic corneas compared to controls; however, both central and regional epithelial thickness was highly irregular and variable in corneas with keratoconus and postoperative corneal ectasia. These thickness variations may alter preoperative topographic features and measurements in unpredictable ways, especially steepest K values. Regional epithelial thickness cannot be assumed to be uniform in ectatic corneas and therefore may require direct measurement when considering treatments for which underlying stromal thickness is particularly important

  13. 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.

  14. Current density calculation using rectilinear region splitting algorithm for very large scale integration metal migration analysis

    NASA Astrophysics Data System (ADS)

    Cha, Hungse

    1990-07-01

    In Very Large Scale Integration (VLSI) chips, metal migration (MM) is an important problem from the reliability standpoint. Furthermore, as the feature size is scaled down, MM becomes an even greater problem because of the higher current densities that would exist in the power and ground busses. Because of the complexity of VLSI power busses, there exists a need for a computer-aided design tool to correctly predict the likely failure site(s). A primitive splitting algorithm that calculates current density waveforms efficiently is examined. These waveforms are used to find the Median Time to Failure (MTF), a major parameter of concern in predicting MM. This algorithm was motivated by examining the equipotential plots obtained through finite element method analysis of simple regions. It was successfully implemented and tested, and some examples are described.

  15. 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).

  16. 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.

  17. 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

  18. 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.

  19. Systematics of basidiomycetous yeasts: a comparison of large subunit D1/D2 and internal transcribed spacer rDNA regions.

    PubMed

    Scorzetti, Gloria; Fell, J W; Fonseca, A; Statzell-Tallman, Adele

    2002-12-01

    Basidiomycetous yeasts in the Urediniomycetes and Hymenomycetes were examined by sequence analysis in two ribosomal DNA regions: the D1/D2 variable domains at the 5' end of the large subunit rRNA gene (D1/D2) and the internal transcribed spacers (ITS) 1 and 2. Four major lineages were recognized in each class: Microbotryum, Sporidiobolus, Erythrobasidium and Agaricostilbum in the Urediniomycetes; Tremellales, Trichosporonales, Filobasidiales and Cystofilobasidiales in the Hymenomycetes. Bootstrap support for many of the clades within those lineages is weak; however, phylogenetic analysis provides a focal point for in-depth study of biological relationships. Combined sequence analysis of the D1/D2 and ITS regions is recommended for species identification, while species definition requires classical biological information such as life cycles and phenotypic characterization.

  20. Gain-of-function Mutations Cluster in Distinct Regions Associated with the Signaling Pathway in the PAS Domain of the Aerotaxis Receptor, Aer

    PubMed Central

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

    2010-01-01

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

  1. Ribosomal L1 domain and lysine-rich region are essential for CSIG/ RSL1D1 to regulate proliferation and senescence

    SciTech Connect

    Ma, Liwei; Zhao, Wenting; Zheng, Quanhui; Chen, Tianda; Qi, Ji; Li, Guodong; Tong, Tanjun

    2016-01-15

    The expression change of cellular senescence-associated genes is underlying the genetic foundation of cellular senescence. Using a suppressive subtractive hybridization system, we identified CSIG (cellular senescence-inhibited gene protein; RSL1D1) as a novel senescence-associated gene. CSIG is implicated in various process including cell cycle regulation, apoptosis, and tumor metastasis. We previously showed that CSIG plays an important role in regulating cell proliferation and cellular senescence progression through inhibiting PTEN, however, which domain or region of CSIG contributes to this function? To clarify this question, we investigated the functional importance of ribosomal L1 domain and lysine (Lys) -rich region of CSIG. The data showed that expression of CSIG potently reduced PTEN expression, increased cell proliferation rates, and reduced the senescent phenotype (lower SA-β-gal activity). By contrast, neither the expression of CSIG N- terminal (NT) fragment containing the ribosomal L1 domain nor C-terminal (CT) fragment containing Lys-rich region could significantly altered the levels of PTEN; instead of promoting cell proliferation and delaying cellular senescence, expression of CSIG-NT or CSIG-CT inhibited cell proliferation and accelerated cell senescence (increased SA-β-gal activity) compared to either CSIG over-expressing or control (empty vector transfected) cells. The further immunofluorescence analysis showed that CSIG-CT and CSIG-NT truncated proteins exhibited different subcellular distribution with that of wild-type CSIG. Conclusively, both ribosomal L1 domain and Lys-rich region of CSIG are critical for CSIG to act as a regulator of cell proliferation and cellular senescence. - Highlights: • The ribosomal L1 domain and lysine-rich region of CSIG were expressed. • They are critical for CSIG to regulate proliferation and senescence. • CSIG and its domains exhibit different subcellular distribution.

  2. Distinct Domains within APOBEC3G and APOBEC3F Interact with Separate Regions of Human Immunodeficiency Virus Type 1 Vif▿

    PubMed Central

    Russell, Rebecca A.; Smith, Jessica; Barr, Rebekah; Bhattacharyya, Darshana; Pathak, Vinay K.

    2009-01-01

    Human APOBEC3G (A3G) and APOBEC3F (A3F) inhibit the replication of Vif-deficient human immunodeficiency virus type 1 (HIV-1). HIV-1 Vif overcomes these host restriction factors by binding to them and inducing their degradation. Thus, the Vif-A3G and Vif-A3F interactions are attractive targets for antiviral drug development, as inhibiting these interactions could allow the host defense mechanism to control HIV-1 replication. Recently, it has been reported that amino acids 105 to 156 of A3G are involved in the interaction with Vif; however, to date, the region of A3F involved in Vif binding has not been identified. Using our previously reported Vif mutants that are capable of binding to only A3G (3G binder) or only A3F (3F binder), in conjunction with a series of A3G-A3F chimeras, we have now mapped the APOBEC3-Vif interaction domains. We found that the A3G domain that interacts with the Vif YRHHY region is located between amino acids 126 and 132 of A3G, which is consistent with the conclusions reported in previous studies. The A3F domain that interacts with the Vif DRMR region did not occur in the homologous domain but instead was located between amino acids 283 and 300 of A3F. These studies are the first to identify the A3F domain that interacts with the Vif DRMR region and show that distinct domains of A3G and A3F interact with different Vif regions. Pharmacological inhibition of either or both of these Vif-A3 interactions should prevent the degradation of the APOBEC3 proteins and could be used as a therapy against HIV-1. PMID:19036809

  3. Structure of Bubbles in the South-East region of the Large Magellanic Cloud

    NASA Astrophysics Data System (ADS)

    Oddone, M. A.; Ambrocio-Cruz, P.; LeCoarer, E.; Goldes, G. V.

    2014-10-01

    In this work we report the kinematical results of the structure located in the South-East region of the Large Magellanic Cloud, the Supershell LMC 9. The observations have been carried out in the frame of a Hα survey of the Magellanic Clouds and the Milky Way, carried out at ESO with a 36cm diameter telescope, equipped with a focal reducer, a scanning Fabry-Perot interferometer and a photon counting camera. The Supershell LMC 9 is composed of four giant shells DEM L 164 and DEM L 165, DEM L 208, DEM L 221, and several HII regions being the most notorious DEM L 202, DEM L206 and DEM L 207. By means of energy balance we determine the characteristics parameters of these structures (superficial brightness, electronic density, emission measure, mass, luminosity, ambient density, age), that would allow us to distinguish which is the origin (stellar wind, supernova explosion or other mechanism) of the different bubbles that compose the Supershell LMC 9. In this way we try to discern if the studied objects have kinematically some identity as an ensemble, or if they are relatively isolated objects over the diffuse general background to which they belong.

  4. 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.

  5. Forcing the statistical regionalization method WETTREG with large scale models of different resolution: A sensitivity study

    NASA Astrophysics Data System (ADS)

    Spekat, A.; Baumgart, S.; Kreienkamp, F.; Enke, W.

    2010-09-01

    The statistical regionalization method WETTREG is making use of the assumption that future climate changes are linked to changes in large scale atmospheric patterns. The frequency distributions of those patterns and their time-dependency are identified in the output fields of dynamical climate models and applied to force WETTREG. Thus, the magnitude and the time evolution of high-resolution climate signals for time horizons far into the 21st century can be computed. The model results employed to force WETTREG include the GCMS ECHAM5C, HadCM3C and CNRM. Additionally results from the dynamical regional models CLM, DMI, HadRM, RACMO and REMO, nested into one or more of these global models, are used in their pattern-generating capacity to force WETTREG. The study yield insight concerning the forcing-dependent sensitivity of WETTREG as well as the bandwidth of climate change signals. Recent results for the German State of Hesse will be presented in an intercomparison study.

  6. 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.

  7. 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.

  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

    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

  9. 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

  10. 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.

  11. THE GOULD’S BELT VERY LARGE ARRAY SURVEY. V. THE PERSEUS REGION

    SciTech Connect

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

    2016-02-20

    We present multiepoch, large-scale (∼2000 arcmin{sup 2}), fairly deep (∼16 μJy), high-resolution (∼1″) radio observations of the Perseus star-forming complex obtained with the Karl G. Jansky Very Large Array at frequencies of 4.5 and 7.5 GHz. These observations were mainly focused on the clouds NGC 1333 and IC 348, although we also observed several fields in other parts of the Perseus complex. We detect a total of 206 sources, 42 of which are associated with young stellar objects (YSOs). The radio properties of about 60% of the YSOs are compatible with a nonthermal radio emission origin. Based on our sample, we find a fairly clear relation between the prevalence of nonthermal radio emission and evolutionary status of the YSOs. By comparing our results with previously reported X-ray observations, we show that YSOs in Perseus follow a Güdel–Benz relation with κ = 0.03, consistent with other regions of star formation. We argue that most of the sources detected in our observations but not associated with known YSOs are extragalactic, but provide a list of 20 unidentified radio sources whose radio properties are consistent with being YSO candidates. Finally, we also detect five sources with extended emission features that can clearly be associated with radio galaxies.

  12. The high luminosity interaction region for a ring-ring Large Hadron Electron Collider

    NASA Astrophysics Data System (ADS)

    Appleby, R. B.; Thompson, L.; Holzer, B.; Fitterer, M.; Bernard, N.; Kostka, P.

    2013-12-01

    The Large Hadron Electron Collider (LHeC) project is a proposal for high luminosity TeV-scale electron-proton (ep) collisions at the LHC. The LHeC Conceptual Design Report presented an early overview of the machine, including an electron linac solution and a solution involving a 60 GeV electron storage ring. Here we present a new complete solution for the collision insertion of this electron ring, incorporating all constraints including those imposed by the LHC and, for the first time, proving the feasibility of ep collisions at a luminosity of ˜1033 cm-2s-1 in the LHC era. The solution presented offers high luminosity while maintaining the large detector coverage required by the particle physics programme. This negates the earlier need for two separate interaction region designs, one optimized for high luminosity at the cost of detector coverage, and the other for lower luminosity but higher coverage. Synchrotron radiation emission is also a major factor in electron accelerator design, and studies are presented showing the feasibil