Two optical bistability domains in composites of metal nanoparticles with nonlinear dielectric core

Energy Technology Data Exchange (ETDEWEB)

Shewamare, Sisay, E-mail: sisayshewa20@yahoo.com [Department of Physics, Addis Ababa University, P.O. Box 1176, Addis Ababa (Ethiopia); Mal' nev, V.N., E-mail: vadimnmalnev@yahoo.com [Department of Physics, Addis Ababa University, P.O. Box 1176, Addis Ababa (Ethiopia)

2012-12-15

It is shown that the local field in metal spherical particles with a dielectric core in an external varying electric field has two maxima at two different frequencies. The second maximum becomes more important with an increment in the metal fraction. Due to the nonlinear dielectric function of the core, the composite of these inclusions may have two optically induced bistability domains at different frequencies. At rather high metal fraction, two bistability domains merge and form one entire bistability domain. The parameters of these domains are studied numerically. The paper focuses on the second bistability domain, which has not been discussed in the literature so far. This domain exists in a comparatively narrow frequency range and its onset fields are lower than those of the first bistability domain. The lowest bistability onset fields are obtained in the entire domain. This peculiarity of the optical induced bistability in the metal composite with small dielectric cores can be attractive for possible applications.

Two optical bistability domains in composites of metal nanoparticles with nonlinear dielectric core

International Nuclear Information System (INIS)

Shewamare, Sisay; Mal'nev, V.N.

2012-01-01

It is shown that the local field in metal spherical particles with a dielectric core in an external varying electric field has two maxima at two different frequencies. The second maximum becomes more important with an increment in the metal fraction. Due to the nonlinear dielectric function of the core, the composite of these inclusions may have two optically induced bistability domains at different frequencies. At rather high metal fraction, two bistability domains merge and form one entire bistability domain. The parameters of these domains are studied numerically. The paper focuses on the second bistability domain, which has not been discussed in the literature so far. This domain exists in a comparatively narrow frequency range and its onset fields are lower than those of the first bistability domain. The lowest bistability onset fields are obtained in the entire domain. This peculiarity of the optical induced bistability in the metal composite with small dielectric cores can be attractive for possible applications.

The Three-Dimensional Solution Structure of the Src Homology Domain-2 of the Growth Factor Receptor-Bound Protein-2

International Nuclear Information System (INIS)

Senior, Mary M.; Frederick, Anne F.; Black, Stuart; Murgolo, Nicholas J.; Perkins, Louise M.; Wilson, Oswald; Snow, Mark E.; Wang Yusen

1998-01-01

A set of high-resolution three-dimensional solution structures of the Src homology region-2 (SH2) domain of the growth factor receptor-bound protein-2 was determined using heteronuclear NMR spectroscopy. The NMR data used in this study were collected on a stable monomeric protein solution that was free of protein aggregates and proteolysis. The solution structure was determined based upon a total of 1439 constraints, which included 1326 nuclear Overhauser effect distance constraints, 70 hydrogen bond constraints, and 43 dihedral angle constraints. Distance geometry-simulated annealing calculations followed by energy minimization yielded a family of 18 structures that converged to a root-mean-square deviation of 1.09 A for all backbone atoms and 0.40 A for the backbone atoms of the central β-sheet. The core structure of the SH2 domain contains an antiparallel β-sheet flanked by two parallel α-helices displaying an overall architecture that is similar to other known SH2 domain structures. This family of NMR structures is compared to the X-ray structure and to another family of NMR solution structures determined under different solution conditions

A Preliminary Core Domain Set for Clinical Trials of Shoulder Disorders: A Report from the OMERACT 2016 Shoulder Core Outcome Set Special Interest Group.

Science.gov (United States)

Buchbinder, Rachelle; Page, Matthew J; Huang, Hsiaomin; Verhagen, Arianne P; Beaton, Dorcas; Kopkow, Christian; Lenza, Mario; Jain, Nitin B; Richards, Bethan; Richards, Pamela; Voshaar, Marieke; van der Windt, Danielle; Gagnier, Joel J

2017-12-01

The Outcome Measures in Rheumatology (OMERACT) Shoulder Core Outcome Set Special Interest Group (SIG) was established to develop a core outcome set (COS) for clinical trials of shoulder disorders. In preparation for OMERACT 2016, we systematically examined all outcome domains and measurement instruments reported in 409 randomized trials of interventions for shoulder disorders published between 1954 and 2015. Informed by these data, we conducted an international Delphi consensus study including shoulder trial experts, clinicians, and patients to identify key domains that should be included in a shoulder disorder COS. Findings were discussed at a stakeholder premeeting of OMERACT. At OMERACT 2016, we sought consensus on a preliminary core domain set and input into next steps. There were 13 and 15 participants at the premeeting and the OMERACT 2016 SIG meeting, respectively (9 attended both meetings). Consensus was reached on a preliminary core domain set consisting of an inner core of 4 domains: pain, physical function/activity, global perceived effect, and adverse events including death. A middle core consisted of 3 domains: emotional well-being, sleep, and participation (recreation and work). An outer core of research required to inform the final COS was also formulated. Our next steps are to (1) analyze whether participation (recreation and work) should be in the inner core, (2) conduct a third Delphi round to finalize definitions and wording of domains and reach final endorsement for the domains, and (3) determine which instruments fulfill the OMERACT criteria for measuring each domain.

Generalized Robin Boundary Conditions, Robin-to-Dirichlet Maps, and Krein-Type Resolvent Formulas for Schr\\"odinger Operators on Bounded Lipschitz Domains

OpenAIRE

Gesztesy, Fritz; Mitrea, Marius

2008-01-01

We study generalized Robin boundary conditions, Robin-to-Dirichlet maps, and Krein-type resolvent formulas for Schr\\"odinger operators on bounded Lipschitz domains in $\\bbR^n$, $n\\ge 2$. We also discuss the case of bounded $C^{1,r}$-domains, $(1/2)

Core outcome domains for clinical trials in non-specific low back pain.

Science.gov (United States)

Chiarotto, Alessandro; Deyo, Richard A; Terwee, Caroline B; Boers, Maarten; Buchbinder, Rachelle; Corbin, Terry P; Costa, Leonardo O P; Foster, Nadine E; Grotle, Margreth; Koes, Bart W; Kovacs, Francisco M; Lin, Chung-Wei Christine; Maher, Chris G; Pearson, Adam M; Peul, Wilco C; Schoene, Mark L; Turk, Dennis C; van Tulder, Maurits W; Ostelo, Raymond W

2015-06-01

Inconsistent reporting of outcomes in clinical trials of patients with non-specific low back pain (NSLBP) hinders comparison of findings and the reliability of systematic reviews. A core outcome set (COS) can address this issue as it defines a minimum set of outcomes that should be reported in all clinical trials. In 1998, Deyo et al. recommended a standardized set of outcomes for LBP clinical research. The aim of this study was to update these recommendations by determining which outcome domains should be included in a COS for clinical trials in NSLBP. An International Steering Committee established the methodology to develop this COS. The OMERACT Filter 2.0 framework was used to draw a list of potential core domains that were presented in a Delphi study. Researchers, care providers and patients were invited to participate in three Delphi rounds and were asked to judge which domains were core. A priori criteria for consensus were established before each round and were analysed together with arguments provided by panellists on importance, overlap, aggregation and/or addition of potential core domains. The Steering Committee discussed the final results and made final decisions. A set of 280 experts was invited to participate in the Delphi; response rates in the three rounds were 52, 50 and 45%. Of 41 potential core domains presented in the first round, 13 had sufficient support to be presented for rating in the third round. Overall consensus was reached for the inclusion of three domains in this COS: 'physical functioning', 'pain intensity' and 'health-related quality of life'. Consensus on 'physical functioning' and 'pain intensity' was consistent across all stakeholders, 'health-related quality of life' was not supported by the patients, and all the other domains were not supported by two or more groups of stakeholders. Weighting all possible argumentations, the Steering Committee decided to include in the COS the three domains that reached overall consensus and

Continuous and Lp estimates for the complex Monge-Ampère equation on bounded domains in ℂn

Directory of Open Access Journals (Sweden)

Patrick W. Darko

2002-01-01

Full Text Available Continuous solutions with continuous data and Lp solutions with Lp data are obtained for the complex Monge-Ampère equation on bounded domains, without requiring any smoothness of the domains.

Upper-bound fission product release assessment for large break LOCA in CANFLEX bundle reactor core

International Nuclear Information System (INIS)

Oh, Duk Ju; Lee, Kang Moon

1996-07-01

Quarter-core gap inventory assessment for CANDU-6 reactor core loaded with CANFLEX fuel bundles has been performed as one of the licensing safety analyses required for 24 natural uranium CANFLEX bundle irradiation in CANDU-6 reactor. The quarter-core gap inventory for the CANFLEX bundle core is 5 - 10 times lower than that for the standard bundle core, depending on the half-life of the isotope. The lower gap inventory of the CANFLEX bundle core is attributed to the lower linear power of the CANFLEX bundle compared with the standard bundle. However, the whole core total inventories for both the CANFLEX and standard bundle cores are nearly the same. The 6 - 8 times lower upper-bound fission product releases of the CANFLEX bundle core for large break LOCA than those of the standard bundle core imply that the loading of 24 natural uranium CANFLEX bundles would improve the predicted consequences of the postulated accident described in the Wolsung 2 safety report. 2 tabs., 6 figs., 3 refs. (Author)

On the solvability of the compressible Navier–Stokes system in bounded domains

International Nuclear Information System (INIS)

Danchin, Raphaël

2010-01-01

This paper is dedicated to the well-posedness issue for the barotropic Navier–Stokes system with homogeneous Dirichlet boundary conditions in bounded domains of R N . We aim at considering data in as large a class as possible. Our main result is that if the initial density is bounded away from zero and belongs to some W 1,r with r > N, if the initial velocity is in the Besov space B 2-(2/p) r,p (and satisfies a suitable boundary condition), and if the body force is in L p loc (R + ;L r ) for some p > 1 then the system has a unique local solution. Our regularity assumptions are consistent with a dimensional analysis which shows that critical data would correspond to r = N and p = 1, and improve an old result by Solonnikov (1980 J. Sov. Math. 14 1120–32)

Electric Dipole Antennas With Magnetic-Coated PEC Cores: Reaching the Chu Lower Bound on Q

DEFF Research Database (Denmark)

Kim, Oleksiy S.

2012-01-01

The radiation properties of spherical electric dipole antennas with electric current excitation and material-coated perfectly electrically conducting (PEC) cores are investigated analytically using vector spherical wave functions. Closed-form expressions for electric and magnetic stored energy...... as well as the radiation quality factor $Q$ are derived. Using these, it is shown that properly selected magnetic coating and radius of the PEC core vastly reduce the internal stored energy, and thus make the $Q$ of an electric dipole antenna approach the Chu lower bound....

Facile synthesis and electrochemiluminescence application of concave trisoctahedral Pd@Au core-shell nanocrystals bound by {331} high-index facets.

Science.gov (United States)

Zhang, Ling; Niu, Wenxin; Li, Zhiyuan; Xu, Guobao

2011-10-07

Concave trisoctahedral (TOH) Pd@Au core-shell nanocrystals bound by {331} facets have been synthesized for the first time. Pd nanocubes and cetyltrimethylammonium chloride were used as the structure-directing cores and capping agents, respectively. Their optical and electrocatalytic properties were investigated. This journal is © The Royal Society of Chemistry 2011

Structural insights into calcium-bound S100P and the V domain of the RAGE complex.

Directory of Open Access Journals (Sweden)

Srinivasa R Penumutchu

Full Text Available The S100P protein is a member of the S100 family of calcium-binding proteins and possesses both intracellular and extracellular functions. Extracellular S100P binds to the cell surface receptor for advanced glycation end products (RAGE and activates its downstream signaling cascade to meditate tumor growth, drug resistance and metastasis. Preventing the formation of this S100P-RAGE complex is an effective strategy to treat various disease conditions. Despite its importance, the detailed structural characterization of the S100P-RAGE complex has not yet been reported. In this study, we report that S100P preferentially binds to the V domain of RAGE. Furthermore, we characterized the interactions between the RAGE V domain and Ca(2+-bound S100P using various biophysical techniques, including isothermal titration calorimetry (ITC, fluorescence spectroscopy, multidimensional NMR spectroscopy, functional assays and site-directed mutagenesis. The entropy-driven binding between the V domain of RAGE and Ca(+2-bound S100P was found to lie in the micromolar range (Kd of ∼ 6 µM. NMR data-driven HADDOCK modeling revealed the putative sites that interact to yield a proposed heterotetrameric model of the S100P-RAGE V domain complex. Our study on the spatial structural information of the proposed protein-protein complex has pharmaceutical relevance and will significantly contribute toward drug development for the prevention of RAGE-related multifarious diseases.

Properties of Sub-Wavelength Spherical Antennas With Arbitrarily Lossy Magnetodielectric Cores Approaching the Chu Lower Bound

DEFF Research Database (Denmark)

Hansen, Troels Vejle; Kim, Oleksiy S.; Breinbjerg, Olav

2014-01-01

For a spherical antenna exciting any arbitrary spherical mode, we derive exact closed-form expressions for the dissipated power and stored energy inside (and outside) the lossy magneto-dielectric spherical core, as well as the radiated power, radiation efficiency, and thus the radiation quality...... an increasing magnetic loss tangent initially leads to a decreasing radiation quality factor, but in the limit of a perfect magnetic conductor (PMC) core the dissipated power tends to zero and the radiation quality factor reaches the fundamental Chu lower bound....

Structure of the exon junction core complex with a trapped DEAD-box ATPase bound to RNA

DEFF Research Database (Denmark)

Andersen, Christian Brix Folsted; Ballut, Lionel; Johansen, Jesper Sanderhoff

2006-01-01

exon junction core complex containing the DEAD-box adenosine triphosphatase (ATPase) eukaryotic initiation factor 4AIII (eIF4AIII) bound to an ATP analog, MAGOH, Y14, a fragment of MLN51, and a polyuracil mRNA mimic. eIF4AIII interacts with the phosphate-ribose backbone of six consecutive nucleotides...... and prevents part of the bound RNA from being double stranded. The MAGOH and Y14 subunits lock eIF4AIII in a prehydrolysis state, and activation of the ATPase probably requires only modest conformational changes in eIF4AIII motif I....

Domain Decomposition strategy for pin-wise full-core Monte Carlo depletion calculation with the reactor Monte Carlo Code

Energy Technology Data Exchange (ETDEWEB)

Liang, Jingang; Wang, Kan; Qiu, Yishu [Dept. of Engineering Physics, LiuQing Building, Tsinghua University, Beijing (China); Chai, Xiao Ming; Qiang, Sheng Long [Science and Technology on Reactor System Design Technology Laboratory, Nuclear Power Institute of China, Chengdu (China)

2016-06-15

Because of prohibitive data storage requirements in large-scale simulations, the memory problem is an obstacle for Monte Carlo (MC) codes in accomplishing pin-wise three-dimensional (3D) full-core calculations, particularly for whole-core depletion analyses. Various kinds of data are evaluated and quantificational total memory requirements are analyzed based on the Reactor Monte Carlo (RMC) code, showing that tally data, material data, and isotope densities in depletion are three major parts of memory storage. The domain decomposition method is investigated as a means of saving memory, by dividing spatial geometry into domains that are simulated separately by parallel processors. For the validity of particle tracking during transport simulations, particles need to be communicated between domains. In consideration of efficiency, an asynchronous particle communication algorithm is designed and implemented. Furthermore, we couple the domain decomposition method with MC burnup process, under a strategy of utilizing consistent domain partition in both transport and depletion modules. A numerical test of 3D full-core burnup calculations is carried out, indicating that the RMC code, with the domain decomposition method, is capable of pin-wise full-core burnup calculations with millions of depletion regions.

Super-Grid Modeling of the Elastic Wave Equation in Semi-Bounded Domains

Energy Technology Data Exchange (ETDEWEB)

Petersson, N. Anders; Sjögreen, Björn

2014-10-01

We develop a super-grid modeling technique for solving the elastic wave equation in semi-bounded two- and three-dimensional spatial domains. In this method, waves are slowed down and dissipated in sponge layers near the far-field boundaries. Mathematically, this is equivalent to a coordinate mapping that transforms a very large physical domain to a significantly smaller computational domain, where the elastic wave equation is solved numerically on a regular grid. To damp out waves that become poorly resolved because of the coordinate mapping, a high order artificial dissipation operator is added in layers near the boundaries of the computational domain. We prove by energy estimates that the super-grid modeling leads to a stable numerical method with decreasing energy, which is valid for heterogeneous material properties and a free surface boundary condition on one side of the domain. Our spatial discretization is based on a fourth order accurate finite difference method, which satisfies the principle of summation by parts. We show that the discrete energy estimate holds also when a centered finite difference stencil is combined with homogeneous Dirichlet conditions at several ghost points outside of the far-field boundaries. Therefore, the coefficients in the finite difference stencils need only be boundary modified near the free surface. This allows for improved computational efficiency and significant simplifications of the implementation of the proposed method in multi-dimensional domains. Numerical experiments in three space dimensions show that the modeling error from truncating the domain can be made very small by choosing a sufficiently wide super-grid damping layer. The numerical accuracy is first evaluated against analytical solutions of Lamb’s problem, where fourth order accuracy is observed with a sixth order artificial dissipation. We then use successive grid refinements to study the numerical accuracy in the more

Updating the Psoriatic Arthritis (PsA) Core Domain Set: A Report from the PsA Workshop at OMERACT 2016.

Science.gov (United States)

Orbai, Ana-Maria; de Wit, Maarten; Mease, Philip J; Callis Duffin, Kristina; Elmamoun, Musaab; Tillett, William; Campbell, Willemina; FitzGerald, Oliver; Gladman, Dafna D; Goel, Niti; Gossec, Laure; Hoejgaard, Pil; Leung, Ying Ying; Lindsay, Chris; Strand, Vibeke; van der Heijde, Désirée M; Shea, Bev; Christensen, Robin; Coates, Laura; Eder, Lihi; McHugh, Neil; Kalyoncu, Umut; Steinkoenig, Ingrid; Ogdie, Alexis

2017-10-01

To include the patient perspective in accordance with the Outcome Measures in Rheumatology (OMERACT) Filter 2.0 in the updated Psoriatic Arthritis (PsA) Core Domain Set for randomized controlled trials (RCT) and longitudinal observational studies (LOS). At OMERACT 2016, research conducted to update the PsA Core Domain Set was presented and discussed in breakout groups. The updated PsA Core Domain Set was voted on and endorsed by OMERACT participants. We conducted a systematic literature review of domains measured in PsA RCT and LOS, and identified 24 domains. We conducted 24 focus groups with 130 patients from 7 countries representing 5 continents to identify patient domains. We achieved consensus through 2 rounds of separate surveys with 50 patients and 75 physicians, and a nominal group technique meeting with 12 patients and 12 physicians. We conducted a workshop and breakout groups at OMERACT 2016 in which findings were presented and discussed. The updated PsA Core Domain Set endorsed with 90% agreement by OMERACT 2016 participants included musculoskeletal disease activity, skin disease activity, fatigue, pain, patient's global assessment, physical function, health-related quality of life, and systemic inflammation, which were recommended for all RCT and LOS. These were important, but not required in all RCT and LOS: economic cost, emotional well-being, participation, and structural damage. Independence, sleep, stiffness, and treatment burden were on the research agenda. The updated PsA Core Domain Set was endorsed at OMERACT 2016. Next steps for the PsA working group include evaluation of PsA outcome measures and development of a PsA Core Outcome Measurement Set.

Rift Valley fever phlebovirus NSs protein core domain structure suggests molecular basis for nuclear filaments.

Science.gov (United States)

Barski, Michal; Brennan, Benjamin; Miller, Ona K; Potter, Jane A; Vijayakrishnan, Swetha; Bhella, David; Naismith, James H; Elliott, Richard M; Schwarz-Linek, Ulrich

2017-09-15

Rift Valley fever phlebovirus (RVFV) is a clinically and economically important pathogen increasingly likely to cause widespread epidemics. RVFV virulence depends on the interferon antagonist non-structural protein (NSs), which remains poorly characterized. We identified a stable core domain of RVFV NSs (residues 83-248), and solved its crystal structure, a novel all-helical fold organized into highly ordered fibrils. A hallmark of RVFV pathology is NSs filament formation in infected cell nuclei. Recombinant virus encoding the NSs core domain induced intranuclear filaments, suggesting it contains all essential determinants for nuclear translocation and filament formation. Mutations of key crystal fibril interface residues in viruses encoding full-length NSs completely abrogated intranuclear filament formation in infected cells. We propose the fibrillar arrangement of the NSs core domain in crystals reveals the molecular basis of assembly of this key virulence factor in cell nuclei. Our findings have important implications for fundamental understanding of RVFV virulence.

Mutual friction in superfluid 3He: Effects of bound states in the vortex core

International Nuclear Information System (INIS)

Kopnin, N.B.; Salomaa, M.M.

1991-01-01

The motion of singular quantized vortex lines in superfluid 3 He is considered for the A and B phases. Mutual friction is calculated within a microscopic quantum-mechanical Green's-function formalism, valid for dynamical processes. This enables us to include all the different physical phenomena in a unified approach. We consider axisymmetric vortices for temperatures considerably lower than T c . In this regime, the main contribution to the force exerted on a moving vortex originates from the localized Fermi excitations occupying quantized energy eigenstates in the vortex core. These 3 He quasiparticle states are similar to the quantized motion of charge in a magnetic field; thus vortex motion in 3 He resembles the Hall phenomenon in metals. The outcome is that the viscous drag cannot simply be expressed through the cross sections for 3 He quasiparticles scattering off the vortex, but is rather due to the mutual interactions between the localized quasiparticles and the normal excitations. Our calculations conform with the experimental values for the mutual-friction parameters. We also discuss vortex oscillations, and predict that strong dissipation should be observed at a resonant frequency of about 10 kHz, owing to transitions between the bound-state energy levels. This effect could be used for detecting and measuring the quantization of the bound-state spectrum for superfluid 3 He in the vortex-core matter

DNA binding and unwinding by Hel308 helicase requires dual functions of a winged helix domain.

Science.gov (United States)

Northall, Sarah J; Buckley, Ryan; Jones, Nathan; Penedo, J Carlos; Soultanas, Panos; Bolt, Edward L

2017-09-01

Hel308 helicases promote genome stability linked to DNA replication in archaea, and have homologues in metazoans. In the crystal structure of archaeal Hel308 bound to a tailed DNA duplex, core helicase domains encircle single-stranded DNA (ssDNA) in a "ratchet" for directional translocation. A winged helix domain (WHD) is also present, but its function is mysterious. We investigated the WHD in full-length Hel308, identifying that mutations in a solvent exposed α-helix resulted in reduced DNA binding and unwinding activities. When isolated from the rest of Hel308, the WHD protein alone bound to duplex DNA but not ssDNA, and DNA binding by WHD protein was abolished by the same mutations as were analyzed in full-length Hel308. Isolated WHD from a human Hel308 homologue (HelQ) also bound to duplex DNA. By disrupting the interface between the Hel308 WHD and a RecA-like domain, a topology typical of Ski2 helicases, we show that this is crucial for ATPase and helicase activities. The data suggest a model in which the WHD promotes activity of Hel308 directly, through binding to duplex DNA that is distinct from ssDNA binding by core helicase, and indirectly through interaction with the RecA-like domain. We propose how the WHD may contribute to ssDNA translocation, resulting in DNA helicase activity or in removal of other DNA bound proteins by "reeling" ssDNA. Copyright © 2017 Elsevier B.V. All rights reserved.

Crystal Structure of the Dimeric Oct6 (Pou3fl) POU Domain Bound to Palindromic MORE DNA

Energy Technology Data Exchange (ETDEWEB)

R Jauch; S Choo; C Ng; P Kolatkar

2011-12-31

POU domains (named after their identification in Pit1, Oct1 unc86) are found in around 15 transcription factors encoded in mammalian genomes many of which feature prominently as key regulators at development bifurcations. For example, the POU III class Octamer binding protein 6 (Oct6) is expressed in embryonic stem cells and during neural development and drives the differentia5tion of myelinated cells in the central and peripheral nervous system. Defects in oct6 expression levels are linked to neurological disorders such as schizophrenia. POU proteins contain a bi-partite DNA binding domain that assembles on various DNA motifs with differentially configured subdomains. Intriguingly, alternative configurations of POU domains on different DNA sites were shown to affect the subsequent recruitment of transcriptional coactivators. Namely, binding of Oct1 to a Palindromic Oct-factor Recognition Element (PORE) was shown to facilitate the recruitment of the OBF1 coactivator whereas More of PORE (MORE) bound Oct1 does not. Moreover, Pit1 was shown to recruit the corepressor N-CoR only when bound to a variant MORE motif with a 2 bp half-site spacing. Therefore, POU proteins are seen as a paradigm for DNA induced allosteric effects on transcription factors modulating their regulatory potential. However, a big unresolved conundrum for the POU class and for most if not all other transcription factor classes is how highly similar proteins regulate different sets of genes causing fundamentally different biological responses. Ultimately, there must be subtle features enabling those factors to engage in contrasting molecular interactions in the cell. Thus, the dissection of the molecular details of the transcription-DNA recognition in general, and the formation of multimeric regulatory complexes, in particular, is highly desirable. To contribute to these efforts they solved the 2.05 {angstrom} crystal structure of Oct6 bound as a symmetrical homodimer to palindromic MORE DNA.

Fast conformational exchange between the sulfur-free and persulfide-bound rhodanese domain of E. coli YgaP

Energy Technology Data Exchange (ETDEWEB)

Wang, Wei [Hefei National Laboratory for Physical Sciences at the Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026 (China); Zhou, Peng [High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei, Anhui 230031 (China); He, Yao; Yu, Lu; Xiong, Ying [Hefei National Laboratory for Physical Sciences at the Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026 (China); Tian, Changlin, E-mail: cltian@ustc.edu.cn [Hefei National Laboratory for Physical Sciences at the Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026 (China); High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei, Anhui 230031 (China); Wu, Fangming, E-mail: fmwu@hmfl.ac.cn [High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei, Anhui 230031 (China)

2014-09-26

Highlights: • Three dimensional solution NMR structure of YgaP rhodanese domain. • Function validation of YgaP rhodanese domain to substrate Na{sub 2}S{sub 2}O{sub 3}. • Fast exchange between the intact and persulfide-intermediate rhodanese domain. - Abstract: Rhodanese domains are abundant structural modules that catalyze the transfer of a sulfur atom from thiolsulfates to cyanide via formation of a covalent persulfide intermediate that is bound to an essential conserved cysteine residue. In this study, the three-dimensional structure of the rhodanese domain of YgaP from Escherichia coli was determined using solution NMR. A typical rhodanese domain fold was observed, as expected from the high homology with the catalytic domain of other sulfur transferases. The initial sulfur-transfer step and formation of the rhodanese persulfide intermediate were monitored by addition of sodium thiosulfate using two-dimensional {sup 1}H–{sup 15}N correlation spectroscopy. Discrete sharp signals were observed upon substrate addition, indicting fast exchange between sulfur-free and persulfide-intermediate forms. Residues exhibiting pronounced chemical shift changes were mapped to the structure, and included both substrate binding and surrounding residues.

The core domain as the force sensor of the yeast mechanosensitive TRP channel.

Science.gov (United States)

Su, Zhenwei; Anishkin, Andriy; Kung, Ching; Saimi, Yoshiro

2011-12-01

Stretch-activated conductances are commonly encountered in careful electric recordings. Those of known proteins (TRP, MscL, MscS, K(2p), Kv, etc.) all share a core, which houses the ion pathway and the gate, but no recognizable force-sensing domain. Like animal TRPs, the yeast TRPY1 is polymodal, activated by stretch force, Ca(2+), etc. To test whether its S5-S6 core senses the stretch force, we tried to uncouple it from the peripheral domains by strategic peptide insertions to block the covalent core-periphery interactions. Insertion of long unstructured peptides should distort, if not disrupt, protein structures that transmit force. Such insertions between S6 and the C-terminal tail largely removed Ca(2+) activation, showing their effectiveness. However, such insertions as well as those between S5 and the N-terminal region, which includes S1-S4, did not significantly alter mechanosensitivity. Even insertions at both locations flanking the S5-S6 core did not much alter mechanosensitivity. Tryptophan scanning mutations in S5 were also constructed to perturb possible noncovalent core-periphery contacts. The testable tryptophan mutations also have little or no effects on mechanosensitivity. Boltzmann fits of the wild-type force-response curves agree with a structural homology model for a stretch-induced core expansion of ~2 nm(2) upon opening. We hypothesize that membrane tension pulls on S5-S6, expanding the core and opening the TRPY1 gate. The core being the major force sensor offers the simplest, though not the only, explanation of why so many channels of disparate designs are mechanically sensitive. Compared with the bacterial MscL, TRPY1 is much less sensitive to force, befitting a polymodal channel that relies on multiple stimuli.

Identification of preliminary core outcome domains for communication about childhood vaccination: An online Delphi survey.

Science.gov (United States)

Kaufman, Jessica; Ryan, Rebecca; Lewin, Simon; Bosch-Capblanch, Xavier; Glenton, Claire; Cliff, Julie; Oyo-Ita, Angela; Muloliwa, Artur Manuel; Oku, Afiong; Ames, Heather; Rada, Gabriel; Cartier, Yuri; Hill, Sophie

2017-08-20

Communication interventions for childhood vaccination are promising strategies to address vaccine hesitancy, but current research is limited by the outcomes measured. Most studies measure only vaccination-related outcomes, with minimal consideration of vaccine hesitancy-relevant intermediate outcomes. This impedes understanding of which interventions or elements are effective. It is also unknown which outcomes are important to the range of stakeholders affected by vaccine hesitancy. Outcome selection shapes the evidence base, informing future interventions and trials, and should reflect stakeholder priorities. Therefore, our aim was to identify which outcome domains (i.e. broad outcome categories) are most important to different stakeholders, identifying preliminary core outcome domains to inform evaluation of three common vaccination communication types: (i) communication to inform or educate, (ii) remind or recall, and (iii) enhance community ownership. We conducted a two-stage online Delphi survey, involving four stakeholder groups: parents or community members, healthcare providers, researchers, and government or non-governmental organisation representatives. Participants rated the importance of eight outcome domains for each of the three communication types. They also rated specific outcomes within one domain ("attitudes or beliefs") and provided feedback about the survey. Collectively, stakeholder groups prioritised outcome domains differently when considering the effects of different communication types. For communication that aims to (i) inform or educate, the most important outcome domain is "knowledge or understanding"; for (ii) reminder communication, "vaccination status and behaviours"; and for (iii) community engagement communication, "community participation". All stakeholder groups rated most outcome domains as very important or critical. The highest rated specific outcome within the "attitudes or beliefs" domain was "trust". This Delphi survey

Membrane docking geometry of GRP1 PH domain bound to a target lipid bilayer: an EPR site-directed spin-labeling and relaxation study.

Directory of Open Access Journals (Sweden)

Huai-Chun Chen

Full Text Available The second messenger lipid PIP(3 (phosphatidylinositol-3,4,5-trisphosphate is generated by the lipid kinase PI3K (phosphoinositide-3-kinase in the inner leaflet of the plasma membrane, where it regulates a broad array of cell processes by recruiting multiple signaling proteins containing PIP(3-specific pleckstrin homology (PH domains to the membrane surface. Despite the broad importance of PIP(3-specific PH domains, the membrane docking geometry of a PH domain bound to its target PIP(3 lipid on a bilayer surface has not yet been experimentally determined. The present study employs EPR site-directed spin labeling and relaxation methods to elucidate the membrane docking geometry of GRP1 PH domain bound to bilayer-embedded PIP(3. The model target bilayer contains the neutral background lipid PC and both essential targeting lipids: (i PIP(3 target lipid that provides specificity and affinity, and (ii PS facilitator lipid that enhances the PIP(3 on-rate via an electrostatic search mechanism. The EPR approach measures membrane depth parameters for 18 function-retaining spin labels coupled to the PH domain, and for calibration spin labels coupled to phospholipids. The resulting depth parameters, together with the known high resolution structure of the co-complex between GRP1 PH domain and the PIP(3 headgroup, provide sufficient constraints to define an optimized, self-consistent membrane docking geometry. In this optimized geometry the PH domain engulfs the PIP(3 headgroup with minimal bilayer penetration, yielding the shallowest membrane position yet described for a lipid binding domain. This binding interaction displaces the PIP(3 headgroup from its lowest energy position and orientation in the bilayer, but the headgroup remains within its energetically accessible depth and angular ranges. Finally, the optimized docking geometry explains previous biophysical findings including mutations observed to disrupt membrane binding, and the rapid lateral

The Laplace equation boundary value problems on bounded and unbounded Lipschitz domains

CERN Document Server

Medková, Dagmar

2018-01-01

This book is devoted to boundary value problems of the Laplace equation on bounded and unbounded Lipschitz domains. It studies the Dirichlet problem, the Neumann problem, the Robin problem, the derivative oblique problem, the transmission problem, the skip problem and mixed problems. It also examines different solutions - classical, in Sobolev spaces, in Besov spaces, in homogeneous Sobolev spaces and in the sense of non-tangential limit. It also explains relations between different solutions. The book has been written in a way that makes it as readable as possible for a wide mathematical audience, and includes all the fundamental definitions and propositions from other fields of mathematics. This book is of interest to research students, as well as experts in partial differential equations and numerical analysis.

Accumulating Data to Optimally Predict Obesity Treatment (ADOPT) Core Measures: Behavioral Domain.

Science.gov (United States)

Lytle, Leslie A; Nicastro, Holly L; Roberts, Susan B; Evans, Mary; Jakicic, John M; Laposky, Aaron D; Loria, Catherine M

2018-04-01

The ability to identify and measure behaviors that are related to weight loss and the prevention of weight regain is crucial to understanding the variability in response to obesity treatment and the development of tailored treatments. The overarching goal of the Accumulating Data to Optimally Predict obesity Treatment (ADOPT) Core Measures Project is to provide obesity researchers with guidance on a set of constructs and measures that are related to weight control and that span and integrate obesity-related behavioral, biological, environmental, and psychosocial domains. This article describes how the behavioral domain subgroup identified the initial list of high-priority constructs and measures to be included, and it describes practical considerations for assessing the following four behavioral areas: eating, activity, sleep, and self-monitoring of weight. Challenges and considerations for advancing the science related to weight loss and maintenance behaviors are also discussed. Assessing a set of core behavioral measures in combination with those from other ADOPT domains is critical to improve our understanding of individual variability in response to adult obesity treatment. The selection of behavioral measures is based on the current science, although there continues to be much work needed in this field. © 2018 The Obesity Society.

Development of a Draft Core Set of Domains for Measuring Shared Decision Making in Osteoarthritis

DEFF Research Database (Denmark)

Toupin-April, Karine; Barton, Jennifer; Fraenkel, Liana

2015-01-01

OBJECTIVE: Despite the importance of shared decision making for delivering patient-centered care in rheumatology, there is no consensus on how to measure its process and outcomes. The aim of this Outcome Measures in Rheumatology (OMERACT) working group is to determine the core set of domains...... for measuring shared decision making in intervention studies in adults with osteoarthritis (OA), from the perspectives of patients, health professionals, and researchers. METHODS: We followed the OMERACT Filter 2.0 method to develop a draft core domain set by (1) forming an OMERACT working group; (2) conducting...... a review of domains of shared decision making; and (3) obtaining opinions of all those involved using a modified nominal group process held at a session activity at the OMERACT 12 meeting. RESULTS: In all, 26 people from Europe, North America, and Australia, including 5 patient research partners...

Stabilization of a semilinear parabolic equation in the exterior of a bounded domain by means of boundary controls

International Nuclear Information System (INIS)

Gorshkov, A V

2003-01-01

The problem of the stabilization of a semilinear equation in the exterior of a bounded domain is considered. In view of the impossibility of an exponential stabilization of the form e -σt of the solution of a parabolic equation in an unbounded domain no matter what the boundary control is, one poses the problem of power-like stabilization by means of a boundary control. For a fixed initial condition and parameter k>0 of the rate of stabilization the existence of a boundary control such that the solution approaches zero at the rate 1/t k is demonstrated

Vector tomography for reconstructing electric fields with non-zero divergence in bounded domains

Science.gov (United States)

Koulouri, Alexandra; Brookes, Mike; Rimpiläinen, Ville

2017-01-01

In vector tomography (VT), the aim is to reconstruct an unknown multi-dimensional vector field using line integral data. In the case of a 2-dimensional VT, two types of line integral data are usually required. These data correspond to integration of the parallel and perpendicular projection of the vector field along the integration lines and are called the longitudinal and transverse measurements, respectively. In most cases, however, the transverse measurements cannot be physically acquired. Therefore, the VT methods are typically used to reconstruct divergence-free (or source-free) velocity and flow fields that can be reconstructed solely from the longitudinal measurements. In this paper, we show how vector fields with non-zero divergence in a bounded domain can also be reconstructed from the longitudinal measurements without the need of explicitly evaluating the transverse measurements. To the best of our knowledge, VT has not previously been used for this purpose. In particular, we study low-frequency, time-harmonic electric fields generated by dipole sources in convex bounded domains which arise, for example, in electroencephalography (EEG) source imaging. We explain in detail the theoretical background, the derivation of the electric field inverse problem and the numerical approximation of the line integrals. We show that fields with non-zero divergence can be reconstructed from the longitudinal measurements with the help of two sparsity constraints that are constructed from the transverse measurements and the vector Laplace operator. As a comparison to EEG source imaging, we note that VT does not require mathematical modeling of the sources. By numerical simulations, we show that the pattern of the electric field can be correctly estimated using VT and the location of the source activity can be determined accurately from the reconstructed magnitudes of the field.

Structural and functional aspects of winged-helix domains at the core of transcription initiation complexes.

Science.gov (United States)

Teichmann, Martin; Dumay-Odelot, Hélène; Fribourg, Sébastien

2012-01-01

The winged helix (WH) domain is found in core components of transcription systems in eukaryotes and prokaryotes. It represents a sub-class of the helix-turn-helix motif. The WH domain participates in establishing protein-DNA and protein-protein-interactions. Here, we discuss possible explanations for the enrichment of this motif in transcription systems.

Accumulating Data to Optimally Predict Obesity Treatment (ADOPT) Core Measures: Psychosocial Domain.

Science.gov (United States)

Sutin, Angelina R; Boutelle, Kerri; Czajkowski, Susan M; Epel, Elissa S; Green, Paige A; Hunter, Christine M; Rice, Elise L; Williams, David M; Young-Hyman, Deborah; Rothman, Alexander J

2018-04-01

Within the Accumulating Data to Optimally Predict obesity Treatment (ADOPT) Core Measures Project, the psychosocial domain addresses how psychosocial processes underlie the influence of obesity treatment strategies on weight loss and weight maintenance. The subgroup for the psychosocial domain identified an initial list of high-priority constructs and measures that ranged from relatively stable characteristics about the person (cognitive function, personality) to dynamic characteristics that may change over time (motivation, affect). This paper describes (a) how the psychosocial domain fits into the broader model of weight loss and weight maintenance as conceptualized by ADOPT; (b) the guiding principles used to select constructs and measures for recommendation; (c) the high-priority constructs recommended for inclusion; (d) domain-specific issues for advancing the science; and (e) recommendations for future research. The inclusion of similar measures across trials will help to better identify how psychosocial factors mediate and moderate the weight loss and weight maintenance process, facilitate research into dynamic interactions with factors in the other ADOPT domains, and ultimately improve the design and delivery of effective interventions. © 2018 The Obesity Society.

Modeling of absorption and scattering properties of core -shell nanoparticles for application as nanoantenna in optical domain

Science.gov (United States)

Devi, Jutika; Saikia, Rashmi; Datta, Pranayee

2016-10-01

The present paper describes the study of core-shell nanoparticles for application as nanoantenna in the optical domain. To obtain the absorption and extinction efficiencies as well as the angular distribution of the far field radiation pattern and the resonance wavelengths for these metal-dielectric, dielectric-metal and metal-metal core-shell nanoparticles in optical domain, we have used Finite Element Method based COMSOL Multiphysics Software and Mie Theory. From the comparative study of the extinction efficiencies of core-shell nanoparticles of different materials, it is found that for silica - gold core - shell nanoparticles, the resonant wavelength is greater than that of the gold - silver, silver-gold and gold-silica core - shell nanoparticles and also the radiation pattern of the silica-gold core-shell nanoparticle is the most suitable one from the point of view of directivity. The dielectric functions of the core and shell material as well as of the embedded matrix are extremely important and plays a very major role to tune the directivity and resonance wavelength. Such highly controllable parameters of the dielectric - metal core - shell nanoparticles make them suitable for efficient coupling of optical radiation into nanoscale structures for a broad range of applications in the field of communications.

Modeling of absorption and scattering properties of core -shell nanoparticles for application as nanoantenna in optical domain

International Nuclear Information System (INIS)

Devi, Jutika; Datta, Pranayee; Saikia, Rashmi

2016-01-01

The present paper describes the study of core-shell nanoparticles for application as nanoantenna in the optical domain. To obtain the absorption and extinction efficiencies as well as the angular distribution of the far field radiation pattern and the resonance wavelengths for these metal-dielectric, dielectric-metal and metal-metal core-shell nanoparticles in optical domain, we have used Finite Element Method based COMSOL Multiphysics Software and Mie Theory. From the comparative study of the extinction efficiencies of core-shell nanoparticles of different materials, it is found that for silica - gold core - shell nanoparticles, the resonant wavelength is greater than that of the gold - silver, silver-gold and gold-silica core - shell nanoparticles and also the radiation pattern of the silica-gold core-shell nanoparticle is the most suitable one from the point of view of directivity. The dielectric functions of the core and shell material as well as of the embedded matrix are extremely important and plays a very major role to tune the directivity and resonance wavelength. Such highly controllable parameters of the dielectric - metal core - shell nanoparticles make them suitable for efficient coupling of optical radiation into nanoscale structures for a broad range of applications in the field of communications. (paper)

Virial Expansion Bounds

Science.gov (United States)

Tate, Stephen James

2013-10-01

In the 1960s, the technique of using cluster expansion bounds in order to achieve bounds on the virial expansion was developed by Lebowitz and Penrose (J. Math. Phys. 5:841, 1964) and Ruelle (Statistical Mechanics: Rigorous Results. Benjamin, Elmsford, 1969). This technique is generalised to more recent cluster expansion bounds by Poghosyan and Ueltschi (J. Math. Phys. 50:053509, 2009), which are related to the work of Procacci (J. Stat. Phys. 129:171, 2007) and the tree-graph identity, detailed by Brydges (Phénomènes Critiques, Systèmes Aléatoires, Théories de Jauge. Les Houches 1984, pp. 129-183, 1986). The bounds achieved by Lebowitz and Penrose can also be sharpened by doing the actual optimisation and achieving expressions in terms of the Lambert W-function. The different bound from the cluster expansion shows some improvements for bounds on the convergence of the virial expansion in the case of positive potentials, which are allowed to have a hard core.

Reaching the Chu Lower Bound on Q With Magnetic Dipole Antennas Using a Magnetic-Coated PEC Core

DEFF Research Database (Denmark)

Kim, Oleksiy S.; Breinbjerg, Olav

2011-01-01

We analytically solve the radiation problem for a spherical magnetic dipole antenna with a material-coated perfectly electrically conducting core. Using the closed-form expressions derived for the internal and external stored energies as well as for the radiation quality factor $Q$, we determine...... tends to infinity, the internal stored energy vanishes, and the $Q$ reaches the Chu lower bound, irrespective of the antenna electrical size $ka$ and permittivity of the coating....

Amyloid cores in prion domains: Key regulators for prion conformational conversion.

Science.gov (United States)

Fernández, María Rosario; Batlle, Cristina; Gil-García, Marcos; Ventura, Salvador

2017-01-02

Despite the significant efforts devoted to decipher the particular protein features that encode for a prion or prion-like behavior, they are still poorly understood. The well-characterized yeast prions constitute an ideal model system to address this question, because, in these proteins, the prion activity can be univocally assigned to a specific region of their sequence, known as the prion forming domain (PFD). These PFDs are intrinsically disordered, relatively long and, in many cases, of low complexity, being enriched in glutamine/asparagine residues. Computational analyses have identified a significant number of proteins having similar domains in the human proteome. The compositional bias of these regions plays an important role in the transition of the prions to the amyloid state. However, it is difficult to explain how composition alone can account for the formation of specific contacts that position correctly PFDs and provide the enthalpic force to compensate for the large entropic cost of immobilizing these domains in the initial assemblies. We have hypothesized that short, sequence-specific, amyloid cores embedded in PFDs can perform these functions and, accordingly, act as preferential nucleation centers in both spontaneous and seeded aggregation. We have shown that the implementation of this concept in a prediction algorithm allows to score the prion propensities of putative PFDs with high accuracy. Recently, we have provided experimental evidence for the existence of such amyloid cores in the PFDs of Sup35, Ure2, Swi1, and Mot3 yeast prions. The fibrils formed by these short stretches may recognize and promote the aggregation of the complete proteins inside cells, being thus a promising tool for targeted protein inactivation.

The core spline method for solution of quantum-mechanical systems of differential equations for bound states

International Nuclear Information System (INIS)

Aleksandrov, L.; Drenska, M.; Karadzhov, D.

1986-01-01

A generalization of the core spline method is given in the case of solution of the general bound state problem for a system of M linear differential equations with coefficients depending on the spectral parameter. The recursion scheme for construction of basic splines is described. The wave functions are expressed as linear combinations of basic splines, which are approximate partial solutions of the system. The spectral parameter (the eigenvalue) is determined from the condition for existence of a nontrivial solution of a (MxM) linear algebraic system at the last collocation point. The nontrivial solutions of this system determine (M - 1) coefficients of the linear spans, expressing the wave functions. The last unknown coefficient is determined from a boundary (or normalization) condition for the system. The computational aspects of the method are discussed, in particular, its concrete algorithmic realization used in the RODSOL program. The numerical solution of the Dirac system for the bound states of a hydrogen atom is given is an example

Toward the Development of a Core Set of Outcome Domains to Assess Shared Decision-making Interventions in Rheumatology

DEFF Research Database (Denmark)

Toupin-April, Karine; Barton, Jennifer; Fraenkel, Liana

2017-01-01

OBJECTIVE: The aim of this Outcome Measures in Rheumatology (OMERACT) Working Group was to determine the core set of outcome domains and subdomains for measuring the effectiveness of shared decision-making (SDM) interventions in rheumatology clinical trials. METHODS: Following the OMERACT Filter 2.......0, and based on a previous literature review of SDM outcome domains and a nominal group process at OMERACT 2014, (1) an online Delphi survey was conducted to gather feedback on the draft core set and refine its domains and subdomains, and (2) a workshop was held at the OMERACT 2016 meeting to gain consensus...... ranged from 83% to 100% of respondents). At OMERACT 2016, only 8% of the 96 attendees were patients/caregivers. Despite initial votes of support in breakout groups, there was insufficient comfort about the conceptualization of these 7 domains and 17 subdomains for these to be endorsed at OMERACT 2016...

Binding energies and chemical shifts of least bound core electron excitations in cubic Asub(N)Bsub(8-N) semiconductors

International Nuclear Information System (INIS)

Bechstedt, F.; Enderlein, R.; Wischnewski, R.

1981-01-01

Core electron binding energies Esup(B) with respect to the vacuum level and their chemical shifts are calculated for the least bound core levels of cations and anions of cubic Asub(N)Bsub(8-N) semiconductors. Starting from the HF-binding energy of the free atom absolute values of Esup(B) are obtained by adding core level shifts and relaxation energies. Core level shifts are calculated by means of an electrostatic model with ionic and bond charges according to Phillips' bond charge model. For the calculation of relaxation energies the linear dielectric theory of electronic polarization is applied. Valence and core electrons, and diagonal and non-diagonal screening are taken into account. The theoretical results for chemical shifts of binding energies are compared with experimental values from XPS-measurements corrected by work function data. Good agreement is obtained in all cases within the error limit of about one eV. Chemical and atomic trends of core level shifts, relaxation energies, and binding energies are discussed in terms of changes of atomic and solid state parameters. Chemical shifts and relaxation energies are predicted for various ternary Asub(N)Bsub(8-N) compounds. (author)

Development of a Draft Core Set of Domains for Measuring Shared Decision Making in Osteoarthritis: An OMERACT Working Group on Shared Decision Making

Science.gov (United States)

Toupin April, Karine; Barton, Jennifer; Fraenkel, Liana; Li, Linda; Grandpierre, Viviane; Guillemin, Francis; Rader, Tamara; Stacey, Dawn; Légaré, France; Jull, Janet; Petkovic, Jennifer; Scholte Voshaar, Marieke; Welch, Vivian; Lyddiatt, Anne; Hofstetter, Cathie; De Wit, Maarten; March, Lyn; Meade, Tanya; Christensen, Robin; Gaujoux-Viala, Cécile; Suarez-Almazor, Maria E.; Boonen, Annelies; Pohl, Christoph; Martin, Richard; Tugwell, Peter

2015-01-01

Objective Despite the importance of shared decision making for delivering patient-centred care in rheumatology, there is no consensus on how to measure its process and outcomes. The aim of this OMERACT working group is to determine the core set of domains for measuring shared decision making in intervention studies in adults with osteoarthritis (OA), from the perspective of patients, health professionals and researchers. Methods We followed the OMERACT Filter 2.0 to develop a draft core domain set, which consisted of: (i) forming an OMERACT working group; (ii) conducting a review of domains of shared decision making; and (iii) obtaining the opinions of stakeholders using a modified nominal group process held at a session activity at the OMERACT 2014 meeting. Results 26 stakeholders from Europe, North America and Australia, including 5 patient research partners, participated in the session activity. Participants identified the following domains for measuring shared decision making to be included as part of the Draft Core Set: 1) Identifying the decision; 2) Exchanging Information; 3) Clarifying views; 4) Deliberating; 5) Making the decision; 6) Putting the decision into practice; and 7) Assessing the impact of the decision. Contextual factors were also suggested. Conclusion We propose a Draft Core Set of shared decision making domains for OA intervention research studies. Next steps include a workshop at OMERACT 2016 to reach consensus on these proposed domains in the wider OMERACT group, as well as detail sub-domains and assess instruments to develop a Core Outcome Measurement Set. PMID:25877502

Vector tomography for reconstructing electric fields with non-zero divergence in bounded domains

Energy Technology Data Exchange (ETDEWEB)

Koulouri, Alexandra, E-mail: koulouri@uni-muenster.de [Institute for Computational and Applied Mathematics, University of Münster, Einsteinstrasse 62, D-48149 Münster (Germany); Department of Electrical and Electronic Engineering, Imperial College London, Exhibition Road, London SW7 2BT (United Kingdom); Brookes, Mike [Department of Electrical and Electronic Engineering, Imperial College London, Exhibition Road, London SW7 2BT (United Kingdom); Rimpiläinen, Ville [Institute for Biomagnetism and Biosignalanalysis, University of Münster, Malmedyweg 15, D-48149 Münster (Germany); Department of Mathematics, University of Auckland, Private bag 92019, Auckland 1142 (New Zealand)

2017-01-15

In vector tomography (VT), the aim is to reconstruct an unknown multi-dimensional vector field using line integral data. In the case of a 2-dimensional VT, two types of line integral data are usually required. These data correspond to integration of the parallel and perpendicular projection of the vector field along the integration lines and are called the longitudinal and transverse measurements, respectively. In most cases, however, the transverse measurements cannot be physically acquired. Therefore, the VT methods are typically used to reconstruct divergence-free (or source-free) velocity and flow fields that can be reconstructed solely from the longitudinal measurements. In this paper, we show how vector fields with non-zero divergence in a bounded domain can also be reconstructed from the longitudinal measurements without the need of explicitly evaluating the transverse measurements. To the best of our knowledge, VT has not previously been used for this purpose. In particular, we study low-frequency, time-harmonic electric fields generated by dipole sources in convex bounded domains which arise, for example, in electroencephalography (EEG) source imaging. We explain in detail the theoretical background, the derivation of the electric field inverse problem and the numerical approximation of the line integrals. We show that fields with non-zero divergence can be reconstructed from the longitudinal measurements with the help of two sparsity constraints that are constructed from the transverse measurements and the vector Laplace operator. As a comparison to EEG source imaging, we note that VT does not require mathematical modeling of the sources. By numerical simulations, we show that the pattern of the electric field can be correctly estimated using VT and the location of the source activity can be determined accurately from the reconstructed magnitudes of the field. - Highlights: • Vector tomography is used to reconstruct electric fields generated by dipole

Steric Pressure among Membrane-Bound Polymers Opposes Lipid Phase Separation.

Science.gov (United States)

Imam, Zachary I; Kenyon, Laura E; Carrillo, Adelita; Espinoza, Isai; Nagib, Fatema; Stachowiak, Jeanne C

2016-04-19

Lipid rafts are thought to be key organizers of membrane-protein complexes in cells. Many proteins that interact with rafts have bulky polymeric components such as intrinsically disordered protein domains and polysaccharide chains. Therefore, understanding the interaction between membrane domains and membrane-bound polymers provides insights into the roles rafts play in cells. Multiple studies have demonstrated that high concentrations of membrane-bound polymeric domains create significant lateral steric pressure at membrane surfaces. Furthermore, our recent work has shown that lateral steric pressure at membrane surfaces opposes the assembly of membrane domains. Building on these findings, here we report that membrane-bound polymers are potent suppressors of membrane phase separation, which can destabilize lipid domains with substantially greater efficiency than globular domains such as membrane-bound proteins. Specifically, we created giant vesicles with a ternary lipid composition, which separated into coexisting liquid ordered and disordered phases. Lipids with saturated tails and poly(ethylene glycol) (PEG) chains conjugated to their head groups were included at increasing molar concentrations. When these lipids were sparse on the membrane surface they partitioned to the liquid ordered phase. However, as they became more concentrated, the fraction of GUVs that were phase-separated decreased dramatically, ultimately yielding a population of homogeneous membrane vesicles. Experiments and physical modeling using compositions of increasing PEG molecular weight and lipid miscibility phase transition temperature demonstrate that longer polymers are the most efficient suppressors of membrane phase separation when the energetic barrier to lipid mixing is low. In contrast, as the miscibility transition temperature increases, longer polymers are more readily driven out of domains by the increased steric pressure. Therefore, the concentration of shorter polymers required

Structures of three members of Pfam PF02663 (FmdE) implicated in microbial methanogenesis reveal a conserved α+β core domain and an auxiliary C-terminal treble-clef zinc finger

International Nuclear Information System (INIS)

Axelrod, Herbert L.; Das, Debanu; Abdubek, Polat; Astakhova, Tamara; Bakolitsa, Constantina; Carlton, Dennis; Chen, Connie; Chiu, Hsiu-Ju; Clayton, Thomas; Deller, Marc C.; Duan, Lian; Ellrott, Kyle; Farr, Carol L.; Feuerhelm, Julie; Grant, Joanna C.; Grzechnik, Anna; Han, Gye Won; Jaroszewski, Lukasz; Jin, Kevin K.; Klock, Heath E.; Knuth, Mark W.; Kozbial, Piotr; Krishna, S. Sri; Kumar, Abhinav; Lam, Winnie W.; Marciano, David; McMullan, Daniel; Miller, Mitchell D.; Morse, Andrew T.; Nigoghossian, Edward; Nopakun, Amanda; Okach, Linda; Puckett, Christina; Reyes, Ron; Sefcovic, Natasha; Tien, Henry J.; Trame, Christine B.; Bedem, Henry van den; Weekes, Dana; Wooten, Tiffany; Xu, Qingping; Hodgson, Keith O.; Wooley, John; Elsliger, Marc-André; Deacon, Ashley M.; Godzik, Adam; Lesley, Scott A.; Wilson, Ian A.

2010-01-01

The first structures from the FmdE Pfam family (PF02663) reveal that some members of this family form tightly intertwined dimers consisting of two domains (N-terminal α+β core and C-terminal zinc-finger domains), whereas others contain only the core domain. The presence of the zinc-finger domain suggests that some members of this family may perform functions associated with transcriptional regulation, protein–protein interaction, RNA binding or metal-ion sensing. Examination of the genomic context for members of the FmdE Pfam family (PF02663), such as the protein encoded by the fmdE gene from the methanogenic archaeon Methanobacterium thermoautotrophicum, indicates that 13 of them are co-transcribed with genes encoding subunits of molybdenum formylmethanofuran dehydrogenase (EC 1.2.99.5), an enzyme that is involved in microbial methane production. Here, the first crystal structures from PF02663 are described, representing two bacterial and one archaeal species: B8FYU2-DESHY from the anaerobic dehalogenating bacterium Desulfitobacterium hafniense DCB-2, Q2LQ23-SYNAS from the syntrophic bacterium Syntrophus aciditrophicus SB and Q9HJ63-THEAC from the thermoacidophilic archaeon Thermoplasma acidophilum. Two of these proteins, Q9HJ63-THEAC and Q2LQ23-SYNAS, contain two domains: an N-terminal thioredoxin-like α+β core domain (NTD) consisting of a five-stranded, mixed β-sheet flanked by several α-helices and a C-terminal zinc-finger domain (CTD). B8FYU2-DESHY, on the other hand, is composed solely of the NTD. The CTD of Q9HJ63-THEAC and Q2LQ23-SYNAS is best characterized as a treble-clef zinc finger. Two significant structural differences between Q9HJ63-THEAC and Q2LQ23-SYNAS involve their metal binding. First, zinc is bound to the putative active site on the NTD of Q9HJ63-THEAC, but is absent from the NTD of Q2LQ23-SYNAS. Second, whereas the structure of the CTD of Q2LQ23-SYNAS shows four Cys side chains within coordination distance of the Zn atom, the structure

Architecture of the RNA polymerase II-Mediator core initiation complex.

Science.gov (United States)

Plaschka, C; Larivière, L; Wenzeck, L; Seizl, M; Hemann, M; Tegunov, D; Petrotchenko, E V; Borchers, C H; Baumeister, W; Herzog, F; Villa, E; Cramer, P

2015-02-19

The conserved co-activator complex Mediator enables regulated transcription initiation by RNA polymerase (Pol) II. Here we reconstitute an active 15-subunit core Mediator (cMed) comprising all essential Mediator subunits from Saccharomyces cerevisiae. The cryo-electron microscopic structure of cMed bound to a core initiation complex was determined at 9.7 Å resolution. cMed binds Pol II around the Rpb4-Rpb7 stalk near the carboxy-terminal domain (CTD). The Mediator head module binds the Pol II dock and the TFIIB ribbon and stabilizes the initiation complex. The Mediator middle module extends to the Pol II foot with a 'plank' that may influence polymerase conformation. The Mediator subunit Med14 forms a 'beam' between the head and middle modules and connects to the tail module that is predicted to bind transcription activators located on upstream DNA. The Mediator 'arm' and 'hook' domains contribute to a 'cradle' that may position the CTD and TFIIH kinase to stimulate Pol II phosphorylation.

Development of a Draft Core Set of Domains for Measuring Shared Decision Making in Osteoarthritis: An OMERACT Working Group on Shared Decision Making.

Science.gov (United States)

Toupin-April, Karine; Barton, Jennifer; Fraenkel, Liana; Li, Linda; Grandpierre, Viviane; Guillemin, Francis; Rader, Tamara; Stacey, Dawn; Légaré, France; Jull, Janet; Petkovic, Jennifer; Scholte-Voshaar, Marieke; Welch, Vivian; Lyddiatt, Anne; Hofstetter, Cathie; De Wit, Maarten; March, Lyn; Meade, Tanya; Christensen, Robin; Gaujoux-Viala, Cécile; Suarez-Almazor, Maria E; Boonen, Annelies; Pohl, Christoph; Martin, Richard; Tugwell, Peter S

2015-12-01

Despite the importance of shared decision making for delivering patient-centered care in rheumatology, there is no consensus on how to measure its process and outcomes. The aim of this Outcome Measures in Rheumatology (OMERACT) working group is to determine the core set of domains for measuring shared decision making in intervention studies in adults with osteoarthritis (OA), from the perspectives of patients, health professionals, and researchers. We followed the OMERACT Filter 2.0 method to develop a draft core domain set by (1) forming an OMERACT working group; (2) conducting a review of domains of shared decision making; and (3) obtaining opinions of all those involved using a modified nominal group process held at a session activity at the OMERACT 12 meeting. In all, 26 people from Europe, North America, and Australia, including 5 patient research partners, participated in the session activity. Participants identified the following domains for measuring shared decision making to be included as part of the draft core set: (1) identifying the decision, (2) exchanging information, (3) clarifying views, (4) deliberating, (5) making the decision, (6) putting the decision into practice, and (7) assessing the effect of the decision. Contextual factors were also suggested. We proposed a draft core set of shared decision-making domains for OA intervention research studies. Next steps include a workshop at OMERACT 13 to reach consensus on these proposed domains in the wider OMERACT group, as well as to detail subdomains and assess instruments to develop a core outcome measurement set.

Full-length RNA structure prediction of the HIV-1 genome reveals a conserved core domain

DEFF Research Database (Denmark)

Sükösd, Zsuzsanna; Andersen, Ebbe Sloth; Seemann, Ernst Stefan

2015-01-01

of the HIV-1 genome is highly variable in most regions, with a limited number of stable and conserved RNA secondary structures. Most interesting, a set of long distance interactions form a core organizing structure (COS) that organize the genome into three major structural domains. Despite overlapping...

Recommendation for measuring clinical outcome in distal radius fractures: a core set of domains for standardized reporting in clinical practice and research.

Science.gov (United States)

Goldhahn, Jörg; Beaton, Dorcas; Ladd, Amy; Macdermid, Joy; Hoang-Kim, Amy

2014-02-01

Lack of standardization of outcome measurement has hampered an evidence-based approach to clinical practice and research. We adopted a process of reviewing evidence on current use of measures and appropriate theoretical frameworks for health and disability to inform a consensus process that was focused on deriving the minimal set of core domains in distal radius fracture. We agreed on the following seven core recommendations: (1) pain and function were regarded as the primary domains, (2) very brief measures were needed for routine administration in clinical practice, (3) these brief measures could be augmented by additional measures that provide more detail or address additional domains for clinical research, (4) measurement of pain should include measures of both intensity and frequency as core attributes, (5) a numeric pain scale, e.g. visual analogue scale or visual numeric scale or the pain subscale of the patient-reported wrist evaluation (PRWE) questionnaires were identified as reliable, valid and feasible measures to measure these concepts, (6) for function, either the Quick Disability of the arm, shoulder and hand questionnaire or PRWE-function subscale was identified as reliable, valid and feasible measures, and (7) a measure of participation and treatment complications should be considered core outcomes for both clinical practice and research. We used a sound methodological approach to form a comprehensive foundation of content for outcomes in the area of distal radius fractures. We recommend the use of symptom and function as separate domains in the ICF core set in clinical research or practice for patients with wrist fracture. Further research is needed to provide more definitive measurement properties of measures across all domains.

Evaluation Codes from Order Domain Theory

DEFF Research Database (Denmark)

Andersen, Henning Ejnar; Geil, Hans Olav

2008-01-01

bound is easily extended to deal with any generalized Hamming weights. We interpret our methods into the setting of order domain theory. In this way we fill in an obvious gap in the theory of order domains. [28] T. Shibuya and K. Sakaniwa, A Dual of Well-Behaving Type Designed Minimum Distance, IEICE......The celebrated Feng-Rao bound estimates the minimum distance of codes defined by means of their parity check matrices. From the Feng-Rao bound it is clear how to improve a large family of codes by leaving out certain rows in their parity check matrices. In this paper we derive a simple lower bound...... on the minimum distance of codes defined by means of their generator matrices. From our bound it is clear how to improve a large family of codes by adding certain rows to their generator matrices. The new bound is very much related to the Feng-Rao bound as well as to Shibuya and Sakaniwa's bound in [28]. Our...

Centeredness Theory: Understanding and Measuring Well-Being Across Core Life Domains

Directory of Open Access Journals (Sweden)

Zephyr T. Bloch-Jorgensen

2018-05-01

Full Text Available Background: Centeredness Theory (CT is proposed as a new mental health paradigm that focuses on well-being at a systems-level, across the core life domains of the self, the family unit, relationships, community, and work. The current studies aimed to validate the psychometric properties of a new scale that measures CT against existing well-being and mental health measures.Methods: Study 1 included 488 anonymous online respondents (46% females, 28% males, 25% unknown with median age between 31 and 35 years across 38 countries who completed the CT scale. Study 2 included 49 first-year psychology students (90% females, mean age of 19 years from Sydney Australia that completed the CT scale and other well-being and mental health questionnaires at baseline and 2-weeks follow-up.Results: Exploratory and confirmatory factor analyses resulted in a refined 60-item CT scale with five domains, each with four sub-domains. The CT scale demonstrated good internal consistency reliability and test-retest reliability, and showed evidence of convergent validity against other well-being measures (e.g., COMPAS-W Wellbeing Scale, SWLS scale, and Ryff's Psychological Well-being scale.Conclusions: The CT scale appears to be a reliable measure of well-being at a systems-level. Future studies need to confirm these findings in larger heterogeneous samples.

Epistemology and ontology in core ontologies: FOLaw and LRI-Core, two core ontologies for law

NARCIS (Netherlands)

Breukers, J.A.P.J.; Hoekstra, R.J.

2004-01-01

For more than a decade constructing ontologies for legal domains, we, at the Leibniz Center for Law, felt really the need to develop a core ontology for law that would enable us to re-use the common denominator of the various legal domains. In this paper we present two core ontologies for law. The

Crystallographic characterization of the radixin FERM domain bound to the cytoplasmic tail of membrane-type 1 matrix metalloproteinase (MT1-MMP)

International Nuclear Information System (INIS)

Terawaki, Shin-ichi; Kitano, Ken; Aoyama, Miki; Hakoshima, Toshio

2008-01-01

The radixin FERM domain was shown to bind the MT1-MMP cytoplasmic peptide and crystals of the complex were obtained. ERM proteins play a role in the cross-linking found between plasma membranes and actin filaments. The N-terminal FERM domains of ERM proteins are responsible for membrane association through direct interaction with the cytoplasmic tails of integral membrane proteins. During cell migration and movement, membrane-type 1 matrix metalloproteinase (MT1-MMP) on plasma membranes sheds adhesion molecule CD44 in addition to degrading the extracellular matrix. Here, the interaction between the radixin FERM domain and the MT1-MMP cytoplasmic tail is reported and preliminary crystallographic characterization of crystals of the radixin FERM domain bound to the cytoplasmic tail of MT1-MMP is presented. The crystals belong to space group P6 1 22, with unit-cell parameters a = b = 122.7, c = 128.3 Å, and contain one complex in the crystallographic asymmetric unit. The diffraction data were collected to a resolution of 2.4 Å

Small-angle X-ray scattering analysis reveals the ATP-bound monomeric state of the ATPase domain from the homodimeric MutL endonuclease, a GHKL phosphotransferase superfamily protein.

Science.gov (United States)

Iino, Hitoshi; Hikima, Takaaki; Nishida, Yuya; Yamamoto, Masaki; Kuramitsu, Seiki; Fukui, Kenji

2015-05-01

DNA mismatch repair is an excision system that removes mismatched bases chiefly generated by replication errors. In this system, MutL endonucleases direct the excision reaction to the error-containing strand of the duplex by specifically incising the newly synthesized strand. Both bacterial homodimeric and eukaryotic heterodimeric MutL proteins belong to the GHKL ATPase/kinase superfamily that comprises the N-terminal ATPase and C-terminal dimerization regions. Generally, the GHKL proteins show large ATPase cycle-dependent conformational changes, including dimerization-coupled ATP binding of the N-terminal domain. Interestingly, the ATPase domain of human PMS2, a subunit of the MutL heterodimer, binds ATP without dimerization. The monomeric ATP-bound state of the domain has been thought to be characteristic of heterodimeric GHKL proteins. In this study, we characterized the ATP-bound state of the ATPase domain from the Aquifex aeolicus MutL endonuclease, which is a homodimeric GHKL protein unlike the eukaryotic MutL. Gel filtration, dynamic light scattering, and small-angle X-ray scattering analyses clearly showed that the domain binds ATP in a monomeric form despite its homodimeric nature. This indicates that the uncoupling of dimerization and ATP binding is a common feature among bacterial and eukaryotic MutL endonucleases, which we suggest is closely related to the molecular mechanisms underlying mismatch repair.

Mixed first- and second-order transport method using domain decomposition techniques for reactor core calculations

International Nuclear Information System (INIS)

Girardi, E.; Ruggieri, J.M.

2003-01-01

The aim of this paper is to present the last developments made on a domain decomposition method applied to reactor core calculations. In this method, two kind of balance equation with two different numerical methods dealing with two different unknowns are coupled. In the first part the two balance transport equations (first order and second order one) are presented with the corresponding following numerical methods: Variational Nodal Method and Discrete Ordinate Nodal Method. In the second part, the Multi-Method/Multi-Domain algorithm is introduced by applying the Schwarz domain decomposition to the multigroup eigenvalue problem of the transport equation. The resulting algorithm is then provided. The projection operators used to coupled the two methods are detailed in the last part of the paper. Finally some preliminary numerical applications on benchmarks are given showing encouraging results. (authors)

Pair condensation and bound states in fermionic systems

International Nuclear Information System (INIS)

Sedrakian, Armen; Clark, John W.

2006-01-01

We study the finite temperature-density phase diagram of an attractive fermionic system that supports two-body (dimer) and three-body (trimer) bound states in free space. Using interactions characteristic for nuclear systems, we obtain the critical temperature T c2 for the superfluid phase transition and the limiting temperature T c3 for the extinction of trimers. The phase diagram features a Cooper-pair condensate in the high-density, low-temperature domain which, with decreasing density, crosses over to a Bose condensate of strongly bound dimers. The high-temperature, low-density domain is populated by trimers whose binding energy decreases toward the density-temperature domain occupied by the superfluid and vanishes at a critical temperature T c3 >T c2

Lower bounds for the minimum distance of algebraic geometry codes

DEFF Research Database (Denmark)

Beelen, Peter

, such as the Goppa bound, the Feng-Rao bound and the Kirfel-Pellikaan bound. I will finish my talk by giving several examples. Especially for two-point codes, the generalized order bound is fairly easy to compute. As an illustration, I will indicate how a lower bound can be obtained for the minimum distance of some...... description of these codes in terms of order domains has been found. In my talk I will indicate how one can use the ideas behind the order bound to obtain a lower bound for the minimum distance of any AG-code. After this I will compare this generalized order bound with other known lower bounds...

Ethics in Knowledge Organization: Two Conferences Point to a New Core in the Domain

Directory of Open Access Journals (Sweden)

Richard P. Smiraglia

2015-01-01

Full Text Available http://dx.doi.org/10.5007/1518-2924.2015v20nesp1p1 Two conferences called "Ethics in Information Organization (EIO," held in 2009 and 2013, brought together practitioners and scholars in knowledge organization (KO to discuss ethical decision-making for the organization of knowledge. Traditionally the notion of ethics as a component of knowledge organization has occupied a sort of background position. Concepts of cultural warrant clash with concepts of literary warrant to produce harmful knowledge organization systems. Here tools of domain analytical visualization are applied to the two EIO conferences to demonstrate the potential intension of ethics for KO. Co-word analysis helps to visualize the thematic core in the most frequently used terms: user, ethical, knowledge, national, description, and access. There clearly is a meta-level trajectory incorporating ethics and the user, while the intension includes all applied approaches to KO as well as strong recognition of national, regional, and social cultural identities. Another approach to domain analysis is to examine the social semantics (by analyzing the public record of discourse through citation patterns. Author co-citation analysis shows work anchored in the basic theoretical premises of KO, but also bringing ideas from outside the domain to bear on the problems of objective violence. A network visualization shows how the work on ethics in KO is based on the core principles of KO, but relies also on evidence from librarianship and philosophical guidance to bring forward the issues surrounding objective violence in KOS. The authors contributing to this small pair of conferences have laid out a pathway for expanding understanding of the role of ethics in KO.

Examining the similarities and differences of OMERACT core sets using the ICF: first step towards an improved domain specification and development of an item pool to measure functioning and health.

Science.gov (United States)

Escorpizo, Reuben; Boers, Maarten; Stucki, Gerold; Boonen, Annelies

2011-08-01

To contribute to the discussion on a common approach for domain selection in the Outcomes in Rheumatology Clinical Trials (OMERACT) process. First, this article reports on the consistency in the selection and names of the domains of the current OMERACT core set, and next on the comparability of the specifications of concepts that are relevant within the domains. For this purpose, a convenience sample of 4 OMERACT core sets was used: rheumatoid arthritis (RA), psoriatic arthritis (PsA), longitudinal observational studies (LOS) in rheumatology, and ankylosing spondylitis (AS). Domains from the different core sets were compared directly. To be able to compare the specific content of the domains, the concepts contained in the questionnaires that were considered or proposed to measure the domains were identified and linked to the category of the International Classification of Functioning, Disability, and Health (ICF) that best fit that construct. Large differences in the domains, and lack of domain definitions, were noted among the 4 OMERACT core sets. When comparing the concepts in the questionnaires that represent the domains, core sets differed also in the number and type of constructs that were addressed within each of the domains. Especially for the specification of the concepts within the domains Discomfort and Disability, the ICF proved to be useful as external reference to classify the different constructs. Our exercise suggests that the OMERACT process could benefit from a standardized approach to select, define, and specify domains, and demonstrated that the ICF is useful for further classification of the more specific concepts of "what to measure" within the domains. A clear definition and classification of domains and their specification can be useful as a starting point to build a pool of items that could then be used to develop new instruments to assess functioning and health for rheumatological conditions.

Stabilizing a solution of the 2D Navier-Stokes system in the exterior of a bounded domain by means of a control on the boundary

International Nuclear Information System (INIS)

Gorshkov, Aleksei V

2012-01-01

The problem of stabilizing a solution of the 2D Navier-Stokes system defined in the exterior of a bounded domain with smooth boundary is investigated. For a given initial velocity field a control on the boundary of the domain must be constructed such that the solution stabilizes to a prescribed vortex solution or trivial solution at the rate of 1/t k . On the way, related questions are investigated, concerning the behaviour of the spectrum of an operator under a relatively compact perturbation and the existence of attracting invariant manifolds. Bibliography: 21 titles.

A potent transrepression domain in the retinoblastoma protein induces a cell cycle arrest when bound to E2F sites.

Science.gov (United States)

Sellers, W R; Rodgers, J W; Kaelin, W G

1995-01-01

An intact T/E1A-binding domain (the pocket) is necessary, but not sufficient, for the retinoblastoma protein (RB) to bind to DNA-protein complexes containing E2F and for RB to induce a G1/S block. Indirect evidence suggests that the binding of RB to E2F may, in addition to inhibiting E2F transactivation function, generate a complex capable of functioning as a transrepressor. Here we show that a chimera in which the E2F1 transactivation domain was replaced with the RB pocket could, in a DNA-binding and pocket-dependent manner, mimic the ability of RB to repress transcription and induce a cell cycle arrest. In contrast, a transdominant negative E2F1 mutant that is capable of blocking E2F-dependent transactivation did not. Fusion of the RB pocket to a heterologous DNA-binding domain unrelated to E2F likewise generated a transrepressor protein when scored against a suitable reporter. These results suggest that growth suppression by RB is due, at least in part, to transrepression mediated by the pocket domain bound to certain promoters via E2F. Images Fig. 4 Fig. 5 PMID:8524800

An Interval Bound Algorithm of optimizing reactor core loading pattern by using reactivity interval schema

International Nuclear Information System (INIS)

Gong Zhaohu; Wang Kan; Yao Dong

2011-01-01

Highlights: → We present a new Loading Pattern Optimization method - Interval Bound Algorithm (IBA). → IBA directly uses the reactivity of fuel assemblies and burnable poison. → IBA can optimize fuel assembly orientation in a coupled way. → Numerical experiment shows that IBA outperforms genetic algorithm and engineers. → We devise DDWF technique to deal with multiple objectives and constraints. - Abstract: In order to optimize the core loading pattern in Nuclear Power Plants, the paper presents a new optimization method - Interval Bound Algorithm (IBA). Similar to the typical population based algorithms, e.g. genetic algorithm, IBA maintains a population of solutions and evolves them during the optimization process. IBA acquires the solution by statistical learning and sampling the control variable intervals of the population in each iteration. The control variables are the transforms of the reactivity of fuel assemblies or the worth of burnable poisons, which are the crucial heuristic information for loading pattern optimization problems. IBA can deal with the relationship between the dependent variables by defining the control variables. Based on the IBA algorithm, a parallel Loading Pattern Optimization code, named IBALPO, has been developed. To deal with multiple objectives and constraints, the Dynamic Discontinuous Weight Factors (DDWF) for the fitness function have been used in IBALPO. Finally, the code system has been used to solve a realistic reloading problem and a better pattern has been obtained compared with the ones searched by engineers and genetic algorithm, thus the performance of the code is proved.

The Navier-Stokes equations on a bounded domain

International Nuclear Information System (INIS)

Scheffer, V.

1980-01-01

Suppose U is an open bounded subset of 3-space such that the boundary of U has Lebesgue measure zero. Then for any initial condition with finite kinetic energy we can find a global (i.e. for all time) weak solution u to the time dependent Navier-Stokes equations of incompressible fluid flow in U such that the curl of u is continuous outside a locally closed set whose 5/3 dimensional Hausdorff measure is finite. (orig.)

Structures of Staphylococcus aureus D-tagatose-6-phosphate kinase implicate domain motions in specificity and mechanism.

Science.gov (United States)

Miallau, Linda; Hunter, William N; McSweeney, Sean M; Leonard, Gordon A

2007-07-06

High resolution structures of Staphylococcus aureus d-tagatose-6-phosphate kinase (LacC) in two crystal forms are herein reported. The structures define LacC in apoform, in binary complexes with ADP or the co-factor analogue AMP-PNP, and in a ternary complex with AMP-PNP and D-tagatose-6-phosphate. The tertiary structure of the LacC monomer, which is closely related to other members of the pfkB subfamily of carbohydrate kinases, is composed of a large alpha/beta core domain and a smaller, largely beta "lid." Four extended polypeptide segments connect these two domains. Dimerization of LacC occurs via interactions between lid domains, which come together to form a beta-clasp structure. Residues from both subunits contribute to substrate binding. LacC adopts a closed structure required for phosphoryl transfer only when both substrate and co-factor are bound. A reaction mechanism similar to that used by other phosphoryl transferases is proposed, although unusually, when both substrate and co-factor are bound to the enzyme two Mg(2+) ions are observed in the active site. A new motif of amino acid sequence conservation common to the pfkB subfamily of carbohydrate kinases is identified.

Structure of the protein core of translation initiation factor 2 in apo, GTP-bound and GDP-bound forms

International Nuclear Information System (INIS)

Simonetti, Angelita; Marzi, Stefano; Fabbretti, Attilio; Hazemann, Isabelle; Jenner, Lasse; Urzhumtsev, Alexandre; Gualerzi, Claudio O.; Klaholz, Bruno P.

2013-01-01

The crystal structures of the eubacterial translation initiation factor 2 in apo form and with bound GDP and GTP reveal conformational changes upon nucleotide binding and hydrolysis, notably of the catalytically important histidine in the switch II region. Translation initiation factor 2 (IF2) is involved in the early steps of bacterial protein synthesis. It promotes the stabilization of the initiator tRNA on the 30S initiation complex (IC) and triggers GTP hydrolysis upon ribosomal subunit joining. While the structure of an archaeal homologue (a/eIF5B) is known, there are significant sequence and functional differences in eubacterial IF2, while the trimeric eukaryotic IF2 is completely unrelated. Here, the crystal structure of the apo IF2 protein core from Thermus thermophilus has been determined by MAD phasing and the structures of GTP and GDP complexes were also obtained. The IF2–GTP complex was trapped by soaking with GTP in the cryoprotectant. The structures revealed conformational changes of the protein upon nucleotide binding, in particular in the P-loop region, which extend to the functionally relevant switch II region. The latter carries a catalytically important and conserved histidine residue which is observed in different conformations in the GTP and GDP complexes. Overall, this work provides the first crystal structure of a eubacterial IF2 and suggests that activation of GTP hydrolysis may occur by a conformational repositioning of the histidine residue

Structure of the protein core of translation initiation factor 2 in apo, GTP-bound and GDP-bound forms

Energy Technology Data Exchange (ETDEWEB)

Simonetti, Angelita [IGBMC (Institute of Genetics and of Molecular and Cellular Biology), Centre National de la Recherche Scientifique (CNRS) UMR 7104/Institut National de la Santé de la Recherche Médicale - INSERM U964/Université de Strasbourg, 1 Rue Laurent Fries, 67404 Illkirch (France); Marzi, Stefano [Architecture et Réactivité de l’ARN, UPR 9002 CNRS, IBMC (Institute of Molecular and Cellular Biology), 15 Rue R. Descartes, 67084 Strasbourg, France, Université de Strasbourg, 67000 Strasbourg (France); Fabbretti, Attilio [University of Camerino, 62032 Camerino (Monaco) (Italy); Hazemann, Isabelle; Jenner, Lasse [IGBMC (Institute of Genetics and of Molecular and Cellular Biology), Centre National de la Recherche Scientifique (CNRS) UMR 7104/Institut National de la Santé de la Recherche Médicale -INSERM U964/Université de Strasbourg, 1 Rue Laurent Fries, 67404 Illkirch (France); Urzhumtsev, Alexandre [IGBMC (Institute of Genetics and of Molecular and Cellular Biology), Centre National de la Recherche Scientifique (CNRS) UMR 7104/Institut National de la Santé de la Recherche Médicale - INSERM U964/Université de Strasbourg, 1 Rue Laurent Fries, 67404 Illkirch (France); Université de Lorraine, 54506 Vandoeuvre-lès-Nancy (France); Gualerzi, Claudio O. [University of Camerino, 62032 Camerino (Monaco) (Italy); Klaholz, Bruno P., E-mail: klaholz@igbmc.fr [IGBMC (Institute of Genetics and of Molecular and Cellular Biology), Centre National de la Recherche Scientifique (CNRS) UMR 7104/Institut National de la Santé de la Recherche Médicale - INSERM U964/Université de Strasbourg, 1 Rue Laurent Fries, 67404 Illkirch (France)

2013-06-01

The crystal structures of the eubacterial translation initiation factor 2 in apo form and with bound GDP and GTP reveal conformational changes upon nucleotide binding and hydrolysis, notably of the catalytically important histidine in the switch II region. Translation initiation factor 2 (IF2) is involved in the early steps of bacterial protein synthesis. It promotes the stabilization of the initiator tRNA on the 30S initiation complex (IC) and triggers GTP hydrolysis upon ribosomal subunit joining. While the structure of an archaeal homologue (a/eIF5B) is known, there are significant sequence and functional differences in eubacterial IF2, while the trimeric eukaryotic IF2 is completely unrelated. Here, the crystal structure of the apo IF2 protein core from Thermus thermophilus has been determined by MAD phasing and the structures of GTP and GDP complexes were also obtained. The IF2–GTP complex was trapped by soaking with GTP in the cryoprotectant. The structures revealed conformational changes of the protein upon nucleotide binding, in particular in the P-loop region, which extend to the functionally relevant switch II region. The latter carries a catalytically important and conserved histidine residue which is observed in different conformations in the GTP and GDP complexes. Overall, this work provides the first crystal structure of a eubacterial IF2 and suggests that activation of GTP hydrolysis may occur by a conformational repositioning of the histidine residue.

Bidirectional lipid droplet velocities are controlled by differential binding strengths of HCV core DII protein.

Directory of Open Access Journals (Sweden)

Rodney K Lyn

Full Text Available Host cell lipid droplets (LD are essential in the hepatitis C virus (HCV life cycle and are targeted by the viral capsid core protein. Core-coated LDs accumulate in the perinuclear region and facilitate viral particle assembly, but it is unclear how mobility of these LDs is directed by core. Herein we used two-photon fluorescence, differential interference contrast imaging, and coherent anti-Stokes Raman scattering microscopies, to reveal novel core-mediated changes to LD dynamics. Expression of core protein's lipid binding domain II (DII-core induced slower LD speeds, but did not affect directionality of movement on microtubules. Modulating the LD binding strength of DII-core further impacted LD mobility, revealing the temporal effects of LD-bound DII-core. These results for DII-core coated LDs support a model for core-mediated LD localization that involves core slowing down the rate of movement of LDs until localization at the perinuclear region is accomplished where LD movement ceases. The guided localization of LDs by HCV core protein not only is essential to the viral life cycle but also poses an interesting target for the development of antiviral strategies against HCV.

Crystal structure of a prolactin receptor antagonist bound to the extracellular domain of the prolactin receptor

DEFF Research Database (Denmark)

Svensson, L Anders; Bondensgaard, Kent; Nørskov-Lauritsen, Leif

2008-01-01

The crystal structure of the complex between an N-terminally truncated G129R human prolactin (PRL) variant and the extracellular domain of the human prolactin receptor (PRLR) was determined at 2.5A resolution by x-ray crystallography. This structure represents the first experimental structure...... studies, the structural data imply that the definition of PRL binding site 1 should be extended to include residues situated in the N-terminal part of loop 1 and in the C terminus. Comparison of the structure of the receptor-bound PRL variant with the structure reported for the unbound form of a similar...... scale rearrangements and structuring occur in the flexible N-terminal part of loop 1. Hydrogen exchange mass spectrometry data imply that the dynamics of the four-helix bundle in solution generally become stabilized upon receptor interaction at binding site 1....

Convectons in periodic and bounded domains

International Nuclear Information System (INIS)

Mercader, Isabel; Batiste, Oriol; Alonso, Arantxa; Knobloch, Edgar

2010-01-01

Numerical continuation is used to compute spatially localized convection in a binary fluid with no-slip laterally insulating boundary conditions and the results are compared with the corresponding ones for periodic boundary conditions (PBC). The change in the boundary conditions produces a dramatic change in the snaking bifurcation diagram that describes the organization of localized states with PBC: the snaking branches turn continuously into a large amplitude state that resembles periodic convection with defects at the sidewalls. Odd parity convectons are more affected by the boundary conditions since the sidewalls suppress the horizontal pumping action that accompanies these states in spatially periodic domains.

Convectons in periodic and bounded domains

Energy Technology Data Exchange (ETDEWEB)

Mercader, Isabel; Batiste, Oriol; Alonso, Arantxa [Departament de Fisica Aplicada, Universitat Politecnica de Catalunya, Barcelona (Spain); Knobloch, Edgar [Department of Physics, University of California, Berkeley, CA 94720 (United States)

2010-04-15

Numerical continuation is used to compute spatially localized convection in a binary fluid with no-slip laterally insulating boundary conditions and the results are compared with the corresponding ones for periodic boundary conditions (PBC). The change in the boundary conditions produces a dramatic change in the snaking bifurcation diagram that describes the organization of localized states with PBC: the snaking branches turn continuously into a large amplitude state that resembles periodic convection with defects at the sidewalls. Odd parity convectons are more affected by the boundary conditions since the sidewalls suppress the horizontal pumping action that accompanies these states in spatially periodic domains.

Charge order-superfluidity transition in a two-dimensional system of hard-core bosons and emerging domain structures

Science.gov (United States)

Moskvin, A. S.; Panov, Yu. D.; Rybakov, F. N.; Borisov, A. B.

2017-11-01

We have used high-performance parallel computations by NVIDIA graphics cards applying the method of nonlinear conjugate gradients and Monte Carlo method to observe directly the developing ground state configuration of a two-dimensional hard-core boson system with decrease in temperature, and its evolution with deviation from a half-filling. This has allowed us to explore unconventional features of a charge order—superfluidity phase transition, specifically, formation of an irregular domain structure, emergence of a filamentary superfluid structure that condenses within of the charge-ordered phase domain antiphase boundaries, and formation and evolution of various topological structures.

Polyharmonic boundary value problems positivity preserving and nonlinear higher order elliptic equations in bounded domains

CERN Document Server

Gazzola, Filippo; Sweers, Guido

2010-01-01

This monograph covers higher order linear and nonlinear elliptic boundary value problems in bounded domains, mainly with the biharmonic or poly-harmonic operator as leading principal part. Underlying models and, in particular, the role of different boundary conditions are explained in detail. As for linear problems, after a brief summary of the existence theory and Lp and Schauder estimates, the focus is on positivity or - since, in contrast to second order equations, a general form of a comparison principle does not exist - on “near positivity.” The required kernel estimates are also presented in detail. As for nonlinear problems, several techniques well-known from second order equations cannot be utilized and have to be replaced by new and different methods. Subcritical, critical and supercritical nonlinearities are discussed and various existence and nonexistence results are proved. The interplay with the positivity topic from the first part is emphasized and, moreover, a far-reaching Gidas-Ni-Nirenbe...

Residues in the membrane-spanning domain core modulate conformation and fusogenicity of the HIV-1 envelope glycoprotein

International Nuclear Information System (INIS)

Shang Liang; Hunter, Eric

2010-01-01

The membrane-spanning domain (MSD) of human immunodeficiency virus type I (HIV-1) envelope glycoprotein (Env) is critical for its biological activity. Initial studies have defined an almost invariant 'core' structure in the MSD and demonstrated that it is crucial for anchoring Env in the membrane and virus entry. We show here that amino acid substitutions in the MSD 'core' do not influence specific virus-cell attachment, nor CD4 receptor and CXCR4 coreceptor recognition by Env. However, substitutions within the MSD 'core' delayed the kinetics and reduced the efficiency of cell-cell fusion mediated by Env. Although we observed no evidence that membrane fusion mediated by the MSD core mutants was arrested at a hemifusion stage, impaired Env fusogenicity was correlated with minor conformational changes in the V2, C1, and C5 regions in gp120 and the immunodominant loop in gp41. These changes could delay initiation of the conformational changes required in the fusion process.

Hydrophobic core substitutions in calbindin D9k

DEFF Research Database (Denmark)

Kragelund, B B; Jönsson, M; Bifulco, G

1998-01-01

Hydrophobic core residues have a marked influence on the Ca2+-binding properties of calbindin D9k, even though there are no direct contacts between these residues and the bound Ca2+ ions. Eleven different mutants with substitutions in the hydrophobic core were produced, and their equilibrium Ca2+...... that the hydrophobic core residues promote Ca2+ binding both by contributing to the preformation of the Ca2+ sites in the apo state and by preferentially stabilizing the Ca2+-bound state.......Hydrophobic core residues have a marked influence on the Ca2+-binding properties of calbindin D9k, even though there are no direct contacts between these residues and the bound Ca2+ ions. Eleven different mutants with substitutions in the hydrophobic core were produced, and their equilibrium Ca2...... that the mutation causes only very minimal perturbations in the immediate vicinity of residue 61. Substitutions of alanines or glycines for bulky residues in the center of the core were found to have significant effects on both Ca2+ affinity and dissociation rates. These substitutions caused a reduction in affinity...

On the Applicability of Lower Bounds for Solving Rectilinear

DEFF Research Database (Denmark)

Clausen, Jens; Karisch, Stefan E.; Perregaard, M.

1998-01-01

. Recently, lower bounds based on decomposition were proposed for the so called rectilinear QAP that proved to be the strongest for a large class of problem instances. We investigate the strength of these bounds when applied not only at the root node of a search tree but as the bound function used......The quadratic assignment problem (QAP) belongs to the hard core of NP-hard optimization problems. After almost forty years of research only relatively small instances can be solved to optimality. The reason is that the quality of the lower bounds available for exact methods is not sufficient...

Performance Analysis of Fission and Surface Source Iteration Method for Domain Decomposed Monte Carlo Whole-Core Calculation

International Nuclear Information System (INIS)

Jo, Yu Gwon; Oh, Yoo Min; Park, Hyang Kyu; Park, Kang Soon; Cho, Nam Zin

2016-01-01

In this paper, two issues in the FSS iteration method, i.e., the waiting time for surface source data and the variance biases in local tallies are investigated for the domain decomposed, 3-D continuous-energy whole-core calculation. The fission sources are provided as usual, while the surface sources are provided by banking MC particles crossing local domain boundaries. The surface sources serve as boundary conditions for nonoverlapping local problems, so that each local problem can be solved independently. In this paper, two issues in the FSS iteration are investigated. One is quantifying the waiting time of processors to receive surface source data. By using nonblocking communication, 'time penalty' to wait for the arrival of the surface source data is reduced. The other important issue is underestimation of the sample variance of the tally because of additional inter-iteration correlations in surface sources. From the numerical results on a 3-D whole-core test problem, it is observed that the time penalty is negligible in the FSS iteration method and that the real variances of both pin powers and assembly powers are estimated by the HB method. For those purposes, three cases; Case 1 (1 local domain), Case 2 (4 local domains), Case 3 (16 local domains) are tested. For both Cases 2 and 3, the time penalties for waiting are negligible compared to the source-tracking times. However, for finer divisions of local domains, the loss of parallel efficiency caused by the different number of sources for local domains in symmetric locations becomes larger due to the stochastic errors in source distributions. For all test cases, the HB method very well estimates the real variances of local tallies. However, it is also noted that the real variances of local tallies estimated by the HB method show slightly smaller than the real variances obtained from 30 independent batch runs and the deviations become larger for finer divisions of local domains. The batch size used for the HB

The perturbation of tryptophan fluorescence by phenylalanine to alanine mutations identifies the hydrophobic core in a subset of bacterial Ig-like domains.

Science.gov (United States)

Raman, Rajeev; Ptak, Christopher P; Hsieh, Ching-Lin; Oswald, Robert E; Chang, Yung-Fu; Sharma, Yogendra

2013-07-09

Many host-parasite interactions are mediated via surface-exposed proteins containing bacterial immunoglobulin-like (Big) domains. Here, we utilize the spectral properties of a conserved Trp to provide evidence that, along with a Phe, these residues are positioned within the hydrophobic core of a subset of Big_2 domains. The mutation of the Phe to Ala decreases Big_2 domain stability and impairs the ability of LigBCen2 to bind to the host protein, fibronectin.

Characterizing Mobile/Less-Mobile Porosity and Solute Exchange in Dual-Domain Media Using Tracer Experiments and Electrical Measurements in a Hassler-Type Core Holder

Science.gov (United States)

Falzone, S.; Slater, L. D.; Day-Lewis, F. D.; Parker, B. L.; Keating, K.; Robinson, J.

2017-12-01

Mass transfer is the process by which solute is retained in less-mobile porosity domains, and later released into the mobile porosity domain. This process is often responsible for the slow arrival and gradual release of contaminants and solute tracers. Recent studies have outlined methods using dual-domain mass transfer (DDMT) models for characterizing this phenomenon. These models use the non-linear relationship of bulk (σb) and fluid (σf) conductivity, collected from electrical methods during tracer experiments, to characterize the less-mobile/mobile porosity ratio (β) and the mass-transfer rate coefficient (α). DDMT models use the hysteretic σb-σf relationship observed while solute tracers are injected and then flushed from a sample media. Due to limitations in observing the hysteretic σb-σf relationship, this method has not been used to characterize low permeability samples. We have developed an experimental method for testing porous rock cores that allows us to develop a fundamental understanding of contaminant storage and release in consolidated rock. We test the approach on cores from sedimentary rock sites where mass transfer is expected to occur between hydraulically connected fractures and the adjacent low permeability rock matrix. Our method uses a Hassler-type core holder, designed to apply confining pressure around the outside of a sample core, which hydraulically isolates the sample core, allowing water to be injected into it at increased pressures. The experimental apparatus was also designed to measure σb with spectral induced polarization (SIP) measurements, and σf from a sampling port located at the center of the core. Cores were initially saturated with a solution with high electrical conductivity ( 80000 μS/cm). DI water was then injected into the cores at elevated pressures (>60 psi) and the saturating solution was flushed from the cores, in order to generate flow rates fast enough to capture the non-linear σb-σf relationship

Accumulating Data to Optimally Predict Obesity Treatment (ADOPT) Core Measures: Environmental Domain.

Science.gov (United States)

Saelens, Brian E; Arteaga, S Sonia; Berrigan, David; Ballard, Rachel M; Gorin, Amy A; Powell-Wiley, Tiffany M; Pratt, Charlotte; Reedy, Jill; Zenk, Shannon N

2018-04-01

There is growing interest in how environment is related to adults' weight and activity and eating behaviors. However, little is known about whether environmental factors are related to the individual variability seen in adults' intentional weight loss or maintenance outcomes. The environmental domain subgroup of the Accumulating Data to Optimally Predict obesity Treatment (ADOPT) Core Measures Project sought to identify a parsimonious set of objective and perceived neighborhood and social environment constructs and corresponding measures to include in the assessment of response to adult weight-loss treatment. Starting with the home address, the environmental domain subgroup recommended for inclusion in future weight-loss or maintenance studies constructs and measures related to walkability, perceived land use mix, food outlet accessibility (perceived and objective), perceived food availability, socioeconomics, and crime-related safety (perceived and objective) to characterize the home neighborhood environment. The subgroup also recommended constructs and measures related to social norms (perceived and objective) and perceived support to characterize an individual's social environment. The 12 neighborhood and social environment constructs and corresponding measures provide a succinct and comprehensive set to allow for more systematic examination of the impact of environment on adults' weight loss and maintenance. © 2018 The Obesity Society.

The influence of core materials and mix on the performance of a 100 kVA three phase transformer core

Energy Technology Data Exchange (ETDEWEB)

Snell, David E-mail: dave.snell@cogent-power.com; Coombs, Alan

2003-01-01

Various grades of grain-oriented electrical steel, and the effect of mixing domain refined and non-domain refined materials in the same three phase transformer core have been assessed using a developed computer-based test system. Ball unit domain refined material and non-domain refined material can be successfully mixed in the same core, without degrading performance.

The missing evaluation codes from order domain theory

DEFF Research Database (Denmark)

Andersen, Henning Ejnar; Geil, Olav

The Feng-Rao bound gives a lower bound on the minimum distance of codes defined by means of their parity check matrices. From the Feng-Rao bound it is clear how to improve a large family of codes by leaving out certain rows in their parity check matrices. In this paper we derive a simple lower...... generalized Hamming weight. We interpret our methods into the setting of order domain theory. In this way we fill in an obvious gap in the theory of order domains. The improved codes from the present paper are not in general equal to the Feng-Rao improved codes but the constructions are very much related....

P2-16: Dual-Bound Model and the Role of Time Bound in Perceptual Decision Making

Directory of Open Access Journals (Sweden)

Daeseob Lim

2012-10-01

Full Text Available The diffusion model (DM encapsulates the dynamics of perceptual decision within a ‘diffusion field’ that is defined by a basis with sensory-evidence (SE and time vectors. At the core of the DM, it assumes that a decision is not made until an evidence particle drifts in the diffusion field and eventually hits one of the two pre-fixed bounds defined in the SE axis. This assumption dictates when and which choice is made by referring to when and which bound will be hit by the evidence particle. What if urgency pressures the decision system to make a choice even when the evidence particle has yet hit the SE bound? Previous modeling attempts at coping with time pressure, despite differences in detail, all manipulated the coordinate of SE bounds. Here, we offer a novel solution by adopting another bound on the time axis. This ‘dual-bound’ model (DBM posits that decisions can also be made when the evidence particle hits a time bound, which is determined on a trial-by-trial basis by a ‘perceived time interval’ – how long the system can stay in the ‘diffusion’ field. The classic single-bound model (SBM exhibited systematic errors in predicting both the reaction time distributions and the time-varying bias in choice. Those errors were not corrected by previously proposed variants of the SBM until the time bound was introduced. The validity of the DBM was further supported by the strong across-individual correlation between observed precision of interval timing and the predicted trial-by-trial variability of the time bound.

Consensus on core phenomena and statements describing Basic Body Awareness Therapy within the movement awareness domain in physiotherapy.

Science.gov (United States)

Skjaerven, L H; Mattsson, M; Catalan-Matamoros, D; Parker, A; Gard, G; Gyllensten, A Lundvik

2018-02-26

Physiotherapists are facing complex health challenges in the treatment of persons suffering from long-lasting musculoskeletal disorders and mental health problems. Basic Body Awareness Therapy (BBAT) is a physiotherapy approach within the movement awareness domain developed to bridge physical, mental, and relational health challenges. The purpose of this study was to reach a consensus on core phenomena and statements describing BBAT. A consensus-building process was conducted using the nominal group technique (NGT). Twenty-one BBAT experts from 10 European countries participated in a concentrated weekend workshop of 20 hours. All participants signed informed consent. Participants reached a consensus on 138 core phenomena, clustered in three overarching categories: clinical core, historical roots, and research and evaluation phenomena. Of the 106 clinical core phenomena, the participants agreed on three categories of phenomena: movement quality, movement awareness practice, and movement awareness therapy and pedagogy. Furthermore, the participants reached 100 percent consensus on 16 of 30 statements describing BBAT. This study provides a consensus on core phenomena and statements describing BBAT. The data reveal phenomena implemented when promoting movement quality through movement awareness. Data provide clarity in some aspects of the vocabulary as fundamental theory. Further reearch will be developed.

The crystal structures of EAP domains from Staphylococcus aureus reveal an unexpected homology to bacterial superantigens.

Science.gov (United States)

Geisbrecht, Brian V; Hamaoka, Brent Y; Perman, Benjamin; Zemla, Adam; Leahy, Daniel J

2005-04-29

The Eap (extracellular adherence protein) of Staphylococcus aureus functions as a secreted virulence factor by mediating interactions between the bacterial cell surface and several extracellular host proteins. Eap proteins from different Staphylococcal strains consist of four to six tandem repeats of a structurally uncharacterized domain (EAP domain). We have determined the three-dimensional structures of three different EAP domains to 1.8, 2.2, and 1.35 A resolution, respectively. These structures reveal a core fold that is comprised of an alpha-helix lying diagonally across a five-stranded, mixed beta-sheet. Comparison of EAP domains with known structures reveals an unexpected homology with the C-terminal domain of bacterial superantigens. Examination of the structure of the superantigen SEC2 bound to the beta-chain of a T-cell receptor suggests a possible ligand-binding site within the EAP domain (Fields, B. A., Malchiodi, E. L., Li, H., Ysern, X., Stauffacher, C. V., Schlievert, P. M., Karjalainen, K., and Mariuzza, R. (1996) Nature 384, 188-192). These results provide the first structural characterization of EAP domains, relate EAP domains to a large class of bacterial toxins, and will guide the design of future experiments to analyze EAP domain structure/function relationships.

Dense SDM (12-core × 3-mode) transmission over 527 km with 33.2-ns mode-dispersion employing low-complexity parallel MIMO frequency-domain equalization

DEFF Research Database (Denmark)

Shibahara, K.; Mizuno, T.; Takara, H.

We demonstrate 12-core × 3-mode dense SDM transmission over 527 km graded-index multi-core few-mode fiber without mode-dispersion management. Employing low baud rate multi-carrier signal and frequency-domain equalization enables 33.2-ns DMD compensation with low computational complexity. © 2015 OSA...

Monte Carlo simulation of magnetic multi-core nanoparticles

International Nuclear Information System (INIS)

Schaller, Vincent; Wahnstroem, Goeran; Sanz-Velasco, Anke; Enoksson, Peter; Johansson, Christer

2009-01-01

In this paper, a Monte Carlo simulation is carried out to evaluate the equilibrium magnetization of magnetic multi-core nanoparticles in a liquid and subjected to a static magnetic field. The particles contain a magnetic multi-core consisting of a cluster of magnetic single-domains of magnetite. We show that the magnetization of multi-core nanoparticles cannot be fully described by a Langevin model. Inter-domain dipolar interactions and domain magnetic anisotropy contribute to decrease the magnetization of the particles, whereas the single-domain size distribution yields an increase in magnetization. Also, we show that the interactions affect the effective magnetic moment of the multi-core nanoparticles.

Crystal optimization and preliminary diffraction data analysis of the Smad1 MH1 domain bound to a palindromic SBE DNA element

International Nuclear Information System (INIS)

Baburajendran, Nithya; Palasingam, Paaventhan; Ng, Calista Keow Leng; Jauch, Ralf; Kolatkar, Prasanna R.

2009-01-01

Crystals of palindromic SBE DNA-bound Smad1 MH1 domain diffracting to 2.7 Å resolution have been obtained. The bone morphogenetic protein (BMP) signalling pathway regulates diverse processes such as cell differentiation, anterior/posterior axis specification, cell growth and the formation of extra-embryonic tissues. The transcription factor Smad1 relays the BMP signal from the cytoplasm to the nucleus, where it binds short DNA-sequence motifs and regulates gene expression. However, how Smad1 selectively targets particular genomic regions is poorly understood. In order to understand the physical basis of the specific interaction of Smad1 with DNA and to contrast it with the highly homologous but functionally distinct Smad3 protein, the DNA-binding Mad-homology 1 (MH1) domain of Smad1 was cocrystallized with a 17-mer palindromic Smad-binding element (SBE). The extensive optimizations of the length, binding-site spacing and terminal sequences of the DNA element in combination with the other crystallization parameters necessary for obtaining diffraction-quality crystals are described here. A 2.7 Å resolution native data set was collected at the National Synchrotron Radiation Research Centre, Taiwan, from crystals grown in a solution containing 0.2 M ammonium tartrate dibasic, 20% PEG 3350, 3% 2-propanol and 10% glycerol. The data set was indexed and merged in space group P222, with unit-cell parameters a = 73.94, b = 77.49, c = 83.78 Å, α = β = γ = 90°. The solvent content in the unit cell is consistent with the presence of two Smad1 MH1 molecules bound to the duplex DNA in the asymmetric unit

Quantitative analysis of the interaction between the envelope protein domains and the core protein of human hepatitis B virus

International Nuclear Information System (INIS)

Choi, Kyoung-Jae; Lim, Chun-Woo; Yoon, Moon-Young; Ahn, Byung-Yoon; Yu, Yeon Gyu

2004-01-01

Interaction between preformed nucleocapsids and viral envelope proteins is critical for the assembly of virus particles in infected cells. The pre-S1 and pre-S2 and cytosolic regions of the human hepatitis B virus envelope protein had been implicated in the interaction with the core protein of nucleocapsids. The binding affinities of specific subdomains of the envelope protein to the core protein were quantitatively measured by both ELISA and BIAcore assay. While a marginal binding was detected with the pre-S1 or pre-S2, the core protein showed high affinities to pre-S with apparent dissociation constants (K D app ) of 7.3 ± 0.9 and 8.2 ± 0.4 μM by ELISA and BIAcore assay, respectively. The circular dichroism analysis suggested that conformational change occurs in pre-S through interaction with core protein. These results substantiate the importance of specific envelope domains in virion assembly, and demonstrate that the interaction between viral proteins can be quantitatively measured in vitro

Maps of Bounded Rationality

OpenAIRE

Kahneman, Daniel

2002-01-01

The work cited by the Nobel committee was done jointly with the late Amos Tversky (1937-1996) during a long and unusually close collaboration. Together, we explored the psychology of intuitive beliefs and choices and examined their bounded rationality. This essay presents a current perspective on the three major topics of our joint work: heuristics of judgment, risky choice, and framing effects. In all three domains we studied intuitions - thoughts and preferences that come to mind quickly an...

Mutational analyses of the core domain of Avian Leukemia and Sarcoma Viruses integrase: critical residues for concerted integration and multimerization

International Nuclear Information System (INIS)

Moreau, Karen; Faure, Claudine; Violot, Sebastien; Gouet, Patrice; Verdier, Gerard; Ronfort, Corinne

2004-01-01

During replicative cycle of retroviruses, the reverse-transcribed viral DNA is integrated into the cell DNA by the viral integrase (IN) enzyme. The central core domain of IN contains the catalytic site of the enzyme and is involved in binding viral ends and cell DNA as well as dimerization. We previously performed single amino acid substitutions in the core domain of an Avian Leukemia and Sarcoma Virus (ALSV) IN [Arch. Virol. 147 (2002) 1761]. Here, we modeled the resulting IN mutants and analyzed the ability of these mutants to mediate concerted DNA integration in an in vitro assay, and to form dimers by protein-protein cross-linking and size exclusion chromatography. The N197C mutation resulted in the inability of the mutant to perform concerted integration that was concomitant with a loss of IN dimerization. Surprisingly, mutations Q102G and A106V at the dimer interface resulted in mutants with higher efficiencies than the wild-type IN in performing two-ended concerted integration of viral DNA ends. The G139D and A195V mutants had a trend to perform one-ended DNA integration of viral ends instead of two-ended integration. More drastically, the I88L and L135G mutants preferentially mediated nonconcerted DNA integration although the proteins form dimers. Therefore, these mutations may alter the formation of IN complexes of higher molecular size than a dimer that would be required for concerted integration. This study points to the important role of core domain residues in the concerted integration of viral DNA ends as well as in the oligomerization of the enzyme

Uniformly bounded representations of the Lorentz groups

International Nuclear Information System (INIS)

Brega, A.O.

1982-01-01

For the Lorentz group G = SO/sub e/(n + 1, 1)(ngreater than or equal to 2) the author constructs a family of uniformly bounded representations by means of analytically continuing a certain normalization of the unitary principal series. The method the author uses relies on an analysis of various operators under a Mellin transform and extends earlier work of E.N. Wilson. In a series of papers Kunze and Stein initiated the theory of uniformly bounded representations of semisimple Lie groups; the starting point is the unitary principal series T(sigma,s) obtained in a certain subgroup M of G and a purely imaginary number s. From there Kunze and Stein constructed families of representations R(sigma,s) depending analytically on a parameter s in a domain D of C containing the imaginary axis which are unitarily equilvalent to T(sigma,s) for s contained in the set of imaginary numbers and whose operator norms are uniformly bounded for each s in D. In the case of the Lorentz groups SO/sub e/(n + 1, 1)(ngreater than or equal to2) and the trivial representation 1 of M, E.N. Wilson obtained such a family R(1,s) for the domain D = [s contained in the set of C: absolute value Re(s) Vertical Bar2]. For this domain D and for any representation sigma of M the author provides a family R(sigma,s) of uniformly bounded representations analytically continuing T(sigma,s), thereby generalizing Wilson's work. The author has also investigated certain symmetry properties of the representations R(sigma,s) under the action of the Weyl group. The trivial representation is Weyl group invariant and the family R(1,s) obtained by Wilson satisfies R(1,s) = R(1,-s) reflecting this. Obtained was the analogous result R(sigma,s) = R(sigma,-s) for some well known representations sigma that are Weyl group invariant. This involves the explicit computation of certain constants arising in the Fourier transforms of intertwining operators

Alternative to domain wall fermions

International Nuclear Information System (INIS)

Neuberger, H.

2002-01-01

An alternative to commonly used domain wall fermions is presented. Some rigorous bounds on the condition number of the associated linear problem are derived. On the basis of these bounds and some experimentation it is argued that domain wall fermions will in general be associated with a condition number that is of the same order of magnitude as the product of the condition number of the linear problem in the physical dimensions by the inverse bare quark mass. Thus, the computational cost of implementing true domain wall fermions using a single conjugate gradient algorithm is of the same order of magnitude as that of implementing the overlap Dirac operator directly using two nested conjugate gradient algorithms. At a cost of about a factor of two in operation count it is possible to make the memory usage of direct implementations of the overlap Dirac operator independent of the accuracy of the approximation to the sign function and of the same order as that of standard Wilson fermions

MacA, a periplasmic membrane fusion protein of the macrolide transporter MacAB-TolC, binds lipopolysaccharide core specifically and with high affinity.

Science.gov (United States)

Lu, Shuo; Zgurskaya, Helen I

2013-11-01

The Escherichia coli MacAB-TolC transporter has been implicated in efflux of macrolide antibiotics and secretion of enterotoxin STII. In this study, we found that purified MacA, a periplasmic membrane fusion protein, contains one tightly bound rough core lipopolysaccharide (R-LPS) molecule per MacA molecule. R-LPS was bound specifically to MacA protein with affinity exceeding that of polymyxin B. Sequence analyses showed that MacA contains two high-density clusters of positively charged amino acid residues located in the cytoplasmic N-terminal domain and the periplasmic C-terminal domain. Substitutions in the C-terminal cluster reducing the positive-charge density completely abolished binding of R-LPS. At the same time, these substitutions significantly reduced the functionality of MacA in the protection of E. coli against macrolides in vivo and in the in vitro MacB ATPase stimulation assays. Taken together, our results suggest that R-LPS or a similar glycolipid is a physiological substrate of MacAB-TolC.

Harmonic Domain Modelling of Transformer Core Nonlinearities Using the DIgSILENT PowerFactory Software

DEFF Research Database (Denmark)

Bak, Claus Leth; Bak-Jensen, Birgitte; Wiechowski, Wojciech

2008-01-01

This paper demonstrates the results of implementation and verification of an already existing algorithm that allows for calculating saturation characteristics of singlephase power transformers. The algorithm was described for the first time in 1993. Now this algorithm has been implemented using...... the DIgSILENT Programming Language (DPL) as an external script in the harmonic domain calculations of a power system analysis tool PowerFactory [10]. The algorithm is verified by harmonic measurements on a single-phase power transformer. A theoretical analysis of the core nonlinearities phenomena...... in single and three-phase transformers is also presented. This analysis leads to the conclusion that the method can be applied for modelling nonlinearities of three-phase autotransformers....

Comparison of diagnostic classification systems for delirium with new research criteria that incorporate the three core domains.

Science.gov (United States)

Trzepacz, Paula T; Meagher, David J; Franco, José G

2016-05-01

Diagnostic classification systems do not incorporate phenomenological research findings about the three core symptom domains of delirium (Attentional/Cognitive, Circadian, Higher Level Thinking). We evaluated classification performances of novel Trzepacz, Meagher, and Franco research diagnostic criteria (TMF) that incorporate those domains and ICD-10, DSM-III-R, DSM-IV, and DSM-5. Primary data analysis of 641 patients with mixed neuropsychiatric profiles. Delirium (n=429) and nondelirium (n=212) reference standard groups were identified using cluster analysis of symptoms assessed using the Delirium Rating Scale-Revised-98. Accuracy, sensitivity, specificity, positive and negative predictive values (PPV, NPV), and likelihood ratios (LR+, LR-) are reported. TMF criteria had high sensitivity and specificity (87.4% and 89.2%), more balanced than DSM-III-R (100% and 31.6%), DSM-IV (97.7% and 74.1%), DSM-5 (97.7% and 72.6%), and ICD-10 (66.2% and 100%). PPV of DSM-III-R, DSM-IV, and DSM-5 were 90%. ICD-10 had the lowest NPV (59.4%). TMF had the highest LR+ (8.06) and DSM-III-R the lowest LR- (0.0). Overall, values for DSM-IV and DSM-5 were similar, whereas for ICD-10 and DSM-III-R were inverse of each other. In the pre-existing cognitive impairment/dementia subsample (n=128), TMF retained its highest LR+ though specificity (58.3%) became less well balanced with sensitivity (87.9%), which still exceeded that of DSM. TMF research diagnostic criteria performed well, with more balanced sensitivity and specificity and the highest likelihood ratio for delirium identification. Reflecting the three core domains of delirium, TMF criteria may have advantages in biological research where delineation of this syndrome is important. Copyright © 2016. Published by Elsevier Inc.

Scanning microscopy of magnetic domains using the Fe 3p core level transverse magneto-optical Kerr effect

Science.gov (United States)

Friedrich, J.; Rozhko, I.; Voss, J.; Hillebrecht, F. U.; Kisker, E.; Wedemeier, V.

1999-04-01

We demonstrate the feasibility of the vacuum ultraviolet analog to visible-light magneto-optical imaging of magnetic structures using the resonantly enhanced transverse magneto-optical Kerr effect at core level thresholds with incident p-polarized radiation. The advantages are element specificity and a variable information depth. We used the scanning x-ray microscope at HASYLAB capable of obtaining about 1 μm resolution by means of its focusing ellipsoidal ring mirror. The p-polarized component of the reflected light was selected using multilayer reflection at an additional plane mirror downstream to the sample. Micrographs of the optical reflectivity were taken in the vicinity of the Fe 3p core level threshold at 53.7 and 56.5 eV photon energy where the magneto-optical effect is of opposite sign. Magnetic domains are visible in the difference of both recorded images.

Quanty for core level spectroscopy - excitons, resonances and band excitations in time and frequency domain

International Nuclear Information System (INIS)

Haverkort, Maurits W.

2016-01-01

Depending on the material and edge under consideration, core level spectra manifest themselves as local excitons with multiplets, edge singularities, resonances, or the local projected density of states. Both extremes, i.e., local excitons and non-interacting delocalized excitations are theoretically well under control. Describing the intermediate regime, where local many body interactions and band-formation are equally important is a challenge. Here we discuss how Quanty , a versatile quantum many body script language, can be used to calculate a variety of different core level spectroscopy types on solids and molecules, both in the frequency as well as the time domain. The flexible nature of Quanty allows one to choose different approximations for different edges and materials. For example, using a newly developed method merging ideas from density renormalization group and quantum chemistry [1-3], Quanty can calculate excitons, resonances and band-excitations in x-ray absorption, photoemission, x-ray emission, fluorescence yield, non-resonant inelastic x-ray scattering, resonant inelastic x-ray scattering and many more spectroscopy types. Quanty can be obtained from: http://www.quanty.org. (paper)

A structural role for the PHP domain in E. coli DNA polymerase III.

Science.gov (United States)

Barros, Tiago; Guenther, Joel; Kelch, Brian; Anaya, Jordan; Prabhakar, Arjun; O'Donnell, Mike; Kuriyan, John; Lamers, Meindert H

2013-05-14

In addition to the core catalytic machinery, bacterial replicative DNA polymerases contain a Polymerase and Histidinol Phosphatase (PHP) domain whose function is not entirely understood. The PHP domains of some bacterial replicases are active metal-dependent nucleases that may play a role in proofreading. In E. coli DNA polymerase III, however, the PHP domain has lost several metal-coordinating residues and is likely to be catalytically inactive. Genomic searches show that the loss of metal-coordinating residues in polymerase PHP domains is likely to have coevolved with the presence of a separate proofreading exonuclease that works with the polymerase. Although the E. coli Pol III PHP domain has lost metal-coordinating residues, the structure of the domain has been conserved to a remarkable degree when compared to that of metal-binding PHP domains. This is demonstrated by our ability to restore metal binding with only three point mutations, as confirmed by the metal-bound crystal structure of this mutant determined at 2.9 Å resolution. We also show that Pol III, a large multi-domain protein, unfolds cooperatively and that mutations in the degenerate metal-binding site of the PHP domain decrease the overall stability of Pol III and reduce its activity. While the presence of a PHP domain in replicative bacterial polymerases is strictly conserved, its ability to coordinate metals and to perform proofreading exonuclease activity is not, suggesting additional non-enzymatic roles for the domain. Our results show that the PHP domain is a major structural element in Pol III and its integrity modulates both the stability and activity of the polymerase.

Faddeev-Yakubovsky technique for weakly bound systems

International Nuclear Information System (INIS)

Hadizadeh, M.R.; Yamashita, M.T.; Tomio, Lauro; Delfino, A.

2011-01-01

Nature shows the existence of weakly bound systems in different sectors, ranging from atomic to nuclear physics. Few-body systems with large scattering length exhibit universal features, which are independent of the details of the interaction, and thus are common to nuclear and atomic systems. Very different methods are used to study the properties of few-body systems, from Faddeev methods to diagonalization methods that rely on an expansion of the wave functions in a complete basis set, like e.g. hyper-spherical harmonics and no core shell model. In this talk we present Faddeev-Yakubovsky method to study the three- and four-body bound states in momentum space. To show the efficiency and accuracy of the method we investigate the three- and four-boson weakly bound states in unitary limit (for zero two-body binding) and we present a pretty complete picture of universality. (author)

The Distributed-SDF Domain

DEFF Research Database (Denmark)

Cuadrado, Daniel Lázaro; Ravn, Anders Peter; Koch, Peter

2005-01-01

The purpose of the Distributed-SDF domain for Ptolemy II is to allow distributed simulation of SDF models. It builds on top of the existing SDF domain by extending it. From the user’s point of view, using the Distributed-SDF director is sufficient to run the distributed version. It provides optio...... distributed nature. First of all, known memory bounds of the JVM can be overcome. Second, it yields smaller simulation times, mainly for models with high degree of parallelism and granularity....

The shock formation distance in a bounded sound beam of finite amplitude.

Science.gov (United States)

Tao, Chao; Ma, Jian; Zhu, Zhemin; Du, Gonghuan; Ping, Zihong

2003-07-01

This paper investigates the shock formation distance in a bounded sound beam of finite amplitude by solving the Khokhlov-Zabolotskaya-Kuznetsov (KZK) equation using frequency-domain numerical method. Simulation results reveal that, besides the nonlinearity and absorption, the diffraction is another important factor that affects the shock formation of a bounded sound beam. More detailed discussions of the shock formation in a bounded sound beam, such as the waveform of sound pressure and the spatial distribution of shock formation, are also presented and compared for different parameters.

Decoherence in Neutrino Propagation Through Matter, and Bounds from IceCube/DeepCore

Energy Technology Data Exchange (ETDEWEB)

Coloma, Pilar [Fermilab; Lopez-Pavon, Jacobo [CERN; Martinez-Soler, Ivan [Madrid, IFT; Nunokawa, Hiroshi [Rio de Janeiro, Pont. U. Catol.

2018-03-12

We revisit neutrino oscillations in matter considering the open quantum system framework which allows to introduce possible decoherence effects generated by New Physics in a phenomenological manner. We assume that the decoherence parameters $\\gamma_{ij}$ may depend on the neutrino energy, as $\\gamma_{ij}=\\gamma_{ij}^{0}(E/\\text{GeV})^n$ $(n = 0,\\pm1,\\pm2) $. The case of non-uniform matter is studied in detail, both within the adiabatic approximation and in the more general non-adiabatic case. In particular, we develop a consistent formalism to study the non-adiabatic case dividing the matter profile into an arbitrary number of layers of constant densities. This formalism is then applied to explore the sensitivity of IceCube and DeepCore to this type of effects. Our study is the first atmospheric neutrino analysis where a consistent treatment of the matter effects in the three-neutrino case is performed in presence of decoherence. We show that matter effects are indeed extremely relevant in this context. We find that IceCube is able to considerably improve over current bounds in the solar sector ($\\gamma_{21}$) and in the atmospheric sector ($\\gamma_{31}$ and $\\gamma_{32}$) for $n=0,1,2$ and, in particular, by several orders of magnitude (between 3 and 9) for the $n=1,2$ cases. For $n=0$ we find $\\gamma_{32},\\gamma_{31}< 4.0\\cdot10^{-24} (1.3\\cdot10^{-24})$ GeV and $\\gamma_{21}<1.3\\cdot10^{-24} (4.1\\cdot10^{-24})$ GeV, for normal (inverted) mass ordering.

Contribution of the C-terminal region within the catalytic core domain of HIV-1 integrase to yeast lethality, chromatin binding and viral replication

Directory of Open Access Journals (Sweden)

Belhumeur Pierre

2008-11-01

Full Text Available Abstract Background HIV-1 integrase (IN is a key viral enzymatic molecule required for the integration of the viral cDNA into the genome. Additionally, HIV-1 IN has been shown to play important roles in several other steps during the viral life cycle, including reverse transcription, nuclear import and chromatin targeting. Interestingly, previous studies have demonstrated that the expression of HIV-1 IN induces the lethal phenotype in some strains of Saccharomyces cerevisiae. In this study, we performed mutagenic analyses of the C-terminal region of the catalytic core domain of HIV-1 IN in order to delineate the critical amino acid(s and/or motif(s required for the induction of the lethal phenotype in the yeast strain HP16, and to further elucidate the molecular mechanism which causes this phenotype. Results Our study identified three HIV-1 IN mutants, V165A, A179P and KR186,7AA, located in the C-terminal region of the catalytic core domain of IN that do not induce the lethal phenotype in yeast. Chromatin binding assays in yeast and mammalian cells demonstrated that these IN mutants were impaired for the ability to bind chromatin. Additionally, we determined that while these IN mutants failed to interact with LEDGF/p75, they retained the ability to bind Integrase interactor 1. Furthermore, we observed that VSV-G-pseudotyped HIV-1 containing these IN mutants was unable to replicate in the C8166 T cell line and this defect was partially rescued by complementation with the catalytically inactive D64E IN mutant. Conclusion Overall, this study demonstrates that three mutations located in the C-terminal region of the catalytic core domain of HIV-1 IN inhibit the IN-induced lethal phenotype in yeast by inhibiting the binding of IN to the host chromatin. These results demonstrate that the C-terminal region of the catalytic core domain of HIV-1 IN is important for binding to host chromatin and is crucial for both viral replication and the promotion of

A conserved glutamine plays a central role in LOV domain signal transmission and duration

Science.gov (United States)

Nash, Abigail I.; Ko, Wen-Huang; Harper, Shannon M.; Gardner, Kevin H.

2009-01-01

Light is a key stimulus for plant biological functions, several of which are controlled by light-activated kinases known as phototropins, a group of kinases that contain two light-sensing domains (LOV, Light-Oxygen-Voltage domains) and a C-terminal serine/threonine kinase domain. The second sensory domain, LOV2, plays a key role in regulating kinase enzymatic activity via the photochemical formation of a covalent adduct between a LOV2 cysteine residue and an internally-bound flavin mononucleotide (FMN) chromophore. Subsequent conformational changes in LOV2 lead to the unfolding of a peripheral Jα helix, and ultimately, phototropin kinase activation. To date, the mechanism coupling bond formation and helix dissociation has remained unclear. Previous studies found that a conserved glutamine residue (Q513 in the Avena sativa phototropin 1 LOV2 (AsLOV2) domain) switches its hydrogen-bonding pattern with FMN upon light stimulation. Located in the immediate vicinity of the FMN binding site, this Gln residue is provided by the Iβ strand that interacts with the Jα helix, suggesting a route for signal propagation from the core of the LOV domain to its peripheral Jα helix. To test whether Q513 plays a key role in tuning the photochemical and transduction properties of AsLOV2, we designed two point mutations, Q513L and Q513N, and monitored the effects on the chromophore and protein using a combination of UV-visible absorbance and circular dichroism spectroscopy, limited proteolysis, and solution NMR. The results show that these mutations significantly dampen the changes between the dark and lit state AsLOV2 structures, leaving the protein in a pseudo-dark state (Q513L) or a pseudo-lit state (Q513N) conformation. Further, both mutations changed the photochemical properties of this receptor, particularly the lifetime of the photoexcited signaling states. Together, these data establish that this residue plays a central role in both spectral tuning and signal propagation from

Maximum error-bounded Piecewise Linear Representation for online stream approximation

KAUST Repository

Xie, Qing; Pang, Chaoyi; Zhou, Xiaofang; Zhang, Xiangliang; Deng, Ke

2014-01-01

Given a time series data stream, the generation of error-bounded Piecewise Linear Representation (error-bounded PLR) is to construct a number of consecutive line segments to approximate the stream, such that the approximation error does not exceed a prescribed error bound. In this work, we consider the error bound in L∞ norm as approximation criterion, which constrains the approximation error on each corresponding data point, and aim on designing algorithms to generate the minimal number of segments. In the literature, the optimal approximation algorithms are effectively designed based on transformed space other than time-value space, while desirable optimal solutions based on original time domain (i.e., time-value space) are still lacked. In this article, we proposed two linear-time algorithms to construct error-bounded PLR for data stream based on time domain, which are named OptimalPLR and GreedyPLR, respectively. The OptimalPLR is an optimal algorithm that generates minimal number of line segments for the stream approximation, and the GreedyPLR is an alternative solution for the requirements of high efficiency and resource-constrained environment. In order to evaluate the superiority of OptimalPLR, we theoretically analyzed and compared OptimalPLR with the state-of-art optimal solution in transformed space, which also achieves linear complexity. We successfully proved the theoretical equivalence between time-value space and such transformed space, and also discovered the superiority of OptimalPLR on processing efficiency in practice. The extensive results of empirical evaluation support and demonstrate the effectiveness and efficiency of our proposed algorithms.

Maximum error-bounded Piecewise Linear Representation for online stream approximation

KAUST Repository

Xie, Qing

2014-04-04

Given a time series data stream, the generation of error-bounded Piecewise Linear Representation (error-bounded PLR) is to construct a number of consecutive line segments to approximate the stream, such that the approximation error does not exceed a prescribed error bound. In this work, we consider the error bound in L∞ norm as approximation criterion, which constrains the approximation error on each corresponding data point, and aim on designing algorithms to generate the minimal number of segments. In the literature, the optimal approximation algorithms are effectively designed based on transformed space other than time-value space, while desirable optimal solutions based on original time domain (i.e., time-value space) are still lacked. In this article, we proposed two linear-time algorithms to construct error-bounded PLR for data stream based on time domain, which are named OptimalPLR and GreedyPLR, respectively. The OptimalPLR is an optimal algorithm that generates minimal number of line segments for the stream approximation, and the GreedyPLR is an alternative solution for the requirements of high efficiency and resource-constrained environment. In order to evaluate the superiority of OptimalPLR, we theoretically analyzed and compared OptimalPLR with the state-of-art optimal solution in transformed space, which also achieves linear complexity. We successfully proved the theoretical equivalence between time-value space and such transformed space, and also discovered the superiority of OptimalPLR on processing efficiency in practice. The extensive results of empirical evaluation support and demonstrate the effectiveness and efficiency of our proposed algorithms.

Hydrogen Exchange Mass Spectrometry of Functional Membrane-bound Chemotaxis Receptor Complexes

Science.gov (United States)

Koshy, Seena S.; Eyles, Stephen J.; Weis, Robert M.; Thompson, Lynmarie K.

2014-01-01

The transmembrane signaling mechanism of bacterial chemotaxis receptors is thought to involve changes in receptor conformation and dynamics. The receptors function in ternary complexes with two other proteins, CheA and CheW, that form extended membrane-bound arrays. Previous studies have shown that attractant binding induces a small (~2 Å) piston displacement of one helix of the periplasmic and transmembrane domains towards the cytoplasm, but it is not clear how this signal propagates through the cytoplasmic domain to control the kinase activity of the CheA bound at the membrane-distal tip, nearly 200 Å away. The cytoplasmic domain has been shown to be highly dynamic, which raises the question of how a small piston motion could propagate through a dynamic domain to control CheA kinase activity. To address this, we have developed a method for measuring dynamics of the receptor cytoplasmic fragment (CF) in functional complexes with CheA and CheW. Hydrogen exchange mass spectrometry (HDX-MS) measurements of global exchange of CF demonstrate that CF exhibits significantly slower exchange in functional complexes than in solution. Since the exchange rates in functional complexes are comparable to that of other proteins of similar structure, the CF appears to be a well-structured protein within these complexes, which is compatible with its role in propagating a signal that appears to be a tiny conformational change in the periplasmic and transmembrane domains of the receptor. We also demonstrate the feasibility of this protocol for local exchange measurements, by incorporating a pepsin digest step to produce peptides with 87% sequence coverage and only 20% back exchange. This method extends HDX-MS to membrane-bound functional complexes without detergents that may perturb the stability or structure of the system. PMID:24274333

LKIF Core: principled ontology development for the legal domain

NARCIS (Netherlands)

Hoekstra, R.; Breuker, J.; Di Bello, M.; Boer, A.; Breuker, J.; Casanovas, P.; Klein, M.C.A.; Francesconi, E.

2009-01-01

In this paper we describe a legal core ontology that is part of the Legal Knowledge Interchange Format: a knowledge representation formalism that enables the translation of legal knowledge bases written in different representation formats and formalisms. A legal (core) ontology can play an important

Crystallization and preliminary X-ray diffraction analysis of the Pax9 paired domain bound to a DC5 enhancer DNA element.

Science.gov (United States)

Narasimhan, Kamesh; Hilbig, Antonia; Udayasuryan, Barath; Jayabal, Sriram; Kolatkar, Prasanna R; Jauch, Ralf

2014-10-01

Pax genes belong to a family of metazoan transcription factors that are known to play a critical role in eye, ear, kidney and neural development. The mammalian Pax family of transcription factors is characterized by a ∼128-amino-acid DNA-binding paired domain that makes sequence-specific contacts with DNA. The diversity in Pax gene activities emerges from complex modes of interaction with enhancer regions and heterodimerization with multiple interaction partners. Based on in vitro optimal binding-site selection studies and enhancer identification assays, it has been suggested that Pax proteins may recognize and bind their target DNA elements with different binding modes/topologies, however this hypothesis has not yet been structurally explored. One of the most extensively studied DNA target elements of the Pax6 paired domain is the eye-lens specific DC5 (δ-crystallin) enhancer element. In order to shed light on Pax6-DC5 DNA interactions, the related paired-domain prototype Pax9 was crystallized with the minimal δ-crystallin DC5 enhancer element and preliminary X-ray diffraction analysis was attempted. A 3.0 Å resolution native data set was collected at the National Synchrotron Light Source (NSLS), Brookhaven from crystals grown in a solution consisting of 10%(w/v) PEG 20K, 20%(v/v) PEG 550 MME, 0.03 M NaNO3, 0.03 M Na2HPO4, 0.03 M NH2SO4, 0.1 M MES/imidazole pH 6.5. The data set was indexed and merged in space group C2221, with unit-cell parameters a = 75.74, b = 165.59, c = 70.14 Å, α = β = γ = 90°. The solvent content in the unit cell is consistent with the presence of one Pax9 paired domain bound to duplex DNA in the asymmetric unit.

Crystallization and preliminary X-ray diffraction analysis of the Pax9 paired domain bound to a DC5 enhancer DNA element

Science.gov (United States)

Narasimhan, Kamesh; Hilbig, Antonia; Udayasuryan, Barath; Jayabal, Sriram; Kolatkar, Prasanna R.; Jauch, Ralf

2014-01-01

Pax genes belong to a family of metazoan transcription factors that are known to play a critical role in eye, ear, kidney and neural development. The mammalian Pax family of transcription factors is characterized by a ∼128-amino-acid DNA-binding paired domain that makes sequence-specific contacts with DNA. The diversity in Pax gene activities emerges from complex modes of interaction with enhancer regions and heterodimerization with multiple interaction partners. Based on in vitro optimal binding-site selection studies and enhancer identification assays, it has been suggested that Pax proteins may recognize and bind their target DNA elements with different binding modes/topologies, however this hypothesis has not yet been structurally explored. One of the most extensively studied DNA target elements of the Pax6 paired domain is the eye-lens specific DC5 (δ-crystallin) enhancer element. In order to shed light on Pax6–DC5 DNA interactions, the related paired-domain prototype Pax9 was crystallized with the minimal δ-crystallin DC5 enhancer element and preliminary X-ray diffraction analysis was attempted. A 3.0 Å resolution native data set was collected at the National Synchrotron Light Source (NSLS), Brookhaven from crystals grown in a solution consisting of 10%(w/v) PEG 20K, 20%(v/v) PEG 550 MME, 0.03 M NaNO3, 0.03 M Na2HPO4, 0.03 M NH2SO4, 0.1 M MES/imidazole pH 6.5. The data set was indexed and merged in space group C2221, with unit-cell parameters a = 75.74, b = 165.59, c = 70.14 Å, α = β = γ = 90°. The solvent content in the unit cell is consistent with the presence of one Pax9 paired domain bound to duplex DNA in the asymmetric unit. PMID:25286939

Bounds and maximum principles for the solution of the linear transport equation

International Nuclear Information System (INIS)

Larsen, E.W.

1981-01-01

Pointwise bounds are derived for the solution of time-independent linear transport problems with surface sources in convex spatial domains. Under specified conditions, upper bounds are derived which, as a function of position, decrease with distance from the boundary. Also, sufficient conditions are obtained for the existence of maximum and minimum principles, and a counterexample is given which shows that such principles do not always exist

Data for ion and seed dependent fibril assembly of a spidroin core domain

Directory of Open Access Journals (Sweden)

Martin Humenik

2015-09-01

Full Text Available This data article includes size exclusion chromatography data of soluble eADF4(C16, an engineered spider silk variant based on the core domain sequence of the natural dragline silk protein ADF4 of Araneus diadematus, in combination with light scattering; the protein is monomeric before assembly. The assembled mature fibrils were visualized by transmission electron microscopy (TEM and atomic force microscopy (AFM. Sonicated fibrils were used as seeds to by-pass the nucleation lag phase in eADF4(C16 assembly. We also provide data on the sedimentation kinetics of spider silk in the presence of different NaCl concentrations revealing very slow protein aggregation in comparison to the fast assembly triggered by phosphate ions published previously [1]. Experiments in the Data article represent supporting material for our work published recently [1], which described the assembly mechanism of recombinant eADF4(C16 fibrils.

Hepatitis C Virus E2 Envelope Glycoprotein Core Structure

Energy Technology Data Exchange (ETDEWEB)

Kong, Leopold; Giang, Erick; Nieusma, Travis; Kadam, Rameshwar U.; Cogburn, Kristin E.; Hua, Yuanzi; Dai, Xiaoping; Stanfield, Robyn L.; Burton, Dennis R.; Ward, Andrew B.; Wilson, Ian A.; Law, Mansun

2014-08-26

Hepatitis C virus (HCV), a Hepacivirus, is a major cause of viral hepatitis, liver cirrhosis, and hepatocellular carcinoma. HCV envelope glycoproteins E1 and E2 mediate fusion and entry into host cells and are the primary targets of the humoral immune response. The crystal structure of the E2 core bound to broadly neutralizing antibody AR3C at 2.65 angstroms reveals a compact architecture composed of a central immunoglobulin-fold β sandwich flanked by two additional protein layers. The CD81 receptor binding site was identified by electron microscopy and site-directed mutagenesis and overlaps with the AR3C epitope. The x-ray and electron microscopy E2 structures differ markedly from predictions of an extended, three-domain, class II fusion protein fold and therefore provide valuable information for HCV drug and vaccine design.

Generalized surface tension bounds in vacuum decay

Science.gov (United States)

Masoumi, Ali; Paban, Sonia; Weinberg, Erick J.

2018-02-01

Coleman and De Luccia (CDL) showed that gravitational effects can prevent the decay by bubble nucleation of a Minkowski or AdS false vacuum. In their thin-wall approximation this happens whenever the surface tension in the bubble wall exceeds an upper bound proportional to the difference of the square roots of the true and false vacuum energy densities. Recently it was shown that there is another type of thin-wall regime that differs from that of CDL in that the radius of curvature grows substantially as one moves through the wall. Not only does the CDL derivation of the bound fail in this case, but also its very formulation becomes ambiguous because the surface tension is not well defined. We propose a definition of the surface tension and show that it obeys a bound similar in form to that of the CDL case. We then show that both thin-wall bounds are special cases of a more general bound that is satisfied for all bounce solutions with Minkowski or AdS false vacua. We discuss the limit where the parameters of the theory attain critical values and the bound is saturated. The bounce solution then disappears and a static planar domain wall solution appears in its stead. The scalar field potential then is of the form expected in supergravity, but this is only guaranteed along the trajectory in field space traced out by the bounce.

DnaA protein DNA-binding domain binds to Hda protein to promote inter-AAA+ domain interaction involved in regulatory inactivation of DnaA.

Science.gov (United States)

Keyamura, Kenji; Katayama, Tsutomu

2011-08-19

Chromosomal replication is initiated from the replication origin oriC in Escherichia coli by the active ATP-bound form of DnaA protein. The regulatory inactivation of DnaA (RIDA) system, a complex of the ADP-bound Hda and the DNA-loaded replicase clamp, represses extra initiations by facilitating DnaA-bound ATP hydrolysis, yielding the inactive ADP-bound form of DnaA. However, the mechanisms involved in promoting the DnaA-Hda interaction have not been determined except for the involvement of an interaction between the AAA+ domains of the two. This study revealed that DnaA Leu-422 and Pro-423 residues within DnaA domain IV, including a typical DNA-binding HTH motif, are specifically required for RIDA-dependent ATP hydrolysis in vitro and that these residues support efficient interaction with the DNA-loaded clamp·Hda complex and with Hda in vitro. Consistently, substitutions of these residues caused accumulation of ATP-bound DnaA in vivo and oriC-dependent inhibition of cell growth. Leu-422 plays a more important role in these activities than Pro-423. By contrast, neither of these residues is crucial for DNA replication from oriC, although they are highly conserved in DnaA orthologues. Structural analysis of a DnaA·Hda complex model suggested that these residues make contact with residues in the vicinity of the Hda AAA+ sensor I that participates in formation of a nucleotide-interacting surface. Together, the results show that functional DnaA-Hda interactions require a second interaction site within DnaA domain IV in addition to the AAA+ domain and suggest that these interactions are crucial for the formation of RIDA complexes that are active for DnaA-ATP hydrolysis.

DnaA Protein DNA-binding Domain Binds to Hda Protein to Promote Inter-AAA+ Domain Interaction Involved in Regulatory Inactivation of DnaA*

Science.gov (United States)

Keyamura, Kenji; Katayama, Tsutomu

2011-01-01

Chromosomal replication is initiated from the replication origin oriC in Escherichia coli by the active ATP-bound form of DnaA protein. The regulatory inactivation of DnaA (RIDA) system, a complex of the ADP-bound Hda and the DNA-loaded replicase clamp, represses extra initiations by facilitating DnaA-bound ATP hydrolysis, yielding the inactive ADP-bound form of DnaA. However, the mechanisms involved in promoting the DnaA-Hda interaction have not been determined except for the involvement of an interaction between the AAA+ domains of the two. This study revealed that DnaA Leu-422 and Pro-423 residues within DnaA domain IV, including a typical DNA-binding HTH motif, are specifically required for RIDA-dependent ATP hydrolysis in vitro and that these residues support efficient interaction with the DNA-loaded clamp·Hda complex and with Hda in vitro. Consistently, substitutions of these residues caused accumulation of ATP-bound DnaA in vivo and oriC-dependent inhibition of cell growth. Leu-422 plays a more important role in these activities than Pro-423. By contrast, neither of these residues is crucial for DNA replication from oriC, although they are highly conserved in DnaA orthologues. Structural analysis of a DnaA·Hda complex model suggested that these residues make contact with residues in the vicinity of the Hda AAA+ sensor I that participates in formation of a nucleotide-interacting surface. Together, the results show that functional DnaA-Hda interactions require a second interaction site within DnaA domain IV in addition to the AAA+ domain and suggest that these interactions are crucial for the formation of RIDA complexes that are active for DnaA-ATP hydrolysis. PMID:21708944

Apo and ligand-bound structures of ModA from the archaeon Methanosarcina acetivorans

International Nuclear Information System (INIS)

Chan, Sum; Giuroiu, Iulia; Chernishof, Irina; Sawaya, Michael R.; Chiang, Janet; Gunsalus, Robert P.; Arbing, Mark A.; Perry, L. Jeanne

2010-01-01

Crystal structures of ModA from M. acetivorans in the apo and ligand-bound conformations confirm domain rotation upon ligand binding. The trace-element oxyanion molybdate, which is required for the growth of many bacterial and archaeal species, is transported into the cell by an ATP-binding cassette (ABC) transporter superfamily uptake system called ModABC. ModABC consists of the ModA periplasmic solute-binding protein, the integral membrane-transport protein ModB and the ATP-binding and hydrolysis cassette protein ModC. In this study, X-ray crystal structures of ModA from the archaeon Methanosarcina acetivorans (MaModA) have been determined in the apoprotein conformation at 1.95 and 1.69 Å resolution and in the molybdate-bound conformation at 2.25 and 2.45 Å resolution. The overall domain structure of MaModA is similar to other ModA proteins in that it has a bilobal structure in which two mixed α/β domains are linked by a hinge region. The apo MaModA is the first unliganded archaeal ModA structure to be determined: it exhibits a deep cleft between the two domains and confirms that upon binding ligand one domain is rotated towards the other by a hinge-bending motion, which is consistent with the ‘Venus flytrap’ model seen for bacterial-type periplasmic binding proteins. In contrast to the bacterial ModA structures, which have tetrahedral coordination of their metal substrates, molybdate-bound MaModA employs octahedral coordination of its substrate like other archaeal ModA proteins

Approximate controllability of the Navier-Stokes system in unbounded domains

International Nuclear Information System (INIS)

Shorygin, P O

2003-01-01

The question of the approximate controllability for the 2- and the 3-dimensional Navier-Stokes system defined in the exterior of a bounded domain ω or in the entire space is studied. It is shown that one can find boundary controls or locally distributed controls (having support in a prescribed bounded domain) defined on the right-hand side of the system such that in prescribed time the solution of the Navier-Stokes system becomes arbitrarily close to an arbitrary prescribed divergence-free vector field

In-core Instrument Subcritical Verification (INCISV) - Core Design Verification Method - 358

International Nuclear Information System (INIS)

Prible, M.C.; Heibel, M.D.; Conner, S.L.; Sebastiani, P.J.; Kistler, D.P.

2010-01-01

According to the standard on reload startup physics testing, ANSI/ANS 19.6.1, a plant must verify that the constructed core behaves sufficiently close to the designed core to confirm that the various safety analyses bound the actual behavior of the plant. A large portion of this verification must occur before the reactor operates at power. The INCISV Core Design Verification Method uses the unique characteristics of a Westinghouse Electric Company fixed in-core self powered detector design to perform core design verification after a core reload before power operation. A Vanadium self powered detector that spans the length of the active fuel region is capable of confirming the required core characteristics prior to power ascension; reactivity balance, shutdown margin, temperature coefficient and power distribution. Using a detector element that spans the length of the active fuel region inside the core provides a signal of total integrated flux. Measuring the integrated flux distributions and changes at various rodded conditions and plant temperatures, and comparing them to predicted flux levels, validates all core necessary core design characteristics. INCISV eliminates the dependence on various corrections and assumptions between the ex-core detectors and the core for traditional physics testing programs. This program also eliminates the need for special rod maneuvers which are infrequently performed by plant operators during typical core design verification testing and allows for safer startup activities. (authors)

Kodiak: An Implementation Framework for Branch and Bound Algorithms

Science.gov (United States)

Smith, Andrew P.; Munoz, Cesar A.; Narkawicz, Anthony J.; Markevicius, Mantas

2015-01-01

Recursive branch and bound algorithms are often used to refine and isolate solutions to several classes of global optimization problems. A rigorous computation framework for the solution of systems of equations and inequalities involving nonlinear real arithmetic over hyper-rectangular variable and parameter domains is presented. It is derived from a generic branch and bound algorithm that has been formally verified, and utilizes self-validating enclosure methods, namely interval arithmetic and, for polynomials and rational functions, Bernstein expansion. Since bounds computed by these enclosure methods are sound, this approach may be used reliably in software verification tools. Advantage is taken of the partial derivatives of the constraint functions involved in the system, firstly to reduce the branching factor by the use of bisection heuristics and secondly to permit the computation of bifurcation sets for systems of ordinary differential equations. The associated software development, Kodiak, is presented, along with examples of three different branch and bound problem types it implements.

A Model-Free No-arbitrage Price Bound for Variance Options

Energy Technology Data Exchange (ETDEWEB)

Bonnans, J. Frederic, E-mail: frederic.bonnans@inria.fr [Ecole Polytechnique, INRIA-Saclay (France); Tan Xiaolu, E-mail: xiaolu.tan@polytechnique.edu [Ecole Polytechnique, CMAP (France)

2013-08-01

We suggest a numerical approximation for an optimization problem, motivated by its applications in finance to find the model-free no-arbitrage bound of variance options given the marginal distributions of the underlying asset. A first approximation restricts the computation to a bounded domain. Then we propose a gradient projection algorithm together with the finite difference scheme to solve the optimization problem. We prove the general convergence, and derive some convergence rate estimates. Finally, we give some numerical examples to test the efficiency of the algorithm.

Reduced conservatism in stability robustness bounds by state transformation

Science.gov (United States)

Yedavalli, R. K.; Liang, Z.

1986-01-01

This note addresses the issue of 'conservatism' in the time domain stability robustness bounds obtained by the Liapunov approach. A state transformation is employed to improve the upper bounds on the linear time-varying perturbation of an asymptotically stable linear time-invariant system for robust stability. This improvement is due to the variance of the conservatism of the Liapunov approach with respect to the basis of the vector space in which the Liapunov function is constructed. Improved bounds are obtained, using a transformation, on elemental and vector norms of perturbations (i.e., structured perturbations) as well as on a matrix norm of perturbations (i.e., unstructured perturbations). For the case of a diagonal transformation, an algorithm is proposed to find the 'optimal' transformation. Several examples are presented to illustrate the proposed analysis.

Bootstrap bound for conformal multi-flavor QCD on lattice

Energy Technology Data Exchange (ETDEWEB)

Nakayama, Yu [Department of Physics, Rikkyo University,Toshima, Tokyo 171-8501 (Japan); Kavli Institute for the Physics and Mathematics of the Universe (WPI), University of Tokyo,5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8583 (Japan)

2016-07-08

The recent work by Iha et al. shows an upper bound on mass anomalous dimension γ{sub m} of multi-flavor massless QCD at the renormalization group fixed point from the conformal bootstrap in SU(N{sub F}){sub V} symmetric conformal field theories under the assumption that the fixed point is realizable with the lattice regularization based on staggered fermions. We show that the almost identical but slightly stronger bound applies to the regularization based on Wilson fermions (or domain wall fermions) by studying the conformal bootstrap in SU(N{sub f}){sub L}×SU(N{sub f}){sub R} symmetric conformal field theories. For N{sub f}=8, our bound implies γ{sub m}<1.31 to avoid dangerously irrelevant operators that are not compatible with the lattice symmetry.

A Rational Engineering Strategy for Designing Protein A-Binding Camelid Single-Domain Antibodies

Science.gov (United States)

Henry, Kevin A.; Sulea, Traian; van Faassen, Henk; Hussack, Greg; Purisima, Enrico O.; MacKenzie, C. Roger; Arbabi-Ghahroudi, Mehdi

2016-01-01

Staphylococcal protein A (SpA) and streptococcal protein G (SpG) affinity chromatography are the gold standards for purifying monoclonal antibodies (mAbs) in therapeutic applications. However, camelid VHH single-domain Abs (sdAbs or VHHs) are not bound by SpG and only sporadically bound by SpA. Currently, VHHs require affinity tag-based purification, which limits their therapeutic potential and adds considerable complexity and cost to their production. Here we describe a simple and rapid mutagenesis-based approach designed to confer SpA binding upon a priori non-SpA-binding VHHs. We show that SpA binding of VHHs is determined primarily by the same set of residues as in human mAbs, albeit with an unexpected degree of tolerance to substitutions at certain core and non-core positions and some limited dependence on at least one residue outside the SpA interface, and that SpA binding could be successfully introduced into five VHHs against three different targets with no adverse effects on expression yield or antigen binding. Next-generation sequencing of llama, alpaca and dromedary VHH repertoires suggested that species differences in SpA binding may result from frequency variation in specific deleterious polymorphisms, especially Ile57. Thus, the SpA binding phenotype of camelid VHHs can be easily modulated to take advantage of tag-less purification techniques, although the frequency with which this is required may depend on the source species. PMID:27631624

Bounded fractional diffusion in geological media: Definition and Lagrangian approximation

Science.gov (United States)

Zhang, Yong; Green, Christopher T.; LaBolle, Eric M.; Neupauer, Roseanna M.; Sun, HongGuang

2016-01-01

Spatiotemporal Fractional-Derivative Models (FDMs) have been increasingly used to simulate non-Fickian diffusion, but methods have not been available to define boundary conditions for FDMs in bounded domains. This study defines boundary conditions and then develops a Lagrangian solver to approximate bounded, one-dimensional fractional diffusion. Both the zero-value and non-zero-value Dirichlet, Neumann, and mixed Robin boundary conditions are defined, where the sign of Riemann-Liouville fractional derivative (capturing non-zero-value spatial-nonlocal boundary conditions with directional super-diffusion) remains consistent with the sign of the fractional-diffusive flux term in the FDMs. New Lagrangian schemes are then proposed to track solute particles moving in bounded domains, where the solutions are checked against analytical or Eularian solutions available for simplified FDMs. Numerical experiments show that the particle-tracking algorithm for non-Fickian diffusion differs from Fickian diffusion in relocating the particle position around the reflective boundary, likely due to the non-local and non-symmetric fractional diffusion. For a non-zero-value Neumann or Robin boundary, a source cell with a reflective face can be applied to define the release rate of random-walking particles at the specified flux boundary. Mathematical definitions of physically meaningful nonlocal boundaries combined with bounded Lagrangian solvers in this study may provide the only viable techniques at present to quantify the impact of boundaries on anomalous diffusion, expanding the applicability of FDMs from infinite do mains to those with any size and boundary conditions.

AGR core safety assessment methodologies

International Nuclear Information System (INIS)

McLachlan, N.; Reed, J.; Metcalfe, M.P.

1996-01-01

To demonstrate the safety of its gas-cooled graphite-moderated AGR reactors, nuclear safety assessments of the cores are based upon a methodology which demonstrates no component failures, geometrical stability of the structure and material properties bounded by a database. All AGRs continue to meet these three criteria. However, predictions of future core behaviour indicate that the safety case methodology will eventually need to be modified to deal with new phenomena. A new approach to the safety assessment of the cores is currently under development, which can take account of these factors while at the same time providing the same level of protection for the cores. This approach will be based on the functionality of the core: unhindered movement of control rods, continued adequate cooling of the fuel and the core, continued ability to charge and discharge fuel. (author). 5 figs

Solution structure of the Grb2 SH2 domain complexed with a high-affinity inhibitor

International Nuclear Information System (INIS)

Ogura, Kenji; Shiga, Takanori; Yokochi, Masashi; Yuzawa, Satoru; Burke, Terrence R.; Inagaki, Fuyuhiko

2008-01-01

The solution structure of the growth factor receptor-bound protein 2 (Grb2) SH2 domain complexed with a high-affinity inhibitor containing a non-phosphorus phosphate mimetic within a macrocyclic platform was determined by nuclear magnetic resonance (NMR) spectroscopy. Unambiguous assignments of the bound inhibitor and intermolecular NOEs between the Grb2 SH2 domain and the inhibitor was accomplished using perdeuterated Grb2 SH2 protein. The well-defined solution structure of the complex was obtained and compared to those by X-ray crystallography. Since the crystal structure of the Grb2 SH2 domain formed a domain-swapped dimer and several inhibitors were bound to a hinge region, there were appreciable differences between the solution and crystal structures. Based on the binding interactions between the inhibitor and the Grb2 SH2 domain in solution, we proposed a design of second-generation inhibitors that could be expected to have higher affinity

Common Core State Standards in the Middle Grades: What's New in the Geometry Domain and How Can Teachers Support Student Learning?

Science.gov (United States)

Teuscher, Dawn; Tran, Dung; Reys, Barbara J.

2015-01-01

The Common Core State Standards for Mathematics (CCSSM) is a primary focus of attention for many stakeholders' (e.g., teachers, district mathematics leaders, and curriculum developers) intent on improving mathematics education. This article reports on specific content shifts related to the geometry domain in the middle grades (6-8)…

Societal and individual burden of illness among fibromyalgia patients in France: Association between disease severity and OMERACT core domains

Directory of Open Access Journals (Sweden)

Perrot Serge

2012-02-01

Full Text Available Abstract Background Patients with fibromyalgia (FM report widespread pain, fatigue, and other functional limitations. This study aimed to provide an assessment of the burden of illness associated with FM in France and its association with disease severity and core domains as defined by Outcome Measures in Rheumatology Clinical Trials (OMERACT for FM. Methods This cross-sectional, observational study recruited patients with a prior diagnosis of FM from 18 community-based physician offices in France. Patients completed questions about FM impact (Fibromyalgia-Impact Questionnaire [FIQ], core symptoms (defined by OMERACT, health-related quality of life (EQ-5D, current overall health status (rated on a scale from 0 to 100, productivity, treatment satisfaction, and out-of-pocket expenses related to FM. Site staff recorded patients' treatment and health resource use based on medical record review. Costs were extrapolated from 4-week patient-reported data and 3-month clinical case report form data and calculated in 2008 Euros using a societal perspective. Tests of significance used the Kruskal-Wallis test or Fisher's Exact test where P Results Eighty-eight patients (mean 55.2 y; female:male 74:14 were recruited. The majority of patients (84.1% were prescribed medications for FM. Patients mainly described medications as a little/not at all effective (40.0% or somewhat effective (52.9%. Current Overall Health rating was 52.9 (± 17.8 and FIQ total score was 54.8 (± 17.3. FIQ total score was used to define FM severity, and 17 patients scored 0- Conclusions In a sample of 88 patients with FM from France, we found that FM poses a substantial economic and human burden on patients and society. FM severity level was significantly associated with patients' health status and core symptom domains.

Core Outcome Domains for early phase clinical trials of sound-, psychology-, and pharmacology-based interventions to manage chronic subjective tinnitus in adults: the COMIT'ID study protocol for using a Delphi process and face-to-face meetings to establish consensus.

Science.gov (United States)

Fackrell, Kathryn; Smith, Harriet; Colley, Veronica; Thacker, Brian; Horobin, Adele; Haider, Haúla F; Londero, Alain; Mazurek, Birgit; Hall, Deborah A

2017-08-23

The reporting of outcomes in clinical trials of subjective tinnitus indicates that many different tinnitus-related complaints are of interest to investigators, from perceptual attributes of the sound (e.g. loudness) to psychosocial impacts (e.g. quality of life). Even when considering one type of intervention strategy for subjective tinnitus, there is no agreement about what is critically important for deciding whether a treatment is effective. The main purpose of this observational study is, therefore to, develop Core Outcome Domain Sets for the three different intervention strategies (sound, psychological, and pharmacological) for adults with chronic subjective tinnitus that should be measured and reported in every clinical trial of these interventions. Secondary objectives are to identify the strengths and limitations of our study design for recruiting and reducing attrition of participants, and to explore uptake of the core outcomes. The 'Core Outcome Measures in Tinnitus: International Delphi' (COMIT'ID) study will use a mixed-methods approach that incorporates input from health care users at the pre-Delphi stage, a modified three-round Delphi survey and final consensus meetings (one for each intervention). The meetings will generate recommendations by stakeholder representatives on agreed Core Outcome Domain Sets specific to each intervention. A subsequent step will establish a common cross-cutting Core Outcome Domain Set by identifying the common outcome domains included in all three intervention-specific Core Outcome Domain Sets. To address the secondary objectives, we will gather feedback from participants about their experience of taking part in the Delphi process. We aspire to conduct an observational cohort study to evaluate uptake of the core outcomes in published studies at 7 years following Core Outcome Set publication. The COMIT'ID study aims to develop a Core Outcome Domain Set that is agreed as critically important for deciding whether a

Domain observations of Fe and Co based amorphous wires

International Nuclear Information System (INIS)

Takajo, M.; Yamasaki, J.

1993-01-01

Domain observations were made on Fe and Co based amorphous magnetic wires that exhibit a large Barkhausen discontinuity during flux reversal. Domain patterns observed on the wire surface were compared with those found on a polished section through the center of the wire. It was confirmed that the Fe based wire consists of a shell and core region as previously proposed, however, there is a third region between them. This fairly thick transition region made up of domains at an angle of about 45 degree to the wire axis clearly lacking the closure domains of the previous model. The Co based wire does not have a clear core and shell domain structure. The center of the wire had a classic domain structure expected of uniaxial anisotropy with the easy axis normal to the wire axis. When a model for the residual stress quenched-in during cooling of large Fe bars is applied to the wire, the expected anisotropy is consistent with the domain patterns in the Fe based wire, however, shape anisotropy still plays a dominant role in defining the wire core in the Co based wire

Fungal mediator tail subunits contain classical transcriptional activation domains.

Science.gov (United States)

Liu, Zhongle; Myers, Lawrence C

2015-04-01

Classical activation domains within DNA-bound eukaryotic transcription factors make weak interactions with coactivator complexes, such as Mediator, to stimulate transcription. How these interactions stimulate transcription, however, is unknown. The activation of reporter genes by artificial fusion of Mediator subunits to DNA binding domains that bind to their promoters has been cited as evidence that the primary role of activators is simply to recruit Mediator. We have identified potent classical transcriptional activation domains in the C termini of several tail module subunits of Saccharomyces cerevisiae, Candida albicans, and Candida dubliniensis Mediator, while their N-terminal domains are necessary and sufficient for their incorporation into Mediator but do not possess the ability to activate transcription when fused to a DNA binding domain. This suggests that Mediator fusion proteins actually are functioning in a manner similar to that of a classical DNA-bound activator rather than just recruiting Mediator. Our finding that deletion of the activation domains of S. cerevisiae Med2 and Med3, as well as C. dubliniensis Tlo1 (a Med2 ortholog), impairs the induction of certain genes shows these domains function at native promoters. Activation domains within coactivators are likely an important feature of these complexes and one that may have been uniquely leveraged by a common fungal pathogen. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Structural Mechanism of the Oxygenase JMJD6 Recognition by the Extraterminal (ET) Domain of BRD4.

Science.gov (United States)

Konuma, Tsuyoshi; Yu, Di; Zhao, Chengcheng; Ju, Ying; Sharma, Rajal; Ren, Chunyan; Zhang, Qiang; Zhou, Ming-Ming; Zeng, Lei

2017-11-24

Jumonji domain-containing protein 6 (JMJD6) is a member of the Jumonji C family of Fe(II) and 2-oxoglutarate (2OG) dependent oxygenases. It possesses unique bi-functional oxygenase activities, acting as both an arginine demethylase and a lysyl-hydroxylase. JMJD6 has been reported to be over-expressed in oral, breast, lung, and colon cancers and plays important roles in regulation of transcription through interactions with transcription regulator BRD4, histones, U2AF65, Luc7L3, and SRSF11. Here, we report a structural mechanism revealed by NMR of JMJD6 recognition by the extraterminal (ET) domain of BRD4 in that a JMJD6 peptide (Lys84-Asn96) adapts an α-helix when bound to the ET domain. This intermolecular recognition is established through JMJD6 interactions with the conserved hydrophobic core of the ET domain, and reinforced by electrostatic interactions of JMJD6 with residues in the inter-helical α1-α2 loop of the ET domain. Notably, this mode of ligand recognition is different from that of ET domain recognition of NSD3, LANA of herpesvirus, and integrase of MLV, which involves formation of an intermolecular amphipathic two- or three- strand antiparallel β sheet. Furthermore, we demonstrate that the association between the BRD4 ET domain and JMJD6 likely requires a protein conformational change induced by single-stranded RNA binding.

The characterization of weighted local hardy spaces on domains and its application.

Science.gov (United States)

Wang, Heng-geng; Yang, Xiao-ming

2004-09-01

In this paper, we give the four equivalent characterizations for the weighted local hardy spaces on Lipschitz domains. Also, we give their application for the harmonic function defined in bounded Lipschitz domains.

Life-time of the bound layer in nanocomposites

Science.gov (United States)

Zhao, Dan; Jestin, Jacques; Kumar, Sanat K.

2015-03-01

It is now well accepted that an effectively irreversibly adsorbed monolayer of polymer forms when a polymer melt is intimately mixed with nanoparticles, in the limit where their enthalpic interactions are favorable. This bound layer has been postulated as being a central player in many of the highly favorable properties that result from polymer based nanocomposite materials. We investigated well-defined nanocomposites formed with different combinations of deuterated and hydrogenated polymers (P2VP and PMMA) and silica nanoparticles. SANS, in conjunction with contrast variation, then provides a direct means of probing the structure of the bound layer as a core-shell and its exchange kinetics with bulk (unbound) chains with annealing time and temperature. SAXS directly provides information on the particle-particle partial structure factor and particle dispersion. Thermodynamic equilibrium of the bound layer is reached around one day at 150 °C while its exchange life time is ~ one hour at 180 °C.

Excitation spectra and wave functions of quasiparticle bound states in bilayer Rashba superconductors

Energy Technology Data Exchange (ETDEWEB)

Higashi, Yoichi, E-mail: higashiyoichi@ms.osakafu-u.ac.jp [Department of Mathematical Sciences, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai 599-8531 (Japan); Nagai, Yuki [CCSE, Japan Atomic Energy Agency, 178-4-4, Wakashiba, Kashiwa, Chiba 277-0871 (Japan); Yoshida, Tomohiro [Graduate School of Science and Technology, Niigata University, Niigata 950-2181 (Japan); Kato, Masaru [Department of Mathematical Sciences, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai 599-8531 (Japan); Yanase, Youichi [Department of Physics, Niigata University, Niigata 950-2181 (Japan)

2015-11-15

Highlights: • We focus on the pair-density wave state in bilayer Rashba superconductors. • The zero energy Bogoliubov wave functions are localized at the edge and vortex core. • We investigate the excitation spectra of edge and vortex bound states. - Abstract: We study the excitation spectra and the wave functions of quasiparticle bound states at a vortex and an edge in bilayer Rashba superconductors under a magnetic field. In particular, we focus on the quasiparticle states at the zero energy in the pair-density wave state in a topologically non-trivial phase. We numerically demonstrate that the quasiparticle wave functions with zero energy are localized at both the edge and the vortex core if the magnetic field exceeds the critical value.

Combinatorial geometry domain decomposition strategies for Monte Carlo simulations

Energy Technology Data Exchange (ETDEWEB)

Li, G.; Zhang, B.; Deng, L.; Mo, Z.; Liu, Z.; Shangguan, D.; Ma, Y.; Li, S.; Hu, Z. [Institute of Applied Physics and Computational Mathematics, Beijing, 100094 (China)

2013-07-01

Analysis and modeling of nuclear reactors can lead to memory overload for a single core processor when it comes to refined modeling. A method to solve this problem is called 'domain decomposition'. In the current work, domain decomposition algorithms for a combinatorial geometry Monte Carlo transport code are developed on the JCOGIN (J Combinatorial Geometry Monte Carlo transport INfrastructure). Tree-based decomposition and asynchronous communication of particle information between domains are described in the paper. Combination of domain decomposition and domain replication (particle parallelism) is demonstrated and compared with that of MERCURY code. A full-core reactor model is simulated to verify the domain decomposition algorithms using the Monte Carlo particle transport code JMCT (J Monte Carlo Transport Code), which has being developed on the JCOGIN infrastructure. Besides, influences of the domain decomposition algorithms to tally variances are discussed. (authors)

Combinatorial geometry domain decomposition strategies for Monte Carlo simulations

International Nuclear Information System (INIS)

Li, G.; Zhang, B.; Deng, L.; Mo, Z.; Liu, Z.; Shangguan, D.; Ma, Y.; Li, S.; Hu, Z.

2013-01-01

Analysis and modeling of nuclear reactors can lead to memory overload for a single core processor when it comes to refined modeling. A method to solve this problem is called 'domain decomposition'. In the current work, domain decomposition algorithms for a combinatorial geometry Monte Carlo transport code are developed on the JCOGIN (J Combinatorial Geometry Monte Carlo transport INfrastructure). Tree-based decomposition and asynchronous communication of particle information between domains are described in the paper. Combination of domain decomposition and domain replication (particle parallelism) is demonstrated and compared with that of MERCURY code. A full-core reactor model is simulated to verify the domain decomposition algorithms using the Monte Carlo particle transport code JMCT (J Monte Carlo Transport Code), which has being developed on the JCOGIN infrastructure. Besides, influences of the domain decomposition algorithms to tally variances are discussed. (authors)

Test plan for core drilling ignitability testing

International Nuclear Information System (INIS)

Witwer, K.S.

1996-01-01

The objective of this testing is to determine if ignition occurs while core drilling in a flammable gas environment. Drilling parameters are chosen so as to provide bounding conditions for the core sampling environment. If ignition does not occur under the conditions set forth in this test, then a satisfactory level of confidence will be obtained which would allow field operations under the normal drilling conditions

Efficient Proof Engines for Bounded Model Checking of Hybrid Systems

DEFF Research Database (Denmark)

Fränzle, Martin; Herde, Christian

2005-01-01

In this paper we present HySat, a new bounded model checker for linear hybrid systems, incorporating a tight integration of a DPLL-based pseudo-Boolean SAT solver and a linear programming routine as core engine. In contrast to related tools like MathSAT, ICS, or CVC, our tool exploits all...

Algorithm-Dependent Generalization Bounds for Multi-Task Learning.

Science.gov (United States)

Liu, Tongliang; Tao, Dacheng; Song, Mingli; Maybank, Stephen J

2017-02-01

Often, tasks are collected for multi-task learning (MTL) because they share similar feature structures. Based on this observation, in this paper, we present novel algorithm-dependent generalization bounds for MTL by exploiting the notion of algorithmic stability. We focus on the performance of one particular task and the average performance over multiple tasks by analyzing the generalization ability of a common parameter that is shared in MTL. When focusing on one particular task, with the help of a mild assumption on the feature structures, we interpret the function of the other tasks as a regularizer that produces a specific inductive bias. The algorithm for learning the common parameter, as well as the predictor, is thereby uniformly stable with respect to the domain of the particular task and has a generalization bound with a fast convergence rate of order O(1/n), where n is the sample size of the particular task. When focusing on the average performance over multiple tasks, we prove that a similar inductive bias exists under certain conditions on the feature structures. Thus, the corresponding algorithm for learning the common parameter is also uniformly stable with respect to the domains of the multiple tasks, and its generalization bound is of the order O(1/T), where T is the number of tasks. These theoretical analyses naturally show that the similarity of feature structures in MTL will lead to specific regularizations for predicting, which enables the learning algorithms to generalize fast and correctly from a few examples.

Inner Core Rotation from Geomagnetic Westward Drift and a Stationary Spherical Vortex in Earth's Core

Science.gov (United States)

Voorhies, C. V.

1999-01-01

The idea that geomagnetic westward drift indicates convective leveling of the planetary momentum gradient within Earth's core is pursued in search of a differentially rotating mean state, upon which various oscillations and secular effects might be superimposed. The desired state conforms to roughly spherical boundary conditions, minimizes dissipative interference with convective cooling in the bulk of the core, yet may aide core cooling by depositing heat in the uppermost core and lower mantle. The variational calculus of stationary dissipation applied to a spherical vortex within the core yields an interesting differential rotation profile akin to spherical Couette flow bounded by thin Hartmann layers. Four boundary conditions are required. To concentrate shear induced dissipation near the core-mantle boundary, these are taken to be: (i) no-slip at the core-mantle interface; (ii) geomagnetically estimated bulk westward flow at the base of the core-mantle boundary layer; (iii) no-slip at the inner-outer core interface; and, to describe magnetic locking of the inner core to the deep outer core, (iv) hydrodynamically stress-free at the inner-outer core boundary. By boldly assuming the axial core angular momentum anomaly to be zero, the super-rotation of the inner core is calculated to be at most 1.5 degrees per year.

Bounded Model Checking and Inductive Verification of Hybrid Discrete-Continuous Systems

DEFF Research Database (Denmark)

Becker, Bernd; Behle, Markus; Eisenbrand, Fritz

2004-01-01

We present a concept to signicantly advance the state of the art for bounded model checking (BMC) and inductive verication (IV) of hybrid discrete-continuous systems. Our approach combines the expertise of partners coming from dierent domains, like hybrid systems modeling and digital circuit veri...

Structural analysis of poly-SUMO chain recognition by the RNF4-SIMs domain.

Science.gov (United States)

Kung, Camy C-H; Naik, Mandar T; Wang, Szu-Huan; Shih, Hsiu-Ming; Chang, Che-Chang; Lin, Li-Ying; Chen, Chia-Lin; Ma, Che; Chang, Chi-Fon; Huang, Tai-Huang

2014-08-15

The E3 ubiquitin ligase RNF4 (RING finger protein 4) contains four tandem SIM [SUMO (small ubiquitin-like modifier)-interaction motif] repeats for selective interaction with poly-SUMO-modified proteins, which it targets for degradation. We employed a multi-faceted approach to characterize the structure of the RNF4-SIMs domain and the tetra-SUMO2 chain to elucidate the interaction between them. In solution, the SIM domain was intrinsically disordered and the linkers of the tetra-SUMO2 were highly flexible. Individual SIMs of the RNF4-SIMs domains bind to SUMO2 in the groove between the β2-strand and the α1-helix parallel to the β2-strand. SIM2 and SIM3 bound to SUMO with a high affinity and together constituted the recognition module necessary for SUMO binding. SIM4 alone bound to SUMO with low affinity; however, its contribution to tetra-SUMO2 binding avidity is comparable with that of SIM3 when in the RNF4-SIMs domain. The SAXS data of the tetra-SUMO2-RNF4-SIMs domain complex indicate that it exists as an ordered structure. The HADDOCK model showed that the tandem RNF4-SIMs domain bound antiparallel to the tetra-SUMO2 chain orientation and wrapped around the SUMO protamers in a superhelical turn without imposing steric hindrance on either molecule.

Novel core promoter elements and a cognate transcription factor in the divergent unicellular eukaryote Trichomonas vaginalis.

Science.gov (United States)

Smith, Alias J; Chudnovsky, Lorissa; Simoes-Barbosa, Augusto; Delgadillo-Correa, Maria G; Jonsson, Zophonias O; Wohlschlegel, James A; Johnson, Patricia J

2011-04-01

A highly conserved DNA initiator (Inr) element has been the only core promoter element described in the divergent unicellular eukaryote Trichomonas vaginalis, although genome analyses reveal that only ∼75% of protein-coding genes appear to contain an Inr. In search of another core promoter element(s), a nonredundant database containing 5' untranslated regions of expressed T. vaginalis genes was searched for overrepresented DNA motifs and known eukaryotic core promoter elements. In addition to identifying the Inr, two elements that lack sequence similarity to the known protein-coding gene core promoter, motif 3 (M3) and motif 5 (M5), were identified. Mutational and functional analyses demonstrate that both are novel core promoter elements. M3 [(A/G/T)(A/G)C(G/C)G(T/C)T(T/A/G)] resembles a Myb recognition element (MRE) and is bound specifically by a unique protein with a Myb-like DNA binding domain. The M5 element (CCTTT) overlaps the transcription start site and replaces the Inr as an alternative, gene-specific initiator element. Transcription specifically initiates at the second cytosine within M5, in contrast to characteristic initiation by RNA polymerase II at an adenosine. In promoters that combine M3 with either M5 or Inr, transcription initiation is regulated by the M3 motif.

Novel Core Promoter Elements and a Cognate Transcription Factor in the Divergent Unicellular Eukaryote Trichomonas vaginalis▿

Science.gov (United States)

Smith, Alias J.; Chudnovsky, Lorissa; Simoes-Barbosa, Augusto; Delgadillo-Correa, Maria G.; Jonsson, Zophonias O.; Wohlschlegel, James A.; Johnson, Patricia J.

2011-01-01

A highly conserved DNA initiator (Inr) element has been the only core promoter element described in the divergent unicellular eukaryote Trichomonas vaginalis, although genome analyses reveal that only ∼75% of protein-coding genes appear to contain an Inr. In search of another core promoter element(s), a nonredundant database containing 5′ untranslated regions of expressed T. vaginalis genes was searched for overrepresented DNA motifs and known eukaryotic core promoter elements. In addition to identifying the Inr, two elements that lack sequence similarity to the known protein-coding gene core promoter, motif 3 (M3) and motif 5 (M5), were identified. Mutational and functional analyses demonstrate that both are novel core promoter elements. M3 [(A/G/T)(A/G)C(G/C)G(T/C)T(T/A/G)] resembles a Myb recognition element (MRE) and is bound specifically by a unique protein with a Myb-like DNA binding domain. The M5 element (CCTTT) overlaps the transcription start site and replaces the Inr as an alternative, gene-specific initiator element. Transcription specifically initiates at the second cytosine within M5, in contrast to characteristic initiation by RNA polymerase II at an adenosine. In promoters that combine M3 with either M5 or Inr, transcription initiation is regulated by the M3 motif. PMID:21245378

Real-time monitoring of disintegration activity of catalytic core domain of HIV-1 integrase using molecular beacon.

Science.gov (United States)

Zhang, Da-wei; Zhao, Ming-ming; He, Hong-qiu; Guo, Shun-xing

2013-09-15

HIV-1 integrase, an essential enzyme for retroviral replication, is a validated target for anti-HIV therapy development. The catalytic core domain of integrase (IN-CCD) is capable of catalyzing disintegration reaction. In this work, a hairpin-shaped disintegration substrate was designed and validated by enzyme-linked immunosorbent assay; a molecular beacon-based assay was developed for disintegration reaction of IN-CCD. Results showed that the disintegration substrate could be recognized and catalyzed by IN-CCD, and the disintegration reaction can be monitored according to the increase of fluorescent signal. The assay can be applied to real-time detection of disintegration with advantages of simplicity, high sensitivity, and excellent specificity. Copyright © 2013 Elsevier Inc. All rights reserved.

Short-time Asymptotics of the Heat Kernel on Bounded Domain with Piecewise Smooth Boundary Conditions and Its Applications to an Ideal Gas

Institute of Scientific and Technical Information of China (English)

E.M.E. ZAYED

2004-01-01

The asymptotic expansion of the heat kernel Θ(t)(∞∑=(i=0))exp (-λi) where({λi}∞i=1) Are the eigen-values of negative Laplacian( -△n=-n∑k=1(θ/θxk)2)in Rn(n=2 or 3) is studied for short-time t for a general bounded domainθΩwith a smooth boundary θΩ.In this paper, we consider the case of a finite number of the Dirichlet conditions φ=0 on Γi (i = J +1,….,J)and the Neumann conditions and (θφ/θ vi) = 0 on Γi (i = J+1,…,k) and the Robin condition (θφ/θ vi+γi) θ=(I=k+1,… m) where γi are piecewise smooth positive impedancem(θφ=mUi=1Γi. )We construct the required asymptotics in the form of a power series over t. The senior coe.cients inthis series are speci.ed as functionals of the geometric shape of the domain Ω.This result is applied to calculatethe one-particle partition function of a "special ideal gas", i.e., the set of non-interacting particles set up in abox with Dirichlet, Neumann and Robin boundary conditions for the appropriate wave function. Calculationof the thermodynamic quantities for the ideal gas such as the internal energy, pressure and speci.c heat revealsthat these quantities alone are incapable of distinguishing between two di.erent shapes of the domain. Thisconclusion seems to be intuitively clear because it is based on a limited information given by a one-particlepartition function; nevertheless, its formal theoretical motivation is of some interest.

Binding of ethidium to the nucleosome core particle. 2. Internal and external binding modes

International Nuclear Information System (INIS)

McMurray, C.T.; Small, E.W.; van Holde, K.E.

1991-01-01

The authors have previously reported that the binding of ethidium bromide to the nucleosome core particle results in a stepwise dissociation of the structure which involves the initial release of one copy each of H2A and H2B. In this report, they have examined the absorbance and fluorescence properties of intercalated and outside bound forms of ethidium bromide. From these properties, they have measured the extent of external, electrostatic binding of the dye versus internal, intercalation binding to the core particle, free from contribution by linker DNA. They have established that dissociation is induced by the intercalation mode of binding to DNA within the core particle DNA, and not by binding to the histones or by nonintercalative binding to DNA. The covalent binding of [ 3 H]-8-azidoethidium to the core particle clearly shows that < 1.0 adduct is formed per histone octamer over a wide range of input ratios. Simultaneously, analyses of steady-state fluorescence enhancement and fluorescence lifetime data from bound ethidium complexes demonstrate extensive intercalation binding. Combined analyses from steady-state fluorescence intensity with equilibrium dialysis or fluorescence lifetime data revealed that dissociation began when ∼14 ethidium molecules are bound by intercalation to each core particle and < 1.0 nonintercalated ion pair was formed per core particle

Absence of positive eigenvalues for hard-core N-body systems

DEFF Research Database (Denmark)

Ito, K.; Skibsted, Erik

We show absence of positive eigenvalues for generalized 2-body hard-core Schrödinger operators under the condition of bounded strictly convex obstacles. A scheme for showing absence of positive eigenvalues for generalized N-body hard-core Schrödinger operators, N≥ 2, is presented. This scheme inv...

Core outcome sets in dermatology: report from the second meeting of the International Cochrane Skin Group Core Outcome Set Initiative.

Science.gov (United States)

Kottner, J; Jacobi, L; Hahnel, E; Alam, M; Balzer, K; Beeckman, D; Busard, C; Chalmers, J; Deckert, S; Eleftheriadou, V; Furlan, K; Horbach, S E R; Kirkham, J; Nast, A; Spuls, P; Thiboutot, D; Thorlacius, L; Weller, K; Williams, H C; Schmitt, J

2018-04-01

Results of clinical trials are the most important information source for generating external clinical evidence. The use of different outcomes across trials, which investigate similar interventions for similar patient groups, significantly limits the interpretation, comparability and clinical application of trial results. Core outcome sets (COSs) aim to overcome this limitation. A COS is an agreed standardized collection of outcomes that should be measured and reported in all clinical trials for a specific clinical condition. The Core Outcome Set Initiative within the Cochrane Skin Group (CSG-COUSIN) supports the development of core outcomes in dermatology. In the second CSG-COUSIN meeting held in 2017, 11 COS development groups working on skin diseases presented their current work. The presentations and discussions identified the following overarching methodological challenges for COS development in dermatology: it is not always easy to define the disease focus of a COS; the optimal method for outcome domain identification and level of detail needed to specify such domains is challenging to many; decision rules within Delphi surveys need to be improved; appropriate ways of patient involvement are not always clear. In addition, there appear to be outcome domains that may be relevant as potential core outcome domains for the majority of skin diseases. The close collaboration between methodologists in the Core Outcome Set Initiative and the international Cochrane Skin Group has major advantages for trialists, systematic reviewers and COS developers. © 2018 British Association of Dermatologists.

Cores, Joins and the Fano-Flow Conjectures

Directory of Open Access Journals (Sweden)

Jin Ligang

2018-02-01

Full Text Available The Fan-Raspaud Conjecture states that every bridgeless cubic graph has three 1-factors with empty intersection. A weaker one than this conjecture is that every bridgeless cubic graph has two 1-factors and one join with empty intersection. Both of these two conjectures can be related to conjectures on Fano-flows. In this paper, we show that these two conjectures are equivalent to some statements on cores and weak cores of a bridgeless cubic graph. In particular, we prove that the Fan-Raspaud Conjecture is equivalent to a conjecture proposed in [E. Steffen, 1-factor and cycle covers of cubic graphs, J. Graph Theory 78 (2015 195–206]. Furthermore, we disprove a conjecture proposed in [G. Mazzuoccolo, New conjectures on perfect matchings in cubic graphs, Electron. Notes Discrete Math. 40 (2013 235–238] and we propose a new version of it under a stronger connectivity assumption. The weak oddness of a cubic graph G is the minimum number of odd components (i.e., with an odd number of vertices in the complement of a join of G. We obtain an upper bound of weak oddness in terms of weak cores, and thus an upper bound of oddness in terms of cores as a by-product.

Purification, crystallization and preliminary X-ray diffraction study of human ribosomal protein L10 core domain

International Nuclear Information System (INIS)

Nishimura, Mitsuhiro; Kaminishi, Tatsuya; Kawazoe, Masahito; Shirouzu, Mikako; Takemoto, Chie; Yokoyama, Shigeyuki; Tanaka, Akiko; Sugano, Sumio; Yoshida, Takuya; Ohkubo, Tadayasu; Kobayashi, Yuji

2007-01-01

A truncated variant of human ribosomal protien L10 was prepared and crystallized. Diffraction data were collected to 2.5 Å resolution. Eukaryotic ribosomal protein L10 is an essential component of the large ribosomal subunit, which organizes the architecture of the aminoacyl-tRNA binding site. The human L10 protein is also called the QM protein and consists of 214 amino-acid residues. For crystallization, the L10 core domain (L10CD, Phe34–Glu182) was recombinantly expressed in Escherichia coli and purified to homogeneity. A hexagonal crystal of L10CD was obtained by the sitting-drop vapour-diffusion method. The L10CD crystal diffracted to 2.5 Å resolution and belongs to space group P3 1 21 or P3 2 21

Solution NMR investigation of the response of the lactose repressor core domain dimer to hydrostatic pressure.

Science.gov (United States)

Fuglestad, Brian; Stetz, Matthew A; Belnavis, Zachary; Wand, A Joshua

2017-12-01

Previous investigations of the sensitivity of the lac repressor to high-hydrostatic pressure have led to varying conclusions. Here high-pressure solution NMR spectroscopy is used to provide an atomic level view of the pressure induced structural transition of the lactose repressor regulatory domain (LacI* RD) bound to the ligand IPTG. As the pressure is raised from ambient to 3kbar the native state of the protein is converted to a partially unfolded form. Estimates of rotational correlation times using transverse optimized relaxation indicates that a monomeric state is never reached and that the predominate form of the LacI* RD is dimeric throughout this pressure change. Spectral analysis suggests that the pressure-induced transition is localized and is associated with a volume change of approximately -115mlmol -1 and an average pressure dependent change in compressibility of approximately 30mlmol -1 kbar -1 . In addition, a subset of resonances emerge at high-pressures indicating the presence of a non-native but folded alternate state. Copyright © 2017 Elsevier B.V. All rights reserved.

Eavesdropping on spin waves inside the domain-wall nanochannel via three-magnon processes

Science.gov (United States)

Zhang, Beining; Wang, Zhenyu; Cao, Yunshan; Yan, Peng; Wang, X. R.

2018-03-01

One recent breakthrough in the field of magnonics is the experimental realization of reconfigurable spin-wave nanochannels formed by a magnetic domain wall with a width of 10-100 nm [Wagner et al., Nat. Nano. 11, 432 (2016), 10.1038/nnano.2015.339]. This remarkable progress enables an energy-efficient spin-wave propagation with a well-defined wave vector along its propagating path inside the wall. In the mentioned experiment, a microfocus Brillouin light scattering spectroscopy was taken in a line-scans manner to measure the frequency of the bounded spin wave. Due to their localization nature, the confined spin waves can hardly be detected from outside the wall channel, which guarantees the information security to some extent. In this work, we theoretically propose a scheme to detect/eavesdrop on the spin waves inside the domain-wall nanochannel via nonlinear three-magnon processes. We send a spin wave (ωi,ki) in one magnetic domain to interact with the bounded mode (ωb,kb) in the wall, where kb is parallel with the domain-wall channel defined as the z ̂ axis. Two kinds of three-magnon processes, i.e., confluence and splitting, are expected to occur. The confluence process is conventional: conservation of energy and momentum parallel with the wall indicates a transmitted wave in the opposite domain with ω (k ) =ωi+ωb and (ki+kb-k ) .z ̂=0 , while the momentum perpendicular to the domain wall is not necessary to be conserved due to the nonuniform internal field near the wall. We predict a stimulated three-magnon splitting (or "magnon laser") effect: the presence of a bound magnon propagating along the domain wall channel assists the splitting of the incident wave into two modes, one is ω1=ωb,k1=kb identical to the bound mode in the channel, and the other one is ω2=ωi-ωb with (ki-kb-k2) .z ̂=0 propagating in the opposite magnetic domain. Micromagnetic simulations confirm our theoretical analysis. These results demonstrate that one is able to uniquely

Structures of the N-acetyltransferase domain of Xylella fastidiosa N-acetyl-L-glutamate synthase/kinase with and without a His tag bound to N-acetyl-L-glutamate.

Science.gov (United States)

Zhao, Gengxiang; Jin, Zhongmin; Allewell, Norma M; Tuchman, Mendel; Shi, Dashuang

2015-01-01

Structures of the catalytic N-acetyltransferase (NAT) domain of the bifunctional N-acetyl-L-glutamate synthase/kinase (NAGS/K) from Xylella fastidiosa bound to N-acetyl-L-glutamate (NAG) with and without an N-terminal His tag have been solved and refined at 1.7 and 1.4 Å resolution, respectively. The NAT domain with an N-terminal His tag crystallized in space group P4(1)2(1)2, with unit-cell parameters a=b=51.72, c=242.31 Å. Two subunits form a molecular dimer in the asymmetric unit, which contains ∼41% solvent. The NAT domain without an N-terminal His tag crystallized in space group P21, with unit-cell parameters a=63.48, b=122.34, c=75.88 Å, β=107.6°. Eight subunits, which form four molecular dimers, were identified in the asymmetric unit, which contains ∼38% solvent. The structures with and without the N-terminal His tag provide an opportunity to evaluate how the His tag affects structure and function. Furthermore, multiple subunits in different packing environments allow an assessment of the plasticity of the NAG binding site, which might be relevant to substrate binding and product release. The dimeric structure of the X. fastidiosa N-acetytransferase (xfNAT) domain is very similar to that of human N-acetyltransferase (hNAT), reinforcing the notion that mammalian NAGS is evolutionally derived from bifunctional bacterial NAGS/K.

Probing Andreev bound states in one-atom superconducting contacts

Energy Technology Data Exchange (ETDEWEB)

Pothier, Hugues; Janvier, Camille; Tosi, Leandro; Girit, Caglar; Goffman, Marcelo; Esteve, Daniel; Urbina, Cristian [Quantronics Group, SPEC, CEA-Saclay (France)

2015-07-01

Superconductors are characterized by a dissipationless current. Since the work of Josephson 50 years ago, it is known that a supercurrent can even flow through tunnel junctions between superconductors. This Josephson effect also occurs through any type of ''weak links'' between superconductors: non-superconducting materials, constrictions,.. A unified understanding of the Josephson effect has emerged from a mesoscopic description of weak links. It relies on the existence of doublets of localized states that have energies below the superconducting gap: the Andreev bound states. I will present experiments performed on the simplest conductor possible, a single-atom contact between superconductors, that illustrate these concepts. The most recent work demonstrates time-domain manipulation of quantum superpositions of Andreev bound states.

Insights into function of PSI domains from structure of the Met receptor PSI domain

International Nuclear Information System (INIS)

Kozlov, Guennadi; Perreault, Audrey; Schrag, Joseph D.; Park, Morag; Cygler, Miroslaw; Gehring, Kalle; Ekiel, Irena

2004-01-01

PSI domains are cysteine-rich modules found in extracellular fragments of hundreds of signaling proteins, including plexins, semaphorins, integrins, and attractins. Here, we report the solution structure of the PSI domain from the human Met receptor, a receptor tyrosine kinase critical for proliferation, motility, and differentiation. The structure represents a cysteine knot with short regions of secondary structure including a three-stranded antiparallel β-sheet and two α-helices. All eight cysteines are involved in disulfide bonds with the pattern consistent with that for the PSI domain from Sema4D. Comparison with the Sema4D structure identifies a structurally conserved core comprising the N-terminal half of the PSI domain. Interestingly, this part links adjacent SEMA and immunoglobulin domains in the Sema4D structure, suggesting that the PSI domain serves as a wedge between propeller and immunoglobulin domains and is responsible for the correct positioning of the ligand-binding site of the receptor

cDNA cloning of the basement membrane chondroitin sulfate proteoglycan core protein, bamacan: a five domain structure including coiled-coil motifs

DEFF Research Database (Denmark)

Wu, R R; Couchman, J R

1997-01-01

Basement membranes contain several proteoglycans, and those bearing heparan sulfate glycosaminoglycans such as perlecan and agrin usually predominate. Most mammalian basement membranes also contain chondroitin sulfate, and a core protein, bamacan, has been partially characterized. We have now....... The protein sequence has low overall homology, apart from very small NH2- and COOH-terminal motifs. At the junctions between the distal globular domains and the coiled-coil regions lie glycosylation sites, with up to three N-linked oligosaccharides and probably three chondroitin chains. Three other Ser...

Alteration of helical vortex core without change in flow topology

DEFF Research Database (Denmark)

Velte, Clara Marika; Okulov, Valery; Hansen, Martin Otto Laver

2011-01-01

topology. The helical symmetry as such is preserved, although the characteristic parameters of helical symmetry of the vortex core transfer from a smooth linear variation to a different trend under the influence of a non-uniform pressure gradient, causing an increase in helical pitch without changing its......The abrupt expansion of the slender vortex core with changes in flow topology is commonly known as vortex breakdown. We present new experimental observations of an alteration of the helical vortex core in wall bounded turbulent flow with abrupt growth in core size, but without change in flow...

Circuit lower bounds in bounded arithmetics

Czech Academy of Sciences Publication Activity Database

Pich, Ján

2015-01-01

Roč. 166, č. 1 (2015), s. 29-45 ISSN 0168-0072 R&D Projects: GA AV ČR IAA100190902 Keywords : bounded arithmetic * circuit lower bounds Subject RIV: BA - General Mathematics Impact factor: 0.582, year: 2015 http://www.sciencedirect.com/science/article/pii/S0168007214000888

Rotary mode core sampling approved checklist: 241-TX-113

International Nuclear Information System (INIS)

Fowler, K.D.

1998-01-01

The safety assessment for rotary mode core sampling was developed using certain bounding assumptions, however, those assumptions were not verified for each of the existing or potential flammable gas tanks. Therefore, a Flammable Gas/Rotary Mode Core Sampling Approved Checklist has been completed for tank 241-TX-113 prior to sampling operations. This transmittal documents the dispositions of the checklist items from the safety assessment

Rotary mode core sampling approved checklist: 241-TX-116

International Nuclear Information System (INIS)

FOWLER, K.D.

1999-01-01

The safety assessment for rotary mode core sampling was developed using certain bounding assumptions, however, those assumptions were not verified for each of the existing or potential flammable gas tanks. Therefore, a Flammable Gas/Rotary Mode Core Sampling Approved Checklist has been completed for tank 241-TX-116 prior to sampling operations. This transmittal documents the dispositions of the checklist items from the safety assessment

A Functional Core of IncA Is Required for Chlamydia trachomatis Inclusion Fusion.

Science.gov (United States)

Weber, Mary M; Noriea, Nicholas F; Bauler, Laura D; Lam, Jennifer L; Sager, Janet; Wesolowski, Jordan; Paumet, Fabienne; Hackstadt, Ted

2016-04-01

Chlamydia trachomatis is an obligate intracellular pathogen that is the etiological agent of a variety of human diseases, including blinding trachoma and sexually transmitted infections. Chlamydiae replicate within a membrane-bound compartment, termed an inclusion, which they extensively modify by the insertion of type III secreted proteins called Inc proteins. IncA is an inclusion membrane protein that encodes two coiled-coil domains that are homologous to eukaryotic SNARE (soluble N-ethylmaleimide-sensitive factor attachment receptor) motifs. Recent biochemical evidence suggests that a functional core, composed of SNARE-like domain 1 (SLD-1) and part of SNARE-like domain 2 (SLD-2), is required for the characteristic homotypic fusion of C. trachomatis inclusions in multiply infected cells. To verify the importance of IncA in homotypic fusion in Chlamydia, we generated an incA::bla mutant. Insertional inactivation of incA resulted in the formation of nonfusogenic inclusions, a phenotype that was completely rescued by complementation with full-length IncA. Rescue of homotypic inclusion fusion was dependent on the presence of the functional core consisting of SLD-1 and part of SLD-2. Collectively, these results confirm in vitro membrane fusion assays identifying functional domains of IncA and expand the genetic tools available for identification of chlamydia with a method for complementation of site-specific mutants. Chlamydia trachomatis replicates within a parasitophorous vacuole termed an inclusion. The chlamydial inclusions are nonfusogenic with vesicles in the endocytic pathway but, in multiply infected cells, fuse with each other to form a single large inclusion. This homotypic fusion is dependent upon the presence of a chlamydial inclusion membrane-localized protein, IncA. Specificity of membrane fusion in eukaryotic cells is regulated by SNARE (soluble N-ethylmaleimide sensitive factor attachment receptor) proteins on the cytosolic face of vesicles and target

A second eigenvalue bound for the Dirichlet Schrodinger equation wtih a radially symmetric potential

Directory of Open Access Journals (Sweden)

Craig Haile

2000-01-01

Full Text Available We study the time-independent Schrodinger equation with radially symmetric potential $k|x|^alpha$, $k ge 0$, $k in mathbb{R}, alpha ge 2$ on a bounded domain $Omega$ in $mathbb{R}^n$, $(n ge 2$ with Dirichlet boundary conditions. In particular, we compare the eigenvalue $lambda_2(Omega$ of the operator $-Delta + k |x|^alpha $ on $Omega$ with the eigenvalue $lambda_2(S_1$ of the same operator $-Delta +kr^alpha$ on a ball $S_1$, where $S_1$ has radius such that the first eigenvalues are the same ($lambda_1(Omega = lambda_1(S_1$. The main result is to show $lambda_2(Omega le lambda_2(S_1$. We also give an extension of the main result to the case of a more general elliptic eigenvalue problem on a bounded domain $Omega$ with Dirichlet boundary conditions.

Towards an ICF- and IMMPACT-based pain vocational rehabilitation core set in the Netherlands.

Science.gov (United States)

Reneman, M F; Beemster, T T; Edelaar, M J A; van Velzen, J M; van Bennekom, C; Escorpizo, R

2013-12-01

For clinical use and research of pain within the context of vocational rehabilitation, a specific core set of measurements is needed. The recommendations of the International Classification of Functioning, Disability and Health (ICF) brief Core Set for Vocational Rehabilitation (VR) and those of Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) cover two broad areas. These two sources can be integrated when made applicable to vocational rehabilitation and pain. Objective To develop a core set of diagnostic and evaluative measures specifically for vocational rehabilitation of patients with subacute and chronic musculoskeletal pain, while using the brief ICF core set for VR as the reference framework in VR, and the IMMPACT recommendations in the outcome measurements around pain. Three main steps were taken. The first step was to remove irrelevant and duplicate domains of the brief ICF Core Set for Vocational Rehabilitation and the IMMPACT recommendations around pain. The second step was to match the remaining domains with existing instruments or measures. Instruments were proposed based on availability and its proven use in Dutch practice and based on proof of sufficient clinimetric properties. In step 3, the preliminary VR-Pain core set was presented to 3 expert panels: proposed users, Dutch pain rehabilitation experts, and international VR experts. Experts agreed with the majority of the proposed domains and instruments. The final VR-Pain Core Set consists of 18 domains measured with 12 instruments. All instruments possessed basic clinimetric properties. An agreed-upon VR-Pain Core Set with content that covers relevant domains for pain and VR and validated instruments measuring these domains has been developed. The VR-Pain Core Set may be used for regular clinical purposes and research in the field of vocational rehabilitation and pain, but adaptations should be considered for use outside the Netherlands.

Endophilin-A1 BAR domain interaction with arachidonyl CoA.

Science.gov (United States)

Petoukhov, Maxim V; Weissenhorn, Winfried; Svergun, Dmitri I

2014-01-01

Endophilin-A1 belongs to the family of BAR domain containing proteins that catalyze membrane remodeling processes via sensing, inducing and stabilizing membrane curvature. We show that the BAR domain of endophilin-A1 binds arachidonic acid and molds its coenzyme A (CoA) activated form, arachidonyl-CoA into a defined structure. We studied low resolution structures of endophilin-A1-BAR and its complex with arachidonyl-CoA in solution using synchrotron small-angle X-ray scattering (SAXS). The free endophilin-A1-BAR domain is shown to be dimeric at lower concentrations but builds tetramers and higher order complexes with increasing concentrations. Extensive titration SAXS studies revealed that the BAR domain produces a homogenous complex with the lipid micelles. The structural model of the complexes revealed two arachidonyl-CoA micelles bound to the distal arms of an endophilin-A1-BAR dimer. Intriguingly, the radius of the bound micelles significantly decreases compared to that of the free micelles, and this structural result may provide hints on the potential biological relevance of the endophilin-A1-BAR interaction with arachidonyl CoA.

Feasibility and Domain Validation of Rheumatoid Arthritis (RA) Flare Core Domain Set

DEFF Research Database (Denmark)

Bartlett, Susan J; Bykerk, Vivian P; Cooksey, Roxanne

2015-01-01

, and stiffness scores averaged ≥ 2 times higher (2 of 11 points) in flaring individuals. Correlations between flare domains and corresponding legacy instruments were obtained: r = 0.46 to 0.93. A combined definition (patient report of flare and 28-joint Disease Activity Score increase) was evaluated in 2 other...... provided input for stiffness, self-management, contextual factors, and measurement considerations. RESULTS: Flare data from 501 patients in an observational study indicated 39% were in flare, with mean (SD) severity of 6.0 (2.6) and 55% lasting > 14 days. Pain, physical function, fatigue, participation...

Incompleteness in the finite domain

Czech Academy of Sciences Publication Activity Database

Pudlák, Pavel

2017-01-01

Roč. 23, č. 4 (2017), s. 405-441 ISSN 1079-8986 EU Projects: European Commission(XE) 339691 - FEALORA Institutional support: RVO:67985840 Keywords : finite domain Subject RIV: BA - General Mathematics OBOR OECD: Pure mathematics Impact factor: 0.742, year: 2016 https://www.cambridge.org/core/journals/bulletin-of-symbolic-logic/article/incompleteness-in-the-finite-domain/D239B1761A73DCA534A4805A76D81C76

C-Terminal Substitution of HBV Core Proteins with Those from DHBV Reveals That Arginine-Rich 167RRRSQSPRR175 Domain Is Critical for HBV Replication

Science.gov (United States)

Kim, Taeyeung; Shin, Bo-Hye; Park, Gil-Soon; Park, Sun; Chwae, Yong-Joon; Shin, Ho-Joon; Kim, Kyongmin

2012-01-01

To investigate the contributions of carboxyl-terminal nucleic acid binding domain of HBV core (C) protein for hepatitis B virus (HBV) replication, chimeric HBV C proteins were generated by substituting varying lengths of the carboxyl-terminus of duck hepatitis B virus (DHBV) C protein for the corresponding regions of HBV C protein. All chimeric C proteins formed core particles. A chimeric C protein with 221–262 amino acids of DHBV C protein, in place of 146–185 amino acids of the HBV C protein, supported HBV pregenomic RNA (pgRNA) encapsidation and DNA synthesis: 40% amino acid sequence identity or 45% homology in the nucleic-acid binding domain of HBV C protein was sufficient for pgRNA encapsidation and DNA synthesis, although we predominantly detected spliced DNA. A chimeric C protein with 221–241 and 251–262 amino acids of DHBV C, in place of HBV C 146–166 and 176–185 amino acids, respectively, could rescue full-length DNA synthesis. However, a reciprocal C chimera with 242–250 of DHBV C (242RAGSPLPRS 250) introduced in place of 167–175 of HBV C (167RRRSQSPRR 175) significantly decreased pgRNA encapsidation and DNA synthesis, and full-length DNA was not detected, demonstrating that the arginine-rich 167RRRSQSPRR175 domain may be critical for efficient viral replication. Five amino acids differing between viral species (underlined above) were tested for replication rescue; R169 and R175 were found to be important. PMID:22911745

The PH Domain of PDK1 Exhibits a Novel, Phospho-Regulated Monomer-Dimer Equilibrium With Important Implications for Kinase Domain Activation: Single Molecule and Ensemble Studies†

Science.gov (United States)

Ziemba, Brian P.; Pilling, Carissa; Calleja, Véronique; Larijani, Banafshé; Falke, Joseph J.

2013-01-01

Phosphoinositide-Dependent Kinase-1 (PDK1) is an essential master kinase recruited to the plasma membrane by the binding of its C-terminal PH domain to the signaling lipid phosphatidylinositol-3,4-5-trisphosphate (PIP3). Membrane binding leads to PDK1 phospho-activation, but despite the central role of PDK1 in signaling and cancer biology this activation mechanism remains poorly understood. PDK1 has been shown to exist as a dimer in cells, and one crystal structure of its isolated PH domain exhibits a putative dimer interface. It has been proposed that phosphorylation of PH domain residue T513 (or the phospho-mimetic T513E mutation) may regulate a novel PH domain dimer-monomer equilibrium, thereby converting an inactive PDK1 dimer to an active monomer. However, the oligomeric state(s) of the PH domain on the membrane have not yet been determined, nor whether a negative charge at position 513 is sufficient to regulate its oligomeric state. The present study investigates the binding of purified WT and T513E PDK1 PH domains to lipid bilayers containing the PIP3 target lipid, using both single molecule and ensemble measurements. Single molecule analysis of the brightness of fluorescent PH domain shows that the PIP3-bound WT PH domain on membranes is predominantly dimeric, while the PIP3-bound T513E PH domain is monomeric, demonstrating that negative charge at the T513 position is sufficient to dissociate the PH domain dimer and is thus likely to play a central role in PDK1 monomerization and activation. Single molecule analysis of 2-D diffusion of PH domain-PIP3 complexes reveals that the dimeric WT PH domain diffuses at the same rate a single lipid molecule, indicating that only one of its two PIP3 binding sites is occupied and there is little protein penetration into the bilayer as observed for other PH domains. The 2-D diffusion of T513E PH domain is slower, suggesting the negative charge disrupts local structure in a way that enables greater protein insertion into

Generalized predictive control in the delta-domain

DEFF Research Database (Denmark)

Lauritsen, Morten Bach; Jensen, Morten Rostgaard; Poulsen, Niels Kjølstad

1995-01-01

This paper describes new approaches to generalized predictive control formulated in the delta (δ) domain. A new δ-domain version of the continuous-time emulator-based predictor is presented. It produces the optimal estimate in the deterministic case whenever the predictor order is chosen greater...... than or equal to the number of future predicted samples, however a “good” estimate is usually obtained in a much longer range of samples. This is particularly advantageous at fast sampling rates where a “conventional” predictor is bound to become very computationally demanding. Two controllers...

Evolutionary dynamics of protein domain architecture in plants

Directory of Open Access Journals (Sweden)

Zhang Xue-Cheng

2012-01-01

Full Text Available Abstract Background Protein domains are the structural, functional and evolutionary units of the protein. Protein domain architectures are the linear arrangements of domain(s in individual proteins. Although the evolutionary history of protein domain architecture has been extensively studied in microorganisms, the evolutionary dynamics of domain architecture in the plant kingdom remains largely undefined. To address this question, we analyzed the lineage-based protein domain architecture content in 14 completed green plant genomes. Results Our analyses show that all 14 plant genomes maintain similar distributions of species-specific, single-domain, and multi-domain architectures. Approximately 65% of plant domain architectures are universally present in all plant lineages, while the remaining architectures are lineage-specific. Clear examples are seen of both the loss and gain of specific protein architectures in higher plants. There has been a dynamic, lineage-wise expansion of domain architectures during plant evolution. The data suggest that this expansion can be largely explained by changes in nuclear ploidy resulting from rounds of whole genome duplications. Indeed, there has been a decrease in the number of unique domain architectures when the genomes were normalized into a presumed ancestral genome that has not undergone whole genome duplications. Conclusions Our data show the conservation of universal domain architectures in all available plant genomes, indicating the presence of an evolutionarily conserved, core set of protein components. However, the occurrence of lineage-specific domain architectures indicates that domain architecture diversity has been maintained beyond these core components in plant genomes. Although several features of genome-wide domain architecture content are conserved in plants, the data clearly demonstrate lineage-wise, progressive changes and expansions of individual protein domain architectures, reinforcing

Structural domain walls in polar hexagonal manganites

Science.gov (United States)

Kumagai, Yu

2014-03-01

The domain structure in the multiferroic hexagonal manganites is currently intensely investigated, motivated by the observation of intriguing sixfold topological defects at their meeting points [Choi, T. et al,. Nature Mater. 9, 253 (2010).] and nanoscale electrical conductivity at the domain walls [Wu, W. et al., Phys. Rev. Lett. 108, 077203 (2012).; Meier, D. et al., Nature Mater. 11, 284 (2012).], as well as reports of coupling between ferroelectricity, magnetism and structural antiphase domains [Geng, Y. et al., Nano Lett. 12, 6055 (2012).]. The detailed structure of the domain walls, as well as the origin of such couplings, however, was previously not fully understood. In the present study, we have used first-principles density functional theory to calculate the structure and properties of the low-energy structural domain walls in the hexagonal manganites [Kumagai, Y. and Spaldin, N. A., Nature Commun. 4, 1540 (2013).]. We find that the lowest energy domain walls are atomically sharp, with {210}orientation, explaining the orientation of recently observed stripe domains and suggesting their topological protection [Chae, S. C. et al., Phys. Rev. Lett. 108, 167603 (2012).]. We also explain why ferroelectric domain walls are always simultaneously antiphase walls, propose a mechanism for ferroelectric switching through domain-wall motion, and suggest an atomistic structure for the cores of the sixfold topological defects. This work was supported by ETH Zurich, the European Research Council FP7 Advanced Grants program me (grant number 291151), the JSPS Postdoctoral Fellowships for Research Abroad, and the MEXT Elements Strategy Initiative to Form Core Research Center TIES.

Status of the TMI-2 core: a review of damage assessments

International Nuclear Information System (INIS)

Croucher, D.W.

1981-01-01

Assessments of the damage within the core of the Three Mile Island Unit 2 reactor, performed by reconstructing the transient thermal-hydraulic sequence of events, estimating the amount of hydrogen generation, and evaluating the amount of fission products released, are reviewed and summarized. Minimum and maximum bounds of damage to the core are identified

Using the International Classification of Functioning, Disability, and Health to identify outcome domains for a core outcome set for aphasia: a comparison of stakeholder perspectives.

Science.gov (United States)

Wallace, Sarah J; Worrall, Linda; Rose, Tanya; Le Dorze, Guylaine

2017-11-12

This study synthesised the findings of three separate consensus processes exploring the perspectives of key stakeholder groups about important aphasia treatment outcomes. This process was conducted to generate recommendations for outcome domains to be included in a core outcome set for aphasia treatment trials. International Classification of Functioning, Disability, and Health codes were examined to identify where the groups of: (1) people with aphasia, (2) family members, (3) aphasia researchers, and (4) aphasia clinicians/managers, demonstrated congruence in their perspectives regarding important treatment outcomes. Codes were contextualized using qualitative data. Congruence across three or more stakeholder groups was evident for ICF chapters: Mental functions; Communication; and Services, systems, and policies. Quality of life was explicitly identified by clinicians/managers and researchers, while people with aphasia and their families identified outcomes known to be determinants of quality of life. Core aphasia outcomes include: language, emotional wellbeing, communication, patient-reported satisfaction with treatment and impact of treatment, and quality of life. International Classification of Functioning, Disability, and Health coding can be used to compare stakeholder perspectives and identify domains for core outcome sets. Pairing coding with qualitative data may ensure important nuances of meaning are retained. Implications for rehabilitation The outcomes measured in treatment research should be relevant to stakeholders and support health care decision making. Core outcome sets (agreed, minimum set of outcomes, and outcome measures) are increasingly being used to ensure the relevancy and consistency of the outcomes measured in treatment studies. Important aphasia treatment outcomes span all components of the International Classification of Functioning, Disability, and Health. Stakeholders demonstrated congruence in the identification of important

Symmetry Parameter Constraints from a Lower Bound on Neutron-matter Energy

Energy Technology Data Exchange (ETDEWEB)

Tews, Ingo [Institute for Nuclear Theory, University of Washington, Seattle, WA 98195-1550 (United States); Lattimer, James M. [Department of Physics and Astronomy, Stony Brook University, Stony Brook, NY 11794-3800 (United States); Ohnishi, Akira [Yukawa Institute for Theoretical Physics, Kyoto University, Kyoto 606-8502 (Japan); Kolomeitsev, Evgeni E., E-mail: itews@uw.edu, E-mail: james.lattimer@stonybrook.edu, E-mail: ohnishi@yukawa.kyoto-u.ac.jp, E-mail: e.kolomeitsev@gsi.de [Faculty of Natural Sciences, Matej Bel University, Tajovskeho 40, SK-97401 Banska Bystrica (Slovakia)

2017-10-20

We propose the existence of a lower bound on the energy of pure neutron matter (PNM) on the basis of unitary-gas considerations. We discuss its justification from experimental studies of cold atoms as well as from theoretical studies of neutron matter. We demonstrate that this bound results in limits to the density-dependent symmetry energy, which is the difference between the energies of symmetric nuclear matter and PNM. In particular, this bound leads to a lower limit to the volume symmetry energy parameter S {sub 0}. In addition, for assumed values of S {sub 0} above this minimum, this bound implies both upper and lower limits to the symmetry energy slope parameter L , which describes the lowest-order density dependence of the symmetry energy. A lower bound on neutron-matter incompressibility is also obtained. These bounds are found to be consistent with both recent calculations of the energies of PNM and constraints from nuclear experiments. Our results are significant because several equations of state that are currently used in astrophysical simulations of supernovae and neutron star mergers, as well as in nuclear physics simulations of heavy-ion collisions, have symmetry energy parameters that violate these bounds. Furthermore, below the nuclear saturation density, the bound on neutron-matter energies leads to a lower limit to the density-dependent symmetry energy, which leads to upper limits to the nuclear surface symmetry parameter and the neutron-star crust–core boundary. We also obtain a lower limit to the neutron-skin thicknesses of neutron-rich nuclei. Above the nuclear saturation density, the bound on neutron-matter energies also leads to an upper limit to the symmetry energy, with implications for neutron-star cooling via the direct Urca process.

Contribution of domain wall networks to the CMB power spectrum

International Nuclear Information System (INIS)

Lazanu, A.; Martins, C.J.A.P.; Shellard, E.P.S.

2015-01-01

We use three domain wall simulations from the radiation era to the late-time dark energy domination era based on the PRS algorithm to calculate the energy–momentum tensor components of domain wall networks in an expanding universe. Unequal time correlators in the radiation, matter and cosmological constant epochs are calculated using the scaling regime of each of the simulations. The CMB power spectrum of a network of domain walls is determined. The first ever quantitative constraint for the domain wall surface tension is obtained using a Markov chain Monte Carlo method; an energy scale of domain walls of 0.93 MeV, which is close but below the Zel'dovich bound, is determined

Contribution of domain wall networks to the CMB power spectrum

Energy Technology Data Exchange (ETDEWEB)

Lazanu, A., E-mail: A.Lazanu@damtp.cam.ac.uk [Centre for Theoretical Cosmology, Department of Applied Mathematics and Theoretical Physics, Wilberforce Road, Cambridge CB3 0WA (United Kingdom); Martins, C.J.A.P., E-mail: Carlos.Martins@astro.up.pt [Centro de Astrofísica, Universidade do Porto, Rua das Estrelas, 4150-762 Porto (Portugal); Instituto de Astrofísica e Ciências do Espaço, CAUP, Rua das Estrelas, 4150-762 Porto (Portugal); Shellard, E.P.S., E-mail: E.P.S.Shellard@damtp.cam.ac.uk [Centre for Theoretical Cosmology, Department of Applied Mathematics and Theoretical Physics, Wilberforce Road, Cambridge CB3 0WA (United Kingdom)

2015-07-30

We use three domain wall simulations from the radiation era to the late-time dark energy domination era based on the PRS algorithm to calculate the energy–momentum tensor components of domain wall networks in an expanding universe. Unequal time correlators in the radiation, matter and cosmological constant epochs are calculated using the scaling regime of each of the simulations. The CMB power spectrum of a network of domain walls is determined. The first ever quantitative constraint for the domain wall surface tension is obtained using a Markov chain Monte Carlo method; an energy scale of domain walls of 0.93 MeV, which is close but below the Zel'dovich bound, is determined.

Contribution of domain wall networks to the CMB power spectrum

Directory of Open Access Journals (Sweden)

A. Lazanu

2015-07-01

Full Text Available We use three domain wall simulations from the radiation era to the late-time dark energy domination era based on the PRS algorithm to calculate the energy–momentum tensor components of domain wall networks in an expanding universe. Unequal time correlators in the radiation, matter and cosmological constant epochs are calculated using the scaling regime of each of the simulations. The CMB power spectrum of a network of domain walls is determined. The first ever quantitative constraint for the domain wall surface tension is obtained using a Markov chain Monte Carlo method; an energy scale of domain walls of 0.93 MeV, which is close but below the Zel'dovich bound, is determined.

Perceptron Mistake Bounds

OpenAIRE

Mohri, Mehryar; Rostamizadeh, Afshin

2013-01-01

We present a brief survey of existing mistake bounds and introduce novel bounds for the Perceptron or the kernel Perceptron algorithm. Our novel bounds generalize beyond standard margin-loss type bounds, allow for any convex and Lipschitz loss function, and admit a very simple proof.

Vortex Ring Dynamics in Radially Confined Domains

Science.gov (United States)

Stewart, Kelley; Niebel, Casandra; Jung, Sunghwan; Vlachos, Pavlos

2010-11-01

Vortex ring dynamics have been studied extensively in semi-infinite quiescent volumes. However, very little is known about vortex-ring formation in wall-bounded domains where vortex wall interaction will affect both the vortex ring pinch-off and propagation velocity. This study addresses this limitation and studies vortex formation in radially confined domains to analyze the affect of vortex-ring wall interaction on the formation and propagation of the vortex ring. Vortex rings were produced using a pneumatically driven piston cylinder arrangement and were ejected into a long cylindrical tube which defined the confined downstream domain. A range of confinement domains were studied with varying confinement diameters Velocity field measurements were performed using planar Time Resolved Digital Particle Image Velocimetry (TRDPIV) and were processed using an in-house developed cross-correlation PIV algorithm. The experimental analysis was used to facilitate the development of a theoretical model to predict the variations in vortex ring circulation over time within confined domains.

HCV Core Residues Critical for Infectivity Are Also Involved in Core-NS5A Complex Formation

Science.gov (United States)

Gawlik, Katarzyna; Baugh, James; Chatterji, Udayan; Lim, Precious J.; Bobardt, Michael D.; Gallay, Philippe A.

2014-01-01

Hepatitis C virus (HCV) infection is a major cause of liver disease. The molecular machinery of HCV assembly and particle release remains obscure. A better understanding of the assembly events might reveal new potential antiviral strategies. It was suggested that the nonstructural protein 5A (NS5A), an attractive recent drug target, participates in the production of infectious particles as a result of its interaction with the HCV core protein. However, prior to the present study, the NS5A-binding site in the viral core remained unknown. We found that the D1 domain of core contains the NS5A-binding site with the strongest interacting capacity in the basic P38-K74 cluster. We also demonstrated that the N-terminal basic residues of core at positions 50, 51, 59 and 62 were required for NS5A binding. Analysis of all substitution combinations of R50A, K51A, R59A, and R62A, in the context of the HCVcc system, showed that single, double, triple, and quadruple mutants were fully competent for viral RNA replication, but deficient in secretion of viral particles. Furthermore, we found that the extracellular and intracellular infectivity of all the mutants was abolished, suggesting a defect in the formation of infectious particles. Importantly, we showed that the interaction between the single and quadruple core mutants and NS5A was impaired in cells expressing full-length HCV genome. Interestingly, mutations of the four basic residues of core did not alter the association of core or NS5A with lipid droplets. This study showed for the first time that basic residues in the D1 domain of core that are critical for the formation of infectious extracellular and intracellular particles also play a role in core-NS5A interactions. PMID:24533158

Multiple domains of fission yeast Cdc19p (MCM2) are required for its association with the core MCM complex.

Science.gov (United States)

Sherman, D A; Pasion, S G; Forsburg, S L

1998-07-01

The members of the MCM protein family are essential eukaryotic DNA replication factors that form a six-member protein complex. In this study, we use antibodies to four MCM proteins to investigate the structure of and requirements for the formation of fission yeast MCM complexes in vivo, with particular regard to Cdc19p (MCM2). Gel filtration analysis shows that the MCM protein complexes are unstable and can be broken down to subcomplexes. Using coimmunoprecipitation, we find that Mis5p (MCM6) and Cdc21p (MCM4) are tightly associated with one another in a core complex with which Cdc19p loosely associates. Assembly of Cdc19p with the core depends upon Cdc21p. Interestingly, there is no obvious change in Cdc19p-containing MCM complexes through the cell cycle. Using a panel of Cdc19p mutants, we find that multiple domains of Cdc19p are required for MCM binding. These studies indicate that MCM complexes in fission yeast have distinct substructures, which may be relevant for function.

Universal localizing bounds for compact invariant sets of natural polynomial Hamiltonian systems

International Nuclear Information System (INIS)

Starkov, Konstantin E.

2008-01-01

In this Letter we study the localization problem of compact invariant sets of natural Hamiltonian systems with a polynomial Hamiltonian. Our results are based on applying the first order extremum conditions. We compute universal localizing bounds for some domain containing all compact invariant sets of a Hamiltonian system by using one quadratic function of a simple form. These bounds depend on the value of the total energy of the system, degree and some coefficients of a potential and, in addition, some positive number got as a result of a solution of one maximization problem. Besides, under some quasihomogeneity condition(s) we generalize our construction of the localization set

Universal localizing bounds for compact invariant sets of natural polynomial Hamiltonian systems

Energy Technology Data Exchange (ETDEWEB)

Starkov, Konstantin E. [CITEDI-IPN, Av. del Parque 1310, Mesa de Otay, Tijuana, BC (Mexico)], E-mail: konst@citedi.mx

2008-10-06

In this Letter we study the localization problem of compact invariant sets of natural Hamiltonian systems with a polynomial Hamiltonian. Our results are based on applying the first order extremum conditions. We compute universal localizing bounds for some domain containing all compact invariant sets of a Hamiltonian system by using one quadratic function of a simple form. These bounds depend on the value of the total energy of the system, degree and some coefficients of a potential and, in addition, some positive number got as a result of a solution of one maximization problem. Besides, under some quasihomogeneity condition(s) we generalize our construction of the localization set.

Occupancy of a C2-C2 type 'zinc-finger' protein domain by copper. Direct observation by electrospray ionization mass spectrometry.

Science.gov (United States)

Hutchens, T W; Allen, M H; Li, C M; Yip, T T

1992-09-07

The metal ion specificity of most 'zinc-finger' metal binding domains is unknown. The human estrogen receptor protein contains two different C2-C2 type 'zinc-finger' sequences within its DNA-binding domain (ERDBD). Copper inhibits the function of this protein by mechanisms which remain unclear. We have used electrospray ionization mass spectrometry to evaluate directly the 71-residue ERDBD (K180-M250) in the absence and presence of Cu(II) ions. The ERDBD showed a high affinity for Cu and was completely occupied with 4 Cu bound; each Cu ion was evidently bound to only two ligand residues (net loss of only 2 Da per bound Cu). The Cu binding stoichiometry was confirmed by atomic absorption. These results (i) provide the first direct physical evidence for the ability of the estrogen receptor DNA-binding domain to bind Cu and (ii) document a twofold difference in the Zn- and Cu-binding capacity. Differences in the ERDBD domain structure with bound Zn and Cu are predicted. Given the relative intracellular contents of Zn and Cu, our findings demonstrate the need to investigate further the Cu occupancy of this and other zinc-finger domains both in vitro and in vivo.

Apo and ligand-bound structures of ModA from the archaeon Methanosarcina acetivorans.

Science.gov (United States)

Chan, Sum; Giuroiu, Iulia; Chernishof, Irina; Sawaya, Michael R; Chiang, Janet; Gunsalus, Robert P; Arbing, Mark A; Perry, L Jeanne

2010-03-01

The trace-element oxyanion molybdate, which is required for the growth of many bacterial and archaeal species, is transported into the cell by an ATP-binding cassette (ABC) transporter superfamily uptake system called ModABC. ModABC consists of the ModA periplasmic solute-binding protein, the integral membrane-transport protein ModB and the ATP-binding and hydrolysis cassette protein ModC. In this study, X-ray crystal structures of ModA from the archaeon Methanosarcina acetivorans (MaModA) have been determined in the apoprotein conformation at 1.95 and 1.69 A resolution and in the molybdate-bound conformation at 2.25 and 2.45 A resolution. The overall domain structure of MaModA is similar to other ModA proteins in that it has a bilobal structure in which two mixed alpha/beta domains are linked by a hinge region. The apo MaModA is the first unliganded archaeal ModA structure to be determined: it exhibits a deep cleft between the two domains and confirms that upon binding ligand one domain is rotated towards the other by a hinge-bending motion, which is consistent with the 'Venus flytrap' model seen for bacterial-type periplasmic binding proteins. In contrast to the bacterial ModA structures, which have tetrahedral coordination of their metal substrates, molybdate-bound MaModA employs octahedral coordination of its substrate like other archaeal ModA proteins.

The PWR cores management

International Nuclear Information System (INIS)

Barral, J.C.; Rippert, D.; Johner, J.

2000-01-01

During the meeting of the 25 january 2000, organized by the SFEN, scientists and plant operators in the domain of the PWR debated on the PWR cores management. The five first papers propose general and economic information on the PWR and also the fast neutron reactors chains in the electric power market: statistics on the electric power industry, nuclear plant unit management, the ITER project and the future of the thermonuclear fusion, the treasurer's and chairman's reports. A second part offers more technical papers concerning the PWR cores management: performance and optimization, in service load planning, the cores management in the other countries, impacts on the research and development programs. (A.L.B.)

The need to study of bounding accident in reprocessing plant

International Nuclear Information System (INIS)

Segawa, Satoshi; Fujita, Kunio

2013-01-01

There is a clear consensus that the severe accident corresponds to the core damage accident for power reactors. On the other hand, for FCFs, there is no clear consensus on what is the accident to assess the safety in the region of beyond design basis, or what is the accident which has very low probability but large consequence. The need to examine a bounding consequence of each type of accident is explained to advance the rationality of safety management and regulation and, as a result, to reinforce the safety of a reprocessing plant. The likelihood of occurrence of an accident causing a bounding consequence should correspond to that of a severe accident at a nuclear power plant. The bounding consequence will be derived using the deterministic method and sound engineering judgment supplemented by the probabilistic method. Once an agreement on such a concept is reached among regulators, operators and related experts it will help to provide a solid basis to ensure the safety of a reprocessing plant independent of that of a nuclear power plant. In this paper, we show a preliminary risk profile of RRP calculated by QSA (Quantitative Safety Assessment) which JNFL developed. The profile shows that bounding consequences of various accidents in a range of occurrence frequency corresponding to a severe accident at a nuclear power plant. And we find that the bounding consequence of high-level liquid waste boiling is the largest among all in this range. Therefore, the risk of this event is shown in this paper as an example. To build a common consensus about bounding accidents among concerned parties will encourage regulatory body to introduce such an idea for more effective regulation with scientific rationality. Additionally the study of bounding accidents can contribute to substantial development for accident management strategy as reprocessing operators. (authors)

Clojure for domain-specific languages

CERN Document Server

Kelker, Ryan D

2013-01-01

An example-oriented approach to develop custom domain-specific languages.If you've already developed a few Clojure applications and wish to expand your knowledge on Clojure or domain-specific languages in general, then this book is for you. If you're an absolute Clojure beginner, then you may only find the detailed examples of the core Clojure components of value. If you've developed DSLs in other languages, this Lisp and Java-based book might surprise you with the power of Clojure.

Domain structure of a NHEJ DNA repair ligase from Mycobacterium tuberculosis.

Science.gov (United States)

Pitcher, Robert S; Tonkin, Louise M; Green, Andrew J; Doherty, Aidan J

2005-08-19

A prokaryotic non-homologous end-joining (NHEJ) system for the repair of DNA double-strand breaks (DSBs), composed of a Ku homodimer (Mt-Ku) and a multidomain multifunctional ATP-dependent DNA ligase (Mt-Lig), has been described recently in Mycobacterium tuberculosis. Mt-Lig exhibits polymerase and nuclease activity in addition to DNA ligation activity. These functions were ascribed to putative polymerase, nuclease and ligase domains that together constitute a monomeric protein. Here, the separate polymerase, nuclease and ligase domains of Mt-Lig were cloned individually, over-expressed and the soluble proteins purified to homogeneity. The polymerase domain demonstrated DNA-dependent RNA primase activity, catalysing the synthesis of unprimed oligoribonucleotides on single-stranded DNA templates. The polymerase domain can also extend DNA in a template-dependent manner. This activity was eliminated when the catalytic aspartate residues were replaced with alanine. The ligase domain catalysed the sealing of nicked double-stranded DNA designed to mimic a DSB, consistent with the role of Mt-Lig in NHEJ. Deletion of the active-site lysine residue prevented the formation of an adenylated ligase complex and consequently thwarted ligation. The nuclease domain did not function independently as a 3'-5' exonuclease. DNA-binding assays revealed that both the polymerase and ligase domains bind DNA in vitro, the latter with considerably higher affinity. Mt-Ku directly stimulated the polymerase and nuclease activities of Mt-Lig. The polymerase domain bound Mt-Ku in vitro, suggesting it may recruit Mt-Lig to Ku-bound DNA in vivo. Consistent with these data, Mt-Ku stimulated the primer extension activity of the polymerase domain, suggestive of a functional interaction relevant to NHEJ-mediated DSB repair processes.

Domain decomposition methods for the neutron diffusion problem

International Nuclear Information System (INIS)

Guerin, P.; Baudron, A. M.; Lautard, J. J.

2010-01-01

The neutronic simulation of a nuclear reactor core is performed using the neutron transport equation, and leads to an eigenvalue problem in the steady-state case. Among the deterministic resolution methods, simplified transport (SPN) or diffusion approximations are often used. The MINOS solver developed at CEA Saclay uses a mixed dual finite element method for the resolution of these problems. and has shown his efficiency. In order to take into account the heterogeneities of the geometry, a very fine mesh is generally required, and leads to expensive calculations for industrial applications. In order to take advantage of parallel computers, and to reduce the computing time and the local memory requirement, we propose here two domain decomposition methods based on the MINOS solver. The first approach is a component mode synthesis method on overlapping sub-domains: several Eigenmodes solutions of a local problem on each sub-domain are taken as basis functions used for the resolution of the global problem on the whole domain. The second approach is an iterative method based on a non-overlapping domain decomposition with Robin interface conditions. At each iteration, we solve the problem on each sub-domain with the interface conditions given by the solutions on the adjacent sub-domains estimated at the previous iteration. Numerical results on parallel computers are presented for the diffusion model on realistic 2D and 3D cores. (authors)

Crystals of Na(+)/K(+)-ATPase with bound cisplatin.

Science.gov (United States)

Huliciak, Miroslav; Reinhard, Linda; Laursen, Mette; Fedosova, Natalya; Nissen, Poul; Kubala, Martin

2014-12-01

Cisplatin is the most widely used chemotherapeutics for cancer treatment, however, its administration is connected to inevitable adverse effects. Previous studies suggested that cisplatin is able to inhibit Na(+)/K(+)-ATPase (NKA), the enzyme responsible for maintaining electrochemical potential and sodium gradient across the plasma membrane. Here we report a crystallographic analysis of cisplatin bound to NKA in the ouabain bound E2P form. Despite a moderate resolution (7.4 Å and 7.9 Å), the anomalous scattering from platinum and a model representation from a recently published structure enabled localization of seven cisplatin binding sites by anomalous difference Fourier maps. Comparison with NKA structures in the E1P conformation suggested two possible inhibitory mechanisms for cisplatin. Binding to Met151 can block the N-terminal pathway for transported cations, while binding to Met171 can hinder the interaction of cytoplasmic domains during the catalytic cycle. Copyright © 2014 Elsevier Inc. All rights reserved.

The PH domain of phosphoinositide-dependent kinase-1 exhibits a novel, phospho-regulated monomer-dimer equilibrium with important implications for kinase domain activation: single-molecule and ensemble studies.

Science.gov (United States)

Ziemba, Brian P; Pilling, Carissa; Calleja, Véronique; Larijani, Banafshé; Falke, Joseph J

2013-07-16

Phosphoinositide-dependent kinase-1 (PDK1) is an essential master kinase recruited to the plasma membrane by the binding of its C-terminal PH domain to the signaling lipid phosphatidylinositol-3,4,5-trisphosphate (PIP3). Membrane binding leads to PDK1 phospho-activation, but despite the central role of PDK1 in signaling and cancer biology, this activation mechanism remains poorly understood. PDK1 has been shown to exist as a dimer in cells, and one crystal structure of its isolated PH domain exhibits a putative dimer interface. It has been proposed that phosphorylation of PH domain residue T513 (or the phospho-mimetic T513E mutation) may regulate a novel PH domain dimer-monomer equilibrium, thereby converting an inactive PDK1 dimer to an active monomer. However, the oligomeric states of the PH domain on the membrane have not yet been determined, nor whether a negative charge at position 513 is sufficient to regulate its oligomeric state. This study investigates the binding of purified wild-type (WT) and T513E PDK1 PH domains to lipid bilayers containing the PIP3 target lipid, using both single-molecule and ensemble measurements. Single-molecule analysis of the brightness of the fluorescent PH domain shows that the PIP3-bound WT PH domain on membranes is predominantly dimeric while the PIP3-bound T513E PH domain is monomeric, demonstrating that negative charge at the T513 position is sufficient to dissociate the PH domain dimer and is thus likely to play a central role in PDK1 monomerization and activation. Single-molecule analysis of two-dimensional (2D) diffusion of PH domain-PIP3 complexes reveals that the dimeric WT PH domain diffuses at the same rate as a single lipid molecule, indicating that only one of its two PIP3 binding sites is occupied and there is little penetration of the protein into the bilayer as observed for other PH domains. The 2D diffusion of T513E PH domain is slower, suggesting the negative charge disrupts local structure in a way that allows

Identifying core domains to assess flare in rheumatoid arthritis

DEFF Research Database (Denmark)

Bartlett, Susan J; Hewlett, Sarah; Bingham, Clifton O

2012-01-01

For rheumatoid arthritis (RA), there is no consensus on how to define and assess flare. Variability in flare definitions impairs understanding of findings across studies and limits ability to pool results. The OMERACT RA Flare Group sought to identify domains to define RA flares from patient...

Spectrum of the multigroup neutron transport operator for bounded spatial domains

International Nuclear Information System (INIS)

Larsen, E.W.

1979-01-01

The spectrum of the multigroup neutron transport operator A is studied for bounded spatial regions D which consist of a finite number of material subregions. Our main results provide simple conditions on the material cross sections which guarantee that (1) A possesses eigenvalues in the finite plane; (2) A possesses a ''leading'' eigenvalue lambda 0 which is real, not less than the real part of any other eigenvalue, and to which there corresponds at least one nonnegative eigenfunction psi/sub lambda/0; and (3) A possesses a ''dominant'' eigenvalue lambda 0 which is real, simple, greater than the real part of any other eigenvalue, and whose eigenfunction psi/sub lambda/0 satisfies psi/sub lambda/0> or =0 and ∫psi/sub lambda/0d 2 Ω>0. We give examples to illustrate the results and to show that a leading eigenvalue need not be simple, nor its eigenfunction(s) positive

Accessibility of receptor-bound urokinase to type-1 plasminogen activator inhibitor

Energy Technology Data Exchange (ETDEWEB)

Cubellis, M.V.; Andreasen, P.; Ragno, P.; Mayer, M.; Dano, K.; Blasi, F. (Univ. of Copenhagen (Denmark))

1989-07-01

Urokinase plasminogen activator (uPA) interacts with a surface receptor and with specific inhibitors, such as plasminogen activator inhibitor type 1 (PAI-1). These interactions are mediated by two functionally independent domains of the molecule: the catalytic domain (at the carboxyl terminus) and the growth factor domain (at the amino terminus). The authors have now investigated whether PAI-1 can bind and inhibit receptor-bound uPA. Binding of {sup 125}I-labeled ATF (amino-terminal fragment of uPA) to human U937 monocyte-like cells can be competed for by uPA-PAI-1 complexes, but not by PAI-1 alone. Preformed {sup 125}I-labeled uPA-PAI-1 complexes can bind to uPA receptor with the same binding specificity as uPA. PAI-1 also binds to, and inhibits the activity of, receptor-bound uPA in U937 cells, as shown in U937 cells by a caseinolytic plaque assay. Plasminogen activator activity of these cells is dependent on exogenous uPA, is competed for by receptor-binding diisopropyl fluorophosphate-treated uPA, and is inhibited by the addition of PAI-1. In conclusion, in U937 cells the binding to the receptor does not shield uPA from the action of PAI-1. The possibility that in adherent cells a different localization of PAI-1 and uPA leads to protection of uPA from PAI-1 is to be considered.

Entropy lower bounds of quantum decision tree complexity

OpenAIRE

Shi, Yaoyun

2000-01-01

We prove a general lower bound of quantum decision tree complexity in terms of some entropy notion. We regard the computation as a communication process in which the oracle and the computer exchange several rounds of messages, each round consisting of O(log(n)) bits. Let E(f) be the Shannon entropy of the random variable f(X), where X is uniformly random in f's domain. Our main result is that it takes \\Omega(E(f)) queries to compute any \\emph{total} function f. It is interesting to contrast t...

Short versus long range interactions and the size of two-body weakly bound objects

International Nuclear Information System (INIS)

Lombard, R.J.; Volpe, C.

2003-01-01

Very weakly bound systems may manifest intriguing ''universal'' properties, independent of the specific interaction which keeps the system bound. An interesting example is given by relations between the size of the system and the separation energy, or scaling laws. So far, scaling laws have been investigated for short-range and long-range (repulsive) potentials. We report here on scaling laws for weakly bound two-body systems valid for a larger class of potentials, i.e. short-range potentials having a repulsive core and long-range attractive potentials. We emphasize analogies and differences between the short- and the long-range case. In particular, we show that the emergence of halos is a threshold phenomenon which can arise when the system is bound not only by short-range interactions but also by long-range ones, and this for any value of the orbital angular momentum l. These results enlarge the image of halo systems we are accustomed to. (orig.)

Existence of bounded solutions of Neumann problem for a nonlinear degenerate elliptic equation

Directory of Open Access Journals (Sweden)

Salvatore Bonafede

2017-10-01

Full Text Available We prove the existence of bounded solutions of Neumann problem for nonlinear degenerate elliptic equations of second order in divergence form. We also study some properties as the Phragmen-Lindelof property and the asymptotic behavior of the solutions of Dirichlet problem associated to our equation in an unbounded domain.

High resolution crystal structure of the Grb2 SH2 domain with a phosphopeptide derived from CD28.

Directory of Open Access Journals (Sweden)

Kunitake Higo

Full Text Available Src homology 2 (SH2 domains play a critical role in cellular signal transduction. They bind to peptides containing phosphotyrosine (pY with various specificities that depend on the flanking amino-acid residues. The SH2 domain of growth-factor receptor-bound protein 2 (Grb2 specifically recognizes pY-X-N-X, whereas the SH2 domains in phosphatidylinositol 3-kinase (PI3K recognize pY-X-X-M. Binding of the pY site in CD28 (pY-M-N-M by PI3K and Grb2 through their SH2 domains is a key step that triggers the CD28 signal transduction for T cell activation and differentiation. In this study, we determined the crystal structure of the Grb2 SH2 domain in complex with a pY-containing peptide derived from CD28 at 1.35 Å resolution. The peptide was found to adopt a twisted U-type conformation, similar to, but distinct from type-I β-turn. In all previously reported crystal structures, the peptide bound to the Grb2 SH2 domains adopts a type-I β-turn conformation, except those with a proline residue at the pY+3 position. Molecular modeling also suggests that the same peptide bound to PI3K might adopt a very different conformation.

High resolution crystal structure of the Grb2 SH2 domain with a phosphopeptide derived from CD28.

Science.gov (United States)

Higo, Kunitake; Ikura, Teikichi; Oda, Masayuki; Morii, Hisayuki; Takahashi, Jun; Abe, Ryo; Ito, Nobutoshi

2013-01-01

Src homology 2 (SH2) domains play a critical role in cellular signal transduction. They bind to peptides containing phosphotyrosine (pY) with various specificities that depend on the flanking amino-acid residues. The SH2 domain of growth-factor receptor-bound protein 2 (Grb2) specifically recognizes pY-X-N-X, whereas the SH2 domains in phosphatidylinositol 3-kinase (PI3K) recognize pY-X-X-M. Binding of the pY site in CD28 (pY-M-N-M) by PI3K and Grb2 through their SH2 domains is a key step that triggers the CD28 signal transduction for T cell activation and differentiation. In this study, we determined the crystal structure of the Grb2 SH2 domain in complex with a pY-containing peptide derived from CD28 at 1.35 Å resolution. The peptide was found to adopt a twisted U-type conformation, similar to, but distinct from type-I β-turn. In all previously reported crystal structures, the peptide bound to the Grb2 SH2 domains adopts a type-I β-turn conformation, except those with a proline residue at the pY+3 position. Molecular modeling also suggests that the same peptide bound to PI3K might adopt a very different conformation.

Formation and biochemical characterization of tube/pelle death domain complexes: critical regulators of postreceptor signaling by the Drosophila toll receptor.

Science.gov (United States)

Schiffmann, D A; White, J H; Cooper, A; Nutley, M A; Harding, S E; Jumel, K; Solari, R; Ray, K P; Gay, N J

1999-09-07

In Drosophila, the Toll receptor signaling pathway is required for embryonic dorso-ventral patterning and at later developmental stages for innate immune responses. It is thought that dimerization of the receptor by binding of the ligand spätzle causes the formation of a postreceptor activation complex at the cytoplasmic surface of the membrane. Two components of this complex are the adaptor tube and protein kinase pelle. These proteins both have "death domains", protein interaction motifs found in a number of signaling pathways, particularly those involved in apoptotic cell death. It is thought that pelle is bound by tube during formation of the activation complexes, and that this interaction is mediated by the death domains. In this paper, we show using the yeast two-hybrid system that the wild-type tube and pelle death domains bind together. Mutant tube proteins which do not support signaling in the embryo are also unable to bind pelle in the 2-hybrid assay. We have purified proteins corresponding to the death domains of tube and pelle and show that these form corresponding heterodimeric complexes in vitro. Partial proteolysis reveals a smaller core consisting of the minimal death domain sequences. We have studied the tube/pelle interaction with the techniques of surface plasmon resonance, analytical ultracentrifugation and isothermal titration calorimetry. These measurements produce a value of K(d) for the complex of about 0.5 microM.

A two-domain elevator mechanism for sodium/proton antiport.

Science.gov (United States)

Lee, Chiara; Kang, Hae Joo; von Ballmoos, Christoph; Newstead, Simon; Uzdavinys, Povilas; Dotson, David L; Iwata, So; Beckstein, Oliver; Cameron, Alexander D; Drew, David

2013-09-26

Sodium/proton (Na(+)/H(+)) antiporters, located at the plasma membrane in every cell, are vital for cell homeostasis. In humans, their dysfunction has been linked to diseases, such as hypertension, heart failure and epilepsy, and they are well-established drug targets. The best understood model system for Na(+)/H(+) antiport is NhaA from Escherichia coli, for which both electron microscopy and crystal structures are available. NhaA is made up of two distinct domains: a core domain and a dimerization domain. In the NhaA crystal structure a cavity is located between the two domains, providing access to the ion-binding site from the inward-facing surface of the protein. Like many Na(+)/H(+) antiporters, the activity of NhaA is regulated by pH, only becoming active above pH 6.5, at which point a conformational change is thought to occur. The only reported NhaA crystal structure so far is of the low pH inactivated form. Here we describe the active-state structure of a Na(+)/H(+) antiporter, NapA from Thermus thermophilus, at 3 Å resolution, solved from crystals grown at pH 7.8. In the NapA structure, the core and dimerization domains are in different positions to those seen in NhaA, and a negatively charged cavity has now opened to the outside. The extracellular cavity allows access to a strictly conserved aspartate residue thought to coordinate ion binding directly, a role supported here by molecular dynamics simulations. To alternate access to this ion-binding site, however, requires a surprisingly large rotation of the core domain, some 20° against the dimerization interface. We conclude that despite their fast transport rates of up to 1,500 ions per second, Na(+)/H(+) antiporters operate by a two-domain rocking bundle model, revealing themes relevant to secondary-active transporters in general.

Fido, a novel AMPylation domain common to fic, doc, and AvrB.

Directory of Open Access Journals (Sweden)

Lisa N Kinch

2009-06-01

Full Text Available The Vibrio parahaemolyticus type III secreted effector VopS contains a fic domain that covalently modifies Rho GTPase threonine with AMP to inhibit downstream signaling events in host cells. The VopS fic domain includes a conserved sequence motif (HPFx[D/E]GN[G/K]R that contributes to AMPylation. Fic domains are found in a variety of species, including bacteria, a few archaea, and metazoan eukaryotes.We show that the AMPylation activity extends to a eukaryotic fic domain in Drosophila melanogaster CG9523, and use sequence and structure based computational methods to identify related domains in doc toxins and the type III effector AvrB. The conserved sequence motif that contributes to AMPylation unites fic with doc. Although AvrB lacks this motif, its structure reveals a similar topology to the fic and doc folds. AvrB binds to a peptide fragment of its host virulence target in a similar manner as fic binds peptide substrate. AvrB also orients a phosphate group from a bound ADP ligand near the peptide-binding site and in a similar position as a bound fic phosphate.The demonstrated eukaryotic fic domain AMPylation activity suggests that the VopS effector has exploited a novel host posttranslational modification. Fic domain-related structures give insight to the AMPylation active site and to the VopS fic domain interaction with its host GTPase target. These results suggest that fic, doc, and AvrB stem from a common ancestor that has evolved to AMPylate protein substrates.

Inner core boundary topography explored with reflected and diffracted P waves

Science.gov (United States)

deSilva, Susini; Cormier, Vernon F.; Zheng, Yingcai

2018-03-01

The existence of topography of the inner core boundary (ICB) can affect the amplitude, phase, and coda of body waves incident on the inner core. By applying pseudospectral and boundary element methods to synthesize compressional waves interacting with the ICB, these effects are predicted and compared with waveform observations in pre-critical, critical, post-critical, and diffraction ranges of the PKiKP wave reflected from the ICB. These data sample overlapping regions of the inner core beneath the circum-Pacific belt and the Eurasian, North American, and Australian continents, but exclude large areas beneath the Pacific and Indian Oceans and the poles. In the pre-critical range, PKiKP waveforms require an upper bound of 2 km at 1-20 km wavelength for any ICB topography. Higher topography sharply reduces PKiKP amplitude and produces time-extended coda not observed in PKiKP waveforms. The existence of topography of this scale smooths over minima and zeros in the pre-critical ICB reflection coefficient predicted from standard earth models. In the range surrounding critical incidence (108-130 °), this upper bound of topography does not strongly affect the amplitude and waveform behavior of PKIKP + PKiKP at 1.5 Hz, which is relatively insensitive to 10-20 km wavelength topography height approaching 5 km. These data, however, have a strong overlap in the regions of the ICB sampled by pre-critical PKiKP that require a 2 km upper bound to topography height. In the diffracted range (>152°), topography as high as 5 km attenuates the peak amplitudes of PKIKP and PKPCdiff by similar amounts, leaving the PKPCdiff/PKIKP amplitude ratio unchanged from that predicted by a smooth ICB. The observed decay of PKPCdiff into the inner core shadow and the PKIKP-PKPCdiff differential travel time are consistent with a flattening of the outer core P velocity gradient near the ICB and iron enrichment at the bottom of the outer core.

Exponential attractors for a Cahn-Hilliard model in bounded domains with permeable walls

Directory of Open Access Journals (Sweden)

Ciprian G. Gal

2006-11-01

Full Text Available In a previous article [7], we proposed a model of phase separation in a binary mixture confined to a bounded region which may be contained within porous walls. The boundary conditions were derived from a mass conservation law and variational methods. In the present paper, we study the problem further. Using a Faedo-Galerkin method, we obtain the existence and uniqueness of a global solution to our problem, under more general assumptions than those in [7]. We then study its asymptotic behavior and prove the existence of an exponential attractor (and thus of a global attractor with finite dimension.

Designing Domain-Specific Heterogeneous Architectures from Dataflow Programs

Directory of Open Access Journals (Sweden)

Süleyman Savas

2018-04-01

Full Text Available The last ten years have seen performance and power requirements pushing computer architectures using only a single core towards so-called manycore systems with hundreds of cores on a single chip. To further increase performance and energy efficiency, we are now seeing the development of heterogeneous architectures with specialized and accelerated cores. However, designing these heterogeneous systems is a challenging task due to their inherent complexity. We proposed an approach for designing domain-specific heterogeneous architectures based on instruction augmentation through the integration of hardware accelerators into simple cores. These hardware accelerators were determined based on their common use among applications within a certain domain.The objective was to generate heterogeneous architectures by integrating many of these accelerated cores and connecting them with a network-on-chip. The proposed approach aimed to ease the design of heterogeneous manycore architectures—and, consequently, exploration of the design space—by automating the design steps. To evaluate our approach, we enhanced our software tool chain with a tool that can generate accelerated cores from dataflow programs. This new tool chain was evaluated with the aid of two use cases: radar signal processing and mobile baseband processing. We could achieve an approximately 4 × improvement in performance, while executing complete applications on the augmented cores with a small impact (2.5–13% on area usage. The generated accelerators are competitive, achieving more than 90% of the performance of hand-written implementations.

Full domain closure of the ligand-binding core of the ionotropic glutamate receptor iGluR5 induced by the high affinity agonist dysiherbaine and the functional antagonist 8,9-dideoxyneodysiherbaine

DEFF Research Database (Denmark)

Frydenvang, Karla Andrea; Lash, L Leanne; Naur, Peter

2009-01-01

The prevailing structural model for ligand activation of ionotropic glutamate receptors posits that agonist efficacy arises from the stability and magnitude of induced domain closure in the ligand-binding core structure. Here we describe an exception to the correlation between ligand efficacy and...

Two Novel Rab2 Interactors Regulate Dense-core Vesicle Maturation

Science.gov (United States)

Ailion, Michael; Hannemann, Mandy; Dalton, Susan; Pappas, Andrea; Watanabe, Shigeki; Hegermann, Jan; Liu, Qiang; Han, Hsiao-Fen; Gu, Mingyu; Goulding, Morgan Q.; Sasidharan, Nikhil; Schuske, Kim; Hullett, Patrick; Eimer, Stefan; Jorgensen, Erik M.

2014-01-01

Summary Peptide neuromodulators are released from a unique organelle: the dense-core vesicle. Dense-core vesicles are generated at the trans-Golgi, and then sort cargo during maturation before being secreted. To identify proteins that act in this pathway, we performed a genetic screen in Caenorhabditis elegans for mutants defective in dense-core vesicle function. We identified two conserved Rab2-binding proteins: RUND-1, a RUN domain protein, and CCCP-1, a coiled-coil protein. RUND-1 and CCCP-1 colocalize with RAB-2 at the Golgi, and rab-2, rund-1 and cccp-1 mutants have similar defects in sorting soluble and transmembrane dense-core vesicle cargos. RUND-1 also interacts with the Rab2 GAP protein TBC-8 and the BAR domain protein RIC-19, a RAB-2 effector. In summary, a new pathway of conserved proteins controls the maturation of dense-core vesicles at the trans-Golgi network. PMID:24698274

Core homogenization method for pebble bed reactors

International Nuclear Information System (INIS)

Kulik, V.; Sanchez, R.

2005-01-01

This work presents a core homogenization scheme for treating a stochastic pebble bed loading in pebble bed reactors. The reactor core is decomposed into macro-domains that contain several pebble types characterized by different degrees of burnup. A stochastic description is introduced to account for pebble-to-pebble and pebble-to-helium interactions within a macro-domain as well as for interactions between macro-domains. Performance of the proposed method is tested for the PROTEUS and ASTRA critical reactor facilities. Numerical simulations accomplished with the APOLLO2 transport lattice code show good agreement with the experimental data for the PROTEUS reactor facility and with the TRIPOLI4 Monte Carlo simulations for the ASTRA reactor configuration. The difference between the proposed method and the traditional volume-averaged homogenization technique is negligible while only one type of fuel pebbles present in the system, but it grows rapidly with the level of pebble heterogeneity. (authors)

Complex Kohn variational principle for two-nucleon bound-state and scattering with the tensor potential

International Nuclear Information System (INIS)

Araujo Junior, C.F. de; Adhikari, S.K.; Tomio, L.

1993-10-01

Complex Kohn variational principle is applied to the numerical solution of the fully off-shell Lippmann-Schwinger equation for nucleon-nucleon scattering for various partial waves including the coupled 3 S 1 - 3 D 1 channel. Analytic expressions are obtained for all the integrals in the method for a suitable choice of expansion functions. Calculations with the partial waves 1 S 0 , 1 P 1 , 1 D 2 , and 3 S 1 - 3 D 1 of the Reid soft core potential show that the method converges faster than other solution schemes not only for the phase shift but also for the off-shell t matrix elements. It is also shown that its is trivial to modify this variational principle in order to make it suitable for bound-stage calculations. The bound-state approach is illustrated for the 3 S 1 - 3 D 1 channel of the Reid soft-core potential for calculating the deuteron binding, wave function and the D state asymptotic parameters. (author)

Structures of SRP54 and SRP19, the two proteins that organize the ribonucleic core of the signal recognition particle from Pyrococcus furiosus.

Directory of Open Access Journals (Sweden)

Pascal F Egea

Full Text Available In all organisms the Signal Recognition Particle (SRP, binds to signal sequences of proteins destined for secretion or membrane insertion as they emerge from translating ribosomes. In Archaea and Eucarya, the conserved ribonucleoproteic core is composed of two proteins, the accessory protein SRP19, the essential GTPase SRP54, and an evolutionarily conserved and essential SRP RNA. Through the GTP-dependent interaction between the SRP and its cognate receptor SR, ribosomes harboring nascent polypeptidic chains destined for secretion are dynamically transferred to the protein translocation apparatus at the membrane. We present here high-resolution X-ray structures of SRP54 and SRP19, the two RNA binding components forming the core of the signal recognition particle from the hyper-thermophilic archaeon Pyrococcus furiosus (Pfu. The 2.5 A resolution structure of free Pfu-SRP54 is the first showing the complete domain organization of a GDP bound full-length SRP54 subunit. In its ras-like GTPase domain, GDP is found tightly associated with the protein. The flexible linker that separates the GTPase core from the hydrophobic signal sequence binding M domain, adopts a purely alpha-helical structure and acts as an articulated arm allowing the M domain to explore multiple regions as it scans for signal peptides as they emerge from the ribosomal tunnel. This linker is structurally coupled to the GTPase catalytic site and likely to propagate conformational changes occurring in the M domain through the SRP RNA upon signal sequence binding. Two different 1.8 A resolution crystal structures of free Pfu-SRP19 reveal a compact, rigid and well-folded protein even in absence of its obligate SRP RNA partner. Comparison with other SRP19*SRP RNA structures suggests the rearrangement of a disordered loop upon binding with the RNA through a reciprocal induced-fit mechanism and supports the idea that SRP19 acts as a molecular scaffold and a chaperone, assisting the SRP

Structural and Histone Binding Ability Characterizations of Human PWWP Domains

Energy Technology Data Exchange (ETDEWEB)

Wu, Hong; Zeng, Hong; Lam, Robert; Tempel, Wolfram; Amaya, Maria F.; Xu, Chao; Dombrovski, Ludmila; Qiu, Wei; Wang, Yanming; Min, Jinrong (Toronto); (Penn)

2013-09-25

The PWWP domain was first identified as a structural motif of 100-130 amino acids in the WHSC1 protein and predicted to be a protein-protein interaction domain. It belongs to the Tudor domain 'Royal Family', which consists of Tudor, chromodomain, MBT and PWWP domains. While Tudor, chromodomain and MBT domains have long been known to bind methylated histones, PWWP was shown to exhibit histone binding ability only until recently. The PWWP domain has been shown to be a DNA binding domain, but sequence analysis and previous structural studies show that the PWWP domain exhibits significant similarity to other 'Royal Family' members, implying that the PWWP domain has the potential to bind histones. In order to further explore the function of the PWWP domain, we used the protein family approach to determine the crystal structures of the PWWP domains from seven different human proteins. Our fluorescence polarization binding studies show that PWWP domains have weak histone binding ability, which is also confirmed by our NMR titration experiments. Furthermore, we determined the crystal structures of the BRPF1 PWWP domain in complex with H3K36me3, and HDGF2 PWWP domain in complex with H3K79me3 and H4K20me3. PWWP proteins constitute a new family of methyl lysine histone binders. The PWWP domain consists of three motifs: a canonical {beta}-barrel core, an insertion motif between the second and third {beta}-strands and a C-terminal {alpha}-helix bundle. Both the canonical {beta}-barrel core and the insertion motif are directly involved in histone binding. The PWWP domain has been previously shown to be a DNA binding domain. Therefore, the PWWP domain exhibits dual functions: binding both DNA and methyllysine histones.

Influenza Polymerase Can Adopt an Alternative Configuration Involving a Radical Repacking of PB2 Domains.

Science.gov (United States)

Thierry, Eric; Guilligay, Delphine; Kosinski, Jan; Bock, Thomas; Gaudon, Stephanie; Round, Adam; Pflug, Alexander; Hengrung, Narin; El Omari, Kamel; Baudin, Florence; Hart, Darren J; Beck, Martin; Cusack, Stephen

2016-01-07

Influenza virus polymerase transcribes or replicates the segmented RNA genome (vRNA) into respectively viral mRNA or full-length copies and initiates RNA synthesis by binding the conserved 3' and 5' vRNA ends (the promoter). In recent structures of promoter-bound polymerase, the cap-binding and endonuclease domains are configured for cap snatching, which generates capped transcription primers. Here, we present a FluB polymerase structure with a bound complementary cRNA 5' end that exhibits a major rearrangement of the subdomains within the C-terminal two-thirds of PB2 (PB2-C). Notably, the PB2 nuclear localization signal (NLS)-containing domain translocates ∼90 Å to bind to the endonuclease domain. FluA PB2-C alone and RNA-free FluC polymerase are similarly arranged. Biophysical and cap-dependent endonuclease assays show that in solution the polymerase explores different conformational distributions depending on which RNA is bound. The inherent flexibility of the polymerase allows it to adopt alternative conformations that are likely important during polymerase maturation into active progeny RNPs. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Upper bounds on superpartner masses from upper bounds on the Higgs boson mass.

Science.gov (United States)

Cabrera, M E; Casas, J A; Delgado, A

2012-01-13

The LHC is putting bounds on the Higgs boson mass. In this Letter we use those bounds to constrain the minimal supersymmetric standard model (MSSM) parameter space using the fact that, in supersymmetry, the Higgs mass is a function of the masses of sparticles, and therefore an upper bound on the Higgs mass translates into an upper bound for the masses for superpartners. We show that, although current bounds do not constrain the MSSM parameter space from above, once the Higgs mass bound improves big regions of this parameter space will be excluded, putting upper bounds on supersymmetry (SUSY) masses. On the other hand, for the case of split-SUSY we show that, for moderate or large tanβ, the present bounds on the Higgs mass imply that the common mass for scalars cannot be greater than 10(11)  GeV. We show how these bounds will evolve as LHC continues to improve the limits on the Higgs mass.

Synthesis of triangular Au core-Ag shell nanoparticles

International Nuclear Information System (INIS)

Rai, Akhilesh; Chaudhary, Minakshi; Ahmad, Absar; Bhargava, Suresh; Sastry, Murali

2007-01-01

In this paper, we demonstrate a simple and reproducible method for the synthesis of triangular Au core-Ag shell nanoparticles. The triangular gold core is obtained by the reduction of gold ions by lemongrass extract. Utilizing the negative charge on the gold nanotriangles, silver ions are bound to their surface and thereafter reduced by ascorbic acid under alkaline conditions. The thickness of the silver shell may be modulated by varying the pH of the reaction medium. The formation of the Au core-Ag shell triangular nanostructures has been followed by UV-vis-NIR Spectroscopy, X-ray photoelectron spectroscopy, transmission electron microscopy (TEM) and atomic force microscopy (AFM) measurements. The sharp vertices of the triangles coupled with the core-shell structure is expected to have potential for application in surface enhanced Raman spectroscopy and in the sensitive detection of biomolecules

An intermolecular binding mechanism involving multiple LysM domains mediates carbohydrate recognition by an endopeptidase

DEFF Research Database (Denmark)

Wong, Mei Mei Jaslyn Elizabeth; Midtgaard, Søren Roi; Gysel, Kira

2015-01-01

of multiple LysM domains in substrate binding has so far lacked support from high-resolution structures of ligand-bound complexes. Here, a structural study of the Thermus thermophilus NlpC/P60 endopeptidase containing two LysM domains is presented. The crystal structure and small-angle X-ray scattering...

Weakly and strongly coupled Belousov-Zhabotinsky patterns

Science.gov (United States)

Weiss, Stephan; Deegan, Robert D.

2017-02-01

We investigate experimentally and numerically the synchronization of two-dimensional spiral wave patterns in the Belousov-Zhabotinsky reaction due to point-to-point coupling of two separate domains. Different synchronization modalities appear depending on the coupling strength and the initial patterns in each domain. The behavior as a function of the coupling strength falls into two qualitatively different regimes. The weakly coupled regime is characterized by inter-domain interactions that distorted but do not break wave fronts. Under weak coupling, spiral cores are pushed around by wave fronts in the other domain, resulting in an effective interaction between cores in opposite domains. In the case where each domain initially contains a single spiral, the cores form a bound pair and orbit each other at quantized distances. When the starting patterns consist of multiple randomly positioned spiral cores, the number of cores decreases with time until all that remains are a few cores that are synchronized with a partner in the other domain. The strongly coupled regime is characterized by interdomain interactions that break wave fronts. As a result, the wave patterns in both domains become identical.

Core Competencies for Injury and Violence Prevention

Science.gov (United States)

Stephens-Stidham, Shelli; Peek-Asa, Corinne; Bou-Saada, Ingrid; Hunter, Wanda; Lindemer, Kristen; Runyan, Carol

2009-01-01

Efforts to reduce the burden of injury and violence require a workforce that is knowledgeable and skilled in prevention. However, there has been no systematic process to ensure that professionals possess the necessary competencies. To address this deficiency, we developed a set of core competencies for public health practitioners in injury and violence prevention programs. The core competencies address domains including public health significance, data, the design and implementation of prevention activities, evaluation, program management, communication, stimulating change, and continuing education. Specific learning objectives establish goals for training in each domain. The competencies assist in efforts to reduce the burden of injury and violence and can provide benchmarks against which to assess progress in professional capacity for injury and violence prevention. PMID:19197083

Contribution to the development of methods for nuclear reactor core calculations with APOLLO3 code: domain decomposition in transport theory with nonlinear diffusion acceleration for 2D and 3D geometries

International Nuclear Information System (INIS)

Lenain, Roland

2015-01-01

This thesis is devoted to the implementation of a domain decomposition method applied to the neutron transport equation. The objective of this work is to access high-fidelity deterministic solutions to properly handle heterogeneities located in nuclear reactor cores, for problems' size ranging from color-sets of assemblies to large reactor cores configurations in 2D and 3D. The innovative algorithm developed during the thesis intends to optimize the use of parallelism and memory. The approach also aims to minimize the influence of the parallel implementation on the performances. These goals match the needs of APOLLO3 project, developed at CEA and supported by EDF and AREVA, which must be a portable code (no optimization on a specific architecture) in order to achieve best estimate modeling with resources ranging from personal computer to compute cluster available for engineers analyses. The proposed algorithm is a Parallel Multigroup-Block Jacobi one. Each sub-domain is considered as a multi-group fixed-source problem with volume-sources (fission) and surface-sources (interface flux between the sub-domains). The multi-group problem is solved in each sub-domain and a single communication of the interface flux is required at each power iteration. The spectral radius of the resolution algorithm is made similar to the one of a classical resolution algorithm with a nonlinear diffusion acceleration method: the well-known Coarse Mesh Finite Difference. In this way an ideal scalability is achievable when the calculation is parallelized. The memory organization, taking advantage of shared memory parallelism, optimizes the resources by avoiding redundant copies of the data shared between the sub-domains. Distributed memory architectures are made available by a hybrid parallel method that combines both paradigms of shared memory parallelism and distributed memory parallelism. For large problems, these architectures provide a greater number of processors and the amount of

The DMM Bound

DEFF Research Database (Denmark)

Emiris, Ioannis Z.; Mourrain, Bernard; Tsigaridas, Elias

2010-01-01

) resultant by means of mixed volume, as well as recent advances on aggregate root bounds for univariate polynomials, and are applicable to arbitrary positive dimensional systems. We improve upon Canny's gap theorem [7] by a factor of O(dn-1), where d bounds the degree of the polynomials, and n is the number...... bound on the number of steps that subdivision-based algorithms perform in order to isolate all real roots of a polynomial system. This leads to the first complexity bound of Milne's algorithm [22] in 2D....

The structure of Serratia marcescens Lip, a membrane-bound component of the type VI secretion system

International Nuclear Information System (INIS)

Rao, Vincenzo A.; Shepherd, Sharon M.; English, Grant; Coulthurst, Sarah J.; Hunter, William N.

2011-01-01

The high-resolution crystal structure of S. marcescens Lip reveals a new member of the transthyretin family of proteins. Lip, a core component of the type VI secretion apparatus, is localized to the outer membrane and is positioned to interact with other proteins forming this complex system. Lip is a membrane-bound lipoprotein and a core component of the type VI secretion system found in Gram-negative bacteria. The structure of a Lip construct (residues 29–176) from Serratia marcescens (SmLip) has been determined at 1.92 Å resolution. Experimental phases were derived using a single-wavelength anomalous dispersion approach on a sample cocrystallized with iodide. The membrane localization of the native protein was confirmed. The structure is that of the globular domain lacking only the lipoprotein signal peptide and the lipidated N-terminus of the mature protein. The protein fold is dominated by an eight-stranded β-sandwich and identifies SmLip as a new member of the transthyretin family of proteins. Transthyretin and the only other member of the family fold, 5-hydroxyisourate hydrolase, form homotetramers important for their function. The asymmetric unit of SmLip is a tetramer with 222 symmetry, but the assembly is distinct from that previously noted for the transthyretin protein family. However, structural comparisons and bacterial two-hybrid data suggest that the SmLip tetramer is not relevant to its role as a core component of the type VI secretion system, but rather reflects a propensity for SmLip to participate in protein–protein interactions. A relatively low level of sequence conservation amongst Lip homologues is noted and is restricted to parts of the structure that might be involved in interactions with physiological partners

The structure of Serratia marcescens Lip, a membrane-bound component of the type VI secretion system

Energy Technology Data Exchange (ETDEWEB)

Rao, Vincenzo A.; Shepherd, Sharon M.; English, Grant; Coulthurst, Sarah J.; Hunter, William N., E-mail: w.n.hunter@dundee.ac.uk [College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland (United Kingdom)

2011-12-01

The high-resolution crystal structure of S. marcescens Lip reveals a new member of the transthyretin family of proteins. Lip, a core component of the type VI secretion apparatus, is localized to the outer membrane and is positioned to interact with other proteins forming this complex system. Lip is a membrane-bound lipoprotein and a core component of the type VI secretion system found in Gram-negative bacteria. The structure of a Lip construct (residues 29–176) from Serratia marcescens (SmLip) has been determined at 1.92 Å resolution. Experimental phases were derived using a single-wavelength anomalous dispersion approach on a sample cocrystallized with iodide. The membrane localization of the native protein was confirmed. The structure is that of the globular domain lacking only the lipoprotein signal peptide and the lipidated N-terminus of the mature protein. The protein fold is dominated by an eight-stranded β-sandwich and identifies SmLip as a new member of the transthyretin family of proteins. Transthyretin and the only other member of the family fold, 5-hydroxyisourate hydrolase, form homotetramers important for their function. The asymmetric unit of SmLip is a tetramer with 222 symmetry, but the assembly is distinct from that previously noted for the transthyretin protein family. However, structural comparisons and bacterial two-hybrid data suggest that the SmLip tetramer is not relevant to its role as a core component of the type VI secretion system, but rather reflects a propensity for SmLip to participate in protein–protein interactions. A relatively low level of sequence conservation amongst Lip homologues is noted and is restricted to parts of the structure that might be involved in interactions with physiological partners.

Structural and magnetic domains characterization of magnetite nanoparticles

International Nuclear Information System (INIS)

Santoyo-Salazar, J.; Castellanos-Roman, M.A.; Beatriz Gomez, L.

2007-01-01

Recently, important advances have been achieved in application, reproducibility and response ability of magnetic materials due to the relationships among processing, structure and nanometric size particle. Features like homogeneity of compounds and nanoparticle-sizing have improved some magnetic properties of materials and their field application. Of particular interest is the study of magnetic materials at the atomic and microstuctural level because the orientation and magnetic domains (large numbers of atoms moments coupled together in a preferential direction) can be observed. In this work, magnetite (Fe 3 O 4 ) powders which were obtained by precipitation route in alkaline medium are analyzed to identify the structure and mechanism formation of domains over the core and border of nanoparticles. Results obtained by XRD, atomic force microscopy (AFM) and magnetic force microscopy (MFM) showed a structural phase corresponding to Fe 3 O 4 and nanoparticles in a range of 20-40 nm. Samples scanned by MFM in nanometric resolution and profile images showed orientation of magnetic domains in the border and cores of the material. Finally, an analysis of repulsion and attraction in magnetic field and direction changes of domains formed by magnetite (Fe 3 O 4 ) powders were done

Development of a perturbation code, PERT-K, for hexagonal core geometry

Energy Technology Data Exchange (ETDEWEB)

Kim, Taek Kyum; Kim, Sang Ji; Song, Hoon; Kim, Young Il; Kim, Young Jin [Korea Atomic Energy Research Institute, Taejon (Korea)

1999-01-01

A perturbation code for hexagonal core geometry has been developed based on Nodal Expansion Method. By using relevant output files of DIF3D code, it can calculate the reactivity changes caused by perturbation in composition or/and neutron cross section libraries. The accuracy of PERT-K code has been validated by calculating the reactivity changes due to fuel composition change, the sodium void coefficients, and the sample reactivity worths of BFS-73-1 critical experiments. In the case of 10% reduction in all fuel isotopics at a assembly located in the outer core, PERT-K computation agrees with the direct computation by DIF3D within 60 pcm. The sample reactivity worths of BFS-73-1 critical experiments are predicted with PERT-K code within the experimental error bounds. For 100% sodium void occurrence at the inner core, the maximum difference of reactivity changes between PERT-K and direct DIF3D computations is less than 40 pcm. On the other hand, the same sodium void condition at the outer core leads to a difference of reactivity change greater than 400 pcm. However, as sodium voiding becomes near zero value, the difference becomes less and rapidly falls within the acceptable bound, i.e. 40 pcm. (author). 11 refs., 9 figs., 6 tabs.

Pathogen-Specific Binding Soluble Down Syndrome Cell Adhesion Molecule (Dscam Regulates Phagocytosis via Membrane-Bound Dscam in Crab

Directory of Open Access Journals (Sweden)

Xue-Jie Li

2018-04-01

Full Text Available The Down syndrome cell adhesion molecule (Dscam gene is an extraordinary example of diversity that can produce thousands of isoforms and has so far been found only in insects and crustaceans. Cumulative evidence indicates that Dscam may contribute to the mechanistic foundations of specific immune responses in insects. However, the mechanism and functions of Dscam in relation to pathogens and immunity remain largely unknown. In this study, we identified the genome organization and alternative Dscam exons from Chinese mitten crab, Eriocheir sinensis. These variants, designated EsDscam, potentially produce 30,600 isoforms due to three alternatively spliced immunoglobulin (Ig domains and a transmembrane domain. EsDscam was significantly upregulated after bacterial challenge at both mRNA and protein levels. Moreover, bacterial specific EsDscam isoforms were found to bind specifically with the original bacteria to facilitate efficient clearance. Furthermore, bacteria-specific binding of soluble EsDscam via the complete Ig1–Ig4 domain significantly enhanced elimination of the original bacteria via phagocytosis by hemocytes; this function was abolished by partial Ig1–Ig4 domain truncation. Further studies showed that knockdown of membrane-bound EsDscam inhibited the ability of EsDscam with the same extracellular region to promote bacterial phagocytosis. Immunocytochemistry indicated colocalization of the soluble and membrane-bound forms of EsDscam at the hemocyte surface. Far-Western and coimmunoprecipitation assays demonstrated homotypic interactions between EsDscam isoforms. This study provides insights into a mechanism by which soluble Dscam regulates hemocyte phagocytosis via bacteria-specific binding and specific interactions with membrane-bound Dscam as a phagocytic receptor.

The DnaA N-terminal domain interacts with Hda to facilitate replicase clamp-mediated inactivation of DnaA.

Science.gov (United States)

Su'etsugu, Masayuki; Harada, Yuji; Keyamura, Kenji; Matsunaga, Chika; Kasho, Kazutoshi; Abe, Yoshito; Ueda, Tadashi; Katayama, Tsutomu

2013-12-01

DnaA activity for replication initiation of the Escherichia coli chromosome is negatively regulated by feedback from the DNA-loaded form of the replicase clamp. In this process, called RIDA (regulatory inactivation of DnaA), ATP-bound DnaA transiently assembles into a complex consisting of Hda and the DNA-clamp, which promotes inter-AAA+ domain association between Hda and DnaA and stimulates hydrolysis of DnaA-bound ATP, producing inactive ADP-DnaA. Using a truncated DnaA mutant, we previously demonstrated that the DnaA N-terminal domain is involved in RIDA. However, the precise role of the N-terminal domain in RIDA has remained largely unclear. Here, we used an in vitro reconstituted system to demonstrate that the Asn-44 residue in the N-terminal domain of DnaA is crucial for RIDA but not for replication initiation. Moreover, an assay termed PDAX (pull-down after cross-linking) revealed an unstable interaction between a DnaA-N44A mutant and Hda. In vivo, this mutant exhibited an increase in the cellular level of ATP-bound DnaA. These results establish a model in which interaction between DnaA Asn-44 and Hda stabilizes the association between the AAA+ domains of DnaA and Hda to facilitate DnaA-ATP hydrolysis during RIDA. © 2013 Society for Applied Microbiology and John Wiley & Sons Ltd.

The C Terminus of the Core β-Ladder Domain in Japanese Encephalitis Virus Nonstructural Protein 1 Is Flexible for Accommodation of Heterologous Epitope Fusion.

Science.gov (United States)

Yen, Li-Chen; Liao, Jia-Teh; Lee, Hwei-Jen; Chou, Wei-Yuan; Chen, Chun-Wei; Lin, Yi-Ling; Liao, Ching-Len

2016-02-01

NS1 is the only nonstructural protein that enters the lumen of the endoplasmic reticulum (ER), where NS1 is glycosylated, forms a dimer, and is subsequently secreted during flavivirus replication as dimers or hexamers, which appear to be highly immunogenic to the infected host, as protective immunity can be elicited against homologous flavivirus infections. Here, by using a trans-complementation assay, we identified the C-terminal end of NS1 derived from Japanese encephalitis virus (JEV), which was more flexible than other regions in terms of housing foreign epitopes without a significant impact on virus replication. This mapped flexible region is located in the conserved tip of the core β-ladder domain of the multimeric NS1 structure and is also known to contain certain linear epitopes, readily triggering specific antibody responses from the host. Despite becoming attenuated, recombinant JEV with insertion of a neutralizing epitope derived from enterovirus 71 (EV71) into the C-terminal end of NS1 not only could be normally released from infected cells, but also induced dual protective immunity for the host to counteract lethal challenge with either JEV or EV71 in neonatal mice. These results indicated that the secreted multimeric NS1 of flaviviruses may serve as a natural protein carrier to render epitopes of interest more immunogenic in the C terminus of the core β-ladder domain. The positive-sense RNA genomes of mosquito-borne flaviviruses appear to be flexible in terms of accommodating extra insertions of short heterologous antigens into their virus genes. Here, we illustrate that the newly identified C terminus of the core β-ladder domain in NS1 could be readily inserted into entities such as EV71 epitopes, and the resulting NS1-epitope fusion proteins appeared to maintain normal virus replication, secretion ability, and multimeric formation from infected cells. Nonetheless, such an insertion attenuated the recombinant JEV in mice, despite having retained

An intermolecular binding mechanism involving multiple LysM domains mediates carbohydrate recognition by an endopeptidase

Energy Technology Data Exchange (ETDEWEB)

Wong, Jaslyn E. M. M. [Aarhus University, Gustav Wieds Vej 10C, 8000 Aarhus (Denmark); Midtgaard, Søren Roi [University of Copenhagen, Universitetsparken 5, 2100 Copenhagen (Denmark); Gysel, Kira [Aarhus University, Gustav Wieds Vej 10C, 8000 Aarhus (Denmark); Thygesen, Mikkel B.; Sørensen, Kasper K.; Jensen, Knud J. [University of Copenhagen, Thorvaldsensvej 40, 1871 Frederiksberg C (Denmark); Stougaard, Jens; Thirup, Søren; Blaise, Mickaël, E-mail: mickael.blaise@cpbs.cnrs.fr [Aarhus University, Gustav Wieds Vej 10C, 8000 Aarhus (Denmark)

2015-03-01

The crystal and solution structures of the T. thermophilus NlpC/P60 d, l-endopeptidase as well as the co-crystal structure of its N-terminal LysM domains bound to chitohexaose allow a proposal to be made regarding how the enzyme recognizes peptidoglycan. LysM domains, which are frequently present as repetitive entities in both bacterial and plant proteins, are known to interact with carbohydrates containing N-acetylglucosamine (GlcNAc) moieties, such as chitin and peptidoglycan. In bacteria, the functional significance of the involvement of multiple LysM domains in substrate binding has so far lacked support from high-resolution structures of ligand-bound complexes. Here, a structural study of the Thermus thermophilus NlpC/P60 endopeptidase containing two LysM domains is presented. The crystal structure and small-angle X-ray scattering solution studies of this endopeptidase revealed the presence of a homodimer. The structure of the two LysM domains co-crystallized with N-acetyl-chitohexaose revealed a new intermolecular binding mode that may explain the differential interaction between LysM domains and short or long chitin oligomers. By combining the structural information with the three-dimensional model of peptidoglycan, a model suggesting how protein dimerization enhances the recognition of peptidoglycan is proposed.

Efficient multiscale magnetic-domain analysis of iron-core material under mechanical stress

Science.gov (United States)

Nishikubo, Atsushi; Ito, Shumpei; Mifune, Takeshi; Matsuo, Tetsuji; Kaido, Chikara; Takahashi, Yasuhito; Fujiwara, Koji

2018-05-01

For an efficient analysis of magnetization, a partial-implicit solution method is improved using an assembled domain structure model with six-domain mesoscopic particles exhibiting pinning-type hysteresis. The quantitative analysis of non-oriented silicon steel succeeds in predicting the stress dependence of hysteresis loss with computation times greatly reduced by using the improved partial-implicit method. The effect of cell division along the thickness direction is also evaluated.

What can Andreev bound states tell us about superconductors?

Science.gov (United States)

Millo, Oded; Koren, Gad

2018-08-06

Zero-energy Andreev bound states, which manifest themselves in the tunnelling spectra as zero-bias conductance peaks (ZBCPs), are abundant at interfaces between superconductors and other materials and on the nodal surface of high-temperature superconductors. In this review, we focus on the information such excitations can provide on the properties of superconductor systems. First, a general introduction to the physics of Andreev bound states in superconductor/normal metal interfaces is given with a particular emphasis on why they appear at zero energy in d -wave superconductors. Then, specific spectroscopic tunnelling studies of thin films, bilayers and junctions are described, focusing on the corresponding ZBCP features. Scanning tunnelling spectroscopy (STS) studies show that the ZBCPs on the c -axis YBa 2 Cu 3 O 7- δ (YBCO) films are correlated with the surface morphology and appear only in proximity to (110) facets. STS on c -axis La 1.88 Sr 0.12 CuO 4 (LSCO) films exhibiting the 1/8 anomaly shows spatially modulated peaks near zero bias associated with the anti-phase ordering of the d -wave order parameter predicted at this doping level. ZBCPs were also found in micrometre-size edge junctions of YBCO/SrRuO 3 /YBCO, where SrRuO 3 is ferromagnetic. Here, the results are consistent with a crossed Andreev reflection effect (CARE) at the narrow domain walls of the SrRuO 3 ZBCPs measured in STS studies of manganite/cuprate bilayers could not be attributed to CARE because the manganite's domain wall is much larger than the coherence length in YBCO, and instead are attributed to proximity-induced triplet-pairing superconductivity with non-conventional symmetry. And finally, ZBCPs found in junctions of non-intentionally doped topological insulator films of Bi 2 Se 3 and the s -wave superconductor NbN are attributed to proximity-induced p x  + ip y triplet order parameter in the topological material.This article is part of the theme issue 'Andreev bound states'. �

Risperidone for the core symptom domains of autism: results from the study by the autism network of the research units on pediatric psychopharmacology.

Science.gov (United States)

McDougle, Christopher J; Scahill, Lawrence; Aman, Michael G; McCracken, James T; Tierney, Elaine; Davies, Mark; Arnold, L Eugene; Posey, David J; Martin, Andrès; Ghuman, Jaswinder K; Shah, Bhavik; Chuang, Shirley Z; Swiezy, Naomi B; Gonzalez, Nilda M; Hollway, Jill; Koenig, Kathleen; McGough, James J; Ritz, Louise; Vitiello, Benedetto

2005-06-01

Risperidone has been found efficacious for decreasing severe tantrums, aggression, and self-injurious behavior in children and adolescents with autistic disorder (autism). The authors report on whether risperidone improves the core symptoms of autism, social and communication impairment and repetitive and stereotyped behavior. The database from an 8-week double-blind, placebo-controlled trial (N=101) and 16-week open-label continuation study (N=63) of risperidone for children and adolescents with autism was used to test for drug effects on secondary outcome measures: scores on the Ritvo-Freeman Real Life Rating Scale, the Children's Yale-Brown Obsessive Compulsive Scale, and the maladaptive behavior domain of the Vineland Adaptive Behavior Scales. Compared to placebo, risperidone led to a significantly greater reduction in the overall score on the Ritvo-Freeman Real Life Rating Scale, as well as the scores on the subscales for sensory motor behaviors (subscale I), affectual reactions (subscale III), and sensory responses (subscale IV). No statistically significant difference was observed, however, on the subscale for social relatedness (subscale II) or language (subscale V). Risperidone also resulted in significantly greater reductions in scores on the Children's Yale-Brown Obsessive Compulsive Scale and Vineland maladaptive behavior domain. This pattern of treatment response was maintained for 6 months. Risperidone led to significant improvements in the restricted, repetitive, and stereotyped patterns of behavior, interests, and activities of autistic children but did not significantly change their deficit in social interaction and communication. Further research is necessary to develop effective treatments for the core social and communicative impairments of autism.

The EFR project: core and fuel

International Nuclear Information System (INIS)

Francillon, E.; Barnes, D.W.; Pay, A.; Wehmann, U.

1991-01-01

The draft studies on EFR has beginning, in March 1988. The first part of the summary draft has consisted in the core and fuel domains to harmonize the different approaches used in national projects (SPX2-SNR2-CDFR). Rapidly, the core First Consistent Design has been defined with references to the anterior conceptions. Since this definition, studies have been engaged on the management (mean burnup amelioration) and on the conception (breeding gain, sodium void coefficient reduction). After a presentation of the basis options and on the general conception of the fuel assemblies we make a point on the core and the interfaces with the fuel cycle [fr

Organically bound tritium

International Nuclear Information System (INIS)

Diabate, S.; Strack, S.

1993-01-01

Tritium released into the environment may be incorporated into organic matter. Organically bound tritium in that case will show retention times in organisms that are considerably longer than those of tritiated water which has significant consequences on dose estimates. This article reviews the most important processes of organically bound tritium production and transport through food networks. Metabolic reactions in plant and animal organisms with tritiated water as a reaction partner are of great importance in this respect. The most important production process, in quantitative terms, is photosynthesis in green plants. The translocation of organically bound tritium from the leaves to edible parts of crop plants should be considered in models of organically bound tritium behavior. Organically bound tritium enters the human body on several pathways, either from the primary producers (vegetable food) or at a higher tropic level (animal food). Animal experiments have shown that the dose due to ingestion of organically bound tritium can be up to twice as high as a comparable intake of tritiated water in gaseous or liquid form. In the environment, organically bound tritium in plants and animals is often found to have higher specific tritium concentrations than tissue water. This is not due to some tritium enrichment effects but to the fact that no equilibrium conditions are reached under natural conditions. 66 refs

Physical Uncertainty Bounds (PUB)

Energy Technology Data Exchange (ETDEWEB)

Vaughan, Diane Elizabeth [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Preston, Dean L. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

2015-03-19

This paper introduces and motivates the need for a new methodology for determining upper bounds on the uncertainties in simulations of engineered systems due to limited fidelity in the composite continuum-level physics models needed to simulate the systems. We show that traditional uncertainty quantification methods provide, at best, a lower bound on this uncertainty. We propose to obtain bounds on the simulation uncertainties by first determining bounds on the physical quantities or processes relevant to system performance. By bounding these physics processes, as opposed to carrying out statistical analyses of the parameter sets of specific physics models or simply switching out the available physics models, one can obtain upper bounds on the uncertainties in simulated quantities of interest.

Analysis of Few-Mode Multi-Core Fiber Splice Behavior Using an Optical Vector Network Analyzer

DEFF Research Database (Denmark)

Rommel, Simon; Mendinueta, Jose Manuel Delgado; Klaus, Werner

2017-01-01

The behavior of splices in a 3-mode 36-core fiber is analyzed using optical vector network analysis. Time-domain response analysis confirms splices may cause significant mode-mixing, while frequency-domain analysis shows splices may affect system level mode-dependent loss both positively and negativ......The behavior of splices in a 3-mode 36-core fiber is analyzed using optical vector network analysis. Time-domain response analysis confirms splices may cause significant mode-mixing, while frequency-domain analysis shows splices may affect system level mode-dependent loss both positively...

Gravitational field of spherical domain wall in higher dimension

Indian Academy of Sciences (India)

and examine whether bound orbits are possible or not. This study will be of relevance to the structure formation because it gives some idea about the behaviour of the particles. (created at the early universe) in the gravitational field of the domain walls. Our paper is organized as follows: The basic equations are constructed ...

Development of the Learning Health System Researcher Core Competencies.

Science.gov (United States)

Forrest, Christopher B; Chesley, Francis D; Tregear, Michelle L; Mistry, Kamila B

2017-08-04

To develop core competencies for learning health system (LHS) researchers to guide the development of training programs. Data were obtained from literature review, expert interviews, a modified Delphi process, and consensus development meetings. The competencies were developed from August to December 2016 using qualitative methods. The literature review formed the basis for the initial draft of a competency domain framework. Key informant semi-structured interviews, a modified Delphi survey, and three expert panel (n = 19 members) consensus development meetings produced the final set of competencies. The iterative development process yielded seven competency domains: (1) systems science; (2) research questions and standards of scientific evidence; (3) research methods; (4) informatics; (5) ethics of research and implementation in health systems; (6) improvement and implementation science; and (7) engagement, leadership, and research management. A total of 33 core competencies were prioritized across these seven domains. The real-world milieu of LHS research, the embeddedness of the researcher within the health system, and engagement of stakeholders are distinguishing characteristics of this emerging field. The LHS researcher core competencies can be used to guide the development of learning objectives, evaluation methods, and curricula for training programs. © Health Research and Educational Trust.

Echothymia: environmental dependency in the affective domain.

Science.gov (United States)

Marin, Robert S; Gorovoy, Ian R

2014-01-01

Echothymia is stimulus-bound affective behavior, an echophenomenon in the domain of affect. Like echolalia and echopraxia, it is a concomitant of the environmental dependency associated with dysfunction of the frontal-striatal systems that mediate so-called frontal lobe functions. The authors introduce the definition and phenomenology of echothymia, overview its differential diagnosis and clinical significance, and suggest ways in which understanding echothymia may contribute to clinical management.

Core-state manipulation of single Fe impurities in GaAs with a scanning tunneling microscope

NARCIS (Netherlands)

Bocquel, J.; Kortan, V.R.; Sahin, C.; Campion, R.P.; Gallagher, B.L.; Flatte, M.E.; Koenraad, P.M.

2013-01-01

We demonstrate that a scanning tunneling microscope tip can be used to manipulate the tightly bound core (d-electron) state of single Fe ions embedded in GaAs. Increasing tip-sample voltage removes one d electron from the core of a single Fe, changing the dopant from the (Fe2+)(-) ionized acceptor

A lipid binding domain in sphingosine kinase 2

International Nuclear Information System (INIS)

Don, Anthony S.; Rosen, Hugh

2009-01-01

The lipid second messenger sphingosine 1-phosphate (S1P) is a critical mediator of cellular proliferation and survival signals, and is essential for vasculogenesis and neurogenesis. S1P formation is catalysed by sphingosine kinases 1 and 2 (Sphk1 and Sphk2). We have found that the endogenous glycolipid sulfatide (3-O-sulfogalactosylceramide) binds to and inhibits the activity of Sphk2 and the closely related ceramide kinase (Cerk), but not Sphk1. Using sulfatide as a probe, we mapped the lipid binding domain to the N-terminus of Sphk2 (residues 1-175), a region of sequence that is absent in Sphk1, but aligns with a pleckstrin homology domain in Cerk. Accordingly, Sphk2 bound to phosphatidylinositol monophosphates but not to abundant cellular phospholipids. Deleting the N-terminal domain reduced Sphk2 membrane localisation in cells. We have therefore identified a lipid binding domain in Sphk2 that is important for the enzyme's sub-cellular localisation.

Crystal structures of carbamate kinase from Giardia lamblia bound with citric acid and AMP-PNP.

Directory of Open Access Journals (Sweden)

Kap Lim

Full Text Available The parasite Giardia lamblia utilizes the L-arginine dihydrolase pathway to generate ATP from L-arginine. Carbamate kinase (CK catalyzes the last step in this pathway, converting ADP and carbamoyl phosphate to ATP and ammonium carbamate. Because the L-arginine pathway is essential for G. lamblia survival and absent in high eukaryotes including humans, the enzyme is a potential target for drug development. We have determined two crystal structures of G. lamblia CK (glCK with bound ligands. One structure, in complex with a nonhydrolyzable ATP analog, adenosine 5'-adenylyl-β,γ-imidodiphosphate (AMP-PNP, was determined at 2.6 Å resolution. The second structure, in complex with citric acid bound in the postulated carbamoyl phosphate binding site, was determined in two slightly different states at 2.1 and 2.4 Å resolution. These structures reveal conformational flexibility of an auxiliary domain (amino acid residues 123-170, which exhibits open or closed conformations or structural disorder, depending on the bound ligand. The structures also reveal a smaller conformational change in a region associated the AMP-PNP adenine binding site. The protein residues involved in binding, together with a model of the transition state, suggest that catalysis follows an in-line, predominantly dissociative, phosphotransfer reaction mechanism, and that closure of the flexible auxiliary domain is required to protect the transition state from bulk solvent.

The Green Bank Ammonia Survey: Dense Cores under Pressure in Orion A

Energy Technology Data Exchange (ETDEWEB)

Kirk, Helen; Di Francesco, James [NRC Herzberg Astronomy and Astrophysics, 5071 West Saanich Rd, Victoria, BC, V9E 2E7 (Canada); Friesen, Rachel K. [Dunlap Institute for Astronomy and Astrophysics, University of Toronto, 50 St. George St., Toronto, Ontario M5S 3H4 (Canada); Pineda, Jaime E.; Caselli, Paola; Alves, Felipe O.; Chacón-Tanarro, Ana; Punanova, Anna [Max-Planck-Institut für extraterrestrische Physik, Giessenbachstrasse 1, D-85748, Garching (Germany); Rosolowsky, Erik [Department of Physics, University of Alberta, Edmonton, AB (Canada); Offner, Stella S. R. [Department of Astronomy, University of Massachusetts, Amherst, MA 01003 (United States); Matzner, Christopher D.; Singh, Ayushi [Department of Astronomy and Astrophysics, University of Toronto, 50 St. George St., Toronto, Ontario, M5S 3H4 (Canada); Myers, Philip C.; Chen, How-Huan [Harvard-Smithsonian Center for Astrophysics, 60 Garden St., Cambridge, MA 02138 (United States); Chen, Michael Chun-Yuan; Keown, Jared [Department of Physics and Astronomy, University of Victoria, 3800 Finnerty Rd., Victoria, BC, V8P 5C2 (Canada); Seo, Young Min [Jet Propulsion Laboratory, NASA, 4800 Oak Grove Dr., Pasadena, CA 91109 (United States); Shirley, Yancy [Steward Observatory, 933 North Cherry Ave., Tucson, AZ 85721 (United States); Ginsburg, Adam [National Radio Astronomy Observatory, Socorro, NM 87801 (United States); Hall, Christine [Department of Physics, Engineering Physics and Astronomy, Queen’s University, Kingston, Ontario, K7L 3N6 (Canada); and others

2017-09-10

We use data on gas temperature and velocity dispersion from the Green Bank Ammonia Survey and core masses and sizes from the James Clerk Maxwell Telescope Gould Belt Survey to estimate the virial states of dense cores within the Orion A molecular cloud. Surprisingly, we find that almost none of the dense cores are sufficiently massive to be bound when considering only the balance between self-gravity and the thermal and non-thermal motions present in the dense gas. Including the additional pressure binding imposed by the weight of the ambient molecular cloud material and additional smaller pressure terms, however, suggests that most of the dense cores are pressure-confined.

The Green Bank Ammonia Survey: Dense Cores under Pressure in Orion A

International Nuclear Information System (INIS)

Kirk, Helen; Di Francesco, James; Friesen, Rachel K.; Pineda, Jaime E.; Caselli, Paola; Alves, Felipe O.; Chacón-Tanarro, Ana; Punanova, Anna; Rosolowsky, Erik; Offner, Stella S. R.; Matzner, Christopher D.; Singh, Ayushi; Myers, Philip C.; Chen, How-Huan; Chen, Michael Chun-Yuan; Keown, Jared; Seo, Young Min; Shirley, Yancy; Ginsburg, Adam; Hall, Christine

2017-01-01

We use data on gas temperature and velocity dispersion from the Green Bank Ammonia Survey and core masses and sizes from the James Clerk Maxwell Telescope Gould Belt Survey to estimate the virial states of dense cores within the Orion A molecular cloud. Surprisingly, we find that almost none of the dense cores are sufficiently massive to be bound when considering only the balance between self-gravity and the thermal and non-thermal motions present in the dense gas. Including the additional pressure binding imposed by the weight of the ambient molecular cloud material and additional smaller pressure terms, however, suggests that most of the dense cores are pressure-confined.

Conformational determinants of phosphotyrosine peptides complexed with the Src SH2 domain.

Directory of Open Access Journals (Sweden)

Joseph Nachman

2010-06-01

Full Text Available The inhibition of specific SH2 domain mediated protein-protein interactions as an effective chemotherapeutic approach in the treatment of diseases remains a challenge. That different conformations of peptide-ligands are preferred by different SH2 domains is an underappreciated observation from the structural analysis of phosphotyrosine peptide binding to SH2 domains that may aid in future drug design. To explore the nature of ligand binding, we use simulated annealing (SA to sample the conformational space of phosphotyrosine-containing peptides complexed with the Src SH2 domain. While in good agreement with the crystallographic and NMR studies of high-affinity phosphopeptide-SH2 domain complexes, the results suggest that the structural basis for phopsphopeptide- Src SH2 interactions is more complex than the "two-pronged plug two-hole socket" model. A systematic study of peptides of type pYEEX, where pY is phosphotyrosine and X is a hydrophobic residue, indicates that these peptides can assume two conformations, one extended and one helical, representing the balance between the interaction of residue X with the hydrophobic hole on the surface of the Src SH2 domain, and its contribution to the inherent tendency of the two glutamic acids to form an alpha-helix. In contrast, a beta-turn conformation, almost identical to that observed in the crystal structure of pYVNV bound to the Grb2 SH2 domain, predominates for pYXNX peptides, even in the presence of isoleucine at the third position. While peptide binding affinities, as measured by fluorescence polarization, correlate with the relative proportion of extended peptide conformation, these results suggest a model where all three residues C-terminal to the phosphotyrosine determine the conformation of the bound phosphopeptide. The information obtained in this work can be used in the design of specific SH2 domain inhibitors.

Backbone assignment of the little finger domain of a Y-family DNA polymerase.

Science.gov (United States)

Ma, Dejian; Fowler, Jason D; Suo, Zucai

2011-10-01

Sulfolobus solfataricus DNA polymerase IV (Dpo4), a prototype Y-family DNA polymerase, contains a unique little finger domain besides a catalytic core. Here, we report the chemical shift assignments for the backbone nitrogens, α and β carbons, and amide protons of the little finger domain of Dpo4. This work and our published backbone assignment for the catalytic core provide the basis for investigating the conformational dynamics of Dpo4 during catalysis using solution NMR spectroscopy.

Conformational Landscape of the p28-Bound Human Proteasome Regulatory Particle.

Science.gov (United States)

Lu, Ying; Wu, Jiayi; Dong, Yuanchen; Chen, Shuobing; Sun, Shuangwu; Ma, Yong-Bei; Ouyang, Qi; Finley, Daniel; Kirschner, Marc W; Mao, Youdong

2017-07-20

The proteasome holoenzyme is activated by its regulatory particle (RP) consisting of two subcomplexes, the lid and the base. A key event in base assembly is the formation of a heterohexameric ring of AAA-ATPases, which is guided by at least four RP assembly chaperones in mammals: PAAF1, p28/gankyrin, p27/PSMD9, and S5b. Using cryogenic electron microscopy, we analyzed the non-AAA structure of the p28-bound human RP at 4.5 Å resolution and determined seven distinct conformations of the Rpn1-p28-AAA subcomplex within the p28-bound RP at subnanometer resolutions. Remarkably, the p28-bound AAA ring does not form a channel in the free RP and spontaneously samples multiple "open" and "closed" topologies at the Rpt2-Rpt6 and Rpt3-Rpt4 interfaces. Our analysis suggests that p28 assists the proteolytic core particle to select a specific conformation of the ATPase ring for RP engagement and is released in a shoehorn-like fashion in the last step of the chaperone-mediated proteasome assembly. Copyright © 2017 Elsevier Inc. All rights reserved.

Ground-truthing the Foraminifera-bound Nitrogen Isotope Paleo-proxy in the Modern Sargasso Sea

Science.gov (United States)

Smart, S.; Ren, H. A.; Fawcett, S. E.; Conte, M. H.; Rafter, P. A.; Ellis, K. K.; Weigand, M. A.; Sigman, D. M.

2016-02-01

We present the nitrogen isotope ratios (δ15N) of planktonic foraminifera, a type of calcifying zooplankton, collected from surface ocean net tows, moored sediment traps and core-top sediments at the Bermuda Atlantic Time-series Study site in the Sargasso Sea between 2009 and 2013. Consistent with previous measurements from low-latitude core-top sediments, the annually averaged δ15N of organic matter bound within the shells of euphotic zone-dwelling foraminifera approximates that of thermocline nitrate, the dominant source of new nitrogen to Sargasso Sea surface waters. Based on net tow collections in the upper 200 m of the water column, we observe no systematic difference between the biomass δ15N and shell-bound δ15N of a given foraminifera species. For multiple species, the δ15N of net tow-collected upper ocean shells is lower than shells from sediment traps (by 0.5-2.1‰) and lower than shells from seafloor sediments (by 0.5-1.4‰). We are currently investigating whether these differences reflect actual processes affecting shell-bound δ15N or instead relate to the different time periods over which the three sample types integrate. The foraminiferal biomass δ15N time-series from the surface Sargasso Sea exhibits significant seasonal variations, with the lowest values in fall and the highest values in spring. The roles of hydrography, biogeochemistry, and ecosystem dynamics in driving these seasonal variations will be discussed. These data from the modern subtropical ocean form part of a greater effort to ground-truth the use of foram-bound δ15N to reconstruct past nutrient conditions, not only as a recorder of the isotopic composition of nitrogen supply in oligotrophic environments but also as a recorder of the degree of nitrate consumption in high-latitude regions such as the Southern Ocean.

Lectin Domains of Polypeptide GalNAc Transferases Exhibit Glycopeptide Binding Specificity

DEFF Research Database (Denmark)

Pedersen, Johannes W; Bennett, Eric P; Schjoldager, Katrine T-B G

2011-01-01

UDP-GalNAc:polypeptide a-N-acetylgalactosaminyltransferases (GalNAc-Ts) constitute a family of up to 20 transferases that initiate mucin-type O-glycosylation. The transferases are structurally composed of catalytic and lectin domains. Two modes have been identified for the selection...... of glycosylation sites by GalNAc-Ts: confined sequence recognition by the catalytic domain alone, and concerted recognition of acceptor sites and adjacent GalNAc-glycosylated sites by the catalytic and lectin domains, respectively. Thus far, only the catalytic domain has been shown to have peptide sequence...... on sequences of mucins MUC1, MUC2, MUC4, MUC5AC, MUC6, and MUC7 as well as a random glycopeptide bead library, we examined the binding properties of four different lectin domains. The lectin domains of GalNAc-T1, -T2, -T3, and -T4 bound different subsets of small glycopeptides. These results indicate...

3D Mapping of the SPRY2 domain of ryanodine receptor 1 by single-particle cryo-EM.

Directory of Open Access Journals (Sweden)

Alex Perálvarez-Marín

Full Text Available The type 1 skeletal muscle ryanodine receptor (RyR1 is principally responsible for Ca(2+ release from the sarcoplasmic reticulum and for the subsequent muscle contraction. The RyR1 contains three SPRY domains. SPRY domains are generally known to mediate protein-protein interactions, however the location of the three SPRY domains in the 3D structure of the RyR1 is not known. Combining immunolabeling and single-particle cryo-electron microscopy we have mapped the SPRY2 domain (S1085-V1208 in the 3D structure of RyR1 using three different antibodies against the SPRY2 domain. Two obstacles for the image processing procedure; limited amount of data and signal dilution introduced by the multiple orientations of the antibody bound in the tetrameric RyR1, were overcome by modifying the 3D reconstruction scheme. This approach enabled us to ascertain that the three antibodies bind to the same region, to obtain a 3D reconstruction of RyR1 with the antibody bound, and to map SPRY2 to the periphery of the cytoplasmic domain of RyR1. We report here the first 3D localization of a SPRY2 domain in any known RyR isoform.

Exploring the research domain of consultant practice: Perceptions and opinions of consultant radiographers

International Nuclear Information System (INIS)

Harris, R.; Paterson, A.

2016-01-01

Aim: This paper reports on one part of a larger study. The aim was to explore what the core domain of research means to consultant radiographers in clinical practice and to identify the key factors that facilitate or hinder research activity by this staff group. Design and method: Grounded theory research methodology was employed. This first part of the study involved electronic questionnaires being sent to all those known in consultant radiographer posts in the United Kingdom. Results: Results indicate there are variations across clinical specialties as to the amount and level of research undertaken by consultant radiographers, and not all agreed that research should be a core domain of consultant practice. Main facilitators to research were noted as: time; skills and knowledge of the researcher; a well defined research question. Main barriers to research were noted as: lack of allocated time; lack of skills/experience; clinical workload. Conclusion: Research is one of the four core domains of consultant allied health professional and nursing roles but, as yet, it is not fully embedded into those of all consultant radiographers. Many consultant radiographers appear to spend more of their time on the ‘clinical expert’ element of their role at the expense of the research domain. This study concludes that there is an urgent need for consultant radiographers to understand that research is one of the four core domains and to recognise the need to embed research into their clinical practice. - Highlights: • Consultant radiographers undertake research but have concerns about their research skills. • Research aims to improve practice and patients' experiences. • Relatively few consultant radiographers publish their work routinely. • Consultant radiographers allocate little protected time for research due to clinical demands. • Almost half of the consultant radiographers feel research should not be a core part of their roles.

Screening of ionic cores in partially ionized plasmas within linear response

International Nuclear Information System (INIS)

Gericke, D. O.; Vorberger, J.; Wuensch, K.; Gregori, G.

2010-01-01

We employ a pseudopotential approach to investigate the screening of ionic cores in partially ionized plasmas. Here, the effect of the tightly bound electrons is condensed into an effective potential between the (free) valence electrons and the ionic cores. Even for weak electron-ion coupling, the corresponding screening clouds show strong modifications from the Debye result for elements heavier than helium. Modifications of the theoretically predicted x-ray scattering signal and implications on measurements are discussed.

Role of the σ⁵⁴ Activator Interacting Domain in Bacterial Transcription Initiation

Energy Technology Data Exchange (ETDEWEB)

Siegel, Alexander R. [Univ. of California, Berkeley, CA (United States); Wemmer, David E. [Univ. of California, Berkeley, CA (United States)

2016-10-11

Bacterial sigma factors are subunits of RNA polymerase that direct the holoenzyme to specific sets of promoters in the genome and are a central element of regulating transcription. Most polymerase holoenzymes open the promoter and initiate transcription rapidly after binding. However, polymerase containing the members of the σ⁵⁴ family must be acted on by a transcriptional activator before DNA opening and initiation occur. A key domain in these transcriptional activators forms a hexameric AAA + ATPase that acts through conformational changes brought on by ATP hydrolysis. Contacts between the transcriptional activator and σ⁵⁴ are primarily made through an N-terminal σ⁵⁴ activator interacting domain (AID). To better understand this mechanism of bacterial transcription initiation, we characterized the σ⁵⁴ AID by NMR spectroscopy and other biophysical methods and show that it is an intrinsically disordered domain in σ⁵⁴ alone. In this paper, we identified a minimal construct of the Aquifex aeolicus σ⁵⁴ AID that consists of two predicted helices and retains native-like binding affinity for the transcriptional activator NtrC1. Using the NtrC1 ATPase domain, bound with the non-hydrolyzable ATP analog ADP-beryllium fluoride, we studied the NtrC1–σ⁵⁴ AID complex using NMR spectroscopy. We show that the σ⁵⁴ AID becomes structured after associating with the core loops of the transcriptional activators in their ATP state and that the primary site of the interaction is the first predicted helix. Finally, understanding this complex, formed as the first step toward initiation, will help unravel the mechanism of σ⁵⁴ bacterial transcription initiation.

Strong solutions for the Navier-Stokes equations on bounded and unbounded domains with a moving boundary

Directory of Open Access Journals (Sweden)

Juergen Saal

2007-02-01

Full Text Available It is proved under mild regularity assumptions on the data that the Navier-Stokes equations in bounded and unbounded noncylindrical regions admit a unique local-in-time strong solution. The result is based on maximal regularity estimates for the in spatial regions with a moving boundary obtained in [16] and the contraction mapping principle.

Core Health Outcomes In Childhood Epilepsy (CHOICE): protocol for the selection of a core outcome set.

Science.gov (United States)

Morris, Christopher; Dunkley, Colin; Gibbon, Frances M; Currier, Janet; Roberts, Deborah; Rogers, Morwenna; Crudgington, Holly; Bray, Lucy; Carter, Bernie; Hughes, Dyfrig; Tudur Smith, Catrin; Williamson, Paula R; Gringras, Paul; Pal, Deb K

2017-11-28

There is increasing recognition that establishing a core set of outcomes to be evaluated and reported in trials of interventions for particular conditions will improve the usefulness of health research. There is no established core outcome set for childhood epilepsy. The aim of this work is to select a core outcome set to be used in evaluative research of interventions for children with rolandic epilepsy, as an exemplar of common childhood epilepsy syndromes. First we will identify what outcomes should be measured; then we will decide how to measure those outcomes. We will engage relevant UK charities and health professional societies as partners, and convene advisory panels for young people with epilepsy and parents of children with epilepsy. We will identify candidate outcomes from a search for trials of interventions for childhood epilepsy, statutory guidance and consultation with our advisory panels. Families, charities and health, education and neuropsychology professionals will be invited to participate in a Delphi survey following recommended practices in the development of core outcome sets. Participants will be able to recommend additional outcome domains. Over three rounds of Delphi survey participants will rate the importance of candidate outcome domains and state the rationale for their decisions. Over the three rounds we will seek consensus across and between families and health professionals on the more important outcomes. A face-to-face meeting will be convened to ratify the core outcome set. We will then review and recommend ways to measure the shortlisted outcomes using clinical assessment and/or patient-reported outcome measures. Our methodology is a proportionate and pragmatic approach to expediently produce a core outcome set for evaluative research of interventions aiming to improve the health of children with epilepsy. A number of decisions have to be made when designing a study to develop a core outcome set including defining the scope

Freedom of choice and bounded rationality: a brief appraisal of behavioral economists' plea for light paternalism

Directory of Open Access Journals (Sweden)

Roberta Muramatsu

2012-09-01

Full Text Available Behavioral economics has addressed interesting positive and normative questions underlying the standard rational choice theory. More recently, it suggests that, in a real world of boundedly rational agents, economists could help people to improve the quality of their choices without any harm to autonomy and freedom of choice. This paper aims to scrutinize available arguments for and against current proposals of light paternalistic interventions mainly in the domain of intertemporal choice. It argues that incorporating the notion of bounded rationality in economic analysis and empirical findings of cognitive biases and self-control problems cannot make an indisputable case for paternalism.

In vitro guanine nucleotide exchange activity of DHR-2/DOCKER/CZH2 domains.

Science.gov (United States)

Côté, Jean-François; Vuori, Kristiina

2006-01-01

Rho family GTPases regulate a large variety of biological processes, including the reorganization of the actin cytoskeleton. Like other members of the Ras superfamily of small GTP-binding proteins, Rho GTPases cycle between a GDP-bound (inactive) and a GTP-bound (active) state, and, when active, the GTPases relay extracellular signals to a large number of downstream effectors. Guanine nucleotide exchange factors (GEFs) promote the exchange of GDP for GTP on Rho GTPases, thereby activating them. Most Rho-GEFs mediate their effects through their signature domain known as the Dbl Homology-Pleckstrin Homology (DH-PH) module. Recently, we and others identified a family of evolutionarily conserved, DOCK180-related proteins that also display GEF activity toward Rho GTPases. The DOCK180-family of proteins lacks the canonical DH-PH module. Instead, they rely on a novel domain, termed DHR-2, DOCKER, or CZH2, to exchange GDP for GTP on Rho targets. In this chapter, the experimental approach that we used to uncover the exchange activity of the DHR-2 domain of DOCK180-related proteins will be described.

The structure of the nucleoprotein binding domain of lyssavirus phosphoprotein reveals a structural relationship between the N-RNA binding domains of Rhabdoviridae and Paramyxoviridae.

Science.gov (United States)

Delmas, Olivier; Assenberg, Rene; Grimes, Jonathan M; Bourhy, Hervé

2010-01-01

The phosphoprotein P of non-segmented negative-sense RNA viruses is an essential component of the replication and transcription complex and acts as a co-factor for the viral RNA-dependent RNA polymerase. P recruits the viral polymerase to the nucleoprotein-bound viral RNA (N-RNA) via an interaction between its C-terminal domain and the N-RNA complex. We have obtained the structure of the C-terminal domain of P of Mokola virus (MOKV), a lyssavirus that belongs to the Rhabdoviridae family and mapped at the amino acid level the crucial positions involved in interaction with N and in the formation of the viral replication complex. Comparison of the N-RNA binding domains of P solved to date suggests that the N-RNA binding domains are structurally conserved among paramyxoviruses and rhabdoviruses in spite of low sequence conservation. We also review the numerous other functions of this domain and more generally of the phosphoprotein.

78 FR 18326 - Agency Information Collection Activities; Comment Request; Upward Bound and Upward Bound Math...

Science.gov (United States)

2013-03-26

...; Comment Request; Upward Bound and Upward Bound Math Science Annual Performance Report AGENCY: The Office... considered public records. Title of Collection: Upward Bound and Upward Bound Math Science Annual Performance...) and Upward Bound Math and Science (UBMS) Programs. The Department is requesting a new APR because of...

Universal bounds on current fluctuations.

Science.gov (United States)

Pietzonka, Patrick; Barato, Andre C; Seifert, Udo

2016-05-01

For current fluctuations in nonequilibrium steady states of Markovian processes, we derive four different universal bounds valid beyond the Gaussian regime. Different variants of these bounds apply to either the entropy change or any individual current, e.g., the rate of substrate consumption in a chemical reaction or the electron current in an electronic device. The bounds vary with respect to their degree of universality and tightness. A universal parabolic bound on the generating function of an arbitrary current depends solely on the average entropy production. A second, stronger bound requires knowledge both of the thermodynamic forces that drive the system and of the topology of the network of states. These two bounds are conjectures based on extensive numerics. An exponential bound that depends only on the average entropy production and the average number of transitions per time is rigorously proved. This bound has no obvious relation to the parabolic bound but it is typically tighter further away from equilibrium. An asymptotic bound that depends on the specific transition rates and becomes tight for large fluctuations is also derived. This bound allows for the prediction of the asymptotic growth of the generating function. Even though our results are restricted to networks with a finite number of states, we show that the parabolic bound is also valid for three paradigmatic examples of driven diffusive systems for which the generating function can be calculated using the additivity principle. Our bounds provide a general class of constraints for nonequilibrium systems.

Out-of-Core Computations of High-Resolution Level Sets by Means of Code Transformation

DEFF Research Database (Denmark)

Christensen, Brian Bunch; Nielsen, Michael Bang; Museth, Ken

2012-01-01

We propose a storage efficient, fast and parallelizable out-of-core framework for streaming computations of high resolution level sets. The fundamental techniques are skewing and tiling transformations of streamed level set computations which allow for the combination of interface propagation, re...... computations are now CPU bound and consequently the overall performance is unaffected by disk latency and bandwidth limitations. We demonstrate this with several benchmark tests that show sustained out-of-core throughputs close to that of in-core level set simulations....

Structure and Function of the Catalytic Domain of the Dihydrolipoyl Acetyltransferase Component in Escherichia coli Pyruvate Dehydrogenase Complex*

Science.gov (United States)

Wang, Junjie; Nemeria, Natalia S.; Chandrasekhar, Krishnamoorthy; Kumaran, Sowmini; Arjunan, Palaniappa; Reynolds, Shelley; Calero, Guillermo; Brukh, Roman; Kakalis, Lazaros; Furey, William; Jordan, Frank

2014-01-01

The Escherichia coli pyruvate dehydrogenase complex (PDHc) catalyzing conversion of pyruvate to acetyl-CoA comprises three components: E1p, E2p, and E3. The E2p is the five-domain core component, consisting of three tandem lipoyl domains (LDs), a peripheral subunit binding domain (PSBD), and a catalytic domain (E2pCD). Herein are reported the following. 1) The x-ray structure of E2pCD revealed both intra- and intertrimer interactions, similar to those reported for other E2pCDs. 2) Reconstitution of recombinant LD and E2pCD with E1p and E3p into PDHc could maintain at least 6.4% activity (NADH production), confirming the functional competence of the E2pCD and active center coupling among E1p, LD, E2pCD, and E3 even in the absence of PSBD and of a covalent link between domains within E2p. 3) Direct acetyl transfer between LD and coenzyme A catalyzed by E2pCD was observed with a rate constant of 199 s−1, comparable with the rate of NADH production in the PDHc reaction. Hence, neither reductive acetylation of E2p nor acetyl transfer within E2p is rate-limiting. 4) An unprecedented finding is that although no interaction could be detected between E1p and E2pCD by itself, a domain-induced interaction was identified on E1p active centers upon assembly with E2p and C-terminally truncated E2p proteins by hydrogen/deuterium exchange mass spectrometry. The inclusion of each additional domain of E2p strengthened the interaction with E1p, and the interaction was strongest with intact E2p. E2p domain-induced changes at the E1p active site were also manifested by the appearance of a circular dichroism band characteristic of the canonical 4′-aminopyrimidine tautomer of bound thiamin diphosphate (AP). PMID:24742683

[caCORE: core architecture of bioinformation on cancer research in America].

Science.gov (United States)

Gao, Qin; Zhang, Yan-lei; Xie, Zhi-yun; Zhang, Qi-peng; Hu, Zhang-zhi

2006-04-18

A critical factor in the advancement of biomedical research is the ease with which data can be integrated, redistributed and analyzed both within and across domains. This paper summarizes the Biomedical Information Core Infrastructure built by National Cancer Institute Center for Bioinformatics in America (NCICB). The main product from the Core Infrastructure is caCORE--cancer Common Ontologic Reference Environment, which is the infrastructure backbone supporting data management and application development at NCICB. The paper explains the structure and function of caCORE: (1) Enterprise Vocabulary Services (EVS). They provide controlled vocabulary, dictionary and thesaurus services, and EVS produces the NCI Thesaurus and the NCI Metathesaurus; (2) The Cancer Data Standards Repository (caDSR). It provides a metadata registry for common data elements. (3) Cancer Bioinformatics Infrastructure Objects (caBIO). They provide Java, Simple Object Access Protocol and HTTP-XML application programming interfaces. The vision for caCORE is to provide a common data management framework that will support the consistency, clarity, and comparability of biomedical research data and information. In addition to providing facilities for data management and redistribution, caCORE helps solve problems of data integration. All NCICB-developed caCORE components are distributed under open-source licenses that support unrestricted usage by both non-profit and commercial entities, and caCORE has laid the foundation for a number of scientific and clinical applications. Based on it, the paper expounds caCORE-base applications simply in several NCI projects, of which one is CMAP (Cancer Molecular Analysis Project), and the other is caBIG (Cancer Biomedical Informatics Grid). In the end, the paper also gives good prospects of caCORE, and while caCORE was born out of the needs of the cancer research community, it is intended to serve as a general resource. Cancer research has historically

Quivers of Bound Path Algebras and Bound Path Coalgebras

Directory of Open Access Journals (Sweden)

Dr. Intan Muchtadi

2010-09-01

Full Text Available bras and coalgebras can be represented as quiver (directed graph, and from quiver we can construct algebras and coalgebras called path algebras and path coalgebras. In this paper we show that the quiver of a bound path coalgebra (resp. algebra is the dual quiver of its bound path algebra (resp. coalgebra.

The 1.7 Å X-ray crystal structure of the porcine factor VIII C2 domain and binding analysis to anti-human C2 domain antibodies and phospholipid surfaces.

Directory of Open Access Journals (Sweden)

Caileen M Brison

Full Text Available The factor VIII C2 domain is essential for binding to activated platelet surfaces as well as the cofactor activity of factor VIII in blood coagulation. Inhibitory antibodies against the C2 domain commonly develop following factor VIII replacement therapy for hemophilia A patients, or they may spontaneously arise in cases of acquired hemophilia. Porcine factor VIII is an effective therapeutic for hemophilia patients with inhibitor due to its low cross-reactivity; however, the molecular basis for this behavior is poorly understood. In this study, the X-ray crystal structure of the porcine factor VIII C2 domain was determined, and superposition of the human and porcine C2 domains demonstrates that most surface-exposed differences cluster on the face harboring the "non-classical" antibody epitopes. Furthermore, antibody-binding results illustrate that the "classical" 3E6 antibody can bind both the human and porcine C2 domains, although the inhibitory titer to human factor VIII is 41 Bethesda Units (BU/mg IgG versus 0.8 BU/mg IgG to porcine factor VIII, while the non-classical G99 antibody does not bind to the porcine C2 domain nor inhibit porcine factor VIII activity. Further structural analysis of differences between the electrostatic surface potentials suggest that the C2 domain binds to the negatively charged phospholipid surfaces of activated platelets primarily through the 3E6 epitope region. In contrast, the G99 face, which contains residue 2227, should be distal to the membrane surface. Phospholipid binding assays indicate that both porcine and human factor VIII C2 domains bind with comparable affinities, and the human K2227A and K2227E mutants bind to phospholipid surfaces with similar affinities as well. Lastly, the G99 IgG bound to PS-immobilized factor VIII C2 domain with an apparent dissociation constant of 15.5 nM, whereas 3E6 antibody binding to PS-bound C2 domain was not observed.

High-precision calculation of loosely bound states of LiPs+ and NaPs+

International Nuclear Information System (INIS)

Yamashita, Takuma; Kino, Yasushi

2015-01-01

A positronic alkali atom would be the first step to investigate behavior of a positronium(Ps) in an external field from atoms/molecules because the system can be regarded as a simple three-body system using model potentials reflecting electron orbitals of the ion core. In order to precisely determine binding energies and structures of positronic alkali atoms (LiPs + and NaPs + ), we improve the model potential so as to reproduce highly excited atomic energy levels of alkali atoms (Li and Na). The polarization potential included by the model potential is expanded in terms of Gaussian functions to finely determine a short range part of the potential which has been assumed to be a simple form. We find better reproducibility not only of atomic levels of the alkali atoms but also of the dipole polarizability of the core ion than previous works. We construct a model potential between a positron and an ion core based on the model potential between the valence electron and ion core. Binding energies associated with a dissociation of the alkali ion core and positronium, and interparticle distances are recalculated. Our results show slightly deeper bound than other previous studies. (paper)

Analysis of core damage frequency: Surry, Unit 1 internal events

International Nuclear Information System (INIS)

Bertucio, R.C.; Julius, J.A.; Cramond, W.R.

1990-04-01

This document contains the accident sequence analysis of internally initiated events for the Surry Nuclear Station, Unit 1. This is one of the five plant analyses conducted as part of the NUREG-1150 effort by the Nuclear Regulatory Commission. NUREG-1150 documents the risk of a selected group of nuclear power plants. The work performed and described here is an extensive of that published in November 1986 as NUREG/CR-4450, Volume 3. It addresses comments form numerous reviewers and significant changes to the plant systems and procedures made since the first report. The uncertainty analysis and presentation of results are also much improved. The context and detail of this report are directed toward PRA practitioners who need to know how the work was performed and the details for use in further studies. The mean core damage frequency at Surry was calculated to be 4.05-E-5 per year, with a 95% upper bound of 1.34E-4 and 5% lower bound of 6.8E-6 per year. Station blackout type accidents (loss of all AC power) were the largest contributors to the core damage frequency, accounting for approximately 68% of the total. The next type of dominant contributors were Loss of Coolant Accidents (LOCAs). These sequences account for 15% of core damage frequency. No other type of sequence accounts for more than 10% of core damage frequency. 49 refs., 52 figs., 70 tabs

ROSA full-core and DNBR capabilities

International Nuclear Information System (INIS)

Gibcus, H.P.M.; Verhagen, F.C.M.; Wakker, P.H.

2013-01-01

The latest developments of the ROSA (Reloading Optimization by Simulated Annealing) code system with an emphasis on the first full-core version and the minimum DNBR (Departure from Nucleate Boiling Ratio) as a new optimization parameter are presented. Designing the core loading pattern of nuclear power plants is becoming a more and more complex task. This task becomes even more complicated if asymmetries in the core loading pattern arise, for instance due to damaged fuel assemblies. For over almost 2 decades ROSA, NRG's (Nuclear Research and consultancy Group) loading pattern optimization code system for PWRs, has proven to be a valuable tool to reactor operators in accomplishing this task. To improve the use of ROSA for designing asymmetric loading patterns, NRG has developed a full-core version of ROSA besides the original quarter-core version which requires rotational symmetry in the computational domain. The extension of ROSA with DNBR as an optimization parameter is part of ROSA's continuous development. (orig.)

ROSA full-core and DNBR capabilities

International Nuclear Information System (INIS)

Gibcus, H.P.M.; Verhagen, F.C.M.; Wakker, P.H.

2012-01-01

This paper presents the latest developments of the ROSA (Reloading Optimization by Simulated Annealing) code system with an emphasis on the first full-core version and the minimum DNBR (Departure from Nucleate Boiling Ratio) as a new optimization parameter. Designing the core loading pattern of nuclear power plants is becoming a more and more complex task. This task becomes even more complicated if asymmetries in the core loading pattern arise, for instance due to damaged fuel assemblies. For over almost two decades ROSA, NRG's (Nuclear Research and consultancy Group) loading pattern optimization code system for PWRs, has proven to be a valuable tool to reactor operators in accomplishing this task. To improve the use of ROSA for designing asymmetric loading patterns, NRG has developed a full-core version of ROSA besides the original quarter-core version which requires rotational symmetry in the computational domain. The extension of ROSA with DNBR as an optimization parameter is part of ROSA's continuous development. (orig.)

Training of adolescent multipliers from the perspective of health promotion core competencies

Directory of Open Access Journals (Sweden)

Kely Vanessa Leite Gomes da Silva

Full Text Available ABSTRACT Objective: Recognize the domains of health promotion core competencies in the training process of adolescents carried out by nursing students. Method: Qualitative and descriptive study, which used the theoretical methodological contribution Developing Competencies and Professional Standards for Health Promotion Capacity Building in Europe (CompHP, carried out with 14 nursing students. Results: There were four domains: Enable Change; Mediate through Partnership; Communication; and Leadership. These domains came from the interest and commitment of adolescents in intersectoral partnership, the use of communication techniques, and the role of facilitator to catalyze learning and empowerment. Conclusion: There were some domains of core competency in the training of adolescents, suggesting that nursing students act as health promoters. Challenges for Nursing are the implementation of a theoretical contribution of CompHP in undergraduate and ongoing training to carry out health promotion action.

Crossover from bound to free states in plasmas

International Nuclear Information System (INIS)

Lankin, Alexander V; Norman, Genri E

2009-01-01

A self-consistent joint description of free and weakly bound electron states in strongly coupled plasmas is presented. The existence of two problems is emphasized. The first one is a well-known restriction of the number of atomic excited states. Another one is a description of the smooth crossover from bound pair electron-ion excited states to collective excitations of free electrons. The fluctuation approach is developed to study the spectrum domain intermediate between low-lying excited atoms and free electron continuous energy levels. The molecular dynamics method is applied to study the plasma model since the method is able to distinguish all kinds of fluctuations. The electron-ion interaction is described by the temperature-independent cut-off Coulomb potential. The diagnostics of pair electron-ion fluctuations is developed. The concept of pair fluctuations elucidates the smooth vanishing of atomic states near the ionization limit. The approach suggested removes the artificial break of the electron state density at the ionization limit: atomic state density divergent at the negative energy side and free electron state density starting from zero density at the positive energy side

Redefining the modular organization of the core Mediator complex.

Science.gov (United States)

Wang, Xuejuan; Sun, Qianqian; Ding, Zhenrui; Ji, Jinhua; Wang, Jianye; Kong, Xiao; Yang, Jianghong; Cai, Gang

2014-07-01

The Mediator complex plays an essential role in the regulation of eukaryotic transcription. The Saccharomyces cerevisiae core Mediator comprises 21 subunits, which are organized into Head, Middle and Tail modules. Previously, the Head module was assigned to a distinct dense domain at the base, and the Middle and Tail modules were identified to form a tight structure above the Head module, which apparently contradicted findings from many biochemical and functional studies. Here, we compared the structures of the core Mediator and its subcomplexes, especially the first 3D structure of the Head + Middle modules, which permitted an unambiguous assignment of the three modules. Furthermore, nanogold labeling pinpointing four Mediator subunits from different modules conclusively validated the modular assignment, in which the Head and Middle modules fold back on one another and form the upper portion of the core Mediator, while the Tail module forms a distinct dense domain at the base. The new modular model of the core Mediator has reconciled the previous inconsistencies between the structurally and functionally defined Mediator modules. Collectively, these analyses completely redefine the modular organization of the core Mediator, which allow us to integrate the structural and functional information into a coherent mechanism for the Mediator's modularity and regulation in transcription initiation.

Polycomb domain formation depends on short and long distance regulatory cues.

Directory of Open Access Journals (Sweden)

Bernd Schuettengruber

Full Text Available BACKGROUND: Polycomb group (PcG proteins dynamically define cellular identities through the epigenetic repression of key developmental genes. In Drosophila, cis-regulatory regions termed PcG response elements (PREs act as nucleation sites for PcG proteins to create large repressive PcG domains that are marked by trimethylation of lysine 27 on histone H3 (H3K27me3. In addition to an action in cis, PREs can interact over long distances, thereby enhancing PcG dependent silencing. How PcG domains are established, which factors limit their propagation in cis, and how long range interactions of PREs in trans affect the chromatin structure is largely unknown. PRINCIPAL FINDINGS: We demonstrate that the insertion of a PRE-containing transgene in the Drosophila genome generates an artificial PcG domain and we analyze its organization by quantitative ChIP and ChIP-on-chip experiments. Intriguingly, a boundary element and known insulator proteins do not necessarily interfere with spreading of H3K27me3. Instead, domain borders correlate with the presence of promoter regions bound by RNA Polymerase II and active chromatin marks. In contrast, genes that are silent during early fly development get included within the PcG domain and this incorporation interferes with gene activation at later developmental stages. Moreover, trans-interaction of the transgenic PRE with its homologous endogenous PRE results in increased PcG binding, correlating with reinforced silencing of genes within the domain borders. CONCLUSIONS: Our results suggest that higher-order organization of PcG-bound chromatin can stabilize gene silencing within PcG domains. Further we propose that multi-protein complexes associated with active promoters are able to define the limits of PcG domains. Future work aimed to pinpoint the factors providing this barrier function will be required to understand the precise molecular mechanism by which active promoter regions can act as boundaries to stop

En route to surface-bound electric field-driven molecular motors.

Science.gov (United States)

Jian, Huahua; Tour, James M

2003-06-27

Four caltrop-shaped molecules that might be useful as surface-bound electric field-driven molecular motors have been synthesized. The caltrops are comprised of a pair of electron donor-acceptor arms and a tripod base. The molecular arms are based on a carbazole or oligo(phenylene ethynylene) core with a strong net dipole. The tripod base uses a silicon atom as its core. The legs of the tripod bear sulfur-tipped bonding units, as acetyl-protected benzylic thiols, for bonding to a gold surface. The geometry of the tripod base allows the caltrop to project upward from a metallic surface after self-assembly. Ellipsometric studies show that self-assembled monolayers of the caltrops are formed on Au surfaces with molecular thicknesses consistent with the desired upright-shaft arrangement. As a result, the zwitterionic molecular arms might be controllable when electric fields are applied around the caltrops, thereby constituting field-driven motors.

Enhanced Nonadiabaticity in Vortex Cores due to the Emergent Hall Effect

KAUST Repository

Bisig, André

2017-01-04

We present a combined theoretical and experimental study, investigating the origin of the enhanced nonadiabaticity of magnetic vortex cores. Scanning transmission x-ray microscopy is used to image the vortex core gyration dynamically to measure the nonadiabaticity with high precision, including a high confidence upper bound. We show theoretically, that the large nonadiabaticity parameter observed experimentally can be explained by the presence of local spin currents arising from a texture induced emergent Hall effect. This study demonstrates that the magnetic damping α and nonadiabaticity parameter β are very sensitive to the topology of the magnetic textures, resulting in an enhanced ratio (β/α>1) in magnetic vortex cores or Skyrmions.

Enhanced Nonadiabaticity in Vortex Cores due to the Emergent Hall Effect

KAUST Repository

Bisig, André ; Akosa, Collins Ashu; Moon, Jung-Hwan; Rhensius, Jan; Moutafis, Christoforos; von Bieren, Arndt; Heidler, Jakoba; Kiliani, Gillian; Kammerer, Matthias; Curcic, Michael; Weigand, Markus; Tyliszczak, Tolek; Van Waeyenberge, Bartel; Stoll, Hermann; Schü tz, Gisela; Lee, Kyung-Jin; Manchon, Aurelien; Klä ui, Mathias

2017-01-01

We present a combined theoretical and experimental study, investigating the origin of the enhanced nonadiabaticity of magnetic vortex cores. Scanning transmission x-ray microscopy is used to image the vortex core gyration dynamically to measure the nonadiabaticity with high precision, including a high confidence upper bound. We show theoretically, that the large nonadiabaticity parameter observed experimentally can be explained by the presence of local spin currents arising from a texture induced emergent Hall effect. This study demonstrates that the magnetic damping α and nonadiabaticity parameter β are very sensitive to the topology of the magnetic textures, resulting in an enhanced ratio (β/α>1) in magnetic vortex cores or Skyrmions.

Antimicrobial activity of a novel hypervariable immunoglobulin domain-containing receptor Dscam in Cherax quadricarinatus.

Science.gov (United States)

Li, Dan; Yu, Ai-Qing; Li, Xue-Jie; Zhu, You-Ting; Jin, Xing-Kun; Li, Wei-Wei; Wang, Qun

2015-12-01

Down syndrome cell adhesion molecule (Dscam) mediates innate immunity against pathogens in arthropods. Here, a novel Dscam from red claw crayfish Cherax quadricarinatus (CqDscam) was isolated. The CqDscam protein contains one signal peptide, ten immunoglobulin domains, six fibronectin type III domains, one transmembrane domain and cytoplasmic tail. CqDscam phylogenetically clustered with other invertebrate Dscams. Variable regions of CqDscam in N-terminal halves of Ig2 and Ig3 domains, complete Ig7 domain and TM domain can be reshuffled after transcription to produce a deluge of >37,620 potential alternative splice forms. CqDscam was detected in all tissues tested and abundantly expressed in immune system and nerve system. Upon lipopolysaccharides (LPS) and b-1, 3-glucans (Glu) challenged, the expression of CqDscam was up-regulated, while no response in expression occurred after injection with peptidoglycans (PG). Membrane-bound and secreted types of CqDscam were separated on the protein level, and were both extensively induced post LPS challenge. Membrane-bound CqDscam protein was not detected in the serum, but localized to the hemocyte surface by immuno-localization assay. In the antimicrobial assays, the recombinant LPS-induced isoform of CqDscam protein displayed bacterial binding and growth inhibitory activities, especially with Escherichia coli. These results suggested that CqDscam, as one of pattern-recognition receptors (PRRs), involved in innate immune recognition and defense mechanisms in C. quadricarinatus, possibly through alternative splicing. Copyright © 2015 Elsevier Ltd. All rights reserved.

Crystal structure of product-bound complex of UDP-N-acetyl-d-mannosamine dehydrogenase from Pyrococcus horikoshii OT3.

Science.gov (United States)

Pampa, K J; Lokanath, N K; Girish, T U; Kunishima, N; Rai, V R

2014-10-24

UDP-N-acetyl-d-mannosamine dehydrogenase (UDP-d-ManNAcDH) belongs to UDP-glucose/GDP-mannose dehydrogenase family and catalyzes Uridine-diphospho-N-acetyl-d-mannosamine (UDP-d-ManNAc) to Uridine-diphospho-N-acetyl-d-mannosaminuronic acid (UDP-d-ManNAcA) through twofold oxidation of NAD(+). In order to reveal the structural features of the Pyrococcus horikoshii UDP-d-ManNAcADH, we have determined the crystal structure of the product-bound enzyme by X-ray diffraction to resolution of 1.55Å. The protomer folds into three distinct domains; nucleotide binding domain (NBD), substrate binding domain (SBD) and oligomerization domain (OD, involved in the dimerization). The clear electron density of the UDP-d-ManNAcA is observed and the residues binding are identified for the first time. Crystal structures reveal a tight dimeric polymer chains with product-bound in all the structures. The catalytic residues Cys258 and Lys204 are conserved. The Cys258 acts as catalytic nucleophile and Lys204 as acid/base catalyst. The product is directly interacts with residues Arg211, Thr249, Arg244, Gly255, Arg289, Lys319 and Arg398. In addition, the structural parameters responsible for thermostability and oligomerization of the three dimensional structure are analyzed. Copyright © 2014 Elsevier Inc. All rights reserved.

UV-Visible Spectroscopy-Based Quantification of Unlabeled DNA Bound to Gold Nanoparticles.

Science.gov (United States)

Baldock, Brandi L; Hutchison, James E

2016-12-20

DNA-functionalized gold nanoparticles have been increasingly applied as sensitive and selective analytical probes and biosensors. The DNA ligands bound to a nanoparticle dictate its reactivity, making it essential to know the type and number of DNA strands bound to the nanoparticle surface. Existing methods used to determine the number of DNA strands per gold nanoparticle (AuNP) require that the sequences be fluorophore-labeled, which may affect the DNA surface coverage and reactivity of the nanoparticle and/or require specialized equipment and other fluorophore-containing reagents. We report a UV-visible-based method to conveniently and inexpensively determine the number of DNA strands attached to AuNPs of different core sizes. When this method is used in tandem with a fluorescence dye assay, it is possible to determine the ratio of two unlabeled sequences of different lengths bound to AuNPs. Two sizes of citrate-stabilized AuNPs (5 and 12 nm) were functionalized with mixtures of short (5 base) and long (32 base) disulfide-terminated DNA sequences, and the ratios of sequences bound to the AuNPs were determined using the new method. The long DNA sequence was present as a lower proportion of the ligand shell than in the ligand exchange mixture, suggesting it had a lower propensity to bind the AuNPs than the short DNA sequence. The ratio of DNA sequences bound to the AuNPs was not the same for the large and small AuNPs, which suggests that the radius of curvature had a significant influence on the assembly of DNA strands onto the AuNPs.

On a Paneitz type equation in six dimensional domains

International Nuclear Information System (INIS)

Chtioui, Hichem; El Mehdi, Khalil

2003-09-01

In this paper, we consider the equation Δ 2 u = Ku 5 , u > 0 in Ω, u = Δu = 0 on ∂Ω, where K is a positive function and Ω is a bounded and smooth domain in R 6 . Using the theory of critical points at infinity, we give some topological conditions on K to ensure some existence results. (author)

Core Outcomes for Colorectal Cancer Surgery: A Consensus Study.

Directory of Open Access Journals (Sweden)

Angus G K McNair

2016-08-01

Full Text Available Colorectal cancer (CRC is a major cause of worldwide morbidity and mortality. Surgical treatment is common, and there is a great need to improve the delivery of such care. The gold standard for evaluating surgery is within well-designed randomized controlled trials (RCTs; however, the impact of RCTs is diminished by a lack of coordinated outcome measurement and reporting. A solution to these issues is to develop an agreed standard "core" set of outcomes to be measured in all trials to facilitate cross-study comparisons, meta-analysis, and minimize outcome reporting bias. This study defines a core outcome set for CRC surgery.The scope of this COS includes clinical effectiveness trials of surgical interventions for colorectal cancer. Excluded were nonsurgical oncological interventions. Potential outcomes of importance to patients and professionals were identified through systematic literature reviews and patient interviews. All outcomes were transcribed verbatim and categorized into domains by two independent researchers. This informed a questionnaire survey that asked stakeholders (patients and professionals from United Kingdom CRC centers to rate the importance of each domain. Respondents were resurveyed following group feedback (Delphi methods. Outcomes rated as less important were discarded after each survey round according to predefined criteria, and remaining outcomes were considered at three consensus meetings; two involving international professionals and a separate one with patients. A modified nominal group technique was used to gain the final consensus. Data sources identified 1,216 outcomes of CRC surgery that informed a 91 domain questionnaire. First round questionnaires were returned from 63 out of 81 (78% centers, including 90 professionals, and 97 out of 267 (35% patients. Second round response rates were high for all stakeholders (>80%. Analysis of responses lead to 45 and 23 outcome domains being retained after the first and

Effective particle magnetic moment of multi-core particles

Energy Technology Data Exchange (ETDEWEB)

Ahrentorp, Fredrik; Astalan, Andrea; Blomgren, Jakob; Jonasson, Christian [Acreo Swedish ICT AB, Arvid Hedvalls backe 4, SE-411 33 Göteborg (Sweden); Wetterskog, Erik; Svedlindh, Peter [Department of Engineering Sciences, Uppsala University, Box 534, SE-751 21 Uppsala (Sweden); Lak, Aidin; Ludwig, Frank [Institute of Electrical Measurement and Fundamental Electrical Engineering, TU Braunschweig, D‐38106 Braunschweig Germany (Germany); IJzendoorn, Leo J. van [Department of Applied Physics, Eindhoven University of Technology, 5600 MB Eindhoven (Netherlands); Westphal, Fritz; Grüttner, Cordula [Micromod Partikeltechnologie GmbH, D ‐18119 Rostock (Germany); Gehrke, Nicole [nanoPET Pharma GmbH, D ‐10115 Berlin Germany (Germany); Gustafsson, Stefan; Olsson, Eva [Department of Applied Physics, Chalmers University of Technology, SE-412 96 Göteborg (Sweden); Johansson, Christer, E-mail: christer.johansson@acreo.se [Acreo Swedish ICT AB, Arvid Hedvalls backe 4, SE-411 33 Göteborg (Sweden)

2015-04-15

In this study we investigate the magnetic behavior of magnetic multi-core particles and the differences in the magnetic properties of multi-core and single-core nanoparticles and correlate the results with the nanostructure of the different particles as determined from transmission electron microscopy (TEM). We also investigate how the effective particle magnetic moment is coupled to the individual moments of the single-domain nanocrystals by using different measurement techniques: DC magnetometry, AC susceptometry, dynamic light scattering and TEM. We have studied two magnetic multi-core particle systems – BNF Starch from Micromod with a median particle diameter of 100 nm and FeraSpin R from nanoPET with a median particle diameter of 70 nm – and one single-core particle system – SHP25 from Ocean NanoTech with a median particle core diameter of 25 nm.

Effective particle magnetic moment of multi-core particles

International Nuclear Information System (INIS)

Ahrentorp, Fredrik; Astalan, Andrea; Blomgren, Jakob; Jonasson, Christian; Wetterskog, Erik; Svedlindh, Peter; Lak, Aidin; Ludwig, Frank; IJzendoorn, Leo J. van; Westphal, Fritz; Grüttner, Cordula; Gehrke, Nicole; Gustafsson, Stefan; Olsson, Eva; Johansson, Christer

2015-01-01

In this study we investigate the magnetic behavior of magnetic multi-core particles and the differences in the magnetic properties of multi-core and single-core nanoparticles and correlate the results with the nanostructure of the different particles as determined from transmission electron microscopy (TEM). We also investigate how the effective particle magnetic moment is coupled to the individual moments of the single-domain nanocrystals by using different measurement techniques: DC magnetometry, AC susceptometry, dynamic light scattering and TEM. We have studied two magnetic multi-core particle systems – BNF Starch from Micromod with a median particle diameter of 100 nm and FeraSpin R from nanoPET with a median particle diameter of 70 nm – and one single-core particle system – SHP25 from Ocean NanoTech with a median particle core diameter of 25 nm

Effective particle magnetic moment of multi-core particles

Science.gov (United States)

Ahrentorp, Fredrik; Astalan, Andrea; Blomgren, Jakob; Jonasson, Christian; Wetterskog, Erik; Svedlindh, Peter; Lak, Aidin; Ludwig, Frank; van IJzendoorn, Leo J.; Westphal, Fritz; Grüttner, Cordula; Gehrke, Nicole; Gustafsson, Stefan; Olsson, Eva; Johansson, Christer

2015-04-01

In this study we investigate the magnetic behavior of magnetic multi-core particles and the differences in the magnetic properties of multi-core and single-core nanoparticles and correlate the results with the nanostructure of the different particles as determined from transmission electron microscopy (TEM). We also investigate how the effective particle magnetic moment is coupled to the individual moments of the single-domain nanocrystals by using different measurement techniques: DC magnetometry, AC susceptometry, dynamic light scattering and TEM. We have studied two magnetic multi-core particle systems - BNF Starch from Micromod with a median particle diameter of 100 nm and FeraSpin R from nanoPET with a median particle diameter of 70 nm - and one single-core particle system - SHP25 from Ocean NanoTech with a median particle core diameter of 25 nm.

Crustal concealing of small-scale core-field secular variation

DEFF Research Database (Denmark)

Hulot, G.; Olsen, Nils; Thebault, E.

2009-01-01

of internal origin happen to be detectable now in spherical harmonic degrees up to, perhaps, 16. All of these changes are usually attributed to changes in the core field itself, the secular variation, on the ground that the lithospheric magnetization cannot produce such signals. It has, however, been pointed...... out, on empirical grounds, that temporal changes in the field of internal origin produced by the induced part of the lithospheric magnetization could dominate the core field signal beyond degree 22. This short note revisits this issue by taking advantage of our improved knowledge of the small...... cause of the observed changes in the field of internal origin up to some critical degree, N-C, is indeed likely to be the secular variation of the core field, but that the signal produced by the time-varying lithospheric field is bound to dominate and conceal the time-varying core signal beyond...

Structural requirements for cub domain containing protein 1 (CDCP1 and Src dependent cell transformation.

Directory of Open Access Journals (Sweden)

Gwendlyn Kollmorgen

Full Text Available Cub domain containing protein 1 (CDCP1 is strongly expressed in tumors derived from lung, colon, ovary, or kidney. It is a membrane protein that is phosphorylated and then bound by Src family kinases. Although expression and phosphorylation of CDCP1 have been investigated in many tumor cell lines, the CDCP1 features responsible for transformation have not been fully evaluated. This is in part due to the lack of an experimental system in which cellular transformation depends on expression of exogenous CDCP1 and Src. Here we use retrovirus mediated co-overexpression of c-Src and CDCP1 to induce focus formation of NIH3T3 cells. Employing different mutants of CDCP1 we show that for a full transformation capacity, the intact amino- and carboxy-termini of CDCP1 are essential. Mutation of any of the core intracellular tyrosine residues (Y734, Y743, or Y762 abolished transformation, and mutation of a palmitoylation motif (C689,690G strongly reduced it. Src kinase binding to CDCP1 was not required since Src with a defective SH2 domain generated even more CDCP1 dependent foci whereas Src myristoylation was necessary. Taken together, the focus formation assay allowed us to define structural requirements of CDCP1/Src dependent transformation and to characterize the interaction of CDCP1 and Src.

Experience in forming and core mixtures by Alphaset technology

Directory of Open Access Journals (Sweden)

I. Vasková

2008-07-01

Full Text Available Chemically bound mixtures have had the evolution effect upon the economical and quality aspects of the foundry operations since they presentation at the market. The higher output and significantly increased production efficiency of moulds and cores has lead to the material increase in the quality and profit of the foundries. It can be seen that in last several years the knowledge of bounds based on the organic resins has made enormous advances. The higher strength, improved properties under elevated temperatures, the reduction of the environmental impacts of the organic bounds and at the same their highly improved regenerationability ensure that these systems will be still more significant binding system. The organic binding systems are predominantly being developed recemtly. The technology AlpHaset is ranked among the alkali binding systems. This technology has certain disadvantages – lower strength, speed of hardening- which have been gradually eliminated.

TRF2 Protein Interacts with Core Histones to Stabilize Chromosome Ends.

Science.gov (United States)

Konishi, Akimitsu; Izumi, Takashi; Shimizu, Shigeomi

2016-09-23

Mammalian chromosome ends are protected by a specialized nucleoprotein complex called telomeres. Both shelterin, a telomere-specific multi-protein complex, and higher order telomeric chromatin structures combine to stabilize the chromosome ends. Here, we showed that TRF2, a component of shelterin, binds to core histones to protect chromosome ends from inappropriate DNA damage response and loss of telomeric DNA. The N-terminal Gly/Arg-rich domain (GAR domain) of TRF2 directly binds to the globular domain of core histones. The conserved arginine residues in the GAR domain of TRF2 are required for this interaction. A TRF2 mutant with these arginine residues substituted by alanine lost the ability to protect telomeres and induced rapid telomere shortening caused by the cleavage of a loop structure of the telomeric chromatin. These findings showed a previously unnoticed interaction between the shelterin complex and nucleosomal histones to stabilize the chromosome ends. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

TRF2 Protein Interacts with Core Histones to Stabilize Chromosome Ends*

Science.gov (United States)

Izumi, Takashi; Shimizu, Shigeomi

2016-01-01

Mammalian chromosome ends are protected by a specialized nucleoprotein complex called telomeres. Both shelterin, a telomere-specific multi-protein complex, and higher order telomeric chromatin structures combine to stabilize the chromosome ends. Here, we showed that TRF2, a component of shelterin, binds to core histones to protect chromosome ends from inappropriate DNA damage response and loss of telomeric DNA. The N-terminal Gly/Arg-rich domain (GAR domain) of TRF2 directly binds to the globular domain of core histones. The conserved arginine residues in the GAR domain of TRF2 are required for this interaction. A TRF2 mutant with these arginine residues substituted by alanine lost the ability to protect telomeres and induced rapid telomere shortening caused by the cleavage of a loop structure of the telomeric chromatin. These findings showed a previously unnoticed interaction between the shelterin complex and nucleosomal histones to stabilize the chromosome ends. PMID:27514743

Closed-form estimates of the domain of attraction for nonlinear systems via fuzzy-polynomial models.

Science.gov (United States)

Pitarch, José Luis; Sala, Antonio; Ariño, Carlos Vicente

2014-04-01

In this paper, the domain of attraction of the origin of a nonlinear system is estimated in closed form via level sets with polynomial boundaries, iteratively computed. In particular, the domain of attraction is expanded from a previous estimate, such as a classical Lyapunov level set. With the use of fuzzy-polynomial models, the domain of attraction analysis can be carried out via sum of squares optimization and an iterative algorithm. The result is a function that bounds the domain of attraction, free from the usual restriction of being positive and decrescent in all the interior of its level sets.

Photon virtual bound state

International Nuclear Information System (INIS)

Inoue, J.; Ohtaka, K.

2004-01-01

We study virtual bound states in photonics, which are a vectorial extension of electron virtual bound states. The condition for these states is derived. It is found that the Mie resonant state which satisfies the condition that the size parameter is less than the angular momentum should be interpreted as a photon virtual bound state. In order to confirm the validity of the concept, we compare the photonic density of states, the width of which represents the lifetime of the photon virtual bound states, with numerical results

A conserved domain in type III secretion links the cytoplasmic domain of InvA to elements of the basal body

International Nuclear Information System (INIS)

Lilic, Mirjana; Quezada, Cindy M.; Stebbins, C. Erec

2010-01-01

The cytoplasmic domain of Salmonella InvA shares homology to a recurring scaffold in the membrane-spanning components of the type II and type III secretion systems. Protein type III secretion systems (T3SSs) are organic nanosyringes that achieve an energy-dependent translocation of bacterial proteins through the two membranes of Gram-negative organisms. Examples include the pathogenic systems of animals, plants and symbiotic bacteria that inject factors into eukaryotic cells, and the flagellar export system that secretes flagellin. T3SSs possess a core of several membrane-associated proteins that are conserved across all known bacterial species that use this system. The Salmonella protein InvA is one of the most highly conserved proteins of this core of critical T3SS components. The crystal structure of a C-terminal domain of InvA reveals an unexpected homology to domains that have been repeatedly found as building blocks of other elements of the T3SS apparatus. This suggests the surprising hypothesis that evolution has produced a significant component of the apparatus structure through a series of gene-duplication and gene-rearrangement events

Quark matter coupled to domain walls in Bianchi types II, VIII and IX ...

Indian Academy of Sciences (India)

In this study of Bianchi types II, VIII and IX Universes, quark matter coupled to domain walls in the ... The self-bound state appears to be at ρ ... The observations suggest that the Hubble expansion of the Universe ... Taking motivation from.

Guaranteed Bounds on Information-Theoretic Measures of Univariate Mixtures Using Piecewise Log-Sum-Exp Inequalities

KAUST Repository

Nielsen, Frank

2016-12-09

Information-theoreticmeasures, such as the entropy, the cross-entropy and the Kullback-Leibler divergence between two mixture models, are core primitives in many signal processing tasks. Since the Kullback-Leibler divergence of mixtures provably does not admit a closed-form formula, it is in practice either estimated using costly Monte Carlo stochastic integration, approximated or bounded using various techniques. We present a fast and generic method that builds algorithmically closed-form lower and upper bounds on the entropy, the cross-entropy, the Kullback-Leibler and the α-divergences of mixtures. We illustrate the versatile method by reporting our experiments for approximating the Kullback-Leibler and the α-divergences between univariate exponential mixtures, Gaussian mixtures, Rayleigh mixtures and Gamma mixtures.

Study of the core compaction effects and its monitoring in sodium cooled fast reactors

International Nuclear Information System (INIS)

Zylbersztejn, F.

2012-01-01

Conclusions: • On calculation of reactivity impacts of core compaction/flowering: → Upper bound of the reactivity coefficients for each type of deformation; → Uniform compaction model: significant reactivity impact; Circular symmetric model: small reactivity impact. • On the visibility of these phenomena by the neutron detectors: → The direct monitoring of the core compaction by neutron detector in the BCC is not possible. (the identification that the reactivity perturbations observed are due to variation of the core geometry). Perspectives of solutions: → Improved core design: reducing the effects. → Physical improvements: Steel resistance to deformations (irradiation, flexion); Direct devices: core constraint (prevents deformations). → Additional calculations: Considering more localized deformations; Advanced monitoring with neutron noise (in progress)

Segregated nodal domains of two-dimensional multispecies Bose-Einstein condensates

Science.gov (United States)

Chang, Shu-Ming; Lin, Chang-Shou; Lin, Tai-Chia; Lin, Wen-Wei

2004-09-01

In this paper, we study the distribution of m segregated nodal domains of the m-mixture of Bose-Einstein condensates under positive and large repulsive scattering lengths. It is shown that components of positive bound states may repel each other and form segregated nodal domains as the repulsive scattering lengths go to infinity. Efficient numerical schemes are created to confirm our theoretical results and discover a new phenomenon called verticillate multiplying, i.e., the generation of multiple verticillate structures. In addition, our proposed Gauss-Seidel-type iteration method is very effective in that it converges linearly in 10-20 steps.

Single-molecule folding mechanisms of the apo- and Mg2+-bound states of human neuronal calcium sensor-1

DEFF Research Database (Denmark)

Naqvi, Mohsin M; Heiðarsson, Pétur Orri; Otazo, Mariela R

2015-01-01

, at least transiently, at resting Ca(2+) conditions. Here, we used optical tweezers to study the folding behavior of individual NCS-1 molecules in the presence of Mg(2+) and in the absence of divalent ions. Under tension, the Mg(2+)-bound state of NCS-1 unfolds and refolds in a three-state process...... in a variety of cellular processes in which it has been linked to a number of disorders such as schizophrenia and autism. Despite extensive studies on the Ca(2+)-activated state of NCS proteins, little is known about the conformational dynamics of the Mg(2+)-bound and apo states, both of which are populated...... by populating one intermediate state consisting of a folded C-domain and an unfolded N-domain. The interconversion at equilibrium between the different molecular states populated by NCS-1 was monitored in real time through constant-force measurements and the energy landscapes underlying the observed transitions...

Towards a Certified Lightweight Array Bound Checker for Java Bytecode

Science.gov (United States)

Pichardie, David

2009-01-01

Dynamic array bound checks are crucial elements for the security of a Java Virtual Machines. These dynamic checks are however expensive and several static analysis techniques have been proposed to eliminate explicit bounds checks. Such analyses require advanced numerical and symbolic manipulations that 1) penalize bytecode loading or dynamic compilation, 2) complexify the trusted computing base. Following the Foundational Proof Carrying Code methodology, our goal is to provide a lightweight bytecode verifier for eliminating array bound checks that is both efficient and trustable. In this work, we define a generic relational program analysis for an imperative, stackoriented byte code language with procedures, arrays and global variables and instantiate it with a relational abstract domain as polyhedra. The analysis has automatic inference of loop invariants and method pre-/post-conditions, and efficient checking of analysis results by a simple checker. Invariants, which can be large, can be specialized for proving a safety policy using an automatic pruning technique which reduces their size. The result of the analysis can be checked efficiently by annotating the program with parts of the invariant together with certificates of polyhedral inclusions. The resulting checker is sufficiently simple to be entirely certified within the Coq proof assistant for a simple fragment of the Java bytecode language. During the talk, we will also report on our ongoing effort to scale this approach for the full sequential JVM.

Computing Bounds on Resource Levels for Flexible Plans

Science.gov (United States)

Muscvettola, Nicola; Rijsman, David

2009-01-01

A new algorithm efficiently computes the tightest exact bound on the levels of resources induced by a flexible activity plan (see figure). Tightness of bounds is extremely important for computations involved in planning because tight bounds can save potentially exponential amounts of search (through early backtracking and detection of solutions), relative to looser bounds. The bound computed by the new algorithm, denoted the resource-level envelope, constitutes the measure of maximum and minimum consumption of resources at any time for all fixed-time schedules in the flexible plan. At each time, the envelope guarantees that there are two fixed-time instantiations one that produces the minimum level and one that produces the maximum level. Therefore, the resource-level envelope is the tightest possible resource-level bound for a flexible plan because any tighter bound would exclude the contribution of at least one fixed-time schedule. If the resource- level envelope can be computed efficiently, one could substitute looser bounds that are currently used in the inner cores of constraint-posting scheduling algorithms, with the potential for great improvements in performance. What is needed to reduce the cost of computation is an algorithm, the measure of complexity of which is no greater than a low-degree polynomial in N (where N is the number of activities). The new algorithm satisfies this need. In this algorithm, the computation of resource-level envelopes is based on a novel combination of (1) the theory of shortest paths in the temporal-constraint network for the flexible plan and (2) the theory of maximum flows for a flow network derived from the temporal and resource constraints. The measure of asymptotic complexity of the algorithm is O(N O(maxflow(N)), where O(x) denotes an amount of computing time or a number of arithmetic operations proportional to a number of the order of x and O(maxflow(N)) is the measure of complexity (and thus of cost) of a maximumflow

Analysis of core damage frequency, Surry, Unit 1 internal events appendices

International Nuclear Information System (INIS)

Bertucio, R.C.; Julius, J.A.; Cramond, W.R.

1990-04-01

This document contains the appendices for the accident sequence analyses of internally initiated events for the Surry Nuclear Station, Unit 1. This is one of the five plant analyses conducted as part of the NUREG-1150 effort by the Nuclear Regulatory Commission. NUREG-1150 documents the risk of a selected group of nuclear power plants. The work performed is an extensive reanalysis of that published in November 1986 as NUREG/CR-4450, Volume 3. It addresses comments from numerous reviewers and significant changes to the plant systems and procedures made since the first report. The uncertainty analysis and presentation of results are also much improved. The context and detail of this report are directed toward PRA practitioners who need to know how the work was performed and the details for use in further studies. The mean core damage frequency at Surry was calculated to be 4.0E-5 per year, with a 95% upper bound of 1.3E-4 and 5% lower bound of 6.8E-6 per year. Station blackout type accidents (loss of all AC power) were the largest contributors to the core damage frequency, accounting for approximately 68% of the total. The next type of dominant contributors were Loss of Coolant Accidents (LOCAs). These sequences account for 15% of core damage frequency. No other type of sequence accounts for more than 10% of core damage frequency

On a Paneitz type equation in six dimensional domains

Energy Technology Data Exchange (ETDEWEB)

Chtioui, Hichem [Departement de Mathematiques, Faculte des Sciences de Sfax, Route Soukra, Sfax (Tunisia); El Mehdi, Khalil [Faculte des Sciences et Techniques, Universite de Nouakchott, Nouakchott (Morocco); [Abdus Salam International Centre for Theoretical Physics, Trieste (Italy)]. E-mail: khalil@univ-nkc.mr; it, elmehdik@ictp trieste

2003-09-01

In this paper, we consider the equation {delta}{sup 2}u = Ku{sup 5}, u > 0 in {omega}, u = {delta}u = 0 on {partial_derivative}{omega}, where K is a positive function and {omega} is a bounded and smooth domain in R{sup 6}. Using the theory of critical points at infinity, we give some topological conditions on K to ensure some existence results. (author)

Application of Periodic 3DPCM for Core Monitoring System

International Nuclear Information System (INIS)

Jeong, Wi-Soo; Lee, Hae-Chan; Kim, Hyeong-Seog; Lee, Chang-Kue; Park, Sang-weon; Baek, Jin-su

2014-01-01

The OASIS (Online core Analysis and Simulation System) was developed for WH type PWR which has movable in-core detector. 3DPCM (3D Power Connection Method) was also developed to measure 3D core power distribution using the fixed in-core detector signals and tested for KSNP (Korea Standard Nuclear Plant) such as OPR1000 and APR1400. According to previous study, 3DPCM coupling with neutronics code shows high accuracy. However, this method requires the neutronics code results at each calculation. Therefore, the long calculation time makes it impractical in the online monitoring system requiring the real-time 3D power distribution. In this paper, the 3DPCM based alternative methodology which called periodic 3DPCM is proposed to reduce the calculation time within the reasonable accuracy. The periodic 3DPCM is proposed to reduce the number of neutronics calculation with reasonable accuracy for the application to the online monitoring system development. The periodic 3DPCM is analyzed by 3 cases of sensitivity studies. The errors for the results of power changing operation, ASI changing simulation, and lead control rod insertion are bounded in 0.25%, 1.07%, and 1.15%, respectively. If the update time is shorten as 1 hour, the errors for power changing operation and ASI changing simulation are bounded in 0.07% and 0.56%, respectively. As a result, the update time of 1 hour and prompt update at 30% control rod position change are reasonable considering both conservativeness and effectiveness to update the prediction values. OASIS program utilizing periodic 3DPCM is verified using the plant measurement data and snapshot files which were generated during 45 days operation

Structural changes of the regulatory proteins bound to the thin filaments in skeletal muscle contraction by X-ray fiber diffraction

International Nuclear Information System (INIS)

Sugimoto, Yasunobu; Takezawa, Yasunori; Matsuo, Tatsuhito; Ueno, Yutaka; Minakata, Shiho; Tanaka, Hidehiro; Wakabayashi, Katsuzo

2008-01-01

In order to clarify the structural changes related to the regulation mechanism in skeletal muscle contraction, the intensity changes of thin filament-based reflections were investigated by X-ray fiber diffraction. The time course and extent of intensity changes of the first to third order troponin (TN)-associated meridional reflections with a basic repeat of 38.4 nm were different for each of these reflections. The intensity of the first and second thin filament layer lines changed in a reciprocal manner both during initial activation and during the force generation process. The axial spacings of the TN-meridional reflections decreased by ∼0.1% upon activation relative to the relaxing state and increased by ∼0.24% in the force generation state, in line with that of the 2.7-nm reflection. Ca 2+ -binding to TN triggered the shortening and a change in the helical symmetry of the thin filaments. Modeling of the structural changes using the intensities of the thin filament-based reflections suggested that the conformation of the globular core domain of TN altered upon activation, undergoing additional conformational changes at the tension plateau. The tail domain of TN moved together with tropomyosin during contraction. The results indicate that the structural changes of regulatory proteins bound to the actin filaments occur in two steps, the first in response to the Ca 2+ -binding and the second induced by actomyosin interaction

TURBULENCE DECAY AND CLOUD CORE RELAXATION IN MOLECULAR CLOUDS

International Nuclear Information System (INIS)

Gao, Yang; Law, Chung K.; Xu, Haitao

2015-01-01

The turbulent motion within molecular clouds is a key factor controlling star formation. Turbulence supports molecular cloud cores from evolving to gravitational collapse and hence sets a lower bound on the size of molecular cloud cores in which star formation can occur. On the other hand, without a continuous external energy source maintaining the turbulence, such as in molecular clouds, the turbulence decays with an energy dissipation time comparable to the dynamic timescale of clouds, which could change the size limits obtained from Jean's criterion by assuming constant turbulence intensities. Here we adopt scaling relations of physical variables in decaying turbulence to analyze its specific effects on the formation of stars. We find that the decay of turbulence provides an additional approach for Jeans' criterion to be achieved, after which gravitational infall governs the motion of the cloud core. This epoch of turbulence decay is defined as cloud core relaxation. The existence of cloud core relaxation provides a more complete understanding of the effect of the competition between turbulence and gravity on the dynamics of molecular cloud cores and star formation

PH Domain-Arf G Protein Interactions Localize the Arf-GEF Steppke for Cleavage Furrow Regulation in Drosophila.

Directory of Open Access Journals (Sweden)

Donghoon M Lee

Full Text Available The recruitment of GDP/GTP exchange factors (GEFs to specific subcellular sites dictates where they activate small G proteins for the regulation of various cellular processes. Cytohesins are a conserved family of plasma membrane GEFs for Arf small G proteins that regulate endocytosis. Analyses of mammalian cytohesins have identified a number of recruitment mechanisms for these multi-domain proteins, but the conservation and developmental roles for these mechanisms are unclear. Here, we report how the pleckstrin homology (PH domain of the Drosophila cytohesin Steppke affects its localization and activity at cleavage furrows of the early embryo. We found that the PH domain is necessary for Steppke furrow localization, and for it to regulate furrow structure. However, the PH domain was not sufficient for the localization. Next, we examined the role of conserved PH domain amino acid residues that are required for mammalian cytohesins to bind PIP3 or GTP-bound Arf G proteins. We confirmed that the Steppke PH domain preferentially binds PIP3 in vitro through a conserved mechanism. However, disruption of residues for PIP3 binding had no apparent effect on GFP-Steppke localization and effects. Rather, residues for binding to GTP-bound Arf G proteins made major contributions to this Steppke localization and activity. By analyzing GFP-tagged Arf and Arf-like small G proteins, we found that Arf1-GFP, Arf6-GFP and Arl4-GFP, but not Arf4-GFP, localized to furrows. However, analyses of embryos depleted of Arf1, Arf6 or Arl4 revealed either earlier defects than occur in embryos depleted of Steppke, or no detectable furrow defects, possibly because of redundancies, and thus it was difficult to assess how individual Arf small G proteins affect Steppke. Nonetheless, our data show that the Steppke PH domain and its conserved residues for binding to GTP-bound Arf G proteins have substantial effects on Steppke localization and activity in early Drosophila embryos.

T-CREST: Time-predictable multi-core architecture for embedded systems

DEFF Research Database (Denmark)

Schoeberl, Martin; Abbaspourseyedi, Sahar; Jordan, Alexander

2015-01-01

-core architectures that are optimized for the WCET instead of the average-case execution time. The resulting time-predictable resources (processors, interconnect, memory arbiter, and memory controller) and tools (compiler, WCET analysis) are designed to ease WCET analysis and to optimize WCET performance. Compared...... domain shows that the WCET can be reduced for computation-intensive tasks when distributing the tasks on several cores and using the network-on-chip for communication. With three cores the WCET is improved by a factor of 1.8 and with 15 cores by a factor of 5.7.The T-CREST project is the result...

Frequency-Domain Robust Performance Condition for Controller Uncertainty in SISO LTI Systems: A Geometric Approach

Directory of Open Access Journals (Sweden)

Vahid Raissi Dehkordi

2009-01-01

Full Text Available This paper deals with the robust performance problem of a linear time-invariant control system in the presence of robust controller uncertainty. Assuming that plant uncertainty is modeled as an additive perturbation, a geometrical approach is followed in order to find a necessary and sufficient condition for robust performance in the form of a bound on the magnitude of controller uncertainty. This frequency domain bound is derived by converting the problem into an optimization problem, whose solution is shown to be more time-efficient than a conventional structured singular value calculation. The bound on controller uncertainty can be used in controller order reduction and implementation problems.

Two high-mobility group box domains act together to underwind and kink DNA

Energy Technology Data Exchange (ETDEWEB)

Sánchez-Giraldo, R.; Acosta-Reyes, F. J. [Universitat Politecnica de Catalunya, 08028 Barcelona (Spain); Malarkey, C. S. [University of Colorado School of Medicine, Aurora, CO 80045 (United States); Saperas, N. [Universitat Politecnica de Catalunya, 08028 Barcelona (Spain); Churchill, M. E. A., E-mail: mair.churchill@ucdenver.edu [University of Colorado School of Medicine, Aurora, CO 80045 (United States); Campos, J. L., E-mail: mair.churchill@ucdenver.edu [Universitat Politecnica de Catalunya, 08028 Barcelona (Spain)

2015-06-30

The crystal structure of HMGB1 box A bound to an unmodified AT-rich DNA fragment is reported at a resolution of 2 Å. A new mode of DNA recognition for HMG box proteins is found in which two box A domains bind in an unusual configuration generating a highly kinked DNA structure. High-mobility group protein 1 (HMGB1) is an essential and ubiquitous DNA architectural factor that influences a myriad of cellular processes. HMGB1 contains two DNA-binding domains, box A and box B, which have little sequence specificity but have remarkable abilities to underwind and bend DNA. Although HMGB1 box A is thought to be responsible for the majority of HMGB1–DNA interactions with pre-bent or kinked DNA, little is known about how it recognizes unmodified DNA. Here, the crystal structure of HMGB1 box A bound to an AT-rich DNA fragment is reported at a resolution of 2 Å. Two box A domains of HMGB1 collaborate in an unusual configuration in which the Phe37 residues of both domains stack together and intercalate the same CG base pair, generating highly kinked DNA. This represents a novel mode of DNA recognition for HMGB proteins and reveals a mechanism by which structure-specific HMG boxes kink linear DNA.

Two high-mobility group box domains act together to underwind and kink DNA

International Nuclear Information System (INIS)

Sánchez-Giraldo, R.; Acosta-Reyes, F. J.; Malarkey, C. S.; Saperas, N.; Churchill, M. E. A.; Campos, J. L.

2015-01-01

The crystal structure of HMGB1 box A bound to an unmodified AT-rich DNA fragment is reported at a resolution of 2 Å. A new mode of DNA recognition for HMG box proteins is found in which two box A domains bind in an unusual configuration generating a highly kinked DNA structure. High-mobility group protein 1 (HMGB1) is an essential and ubiquitous DNA architectural factor that influences a myriad of cellular processes. HMGB1 contains two DNA-binding domains, box A and box B, which have little sequence specificity but have remarkable abilities to underwind and bend DNA. Although HMGB1 box A is thought to be responsible for the majority of HMGB1–DNA interactions with pre-bent or kinked DNA, little is known about how it recognizes unmodified DNA. Here, the crystal structure of HMGB1 box A bound to an AT-rich DNA fragment is reported at a resolution of 2 Å. Two box A domains of HMGB1 collaborate in an unusual configuration in which the Phe37 residues of both domains stack together and intercalate the same CG base pair, generating highly kinked DNA. This represents a novel mode of DNA recognition for HMGB proteins and reveals a mechanism by which structure-specific HMG boxes kink linear DNA

End States, Ladder Compounds, and Domain-Wall Fermions

International Nuclear Information System (INIS)

Creutz, M.

1999-01-01

A magnetic field applied to a cross-linked ladder compound can generate isolated electronic states bound to the ends of the chain. After exploring the interference phenomena responsible, I discuss a connection to the domain-wall approach to chiral fermions in lattice gauge theory. The robust nature of the states under small variations of the bond strengths is tied to chiral symmetry and the multiplicative renormalization of fermion masses. copyright 1999 The American Physical Society

Physical and chemical characteristics of L1689-SMM16, an oscillating prestellar core in Ophiuchus

International Nuclear Information System (INIS)

Chitsazzadeh, S.; Di Francesco, J.; Sadavoy, S. I.; Schnee, S.; Friesen, R. K.; Shimajiri, Y.; Langston, G. I.; Bourke, T. L.; Keto, E. R.; Pineda, J. E.; Takakuwa, S.; Tatematsu, K.

2014-01-01

We present single-dish observations of the L1689-SMM16 core in the Ophiuchus molecular cloud in NH 3 (1, 1) and (2, 2) emission using the Green Bank Telescope, in N 2 H + (1-0) emission using the Nobeyama Radio Observatory, and in NH 2 D (1 1,1 a (--)1 0,1 s ), HCN (1-0), HNC (1-0), H 13 CO + (1-0), and HCO + (1-0) emission using the Mopra telescope. The morphologies of the integrated NH 3 (1, 1) and N 2 H + (1-0) emission well match that of 250 μm continuum emission. Line widths of NH 3 (1, 1) and N 2 H + (1-0) show the presence of transonic turbulence across the core. Jeans and virial analyses made using updated measurements of core mass and size confirm that L1689-SMM16 is prestellar, i.e., gravitationally bound. It also has accumulated more mass compared to its corresponding Jeans mass in the absence of magnetic fields and therefore is a 'super-Jeans' core. The high levels of X(NH 3 )/X(N 2 H + ) and deuterium fractionation reinforce the idea that the core has not yet formed a protostar. Comparing the physical parameters of the core with those of a Bonnor-Ebert sphere reveals the advanced evolutionary stage of L1689-SMM16 and shows that it might be unstable to collapse. We do not detect any evidence of infall motions toward the core. Instead, red asymmetry in the line profiles of HCN (1-0) and HNC (1-0) indicates the expansion of the outer layers of the core at a speed of ∼0.2 km s –1 to 0.3 km s –1 . For a gravitationally bound core, expansion in the outer layers might indicate that the core is experiencing oscillations.

Core competencies for pain management: results of an interprofessional consensus summit.

Science.gov (United States)

Fishman, Scott M; Young, Heather M; Lucas Arwood, Ellyn; Chou, Roger; Herr, Keela; Murinson, Beth B; Watt-Watson, Judy; Carr, Daniel B; Gordon, Debra B; Stevens, Bonnie J; Bakerjian, Debra; Ballantyne, Jane C; Courtenay, Molly; Djukic, Maja; Koebner, Ian J; Mongoven, Jennifer M; Paice, Judith A; Prasad, Ravi; Singh, Naileshni; Sluka, Kathleen A; St Marie, Barbara; Strassels, Scott A

2013-07-01

The objective of this project was to develop core competencies in pain assessment and management for prelicensure health professional education. Such core pain competencies common to all prelicensure health professionals have not been previously reported. An interprofessional executive committee led a consensus-building process to develop the core competencies. An in-depth literature review was conducted followed by engagement of an interprofessional Competency Advisory Committee to critique competencies through an iterative process. A 2-day summit was held so that consensus could be reached. The consensus-derived competencies were categorized within four domains: multidimensional nature of pain, pain assessment and measurement, management of pain, and context of pain management. These domains address the fundamental concepts and complexity of pain; how pain is observed and assessed; collaborative approaches to treatment options; and application of competencies across the life span in the context of various settings, populations, and care team models. A set of values and guiding principles are embedded within each domain. These competencies can serve as a foundation for developing, defining, and revising curricula and as a resource for the creation of learning activities across health professions designed to advance care that effectively responds to pain. Wiley Periodicals, Inc.

Curvature bound from gravitational catalysis

Science.gov (United States)

Gies, Holger; Martini, Riccardo

2018-04-01

We determine bounds on the curvature of local patches of spacetime from the requirement of intact long-range chiral symmetry. The bounds arise from a scale-dependent analysis of gravitational catalysis and its influence on the effective potential for the chiral order parameter, as induced by fermionic fluctuations on a curved spacetime with local hyperbolic properties. The bound is expressed in terms of the local curvature scalar measured in units of a gauge-invariant coarse-graining scale. We argue that any effective field theory of quantum gravity obeying this curvature bound is safe from chiral symmetry breaking through gravitational catalysis and thus compatible with the simultaneous existence of chiral fermions in the low-energy spectrum. With increasing number of dimensions, the curvature bound in terms of the hyperbolic scale parameter becomes stronger. Applying the curvature bound to the asymptotic safety scenario for quantum gravity in four spacetime dimensions translates into bounds on the matter content of particle physics models.

Stabilization of solutions of quasilinear second order parabolic equations in domains with non-compact boundaries

International Nuclear Information System (INIS)

Karimov, Ruslan Kh; Kozhevnikova, Larisa M

2010-01-01

The first mixed problem with homogeneous Dirichlet boundary condition and initial function with compact support is considered for quasilinear second order parabolic equations in a cylindrical domain D=(0,∞)xΩ. Upper bounds are obtained, which give the rate of decay of the solutions as t→∞ as a function of the geometry of the unbounded domain Ω subset of R n , n≥2. Bibliography: 18 titles.

Non-cooperative immobilization of residual water bound in lyophilized photosynthetic lamellae.

Science.gov (United States)

Harańczyk, Hubert; Baran, Ewelina; Nowak, Piotr; Florek-Wojciechowska, Małgorzata; Leja, Anna; Zalitacz, Dorota; Strzałka, Kazimierz

2015-12-01

This study applied 1H-NMR in time and in frequency domain measurements to monitor the changes that occur in bound water dynamics at decreased temperature and with increased hydration level in lyophilizates of native wheat photosynthetic lamellae and in photosynthetic lamellae reconstituted from lyophilizate. Proton relaxometry (measured as free induction decay = FID) distinguishes a Gaussian component S within the NMR signal (o). This comes from protons of the solid matrix of the lamellae and consists of (i) an exponentially decaying contribution L1 from mobile membrane protons, presumably from lipids, and from water that is tightly bound to the membrane surface and thus restricted in mobility; and (ii) an exponentially decaying component L2 from more mobile, loosely bound water pool. Both proton relaxometry data and proton spectroscopy show that dry lyophilizate incubated in dry air, i.e., at a relative humidity (p/p0) of 0% reveals a relatively high hydration level. The observed liquid signal most likely originates from mobile membrane protons and a tightly bound water fraction that is sealed in pores of dry lyophilizate and thus restricted in mobility. The estimations suggest that the amount of sealed water does not exceed the value characteristic for the main hydration shell of a phospholipid. Proton spectra collected for dry lyophilizate of photosynthetic lamellae show a continuous decrease in the liquid signal component without a distinct freezing transition when it is cooled down to -60ºC, which is significantly lower than the homogeneous ice nucleation temperature [Bronshteyn, V.L. et al. Biophys. J. 65 (1993) 1853].

USE OF BOUNDING ANALYSES TO ESTIMATE THE PREFORMANCE OF A SEISMICALLY ISOLATED STRUCTURE

Directory of Open Access Journals (Sweden)

Gökhan ÖZDEMİR

2017-03-01

Full Text Available Current design approach for seismic isolated structures is to perform bounding analyses. These analyses provide an envelope for the response of the seismic isolated structure rather than focusing on the actual performance. In this study, the success of bounding analyses to estimate performance of a seismic isolated structure, in which the isolation is provided by means of lead rubber bearings (LRBs, is evaluated in a comparative manner. For this purpose, nonlinear response history analyses were performed under the effect of bidirectional ground motion excitations. In bounding analyses, non-deteriorating hysteretic representations were used to model the hysteretic behavior of LRBs. On the other hand, to estimate the actual performance of both the superstructure and isolator units, deteriorating hysteretic idealizations were employed. The deterioration in strength of LRBs was defined as a function of temperature rise in the lead core. The analyzed structure is an existing seismically isolated hospital building and analytically modeled in accordance with its reported design properties for both isolation units and superstructure. Results obtained from analyses where LRBs are idealized by both deteriorating and non-deteriorating hysteretic representations are used in the comparisons. The response quantities used in the comparisons are maximum isolator displacement, maximum isolator force, maximum absolute floor acceleration, and maximum relative story displacements. In an average sense, bounding analyses is found to provide conservative estimates for the selected response quantities and fulfills its intended purpose. However, it is revealed that there may be individual cases where bounding analyses fails to provide a safe envelope.

Electrically Small Magnetic Dipole Antennas With Quality Factors Approaching the Chu Lower Bound

DEFF Research Database (Denmark)

Kim, Oleksiy S.; Breinbjerg, Olav; Yaghjian, Arthur D.

2010-01-01

We investigate the quality factor Q for electrically small current distributions and practical antenna designs radiating the TE10 magnetic dipole field. The current distributions and the antenna designs employ electric currents on a spherical surface enclosing a magneto-dielectric material...... numerically. It is found that for a given antenna size and permittivity there is an optimum permeability that ensures the lowest possible Q, and this optimum permeability is inversely proportional to the square of the antenna electrical radius. When the relative permittivity is equal to 1, the optimum...... permeability yields the quality factor Q that constitutes the lower bound for a magnetic dipole antenna with a magneto-dielectric core. Furthermore, the smaller the antenna the closer its quality factor Q can approach the Chu lower bound. Simulated results for the TE10-mode multiarm spherical helix antenna...

Time domain-nuclear magnetic resonance study of chars from southern hardwoods

International Nuclear Information System (INIS)

Elder, Thomas; Labbe, Nicole; Harper, David; Rials, Timothy

2006-01-01

Chars from the thermal degradation of silver maple (Acer saccharinum), red maple (Acer rubrum), sugar maple (Acer saccharum), and white oak (Quercus spp.), performed at temperatures from 250 to 350 o C, were examined using time domain-nuclear magnetic resonance spectroscopy. Prior to analysis, the chars were equilibrated under conditions insuring the presence of bound water only and both bound water and free water. Transverse relaxation times were found to be related to the moisture content of the chars, which varied with temperature. At elevated temperatures the number of signals assigned to free water decreased, indicative of an increase in pore size within the chars

Phosphorylation Regulates the Bound Structure of an Intrinsically Disordered Protein: The p53-TAZ2 Case.

Directory of Open Access Journals (Sweden)

Raúl Esteban Ithuralde

Full Text Available Disordered regions and Intrinsically Disordered Proteins (IDPs are involved in critical cellular processes and may acquire a stable three-dimensional structure only upon binding to their partners. IDPs may follow a folding-after-binding process, known as induced folding, or a folding-before-binding process, known as conformational selection. The transcription factor p53 is involved in the regulation of cellular events that arise upon stress or DNA damage. The p53 domain structure is composed of an N-terminal transactivation domain (p53TAD, a DNA Binding Domain and a tetramerization domain. The activity of TAD is tightly regulated by interactions with cofactors, inhibitors and phosphorylation. To initiate transcription, p53TAD binds to the TAZ2 domain of CBP, a co-transcription factor, and undergoes a folding and binding process, as revealed by the recent NMR structure of the complex. The activity of p53 is regulated by phosphorylation at multiple sites on the TAD domain and recent studies have shown that modifications at three residues affect the binding towards TAZ2. However, we still do not know how these phosphorylations affect the structure of the bound state and, therefore, how they regulate the p53 function. In this work, we have used computational simulations to understand how phosphorylation affects the structure of the p53TAD:TAZ2 complex and regulates the recognition mechanism. Phosphorylation has been proposed to enhance binding by direct interaction with the folded protein or by changing the unbound conformation of IDPs, for example by pre-folding the protein favoring the recognition mechanism. Here, we show an interesting turn in the p53 case: phosphorylation mainly affects the bound structure of p53TAD, highlighting the complexity of IDP protein-protein interactions. Our results are in agreement with previous experimental studies, allowing a clear picture of how p53 is regulated by phosphorylation and giving new insights into how

A disappearing heritage: the clinical core of schizophrenia

DEFF Research Database (Denmark)

Parnas, Josef

2011-01-01

("schizoidia" and "latent schizophrenia"). The fundamental features are manifest across all domains of consciousness: subjective experience, expression, cognition, affectivity, behavior, and willing. Yet, the specificity of the core was only graspable at a more comprehensive Gestalt-level, variously designated...

Domain activities of PapC usher reveal the mechanism of action of an Escherichia coli molecular machine.

Science.gov (United States)

Volkan, Ender; Ford, Bradley A; Pinkner, Jerome S; Dodson, Karen W; Henderson, Nadine S; Thanassi, David G; Waksman, Gabriel; Hultgren, Scott J

2012-06-12

P pili are prototypical chaperone-usher pathway-assembled pili used by Gram-negative bacteria to adhere to host tissues. The PapC usher contains five functional domains: a transmembrane β-barrel, a β-sandwich Plug, an N-terminal (periplasmic) domain (NTD), and two C-terminal (periplasmic) domains, CTD1 and CTD2. Here, we delineated usher domain interactions between themselves and with chaperone-subunit complexes and showed that overexpression of individual usher domains inhibits pilus assembly. Prior work revealed that the Plug domain occludes the pore of the transmembrane domain of a solitary usher, but the chaperone-adhesin-bound usher has its Plug displaced from the pore, adjacent to the NTD. We demonstrate an interaction between the NTD and Plug domains that suggests a biophysical basis for usher gating. Furthermore, we found that the NTD exhibits high-affinity binding to the chaperone-adhesin (PapDG) complex and low-affinity binding to the major tip subunit PapE (PapDE). We also demonstrate that CTD2 binds with lower affinity to all tested chaperone-subunit complexes except for the chaperone-terminator subunit (PapDH) and has a catalytic role in dissociating the NTD-PapDG complex, suggesting an interplay between recruitment to the NTD and transfer to CTD2 during pilus initiation. The Plug domain and the NTD-Plug complex bound all of the chaperone-subunit complexes tested including PapDH, suggesting that the Plug actively recruits chaperone-subunit complexes to the usher and is the sole recruiter of PapDH. Overall, our studies reveal the cooperative, active roles played by periplasmic domains of the usher to initiate, grow, and terminate a prototypical chaperone-usher pathway pilus.

Deeply bound pionic atom

International Nuclear Information System (INIS)

Toki, Hiroshi; Yamazaki, Toshimitsu

1989-01-01

The standard method of pionic atom formation does not produce deeply bound pionic atoms. A study is made on the properties of deeply bound pionic atom states by using the standard pion-nucleus optical potential. Another study is made to estimate the cross sections of the formation of ls pionic atom states by various methods. The pion-nucleus optical potential is determined by weakly bound pionic atom states and pion nucleus scattering. Although this potential may not be valid for deeply bound pionic atoms, it should provide some hint on binding energies and level widths of deeply bound states. The width of the ls state comes out to be 0.3 MeV and is well separated from the rest. The charge dependence of the ls state is investigated. The binding energies and the widths increase linearly with Z azbove a Z of 30. The report then discusses various methods to populate deeply bound pionic atoms. In particular, 'pion exchange' reactions are proposed. (n, pπ) reaction is discussed first. The cross section is calculated by assuming the in- and out-going nucleons on-shell and the produced pion in (n1) pionic atom states. Then, (n, dπ - ) cross sections are estimated. (p, 2 Heπ - ) reaction would have cross sections similar to the cross section of (n, dπ - ) reaction. In conclusion, it seems best to do (n, p) experiment on heavy nuclei for deeply bound pionic atom. (Nogami, K.)

Bounding species distribution models

Directory of Open Access Journals (Sweden)

Thomas J. STOHLGREN, Catherine S. JARNEVICH, Wayne E. ESAIAS,Jeffrey T. MORISETTE

2011-10-01

Full Text Available Species distribution models are increasing in popularity for mapping suitable habitat for species of management concern. Many investigators now recognize that extrapolations of these models with geographic information systems (GIS might be sensitive to the environmental bounds of the data used in their development, yet there is no recommended best practice for “clamping” model extrapolations. We relied on two commonly used modeling approaches: classification and regression tree (CART and maximum entropy (Maxent models, and we tested a simple alteration of the model extrapolations, bounding extrapolations to the maximum and minimum values of primary environmental predictors, to provide a more realistic map of suitable habitat of hybridized Africanized honey bees in the southwestern United States. Findings suggest that multiple models of bounding, and the most conservative bounding of species distribution models, like those presented here, should probably replace the unbounded or loosely bounded techniques currently used [Current Zoology 57 (5: 642–647, 2011].

Bounding Species Distribution Models

Science.gov (United States)

Stohlgren, Thomas J.; Jarnevich, Cahterine S.; Morisette, Jeffrey T.; Esaias, Wayne E.

2011-01-01

Species distribution models are increasing in popularity for mapping suitable habitat for species of management concern. Many investigators now recognize that extrapolations of these models with geographic information systems (GIS) might be sensitive to the environmental bounds of the data used in their development, yet there is no recommended best practice for "clamping" model extrapolations. We relied on two commonly used modeling approaches: classification and regression tree (CART) and maximum entropy (Maxent) models, and we tested a simple alteration of the model extrapolations, bounding extrapolations to the maximum and minimum values of primary environmental predictors, to provide a more realistic map of suitable habitat of hybridized Africanized honey bees in the southwestern United States. Findings suggest that multiple models of bounding, and the most conservative bounding of species distribution models, like those presented here, should probably replace the unbounded or loosely bounded techniques currently used [Current Zoology 57 (5): 642-647, 2011].

Dark matter halos with cores from hierarchical structure formation

International Nuclear Information System (INIS)

Strigari, Louis E.; Kaplinghat, Manoj; Bullock, James S.

2007-01-01

We show that dark matter emerging from late decays (z or approx. 0.1 Mpc), and simultaneously generates observable constant-density cores in small dark matter halos. We refer to this class of models as meta-cold dark matter (mCDM), because it is born with nonrelativistic velocities from the decays of cold thermal relics. The constant-density cores are a result of the low phase-space density of mCDM at birth. Warm dark matter cannot produce similar size phase-space limited cores without saturating the Lyα power spectrum bounds. Dark matter-dominated galaxy rotation curves and stellar velocity dispersion profiles may provide the best means to discriminate between mCDM and CDM. mCDM candidates are motivated by the particle spectrum of supersymmetric and extra dimensional extensions to the standard model of particle physics

Vortex cores and vortex motion in superconductors with anisotropic Fermi surfaces

Energy Technology Data Exchange (ETDEWEB)

Galvis, J.A. [Laboratorio de Bajas Temperaturas, Departamento de Física de la Materia Condensada, Instituto de Ciencia de Materiales Nicolás Cabrera, Condensed Matter Physics Center (IFIMAC), Facultad de Ciencias, Universidad Autónoma de Madrid, E-28049 Madrid (Spain); Departamento de Ciencias Naturales, Facultad de ingeniería y Ciencias Básicas, Universidad Central, Bogotá (Colombia); National High Magnetic Field Laboratory, Florida State University, Tallahassee, Florida 32310 (United States); Herrera, E.; Guillamón, I.; Vieira, S. [Laboratorio de Bajas Temperaturas, Departamento de Física de la Materia Condensada, Instituto de Ciencia de Materiales Nicolás Cabrera, Condensed Matter Physics Center (IFIMAC), Facultad de Ciencias, Universidad Autónoma de Madrid, E-28049 Madrid (Spain); Unidad Asociada de Altos Campos Magnéticos y Bajas Temperaturas, UAM, CSIC, Madrid (Spain); Suderow, H., E-mail: hermann.suderow@uam.es [Laboratorio de Bajas Temperaturas, Departamento de Física de la Materia Condensada, Instituto de Ciencia de Materiales Nicolás Cabrera, Condensed Matter Physics Center (IFIMAC), Facultad de Ciencias, Universidad Autónoma de Madrid, E-28049 Madrid (Spain); Unidad Asociada de Altos Campos Magnéticos y Bajas Temperaturas, UAM, CSIC, Madrid (Spain)

2017-02-15

Highlights: • The observation of vortex cores is reviewed, with emphasis in new experiments. • Vortex cores are follow superconducting gap and Fermi surface shapes. • The vortex core shape influences vortex dynamics. - Abstract: Explaning static and dynamic properties of the vortex lattice in anisotropic superconductors requires a careful characterization of vortex cores. The vortex core contains Andreev bound states whose spatial extension depends on the anisotropy of the electronic band-structure and superconducting gap. This might have an impact on the anisotropy of the superconducting properties and on vortex dynamics. Here we briefly summarize basic concepts to understand anisotropic vortex cores and review vortex core imaging experiments. We further discuss moving vortex lattices and the influence of vortex core shape in vortex motion. We find vortex motion in highly tilted magnetic fields. We associate vortex motion to the vortex entry barrier and the screening currents at the surface. We find preferential vortex motion along the main axis of the vortex lattice. After travelling integers of the intervortex distance, we find that vortices move more slowly due to the washboard potential of the vortex lattice.

Vortex cores and vortex motion in superconductors with anisotropic Fermi surfaces

International Nuclear Information System (INIS)

Galvis, J.A.; Herrera, E.; Guillamón, I.; Vieira, S.; Suderow, H.

2017-01-01

Highlights: • The observation of vortex cores is reviewed, with emphasis in new experiments. • Vortex cores are follow superconducting gap and Fermi surface shapes. • The vortex core shape influences vortex dynamics. - Abstract: Explaning static and dynamic properties of the vortex lattice in anisotropic superconductors requires a careful characterization of vortex cores. The vortex core contains Andreev bound states whose spatial extension depends on the anisotropy of the electronic band-structure and superconducting gap. This might have an impact on the anisotropy of the superconducting properties and on vortex dynamics. Here we briefly summarize basic concepts to understand anisotropic vortex cores and review vortex core imaging experiments. We further discuss moving vortex lattices and the influence of vortex core shape in vortex motion. We find vortex motion in highly tilted magnetic fields. We associate vortex motion to the vortex entry barrier and the screening currents at the surface. We find preferential vortex motion along the main axis of the vortex lattice. After travelling integers of the intervortex distance, we find that vortices move more slowly due to the washboard potential of the vortex lattice.

Structural evaluation of fast reactor core restraint with irradiation creep-swelling opposition effects

International Nuclear Information System (INIS)

Kalinowski, J.E.

1979-01-01

Irradiation creep and swelling correlations are derived from primary loading in-reactor experiments in which irradiation creep and swelling act in the same direction. When correlation uncertainty bands are applied in core restraint evaluations, significant variability in sub-assembly behavior is predicted. For example, sub-assemblies in the outer core region where neutron flux and duct temperature gradients are significant exhibit bowing responses ranging from a creep dominated outward bow to a swelling dominated inward bow. Furthermore, solutions based on upper bound and lower bound correlation uncertainty combinations are observed to cross-over indicating that such combinations are physically unrealistic in the assessment of creep-swelling opposition effects. In order to obtain realistic upper and lower bound sub-assembly responses, judgement must be applied in the selection of creep-swelling equation uncertainty combinations. Experimental programs have been defined which will provide the needed basic as well as prototypic creep-swelling opposition data for reference and advanced sub-assembly duct alloys. The first of these is an irradiation of cylindrical capsules subjected to a through-wall temperature gradient. This test which is presently underway in the EBR-II reactor will provide the data needed to refine irradiation creep and swelling correlations and their associated uncertainties when applied to core restraint evaluations. Restrained pin and duct bowing experiments in FFTF have also been defined. These will provide the prototypic data necessary to verify irradiated duct bowing methodology. The results of this experimental program are expected to reduce creep and swelling uncertainties and permit better definition of the design window for load plane gaps. (orig.)

Negative Nominal Interest Rates: Three ways to overcome the zero lower bound

OpenAIRE

Willem H. Buiter

2009-01-01

The paper considers three methods for eliminating the zero lower bound on nominal interest rates and thus for restoring symmetry to domain over which the central bank can vary its policy rate. They are: (1) abolishing currency (which would also be a useful crime-fighting measure); (2) paying negative interest on currency by taxing currency; and (3) decoupling the numéraire from the currency/medium of exchange/means of payment and introducing an exchange rate between the numéraire and the curr...

Expression, purification, and functional analysis of the C-terminal domain of Herbaspirillum seropedicae NifA protein.

Science.gov (United States)

Monteiro, Rose A; Souza, Emanuel M; Geoffrey Yates, M; Steffens, M Berenice R; Pedrosa, Fábio O; Chubatsu, Leda S

2003-02-01

The Herbaspirillum seropedicae NifA protein is responsible for nif gene expression. The C-terminal domain of the H. seropedicae NifA protein, fused to a His-Tag sequence (His-Tag-C-terminal), was over-expressed and purified by metal-affinity chromatography to yield a highly purified and active protein. Band-shift assays showed that the NifA His-Tag-C-terminal bound specifically to the H. seropedicae nifB promoter region in vitro. In vivo analysis showed that this protein inhibited the Central + C-terminal domains of NifA protein from activating the nifH promoter of K. pneumoniae in Escherichia coli, indicating that the protein must be bound to the NifA-binding site (UAS site) at the nifH promoter region to activate transcription. Copyright 2002 Elsevier Science (USA)

Factors Affecting the Binding of a Recombinant Heavy Metal-Binding Domain (CXXC motif Protein to Heavy Metals

Directory of Open Access Journals (Sweden)

Kamala Boonyodying

2012-06-01

Full Text Available A number of heavy metal-binding proteins have been used to study bioremediation. CXXC motif, a metal binding domain containing Cys-X-X-Cys motif, has been identified in various organisms. These proteins are capable of binding various types of heavy metals. In this study, heavy metal binding domain (CXXC motif recombinant protein encoded from mcsA gene of S. aureus were cloned and overexpressed in Escherichia coli. The factors involved in the metal-binding activity were determined in order to analyze the potential of recombinant protein for bioremediation. A recombinant protein can be bound to Cd2+, Co2+, Cu2+ and Zn2+. The thermal stability of a recombinant protein was tested, and the results showed that the metal binding activity to Cu2+ and Zn2+ still exist after treating the protein at 85ºC for 30 min. The temperature and pH that affected the metal binding activity was tested and the results showed that recombinant protein was still bound to Cu2+ at 65ºC, whereas a pH of 3-7 did not affect the metal binding E. coli harboring a pRset with a heavy metal-binding domain CXXC motif increased the resistance of heavy metals against CuCl2 and CdCl2. This study shows that metal binding domain (CXXC motif recombinant protein can be effectively bound to various types of heavy metals and may be used as a potential tool for studying bioremediation.

Using context to improve protein domain identification

Directory of Open Access Journals (Sweden)

Llinás Manuel

2011-03-01

Full Text Available Abstract Background Identifying domains in protein sequences is an important step in protein structural and functional annotation. Existing domain recognition methods typically evaluate each domain prediction independently of the rest. However, the majority of proteins are multidomain, and pairwise domain co-occurrences are highly specific and non-transitive. Results Here, we demonstrate how to exploit domain co-occurrence to boost weak domain predictions that appear in previously observed combinations, while penalizing higher confidence domains if such combinations have never been observed. Our framework, Domain Prediction Using Context (dPUC, incorporates pairwise "context" scores between domains, along with traditional domain scores and thresholds, and improves domain prediction across a variety of organisms from bacteria to protozoa and metazoa. Among the genomes we tested, dPUC is most successful at improving predictions for the poorly-annotated malaria parasite Plasmodium falciparum, for which over 38% of the genome is currently unannotated. Our approach enables high-confidence annotations in this organism and the identification of orthologs to many core machinery proteins conserved in all eukaryotes, including those involved in ribosomal assembly and other RNA processing events, which surprisingly had not been previously known. Conclusions Overall, our results demonstrate that this new context-based approach will provide significant improvements in domain and function prediction, especially for poorly understood genomes for which the need for additional annotations is greatest. Source code for the algorithm is available under a GPL open source license at http://compbio.cs.princeton.edu/dpuc/. Pre-computed results for our test organisms and a web server are also available at that location.

Big Data analytics in the Geo-Spatial Domain

NARCIS (Netherlands)

R.A. Goncalves (Romulo); M.G. Ivanova (Milena); M.L. Kersten (Martin); H. Scholten; S. Zlatanova; F. Alvanaki (Foteini); P. Nourian (Pirouz); E. Dias

2014-01-01

htmlabstractBig data collections in many scientific domains have inherently rich spatial and geo-spatial features. Spatial location is among the core aspects of data in Earth observation sciences, astronomy, and seismology to name a few. The goal of our project is to design an efficient data

Quantifying information transfer by protein domains: Analysis of the Fyn SH2 domain structure

Directory of Open Access Journals (Sweden)

Serrano Luis

2008-10-01

Full Text Available Abstract Background Efficient communication between distant sites within a protein is essential for cooperative biological response. Although often associated with large allosteric movements, more subtle changes in protein dynamics can also induce long-range correlations. However, an appropriate formalism that directly relates protein structural dynamics to information exchange between functional sites is still lacking. Results Here we introduce a method to analyze protein dynamics within the framework of information theory and show that signal transduction within proteins can be considered as a particular instance of communication over a noisy channel. In particular, we analyze the conformational correlations between protein residues and apply the concept of mutual information to quantify information exchange. Mapping out changes of mutual information on the protein structure then allows visualizing how distal communication is achieved. We illustrate the approach by analyzing information transfer by the SH2 domain of Fyn tyrosine kinase, obtained from Monte Carlo dynamics simulations. Our analysis reveals that the Fyn SH2 domain forms a noisy communication channel that couples residues located in the phosphopeptide and specificity binding sites and a number of residues at the other side of the domain near the linkers that connect the SH2 domain to the SH3 and kinase domains. We find that for this particular domain, communication is affected by a series of contiguous residues that connect distal sites by crossing the core of the SH2 domain. Conclusion As a result, our method provides a means to directly map the exchange of biological information on the structure of protein domains, making it clear how binding triggers conformational changes in the protein structure. As such it provides a structural road, next to the existing attempts at sequence level, to predict long-range interactions within protein structures.

Labeling schemes for bounded degree graphs

DEFF Research Database (Denmark)

Adjiashvili, David; Rotbart, Noy Galil

2014-01-01

We investigate adjacency labeling schemes for graphs of bounded degree Δ = O(1). In particular, we present an optimal (up to an additive constant) log n + O(1) adjacency labeling scheme for bounded degree trees. The latter scheme is derived from a labeling scheme for bounded degree outerplanar...... graphs. Our results complement a similar bound recently obtained for bounded depth trees [Fraigniaud and Korman, SODA 2010], and may provide new insights for closing the long standing gap for adjacency in trees [Alstrup and Rauhe, FOCS 2002]. We also provide improved labeling schemes for bounded degree...

iPfam: a database of protein family and domain interactions found in the Protein Data Bank.

Science.gov (United States)

Finn, Robert D; Miller, Benjamin L; Clements, Jody; Bateman, Alex

2014-01-01

The database iPfam, available at http://ipfam.org, catalogues Pfam domain interactions based on known 3D structures that are found in the Protein Data Bank, providing interaction data at the molecular level. Previously, the iPfam domain-domain interaction data was integrated within the Pfam database and website, but it has now been migrated to a separate database. This allows for independent development, improving data access and giving clearer separation between the protein family and interactions datasets. In addition to domain-domain interactions, iPfam has been expanded to include interaction data for domain bound small molecule ligands. Functional annotations are provided from source databases, supplemented by the incorporation of Wikipedia articles where available. iPfam (version 1.0) contains >9500 domain-domain and 15 500 domain-ligand interactions. The new website provides access to this data in a variety of ways, including interactive visualizations of the interaction data.

Dissecting zero modes and bound states on BPS vortices in Ginzburg-Landau superconductors

Energy Technology Data Exchange (ETDEWEB)

Izquierdo, A. Alonso [Departamento de Matematica Aplicada, Universidad de Salamanca,Facultad de Ciencias Agrarias y Ambientales,Av. Filiberto Villalobos 119, E-37008 Salamanca (Spain); Fuertes, W. Garcia [Departamento de Fisica, Universidad de Oviedo, Facultad de Ciencias,Calle Calvo Sotelo s/n, E-33007 Oviedo (Spain); Guilarte, J. Mateos [Departamento de Fisica Fundamental, Universidad de Salamanca, Facultad de Ciencias,Plaza de la Merced, E-37008 Salamanca (Spain)

2016-05-12

In this paper the zero modes of fluctuation of cylindrically symmetric self-dual vortices are analyzed and described in full detail. These BPS topological defects arise at the critical point between Type II and Type I superconductors, or, equivalently, when the masses of the Higgs particle and the vector boson in the Abelian Higgs model are equal. In addition, novel bound states of Higss and vector bosons trapped by the self-dual vortices at their core are found and investigated.

Domain decomposition methods for the mixed dual formulation of the critical neutron diffusion problem; Methodes de decomposition de domaine pour la formulation mixte duale du probleme critique de la diffusion des neutrons

Energy Technology Data Exchange (ETDEWEB)

Guerin, P

2007-12-15

The neutronic simulation of a nuclear reactor core is performed using the neutron transport equation, and leads to an eigenvalue problem in the steady-state case. Among the deterministic resolution methods, diffusion approximation is often used. For this problem, the MINOS solver based on a mixed dual finite element method has shown his efficiency. In order to take advantage of parallel computers, and to reduce the computing time and the local memory requirement, we propose in this dissertation two domain decomposition methods for the resolution of the mixed dual form of the eigenvalue neutron diffusion problem. The first approach is a component mode synthesis method on overlapping sub-domains. Several Eigenmodes solutions of a local problem solved by MINOS on each sub-domain are taken as basis functions used for the resolution of the global problem on the whole domain. The second approach is a modified iterative Schwarz algorithm based on non-overlapping domain decomposition with Robin interface conditions. At each iteration, the problem is solved on each sub domain by MINOS with the interface conditions deduced from the solutions on the adjacent sub-domains at the previous iteration. The iterations allow the simultaneous convergence of the domain decomposition and the eigenvalue problem. We demonstrate the accuracy and the efficiency in parallel of these two methods with numerical results for the diffusion model on realistic 2- and 3-dimensional cores. (author)

Structure and function of the catalytic domain of the dihydrolipoyl acetyltransferase component in Escherichia coli pyruvate dehydrogenase complex.

Science.gov (United States)

Wang, Junjie; Nemeria, Natalia S; Chandrasekhar, Krishnamoorthy; Kumaran, Sowmini; Arjunan, Palaniappa; Reynolds, Shelley; Calero, Guillermo; Brukh, Roman; Kakalis, Lazaros; Furey, William; Jordan, Frank

2014-05-30

The Escherichia coli pyruvate dehydrogenase complex (PDHc) catalyzing conversion of pyruvate to acetyl-CoA comprises three components: E1p, E2p, and E3. The E2p is the five-domain core component, consisting of three tandem lipoyl domains (LDs), a peripheral subunit binding domain (PSBD), and a catalytic domain (E2pCD). Herein are reported the following. 1) The x-ray structure of E2pCD revealed both intra- and intertrimer interactions, similar to those reported for other E2pCDs. 2) Reconstitution of recombinant LD and E2pCD with E1p and E3p into PDHc could maintain at least 6.4% activity (NADH production), confirming the functional competence of the E2pCD and active center coupling among E1p, LD, E2pCD, and E3 even in the absence of PSBD and of a covalent link between domains within E2p. 3) Direct acetyl transfer between LD and coenzyme A catalyzed by E2pCD was observed with a rate constant of 199 s(-1), comparable with the rate of NADH production in the PDHc reaction. Hence, neither reductive acetylation of E2p nor acetyl transfer within E2p is rate-limiting. 4) An unprecedented finding is that although no interaction could be detected between E1p and E2pCD by itself, a domain-induced interaction was identified on E1p active centers upon assembly with E2p and C-terminally truncated E2p proteins by hydrogen/deuterium exchange mass spectrometry. The inclusion of each additional domain of E2p strengthened the interaction with E1p, and the interaction was strongest with intact E2p. E2p domain-induced changes at the E1p active site were also manifested by the appearance of a circular dichroism band characteristic of the canonical 4'-aminopyrimidine tautomer of bound thiamin diphosphate (AP). © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

SH2 domains of the p85 alpha subunit of phosphatidylinositol 3-kinase regulate binding to growth factor receptors.

Science.gov (United States)

McGlade, C J; Ellis, C; Reedijk, M; Anderson, D; Mbamalu, G; Reith, A D; Panayotou, G; End, P; Bernstein, A; Kazlauskas, A

1992-01-01

The binding of cytoplasmic signaling proteins such as phospholipase C-gamma 1 and Ras GTPase-activating protein to autophosphorylated growth factor receptors is directed by their noncatalytic Src homology region 2 (SH2) domains. The p85 alpha regulatory subunit of phosphatidylinositol (PI) 3-kinase, which associates with several receptor protein-tyrosine kinases, also contains two SH2 domains. Both p85 alpha SH2 domains, when expressed individually as fusion proteins in bacteria, bound stably to the activated beta receptor for platelet-derived growth factor (PDGF). Complex formation required PDGF stimulation and was dependent on receptor tyrosine kinase activity. The bacterial p85 alpha SH2 domains recognized activated beta PDGF receptor which had been immobilized on a filter, indicating that SH2 domains contact autophosphorylated receptors directly. Several receptor tyrosine kinases within the PDGF receptor subfamily, including the colony-stimulating factor 1 receptor and the Steel factor receptor (Kit), also associate with PI 3-kinase in vivo. Bacterially expressed SH2 domains derived from the p85 alpha subunit of PI 3-kinase bound in vitro to the activated colony-stimulating factor 1 receptor and to Kit. We infer that the SH2 domains of p85 alpha bind to high-affinity sites on these receptors, whose creation is dependent on receptor autophosphorylation. The SH2 domains of p85 are therefore primarily responsible for the binding of PI 3-kinase to activated growth factor receptors. Images PMID:1372092

Differential Stoichiometry among Core Ribosomal Proteins

Directory of Open Access Journals (Sweden)

Nikolai Slavov

2015-11-01

Full Text Available Understanding the regulation and structure of ribosomes is essential to understanding protein synthesis and its dysregulation in disease. While ribosomes are believed to have a fixed stoichiometry among their core ribosomal proteins (RPs, some experiments suggest a more variable composition. Testing such variability requires direct and precise quantification of RPs. We used mass spectrometry to directly quantify RPs across monosomes and polysomes of mouse embryonic stem cells (ESC and budding yeast. Our data show that the stoichiometry among core RPs in wild-type yeast cells and ESC depends both on the growth conditions and on the number of ribosomes bound per mRNA. Furthermore, we find that the fitness of cells with a deleted RP-gene is inversely proportional to the enrichment of the corresponding RP in polysomes. Together, our findings support the existence of ribosomes with distinct protein composition and physiological function.

Core-shell microparticles for protein sequestration and controlled release of a protein-laden core.

Science.gov (United States)

Rinker, Torri E; Philbrick, Brandon D; Temenoff, Johnna S

2017-07-01

core-shell heparin-PEG microparticles presented here overcome this limitation by sequestering proteins through a PEG-based shell onto a protein-protective heparin core, temporarily isolating bound proteins from the cellular microenvironment, and re-delivering proteins only after degradation of the PEG-based shell. Thus, these core-shell microparticles have potential to be a novel tool to harness and isolate proteins produced in the cellular environment and then control when proteins are re-introduced for the most effective tissue regeneration and repair. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

ATP forms a stable complex with the essential histidine kinase WalK (YycG) domain

Energy Technology Data Exchange (ETDEWEB)

Celikel, Reha; Veldore, Vidya Harini [University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205 (United States); Mathews, Irimpan [Stanford Synchrotron Radiation Lightsource, 2575 Sand Hill Road, Menlo Park, CA 94025 (United States); Devine, Kevin M., E-mail: kdevine@tcd.ie [Trinity College Dublin, Dublin 2 (Ireland); Varughese, Kottayil I., E-mail: kdevine@tcd.ie [University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205 (United States)

2012-07-01

The histidine WalK (YycG) plays a crucial role in coordinating murein synthesis with cell division and the crystal structure of its ATP binding domain has been determined. Interestingly the bound ATP was not hydrolyzed during crystallization and remains intact in the crystal lattice. In Bacillus subtilis, the WalRK (YycFG) two-component system coordinates murein synthesis with cell division. It regulates the expression of autolysins that function in cell-wall remodeling and of proteins that modulate autolysin activity. The transcription factor WalR is activated upon phosphorylation by the histidine kinase WalK, a multi-domain homodimer. It autophosphorylates one of its histidine residues by transferring the γ-phosphate from ATP bound to its ATP-binding domain. Here, the high-resolution crystal structure of the ATP-binding domain of WalK in complex with ATP is presented at 1.61 Å resolution. The bound ATP remains intact in the crystal lattice. It appears that the strong binding interactions and the nature of the binding pocket contribute to its stability. The triphosphate moiety of ATP wraps around an Mg{sup 2+} ion, providing three O atoms for coordination in a near-ideal octahedral geometry. The ATP molecule also makes strong interactions with the protein. In addition, there is a short contact between the exocyclic O3′ of the sugar ring and O2B of the β-phosphate, implying an internal hydrogen bond. The stability of the WalK–ATP complex in the crystal lattice suggests that such a complex may exist in vivo poised for initiation of signal transmission. This feature may therefore be part of the sensing mechanism by which the WalRK two-component system is so rapidly activated when cells encounter conditions conducive for growth.

Computation of Lie transformations from a power series: Bounds and optimum truncation

International Nuclear Information System (INIS)

Gjaja, I.

1996-01-01

The problem considered is the computation of an infinite product (composition) of Lie transformations generated by homogeneous polynomials of increasing order from a given asymptotic power series. Bounds are computed for the infinitesimal form of the Lie transformations and for the domain of analyticity of the first n of them. Even when the power series is convergent, the estimates exhibit a factorial-type growth, and thus do not guarantee convergence of the product. The optimum truncation is determined by minimizing the remainder after the first n Lie transformations have been applied

Identification of the functional domains of ANT-1, a novel coactivator of the androgen receptor

International Nuclear Information System (INIS)

Fan Shuli; Goto, Kiminobu; Chen Guangchun; Morinaga, Hidetaka; Nomura, Masatoshi; Okabe, Taijiro; Nawata, Hajime; Yanase, Toshihiko

2006-01-01

Previously, we identified a transcriptional coactivator for the activation function-1 (AF-1) domain of the human androgen receptor (AR) and designated it androgen receptor N-terminal domain transactivating protein-1 (ANT-1). This coactivator, which contains multiple tetratricopeptide repeat (TPR) motifs from amino acid (aa) 294, is identical to a component of U5 small nuclear ribonucleoprotein particles and binds specifically to the AR or glucocorticoid receptor. Here, we identified four distinct functional domains. The AR-AF-1-binding domain, which bound to either aa 180-360 or 360-532 in AR-AF-1, clearly overlapped with TAU-1 and TAU-5. This domain and the subnuclear speckle formation domain in ANT-1 were assigned within the TPR motifs, while the transactivating and nuclear localization signal domains resided within the N-terminal sequence. The existence of these functional domains may further support the idea that ANT-1 can function as an AR-AF-1-specific coactivator while mediating a transcription-splicing coupling

Charged domain-wall dynamics in doped antiferromagnets and spin fluctuations in cuprate superconductors

International Nuclear Information System (INIS)

Zaanen, J.; Horbach, M.L.; van Saarloos, W.

1996-01-01

Evidence is accumulating that the electron liquid in the cuprate superconductors is characterized by many-hole correlations of the charged magnetic domain-wall type. Here we focus on the strong-coupling limit where all holes are bound to domain walls. We assert that at high temperatures a classical domain-wall fluid is realized and show that the dynamics of such a fluid is characterized by spatial and temporal crossover scales set by temperature itself. The fundamental parameters of this fluid are such that the domain-wall motions dominate the low-frequency spin fluctuations and we derive predictions for the behavior of the dynamical magnetic susceptibility. We argue that a crossover occurs from a high-temperature classical to a low-temperature quantum regime, in direct analogy with helium. We discuss some general characteristics of the domain-wall quantum liquid, realized at low temperatures. copyright 1996 The American Physical Society

Domain decomposition methods for the mixed dual formulation of the critical neutron diffusion problem

International Nuclear Information System (INIS)

Guerin, P.

2007-12-01

The neutronic simulation of a nuclear reactor core is performed using the neutron transport equation, and leads to an eigenvalue problem in the steady-state case. Among the deterministic resolution methods, diffusion approximation is often used. For this problem, the MINOS solver based on a mixed dual finite element method has shown his efficiency. In order to take advantage of parallel computers, and to reduce the computing time and the local memory requirement, we propose in this dissertation two domain decomposition methods for the resolution of the mixed dual form of the eigenvalue neutron diffusion problem. The first approach is a component mode synthesis method on overlapping sub-domains. Several Eigenmodes solutions of a local problem solved by MINOS on each sub-domain are taken as basis functions used for the resolution of the global problem on the whole domain. The second approach is a modified iterative Schwarz algorithm based on non-overlapping domain decomposition with Robin interface conditions. At each iteration, the problem is solved on each sub domain by MINOS with the interface conditions deduced from the solutions on the adjacent sub-domains at the previous iteration. The iterations allow the simultaneous convergence of the domain decomposition and the eigenvalue problem. We demonstrate the accuracy and the efficiency in parallel of these two methods with numerical results for the diffusion model on realistic 2- and 3-dimensional cores. (author)

Scattering by bound nucleons

International Nuclear Information System (INIS)

Tezuka, Hirokazu.

1984-10-01

Scattering of a particle by bound nucleons is discussed. Effects of nucleons that are bound in a nucleus are taken as a structure function. The way how to calculate the structure function is given. (author)

Site-specific incorporation of 5-fluorotryptophan as a probe of the structure and function of the membrane-bound D-lactate dehydrogenase of Escherichia coli: A 19F nuclear magnetic resonance study

International Nuclear Information System (INIS)

Peersen, O.B.; Pratt, E.A.; Truong, H.T. N.; Ho, C.; Rule, G.S.

1990-01-01

The structure and function of the membrane-bound D-lactate dehydrogenase of Escherichia coli have been investigated by fluorine-19 nuclear magnetic resonance spectroscopy of 5-fluorotryptophan-labeled enzyme in conjunction with oligonucleotide-directed, site-specific mutagenesis. 5-Fluorotryptophan has been substituted for nine phenylalanine, tyrosine, and leucine residues in the enzyme molecule without loss of activity. The 19 F signals from these additional tryptophan residues have been used as markers for sensitivity to substrate, exposure to aqueous solvent, and proximity to a lipid-bound spin-label. The nuclear magnetic resonance data show that two mutational sites, at amino acid residues 340 and 361, are near the lipid environment used to stabilize the enzyme. There are a number of amino acid residues on the carboxyl side of this region that are strongly sensitive to the aqueous solvent. The environment of the wide-type tryptophan residue at position 469 changes as a result of two of the substitution mutations, suggesting some amino acid residue-residue interactions. Secondary structure prediction methods indicate a possible binding site for the flavin adenine dinucleotide cofactor in the carboxyl end of the enzyme molecule. These results suggest that the membrane-bound D-lactate dehydrogenase may have the two-domain structure of many cytoplasmic dehydrogenases but with the addition of a membrane-binding domain between the catalytic and cofactor-binding domains. This type of three-domain structure may be of general significance for understanding the structure of membrane-bound proteins which do not traverse the lipid bilayer of membranes

Core Competencies for Pain Management: Results of an Interprofessional Consensus Summit

Science.gov (United States)

Fishman, Scott M; Young, Heather M; Lucas Arwood, Ellyn; Chou, Roger; Herr, Keela; Murinson, Beth B; Watt-Watson, Judy; Carr, Daniel B; Gordon, Debra B; Stevens, Bonnie J; Bakerjian, Debra; Ballantyne, Jane C; Courtenay, Molly; Djukic, Maja; Koebner, Ian J; Mongoven, Jennifer M; Paice, Judith A; Prasad, Ravi; Singh, Naileshni; Sluka, Kathleen A; St Marie, Barbara; Strassels, Scott A

2013-01-01

Objective The objective of this project was to develop core competencies in pain assessment and management for prelicensure health professional education. Such core pain competencies common to all prelicensure health professionals have not been previously reported. Methods An interprofessional executive committee led a consensus-building process to develop the core competencies. An in-depth literature review was conducted followed by engagement of an interprofessional Competency Advisory Committee to critique competencies through an iterative process. A 2-day summit was held so that consensus could be reached. Results The consensus-derived competencies were categorized within four domains: multidimensional nature of pain, pain assessment and measurement, management of pain, and context of pain management. These domains address the fundamental concepts and complexity of pain; how pain is observed and assessed; collaborative approaches to treatment options; and application of competencies across the life span in the context of various settings, populations, and care team models. A set of values and guiding principles are embedded within each domain. Conclusions These competencies can serve as a foundation for developing, defining, and revising curricula and as a resource for the creation of learning activities across health professions designed to advance care that effectively responds to pain. PMID:23577878

Crystal structure of the sodium-potassium pump (Na+,K+-ATPase) with bound potassium and ouabain

Science.gov (United States)

Ogawa, Haruo; Shinoda, Takehiro; Cornelius, Flemming; Toyoshima, Chikashi

2009-01-01

The sodium-potassium pump (Na+,K+-ATPase) is responsible for establishing Na+ and K+ concentration gradients across the plasma membrane and therefore plays an essential role in, for instance, generating action potentials. Cardiac glycosides, prescribed for congestive heart failure for more than 2 centuries, are efficient inhibitors of this ATPase. Here we describe a crystal structure of Na+,K+-ATPase with bound ouabain, a representative cardiac glycoside, at 2.8 Å resolution in a state analogous to E2·2K+·Pi. Ouabain is deeply inserted into the transmembrane domain with the lactone ring very close to the bound K+, in marked contrast to previous models. Due to antagonism between ouabain and K+, the structure represents a low-affinity ouabain-bound state. Yet, most of the mutagenesis data obtained with the high-affinity state are readily explained by the present crystal structure, indicating that the binding site for ouabain is essentially the same. According to a homology model for the high affinity state, it is a closure of the binding cavity that confers a high affinity. PMID:19666591

Crystal structure of the sodium-potassium pump (Na+,K+-ATPase) with bound potassium and ouabain.

Science.gov (United States)

Ogawa, Haruo; Shinoda, Takehiro; Cornelius, Flemming; Toyoshima, Chikashi

2009-08-18

The sodium-potassium pump (Na(+),K(+)-ATPase) is responsible for establishing Na(+) and K(+) concentration gradients across the plasma membrane and therefore plays an essential role in, for instance, generating action potentials. Cardiac glycosides, prescribed for congestive heart failure for more than 2 centuries, are efficient inhibitors of this ATPase. Here we describe a crystal structure of Na(+),K(+)-ATPase with bound ouabain, a representative cardiac glycoside, at 2.8 A resolution in a state analogous to E2.2K(+).Pi. Ouabain is deeply inserted into the transmembrane domain with the lactone ring very close to the bound K(+), in marked contrast to previous models. Due to antagonism between ouabain and K(+), the structure represents a low-affinity ouabain-bound state. Yet, most of the mutagenesis data obtained with the high-affinity state are readily explained by the present crystal structure, indicating that the binding site for ouabain is essentially the same. According to a homology model for the high affinity state, it is a closure of the binding cavity that confers a high affinity.

Faraday instability in deformable domains

International Nuclear Information System (INIS)

Pucci, G.

2013-01-01

Hydrodynamical instabilities are usually studied either in bounded regions or free to grow in space. In this article we review the experimental results of an intermediate situation, in which an instability develops in deformable domains. The Faraday instability, which consists in the formation of surface waves on a liquid experiencing a vertical forcing, is triggered in floating liquid lenses playing the role of deformable domains. Faraday waves deform the lenses from the initial circular shape and the mutual adaptation of instability patterns with the lens boundary is observed. Two archetypes of behaviour have been found. In the first archetype a stable elongated shape is reached, the wave vector being parallel to the direction of elongation. In the second archetype the waves exceed the response of the lens border and no equilibrium shape is reached. The lens stretches and eventually breaks into fragments that have a complex dynamics. The difference between the two archetypes is explained by the competition between the radiation pressure the waves exert on the lens border and its response due to surface tension.

Bounds for Asian basket options

Science.gov (United States)

Deelstra, Griselda; Diallo, Ibrahima; Vanmaele, Michèle

2008-09-01

In this paper we propose pricing bounds for European-style discrete arithmetic Asian basket options in a Black and Scholes framework. We start from methods used for basket options and Asian options. First, we use the general approach for deriving upper and lower bounds for stop-loss premia of sums of non-independent random variables as in Kaas et al. [Upper and lower bounds for sums of random variables, Insurance Math. Econom. 27 (2000) 151-168] or Dhaene et al. [The concept of comonotonicity in actuarial science and finance: theory, Insurance Math. Econom. 31(1) (2002) 3-33]. We generalize the methods in Deelstra et al. [Pricing of arithmetic basket options by conditioning, Insurance Math. Econom. 34 (2004) 55-57] and Vanmaele et al. [Bounds for the price of discrete sampled arithmetic Asian options, J. Comput. Appl. Math. 185(1) (2006) 51-90]. Afterwards we show how to derive an analytical closed-form expression for a lower bound in the non-comonotonic case. Finally, we derive upper bounds for Asian basket options by applying techniques as in Thompson [Fast narrow bounds on the value of Asian options, Working Paper, University of Cambridge, 1999] and Lord [Partially exact and bounded approximations for arithmetic Asian options, J. Comput. Finance 10 (2) (2006) 1-52]. Numerical results are included and on the basis of our numerical tests, we explain which method we recommend depending on moneyness and time-to-maturity.

The Expanded FindCore Method for Identification of a Core Atom Set for Assessment of Protein Structure Prediction

Science.gov (United States)

Snyder, David A.; Grullon, Jennifer; Huang, Yuanpeng J.; Tejero, Roberto; Montelione, Gaetano T.

2014-01-01

Maximizing the scientific impact of NMR-based structure determination requires robust and statistically sound methods for assessing the precision of NMR-derived structures. In particular, a method to define a core atom set for calculating superimpositions and validating structure predictions is critical to the use of NMR-derived structures as targets in the CASP competition. FindCore (D.A. Snyder and G.T. Montelione PROTEINS 2005;59:673–686) is a superimposition independent method for identifying a core atom set, and partitioning that set into domains. However, as FindCore optimizes superimposition by sensitively excluding not-well-defined atoms, the FindCore core may not comprise all atoms suitable for use in certain applications of NMR structures, including the CASP assessment process. Adapting the FindCore approach to assess predicted models against experimental NMR structures in CASP10 required modification of the FindCore method. This paper describes conventions and a standard protocol to calculate an “Expanded FindCore” atom set suitable for validation and application in biological and biophysical contexts. A key application of the Expanded FindCore method is to identify a core set of atoms in the experimental NMR structure for which it makes sense to validate predicted protein structure models. We demonstrate the application of this Expanded FindCore method in characterizing well-defined regions of 18 NMR-derived CASP10 target structures. The Expanded FindCore protocol defines “expanded core atom sets” that match an expert’s intuition of which parts of the structure are sufficiently well-defined to use in assessing CASP model predictions. We also illustrate the impact of this analysis on the CASP GDT assessment scores. PMID:24327305

Domain-General Factors Influencing Numerical and Arithmetic Processing

Directory of Open Access Journals (Sweden)

André Knops

2017-12-01

Full Text Available This special issue contains 18 articles that address the question how numerical processes interact with domain-general factors. We start the editorial with a discussion of how to define domain-general versus domain-specific factors and then discuss the contributions to this special issue grouped into two core numerical domains that are subject to domain-general influences (see Figure 1. The first group of contributions addresses the question how numbers interact with spatial factors. The second group of contributions is concerned with factors that determine and predict arithmetic understanding, performance and development. This special issue shows that domain-general (Table 1a as well as domain-specific (Table 1b abilities influence numerical and arithmetic performance virtually at all levels and make it clear that for the field of numerical cognition a sole focus on one or several domain-specific factors like the approximate number system or spatial-numerical associations is not sufficient. Vice versa, in most studies that included domain-general and domain-specific variables, domain-specific numerical variables predicted arithmetic performance above and beyond domain-general variables. Therefore, a sole focus on domain-general aspects such as, for example, working memory, to explain, predict and foster arithmetic learning is also not sufficient. Based on the articles in this special issue we conclude that both domain-general and domain-specific factors contribute to numerical cognition. But the how, why and when of their contribution still needs to be better understood. We hope that this special issue may be helpful to readers in constraining future theory and model building about the interplay of domain-specific and domain-general factors.

Mapping of immunogenic and protein-interacting regions at the surface of the seven-bladed β-propeller domain of the HIV-1 cellular interactor EED

Directory of Open Access Journals (Sweden)

Gouet Patrice

2008-02-01

-binding sites at the surface of the EED isoform 3 provided a global picture of the immunogenic and protein-protein interacting regions in the EED C-terminal domain, organized as a seven-bladed β-propeller protein. Mapping of the HIV-1 MA and IN binding sites on the 3D-model of EED core predicted that EED-bound MA and IN ligands would be in close vicinity at the surface of the β-propeller, and that the occurrence of a ternary complex MA-EED-IN would be possible.

The Lifetimes and Evolution of Molecular Cloud Cores

Science.gov (United States)

Vázquez-Semadeni, Enrique; Kim, Jongsoo; Shadmehri, Mohsen; Ballesteros-Paredes, Javier

2005-01-01

We discuss the lifetimes and evolution of clumps and cores formed as turbulent density fluctuations in nearly isothermal molecular clouds. In order to maintain a broad perspective, we consider both the magnetic and nonmagnetic cases. In the latter, we argue that clumps are unlikely to reach a hydrostatic state if molecular clouds can in general be described as single-phase media with an effective polytropic exponent γecriticality of their ``parent clouds'' (the numerical boxes). In subcritical boxes, magnetostatic clumps do not form. A minority of moderately gravitationally bound clumps form, which however are dispersed by the turbulence in ~1.3 Myr, suggesting that these few longer lived cores can marginally be ``captured'' by AD to increase their mass-to-flux ratio and eventually collapse, although on timescales not significantly longer than the dynamical ones. In supercritical boxes, some cores manage to become locally supercritical and collapse in typical timescales of 2 tfc (~1 Myr). In the most supercritical simulation, a few longer lived cores are observed, which last for up to ~3 Myr, but these end up re-expanding rather than collapsing, because they are sub-Jeans in spite of being supercritical. Fewer clumps and cores form in these simulations than in their nonmagnetic counterpart. Our results suggest the following: (1) not all cores observed in molecular clouds will necessarily form stars and that a class of ``failed cores'' should exist, which will eventually redisperse and which may be related to the observed starless cores; (2) cores may be out-of-equilibrium, transient structures, rather than quasi-magnetostatic configurations; (3) the magnetic field may help reduce the star formation efficiency by reducing the probability of core formation, rather than by significantly delaying the collapse of individual cores, even in magnetically supercritical clouds.

Market access through bound tariffs

DEFF Research Database (Denmark)

Sala, Davide; Yalcin, Erdal; Schröder, Philipp

2010-01-01

on the risk that exporters face in destination markets. The present paper formalizes the underlying interaction of risk, fixed export costs and firms' market entry decisions based on techniques known from the real options literature; doing so we highlight the important role of bound tariffs at the extensive...... margin of trade. We find that bound tariffs are more effective with higher risk destination markets, that a large binding overhang may still command substantial market access, and that reductions in bound tariffs generate effective market access even when bound rates are above current and longterm...

Market Access through Bound Tariffs

DEFF Research Database (Denmark)

Sala, Davide; Schröder, Philipp J.H.; Yalcin, Erdal

on the risk that exporters face in destination markets. The present paper formalizes the underlying interaction of risk, fixed export costs and firms' market entry decisions based on techniques known from the real options literature; doing so we highlight the important role of bound tariffs at the extensive...... margin of trade. We find that bound tariffs are more effective with higher risk destination markets, that a large binding overhang may still command substantial market access, and that reductions in bound tariffs generate effective market access even when bound rates are above current and long...

Crystal structures of active fully assembled substrate- and product-bound complexes of UDP-N-acetylmuramic acid:L-alanine ligase (MurC) from Haemophilus influenzae.

Science.gov (United States)

Mol, Clifford D; Brooun, Alexei; Dougan, Douglas R; Hilgers, Mark T; Tari, Leslie W; Wijnands, Robert A; Knuth, Mark W; McRee, Duncan E; Swanson, Ronald V

2003-07-01

UDP-N-acetylmuramic acid:L-alanine ligase (MurC) catalyzes the addition of the first amino acid to the cytoplasmic precursor of the bacterial cell wall peptidoglycan. The crystal structures of Haemophilus influenzae MurC in complex with its substrate UDP-N-acetylmuramic acid (UNAM) and Mg(2+) and of a fully assembled MurC complex with its product UDP-N-acetylmuramoyl-L-alanine (UMA), the nonhydrolyzable ATP analogue AMPPNP, and Mn(2+) have been determined to 1.85- and 1.7-A resolution, respectively. These structures reveal a conserved, three-domain architecture with the binding sites for UNAM and ATP formed at the domain interfaces: the N-terminal domain binds the UDP portion of UNAM, and the central and C-terminal domains form the ATP-binding site, while the C-terminal domain also positions the alanine. An active enzyme structure is thus assembled at the common domain interfaces when all three substrates are bound. The MurC active site clearly shows that the gamma-phosphate of AMPPNP is positioned between two bound metal ions, one of which also binds the reactive UNAM carboxylate, and that the alanine is oriented by interactions with the positively charged side chains of two MurC arginine residues and the negatively charged alanine carboxyl group. These results indicate that significant diversity exists in binding of the UDP moiety of the substrate by MurC and the subsequent ligases in the bacterial cell wall biosynthesis pathway and that alterations in the domain packing and tertiary structure allow the Mur ligases to bind sequentially larger UNAM peptide substrates.

Understanding cAMP-dependent allostery by NMR spectroscopy: comparative analysis of the EPAC1 cAMP-binding domain in its apo and cAMP-bound states.

Science.gov (United States)

Mazhab-Jafari, Mohammad T; Das, Rahul; Fotheringham, Steven A; SilDas, Soumita; Chowdhury, Somenath; Melacini, Giuseppe

2007-11-21

cAMP (adenosine 3',5'-cyclic monophosphate) is a ubiquitous second messenger that activates a multitude of essential cellular responses. Two key receptors for cAMP in eukaryotes are protein kinase A (PKA) and the exchange protein directly activated by cAMP (EPAC), which is a recently discovered guanine nucleotide exchange factor (GEF) for the small GTPases Rap1 and Rap2. Previous attempts to investigate the mechanism of allosteric activation of eukaryotic cAMP-binding domains (CBDs) at atomic or residue resolution have been hampered by the instability of the apo form, which requires the use of mixed apo/holo systems, that have provided only a partial picture of the CBD apo state and of the allosteric networks controlled by cAMP. Here, we show that, unlike other eukaryotic CBDs, both apo and cAMP-bound states of the EPAC1 CBD are stable under our experimental conditions, providing a unique opportunity to define at an unprecedented level of detail the allosteric interactions linking two critical functional sites of this CBD. These are the phosphate binding cassette (PBC), where cAMP binds, and the N-terminal helical bundle (NTHB), which is the site of the inhibitory interactions between the regulatory and catalytic regions of EPAC. Specifically, the combined analysis of the cAMP-dependent changes in chemical shifts, 2 degrees structure probabilities, hydrogen/hydrogen exchange (H/H) and hydrogen/deuterium exchange (H/D) protection factors reveals that the long-range communication between the PBC and the NTHB is implemented by two distinct intramolecular cAMP-signaling pathways, respectively, mediated by the beta2-beta3 loop and the alpha6 helix. Docking of cAMP into the PBC perturbs the NTHB inner core packing and the helical probabilities of selected NTHB residues. The proposed model is consistent with the allosteric role previously hypothesized for L273 and F300 based on site-directed mutagenesis; however, our data show that such a contact is part of a

Core power capability verification for PWR NPP

International Nuclear Information System (INIS)

Xian Chunyu; Liu Changwen; Zhang Hong; Liang Wei

2002-01-01

The Principle and methodology of pressurized water reactor nuclear power plant core power capability verification for reload are introduced. The radial and axial power distributions of normal operation (category I or condition I) and abnormal operation (category II or condition II) are simulated by using neutronics calculation code. The linear power density margin and DNBR margin for both categories, which reflect core safety, are analyzed from the point view of reactor physics and T/H, and thus category I operating domain and category II protection set point are verified. Besides, the verification results of reference NPP are also given

Modularized Functions of the Fanconi Anemia Core Complex

Directory of Open Access Journals (Sweden)

Yaling Huang

2014-06-01

Full Text Available The Fanconi anemia (FA core complex provides the essential E3 ligase function for spatially defined FANCD2 ubiquitination and FA pathway activation. Of the seven FA gene products forming the core complex, FANCL possesses a RING domain with demonstrated E3 ligase activity. The other six components do not have clearly defined roles. Through epistasis analyses, we identify three functional modules in the FA core complex: a catalytic module consisting of FANCL, FANCB, and FAAP100 is absolutely required for the E3 ligase function, and the FANCA-FANCG-FAAP20 and the FANCC-FANCE-FANCF modules provide nonredundant and ancillary functions that help the catalytic module bind chromatin or sites of DNA damage. Disruption of the catalytic module causes complete loss of the core complex function, whereas loss of any ancillary module component does not. Our work reveals the roles of several FA gene products with previously undefined functions and a modularized assembly of the FA core complex.

Bound and rebound states

International Nuclear Information System (INIS)

Orzalesi, C.A.

1979-01-01

In relativistic quantum theory, bound states generate forces in the crossed channel; such forces can affect the binding and self-consistent solutions should be sought for the bound-state problem. The author investigates how self-consistency can be achieved by successive approximations, in a simple scalar model and with successive relativistic eikonal approximations (EAs). Within the generalized ladder approximation, some exact properties of the resulting ''first generation'' bound states are discussed. The binding energies in this approximation are rather small even for rather large values of the primary coupling constant. The coupling of the constituent particles to the first-generation reggeon is determined by a suitable EA and a new generalized ladder amplitude is constructed with rungs given either by the primary gluons or by the first-generation reggeons. The resulting new (second-generation) bound states are found in a reggeized EA. The size of the corrections to the binding energies due to the rebinding effects is surprisingly large. The procedure is then iterated, so as to find - again in an EA - the third-generation bound states. The procedure is found to be self-consistent already at this stage: the third-generation bound states coincide with those of second generation, and no further rebinding takes place in the higher iterations of the approximation method. Features - good and bad - of the model are discussed, as well as the possible relevance of rebinding mechanisms in hadron dynamics. (author)

Crystal optimization and preliminary diffraction data analysis of the Smad1 MH1 domain bound to a palindromic SBE DNA element

Science.gov (United States)

Baburajendran, Nithya; Palasingam, Paaventhan; Ng, Calista Keow Leng; Jauch, Ralf; Kolatkar, Prasanna R.

2009-01-01

The bone morphogenetic protein (BMP) signalling pathway regulates diverse processes such as cell differentiation, anterior/posterior axis specification, cell growth and the formation of extra-embryonic tissues. The transcription factor Smad1 relays the BMP signal from the cytoplasm to the nucleus, where it binds short DNA-sequence motifs and regulates gene expression. However, how Smad1 selectively targets particular genomic regions is poorly understood. In order to understand the physical basis of the specific interaction of Smad1 with DNA and to contrast it with the highly homologous but functionally distinct Smad3 protein, the DNA-binding Mad-homology 1 (MH1) domain of Smad1 was cocrystallized with a 17-mer palindromic Smad-binding element (SBE). The extensive optimizations of the length, binding-site spacing and terminal sequences of the DNA element in combination with the other crystallization parameters necessary for obtaining diffraction-quality crystals are described here. A 2.7 Å resolution native data set was collected at the National Synchrotron Radiation Research Centre, Taiwan, from crystals grown in a solution containing 0.2 M ammonium tartrate dibasic, 20% PEG 3350, 3% 2-­propanol and 10% glycerol. The data set was indexed and merged in space group P222, with unit-cell parameters a = 73.94, b = 77.49, c = 83.78 Å, α = β = γ = 90°. The solvent content in the unit cell is consistent with the presence of two Smad1 MH1 molecules bound to the duplex DNA in the asymmetric unit. PMID:19923727

Crystal structure of product-bound complex of UDP-N-acetyl-D-mannosamine dehydrogenase from Pyrococcus horikoshii OT3

Energy Technology Data Exchange (ETDEWEB)

Pampa, K.J., E-mail: sagarikakj@gmail.com [Department of Studies in Microbiology, University of Mysore, Mysore 570 006 (India); Lokanath, N.K. [Department of Studies in Physics, University of Mysore, Mysore 570 006 (India); Girish, T.U. [Department of General Surgery, JSS Medical College and Hospital, JSS University, Mysore 570 015 (India); Kunishima, N. [Advanced Protein Crystallography Research Group, RIKEN SPring-8 Center, Harima Institute, Hyogo 679-5148 (Japan); Rai, V.R. [Department of Studies in Microbiology, University of Mysore, Mysore 570 006 (India)

2014-10-24

Highlights: • Determined the structure of UDP-D-ManNAcADH to a resolution of 1.55 Å. • First complex structure of PhUDP-D-ManNAcADH with UDP-D-ManMAcA. • The monomeric structure consists of three distinct domains. • Cys258 acting as catalytic nucleophilic and Lys204 acts as acid/base catalyst. • Oligomeric state plays an important role for the catalytic function. - Abstract: UDP-N-acetyl-D-mannosamine dehydrogenase (UDP-D-ManNAcDH) belongs to UDP-glucose/GDP-mannose dehydrogenase family and catalyzes Uridine-diphospho-N-acetyl-D-mannosamine (UDP-D-ManNAc) to Uridine-diphospho-N-acetyl-D-mannosaminuronic acid (UDP-D-ManNAcA) through twofold oxidation of NAD{sup +}. In order to reveal the structural features of the Pyrococcus horikoshii UDP-D-ManNAcADH, we have determined the crystal structure of the product-bound enzyme by X-ray diffraction to resolution of 1.55 Å. The protomer folds into three distinct domains; nucleotide binding domain (NBD), substrate binding domain (SBD) and oligomerization domain (OD, involved in the dimerization). The clear electron density of the UDP-D-ManNAcA is observed and the residues binding are identified for the first time. Crystal structures reveal a tight dimeric polymer chains with product-bound in all the structures. The catalytic residues Cys258 and Lys204 are conserved. The Cys258 acts as catalytic nucleophile and Lys204 as acid/base catalyst. The product is directly interacts with residues Arg211, Thr249, Arg244, Gly255, Arg289, Lys319 and Arg398. In addition, the structural parameters responsible for thermostability and oligomerization of the three dimensional structure are analyzed.

An α-Helical Core Encodes the Dual Functions of the Chlamydial Protein IncA*

Science.gov (United States)

Ronzone, Erik; Wesolowski, Jordan; Bauler, Laura D.; Bhardwaj, Anshul; Hackstadt, Ted; Paumet, Fabienne

2014-01-01

Chlamydia is an intracellular bacterium that establishes residence within parasitophorous compartments (inclusions) inside host cells. Chlamydial inclusions are uncoupled from the endolysosomal pathway and undergo fusion with cellular organelles and with each other. To do so, Chlamydia expresses proteins on the surface of the inclusion using a Type III secretion system. These proteins, termed Incs, are located at the interface between host and pathogen and carry out the functions necessary for Chlamydia survival. Among these Incs, IncA plays a critical role in both protecting the inclusion from lysosomal fusion and inducing the homotypic fusion of inclusions. Within IncA are two regions homologous to eukaryotic SNARE (soluble N-ethylmaleimide-sensitive factor attachment receptor) domains referred to as SNARE-like domain 1 (SLD1) and SNARE-like domain 2 (SLD2). Using a multidisciplinary approach, we have discovered the functional core of IncA that retains the ability to both inhibit SNARE-mediated fusion and promote the homotypic fusion of Chlamydia inclusions. Circular dichroism and analytical ultracentrifugation experiments show that this core region is composed almost entirely of α-helices and assembles into stable homodimers in solution. Altogether, we propose that both IncA functions are encoded in a structured core domain that encompasses SLD1 and part of SLD2. PMID:25324548

Gap analysis: a method to assess core competency development in the curriculum.

Science.gov (United States)

Fater, Kerry H

2013-01-01

To determine the extent to which safety and quality improvement core competency development occurs in an undergraduate nursing program. Rapid change and increased complexity of health care environments demands that health care professionals are adequately prepared to provide high quality, safe care. A gap analysis compared the present state of competency development to a desirable (ideal) state. The core competencies, Nurse of the Future Nursing Core Competencies, reflect the ideal state and represent minimal expectations for entry into practice from pre-licensure programs. Findings from the gap analysis suggest significant strengths in numerous competency domains, deficiencies in two competency domains, and areas of redundancy in the curriculum. Gap analysis provides valuable data to direct curriculum revision. Opportunities for competency development were identified, and strategies were created jointly with the practice partner, thereby enhancing relevant knowledge, attitudes, and skills nurses need for clinical practice currently and in the future.

Achievement, Language, and Technology Use Among College-Bound Deaf Learners.

Science.gov (United States)

Crowe, Kathryn; Marschark, Marc; Dammeyer, Jesper; Lehane, Christine

2017-10-01

Deaf learners are a highly heterogeneous group who demonstrate varied levels of academic achievement and attainment. Most prior research involving this population has focused on factors facilitating academic success in young deaf children, with less attention paid to older learners. Recent studies, however, have suggested that while factors such as early cochlear implantation and early sign language fluency are positively associated with academic achievement in younger deaf children, they no longer predict achievement once children reach high school age. This study, involving data from 980 college-bound high school students with hearing loss, examined relations between academic achievement, communication variables (audiological, language), and use of assistive technologies (e.g., cochlear implants [CIs], FM systems) and other support services (e.g., interpreting, real-time text) in the classroom. Spoken language skills were positively related to achievement in some domains, while better sign language skills were related to poorer achievement in others. Among these college-bound students, use of CIs and academic support services in high school accounted for little variability in their college entrance examination scores. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Toxicological Assessment of a Lignin Core Nanoparticle Doped with Silver as an Alternative to Conventional Silver Core Nanoparticles

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Cassandra E. Nix

2018-05-01

Full Text Available Elevated levels of silver in the environment are anticipated with an increase in silver nanoparticle (AgNP production and use in consumer products. To potentially reduce the burden of silver ion release from conventional solid core AgNPs, a lignin-core particle doped with silver ions and surface-stabilized with a polycationic electrolyte layer was engineered. Our objective was to determine whether any of the formulation components elicit toxicological responses using embryonic zebrafish. Ionic silver and free surface stabilizer were the most toxic constituents, although when associated separately or together with the lignin core particles, the toxicity of the formulations decreased significantly. The overall toxicity of lignin formulations containing silver was similar to other studies on a silver mass basis, and led to a significantly higher prevalence of uninflated swim bladder and yolk sac edema. Comparative analysis of dialyzed samples which had leached their loosely bound Ag+, showed a significant increase in mortality immediately after dialysis, in addition to eliciting significant increases in types of sublethal responses relative to the freshly prepared non-dialyzed samples. ICP-OES/MS analysis indicated that silver ion release from the particle into solution was continuous, and the rate of release differed when the surface stabilizer was not present. Overall, our study indicates that the lignin core is an effective alternative to conventional solid core AgNPs for potentially reducing the burden of silver released into the environment from a variety of consumer products.

High-performance whole core Pin-by-Pin calculation based on EFEN-SP_3 method

International Nuclear Information System (INIS)

Yang Wen; Zheng Youqi; Wu Hongchun; Cao Liangzhi; Li Yunzhao

2014-01-01

The EFEN code for high-performance PWR whole core pin-by-pin calculation based on the EFEN-SP_3 method can be achieved by employing spatial parallelization based on MPI. To take advantage of the advanced computing and storage power, the entire problem spatial domain can be appropriately decomposed into sub-domains and the assigned to parallel CPUs to balance the computing load and minimize communication cost. Meanwhile, Red-Black Gauss-Seidel nodal sweeping scheme is employed to avoid the within-group iteration deterioration due to spatial parallelization. Numerical results based on whole core pin-by-pin problems designed according to commercial PWRs demonstrate the following conclusions: The EFEN code can provide results with acceptable accuracy; Communication period impacts neither the accuracy nor the parallel efficiency; Domain decomposition methods with smaller surface to volume ratio leads to greater parallel efficiency; A PWR whole core pin-by-pin calculation with a spatial mesh 289 × 289 × 218 and 4 energy groups could be completed about 900 s by using 125 CPUs, and its parallel efficiency is maintained at about 90%. (authors)

Structures of glide-set 90 deg. partial dislocation cores in diamond cubic semiconductors

International Nuclear Information System (INIS)

Beckman, S.P.; Chrzan, D.C.

2003-01-01

Two core reconstructions of the 90 deg. partial dislocations in diamond cubic semiconductors, the so-called single- and double-period structures, are often found to be nearly degenerate in energy. This near degeneracy suggests the possibility that both core reconstructions may be present simultaneously along the same dislocation core, with the domain sizes of the competing reconstructions dependent on temperature and the local stress state. To explore this dependence, a simple statistical mechanics-based model of the dislocation core reconstructions is developed and analyzed. Predictions for the temperature-dependent structure of the dislocation core are presented

Physical and chemical characteristics of L1689-SMM16, an oscillating prestellar core in Ophiuchus

Energy Technology Data Exchange (ETDEWEB)

Chitsazzadeh, S.; Di Francesco, J.; Sadavoy, S. I. [Department of Physics and Astronomy, The University of Victoria, Victoria, BC V8P 5C2 (Canada); Schnee, S. [National Radio Astronomy Observatory, 520 Edgemont Road, Charlottesville, VA 22903 (United States); Friesen, R. K. [The Dunlap Institute for Astronomy and Astrophysics, University of Toronto, 50 St. George St., Toronto, ON M5S 3H4 (Canada); Shimajiri, Y. [Laboratoire AIM, CEA/DSM-CNRS-Université Paris Diderot, IRFU/Service d' Astrophysique, CEA Saclay, F-91191 Gif-sur-Yvette (France); Langston, G. I. [National Radio Astronomy Observatory, P.O. Box 2, Green Bank, WV 24944 (United States); Bourke, T. L.; Keto, E. R. [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Pineda, J. E. [Institute for Astronomy, ETH Zurich, Wolfgang-Pauli-Strasse 27, CH-8093 Zurich (Switzerland); Takakuwa, S. [Academia Sinica Institute of Astronomy and Astrophysics, P.O. Box 23-141, Taipei 10617, Taiwan (China); Tatematsu, K., E-mail: schitsaz@uvic.ca [National Astronomical Observatory of Japan, 2-21-1 Osawa, Mitaka, Tokyo 181-8588 (Japan)

2014-08-01

We present single-dish observations of the L1689-SMM16 core in the Ophiuchus molecular cloud in NH{sub 3} (1, 1) and (2, 2) emission using the Green Bank Telescope, in N{sub 2}H{sup +} (1-0) emission using the Nobeyama Radio Observatory, and in NH{sub 2}D (1{sub 1,1}{sup a}(--)1{sub 0,1}{sup s}), HCN (1-0), HNC (1-0), H{sup 13}CO{sup +} (1-0), and HCO{sup +} (1-0) emission using the Mopra telescope. The morphologies of the integrated NH{sub 3} (1, 1) and N{sub 2}H{sup +} (1-0) emission well match that of 250 μm continuum emission. Line widths of NH{sub 3} (1, 1) and N{sub 2}H{sup +} (1-0) show the presence of transonic turbulence across the core. Jeans and virial analyses made using updated measurements of core mass and size confirm that L1689-SMM16 is prestellar, i.e., gravitationally bound. It also has accumulated more mass compared to its corresponding Jeans mass in the absence of magnetic fields and therefore is a 'super-Jeans' core. The high levels of X(NH{sub 3})/X(N{sub 2}H{sup +}) and deuterium fractionation reinforce the idea that the core has not yet formed a protostar. Comparing the physical parameters of the core with those of a Bonnor-Ebert sphere reveals the advanced evolutionary stage of L1689-SMM16 and shows that it might be unstable to collapse. We do not detect any evidence of infall motions toward the core. Instead, red asymmetry in the line profiles of HCN (1-0) and HNC (1-0) indicates the expansion of the outer layers of the core at a speed of ∼0.2 km s{sup –1} to 0.3 km s{sup –1}. For a gravitationally bound core, expansion in the outer layers might indicate that the core is experiencing oscillations.

Domain decomposition methods for fluid dynamics

International Nuclear Information System (INIS)

Clerc, S.

1995-01-01

A domain decomposition method for steady-state, subsonic fluid dynamics calculations, is proposed. The method is derived from the Schwarz alternating method used for elliptic problems, extended to non-linear hyperbolic problems. Particular emphasis is given on the treatment of boundary conditions. Numerical results are shown for a realistic three-dimensional two-phase flow problem with the FLICA-4 code for PWR cores. (from author). 4 figs., 8 refs

Concerted action of the PHD, chromo and motor domains regulates the human chromatin remodelling ATPase CHD4

OpenAIRE

Morra, Rosa; Lee, Benjamin M; Shaw, Heather; Tuma, Roman; Mancini, Erika J

2012-01-01

CHD4, the core subunit of the Nucleosome Remodelling and Deacetylase (NuRD) complex, is a chromatin remodelling ATPase that, in addition to a helicase domain, harbors tandem plant homeo finger and chromo domains. By using a panel of domain constructs we dissect their roles and demonstrate that DNA binding, histone binding and ATPase activities are allosterically regulated. Molecular shape reconstruction from small-angle X-ray scattering reveals extensive domain-domain interactions, which prov...

Rosette Assay: Highly Customizable Dot-Blot for SH2 Domain Screening.

Science.gov (United States)

Ng, Khong Y; Machida, Kazuya

2017-01-01

With a growing number of high-throughput studies, structural analyses, and availability of protein-protein interaction databases, it is now possible to apply web-based prediction tools to SH2 domain-interactions. However, in silico prediction is not always reliable and requires experimental validation. Rosette assay is a dot blot-based reverse-phase assay developed for the assessment of binding between SH2 domains and their ligands. It is conveniently customizable, allowing for low- to high-throughput analysis of interactions between various numbers of SH2 domains and their ligands, e.g., short peptides, purified proteins, and cell lysates. The binding assay is performed in a 96-well plate (MBA or MWA apparatus) in which a sample spotted membrane is incubated with up to 96 labeled SH2 domains. Bound domains are detected and quantified using a chemiluminescence or near-infrared fluorescence (IR) imaging system. In this chapter, we describe a practical protocol for rosette assay to assess interactions between synthesized tyrosine phosphorylated peptides and a library of GST-tagged SH2 domains. Since the methodology is not confined to assessment of SH2-pTyr interactions, rosette assay can be broadly utilized for ligand and drug screening using different protein interaction domains or antibodies.

Preparation of crystals for characterizing the Grb7 SH2 domain before and after complex formation with a bicyclic peptide antagonist.

Science.gov (United States)

Ambaye, Nigus D; Gunzburg, Menachem J; Traore, Daouda A K; Del Borgo, Mark P; Perlmutter, Patrick; Wilce, Matthew C J; Wilce, Jacqueline A

2014-02-01

Human growth factor receptor-bound protein 7 (Grb7) is an adapter protein involved in cell growth, migration and proliferation. It is now recognized that Grb7 is an emerging therapeutic target in specific cancer subtypes. Recently, the discovery of a bicyclic peptide inhibitor that targets the Grb7 SH2 domain, named G7-B1, was reported. In an attempt to probe the foundation of its interaction with Grb7, the crystallization and preliminary data collection of both the apo and G7-B1-bound forms of the Grb7 SH2 domain are reported here. Diffraction-quality crystals were obtained using the hanging-drop vapour-diffusion method. After several rounds of microseeding, crystals of the apo Grb7 SH2 domain were obtained that diffracted to 1.8 Å resolution, while those of the G7-B1-Grb7 SH2 domain complex diffracted to 2.2 Å resolution. The apo Grb7 SH2 domain crystallized in the trigonal space group P63, whereas the G7-B1-Grb7 SH2 domain complex crystallized in the monoclinic space group P21. The experimental aspects of crystallization, crystal optimization and data collection and the preliminary data are reported.

Unstructured characteristic method embedded with variational nodal method using domain decomposition techniques

Energy Technology Data Exchange (ETDEWEB)

Girardi, E.; Ruggieri, J.M. [CEA Cadarache (DER/SPRC/LEPH), 13 - Saint-Paul-lez-Durance (France). Dept. d' Etudes des Reacteurs; Santandrea, S. [CEA Saclay, Dept. Modelisation de Systemes et Structures DM2S/SERMA/LENR, 91 - Gif sur Yvette (France)

2005-07-01

This paper describes a recently-developed extension of our 'Multi-methods,multi-domains' (MM-MD) method for the solution of the multigroup transport equation. Based on a domain decomposition technique, our approach allows us to treat the one-group equation by cooperatively employing several numerical methods together. In this work, we describe the coupling between the Method of Characteristics (integro-differential equation, unstructured meshes) with the Variational Nodal Method (even parity equation, cartesian meshes). Then, the coupling method is applied to the benchmark model of the Phebus experimental facility (Cea Cadarache). Our domain decomposition method give us the capability to employ a very fine mesh in describing a particular fuel bundle with an appropriate numerical method (MOC), while using a much large mesh size in the rest of the core, in conjunction with a coarse-mesh method (VNM). This application shows the benefits of our MM-MD approach, in terms of accuracy and computing time: the domain decomposition method allows us to reduce the Cpu time, while preserving a good accuracy of the neutronic indicators: reactivity, core-to-bundle power coupling coefficient and flux error. (authors)

Unstructured characteristic method embedded with variational nodal method using domain decomposition techniques

International Nuclear Information System (INIS)

Girardi, E.; Ruggieri, J.M.

2005-01-01

This paper describes a recently-developed extension of our 'Multi-methods,multi-domains' (MM-MD) method for the solution of the multigroup transport equation. Based on a domain decomposition technique, our approach allows us to treat the one-group equation by cooperatively employing several numerical methods together. In this work, we describe the coupling between the Method of Characteristics (integro-differential equation, unstructured meshes) with the Variational Nodal Method (even parity equation, cartesian meshes). Then, the coupling method is applied to the benchmark model of the Phebus experimental facility (Cea Cadarache). Our domain decomposition method give us the capability to employ a very fine mesh in describing a particular fuel bundle with an appropriate numerical method (MOC), while using a much large mesh size in the rest of the core, in conjunction with a coarse-mesh method (VNM). This application shows the benefits of our MM-MD approach, in terms of accuracy and computing time: the domain decomposition method allows us to reduce the Cpu time, while preserving a good accuracy of the neutronic indicators: reactivity, core-to-bundle power coupling coefficient and flux error. (authors)

Identifying the node spreading influence with largest k-core values

International Nuclear Information System (INIS)

Lin, Jian-Hong; Guo, Qiang; Dong, Wen-Zhao; Tang, Li-Ying; Liu, Jian-Guo

2014-01-01

Identifying the nodes with largest spreading influence of complex networks is one of the most promising domains. By taking into account the neighbors' k-core values, we present an improved neighbors' k-core (INK) method which is the sum of the neighbors' k-core values with a tunable parameter α to evaluate the node spreading influence with largest k-core values. Comparing with the Susceptible–Infected–Recovered (SIR) results for four real networks, the INK method could identify the node spreading influence with largest k-core values more accurately than the ones generated by the degree k, closeness C, betweenness B and coreness centrality method. - Highlights: • We present an improved neighbors' k-core (INK) method to evaluate the node spreading influence with largest k-core values. • The INK method could identify the node spreading influence with largest k-core values more accurately. • Kendall's tau τ of INK method with α=1 are highly identical to rank the node influence

Magnetic domain wall gratings for magnetization reversal tuning and confined dynamic mode localization.

Science.gov (United States)

Trützschler, Julia; Sentosun, Kadir; Mozooni, Babak; Mattheis, Roland; McCord, Jeffrey

2016-08-04

High density magnetic domain wall gratings are imprinted in ferromagnetic-antiferromagnetic thin films by local ion irradiation by which alternating head-to-tail-to-head-to-tail and head-to-head-to-tail-to-tail spatially overlapping domain wall networks are formed. Unique magnetic domain processes result from the interaction of anchored domain walls. Non-linear magnetization response is introduced by the laterally distributed magnetic anisotropy phases. The locally varying magnetic charge distribution gives rise to localized and guided magnetization spin-wave modes directly constrained by the narrow domain wall cores. The exchange coupled multiphase material structure leads to unprecedented static and locally modified dynamic magnetic material properties.

Effects of Lateral and Terminal Chains of X-Shaped Bolapolyphiles with Oligo(phenylene ethynylene Cores on Self-Assembly Behavior. Part 2: Domain Formation by Self-Assembly in Lipid Bilayer Membranes

Directory of Open Access Journals (Sweden)

Stefan Werner

2017-09-01

Full Text Available Supramolecular self-assembly of membrane constituents within a phospholipid bilayer creates complex functional platforms in biological cells that operate in intracellular signaling, trafficking and membrane remodeling. Synthetic polyphilic compounds of macromolecular or small size can be incorporated into artificial phospholipid bilayers. Featuring three or four moieties of different philicities, they reach beyond ordinary amphiphilicity and open up avenues to new functions and interaction concepts. Here, we have incorporated a series of X-shaped bolapolyphiles into DPPC (1,2-dipalmitoyl-sn-glycero-3-phosphocholine bilayers of giant unilamellar vesicles. The bolapolyphiles consist of a rod-like oligo(phenylene ethynylene (OPE core, hydrophilic glycerol-based headgroups with or without oligo(ethylene oxide expansions at both ends and two lateral alkyl chains attached near the center of the OPE core. In the absence of DPPC and water, the compounds showed thermotropic liquid-crystalline behavior with a transition between polyphilic and amphiphilic assembly (see part 1 in this issue. In DPPC membranes, various trends in the domain morphologies were observed upon structure variations, which entailed branched alkyl chains of various sizes, alkyl chain semiperfluorination and size expansion of the headgroups. Observed effects on domain morphology are interpreted in the context of the bulk behavior (part 1 and of a model that was previously developed based on spectroscopic and physicochemical data.

Mapping the structural and dynamical features of kinesin motor domains.

Directory of Open Access Journals (Sweden)

Guido Scarabelli

Full Text Available Kinesin motor proteins drive intracellular transport by coupling ATP hydrolysis to conformational changes that mediate directed movement along microtubules. Characterizing these distinct conformations and their interconversion mechanism is essential to determining an atomic-level model of kinesin action. Here we report a comprehensive principal component analysis of 114 experimental structures along with the results of conventional and accelerated molecular dynamics simulations that together map the structural dynamics of the kinesin motor domain. All experimental structures were found to reside in one of three distinct conformational clusters (ATP-like, ADP-like and Eg5 inhibitor-bound. These groups differ in the orientation of key functional elements, most notably the microtubule binding α4-α5, loop8 subdomain and α2b-β4-β6-β7 motor domain tip. Group membership was found not to correlate with the nature of the bound nucleotide in a given structure. However, groupings were coincident with distinct neck-linker orientations. Accelerated molecular dynamics simulations of ATP, ADP and nucleotide free Eg5 indicate that all three nucleotide states could sample the major crystallographically observed conformations. Differences in the dynamic coupling of distal sites were also evident. In multiple ATP bound simulations, the neck-linker, loop8 and the α4-α5 subdomain display correlated motions that are absent in ADP bound simulations. Further dissection of these couplings provides evidence for a network of dynamic communication between the active site, microtubule-binding interface and neck-linker via loop7 and loop13. Additional simulations indicate that the mutations G325A and G326A in loop13 reduce the flexibility of these regions and disrupt their couplings. Our combined results indicate that the reported ATP and ADP-like conformations of kinesin are intrinsically accessible regardless of nucleotide state and support a model where neck

Combining Domain-driven Design and Mashups for Service Development

Science.gov (United States)

Iglesias, Carlos A.; Fernández-Villamor, José Ignacio; Del Pozo, David; Garulli, Luca; García, Boni

This chapter presents the Romulus project approach to Service Development using Java-based web technologies. Romulus aims at improving productivity of service development by providing a tool-supported model to conceive Java-based web applications. This model follows a Domain Driven Design approach, which states that the primary focus of software projects should be the core domain and domain logic. Romulus proposes a tool-supported model, Roma Metaframework, that provides an abstraction layer on top of existing web frameworks and automates the application generation from the domain model. This metaframework follows an object centric approach, and complements Domain Driven Design by identifying the most common cross-cutting concerns (security, service, view, ...) of web applications. The metaframework uses annotations for enriching the domain model with these cross-cutting concerns, so-called aspects. In addition, the chapter presents the usage of mashup technology in the metaframework for service composition, using the web mashup editor MyCocktail. This approach is applied to a scenario of the Mobile Phone Service Portability case study for the development of a new service.

Metabolism of organically bound tritium

International Nuclear Information System (INIS)

Travis, C.C.

1984-01-01

The classic methodology for estimating dose to man from environmental tritium ignores the fact that organically bound tritium in foodstuffs may be directly assimilated in the bound compartment of tissues without previous oxidation. We propose a four-compartment model consisting of a free body water compartment, two organic compartments, and a small, rapidly metabolizing compartment. The utility of this model lies in the ability to input organically bound tritium in foodstuffs directly into the organic compartments of the model. We found that organically bound tritium in foodstuffs can increase cumulative total body dose by a factor of 1.7 to 4.5 times the free body water dose alone, depending on the bound-to-loose ratio of tritium in the diet. Model predictions are compared with empirical measurements of tritium in human urine and tissue samples, and appear to be in close agreement. 10 references, 4 figures, 3 tables

Configuration of ripple domains and their topological defects formed under local mechanical stress on hexagonal monolayer graphene.

Science.gov (United States)

Park, Yeonggu; Choi, Jin Sik; Choi, Taekjib; Lee, Mi Jung; Jia, Quanxi; Park, Minwoo; Lee, Hoonkyung; Park, Bae Ho

2015-03-24

Ripples in graphene are extensively investigated because they ensure the mechanical stability of two-dimensional graphene and affect its electronic properties. They arise from spontaneous symmetry breaking and are usually manifested in the form of domains with long-range order. It is expected that topological defects accompany a material exhibiting long-range order, whose functionality depends on characteristics of domains and topological defects. However, there remains a lack of understanding regarding ripple domains and their topological defects formed on monolayer graphene. Here we explore configuration of ripple domains and their topological defects in exfoliated monolayer graphenes on SiO2/Si substrates using transverse shear microscope. We observe three-color domains with three different ripple directions, which meet at a core. Furthermore, the closed domain is surrounded by an even number of cores connected together by domain boundaries, similar to topological vortex and anti-vortex pairs. In addition, we have found that axisymmetric three-color domains can be induced around nanoparticles underneath the graphene. This fascinating configuration of ripple domains may result from the intrinsic hexagonal symmetry of two-dimensional graphene, which is supported by theoretical simulation using molecular dynamics. Our findings are expected to play a key role in understanding of ripple physics in graphene and other two-dimensional materials.

First experience with the new .cern Top Level Domain

Science.gov (United States)

Alvarez, E.; Malo de Molina, M.; Salwerowicz, M.; Silva De Sousa, B.; Smith, T.; Wagner, A.

2017-10-01

In October 2015, CERN’s core website has been moved to a new address, http://home.cern, marking the launch of the brand new top-level domain .cern. In combination with a formal governance and registration policy, the IT infrastructure needed to be extended to accommodate the hosting of Web sites in this new top level domain. We will present the technical implementation in the framework of the CERN Web Services that allows to provide virtual hosting, a reverse proxy solution and that also includes the provisioning of SSL server certificates for secure communications.

Bound states in string nets

Science.gov (United States)

Schulz, Marc Daniel; Dusuel, Sébastien; Vidal, Julien

2016-11-01

We discuss the emergence of bound states in the low-energy spectrum of the string-net Hamiltonian in the presence of a string tension. In the ladder geometry, we show that a single bound state arises either for a finite tension or in the zero-tension limit depending on the theory considered. In the latter case, we perturbatively compute the binding energy as a function of the total quantum dimension. We also address this issue in the honeycomb lattice where the number of bound states in the topological phase depends on the total quantum dimension. Finally, the internal structure of these bound states is analyzed in the zero-tension limit.

Molecular dynamics simulations of DNA-free and DNA-bound TAL effectors.

Directory of Open Access Journals (Sweden)

Hua Wan

Full Text Available TAL (transcriptional activator-like effectors (TALEs are DNA-binding proteins, containing a modular central domain that recognizes specific DNA sequences. Recently, the crystallographic studies of TALEs revealed the structure of DNA-recognition domain. In this article, molecular dynamics (MD simulations are employed to study two crystal structures of an 11.5-repeat TALE, in the presence and absence of DNA, respectively. The simulated results indicate that the specific binding of RVDs (repeat-variable diresidues with DNA leads to the markedly reduced fluctuations of tandem repeats, especially at the two ends. In the DNA-bound TALE system, the base-specific interaction is formed mainly by the residue at position 13 within a TAL repeat. Tandem repeats with weak RVDs are unfavorable for the TALE-DNA binding. These observations are consistent with experimental studies. By using principal component analysis (PCA, the dominant motions are open-close movements between the two ends of the superhelical structure in both DNA-free and DNA-bound TALE systems. The open-close movements are found to be critical for the recognition and binding of TALE-DNA based on the analysis of free energy landscape (FEL. The conformational analysis of DNA indicates that the 5' end of DNA target sequence has more remarkable structural deformability than the other sites. Meanwhile, the conformational change of DNA is likely associated with the specific interaction of TALE-DNA. We further suggest that the arrangement of N-terminal repeats with strong RVDs may help in the design of efficient TALEs. This study provides some new insights into the understanding of the TALE-DNA recognition mechanism.

Bounding approaches to system identification

CERN Document Server

Norton, John; Piet-Lahanier, Hélène; Walter, Éric

1996-01-01

In response to the growing interest in bounding error approaches, the editors of this volume offer the first collection of papers to describe advances in techniques and applications of bounding of the parameters, or state variables, of uncertain dynamical systems. Contributors explore the application of the bounding approach as an alternative to the probabilistic analysis of such systems, relating its importance to robust control-system design.

Stalled RNAP-II molecules bound to non-coding rDNA spacers are required for normal nucleolus architecture.

Science.gov (United States)

Freire-Picos, M A; Landeira-Ameijeiras, V; Mayán, María D

2013-07-01

The correct distribution of nuclear domains is critical for the maintenance of normal cellular processes such as transcription and replication, which are regulated depending on their location and surroundings. The most well-characterized nuclear domain, the nucleolus, is essential for cell survival and metabolism. Alterations in nucleolar structure affect nuclear dynamics; however, how the nucleolus and the rest of the nuclear domains are interconnected is largely unknown. In this report, we demonstrate that RNAP-II is vital for the maintenance of the typical crescent-shaped structure of the nucleolar rDNA repeats and rRNA transcription. When stalled RNAP-II molecules are not bound to the chromatin, the nucleolus loses its typical crescent-shaped structure. However, the RNAP-II interaction with Seh1p, or cryptic transcription by RNAP-II, is not critical for morphological changes. Copyright © 2013 John Wiley & Sons, Ltd.

From time-based to competency-based standards: core transitional competencies in plastic surgery.

Science.gov (United States)

Lutz, Kristina; Yazdani, Arjang; Ross, Douglas

2015-01-01

Competency-based medical education is becoming increasingly prevalent and is likely to be mandated by the Royal College in the near future. The objective of this study was to define the core technical competencies that should be possessed by plastic surgery residents as they transition into their senior (presently postgraduate year 3) years of training. A list of potential core competencies was generated using a modified Delphi method that included the investigators and 6 experienced, academic plastic surgeons from across Canada and the United States. Generated items were divided into 7 domains: basic surgical skills, anesthesia, hand surgery, cutaneous surgery, esthetic surgery, breast surgery, and craniofacial surgery. Members of the Delphi group were asked to rank particular skills on a 4-point scale with anchored descriptors. Item reduction resulted in a survey consisting of 48 skills grouped into the aforementioned domains. This self-administered survey was distributed to all Canadian program directors (n = 11) via e-mail for validation and further item reduction. The response rate was 100% (11/11). Using the average rankings of program directors, 26 "core" skills were identified. There was agreement of core skills across all domains except for breast surgery and esthetic surgery. Of them, 7 skills were determined to be above the level of a trainee at this stage; a further 15 skills were agreed to be important, but not core, competencies. Overall, 26 competencies have been identified as "core" for plastic surgery residents to possess as they begin their senior, on-service years. The nature of these skills makes them suitable for teaching in a formal, simulated environment, which would ensure that all plastic surgery trainees are competent in these tasks as they transition to their senior years of residency. Copyright © 2014 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

Crystallization and X-ray crystallographic analysis of the cap-binding domain of influenza A virus H1N1 polymerase subunit PB2

International Nuclear Information System (INIS)

Liu, Yong; Meng, Geng; Luo, Ming; Zheng, Xiaofeng

2013-01-01

Substrate-free cap-binding domain of influenza A virus H1N1 polymerase subunit PB2 has been crystallized to show the structural details and clarify whether obvious conformational changes exist between the substrate-free and substrate-bound cap-binding domain. PB2 is one of the subunits of the influenza virus heterotrimeric polymerase. By its cap-binding domain (PB2 cap ), PB2 captures the 5′ cap of the host pre-mRNA to generate a capped 5′ oligonucleotide primer for virus transcription. The crystal structure of influenza A virus H3N2 PB2 cap with bound cap analogue m 7 GTP has been reported previously. To show the substrate-free structural details of PB2 cap and clarify whether obvious conformational changes exist between the substrate-free and substrate-bound cap-binding domain, we have successfully obtained the crystal of substrate-free H1N1 PB2 cap . The crystal of H1N1 PB2 cap diffracted to a high resolution of 1.32 Å. The crystal symmetry belongs to space group P1 with unit-cell parameters a = 29.49, b = 37.04, c = 38.33 Å, α = 71.10, β = 69.84, γ = 75.85°. There is one molecule in the asymmetric unit

Highly excited bound-state resonances of short-range inverse power-law potentials

Energy Technology Data Exchange (ETDEWEB)

Hod, Shahar [The Ruppin Academic Center, Emeq Hefer (Israel); The Hadassah Academic College, Jerusalem (Israel)

2017-11-15

We study analytically the radial Schroedinger equation with long-range attractive potentials whose asymptotic behaviors are dominated by inverse power-law tails of the form V(r) = -β{sub n}r{sup -n} with n > 2. In particular, assuming that the effective radial potential is characterized by a short-range infinitely repulsive core of radius R, we derive a compact analytical formula for the threshold energy E{sub l}{sup max} = E{sub l}{sup max}(n, β{sub n}, R), which characterizes the most weakly bound-state resonance (the most excited energy level) of the quantum system. (orig.)

The Spaces of Functions of Two Variables of Bounded κΦ-Variation in the Sense of Schramm-Korenblum

Directory of Open Access Journals (Sweden)

A. Azócar

2015-01-01

Full Text Available The purpose of this paper is twofold. Firstly, we introduce the concept of bounded κΦ-variation in the sense of Schramm-Korenblum for real functions with domain in a rectangle of R2. Secondly, we study some properties of these functions and we prove that the space generated by these functions has a structure of Banach algebra.

Decreasing the radiation quality factor of magnetic dipole antennas by a magnetic-coated metal core

DEFF Research Database (Denmark)

Kim, Oleksiy S.; Breinbjerg, Olav

2010-01-01

To achieve the Chu lower bound for the radiation Q, an electrically small magnetic dipole antenna should not store any magnetic energy internally to the minimum sphere enclosing the antenna. As shown in our previous works, the internal stored magnetic energy can be reduced, although not entirely...... eliminated, by introducing a solid magnetic core inside the antenna. In this paper, using analytical results obtained though the vector spherical wave theory, we show that the internal stored magnetic energy can be further reduced, and the Chu lower bound reached, for a spherical magnetic dipole antenna...

Bounded Intention Planning Revisited

OpenAIRE

Sievers Silvan; Wehrle Martin; Helmert Malte

2014-01-01

Bounded intention planning provides a pruning technique for optimal planning that has been proposed several years ago. In addition partial order reduction techniques based on stubborn sets have recently been investigated for this purpose. In this paper we revisit bounded intention planning in the view of stubborn sets.

Bounded Gaussian process regression

DEFF Research Database (Denmark)

Jensen, Bjørn Sand; Nielsen, Jens Brehm; Larsen, Jan

2013-01-01

We extend the Gaussian process (GP) framework for bounded regression by introducing two bounded likelihood functions that model the noise on the dependent variable explicitly. This is fundamentally different from the implicit noise assumption in the previously suggested warped GP framework. We...... with the proposed explicit noise-model extension....

A symmetric Roos bound for linear codes

NARCIS (Netherlands)

Duursma, I.M.; Pellikaan, G.R.

2006-01-01

The van Lint–Wilson AB-method yields a short proof of the Roos bound for the minimum distance of a cyclic code. We use the AB-method to obtain a different bound for the weights of a linear code. In contrast to the Roos bound, the role of the codes A and B in our bound is symmetric. We use the bound

Bounded Tamper Resilience

DEFF Research Database (Denmark)

Damgård, Ivan Bjerre; Faust, Sebastian; Mukherjee, Pratyay

2013-01-01

Related key attacks (RKAs) are powerful cryptanalytic attacks where an adversary can change the secret key and observe the effect of such changes at the output. The state of the art in RKA security protects against an a-priori unbounded number of certain algebraic induced key relations, e.......g., affine functions or polynomials of bounded degree. In this work, we show that it is possible to go beyond the algebraic barrier and achieve security against arbitrary key relations, by restricting the number of tampering queries the adversary is allowed to ask for. The latter restriction is necessary......-protocols (including the Okamoto scheme, for instance) are secure even if the adversary can arbitrarily tamper with the prover’s state a bounded number of times and obtain some bounded amount of leakage. Interestingly, for the Okamoto scheme we can allow also independent tampering with the public parameters. We show...

Rotationally induced fragmentation in the prestellar core L1544

Energy Technology Data Exchange (ETDEWEB)

Klapp, Jaime; Zavala, Miguel [Departamento de Física, Instituto Nacional de Investigaciones Nucleares (ININ), Km. 36.5, Carretera México-Toluca, La Marquesa 52750, Estado de México (Mexico); Sigalotti, Leonardo Di G.; Peña-Polo, Franklin; Troconis, Jorge [Centro de Física, Instituto Venezolano de Investigaciones Científicas (IVIC), Apartado Postal 20632, Caracas 1020A (Venezuela, Bolivarian Republic of)

2014-01-10

Recent observations indicate that there is no correlation between the level of turbulence and fragmentation in detected protostellar cores, suggesting that turbulence works mainly before gravitationally bound prestellar cores form and that their inner parts are likely to be velocity coherent. Based on this evidence, we simulate the collapse and fragmentation of an isolated, initially centrally condensed, uniformly rotating core of total mass M = 5.4 M {sub ☉}, using the smoothed particle hydrodynamics code GADGET-2 modified with the inclusion of sink particles, in order to compare the statistical properties of the resulting stellar ensembles with previous gravoturbulent fragmentation models. The initial conditions are intended to fit the observed properties of the prestellar core L1544. We find that for ratios of the rotational to the gravitational energy β ≥ 0.05, a massive disk is formed at the core center from which a central primary condenses after ∼50 kyr. Soon thereafter the disk fragments into secondary protostars, consistent with an intermediate mode of star formation in which groups of 10-100 stars form from a single core. The models predict peak accretion rates between ∼10{sup –5} and 10{sup –4} M {sub ☉} yr{sup –1} for all stars and reproduce many of the statistical properties predicted from gravoturbulent fragmentation, suggesting that on the small scales of low-mass, dense cores these are independent of whether the contracting gas is turbulent or purely rotating.

Spectral derivation of the classic laws of wall-bounded turbulent flows.

Science.gov (United States)

Gioia, Gustavo; Chakraborty, Pinaki

2017-08-01

We show that the classic laws of the mean-velocity profiles (MVPs) of wall-bounded turbulent flows-the 'law of the wall,' the 'defect law' and the 'log law'-can be predicated on a sufficient condition with no manifest ties to the MVPs, namely that viscosity and finite turbulent domains have a depressive effect on the spectrum of turbulent energy. We also show that this sufficient condition is consistent with empirical data on the spectrum and may be deemed a general property of the energetics of wall turbulence. Our findings shed new light on the physical origin of the classic laws and their immediate offshoot, Prandtl's theory of turbulent friction.

Two memory associated genes regulated by amyloid precursor protein intracellular domain ovel insights into the pathogenesis of learning and memory impairment in Alzheimer's disease

Institute of Scientific and Technical Information of China (English)

Chuandong Zheng; Xi Gu; Zhimei Zhong; Rui Zhu; Tianming Gao; Fang Wang

2012-01-01

In this study, we employed chromatin immunoprecipitation, a useful method for studying the locations of transcription factors bound to specific DNA regions in specific cells, to investigate amyloid precursor protein intracellular domain binding sites in chromatin DNA from hippocampal neurons of rats, and to screen out five putative genes associated with the learning and memory functions. The promoter regions of the calcium/calmodulin-dependent protein kinase II alpha and glutamate receptor-2 genes were amplified by PCR from DNA products immunoprecipitated by amyloid precursor protein intracellular domain. An electrophoretic mobility shift assay and western blot analysis suggested that the promoter regions of these two genes associated with learning and memory were bound by amyloid precursor protein intracellular domain (in complex form). Our experimental findings indicate that the amyloid precursor protein intracellular domain is involved in the transcriptional regulation of learning- and memory-associated genes in hippocampal neurons. These data may provide new insights into the molecular mechanism underlying the symptoms of progressive memory loss in Alzheimer's disease.

Crystal structure of the ligand-bound glucagon-like peptide-1 receptor extracellular domain.

Science.gov (United States)

Runge, Steffen; Thøgersen, Henning; Madsen, Kjeld; Lau, Jesper; Rudolph, Rainer

2008-04-25

The glucagon-like peptide-1 receptor (GLP-1R) belongs to Family B1 of the seven-transmembrane G protein-coupled receptors, and its natural agonist ligand is the peptide hormone glucagon-like peptide-1 (GLP-1). GLP-1 is involved in glucose homeostasis, and activation of GLP-1R in the plasma membrane of pancreatic beta-cells potentiates glucose-dependent insulin secretion. The N-terminal extracellular domain (nGLP-1R) is an important ligand binding domain that binds GLP-1 and the homologous peptide Exendin-4 with differential affinity. Exendin-4 has a C-terminal extension of nine amino acid residues known as the "Trp cage", which is absent in GLP-1. The Trp cage was believed to interact with nGLP-1R and thereby explain the superior affinity of Exendin-4. However, the molecular details that govern ligand binding and specificity of nGLP-1R remain undefined. Here we report the crystal structure of human nGLP-1R in complex with the antagonist Exendin-4(9-39) solved by the multiwavelength anomalous dispersion method to 2.2A resolution. The structure reveals that Exendin-4(9-39) is an amphipathic alpha-helix forming both hydrophobic and hydrophilic interactions with nGLP-1R. The Trp cage of Exendin-4 is not involved in binding to nGLP-1R. The hydrophobic binding site of nGLP-1R is defined by discontinuous segments including primarily a well defined alpha-helix in the N terminus of nGLP-1R and a loop between two antiparallel beta-strands. The structure provides for the first time detailed molecular insight into ligand binding of the human GLP-1 receptor, an established target for treatment of type 2 diabetes.

The high-affinity peptidoglycan binding domain of Pseudomonas phage endolysin KZ144

Energy Technology Data Exchange (ETDEWEB)

Briers, Yves [Division of Gene Technology, Department of Biosystems, Katholieke Universiteit Leuven, Kasteelpark Arenberg 21, B-3001 Leuven (Belgium); Schmelcher, Mathias; Loessner, Martin J. [Institute of Food Science and Nutrition, ETH Zuerich, Schmelzbergstrasse 7, CH-8092 Zuerich (Switzerland); Hendrix, Jelle; Engelborghs, Yves [Laboratory of Biomolecular Dynamics, Department of Chemistry, Katholieke Universiteit Leuven, Celestijnenlaan 200G, B-3001 Leuven (Belgium); Volckaert, Guido [Division of Gene Technology, Department of Biosystems, Katholieke Universiteit Leuven, Kasteelpark Arenberg 21, B-3001 Leuven (Belgium); Lavigne, Rob, E-mail: rob.lavigne@biw.kuleuven.be [Division of Gene Technology, Department of Biosystems, Katholieke Universiteit Leuven, Kasteelpark Arenberg 21, B-3001 Leuven (Belgium)

2009-05-29

The binding affinity of the N-terminal peptidoglycan binding domain of endolysin KZ144 (PBD{sub KZ}), originating from Pseudomonas aeruginosa bacteriophage {phi}KZ, has been examined using a fusion protein of PBD{sub KZ} and green fluorescent protein (PBD{sub KZ}-GFP). A fluorescence recovery after photobleaching analysis of bound PBD{sub KZ}-GFP molecules showed less than 10% fluorescence recovery in the bleached area within 15 min. Surface plasmon resonance analysis confirmed this apparent high binding affinity revealing an equilibrium affinity constant of 2.95 x 10{sup 7} M{sup -1} for the PBD{sub KZ}-peptidoglycan interaction. This unique domain, which binds to the peptidoglycan of all tested Gram-negative species, was harnessed to improve the specific activity of the peptidoglycan hydrolase domain KMV36C. The chimeric peptidoglycan hydrolase (PBD{sub KZ}-KMV36C) exhibits a threefold higher specific activity than the native catalytic domain (KMV36C). These results demonstrate that the modular assembly of functional domains is a rational approach to improve the specific activity of endolysins from phages infecting Gram-negatives.

Fatty acids and Pb-210 geochronology of a sediment core from Buzzards Bay, Massachusetts

International Nuclear Information System (INIS)

Farrington, J.W.; Henrichs, S.M.; Anderson, R.

1977-01-01

Four sections of a Pb-210 dated core of 62 cm length from Buzzards Bay, Massachusetts, were analyzed for fatty acids. A comparison of fatty acids extracted by Soxhlet extraction (unbound fatty acids) with fatty acids extracted by subsequent saponification extraction of the same sample (bound fatty acids) showed that the former did not undergo diagenetic loss any faster than the latter. However, compositional differences between bound and unbound fatty acids were apparent in the top section of 1 to 2 cm and were less apparent in the 54 to 58 cm section. At least 14% of the bound fatty acids are esterified to non-solvent extractable material. The net conversion of fatty acids to other compounds is 32 μg/g dry weight sediment over the first 30 yr after deposition. (author)

POEM a core instrument to measure symptoms in clinical trials: a HOME statement

OpenAIRE

Spuls, Ph.I.; Gerbens, L.A.A.; Simpson, E.; Apfelbacher, C.J.; Chalmers, J.R.; Thomas, K.S.; Prinsen, C.A.C.; Kobyletzki, L.B. von; Singh, J.A.; Williams, Hywel C.; Schmitt, J.

2016-01-01

Background: The Harmonising Outcome Measures for Eczema (HOME) initiative has defined four core outcome domains for a core outcome set (COS) to be measured in all atopic eczema (AE) trials to ensure cross-trial comparison: clinical signs, symptoms, quality of life and longterm control. Objectives: The aim of this paper is to report on the consensus process that was used to select the core instrument to consistently assess symptoms in all future AE trials. Methods: Following the HOME roa...

Comparison of S. cerevisiae F-BAR domain structures reveals a conserved inositol phosphate binding site

Science.gov (United States)

Moravcevic, Katarina; Alvarado, Diego; Schmitz, Karl R.; Kenniston, Jon A.; Mendrola, Jeannine M.; Ferguson, Kathryn M.; Lemmon, Mark A.

2015-01-01

SUMMARY F-BAR domains control membrane interactions in endocytosis, cytokinesis, and cell signaling. Although generally thought to bind curved membranes containing negatively charged phospholipids, numerous functional studies argue that differences in lipid-binding selectivities of F-BAR domains are functionally important. Here, we compare membrane-binding properties of the S. cerevisiae F-BAR domains in vitro and in vivo. Whereas some F-BAR domains (such as Bzz1p and Hof1p F-BARs) bind equally well to all phospholipids, the F-BAR domain from the RhoGAP Rgd1p preferentially binds phosphoinositides. We determined X-ray crystal structures of F-BAR domains from Hof1p and Rgd1p, the latter bound to an inositol phosphate. The structures explain phospholipid-binding selectivity differences, and reveal an F-BAR phosphoinositide binding site that is fully conserved in a mammalian RhoGAP called Gmip, and is partly retained in certain other F-BAR domains. Our findings reveal previously unappreciated determinants of F-BAR domain lipid-binding specificity, and provide a basis for its prediction from sequence. PMID:25620000

Presence of an SH2 domain in the actin-binding protein tensin.

Science.gov (United States)

Davis, S; Lu, M L; Lo, S H; Lin, S; Butler, J A; Druker, B J; Roberts, T M; An, Q; Chen, L B

1991-05-03

The molecular cloning of the complementary DNA coding for a 90-kilodalton fragment of tensin, an actin-binding component of focal contacts and other submembraneous cytoskeletal structures, is reported. The derived amino acid sequence revealed the presence of a Src homology 2 (SH2) domain. This domain is shared by a number of signal transduction proteins including nonreceptor tyrosine kinases such as Abl, Fps, Src, and Src family members, the transforming protein Crk, phospholipase C-gamma 1, PI-3 (phosphatidylinositol) kinase, and guanosine triphosphatase-activating protein (GAP). Like the SH2 domain found in Src, Crk, and Abl, the SH2 domain of tensin bound specifically to a number of phosphotyrosine-containing proteins from v-src-transformed cells. Tensin was also found to be phosphorylated on tyrosine residues. These findings suggest that by possessing both actin-binding and phosphotyrosine-binding activities and being itself a target for tyrosine kinases, tensin may link signal transduction pathways with the cytoskeleton.

Thermal Evolution and Crystallisation Regimes of the Martian Core

Science.gov (United States)

Davies, C. J.; Pommier, A.

2015-12-01

Though it is accepted that Mars has a sulfur-rich metallic core, its chemical and physical state as well as its time-evolution are still unconstrained and debated. Several lines of evidence indicate that an internal magnetic field was once generated on Mars and that this field decayed around 3.7-4.0 Gyrs ago. The standard model assumes that this field was produced by a thermal (and perhaps chemical) dynamo operating in the Martian core. We use this information to construct parameterized models of the Martian dynamo in order to place constraints on the thermochemical evolution of the Martian core, with particular focus on its crystallization regime. Considered compositions are in the FeS system, with S content ranging from ~10 and 16 wt%. Core radius, density and CMB pressure are varied within the errors provided by recent internal structure models that satisfy the available geodetic constraints (planetary mass, moment of inertia and tidal Love number). We also vary the melting curve and adiabat, CMB heat flow and thermal conductivity. Successful models are those that match the dynamo cessation time and fall within the bounds on present-day CMB temperature. The resulting suite of over 500 models suggest three possible crystallization regimes: growth of a solid inner core starting at the center of the planet; freezing and precipitation of solid iron (Fe- snow) from the core-mantle boundary (CMB); and freezing that begins midway through the core. Our analysis focuses on the effects of core properties that are expected to be constrained during the forthcoming Insight mission.

Symmetrical refolding of protein domains and subunits: example of the dimeric two-domain 3-isopropylmalate dehydrogenases.

Science.gov (United States)

Gráczer, Eva; Varga, Andrea; Melnik, Bogdan; Semisotnov, Gennady; Závodszky, Péter; Vas, Mária

2009-02-10

The refolding mechanism of the homodimeric two-domain 3-isopropylmalate dehydrogenase (IPMDH) from the organisms adapted to different temperatures, Thermus thermophilus (Tt), Escherichia coli (Ec), and Vibrio sp. I5 (Vib), is described. In all three cases, instead of a self-template mechanism, the high extent of symmetry and cooperativity in folding of subunits and domains have been concluded from the following experimental findings: The complex time course of refolding, monitored by Trp fluorescence, consists of a fast (the rate constant varies as 16.5, 25.0, and 11.7 min-1 in the order of Tt, Ec, and Vib IPMDHs) and a slow (the rate constants are 0.11, 0.80, and 0.23 min-1 for the three different species) first-order process. However, a burst increase of Trp fluorescence anisotropy to the value of the native states indicates that in all three cases the association of the two polypeptide chains occurs at the beginning of refolding. This dimeric species binds the substrate IPM, but the native-like interactions of the tertiary and quaternary structures are only formed during the slow phase of refolding, accompanied by further increase of protein fluorescence and appearance of FRET between Trp side chain(s) and the bound NADH. Joining the contacting arms of each subunit also takes place exclusively during this slow phase. To monitor refolding of each domain within the intact molecule of T. thermophilus IPMDH, Trp's (located in separate domains) were systematically replaced with Phe's. The refolding processes of the mutants were followed by measuring changes in Trp fluorescence and in FRET between the particular Trp and NADH. The high similarity of time courses (both in biphasicity and in their rates) strongly suggests cooperative folding of the domains during formation of the native three-dimensional structure of IPMDH.

Effects of soft interactions and bound mobility on diffusion in crowded environments: a model of sticky and slippery obstacles

Science.gov (United States)

Stefferson, Michael W.; Norris, Samantha L.; Vernerey, Franck J.; Betterton, Meredith D.; E Hough, Loren

2017-08-01

Crowded environments modify the diffusion of macromolecules, generally slowing their movement and inducing transient anomalous subdiffusion. The presence of obstacles also modifies the kinetics and equilibrium behavior of tracers. While previous theoretical studies of particle diffusion have typically assumed either impenetrable obstacles or binding interactions that immobilize the particle, in many cellular contexts bound particles remain mobile. Examples include membrane proteins or lipids with some entry and diffusion within lipid domains and proteins that can enter into membraneless organelles or compartments such as the nucleolus. Using a lattice model, we studied the diffusive movement of tracer particles which bind to soft obstacles, allowing tracers and obstacles to occupy the same lattice site. For sticky obstacles, bound tracer particles are immobile, while for slippery obstacles, bound tracers can hop without penalty to adjacent obstacles. In both models, binding significantly alters tracer motion. The type and degree of motion while bound is a key determinant of the tracer mobility: slippery obstacles can allow nearly unhindered diffusion, even at high obstacle filling fraction. To mimic compartmentalization in a cell, we examined how obstacle size and a range of bound diffusion coefficients affect tracer dynamics. The behavior of the model is similar in two and three spatial dimensions. Our work has implications for protein movement and interactions within cells.

An α-helical core encodes the dual functions of the chlamydial protein IncA.

Science.gov (United States)

Ronzone, Erik; Wesolowski, Jordan; Bauler, Laura D; Bhardwaj, Anshul; Hackstadt, Ted; Paumet, Fabienne

2014-11-28

Chlamydia is an intracellular bacterium that establishes residence within parasitophorous compartments (inclusions) inside host cells. Chlamydial inclusions are uncoupled from the endolysosomal pathway and undergo fusion with cellular organelles and with each other. To do so, Chlamydia expresses proteins on the surface of the inclusion using a Type III secretion system. These proteins, termed Incs, are located at the interface between host and pathogen and carry out the functions necessary for Chlamydia survival. Among these Incs, IncA plays a critical role in both protecting the inclusion from lysosomal fusion and inducing the homotypic fusion of inclusions. Within IncA are two regions homologous to eukaryotic SNARE (soluble N-ethylmaleimide-sensitive factor attachment receptor) domains referred to as SNARE-like domain 1 (SLD1) and SNARE-like domain 2 (SLD2). Using a multidisciplinary approach, we have discovered the functional core of IncA that retains the ability to both inhibit SNARE-mediated fusion and promote the homotypic fusion of Chlamydia inclusions. Circular dichroism and analytical ultracentrifugation experiments show that this core region is composed almost entirely of α-helices and assembles into stable homodimers in solution. Altogether, we propose that both IncA functions are encoded in a structured core domain that encompasses SLD1 and part of SLD2. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

An Entropy-Based Upper Bound Methodology for Robust Predictive Multi-Mode RCPSP Schedules

Directory of Open Access Journals (Sweden)

Angela Hsiang-Ling Chen

2014-09-01

Full Text Available Projects are an important part of our activities and regardless of their magnitude, scheduling is at the very core of every project. In an ideal world makespan minimization, which is the most commonly sought objective, would give us an advantage. However, every time we execute a project we have to deal with uncertainty; part of it coming from known sources and part remaining unknown until it affects us. For this reason, it is much more practical to focus on making our schedules robust, capable of handling uncertainty, and even to determine a range in which the project could be completed. In this paper we focus on an approach to determine such a range for the Multi-mode Resource Constrained Project Scheduling Problem (MRCPSP, a widely researched, NP-complete problem, but without adding any subjective considerations to its estimation. We do this by using a concept well known in the domain of thermodynamics, entropy and a three-stage approach. First we use Artificial Bee Colony (ABC—an effective and powerful meta-heuristic—to determine a schedule with minimized makespan which serves as a lower bound. The second stage defines buffer times and creates an upper bound makespan using an entropy function, with the advantage over other methods that it only considers elements which are inherent to the schedule itself and does not introduce any subjectivity to the buffer time generation. In the last stage, we use the ABC algorithm with an objective function that seeks to maximize robustness while staying within the makespan boundaries defined previously and in some cases even below the lower boundary. We evaluate our approach with two different benchmarks sets: when using the PSPLIB for the MRCPSP benchmark set, the computational results indicate that it is possible to generate robust schedules which generally result in an increase of less than 10% of the best known solutions while increasing the robustness in at least 20% for practically every

Low resolution solution structure of HAMLET and the importance of its alpha-domains in tumoricidal activity.

Science.gov (United States)

Ho, C S James; Rydstrom, Anna; Manimekalai, Malathy Sony Subramanian; Svanborg, Catharina; Grüber, Gerhard

2012-01-01

HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) is the first member in a new family of protein-lipid complexes with broad tumoricidal activity. Elucidating the molecular structure and the domains crucial for HAMLET formation is fundamental for understanding its tumoricidal function. Here we present the low-resolution solution structure of the complex of oleic acid bound HAMLET, derived from small angle X-ray scattering data. HAMLET shows a two-domain conformation with a large globular domain and an extended part of about 2.22 nm in length and 1.29 nm width. The structure has been superimposed into the related crystallographic structure of human α-lactalbumin, revealing that the major part of α-lactalbumin accommodates well in the shape of HAMLET. However, the C-terminal residues from L105 to L123 of the crystal structure of the human α-lactalbumin do not fit well into the HAMLET structure, resulting in an extended conformation in HAMLET, proposed to be required to form the tumoricidal active HAMLET complex with oleic acid. Consistent with this low resolution structure, we identified biologically active peptide epitopes in the globular as well as the extended domains of HAMLET. Peptides covering the alpha1 and alpha2 domains of the protein triggered rapid ion fluxes in the presence of sodium oleate and were internalized by tumor cells, causing rapid and sustained changes in cell morphology. The alpha peptide-oleate bound forms also triggered tumor cell death with comparable efficiency as HAMLET. In addition, shorter peptides corresponding to those domains are biologically active. These findings provide novel insights into the structural prerequisites for the dramatic effects of HAMLET on tumor cells.

Functional properties of the recombinant kringle-2 domain of tissue plasminogen activator produced in Escherichia coli

International Nuclear Information System (INIS)